antimony-sodium-gluconate and Leishmaniasis--Cutaneous

Pentavalent antimonials (Sb(V)) such as meglumine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®) are used as first-line treatments for leishmaniasis, either alone or in combination with second-line drugs such as amphotericin B (Amp B), miltefosine (MIL), methotrexate (MTX), or cryotherapy. Therapeutic aspects of these drugs are now challenged because of clinical resistance worldwide.. We reviewedthe recent original studies were assessed by searching in electronic databases such as Scopus, Pubmed, Embase, and Web of Science.. Studies on molecular biomarkers involved in drug resistance are essential for monitoring the disease. We reviewed genes and mechanisms of resistance to leishmaniasis, and the geographical distribution of these biomarkers in each country has also been thoroughly investigated.. Due to the emergence of resistant genes mainly in anthroponotic Leishmania species such as L. donovani and L. tropica, as the causative agents of ACL and AVL, respectively, selection of an appropriate treatment modality is essential. Physicians should be aware of the presence of such resistance for the selection of proper treatment modalities in endemic countries.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Biomarkers; Drug Resistance; Humans; Leishmaniasis; Leishmaniasis, Cutaneous; Meglumine Antimoniate

Leishmaniasis remains a public health concern around the world that primarily affects poor folks of the developing world spanning across 98 countries with mortality of 0.2 million to 0.4 million annually. Post kala-azar dermal leishmaniasis (PKDL) is the late skin manifestation of visceral leishmaniasis (VL). It has been reported that about 2.5% to 20% of patients recovered from VL develop PKDL having stilted macular or nodular lesions with parasites. In the Indian subcontinent (ISC), it manifests a few months after recovery from VL, though in Africa it can occur simultaneously with VL or a little later. New cases of PKDL are also observed without prior VL in the ISC. These individuals with PKDL represent an important but largely neglected reservoir of infection that perpetuates anthroponotic Leishmania donovani transmission in the ISC and can jeopardize the VL elimination program as these cases can infect the sand flies and spread the endemic. Therefore, it becomes imperative to eradicate PKDL as a part of the VL elimination program. With the limited treatment options besides little knowledge on PKDL, this review stands out in focusing on different aspects that should be dealt for sustained VL elimination.

Topics: Antimony Sodium Gluconate; Biomarkers; Genetic Predisposition to Disease; Humans; Immunologic Memory; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral

The mainstays of cutaneous leishmaniasis (CL) treatment, in several world regions, are pentavalent antimony (Sbv) compounds administered parenterally, despite their recognized toxicity, which requires frequent laboratory monitoring and complicates their use in areas with scarce infrastructure. As result of these drawbacks, the WHO Expert Committee on leishmaniasis has expanded the recommendations for the use of local therapies, including Sbv intralesional infiltration (IL-Sbv), as CL therapy alternatives even in the New World. However, the efficacy of these approaches has never been compiled. The aim of this study was to critically and systematically assess the efficacy of IL-Sbv for CL treatment.. The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the MEDLINE and LILACS databases and the International Clinical Trials Registry Platform of the World Health Organization. The outcome of interest was a clinical cure, defined as complete re-epithelialization of all lesions. The IL-Sbv pooled cure rate was estimated for several subgroups and direct comparisons were performed when possible.. Thirty nine articles (40 studies) involving 5679 patients treated with IL-Sbv infiltration were included. In direct comparison, only three studies involving 229 patients compared IL-Sbv infiltration versus placebo and no difference was observed (OR: 1,9; 95%IC 0,93 to 3,82) based on cure rate 69.6% (95%CI 17.6-96.1%) and 83,2% (95%CI 66-92.7%) for placebo and IL-Sbv, respectively. In an alternative and non-comparative analysis, gathering all study arms using the intervention, the pooled IL-Sbv efficacy rate was 75% (95%CI 68-81%). In the Old World, the observed overall IL-Sbv efficacy rate was 75% (95%CI 66-82%), and the cure rates were significantly higher with sodium stibogluconate (SSG) than with meglumine antimoniate (MA): 83% (95%CI 75-90%) versus 68% (95%CI 54-79%), p = 0.03. Studies directly comparing IL-Sbv with topical 15% paromomycin ointment, IL hypertonic saline, radiofrequency-induced heat therapy, topical trichloroacetic acid and cryotherapy showed no significant difference in efficacy between the interventions. The analyses suggested a higher efficacy of IL-Sbv combined with cryotherapy (81.8%, 95%IC 62.4-92.4%) when compared with IL-Sbv alone (53.3%, 95%IC 46.1-66%), OR: 3.14 (95%CI 1.1-8.9), p = 0.03. In the New World, the global IL-Sbv efficacy was 77%(95%CI 66-85%). In contrast with the Old World, a significant difference favoring MA in relation to SSG was observed: 61% (95%CI 49-73%) versus 82% (95%CI 70-89%).By comparing IL infiltration schedules, it was determined that patients submitted to IL-Sbv treatments longer than 14 days had higher cure rates.. Despite the high heterogeneity and low methodological quality of studies, an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use. The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications.

Topics: Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Cryotherapy; Databases, Factual; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Treatment Outcome

The worldwide prevalence of leishmaniasis is increasing because of ecologic changes and increased medical profession awareness. Furthermore, solitary cases have been recently reported in Western countries. The authors describe the epidemiology, mode of transmission, and diagnosis of leishmaniasis and present 4 oral cases treated with systemic, localized, or combined therapy. The authors suggest that clinicians should maintain a high index of suspicion for atypical, resistant, oral and perioral lesions in individuals with a history of traveling in certain geographic regions. After diagnosis, treatment should be determined jointly by experts from the fields of oral and maxillofacial surgery, oral medicine, and dermatology based on leishmaniasis species and clinical presentation.

Topics: Adolescent; Adult; Aged; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Diagnosis, Differential; Endemic Diseases; Female; Humans; Leishmania braziliensis; Leishmania infantum; Leishmania major; Leishmaniasis; Leishmaniasis, Cutaneous; Lip Diseases; Male; Mouth Diseases; Young Adult

New World leishmaniasis is an important endemic disease and public health problem in developing countries. The increase in ecologic tourism has extended this problem to developed countries. Few drugs have emerged over the past 50 years, and drug resistance has increased, such that the cure rate is no better than 80% in large studies. Despite these data, there has been no systematic review with a meta-analysis of the therapy used in this important tropical disease. The aim of this study was to determine the best drug management in the treatment of cutaneous leishmaniasis (CL) in Latin America based on the best studies published in the medical literature.. MEDLINE, LILACS, EMBASE, Web of Science, and Cochrane Library databases were searched to identify articles related to CL and therapy. Articles with adequate data on cure and treatment failure, internal and external validity information, and more than four patients in each treatment arm were included.. Fifty-four articles met our inclusion criteria and 12 were included in the meta-analysis. Pentavalent antimonials were the most studied drugs, with a total of 1150 patients, achieving a cure rate of 76.5%. The cure rate of pentamidine was similar to that of pentavalent antimonials. Other drugs showed variable results, and all demonstrated an inferior response.. Although pentavalent antimonials are the drugs of choice in the treatment of CL, pentamidine showed similar results. Nevertheless, several aspects, such as cost, adverse effects, local experience, and availability of drugs to treat CL, must be considered when determining the best management of this disease, especially in developing countries where resources are scarce.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Developing Countries; Endemic Diseases; Humans; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Paromomycin; Pentamidine

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmania; Leishmaniasis, Cutaneous; Military Personnel; Physical Therapy Modalities; Practice Guidelines as Topic; Referral and Consultation; United Kingdom

Leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoa, Leishmania, which resides in macrophages. The parasite is transmitted by an infected female sandfly. The incidence of cutaneous leishmaniasis approaches 2 million new cases per year with 90% of the cases occurring in the "Old World", while the "New World" accounts for the rest. Infection may be restricted to the skin with development of characteristic ulcers, or may affect the mucous membranes in its mucocutaneous form. The clinical diagnosis is verified by the presence of amastigotes in slit-skin smears. Therapeutic modalities include systemic treatments such as the pentavalent antimony compound sodium stibogluconate, liposomal formulations of amphotericin B, oral ketoconazole or itraconazole, as well as topical paromomycin sulphate, local heat, freezing with liquid nitrogen, or photodynamic therapy. An effective vaccine is not available.

Topics: Amphotericin B; Anti-Bacterial Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Controlled Clinical Trials as Topic; Diagnosis, Differential; Double-Blind Method; Humans; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Paromomycin; Photochemotherapy; Time Factors

Leishmaniasis remains a major world health problem that continues to increase in incidence. This review considers epidemiology, clinical features, diagnosis and current treatment options. Recent developments in the treatment of simple cutaneous leishmaniasis are discussed followed by speculation about future therapies.

Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Humans; Immunotherapy; Leishmania; Leishmaniasis, Cutaneous; Paromomycin; Phosphorylcholine

There is an urgent need for a safe, effective, easily administered and cheap treatment for cutaneous leishmaniasis. Unfortunately it remains elusive. There have been a number of contributions during the last year, but none will change present day management. The diagnosis of cutaneous leishmaniasis is established on the basis of a typical lesion, a history of exposure and demonstration of the parasite. Molecular methods, usually based on kinetoplast DNA, are being developed and used increasingly to diagnose and type the infecting organism. Pentavalent antimonials remain the mainstay of treatment.

Topics: Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Child, Preschool; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Mice

Leishmaniasis is a major World health problem, which is increasing in incidence. In Northern Europe it is seen in travellers returning from endemic areas. The protozoa is transmitted by sandflies and may produce a variety of clinical syndromes varying from a simple ulcer to fatal systemic disease. This review considers the management of simple cutaneous leishmaniasis. Patients usually have a single ulcer which may heal spontaneously, requiring only topical, or no treatment at all. Lesions caused by Leishmania braziliensis may evolve into the mucocutaneous form, 'espundia', and should be treated with systemic antimony. Sodium stiboglucoante 20 mg/kg/day i. v. for 20 days is the appropriate first line treatment in these cases. Although it may cause transient bone marrow suppression, liver damage, a chemical pancreatitis, and disturbances in the electrocardiogram, it appears to be safe. The success of treatment should be assessed 6 weeks after it has been completed and patients should be followed up for 6 months.

Topics: Amphotericin B; Animals; Antifungal Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Life Cycle Stages; Macrophages; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Prevalence; Skin

Topics: Allopurinol; Amphotericin B; Antimony Sodium Gluconate; Humans; Incidence; Ketoconazole; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral

Topics: Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Itraconazole; Ketoconazole; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pentamidine

Pentavalent antimonial compounds have been the mainstay of the treatment of visceral, cutaneous, and mucosal leishmaniasis for approximately half a century. Pentostam (sodium stibogluconate) is the pentavalent antimonial compound available in the United States (through the Centers for Disease Control). As dosage regimens for treating leishmaniasis have evolved, the daily dose of antimony and the duration of therapy have been progressively increased to combat unresponsiveness to therapy. In the 1980s, the use of 20 mg/kg/day (instead of 10 mg/kg/day) of antimony was recommended, but only to a maximum daily dose of 850 mg. The authors have concluded on the basis of recent efficacy and toxicity data that this 850-mg restriction should be removed; the evidence to date, which is summarized here, suggests that a regimen of 20 mg/kg/day of pentavalent antimony, without an upper limit on the daily dose, is more efficacious and is not substantially more toxic than regimens with lower daily doses. We recommend treating all forms of leishmaniasis with a full 20 mg/kg/day of pentavalent antimony. We treat cutaneous leishmaniasis for 20 days and visceral and mucosal leishmaniasis for 28 days. Our judgment of cure is based on clinical criteria.

Topics: Antimony Sodium Gluconate; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Leishmaniasis, Visceral

Topics: Adult; Animals; Antimony Sodium Gluconate; Diagnosis, Differential; Fever of Unknown Origin; Humans; Leishmania tropica; Leishmaniasis, Cutaneous; Male; Military Personnel; Saudi Arabia; United States; Veterans

Cutaneous leishmaniasis (CL) is generally caused by Leishmania aethiopica in Ethiopia, and is relatively hard to treat. Sodium stibogluconate (SSG) is the only routinely and widely available antileishmanial treatment, and can be used systemically for severe lesions and locally for smaller lesions. There is limited data on the effectiveness of intralesional (IL) SSG for localized CL in Ethiopia and therefore good data is necessary to improve our understanding of the effectiveness of the treatment.. A pragmatic (before and after Quazi experimental) study was done to assess the effectiveness of intralesional SSG among localized CL patients at Boru Meda general hospital, Northeast Ethiopia. Patients who were assigned to intralesional SSG by the treating physician were eligible for this study. Study subjects were recruited between January and August 2021. Infiltration of intralesional SSG was given weekly to a maximum of six doses. However, when a patient's lesions were already cured before getting 6 doses, treatment was not conintued, and patient were only asked to come for lesion assessment. Skin slit smears (SSS) were taken each week until they became negative. Outcomes were assessed at day 90, with patients who had 100% reepithelization (for ulcerative lesions) and/or flattening (for indurated lesions) defined as cured. Multi-level logistic regression was done to assess factors associated with cure. A total of 83 patients were enrolled, and final outcomes were available for 72 (86.75%). From these 72, 43 (59.7%, 95% confidence interval 0.44-0.69) were cured at day 90. Adverse effects were common with 69/72 patients (95.8%) reporting injection site pain. Factors associated with cure were age (OR 1.07 95% CI: 1.07-1.27), being male (OR 1.79, 95% CI: 1.10-2.25), size of the lesion (OR 0.79, 95% CI: 0.078-0.94) and skin slit smear (SSS) result +1 grading (OR 1.53, 95% CI: 1.24-1.73) and +2 grading (OR 1.51, 95% CI: 1.41-3.89) compared to the SSS grade +6.. Our findings revealed that intralesional sodium stibogluconate resulted in a cure rate of around 60%, with almost all patients experiencing injection site pain. This emphasizes the need for local treatment options which are more patient-friendly and have better cure rates.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Ethiopia; Female; Hospitals, General; Humans; Leishmaniasis, Cutaneous; Male; Pain; Treatment Outcome

Treatment failure to intralesional sodium stibogluconate (IL-SSG) is a health challenge for cutaneous leishmaniasis (CL) in Sri Lanka. A randomized controlled proof of principle clinical trial, with two arms (viz., radio frequency-induced heat therapy [RFHT] by a ThermoMed™ device (Model 1.8, Thermosurgery Technologies, Inc., Phoenix, AZ) and thermotherapy by a handheld exothermic crystallization thermotherapy for CL [HECT-CL] device) was conducted on 40 CL treatment failures to IL-SSG, from three hospitals in Tangalle, Hambantota, and Anuradhapura, from January 2017 to January 2018, followed up for 180 days post-thermotherapy with a final follow-up in February 2020. Intention-to-treat cure rates were calculated at day 90 (initial cure rate) and at day 180 (final cure rate) posttreatment. Radio frequency-induced heat therapy group: the initial cure rate was 100% (20/20) and the final cure rate was 95% (19/20), with one patient relapsing. The HECT-CL group: both the initial and final cure rates were 80% (16/20), with no relapses and one excluded from the trial. In February 2020 (1.6-3 years posttreatment), 27 traceable patients (RFHT = 16, HECT-CL = 11) remained healed. Second-degree burns were observed with RFHT in 65% (13/20), with HECT-CL in 15% (3/20), which completely resolved subsequently. The cure rates between the two treatment groups were comparable (P = 0.15). Radio frequency-induced heat therapy consumed less time and required only a single hospital visit. Handheld exothermic crystallization thermotherapy for CL is potentially usable at community settings with both being less costly than IL-SSG. This study is the first proof that thermotherapy is an efficacious and safe treatment for CL patients in Sri Lanka, complicated by treatment failure to IL-SSG.

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Female; Humans; Hyperthermia, Induced; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Sri Lanka; Treatment Failure; Treatment Outcome; Young Adult

The aim of our study was to assess the efficacy of intralesional metronidazole on Leishmania donovani cutaneous leishmaniasis (CL).. A total of 188 patients with CL were randomly allocated to intralesional sodium stibogluconate (SSG) and intralesional metronidazole. Cure was assessed after 1-10 injections. Cure rates were assessed for statistical significance using chi-square test at p = .05 level (SLCTR/2014/028).. When the treatment cutoff was taken at 100%, the rate of cure for SSG (n = 64, 65.6%) was higher than that of metronidazole (n = 45, 48.9%): statistically significant at p < .05 level (Yates corrected chi-square 5.37, df = 1, p < .5). When the treatment cutoff was taken at >80%, the rate of cure for SSG (n = 75, 77.1%) was also higher than that of metronidazole (n = 58, 63.0%): statistically significant at p < .05 level (Yates corrected chi-square 4.46, df = 1, p < .5). Since it is based on a smaller sample, we estimated the statistical power of the test at a cutoff of 100% [above 80%] results identified a risk ratio of 1.4 [1.3], and a statistical power based on normal approximation at 74.8% [70.0%], respectively.. This study showed that intralesional SSG has the best response against CL, while intralesional metronidazole was an effective alternative treatment.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Double-Blind Method; Female; Humans; Injections, Intralesional; Leishmania donovani; Leishmaniasis, Cutaneous; Male; Metronidazole; Middle Aged; Treatment Outcome; Young Adult

Conventional treatment of cutaneous leishmaniasis often leaves permanent scars with frequent psychosocial sequelae. The aim of this study was to compare the efficacy, safety, associated pain and final cosmetic outcome of fractional carbon dioxide (CO2) laser followed by topical application of sodium stibogluconate vs. sodium stibogluconate injections for the treatment of cutaneous leishmaniasis. A total of 181 lesions (20 patients) were randomly assigned to receive intralesional injections of sodium stibogluconate (control group) or fractional CO2 laser treatment followed by topical application of sodium stibogluconate (study group). The visual analogue scale (VAS) score of the control group was much higher than that of the study group (6.85 vs. 3.5, respectively, p<0.001). Both the patients and 2 blinded dermatologists found the final cosmetic outcome to be superior for laser-treated lesions (p = 0.001 vs. p =0.008 for controls). Fractional CO2 laser treatment followed by topical application of sodium stibogluconate is less painful and leads to a better final cosmetic outcome compared with intralesional injections of sodium stibogluconate.

Topics: Administration, Cutaneous; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Combined Modality Therapy; Female; Humans; Injections, Intralesional; Israel; Laser Therapy; Lasers, Gas; Leishmaniasis, Cutaneous; Male; Middle Aged; Pain Measurement; Patient Satisfaction; Prospective Studies; Skin; Time Factors; Treatment Outcome; Young Adult

Intralesional 7% hypertonic saline (HS) has been shown to be effective and safe against Leishmania donovani and Leishmania major cutaneous leishmaniasis (CL), with cure rates of 92% and 96%, respectively. This study was designed to assess the efficacy and safety of 10% and 15% HS in CL.. A total of 444 patients (643 lesions) were randomly allocated to sodium stibogluconate (SSG), 10% HS and 15% HS at a ratio of 2 : 2 : 1, taking into consideration any unwanted side effects that might arise with 15% HS. The follow-up period was 18 months. Survival analysis using Cox proportional hazard regression was performed to assess the effectiveness of the three treatment modalities. The clinical trial was registered at the Sri Lanka Clinical Trial Registry (SLCTR/2013/024).. Treatment with SSG resulted in a cure rate of 96.3% within one to seven injections (mean: 3.6 injections); the mean (median) duration of treatment was six weeks (6 weeks) per lesion. Treatment with 10% HS showed a cure rate of 93.0% within one to 10 injections (mean: 5.28 injections); the mean (median) duration of treatment was 9.3 weeks (9 weeks) per lesion. Treatment with 15% HS showed a cure rate of 93.6% within two to 10 injections (mean: 5.3 injections); the mean (median) duration of treatment was 11.3 weeks (10.0 weeks) per lesion. Treatment with 10% HS and 15% HS caused cutaneous necrosis in 3.1% and 30.6% of lesions, respectively. Despite continuous data collection for 14 months, we were unable to recruit a sample of sufficient size. Seventeen (3.8%) patients were lost to follow-up, and 24 (5.4%) were partial or non-responders.. This study found 10% HS to be an effective and safe alternative to SSG. Treatment with HS at concentrations of 15% or above was not safe as a result of cutaneous necrosis. Safety was not studied for concentrations of 11-14%, and these concentrations should be avoided pending further evidence. Hypertonic saline is very cheap (< US$1 per 100 ml, whereas SSG is priced at US$160 per 100 ml), is prepared locally and has no systemic side effects and minimal local side effects.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Injections, Intralesional; Leishmania donovani; Leishmaniasis, Cutaneous; Male; Middle Aged; Saline Solution, Hypertonic; Young Adult

The German S1 guidelines from 2009 contain a variety of recommendations for the treatment of cutaneous leishmaniasis.. We report the results of our diagnostic procedures and treatment of 32 international patients in autumn 2010 in northern Afghanistan.. Giemsa stain confirmed the clinical diagnosis within 24 hours. Eleven simple lesions and one larger ulcer responded well to cryotherapy and intralesional sodium stibogluconate. More complex lesions in 19 patients responded well to oral miltefosine. One patient refused outpatient therapy.. Cryotherapy and intralesional antimony compounds showed good results in early lesions of cutaneous leishmaniasis in northern Afghanistan. Outpatient treatment of complex lesions with miltefosine was successful in all cases.

Topics: Administration, Topical; Adult; Afghanistan; Antimony Sodium Gluconate; Antiprotozoal Agents; Combined Modality Therapy; Cryotherapy; Dermatologic Agents; Humans; Internationality; Leishmaniasis, Cutaneous; Male; Military Personnel; Phosphorylcholine; Treatment Outcome; Young Adult

A previously published proof of principle phase IIa trial with 113 patients from Kabul showed that bipolar high-frequency (HF) electro-cauterization (EC) of cutaneous leishmaniasis (CL) ulcers and subsequent moist wound treatment (MWT) closed 85% of all Leishmania (L.) tropica lesions within 60 days.. A three-armed phase IIb, randomized and controlled clinical trial was performed in Mazar-e-Sharif. L. tropica- or L. major-infected CL patients received intradermal sodium stibogluconate (SSG) (Group I); HF-EC followed by MWT with 0.045% DAC N-055 (Group II); or MWT with 0.045% DAC N-055 in basic crème alone (Group III). The primary outcome was complete epithelialisation before day 75 after treatment start.. 87 patients enrolled in the trial were randomized into group I (n = 24), II (n = 32) and III (n = 31). The per-protocol analysis of 69 (79%) patients revealed complete epithelialisation before day 75 in 15 (of 23; 65%) patients of Group I, in 23 (of 23; 100%) patients of Group II, and in 20 (of 23; 87%) patients of Group III (p = 0.004, Fisher's Exact Test). In the per-protocol analysis, wound closure times were significantly different between all regimens in a pair-wise comparison (p = 0.000039, Log-Rank (Mantel-Cox) test). In the intention-to-treat analysis wound survival times in Group II were significantly different from those in Group I (p = 0.000040, Log-Rank (Mantel-Cox) test). Re-ulcerations occurred in four (17%), three (13%) and seven (30%) patients of Group I, II or III, respectively (p = 0.312, Pearson Chi-Square Test).. Treatment of CL ulcers with bipolar HF-EC followed by MWT with 0.045% DAC N-055 or with DAC N-055 alone showed shorter wound closure times than with the standard SSG therapy. The results merit further exploration in larger trials in the light of our current knowledge of in vitro and in vivo activities of chlorite. Clinicaltrials.gov ID: NCT00996463. Registered: 15th October 2009.

Topics: Adult; Afghanistan; Antimony Sodium Gluconate; Antiprotozoal Agents; Bandages; Chlorides; Electrocoagulation; Female; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Skin Ulcer; Time Factors; Treatment Outcome; Wound Healing; Young Adult

New World cutaneous leishmaniasis is mostly acquired in the Amazon Basin of Bolivia where L viannia (V) braziliensis is endemic. Treatment with systemic pentavalent antimonial compounds has been shown to be effective in achieving clinical cure in only 75% of cases.. We sought to assess the efficacy and safety of liposomal amphotericin B (L-AmB) treatment for primary infection of cutaneous L (V) braziliensis.. A prospective observational evaluation was performed for cutaneous leishmaniasis due to L (V) braziliensis which was treated with L-AmB, 3 mg/kg, for 5 consecutive days, and a sixth dose on day 10. This therapy regimen was compared with the treatment regimen of sodium stibogluconate (SSG) 20 mg/kg for 3 weeks.. Our study was divided into two groups; 34 patients received L-AmB and 34 received SSG treatment. Almost all patients were infected in Bolivia. In the L-AmB group, 29 patients (85%) had complete cure compared with 70% in the SSG group (P = not significant), 4 other patients were slow healers, and only one patient needed additional treatment with SSG. No relapses were seen during a mean 29-month follow-up period. Failure rate was 3% in the L-AmB versus 29% in the SSG group (P = .006). Treatment was interrupted in 65% of patients taking SSG because of adverse events, whereas all patients receiving L-AmB completed treatment.. This was a non-blinded comparative study.. Comparison of L-Amb to SSG treatment for L (V) braziliensis shows that the former is effective, better tolerated, and more cost effective. L-AmB should therefore be considered as the first-line treatment option for cutaneous L (V) braziliensis infection.

Topics: Adult; Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Bolivia; Female; Humans; Insurance, Health, Reimbursement; Israel; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Treatment Outcome

Radiofrequency-induced heat therapy (RFHT) has been found to be safe and effective against cutaneous leishmaniasis (CL) in the short term, but its long-term efficacy is unclear.. To compare the long-term efficacy of RFHT vs. intralesional sodium stibogluconate (SSG) injections in the treatment of CL in India.. One hundred patients with a confirmed diagnosis of CL were randomly assigned in a 1 : 1 ratio to receive topical RFHT for 30-60 s or seven intralesional injections of SSG (50 mg cm(-2) of lesion). Improvement and recurrence were monitored every 15 days after the initiation of treatment for 4 months and then at 5, 6, 9, 12 and 18 months post-treatment; the rates of complete cure were compared.. Lesions were healed in 47 out of 50 patients (94%) in the RFHT group and in 46 out of 50 patients (92%) in the SSG group at week 12. Time to complete healing was comparable in the two groups. At 6 months post-treatment, cure rates in the RFHT and SSG groups were 98% [95% confidence interval (CI) 94-100%] and 94% (95% CI 86-100%), respectively. Age, sex and lesion size or number had no effect on cure rates. No relapse of infection was recorded in cured patients in either group up to 12-18 months after initiation of treatment. Skin biopsies of cured lesions in eight out of eight (100%) patients from the RFHT group and three of three from the SSG group at 12 months showed minimal fibrosis and were negative for Leishmania tropica by polymerase chain reaction test.. A single application of RFHT is safe, cosmetically acceptable and effective in inducing a long-term cure of CL.

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Humans; Hyperthermia, Induced; India; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Radiofrequency Therapy; Time Factors; Treatment Outcome; Young Adult

Cutaneous leishmaniasis (CL) is a disease caused by leishmania species. Intralesional sodium stibogluconate (SSG) has been considered the first line therapy for localized cutaneous leishmaniasis. There is still a need for more effective and less time-consuming therapeutic methods for this condition.. The aim of the present study was to investigate if the combination of intramuscular (IM) SSG or oral ketoconazole with intralesional (IL) SSG would be more effective than the intralesional SSG given alone in the treatment of localized cutaneous leishmaniasis.. Thirty patients with confirmed diagnosis of cutaneous leishmaniasis were included in the study. They were randomly assigned to three groups. The first group (10 patients with 12 lesions) was treated with intralesional SSG alone. The second group (10 patients with 15 lesions) was treated with the combination of intralesional SSG + intramuscular SSG. The third group (10 patients with 13 lesions) was treated with the combination of intralesional SSG and oral ketoconazole. A follow-up was performed every 4 weeks for a treatment period of 12 weeks, then monthly for a period of 6 months after the end of the treatment.. Complete cure occurred in 58.3% of lesions in group 1, while 93.3% and 92.3% of lesions were cured in group 2 and 3 respectively. The difference between group 1 and the other groups was statistically significant (P < 0.05).. Combined intramuscular SSG or oral ketoconazole with intralesional SSG is more effective than intralesional SSG alone for the treatment of CL. Oral ketoconazole is much easier and safer therapy than intramuscular SSG in combination with intralesional SSG in the treatment of localized cutaneous leishmaniasis.

Topics: Administration, Oral; Adolescent; Adult; Antifungal Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Injections, Intralesional; Injections, Intramuscular; Ketoconazole; Leishmaniasis, Cutaneous; Male; Middle Aged; Retrospective Studies; Skin; Time Factors; Treatment Outcome; Young Adult

Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan. Optimal treatment for this localized infection has not been defined, but interestingly the parasite is thermosensitive.. Participants with parasitologically confirmed L. major infection were randomized to receive intravenous sodium stibogluconate (SSG) 20mg/kg/day for ten doses or localized ThermoMed (TM) device heat treatment (applied at 50 degrees C for 30 seconds) in one session. Those with facial lesions, infection with other species of Leishmania, or more than 20 lesions were excluded. Primary outcome was complete re-epithelialization or visual healing at two months without relapse over 12 months. Fifty-four/56 enrolled participants received intervention, 27 SSG and 27 TM. In an intent to treat analysis the per subject efficacy at two months with 12 months follow-up was 54% SSG and 48% TM (p = 0.78), and the per lesion efficacy was 59% SSG and 73% TM (p = 0.053). Reversible abdominal pain/pancreatitis, arthralgias, myalgias, headache, fatigue, mild cytopenias, and elevated transaminases were more commonly present in the SSG treated participants, whereas blistering, oozing, and erythema were more common in the TM arm.. Skin lesions due to L. major treated with heat delivered by the ThermoMed device healed at a similar rate and with less associated systemic toxicity than lesions treated with intravenous SSG.. ClinicalTrials.gov NCT 00884377.

Topics: Adolescent; Adult; Animals; Antimony Sodium Gluconate; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hyperthermia, Induced; Injections, Intravenous; Leishmania major; Leishmaniasis, Cutaneous; Male; Middle Aged; Treatment Outcome; Young Adult

Since cutaneous leishmaniasis (CL) is a self healing disease, an ideal therapy should be rapidly effective, easily administered, cheap, available at all times at all centers and should have no side effects.. To determine the efficacy and safety of intralesional 7% hypertonic saline in comparison to intralesional sodium stibogluconate against L. donovani CL.. Intralesional hypertonic saline (HS) and sodium stibogluconate (SSG) were randomly allocated to 154 patients (229 lesions); these were followed-up for 18 months.. The M:F ratio was 1.8:1 (99:55). The average age of our population was 32 years. SSG was given to 87 patients (136 lesions); HS was given to 67 patients (93 lesions). SSG showed a 100% cure rate within one to six injections (average 3.24); HS showed a 92.2% cure rate within one to 10 injections (average 5.27). The average duration of treatment with SSG and HS was 5.11 and 8.78 weeks respectively. There was no difference in efficacy for both therapies with regard to ulcers or papules, and small or large, exposed or unexposed lesions. There was no association between the rapidity of clinical response and the duration and location of lesions. There were no local or systemic side effects except pain during injection. The lesions in the two groups showed post-inflammatory hyperpigmentation after treatment. During 18 months of follow-up there were no recurrences and no visceralization.. The most effective therapy for Leishmania donovani cutaneous leishmaniasis was intralesional SSG (average 3.24 injections). HS was effective, but needed an average of 5.27 injections in total per lesion. HS was cheap, with no risk of systemic side effects and was easily available at all centers.

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Injections, Intralesional; Leishmania donovani; Leishmaniasis, Cutaneous; Male; Middle Aged; Saline Solution, Hypertonic; Treatment Outcome

The efficacy and pharmacokinetics of antimony were explored in 12 young male patients with cutaneous leishmaniasis following intramuscular administration of sodium stibogluconate equivalent to 600 mg of antimony (Sb). Patients' cure rate was evaluated up to 6 weeks after treatment. Blood samples were collected at different time periods on the first and last days of a 3-week treatment. Twenty-four-hour urine samples were also collected on both occasions for the estimation of renal clearance (CL(r)). The blood concentrations of the Sb time profile were best described by a 2-compartment model with a first-order absorption rate. The mean absorption half-life was 0.21 ± 0.023 and 0.36 ± 0.18 hours for the first and last doses, respectively. A rapid distribution phase was followed by a slower elimination phase of a half-life of 9.4 ± 1.9 and 9.69 ± 2.3 hours for both days, respectively. An accumulation index of 2.33 was calculated. The fraction of dose excreted in urine was 0.386 ± 0.11 and 0.326 ± 0.05 on both occasions, respectively. The mean CL(r) was 4.88 ± 1.13 and 4.58 ± 1.05 L/h. In the current study, all of the patients were completely healed by week 6 after the end of treatment, as judged by the treating physician. In conclusion, the blood profile of antimony seems to be multicompartmental in nature.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Half-Life; Humans; Injections, Intramuscular; Leishmaniasis, Cutaneous; Male; Tissue Distribution; Treatment Outcome; Young Adult

Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-gamma and IL-12. We address the role of the differential decline of IL-10 and TGF-beta in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-beta in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-gamma and IL-12 production, and elevation of IL-10 and TGF-beta. Cure corresponded with an elevation in IFN-gamma and IL-12 production and down-regulation of IL-10 and TGF-beta. Both CD4(+) and CD8(+) T cells were involved in IFN-gamma and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-beta in some SAG-treated individuals and the elevation of IL-10 and TGF-beta in PKDL, a sequel to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB treatment of VL resulted in negligible TGF-beta levels and absolute elimination of IL-10, reflecting the better therapeutic activity of AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-beta, IL-10, and Ab production. In addition, the enhancement of CD4(+)CD25(+) T cells in active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease forms.

Topics: Adolescent; Adult; Amphotericin B; Animals; Antimony Sodium Gluconate; Cells, Cultured; Coculture Techniques; Disease Susceptibility; Female; Humans; India; Interleukin-10; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Recurrence; Transforming Growth Factor beta

Antimonials are the first drug of choice for the treatment of American tegumentary leishmaniasis (ATL); however, their efficacy is not predictable, and this may be linked to parasite drug resistance. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Peruvian patients with ATL who were treated with sodium stibogluconate and to correlate this in vitro phenotype with different treatment outcomes.. Thirty-seven clinical isolates were obtained from patients with known disease and treatment histories. These isolates were typed, and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined.. We observed 29 SbV-resistant isolates among 4 species of subgenus Viannia, most of which exhibited primary resistance; isolates resistant only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant to SbV only (the majority of isolates fell into this category). There was no correlation between in vitro susceptibility to both antimonials and the clinical outcome of therapy.. Antimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factors.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Resistance; Humans; Leishmania; Leishmaniasis, Cutaneous; Parasitic Sensitivity Tests; Peru; Prospective Studies; Treatment Outcome

Pentavalent antimony is the agent recommended for treatment of cutaneous leishmaniasis (CL). Its use is problematic, because it is expensive and because of the potential for drug-associated adverse effects during a lengthy and painful treatment course.. We tested the efficacy of thermotherapy for the treatment of CL due to Leishmania tropica in a randomized, controlled trial in Kabul, Afghanistan. We enrolled 401 patients with a single CL lesion and administered thermotherapy using radio-frequency waves (1 treatment of >or=1 consecutive application at 50 degrees C for 30 s) or sodium stibogluconate (SSG), administered either intralesionally (a total of 5 injections of 2-5 mL every 5-7 days, depending on lesion size) or intramuscularly (20 mg/kg daily for 21 days).. Cure, defined as complete reepithelialization at 100 days after treatment initiation, was observed in 75 (69.4%) of 108 patients who received thermotherapy, 70 (75.3%) of 93 patients who received intralesional SSG, and 26 (44.8%) of 58 patients who received intramuscular SSG. The OR for cure with thermotherapy was 2.80 (95% confidence interval [CI], 1.45-5.41), compared with intramuscular SSG treatment (P=.002). No statistically significant difference was observed in the odds of cure in comparison of intralesional SSG and thermotherapy treatments. The OR for cure with intralesional SSG treatment was 3.75 (95% CI, 1.86-7.54), compared with intramuscular SSG treatment (P<.001). The time to cure was significantly shorter in the thermotherapy group (median, 53 days) than in the intralesional SSG or intramuscularly SSG group (median, 75 days and >100 days, respectively; P=.003).. Thermotherapy is an effective, comparatively well-tolerated, and rapid treatment for CL, and it should be considered as an alternative to antimony treatment.

Topics: Adolescent; Adult; Afghanistan; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Female; Humans; Hyperthermia, Induced; Leishmania tropica; Leishmaniasis, Cutaneous; Male; Odds Ratio; Time Factors

The cost of generic pentavalent antimony (generic stibogluconate) is approximately one-sixth that of branded pentavalent antimony (stibogluconate in the form of Pentostam or meglumine antimoniate in the form of Glucantime. We compared generic stibogluconate to Pentostam and Glucantime for the treatment of cutaneous leishmaniasis patients in Bolivia and Colombia. For all 114 patients, the per-protocol cure rates were 83-91% and the intent-to-treat cure rates were 75-83%. The highest values were in the generic stibogluconate group. The incidence of pancreatic enzyme abnormalities was 48-88% and the incidence of liver enzyme abnormalities was 48-87%. The lowest incidences were in the generic stibogluconate group. The efficacy and tolerance of inexpensive generic stibogluconate appears comparable to branded formulations for the treatment of cutaneous leishmaniasis in these endemic regions.

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Bolivia; Colombia; Double-Blind Method; Drugs, Generic; Female; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged; Treatment Outcome

The recommended treatment for cutaneous leishmaniasis is pentavalent antimony at a dosage of 20 mg/kg/day for 20 days. Some studies conducted in locales in which Leishmania is endemic have suggested that shorter courses of treatment may be as efficacious. We conducted a randomized, double-blind, placebo-controlled study of 10 versus 20 days of sodium stibogluconate (SSG) in United States military personnel who contracted cutaneous leishmaniasis while serving overseas; 19 patients received SSG for 10 days (and placebo for 10 days), and 19 patients received SSG for 20 days. Cure rates were 100% (19 of 19 patients) in the 10-day group and 95% (18 of 19 patients) in the 20-day group. Side effects were more common among patients who received 20 days of therapy. In this group of otherwise healthy young adults, SSG at a dosage of 20 mg/kg/day for 10 days appears to have been therapeutically equivalent and less toxic than the standard 20-day course.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Arthralgia; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged; Military Personnel; Pancreatitis; Treatment Outcome; United States

Forty-two CL patients with 60 lesions were treated with cryotherapy using liquid nitrogen twice for two months. Another group of fifty-five CL patients. With 73 lesions were treated with intralesional pentostam with pentostam, 67 of 73 lesions (92%) and with cryotherapy 47 of 60 lesions (78%) healed or markedly improved at the end of three months follow-up. This study shows that intralesional pentostam injection was effective than cryotherapy. However, both lines of treatment were well tolerated by the patients. They showed no severe side effects and no significant changes in laboratory values. It is suggested that cryotherapy is an alternative to intralesional pentostam injection.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Combined Modality Therapy; Cryotherapy; Electrocardiography; Humans; Leishmaniasis, Cutaneous

Cutaneous leishmaniasis (CL) is an endemic disease in Egypt. Systematic treatment with pentostam has its disadvantages and contraindications. In this study, six out of eight parasitologically proved CL patients recovered with intralesion infiltration with a dose of pentostam ranged between 0.8 to 1.6 gm. The other 2 patients did not show response with a dose up to 2 gm. The results were discussed.

Topics: Adult; Ambulatory Care Facilities; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Middle Aged

The response to recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis was evaluated. Twenty patients with cutaneous leishmaniasis who had lesions for 60 days were enrolled in a double-blind placebo trial of GM-CSF with standard parenteral sodium stibogluconate (20 mg/kg-1/day-1) for 20 days. Ten patients were randomized to receive intralesionally injected GM-CSF (200 microgram) at enrollment and 1 week after, and 10 patients received saline as placebo. GM-CSF- and antimony-treated patients healed faster than patients who received antimony alone (49+/-32.8 vs. 110+/-61.6 days, P<.05). Seven of 10 patients were healed of their lesions before 40 days after therapy in the GM-CSF group, compared with only 1 of 10 patients in the placebo group (relative risk, 7; 95% confidence interval, 1.04-47.00). Thus, GM-CSF plus antimony significantly increased the chance of lesion healing in 40 days.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged

Electrical stimulation has been used as a mode of therapy for a number of clinical conditions. However, it has not been used for the treatment of cutaneous leishmaniasis (CL). For this purpose, we designed the "Baghdadin device". A total of 146 lesions of acute CL in 54 patients were treated by this device. Twenty-one lesions in the same patients were left untreated as controls. In addition, 36 lesions in 15 patients were treated with intralesional sodium stibogluconate. Treatment by the Baghdadin device consisted of weekly sessions of 10 minutes of direct current electrical stimulation. The intensity of the direct current ranged between 5 and 15 milliamperes, and the voltage was kept below 40 volts. Of the 146 lesions, 135 (92.5%) showed total clearance or marked improvement in 4-6 weeks time. Approximately 67% of the lesions needed only one or two sessions. Scarring was not observed after resolution. None of the untreated lesions showed any signs of improvement in 6 weeks. Of the lesions treated with sodium stibogluconate, 32 lesions (88.9%) showed total clearance or marked improvement, which was not significantly different from the results with the Baghdadin device.

Topics: Acute Disease; Administration, Topical; Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Electric Stimulation Therapy; Equipment Design; Female; Humans; Iraq; Leishmaniasis, Cutaneous; Male; Middle Aged; Treatment Outcome

A review of 84 patients with cutaneous leishmaniasis treated with sodium stibogluconate (Pentostam) at our institution revealed that three had developed herpes zoster during or shortly after receiving therapy. Because zoster has been associated with depressed cellular immunity, we prospectively followed serial lymphocyte subpopulations in eight patients with cutaneous leishmaniasis who received Pentostam. By day 7 of therapy, the white blood cell count had fallen by a median of 1.15/mm3, the total lymphocyte count by a median of 804/mm3, and the CD4+ lymphocyte count by a median of 306/mm3 (67% of baseline; confidence interval, 52%-78%). An in vitro cell-viability assay demonstrated that Pentostam is not toxic to human mononuclear cells. The administration of Pentostam for the treatment of cutaneous leishmaniasis results in lymphopenia that may be related to the subsequent occurrence of herpes zoster.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; CD4 Lymphocyte Count; Cell Survival; Herpes Zoster; Humans; Leishmaniasis, Cutaneous; Lymphopenia; Male; Military Personnel; Prospective Studies

We conducted a randomized, controlled study in southern Colombia to determine if the addition of allopurinol to stibogluconate was superior to stibogluconate alone in the treatment of cutaneous leishmaniasis. Lesions that healed after a 3-month course of therapy and remained so during a 1-year period of follow-up were considered cured. The cure rate for patients treated with stibogluconate was 39%; the addition of allopurinol increased this rate to 71% (P = .005). For the treatment of cutaneous leishmaniasis, the combination of allopurinol and stibogluconate is significantly more effective than is stibogluconate alone. These results support those of other clinical studies in which allopurinol and stibogluconate were shown to be superior to stibogluconate alone. The aggregate data support the use of allopurinol as an inexpensive, orally administered agent that can be used as an adjunct to stibogluconate or, perhaps, other oral agents in the treatment of cutaneous leishmaniasis.

Topics: Adolescent; Adult; Aged; Allopurinol; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Therapy, Combination; Female; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged

Parasitologically confirmed cases of post-kala-azar dermal leishmaniasis (PKDL) were treated by infusion with amphotericin B deoxycholate (ABD; 1 mg/kg.day on days 1-20, 21-40 and 61-80) or by intramuscular injection with sodium antimony gluconate (SAG; 20-day courses at 20 mg/kg day, with 20-day, drug-free intervals). Of the 11 patients given ABD, all were cured with the three courses, none relapsed in 12 months of follow-up, all developed mild adverse effects (shivering and fever) because of the infusion, five lost their appetites, and three showed increases in their serum creatinine concentrations (although none exceeded 'normal' limits). In contrast, only seven (63%) of the 11 patients given SAG were considered treatment successes (improvement in lesions by the end of the third course) and these took six courses (two cases), nine courses (four cases) or 10 courses (one case) to cure completely. Two of the patients given SAG developed arthralgia and two others developed non-specific ST changes in their electrocardiograms (ECG), although their ECG were normal between courses. The better cure rate with ABD was not statistically significant, probably because of the small sample size. However, ABD appears to be a superior to SAG in terms of the speed of response and cure, although it is more expensive and has some nephrotoxicity. As the effectiveness of SAG against PKDL is apparently declining over time and the cost of ABD is prohibitive in poor countries such as India, a safe, cheap and more effective drug for the treatment of PKDL is needed.

Topics: Adolescent; Adult; Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Female; Follow-Up Studies; Humans; India; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Middle Aged; Treatment Outcome

A comparative clinical trial between two newly introduced intralesional treatments for acute leishmaniasis and the established treatment of intralesionally-administered pentavalent antimony compounds was performed. Treatments were allocated randomly to a total of 63 patients who received 2% zinc sulphate, 7% sodium chloride solutions or sodium stibogluconate intralesionally. A number of patients were left without treatment as controls. Patients were followed-up for 45 days, the results showing that the three treatments gave comparable cure rates by the end of the follow-up period. However, zinc sulphate gave a high cure rate (94.8%) usually with a single injection.

Topics: Acute Disease; Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Sodium Chloride; Treatment Outcome; Zinc Sulfate

Topics: Acute Disease; Alanine Transaminase; Antimony Sodium Gluconate; Chemical and Drug Induced Liver Injury; Glutathione Transferase; Humans; Infusions, Parenteral; Leishmaniasis, Cutaneous; Military Personnel; Paromomycin; Prospective Studies; United Kingdom

Cutaneous leishmaniasis represents a difficult disease to manage in endemic areas. Systemic treatment is hampered by both expense and compliance. Side effects may play a major role in this aspect as well.. The effectiveness of intralesional treatment of leishmaniasis was investigated. Seven hundred and ten patients were treated with injections of sodium stibogluconate intralesionally. The clinical diagnosis was confirmed by demonstrating the parasite in the smears obtained from the lesion. Fine insulin needle was used to infiltrate the lesion with sodium stibogluconate (0.5 to 1.0 mL).. Generally eight injections were sufficient, but some of the complicated lesions needed up to 24 injections. Sixty-two percent of patients were men. The majority of the study population (64%) were children below 15 years of age. The results showed that 72% of lesions healed completely, 23.9% showed some improvement, while 4.1% showed some deterioration. Lesions of the lips, cheeks, chin, and neck healed faster than lesions in other parts of the body. Side effects were mild and limited to pain at the site of the injection and hyperpigmentation in those who were treated by folk medicine.. Intralesional treatment is as effective as the standard systemic antimonials. It offers a less expensive alternative and a low side effects profile. Our findings confirmed the findings of earlier workers. It is recommended for treatment of cutaneous leishmaniasis in endemic areas.

Topics: Acute Disease; Adolescent; Adult; Antimony Sodium Gluconate; Child; Child, Preschool; Female; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Treatment Outcome

To determine the relative efficacy and toxicity of stibogluconate and ketoconazole for the treatment of cutaneous leishmaniasis, a comparative trial was conducted in which 120 Guatemalan men with parasitologically proven cutaneous leishmaniasis were randomly divided into three treatment groups: sodium stibogluconate (20 mg of antimony per kilogram per day intravenously for 20 days), ketoconazole (600 mg per day orally for 28 days), and placebo. Treatment outcome was influenced by species. Among patients infected with Leishmania braziliensis, 24 (96%) of 25 in the stibogluconate group but only 7 (30%) of 23 in the ketoconazole group responded. Among Leishmania mexicana-infected patients, only 4 (57%) of 7 in the stibogluconate group but 8 (89%) of 9 in the ketoconazole group responded. These differences emphasize the importance of speciation in the treatment of leishmaniasis.

Topics: Administration, Oral; Adult; Animals; Antimony Sodium Gluconate; Follow-Up Studies; Guatemala; Humans; Injections, Intravenous; Ketoconazole; Leishmania braziliensis; Leishmania mexicana; Leishmaniasis, Cutaneous; Male

Leishmaniasis is a widely spread zoonotic disease caused by the bite of infected sandflies, particularly in developing countries. Cutaneous leishmaniasis can have a diverse range of presentations, ranging from minor skin nodules to significant mucosal damage. However, nose involvement is infrequent. Our report highlights a 15-year-old female patient with a persistent skin lesion on her nose for three months, which is a rare manifestation of cutaneous leishmaniasis. The lesion started as a raised spot with a brownish-red color and a crust but eventually developed into an ulcer that spread over the entire lobe of the nose and even moved toward the eye. Microscopic examination revealed the presence of Leishmania amastigotes, and a biopsy confirmed a diagnosis of cutaneous leishmaniasis. The patient received daily intravenous sodium stibogluconate doses of 9 mg/kg for 20 days, and three weeks later, there was a significant clinical improvement, with the ulcer beginning to heal and no more amastigotes visible on microscopic examination. It is crucial to keep cutaneous leishmaniasis in mind as a possible diagnosis for patients with skin lesions, even in regions where the condition is not prevalent.

Topics: Adolescent; Animals; Antimony Sodium Gluconate; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Ulcer; Zoonoses

Treatment responses to cutaneous leishmaniasis (CL) observed in Sri Lanka show variability, ranging from quick healing to delayed or failed responses to routine medication. The determinants of these differences in treatment response are not well defined. This study aimed to identify predictive features of treatment response and outcome in localized CL caused by Leishmania donovani, focusing on both clinical and histopathological findings in the patients.. Tissue sections (n = 103) derived from 3 mm punch biopsies of parasitologically confirmed patients were assessed. Patients were followed up weekly until complete healing of skin lesions and were reviewed at the end of 6 months and 1 year.. Healing required 7-21 weekly doses of intralesional sodium stibogluconate (IL-SSG) (mean = 12.2 ± 0.622). Twenty-nine (28.1%) patients were identified as delayed responders. None had recurred at the end of 1 year. The demographic or clinical features (age, gender, lesion type, size, location, and lesion duration) did not significantly influence the treatment response. A heavy parasite load and acanthosis were significant predictors of a delayed response to treatment (P < 0.001). Higher parasite loads were associated with inflammation of the entire dermis (P = 0.008), more intense infiltration of macrophages (p = 0.001), and epidermal atrophy (P = 0.033). Well-formed granulomas were inversely proportional to parasite loads.. Histology findings proved to be better prognostic markers than clinical features for delayed responders to treatment and will aid in targeted patient management when tissue biopsies are performed in the initial diagnosis of CL.

Topics: Antimony Sodium Gluconate; Biopsy; Correlation of Data; Humans; Inflammation; Leishmaniasis, Cutaneous

The effectiveness of systemic treatment for Leishmania tropica cutaneous leishmaniasis remains unclear. The purpose of the study is to evaluate the efficacy and safety of systemic treatments for L. tropica cutaneous leishmaniasis. This retrospective study was performed in 114 patients. Systemic treatments included liposomal amphotericin B and sodium stibogluconate. All patients underwent systemic treatment for L. tropica cutaneous leishmaniasis. Favourable treatment responses were recorded in 72.5% and 70.2% of the patients in the liposomal amphotericin B and sodium stibogluconate groups, respectively; 25.3% and 46% of those in the liposomal amphotericin B and sodium stibogluconate groups respectively, experienced at least one adverse effect. Lesions in cartilaginous areas were associated with higher treatment failure. Prior topical or systemic treatment increased the chance of future systemic treatment success. Liposomal amphotericin B was associated with a shorter intravenous treatment duration and better safety profile. Thus, liposomal amphotericin B is the treatment of choice for L. tropica cutaneous leishmaniasis.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmania tropica; Leishmaniasis, Cutaneous; Retrospective Studies

We evaluated the leishmanicidal activity of commercially available 5α-cholest-7-en-3β-ol [5α-chol], (+)-4-cholesten-3-one [(+)-4-chol] and the equimolar mixture of the two of them in promastigotes and amastigotes of two different strains of Leishmania mexicana (LCL) and (DCL). The leishmanicidal effectiveness of these sterols was determined by promastigote growth-kinetic experiments and promastigote viability using the propidium iodide staining procedure. The proliferation test was performed using the CFSE (5-Carboxyfluorescein N-succinimidyl ester) staining of parasites at different time points. To determine the leishmanicidal effectiveness of these sterols in amastigotes, we evaluated parasite killing inside of macrophages at different time points. The trypan blue exclusion test was used to determine cytotoxicity of sterols in uninfected macrophages. We included in all experiments a control group of parasites treated with 2% DMSO (Dimethyl Sulfoxide) and another one treated with the reference drug sodium stibogluconate (Sb). Our results showed that the equimolar mixture at 2000 times lower concentration presented similar leishmanicidal activity as Sb. This mixture was similarly effective at 100 times lower concentration than individual sterols tested separately indicating the existence of a synergistic effect against LCL and DCL parasites. The therapeutic index of the equimolar mixture was 10,000-16,000 times higher than the one recorded by Sb and was not cytotoxic to macrophages. Therefore, the equimolar mixture of 5α-Chol and (+)-4-chol may represent a potential alternative for the treatment of cutaneous leishmaniasis.

Topics: Antimony Sodium Gluconate; Cholesterol; Humans; Leishmania mexicana; Leishmaniasis, Cutaneous; Sterols

Cutaneous leishmaniasis (CL) is caused by Leishmania donovani in Sri Lanka. Pentavalent antimonials (e.g., sodium stibogluconate [SSG]) remain first-line drugs for CL with no new effective treatments emerging. We studied whole blood and lesion transcriptomes from Sri Lankan patients with CL at presentation and during SSG treatment. From lesions but not whole blood, we identified differential expression of immune-related genes, including immune checkpoint molecules, after onset of treatment. Using spatial profiling and RNA-FISH, we confirmed reduced expression of programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) proteins on treatment in lesions of a second validation cohort and further demonstrated significantly higher expression of these checkpoint molecules on parasite-infected compared with noninfected lesional CD68+ monocytes and macrophages. Crucially, early reduction in PD-L1 but not IDO1 expression was predictive of rate of clinical cure (HR = 4.88) and occurred in parallel with reduction in parasite load. Our data support a model whereby the initial anti-leishmanial activity of antimonial drugs alleviates checkpoint inhibition on T cells, facilitating immune-drug synergism and clinical cure. Our findings demonstrate that PD-L1 expression can be used as a predictor of rapidity of clinical response to SSG treatment in Sri Lanka and support further evaluation of PD-L1 as a host-directed therapeutic in leishmaniasis.

Topics: Adult; Antimony Sodium Gluconate; B7-H1 Antigen; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Leishmaniasis, Cutaneous; Male; Young Adult

Macrophages, within which Leishmania species replicate, generate large amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS) to kill these parasites. The present study assessed the oxidative and nitrosative stress, and specific immune enzymes in the serum of patients with cutaneous leishmaniasis (Cl) before and after treatment and in the control individuals. Serum activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), L-arginase, myeloperoxidase (MPO), and adenosine deaminase (ADA) and the levels of reduced glutathione, malondialdehyde (MDA), and nitric oxide (NO) were studied. The activities of L-arginase, MPO, and ADA and the levels of MDA and NO were significantly elevated (P < 0.001), while the activities of SOD, CAT, and GSH-Px, and the levels of reduced glutathione (GSH) were significantly (P < 0.001) reduced in untreated patients as compared with values of patients after treatment and of control individuals. The treatment, which included intramuscular injection of sodium stibogluconate and meglumine antimoniate, ameliorated these factors in comparison to the untreated group. These results suggest that oxidative and nitrosative stress may play an important role in the pathogenesis of untreated cutaneous leishmaniasis. Furthermore, the reduction in oxidative and nitrosative stress in the treated Cl patients may be due to the drug decreasing energy production by the parasite, which eventually leads to its death.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Case-Control Studies; Humans; Leishmaniasis, Cutaneous; Macrophages; Male; Meglumine Antimoniate; Nitrosative Stress; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species

The first-line treatment for Leishmania donovani-induced cutaneous leishmaniasis (CL) in Sri Lanka is intra-lesional sodium stibogluconate (IL-SSG). Antimony failures in leishmaniasis is a challenge both at regional and global level, threatening the ongoing disease control efforts. There is a dearth of information on treatment failures to routine therapy in Sri Lanka, which hinders policy changes in therapeutics. Laboratory-confirmed CL patients (n = 201) who attended the District General Hospital Hambantota and Base Hospital Tangalle in southern Sri Lanka between 2016 and 2018 were included in a descriptive cohort study and followed up for three months to assess the treatment response of their lesions to IL-SSG. Treatment failure (TF) of total study population was 75.1% and the majority of them were >20 years (127/151,84%). Highest TF was seen in lesions on the trunk (16/18, 89%) while those on head and neck showed the least (31/44, 70%). Nodules were least responsive to therapy (27/31, 87.1%) unlike papules (28/44, 63.6%). Susceptibility to antimony therapy seemed age-dependant with treatment failure associated with factors such as time elapsed since onset to seeking treatment, number and site of the lesions. This is the first detailed study on characteristics of CL treatment failures in Sri Lanka. The findings highlight the need for in depth investigations on pathogenesis of TF and importance of reviewing existing treatment protocols to introduce more effective strategies. Such interventions would enable containment of the rapid spread of L.donovani infections in Sri Lanka that threatens the ongoing regional elimination drive.

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Disease Eradication; Female; Humans; Infant; Infection Control; Leishmaniasis, Cutaneous; Male; Middle Aged; Treatment Failure; Young Adult

Leishmaniasis is a disease predominantly prevalent in the tropics, considered as one of the primary neglected diseases, preferably affects individuals of low socioeconomic status. Although this condition is well described in children, disseminated cutaneous leishmaniasis is a rare form of increasing importance and multiple cases observed in the adult population; however, still little described in children.. We present the case of a 12-year-old male, who has multiple ulcerative and nodular lesions distributed throughout the body, of ∼1 year of evolution that did not respond to antimicrobial treatment. After the diagnostic process, positive serological tests were found for leishmaniasis, with improvement in the picture after the use of sodium stibogluconate.. Disseminated cutaneous leishmaniasis is a clinical form that is described with increasing frequency and should be recognized and treated appropriately, mainly in the pediatric population, avoiding complications and sequelae.

Topics: Adult; Antimony Sodium Gluconate; Child; Humans; Leishmaniasis, Cutaneous; Male; Neglected Diseases; Peru

An increasing number of patients with cutaneous leishmaniasis (CL) are reporting to tertiary care centers in Jammu and Kashmir, an area that has previously been non-endemic for this disease. This merits consideration of CL as a major health problem of considerable epidemiological importance. The aims of this study were firstly to describe the clinico-epidemiological profile, therapeutic characteristics, and outcomes of patients with CL and secondly to highlight this union territory as a new focus of endemicity for CL.. The study included a total of 1300 patients with a mean age of 26.7 ± 18.5 years. The mean duration of the disease was 28.52 ± 13.5 weeks, ranging from 8 to 64 weeks. Lesions were noted mainly on exposed parts of the body, with the face being the most commonly affected site (89.00%). Nodulo-ulcerative plaques were the predominant lesion type observed (73.92%). The presence of Leishman-Donovan bodies could be demonstrated on SSS and histopathology in 60.69% and 39.54% of patients, respectively. The presence of a recognizable histological pattern conforming to CL and a response to a therapeutic trial of SSG was considered to be confirmatory in the remaining patients. Complete cure was achieved in 84.23% of cases during the study period. Single lesions were more likely to respond to treatment as compared to multiple lesions. The route of administration did not have any significant impact on the final outcome.. With the disease showing an escalating trend in Jammu and Kashmir, the possibility of a new focus of endemicity and its impact on public health need to be contemplated, and appropriate measures should be initiated to contain its spread.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Communicable Diseases, Emerging; Epidemiologic Studies; Female; Humans; India; Infant; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Prospective Studies; Skin; Tertiary Care Centers; Treatment Outcome; Young Adult

Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; China; Communicable Diseases, Imported; DNA, Kinetoplast; Humans; Leishmaniasis, Cutaneous; Phosphorylcholine; Psychodidae

We compared demographic, clinical, treatment, and outcome characteristics of facial cutaneous leishmaniasis (CL) and non-facial CL.. In this retrospective cohort study, polymerase chain reaction confirmed Leishmania major CL patients with ≥2 documented hospital visits, 2014-2019, were included.. Overall, 134 patients (34% and 66% with facial and non-facial CL, respectively) were included. Facial CL patients were younger (43% vs. 8% <18 years, P < 0.001), with a higher proportion of females (41% vs. 25%, P = 0.07) compared with non-facial CL. Clinical characteristics, including number and size of lesions and ulcer appearance, were similar in both the groups. Higher paromomycin/methylbenzethonium chloride ointment treatment rates were noted in facial CL (85% vs. 64%, P = 0.02). Intralesional sodium stibogluconate was given to 41% and 53% of facial CL and non-facial CL patients, respectively (P = 0.21). Cryotherapy and surgery were only used in non-facial CL patients (5% and 1% of all CL cases, respectively). Systemic treatment (oral miltefosine, intravenous [IV] sodium stibogluconate, IV liposomal amphotericin B) was used in <5% of the cases in both the groups. Overall, 84% of patients showed signs of improvement, including decreased lesion size or clinical improvement in 73% and 75% of patients, respectively. Only 5% of all cases healed without scarring. Outcome rates were similar in both groups.. Facial CL patients were younger and received more frequently Leishmania-specific topical treatment than non-facial CL patients. In contrast, the two groups were similar regarding clinical characteristics and outcome. These findings suggest differences in disease severity perception by patients and physicians.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Female; Humans; Leishmania major; Leishmaniasis, Cutaneous; Retrospective Studies

Visceral leishmaniasis (VL) or Kala-azar, primarily caused by Leishmania donovani, is a major health concern in many countries including India. Growing unresponsiveness among the parasites toward the available drugs is alarming, and so, it is necessary to decipher the underlying mechanism of such development for designing new therapeutics. Moreover, even after successful treatment, some VL patients develop apparently harmless skin lesions known as post-kala-azar dermal leishmaniasis (PKDL) which may serve as a reservoir of the parasite in the transmission cycle. Furthermore, recent reports of para-kala-azar dermal leishmaniasis (para-KDL) cases having PKDL manifestation with concomitant VL, emphasize the necessity of more attention to address complex nature of the parasite for eradicating the disease effectively. In the present study, whole genome sequencing is performed with sodium stibogluconate (SSG) sensitive and resistant L. donovani strains along with SSG sensitive para-KDL strains, derived from the clinical isolates of Indian patients to identify the genomic variations among them. Notably, the analyses of chromosome somy values and genome wide mutation profile in the coding regions reveal distinct clustering of the para-KDL strains with 24 genes being mutated uniquely in this group. Such distinguishing genomic changes among the para-KDL strains could be significant for the parasites to become dermatotropic. Overall, the study reveals a possible correlation of the development of SSG resistance and the transition towards the manifestation of PKDL with chromosome aneuploidy and non-synonymous genetic variations in the coding sequences of the L. donovani strains from Indian patients.

Topics: Antimony Sodium Gluconate; Genome, Protozoan; Humans; India; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral

The present study evaluates the efficacy of sodium stibogluconate (SSG) co-loaded with ketoconazole (KTZ) in nano-elastic liposomes (NELs) for the topical treatment of cutaneous leishmaniasis (CL). SSG-KTZ co-loaded NELs were developed and assessed for various physicochemical properties and anti-leishmanial potential. The optimized nano-vesicles have an average size of 212.8 ± 3.1 nm and entrapment efficiency of 61.2 ± 2.9%. SSG-KTZ co-loaded NELs displayed 5.37-fold higher skin permeation of SSG as compared to drug solution. SSG and KTZ displayed a synergistic interaction and flow cytometry revealed enhanced killing of DsRed Leishmania mexicana in infected macrophages. In-vitro and in-vivo anti-leishmanial studies indicated a 10.67-fold lower IC

Topics: Administration, Topical; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Carriers; Elasticity; Female; Ketoconazole; Leishmaniasis, Cutaneous; Liposomes; Mice; Mice, Inbred BALB C; Nanoparticles; Organ Culture Techniques; Random Allocation; Skin

Meglumine antimoniate (Glucantime. It was determined that none of the selected resistant

Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Resistance; Female; Genotyping Techniques; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Meglumine Antimoniate; Paromomycin; Phosphorylcholine; Real-Time Polymerase Chain Reaction; Turkey

During the outbreak of cutaneous leishmaniasis in the Kurdistan Region of Iraq that started in 2015, the course of the disease and the treatment were not consistent with the available literature. Physicians, particularly dermatologists, faced challenges with treating the cutaneous leishmaniasis lesions with high rates of treatment failure and resistance to treatment. We used Q-methodology to understand the range and diversities of opinions and the practical experiences of dermatologists about the treatment difficulties of cutaneous leishmaniasis.. This Q-methodology study was carried out in Erbil, Kurdistan Region of Iraq, and involved 37 dermatologists. A set of 40 statements related to different aspects of difficulties and uncertainties of treating cutaneous leishmaniasis was prepared. The dermatologists were requested to distribute the 40 statements into a scaled grid of nine piles from least agree to most agree. We applied by-person factor analysis using PQMethod 2.35 for the data analysis.. The analysis revealed two different viewpoints about the treatment of cutaneous leishmaniasis and a consensus viewpoint. The first viewpoint emphasized the use of sodium stibogluconate-based combination therapy, concerns with treatment failure, and lack of compliance with the treatment. The second viewpoint emphasized the lack of standard treatment and advances in the treatment of cutaneous leishmaniasis. There was a consensus between both groups of respondents about many aspects of the treatment of cutaneous leishmaniasis, including considering sodium stibogluconate the first drug of choice for cutaneous leishmaniasis treatment.. This study revealed a diversity of viewpoints and uncertainties about the effectiveness of the available treatment modalities and treatment difficulties and failure. Interrupted supply and poor quality of the available drugs and lack of a standard and advanced treatment are the main problems facing the treatment of cutaneous leishmaniasis. More research is required to determine the best treatment modalities for the different types of cutaneous leishmaniasis. There is a need for the development of treatment guidelines specific to the Iraqi context with a particular focus on the treatment of the resistant and atypical cases of cutaneous leishmaniasis.

Topics: Adult; Antimony Sodium Gluconate; Attitude; Combined Modality Therapy; Consensus; Dermatologists; Factor Analysis, Statistical; Female; Humans; Incidence; Iraq; Leishmania; Leishmaniasis, Cutaneous; Male; Middle Aged; Qualitative Research; Treatment Failure

Leishmaniasis is endemic in the Indian subcontinent with predominance of visceral leishmaniasis (VL) due to Leishmania donovani. Cutaneous leishmaniasis (CL) is uncommon, and mucocutaneous leishmaniasis (MCL) is rarely reported in this region. Recent reports reveal a changing epidemiology and atypical manifestations. A retrospective study of 52 suspected cases with cutaneous and mucosal involvement seen from January 2008 to December 2018 in a tertiary care setting in a non-endemic state in southern India is reported. Twelve patients were confirmed to have leishmaniasis; seven had MCL, two had CL, and three had post-kala-azar dermal leishmaniasis (PKDL). All cases were male, with a median age of 41.5 years (interquartile range, 30-55.5 years), and the median duration of the disease was 6 years (interquartile range, 1-9.5 years). Patients with MCL had mucosal involvement including destructive ulcero-proliferative lesions due to delayed diagnosis; none had a history of travel to countries endemic for MCL and all were attributable to L. donovani species. On the other hand, Leishmania major which was the causative species in both CL patients was associated with travel to the Middle East. Patients with PKDL presented with multiple plaques and hypopigmented patches; one had concomitant VL and all were from endemic areas. Hitherto uncommon MCL, caused by potentially atypical variants of L. donovani, has emerged as a new manifestation of leishmaniasis in this region. A high index of suspicion based on lesions seen and history of travel combined with PCR-based diagnostics are required to confirm diagnosis for the various skin manifestations of leishmaniasis.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Deoxycholic Acid; Drug Combinations; Humans; India; Itraconazole; Leishmania donovani; Leishmania major; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Middle Aged; Skin

Cutaneous leishmaniasis (CL) is a major health problem worldwide. Although CL is a common disease among children, treatment regimens for the pediatric age group are based on extrapolation of efficacy data in adults. The present study aimed to evaluate the treatment outcome of CL in preschool-age children and the factors influencing the outcome. Two hundred ninety-four children were diagnosed with CL between December 2018 and March 2019 in Sinjar Province, Iraq. All patients were treated with intralesional injections of sodium stibogluconate and followed up for 3 months after the completion of treatment. The treatment success rate was 99% (291/294). A statistically significant association was found between the number of doses per lesion and the number of lesions (

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Child, Preschool; Female; Humans; Iraq; Leishmaniasis, Cutaneous; Male

Cutaneous leishmaniasis (CL), endemic in Bolivia, mostly affects poor people in rainforest areas. The current first-line treatment consists of systemic pentavalent antimonials (SPA) for 20 days and is paid for by the Ministry of Health (MoH). Long periods of drug shortages and a lack of safe conditions to deliver treatment are challenges to implementation. Intralesional pentavalent antimonials (ILPA) are an alternative to SPA. This study aims to compare the cost of ILPA and SPA, and to estimate the health and economic impacts of changing the first-line treatment for CL in a Bolivian endemic area.. The cost-per-patient treated was estimated for SPA and ILPA from the perspectives of the MoH and society. The quantity and unit costs of medications, staff time, transportation and loss of production were obtained through a health facility survey (N = 12), official documents and key informants. A one-way sensitivity analysis was conducted on key parameters to evaluate the robustness of the results. The annual number of patients treated and the budget impact of switching to ILPA as the first-line treatment were estimated under different scenarios of increasing treatment utilization. Costs were reported in 2017 international dollars (1 INT$ = 3.10 BOB).. Treating CL using ILPA was associated with a cost-saving of $248 per-patient-treated from the MoH perspective, and $688 per-patient-treated from the societal perspective. Switching first-line treatment to ILPA while maintaining the current budget would allow two-and-a-half times the current number of patients to be treated. ILPA remained cost-saving compared to SPA in the sensitivity analysis.. The results of this study support a shift to ILPA as the first-line treatment for CL in Bolivia and possibly in other South American countries.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Bolivia; Budgets; Cost Savings; Cost-Benefit Analysis; Drug Costs; Health Care Costs; Humans; Leishmaniasis, Cutaneous; Meglumine Antimoniate

Cutaneous leishmaniasis (CL) is a parasitic disease which has a biphasic life cycle; infection by promastigotes from the sandfly reaches a wound where it is phagocytosed by macrophages, producing the amastigote (the Leishmania donovani body) in the host. A protozoan parasite transmitted by the phlebotomous sandfly causes human leishmaniasis. Cutaneous forms include classical cutaneous, mucocutaneous and post-kala-azar dermal leishmaniasis. It affects c. 300 million individuals in more than 90 nations around the globe. The cutaneous form in the Old World is caused at low altitudes mainly by L. major (which has an animal reservoir, rodents such as mouse) and in swampy regions and high altitudes by L. tropica (which has no animal reservoir). L. aethiopica and L. major lead to disseminated ulcers in Saudi Arabia, Yemen, Iraq, Iran, Pakistan, India, Tunisia, Sudan and Ethiopia, whose main electrophoretic isozyme pattern Zymodeme in Saudi Arabia is LON-4.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Ear Auricle; Humans; Leishmania donovani; Leishmaniasis, Cutaneous; Male; Skin Ulcer; Treatment Outcome

Topics: Anesthesia, Inhalation; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Retrospective Studies

Co-infection with Leishmania major and Schistosoma mansoni may have significant consequences for disease progression, severity and subsequent transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) are used as first line of treatment for Leishmania and Schistosoma infections respectively. However, there is limited insight on how combined therapy with the standard drugs impacts the host in comorbidity. The study aimed to determine the efficacy of combined chemotherapy using Pentostam (P) and PZQ in murine model co-infected with L. major and S. mansoni.. A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm to represent L. major, S. mansoni and L. major + S. mansoni respectively) and four treatment regimens [P, PZQ, P + PZQ, and PBS designating Pentostam (GlaxoSmithKline UK), Praziquantel (Biltricide. Significant changes were observed in the serum Interferon gamma (IFN-γ), and Macrophage inflammatory protein-one alpha (MIP-1α) levels among various treatment groups between week 8 and week 10 (p < 0.05). There was increased IFN-γ in the L. major infected mice subjected to PZQ and PBS, and in L. major + S. mansoni infected BALB/c mice treated with P + PZQ. Subsequently, MIP-1α levels increased significantly in both the L. major infected mice under PZQ and PBS and in L. major + S. mansoni infected BALB/c mice undergoing concurrent chemotherapy with P + PZQ between 8 and 10 weeks (p < 0.05). In the comorbidity, simultaneous chemotherapy resulted in less severe histopathological effects in the liver.. It was evident, combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni. The findings denote simultaneous chemotherapy compliments immunomodulation in the helminth-protozoa comorbidity hence, less severe pathological effects following the parasites infection. Recent cases of increased incidences of polyparasitism in vertebrates call for better ways to manage co-infections. The findings presented necessitate intrinsic biological interest on examining optimal combined chemotherapeutic agents strategies in helminth-protozoa concomitance and the related infections abatement trends vis-a-vis host-parasite relationships.

Topics: Analysis of Variance; Animals; Anthelmintics; Antimony Sodium Gluconate; Antiprotozoal Agents; Chemokine CCL3; Comorbidity; Disease Models, Animal; Drug Therapy, Combination; Interferon-gamma; Leishmania major; Leishmaniasis, Cutaneous; Liver; Mice; Mice, Inbred BALB C; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni

The present health economic evaluation in Afghanistan aims to support public health decision makers and health care managers to allocate resources efficiently to appropriate treatments for cutaneous leishmaniasis (CL) elicited by Leishmania tropica or Leishmania major.. A decision tree was used to analyse the cost and the effectiveness of two wound care regimens versus intra-lesional antimony in CL patients in Afghanistan. Costs were collected from a societal perspective. Effectiveness was measured in wound free days. The incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (NMB) were calculated. The model was parameterized with baseline parameters, sensitivity ranges, and parameter distributions. Finally, the model was simulated and results were evaluated with deterministic and probability sensitivity analyses. Final outcomes were the efficiency of the regimens and a budget impact analysis in the context of Afghanistan.. Average costs per patients were US$ 11 (SE = 0.016) (Group I: Intra-dermal Sodium Stibogluconate [IL SSG]), US$ 16 (SE = 7.58) (Group II: Electro-thermo-debridement [ETD] + Moist wound treatment [MWT]) and US$ 25 (SE = 0.48) (Group III: MWT) in patients with a single chronic CL ulcer. From a societal perspective the budget impact analysis shows that the regimens' drug costs are lower than indirect disease cost. Average effectiveness in wound free days are 177 (SE = 0.36) in Group II, 147 (SE = 0.33) in Group III, and 129 (SE = 0.27) in Group I. The ICER of Group II versus Group I was US$ 0.09 and Group III versus Group I US$ 0.77, which is very cost-effective with a willingness-to-pay threshold of US$ 2 per wound free day. Within a Monte-Carlo probabilistic sensitivity analysis Group II was cost-effective in 80% of the cases starting at a willingness-to-pay of 80 cent per wound free day.. Group II provided the most cost-effective treatment. The non-treatment alternative is not an option in the management of chronic CL ulcers. MWT of Group III should at least be practiced. The cost-effectiveness of Group III depends on the number of dressings necessary until complete wound closure.

Topics: Afghanistan; Antimony Sodium Gluconate; Antiprotozoal Agents; Cost-Benefit Analysis; Debridement; Decision Trees; Humans; Leishmaniasis, Cutaneous; Models, Statistical; Monte Carlo Method; Randomized Controlled Trials as Topic; Ulcer; Wound Healing

We evaluated, for the first time, the leishmanicidal potential of decanethiol functionalized silver nanoparticles (AgNps-SCH) on promastigotes and amastigotes of different strains and species of Leishmania: L. mexicana and L. major isolated from different patients suffering from localized cutaneous leishmaniasis (CL) and L. mexicana isolated from a patient suffering from diffuse cutaneous leishmaniasis (DCL). We recorded the kinetics of promastigote growth by daily parasite counting for 5 days, promastigote mobility, parasite reproduction by CFSE staining's protocol and promastigote killing using the propidium iodide assay. We also recorded IC

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cell Proliferation; Humans; Inhibitory Concentration 50; Kinetics; Leishmania; Leishmaniasis, Cutaneous; Macrophages; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Silver

In Algeria, the treatment of visceral and cutaneous leishmanioses (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Although treatment failure is frequently reported during antimonial therapy of both CL and VL, antimonial resistance has never been thoroughly investigated in Algeria. Determining the level of antimonial susceptibility, amongst Leishmania transmitted in Algeria, is of great importance for the development of public health policies.. Within the framework of the knowledge about the epidemiology of VL and CL amassed during the last 30 years, we sampled Leishmania isolates to determine their susceptibility to antimony. We analyzed a total of 106 isolates including 88 isolates collected between 1976 and 2013 in Algeria from humans, dogs, rodents, and phlebotomines and 18 collected from dogs in France. All the Algerian isolates were collected in 14 localities where leishmaniasis is endemic. The 50% inhibitory concentrations (IC50) of potassium antimony tartrate (the trivalent form of antimony, Sb(III)) and sodium stibogluconate (the pentavalent form of antimony, Sb(V)) were determined in promastigotes and intramacrophage amastigotes, respectively. The epidemiological cutoff (ECOFF) that allowed us to differentiate between Leishmania species causing cutaneous or visceral leishmaniases that were susceptible (S+) or insusceptible (S-) to the trivalent form of antimony was determined. The computed IC50 cutoff values were 23.83 μg/mL and 15.91 μg/mL for VL and CL, respectively. We report a trend of increasing antimony susceptibility in VL isolates during the 30-year period. In contrast, an increase in the frequency of S- phenotypes in isolates causing CL was observed during the same period. In our study, the emergence of S- phenotypes correlates with the inclusion of L. killicki (syn: L. tropica) isolates that cause cutaneous leishmaniasis and that have emerged in Algeria during the last decade.. Our results provide insight into the spatiotemporal dynamics of Leishmania antimony susceptibility in Algeria. We highlight the need for the future implementation of an effective methodology to determine the antimony susceptibility status of Leishmania isolates to detect the emergence of and prevent the dissemination of drug-resistant strains.

Topics: Algeria; Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Dogs; Drug Resistance; Humans; Inhibitory Concentration 50; Leishmania; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Psychodidae; Rodentia

Leishmaniasis is a protozoan zoonotic parasitic infection with cutaneous, mucocutaneous, and visceral manifestations. Israel is endemic for cutaneous leishmaniasis, which is a self-limited disease but is associated with scarring, which is often a source of psychological and social burden for patients. Scars can be especially devastating for children and teenagers. A wide range of physical and medical approaches is used to treat cutaneous leishmaniasis, among which intralesional injections of sodium stibogluconate rank among the most frequently used. Unfortunately, despite being effective, this therapeutic modality can be very painful. Fractional ablative laser creates a controlled mesh-like pattern of tissue ablation in the skin that promotes dermal remodeling and collagen production while at the same time facilitating enhanced delivery of topically applied medications.. Patients were treated with fractional ablative carbon dioxide laser followed by immediate topical application of sodium stibogluconate. All children were diagnosed with cutaneous leishmaniasis prior to treatment initiation... Ten children were treated. One leishmania tropica-positive girl failed to respond. The other nine patients achieved clinical cure and demonstrated good to excellent final cosmesis. Self-rated patient satisfaction and tolerance were high No adverse effects were observed or reported during treatment.. Fractional ablative carbon dioxide laser followed by topical sodium stibogluconate application appears to be a safe and promising treatment for cutaneous leishmaniasis infection in children. Future controlled studies are required to validate these findings and compare this technique with traditional approaches.

Topics: Administration, Cutaneous; Adolescent; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Humans; Lasers, Gas; Leishmania; Leishmaniasis, Cutaneous; Male; Neglected Diseases; Patient Satisfaction; Retrospective Studies; Treatment Outcome

Two pentavalent antimonials, meglumine antimoniate (Glucantime®, France) and sodium stibogluconate (Pentostam®, England), are used to treat cutaneous leishmaniasis (CL) in Turkey. The present study, serving as a guidebook for young researchers, aims to provide basis for conducting drug resistance tests and active ingredient scanning in in vitro and in vivo models.. A CL isolate kept in liquid nitrogen was initially thawed and genotyped by real-time polymerase chain reaction (PCR) using ITS1 prob. In vitro and in vivo tests were conducted to determine drug resistance against meglumine antimoniate and sodium stibogluconate. Hemocytometry and XTT (sodium 3,39-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzenesulfonic acid hydrate) methods were used to investigate in vitro drug resistance. CL mouse models were used to analyze in vivo drug resistance.. The isolate was determined as Leishmania tropica by genotyping by PCR on the internal transcribed spacer 1 (ITS1) gene region. In in vitro drug resistance tests, sodium stibogluconate was observed to be more effective than meglumine antimoniate, but there was no statistically significant difference between the two (p > 0.05). It was observed that the footpad lesions of the animals started to shrink afterward the 5th week of infection following treatment with these agents, and parasitologic recovery was observed at the end of 3 months.. With an aim to be used as a guidebook for young researchers, active ingredient scanning and drug resistance tests in both in vitro and in vivo models were presented in the current study.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Resistance; Humans; Leishmania tropica; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Mice; Microbial Sensitivity Tests; Organometallic Compounds; Pilot Projects; Practice Guidelines as Topic; Turkey

This study sought to determine the endemic Leishmania species, the clinical features of cutaneous leishmaniasis (CL) in the Central Rift Valley in Kenya and to give an account on unresponsiveness to treatment in the region.. Participants were clinically identified and grouped into untreated, classical and recidivate based on clinical manifestation and clinical data. Leishmaniasis recidivans lesions were scaly hyperemic papules that appeared before the classic lesion had healed or after healing. The demographics and socio-economic data were recorded and lesion scraping samples screened through microscopy and Internal Transcribed Spacer 1-PCR. Leishmania species were identified using Restriction Fragment Length Polymorphism.. A total of 52 participants were sampled, of which, 44.2% of the cases were recidivate and L. tropica the only species identified. All patients had been treated using sodium stibogluconate (SSG) which is the recommended first-line drug in Kenya. 60% of the patients experienced prolonged exposure to the drug (>30 days).. L. tropica is the endemic Leishmania species for CL leading to classical and leishmaniasis recidivans. Treatment of CL in the area is not effective hence, alternative measures/therapy should be considered to cope with the unresponsiveness.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Female; Humans; Kenya; Leishmania tropica; Leishmaniasis, Cutaneous; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Skin; Young Adult

Leishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis.. Clinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group.. The data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies.

Topics: Aneuploidy; Antimony Sodium Gluconate; Antiprotozoal Agents; Base Sequence; Chromosomes; Gene Dosage; Gene Ontology; Genome; Heterozygote; Homozygote; Humans; INDEL Mutation; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Open Reading Frames; Phylogeny; Polymorphism, Single Nucleotide; Virulence

This study describes the epidemiological and clinical characteristics of leishmaniasis and the pharmacological treatment of this disease in the municipality of Pueblo Rico, Risaralda, between January 2010 and December 2014. An observational study was conducted using information from the clinical records and epidemiological reports of patients diagnosed and confirmed with leishmaniasis of any age and sex, including sociodemographic, clinical, and pharmacological variables of the therapy received. Univariate and bivariate analyses were performed. A total of 539 cases of leishmaniasis were confirmed, with 29.5% occurring in children under 5 years of age. The median age was 10 years, with predominance in males (55.5%). The indigenous Emberá (aboriginal Americans) were the most affected (50.8%), and 93.3% of cases occurred in people living in scattered rural areas. All lesions corresponded to cutaneous leishmaniasis, of which 251 patients had compromise of the upper limbs (46.6%), 221 of the face (41.0%), and 139 of the lower limbs (25.8%). Pentavalent antimony salts (n-methyl glucamine and sodium stibogluconate) were prescribed in 77.6% (

Topics: Adolescent; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Colombia; Female; Humans; Leishmaniasis, Cutaneous; Male; Phosphorylcholine; Prevalence; Retrospective Studies; Socioeconomic Factors; Urban Population; Young Adult

Sodium stibogluconate (SSG, Pentostam) and meglumine antimoniate (MA, Glucantime) are two antimonials that are widely used to treat cutaneous leishmaniasis (CL), but the relative efficacies of these treatments are not clear. The aim of this study is to compare the efficacy of intralesional SSG with intralesional MA therapy in the treatment of CL. One month after completion of the therapy, 1431 of 1728 patients (82%) who received intralesional MA showed complete clinical cure compared to 1157 of 1728 patients (67%) in the SSG group. Patients who did not respond to the first round of therapy were re-administered the same treatment but with twice weekly injections. Following completion of the second course of therapy, 237 of 297 patients (80%) in the MA group and 407 of 561 patients (72%) in the SSG group healed their lesions by 1-month post-treatment. At both times, the differences in cure rates between MA and SSG groups were statistically significant (p < 0.05). Cure rates in the MA group were always significantly higher than SSG groups irrespective of other parameters including age, gender, lesion site and type of lesion. Intralesional MA is more effective than intralesional SSG in the treatment of CL.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Retrospective Studies; Young Adult

Post kala-azar dermal leishmaniasis (PKDL) is a neglected parasitic disease that occurs after apparent cure from visceral leishmaniasis (VL) and poses a challenge for elimination of VL, being its proposed reservoir. Several epidemiological studies have proposed that sex hormones may account for the increased susceptibility of males towards infectious diseases, including leishmaniasis; however, the role of testosterone and sex bias, if any, in PKDL has not been evaluated.. The study population included 87 patients with PKDL and 39 with VL; levels of testosterone were measured by competitive enzyme-linked immunosorbent assay along with their levels of antileishmanial immunoglobulin and IgG. The association of testosterone, if any, was then correlated with age, gender, humoral response, lesional profile, disease duration, and lag period.. A male predominance was evident in PKDL, not in VL; importantly, this male bias was predominant postpubertal, strongly indicative of an association between sex hormone and disease progression. Male patients with PKDL had significantly higher levels of testosterone, which regressed significantly with miltefosine, not with sodium antimony gluconate. Additionally, a significant correlation was found between plasma testosterone and antileishmanial IgG.. Taken together, our study has established a male dominance in PKDL, which showed a strong association with testosterone. This information should be taken into consideration for disease monitoring and control.

Topics: Adolescent; Adult; Amphotericin B; Antibodies, Protozoan; Antimony Sodium Gluconate; Antiprotozoal Agents; Disease Progression; Female; Humans; Immunoglobulin G; India; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Neglected Diseases; Phosphorylcholine; Sex Factors; Testosterone; Young Adult

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Canada; Female; Humans; Injections, Intralesional; Israel; Leg Dermatoses; Leishmaniasis, Cutaneous; Travel

Visceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients.. In this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient's house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development.. Out of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1-200 μg/L and 200.1-432.0 μg/L were 1.85 (1.13-3.03) and 2.31 (1.39-3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02-2.7; p = 0.04).. Our findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar.

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Arsenic; Child; Child, Preschool; Cohort Studies; Drinking Water; Environmental Exposure; Environmental Pollutants; Female; Humans; India; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Logistic Models; Male; Middle Aged; Odds Ratio; Retrospective Studies; Time Factors; Young Adult

Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans. The different clinical forms of leishmaniasis are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating leishmaniasis. Recent studies suggest that pentavalent antimony (Sb(V)) acts as a pro-drug, which is converted to the more active trivalent form (Sb(III)). However, sensitivity to trivalent antimony varies among different Leishmania species. In general, Leishmania species causing cutaneous leishmaniasis (CL) are more sensitive to Sb(III) than the species responsible for visceral leishmaniasis (VL). Leishmania aquaglyceroporin (AQP1) facilitates the adventitious passage of antimonite down a concentration gradient. In this study, we show that Leishmania species causing CL accumulate more antimonite, and therefore exhibit higher sensitivity to antimonials, than the species responsible for VL. This species-specific differential sensitivity to antimonite is directly proportional to the expression levels of AQP1 mRNA. We show that the stability of AQP1 mRNA in different Leishmania species is regulated by their respective 3'-untranslated regions. The differential regulation of AQP1 mRNA explains the distinct antimonial sensitivity of each species.

Topics: 3' Untranslated Regions; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Aquaglyceroporins; Aquaporin 1; Cell Movement; Drug Resistance; Gene Expression Regulation; Humans; Leishmania; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Meglumine; Meglumine Antimoniate; Organometallic Compounds; RNA, Messenger; RNA, Protozoan

We present a case of imported leishmaniasis in a 31-year-old woman from Slovakia, who visited the countries of South America for three months in 2011. On 29 and 31 August 2011, she was probably infected with Leishmania parasites in the jungles of Ecuador. Approximately one week after returning to Slovakia, a small papules appeared on patient's left leg. Another wound was found after two weeks. Both ulcers were enlarging. We proved amastigote forms of Leishmania spp. only in repeated dermal scrapings from the edge of the ulcer by Giemsa staining after negative results from examination of a wound scrape and biopsy specimen. We identified the species Leishmania (Viannia) panamensis as a causative agent by using the polymerase chain reaction (PCR) method and subsequent sequencing of the ITS region. Closure of wounds and scab formation were observed after 20 days of treatment with sodium stibogluconate. In the control microscopic examination after the end of the treatment, parasites were not present, and the PCR confirmed the negative result (Fig. 2, Ref. 31).

Topics: Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Disease Transmission, Infectious; Ecuador; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Polymerase Chain Reaction; Skin Ulcer; Slovakia; Travel; Treatment Outcome; Wound Healing

In this study, in vitro anti-leishmanial activity of buparvaquone was evaluated against promastigotes and intracellular amastigotes of Pakistani Leishmania tropica isolate KWH23 in relation to the current standard chemotherapy for leishmaniasis (sodium stibogluconate, sodium stibogluconate, amphotericin B and miltefosine). For buparvaquone, mean % inhibition in intracellular amastigotes at four different concentrations (1.35 µM, 0.51 µM, 0.17 µM and 0.057 µM) was 78%, 44%, 20% and 14% respectively, whereas, against promastigotes it was 89%, 77%, 45% and 35% respectively. IC50 values calculated to estimate the anti-leishmanial activity of buparvaquone against intra-cellular amastigotes and promastigotes was 0.53 µM (95% C.I. = 0.32-0.89) and 0.15 µM (95% C.I. = 0.01-1.84) respectively. Amphotericin B was the most potent in-vitro drug tested, with an IC50 of 0.075 µM (95% C.I. = 0.006-0.907) against promastigotes, and 0.065 µM (95% C.I. = 0.048-0.089) against intra-cellular amastigotes. Amphotericin B was more cytotoxic against THP1 cells, with an IC50 of 0.15 µM (95% C.I. = 0.01-0.95) and an apparent in-vitro therapeutic index of 2.0, than was buparvaquone, with an IC50 of 12.03 µM (95% C.I. = 5.36-26.96) against THP1 cells and a therapeutic index of 80.2. The study proposes that buparvaquone may be further investigated as a candidate drug for treatment of cutaneous leishmaniasis.

Topics: Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Cell Line, Tumor; Child; Humans; Inhibitory Concentration 50; Leishmania tropica; Leishmaniasis, Cutaneous; Macrophages; Male; Meglumine; Meglumine Antimoniate; Naphthoquinones; Organometallic Compounds; Pakistan; Parasitic Sensitivity Tests

Military personnel deployed to the Amazon Basin are at high risk for cutaneous leishmaniasis (CL). We responded to an outbreak among Peruvian Army personnel returning from short-term training in the Amazon, conducting active case detection, lesion sample collection, and risk factor assessment. The attack rate was 25% (76/303); the incubation period was 2-36 weeks (median = 8). Most cases had one lesion (66%), primarily ulcerative (49%), and in the legs (57%). Real-time polymerase chain reaction (PCR) identified Leishmania (Viannia) braziliensis (59/61 = 97%) and L. (V.) guyanensis (2/61 = 3%). Being male (risk ratio [RR] = 4.01; P = 0.034), not wearing long-sleeve clothes (RR = 1.71; P = 0.005), and sleeping in open rooms (RR = 1.80; P = 0.009) were associated with CL. Sodium stibogluconate therapy had a 41% cure rate, less than previously reported in Peru (~70%; P < 0.001). After emphasizing pre-deployment education and other basic prevention measures, trainees in the following year had lower incidence (1/278 = 0.4%; P < 0.001). Basic prevention can reduce CL risk in deployed militaries.

Topics: Adolescent; Antimony Sodium Gluconate; Disease Outbreaks; Female; Humans; Leishmania braziliensis; Leishmania guyanensis; Leishmaniasis, Cutaneous; Male; Military Personnel; Peru; Real-Time Polymerase Chain Reaction; Surveys and Questionnaires; Young Adult

Post Kala-azar Dermal Leishmaniasis (PKDL) is a chronic but not life-threatening disease; patients generally do not demand treatment, deserve much more attention because PKDL is highly relevant in the context of Visceral Leishmaniasis (VL) elimination. There is no standard guideline for diagnosis and treatment for PKDL. A species-specific PCR on slit skin smear demonstrated a sensitivity of 93.8%, but it has not been applied for routine diagnostic purpose. The study was conducted to determine the actual disease burden in an endemic area of Malda district, West Bengal, comparison of the three diagnostic tools for PKDL case detection and pattern of lesion regression after treatment. The prevalence of PKDL was determined by active surveillance and confirmed by PCR based diagnosis. Patients were treated with either sodium stibogluconate (SSG) or oral miltefosine and followed up for two years to observe lesion regression period. Twenty six PKDL cases were detected with a prevalence rate of 27.5% among the antileishmanial antibody positive cases. Among three diagnostic methods used, PCR is highly sensitive (88.46%) for case confirmation. In majority of the cases skin lesions persisted after treatment completion which gradually disappeared during 6-12 months post treatment period. Reappearance of lesions noted in two cases after 1.5 years of miltefosine treatment. A significant number of PKDL patients would remain undiagnosed without active mass surveys. Such surveys are required in other endemic areas to attain the ultimate goal of eliminating Kala-azar. PCR-based method is helpful in confirming diagnosis of PKDL, referral laboratory at district or state level can achieve it. So a well-designed study with higher number of samples is essential to establish when/whether PKDL patients are free from parasite after treatment and to determine which PKDL patients need treatment for longer period.

Topics: Administration, Oral; Adolescent; Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Disease Transmission, Infectious; Epidemiological Monitoring; Female; Humans; India; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Phosphorylcholine; Polymerase Chain Reaction; Prevalence; Recurrence; Rural Population; Young Adult

Cutaneous Leishmaniasis (CL) occurs in British troops deployed to Belize, Afghanistan, Iraq and elsewhere. From 1998 to 2009, 156 (45%) of 343 confirmed cases seen in the UK were in military personnel. CL is a rare disease and requires specialist clinical management because numerous pitfalls exist during diagnosis and treatment. A 19-year-old soldier developed CL on his neck 6 weeks after taking part in jungle warfare training in Belize. However, this was not suspected and the diagnosis was not made from either a skin biopsy or following surgical excision. The travel history and the patient's own photograph prompted retrospective investigations that confirmed this was CL due to Leishmania mexicana. Three months after surgery, the disease recurred locally and was treated appropriately with a good outcome. British military personnel with suspected CL should be referred to the UK Role 4 Military Infectious Diseases & Tropical Medicine Service.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Belize; Biopsy; Diagnostic Errors; Humans; Leishmaniasis, Cutaneous; Male; Military Personnel; United Kingdom; Young Adult

A 61-year-old man presented with erysipelas-like cutaneous leishmaniasis.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Cellulitis; Diagnosis, Differential; Disease Progression; DNA, Protozoan; Endemic Diseases; Erysipelas; Eyelid Diseases; Facial Dermatoses; Humans; Hypokalemia; Leishmania donovani; Leishmaniasis, Cutaneous; Long QT Syndrome; Male; Middle Aged; Pancytopenia; Spain; Travel

Limited data are available regarding topical and systemic therapies for Leishmania tropica in children.. We sought to characterize the clinical presentation and evaluate the efficacy and safety of topical and systemic treatments in pediatric patients infected with L tropica.. A retrospective study was performed on 47 children with L tropica cutaneous leishmaniasis. Treatments included topical or systemic therapy with liposomal amphotericin B or pentavalent antimony.. Seventy patients with L tropica cutaneous leishmaniasis were treated at our center between 2008 and 2012, of which 47 (67%) were children. The average age of the pediatric population was 8.8 years, and the face was the most common site of involvement (76%). The average number of lesions was 2.6. 24 children (51%) required systemic therapy. The patients were treated with 3 to 5 mg/kg/d of intravenous liposomal amphotericin B, and a response was observed in 83% of the patients within 3 months.. This was a retrospective study.. The disease burden of L tropica in children is high, and because of facial involvement and a low response to topical therapies, systemic therapy is often required. In our experience, liposomal amphotericin B treatment in children is safe and effective and is required for a considerably shorter duration than treatment with pentavalent antimony.

Topics: Administration, Cutaneous; Administration, Intravenous; Adolescent; Amphotericin B; Antimony Sodium Gluconate; Child; Child, Preschool; Cryotherapy; Facial Dermatoses; Female; Humans; Infant; Injections, Intralesional; Leishmania tropica; Leishmaniasis, Cutaneous; Male; Paromomycin; Retrospective Studies; Trypanocidal Agents

A 45-year-old woman, known case of seronegative arthritis and on immunosuppressive therapy, presented with a 2-week history of a macular lesion on the left calf that became papular and eventually ulcerated. The rest of the history was otherwise unremarkable and systemic examination did not reveal any abnormalities. The lesion was repeatedly biopsied but failed to reveal Leishmania donovani bodies. Concurrent Leishmania IgG was positive but IgM was negative. Leishmania IgG confirmatory testing by ELISA was negative. A biopsy from the lesion eventually tested positive for L. donovani through PCR. The patient was treated with sodium stibogluconate together with intravenous ciprofloxacin and amoxicillin to cover the secondary cutaneous bacterial infection. This led to complete resolution of the lesion.

Topics: Adalimumab; Amoxicillin; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antimony Sodium Gluconate; Antiprotozoal Agents; Arthritis; Ciprofloxacin; Coinfection; DNA, Protozoan; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Leishmania donovani; Leishmaniasis, Cutaneous; Methotrexate; Middle Aged

Topics: Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Injections, Intralesional; Leishmania mexicana; Leishmaniasis, Cutaneous; Male; Peru; Travel; Treatment Outcome; United Kingdom

Cutaneous leishmaniasis (CL), an uncommon disorder in South-East Asia, including Bangladesh, often presents as granulomatous plaque on the exposed areas, with a high index of suspicion required for diagnosis. Here we report the first imported case of CL caused by Leishmania tropica in a migrant Bangladeshi worker in the Kingdom of Saudi Arabia (KSA). The case, initially suspected as a case of cutaneous tuberculosis, arrived at specimens reception unit (SRU) of diagnostic labs of icddr,b being referred by the physician for ALS testing for tuberculosis. At his arrival in the SRU, one of the health personnel of the unit who used to work in KSA suspected him as a case of CL. The diagnosis was confirmed by smear microscopy which revealed plenty of amastigotes within macrophages. PCR was performed to confirm the species. He was treated with sodium stibogluconate at Shahid Suhrawardy Medical College Hospital, Dhaka.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Bangladesh; Emigrants and Immigrants; Humans; Leishmaniasis, Cutaneous; Male; Polymerase Chain Reaction; Saudi Arabia; Treatment Outcome

Cutaneous leishmaniasis (CL) is endemic in the Bikaner region situated in the Thar Desert of Rajasthan, India. This study describes clinicoepidemiological data of pediatric CL in pre-school children (0-5 years of age) from this region during 2001-2012. In total, 151 patients with 217 lesions were reported during the study period. The mean age of the study group was 3.29 ± 1.43 years (0.25-5 years), with many (41.7%) cases being in the age group of 2-4 years. Face was the most common site involved, and morphologically, the lesions were either plaque type or papulonodular. Smear for parasitologic examination was positive in 84 (70%) of 120 cases, and histopathologic examination confirmed CL in 10 (55.55%) of 18 cases. Parasite species identification conducted for 13 randomly selected patients by polymerase chain reaction identified Leishmania tropica as the causative species. Intralesional sodium stibogluconate was the most commonly used treatment and found to be well-tolerated. Other therapies that were effective included oral rifampicin, oral dapsone, radiofrequency heat therapy (RFHT), and combinations of the three therapies.

Topics: Administration, Oral; Antimony Sodium Gluconate; Child, Preschool; Dapsone; Female; Humans; Incidence; India; Infant; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Polymerase Chain Reaction; Pulsed Radiofrequency Treatment; Retrospective Studies; Rifampin

Leishmaniasis is an endemic Andean vector-borne- tropical disease in Peru, whose mucocutaneous clinical presentation is rare. Leishmaniasis can occur in co-infections with HTLV-1 virus and HIV. We describe a case of L. mucocutaneous in a patient infected with HIV, with a history of cutaneous leishmaniasis with inadequate treatment 20 years ago. He was treated with stibogluconate with adequate response to treatment and regression of lesion after 4 weeks. Mucocutaneous leishmaniasis and HIV coinfection is rare and its clinical presentation may be atypically. It is important to consider it in patients coming from endemic areas and with a history of a previous cutaneous clinical presentation.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Male

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Child, Preschool; Dermatitis; Female; Glucocorticoids; Humans; Leishmaniasis, Cutaneous

Cutaneous Leishmaniasis (CL) caused by Leishmania aethiopica is a public health and social problem with a sequel of severe and mutilating skin lesions. It is manifested in three forms: localized CL (LCL), mucosal CL (MCL) and diffuse CL (DCL). Unresponsiveness to sodium stibogluconate (Sb(V)) is common in Ethiopian CL patients. Using the amastigote-macrophage in vitro model the susceptibility of 24 clinical isolates of L. aethiopica derived from untreated patients was investigated. Eight strains of LCL, 9 of MCL, and 7 of DCL patients together with a reference strain (MHOM/ET/82/117/82) were tested against four antileishmanial drugs: amphotericin B, miltefosine, Sb(V) and paromomycin. In the same order of drugs, IC(50) (μg/ml±SD) values for the 24 strains tested were 0.16±0.18, 5.88±4.79, 10.23±8.12, and 13.63±18.74. The susceptibility threshold of isolates originating from the 3 categories of patients to all 4 drugs was not different (p>0.05). Maximal efficacy was superior for miltefosine across all the strains. Further susceptibility test could validate miltefosine as a potential alternative drug in cases of sodium stibogluconate treatment failure in CL patients.

Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cells, Cultured; Ethiopia; Humans; Inhibitory Concentration 50; Leishmania; Leishmaniasis, Cutaneous; Macrophages, Peritoneal; Mice; Parasitic Sensitivity Tests; Paromomycin; Phosphorylcholine

New World cutaneous leishmaniasis (CL) is considered in the differential diagnosis for patients with nonhealing ulcers and a history of travel to high-risk areas. For patients at risk for progression to mucocutaneous leishmaniasis, first-line treatment in the United States entails the use of sodium stibogluconate (SSG), which is obtained from the Centers for Disease Control and Prevention (CDC) under an investigational drug protocol. We report 2 cases of New World CL in travelers to endemic areas who were diagnosed and treated with SSG. These cases demonstrate the logistics of coordinating with the CDC to definitively diagnose New World CL and initiate the necessary treatment.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Centers for Disease Control and Prevention, U.S.; Diagnosis, Differential; Drugs, Investigational; Female; Humans; Leishmaniasis, Cutaneous; Male; Travel; Treatment Outcome; United States; Young Adult

Most natural host populations are exposed to a diversity of parasite communities and co-infection of hosts by multiple parasites is commonplace across a diverse range of systems. Co-infection with Leishmania major and Schistosoma mansoni may have important consequences for disease development, severity and transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) have been relied upon as a first line of treatment for Leishmania and Schistosoma infections respectively. However, it is not clear how combined therapy with the standard drugs will affect the host and parasite burden in concomitance. The aim of the current study was to determine the efficacy of combined chemotherapy using Pentostam and PZQ in BALB/c mice co-infected with L. major and S. mansoni.. The study used BALB/c mice infected with L. major and S. mansoni. A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm designated as groups infected with L. major, S. mansoni and L. major + S. mansoni, respectively) and four treatment regimens [P, PZQ, P + PZQ and PBS designating Pentostam®(GlaxoSmithKline UK), Praziquantel (Biltricide®, Bayer Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline] as factors was applied. In each treatment group, there were 10 mice. Lesion development was monitored for 10 weeks. The parasite load, body weight, weight of the spleen and liver were determined between week 8 and week 10.. Chemotherapy using the first line of treatment for L. major and S. mansoni reduced the lesion size and parasite loads but did not affect the growth response, spleen and liver. In the co-infected BALB/c mice, the use of Pentostam or PZQ did not result in any appreciable disease management. However, treatment with P + PZQ resulted in significantly (p < 0.05) larger reduction of lesions, net increase in the body weight, no changes in the spleen and liver weight and reduced Leishman-Donovan Units (LDU) and worm counts than BALB/c mice treated with Pentostam or PZQ alone.. The present study demonstrated that the combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni in BALB/c mice.

Topics: Animals; Anthelmintics; Antimony Sodium Gluconate; Coinfection; Drug Therapy, Combination; Leishmania major; Leishmaniasis, Cutaneous; Liver; Mice; Mice, Inbred BALB C; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Spleen

Conventional understanding suggests that simultaneous infection with more than one species of Leishmania is unlikely. In Peru, co-infections are clinically relevant because causative species dictates prognosis, treatment response, and follow-up. We describe a case of Leishmania (Viannia) braziliensis and L. (V.) lainsoni co-infection in a Peruvian patient with cutaneous leishmaniasis.

Topics: Adult; Antimony Sodium Gluconate; Coinfection; DNA, Protozoan; Female; Humans; Leishmania braziliensis; Leishmaniasis, Cutaneous; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Protozoan Proteins; Skin Ulcer

Obligate intracellular pathogens such as Leishmania specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase γ (PI3Kγ), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration by initiating actin polymerization and cytoskeletal reorganization, which are processes also critical for phagocytosis. In this study, we demonstrate that class IB PI3K, PI3Kγ, plays a critical role in pathogenesis of chronic cutaneous leishmaniasis caused by L. mexicana. Using the isoform-selective PI3Kγ inhibitor, AS-605240 and PI3Kγ gene-deficient mice, we show that selective blockade or deficiency of PI3Kγ significantly enhances resistance against L. mexicana that is associated with a significant suppression of parasite entry into phagocytes and reduction in recruitment of host phagocytes as well as regulatory T cells to the site of infection. Furthermore, we demonstrate that AS-605240 is as effective as the standard antileishmanial drug sodium stibogluconate in treatment of cutaneous leishmaniasis caused by L. mexicana. These findings reveal a unique role for PI3Kγ in Leishmania invasion and establishment of chronic infection, and demonstrate that therapeutic targeting of host pathways involved in establishment of infection may be a viable strategy for treating infections caused by obligate intracellular pathogens such as Leishmania.

Topics: Animals; Antimony Sodium Gluconate; Disease Resistance; Flow Cytometry; Host-Parasite Interactions; Humans; Leishmania mexicana; Leishmaniasis, Cutaneous; Macrophages; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Neutrophils; Phagocytes; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Quinoxalines; Thiazolidinediones

Leishmaniasis is a parasitic infection caused by the obligate intracellular protazoa leishmania. The most commonly encountered form is cutaneous leishmaniasis (CL), which generally manifests as a chronic, painless ulcer. Recent increases in the incidence of CL worldwide due in large part to increased immigration and international travel, combined often with the lack of familiarity with the disease in non-endemic settings, pose the continued problems of delayed diagnosis and inappropriate treatment. A case is described of imported cutaneous leishmaniasis occurring in a 48 year-old male who presented with multiple painless, progressively ulcerating lesions after returning from a one week trip to Bandiagara, Mali, West Africa. After four months of misdiagnoses and ineffective treatments, he was referred to a tropical disease specialist where the diagnosis was made with a skin biopsy followed by a tissue impression smear, culture and PCR. Appropriate treatment was initiated and the lesions resolved with minimal scarring. The goals of this case report are threefold: first, to stress the importance of associating chronic ulcers in a traveler with potential cutaneous leishmaniasis; second, to emphasize the clinical utility of PCR for the diagnosis; and third, to discuss the clinical approach to treatment.

Topics: Antimony Sodium Gluconate; Biopsy; Diagnosis, Differential; Disease Transmission, Infectious; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Mali; Middle Aged; Polymerase Chain Reaction; Skin Ulcer; Travel; Treatment Outcome

Cutaneous leishmaniasis in Ethiopia is caused mainly by Leishmania aethiopica. In this study, the response of L. aethiopica to sodium stibogluconate (SSG) and liquid nitrogen in Silti has been investigated. Patients were divided into two groups by the treating physician and were treated with either liquid nitrogen or SSG. Punch biopsy samples were collected from 54 patients with mean age of 20.61 (± 9.87 SD) years for histological characterization. The histological spectrum found to be type-1, type-2, type-3 and type-4 were 37.0%, 3.7%, 37.0% and 22.2% respectively. One hundred and three patients with a mean age of 18.4 (± 11.7 SD) years were treated with liquid nitrogen. The mean duration of the lesions before the onset of treatment was 8.5 months (± 6.7 SD). Of the 103 patients 80.6% (83/103) were cured, 13.6% (14/103) were dropouts and 5.8% (6/103) did not respond. Twenty patients with a mean age of 19.55 (+1.64 SD) years were treated with Pentostam on conventional dose. Of the 20 patients 85.0% (17/20) were cured, 10.0% (2/20) were unresponsive and 5.0% (1/20) were dropouts. The per protocol cure rate for cryotherapy and Pentostam was 93.3% and 89.5% respectively. Hence, liquid nitrogen can be used as one of the treatment options especially in resource poor settings.

Topics: Adolescent; Antimony Sodium Gluconate; Antiprotozoal Agents; Cryotherapy; Drugs, Generic; Ethiopia; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Treatment Outcome; Young Adult

Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the safety and efficacy of this approach.. We reviewed records of 67 consecutive NWCL patients, aged 17-61 years, treated as day-cases with 20 mg/kg/day SbV for up to 28 days at our UK centre. Data had been collected in a standardised format at the time of treatment using a care-record tool. Patients reported adverse-effects daily using a structured questionnaire. Blood tests and electrocardiograms were performed twice weekly to monitor for toxicity.. Parenteral SbV treatment was associated with an early, significant suppression of mean lymphocyte and platelet counts. By day four of treatment, lymphocytes reduced by 0.53×10(9)/L (CI 0.29×10(9)/L to 0.76×10(9)/L, p<0.001), and platelets by 31,000/µL (CI 16,000/µL to 46,000/µL, p<0.001). SbV was further associated with significant elevation of serum alanine transaminase concentrations, with a mean peak rise of 107 iu/L by day 13 (CI 52 iu/L to 161 iu/L, p<0.001). These disturbances were temporary and did not result in adverse clinical events. Patient-described symptoms were cumulative and at three weeks of treatment, 59.6% of patients experienced myalgia and 29.8% malaise. Treatment adherence and clinical outcomes were comparable to inpatient treatment studies. A total of 1407 individual doses of SbV resulted in only 26 nights' hospital admission, a saving of 1381 bed-days compared to inpatient treatment.. In specialist centres, NWCL patients aged below 65 years and without co-morbidities can be safely and effectively treated without hospital admission. This reduces the cost of treatment, and is much preferred by patients. Twice weekly blood and electrocardiographic monitoring may be surplus to requirement in clinically well, low-risk patients.

Topics: Adolescent; Adult; Ambulatory Care Facilities; Antimony Sodium Gluconate; Antiprotozoal Agents; Case Management; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infusions, Intravenous; Leishmania; Leishmaniasis, Cutaneous; Lymphocyte Count; Male; Medication Adherence; Middle Aged; Platelet Count; Time Factors; Travel; Treatment Outcome; United Kingdom; Young Adult

The oleanane triterpene saponin PX-6518, with known potent in vitro and in vivo activity against Leishmania donovani, was investigated for its spectrum against the cutaneous species Leishmania mexicana, Leishmania panamensis and Leishmania major.. In vitro activity was based on the reduction of amastigotes in primary peritoneal mouse macrophages. BALB/c mice were injected with 2 × 10(6) amastigotes in the base of the tail (L. panamensis and L. major) or the foot (L. mexicana) and subcutaneously treated with PX-6518 [1-10 mg/kg body weight (BW)] or Pentostam(®) (250 mg/kg BW Sb(V) eq). Evolution of skin lesions was monitored in a prophylactic dose-finding study, and early curative [6 weeks post-infection (pi)] and late curative (>8-10 weeks pi) studies.. While moderate susceptibility to PX-6518 was obtained in vitro (IC(50): 1-4 µg/mL), excellent in vivo activity was demonstrated. In the prophylactic study (six administrations on alternate days, starting at 1 day pi), PX-6518 was 100% effective at 1 mg/kg BW against L. mexicana and L. panamensis, whereas L. major lesions could be prevented at 2 mg/kg BW. In the early curative (1 mg/kg BW once a week for 4 weeks) and late curative (1 mg/kg BW twice a week for 4 weeks) studies, PX-6518 completely healed L. mexicana and L. panamensis lesions, whereas L. major lesions were reduced by ∼ 50%.. This study demonstrates that PX-6518 possesses potent and broad-spectrum prophylactic and curative efficacy against cutaneous leishmaniasis in the BALB/c mouse model. L. major was the least susceptible species tested and parasitological cure could not be obtained.

Topics: Animals; Antibiotic Prophylaxis; Antimony Sodium Gluconate; Leishmania donovani; Leishmania major; Leishmania mexicana; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Macrophages; Mice; Mice, Inbred BALB C; Saponins; Triterpenes

Topics: Administration, Oral; Antimony Sodium Gluconate; Antiparasitic Agents; Biopsy, Needle; Drug Administration Schedule; Drug Resistance; Follow-Up Studies; Humans; Immunohistochemistry; Infusions, Intravenous; Leishmaniasis, Cutaneous; Male; Nitro Compounds; Retreatment; Severity of Illness Index; Thiazoles; Treatment Outcome; Young Adult

Skin lesions occur frequently in travelers to tropical countries. Military personnel acquire skin lesions regularly during jungle training as did Dutch troops who trained in the jungle of Belize in 1998, 2004 and 2009, in an area endemic for cutaneous leishmaniasis. Demographic and clinical data were collected retrospectively. Diagnostic investigations for cutaneous leishmaniasis included Giemsa stain, culture, PCR and NASBA and histopathology of biopsies. Treatment of leishmaniasis was with sodium stibogluconate, given intravenously or intralesionally, the latter with cryotherapy. In 1998 and 2004 cutaneous leishmaniasis due to Leishmania braziliensis and Leishmania mexicana infection was diagnosed in 25 persons out of 99 (attack rate 25.2%) and 14 persons out of 80 (attack rate 17.5%) respectively. In 2009 cutaneous leishmaniasis was not acquired. Skin problems were common during and after jungle training. Cutaneous leishmaniasis was important in the first two cohorts but not observed in the third cohort. Factors that could have played a role in the absence of cutaneous leishmaniasis in the third cohort include variability in transmission and availability of better preventive measures and adherence to these. Sodium stibogluconate treatment, intralesional or intravenous, was effective.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Belize; Humans; Leishmania braziliensis; Leishmania mexicana; Leishmaniasis, Cutaneous; Middle Aged; Military Personnel; Netherlands; Retrospective Studies; Skin; Treatment Outcome; Trypanocidal Agents

Topics: Antimony Sodium Gluconate; Cheek; Child; Diagnosis, Differential; Female; Humans; Leishmaniasis, Cutaneous; Skin; Trypanocidal Agents

Visceral leishmaniasis (VL) is an important cause of morbidity and mortality that affects multiple organs. Post-kala-azar ocular involvement is a serious complication that can manifest as blepharo-conjuctivitis or pan-uveitis. Failure of prompt diagnosis and treatment can result in blindness. We report five cases with pan-uveitis that followed the successful treatment of VL and consequent post-kala-azar dermal leishmaniasis were presented. Two patients lost their sight permanently but the rest were successfully treated. A high index of suspicion and prompt treatment are of paramount importance in order to avoid blindness following post-kala-azar ocular uveitis.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Blindness; Child; Eye Infections, Parasitic; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Panuveitis

Topics: Antimony Sodium Gluconate; Humans; Hyperthermia, Induced; Leishmania; Leishmaniasis, Cutaneous; Paromomycin; Radio Waves; Treatment Outcome

Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+) T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx), a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+) T cells.. We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.. These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Biological Products; Diphtheria Toxin; Drug Therapy, Combination; Humans; Immunologic Factors; Interleukin-2; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Treatment Outcome

Leishmaniasis is an uncommon infectious disease in the UK with a variety of clinical presentations. Physicians should remember to consider this diagnosis in patients with an appropriate travel history (including the Mediterranean basin) and seek help with diagnostics from a specialised parasitology laboratory. Treatment regimens may be unfamiliar to the general physician, and thus should also be discussed with an expert.

Topics: Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Immunocompromised Host; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Middle Aged

Post-kala-azar dermal leishmaniasis (PKDL) is a cutaneous complication appearing after treatment of visceral leishmaniasis, and PKDL patients are considered infectious to sand flies and may therefore play a role in the transmission of VL. We estimated the risk and risk factors of PKDL in patients with past VL treatment in south-eastern Nepal.. Between February and May 2010 we traced all patients who had received VL treatment during 2000-2009 in five high-endemic districts and screened them for PKDL-like skin lesions. Suspected cases were referred to a tertiary care hospital for confirmation by parasitology (slit skin smear (SSS)) and/or histopathology. We calculated the risk of PKDL using Kaplan-Meier survival curves and exact logistic regression for risk factors.. Out of 680 past-treated VL patients, 37(5.4%) presented active skin lesions suspect of PKDL during the survey. Thirty-three of them underwent dermatological assessment, and 16 (2.4%) were ascertained as probable (2) or confirmed (14) PKDL. Survival analysis showed a 1.4% risk of PKDL within 2 years of VL treatment. All 16 had been previously treated with sodium stibogluconate (SSG) for their VL. In 5, treatment had not been completed (≤ 21 injections). Skin lesions developed after a median time interval of 23 months [interquartile range (IQR) 16-40]. We found a higher PKDL rate (29.4%) in those inadequately treated compared to those who received a full SSG course (2.0%). In the logistic regression model, unsupervised treatment [odds ratio (OR) = 8.58, 95% CI 1.21-374.77], and inadequate SSG treatment for VL in the past (OR = 11.68, 95% CI 2.71-45.47) were significantly associated with PKDL.. The occurrence of PKDL after VL treatment in Nepal is low compared to neighboring countries. Supervised and adequate treatment of VL seems essential to reduce the risk of PKDL development and active surveillance for PKDL is needed.

Topics: Adolescent; Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cohort Studies; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Nepal; Prevalence; Psychodidae; Retrospective Studies; Risk Factors; Time Factors; Young Adult

Topics: Adolescent; Antimony Sodium Gluconate; Antiprotozoal Agents; Biopsy; Combined Modality Therapy; Cryotherapy; Diagnosis, Differential; Facial Dermatoses; Female; Humans; Leishmaniasis, Cutaneous; Saudi Arabia; Syria; Travel

A nine year aged male presented with facial lesions and the problem of responding to conventional treatment of leishmaniasis. Multiple injections of antimony and several topical ointments had been administered in hospital but fresh lesions erupted with potential to disfigure. Smears examined from nodular lesions confirmed presence of Leishmania amastigotes and parenteral pentostam was commenced for over eight weeks. A partial clinical outcome was achieved judged by extent of re-epithelialisation. Combined therapy of pentostam and oral allopurinol at a dose of 7mg/kg/day was started and finalised at 120 days. All facial lesions receded and 100% re-epithelialisation of the lesions established.

Topics: Administration, Oral; Allopurinol; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Drug Therapy, Combination; Humans; Kenya; Leishmaniasis, Cutaneous; Male

We have established Leishmania tropica as the causative agent of cutaneous leishmaniasis (CL) in the region of India where the disease is endemic. The association between localized and circulating levels of immune-determinants in CL patients was evaluated. Reverse transcription-polymerase chain reaction analysis revealed up-regulation of interferon-gamma (IFN-gamma), interleukin (IL)-1beta, IL-8, tumour necrosis factor-alpha (TNF-alpha), IL-10 and IL-4 in dermal lesions at the pretreatment stage (n = 31) compared with healthy controls (P < 0.001) and a significant down-regulation after treatment (n = 14, P < 0.05). The results indicated that an unfavourable clinical outcome in CL was not related to an inadequate T helper 1 (Th1) cell response, but rather to impairment in multiple immune functions. Comparative assessment of treatment regimes with rifampicin (RFM) or sodium antimony gluconate (SAG) revealed tissue cytokine levels to be significantly reduced after treatment with RFM (P < 0.005), while no significant decrease was evident in the levels of IFN-gamma, TNF-alpha and IL-10 (P > 0.05) as a result of treatment with SAG. Increased transcripts of monocyte chemoattractant protein-1 (MCP-1) (P < 0.001) and inducible nitric oxide synthase (iNOS) (P < 0.05) were evident before treatment in tissue lesions and remained high after treatment. Immunohistochemistry demonstrated strong expression of myeloperoxidase (MPO) and IL-8, and moderate expression of iNOS in dermal lesions. The expression levels of IL-8, MCP-1 and nitric oxide (NO) were high in patient sera before treatment, as determined using cytokine bead array and enzyme-linked immunosorbent assay (ELISA). At the post-treatment stage, the serum IL-8 levels had decreased; however, the levels of MCP-1 and NO remained high. These data suggest that IL-8 is an effector immune-determinant in the progression of CL, whereas NO facilitates the parasite killing by macrophages via MCP-1-mediated stimulation.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Chemokine CCL2; Child; Child, Preschool; Female; Humans; India; Interferon-gamma; Interleukin-10; Interleukin-4; Interleukin-8; Leishmania tropica; Leishmaniasis, Cutaneous; Macrophages; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase Type II; Nucleic Acid Synthesis Inhibitors; Peroxidase; Retrospective Studies; Rifampin; Th1 Cells; Tumor Necrosis Factor-alpha; Up-Regulation

Cutaneous leishmaniasis (CL) is caused by Leishmania major and L. tropica in the old world. Bikaner, the 'Thar Desert', situated in the north-western corner of India, is an endemic pocket for CL caused by L. tropica. Skin lesions of CL heal slowly, causing disfiguring scars if remaining untreated. Current recommended treatment for CL comprises systemic administration of sodium stibogluconate (SSG) for 2-3 weeks. Five to seven injections of SSG intralesionally have also been found to be effective.. To determine the efficacy of a short-duration, twice-weekly intralesional SSG treatment for CL.. Two hundred and twenty patients with CL having 298 lesions were included in the present study. They were divided into groups A and B (110 patients each). Patients were treated with five to seven intralesional injections of SSG in doses of 50 mg cm(-2) of lesion either once (group A) or twice (group B) weekly. Improvement was recorded at 6, 8, 10, 12, 16, 20 and 24 weeks and the rate of complete cure was compared.. Complete cure rate at 6, 8 and 10 weeks was higher (20%, 57% and 73%, respectively) in group B as compared with group A (12%, 36% and 62%, respectively). The differences in cure rates at these time points were statistically significant (P < 0.05). The complete cure rate at 24 weeks was similar in both groups (96% in group B and 92% in group A). The remaining 4% and 8% of patients in groups B and A were 'nonresponders', respectively. No major side-effects were observed in either group. In all cured cases, there were no relapses reported up to 2 years after treatment.. A short-duration, twice-weekly intralesional SSG treatment for CL accelerates cure and is highly effective and well tolerated.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; India; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Young Adult

Cutaneous leishmaniasis is endemic in Israel. Leishmania major is the most prevalent species that cause cutaneous leishmaniasis. Current treatment options are limited and there are few investigations in search of alternative ones.. This study aims to assess our experience with intralesional sodium stibogluconate (SSG) in the treatment of cutaneous leishmaniasis.. A retrospective evaluation for all adult cases of cutaneous leishmaniasis treated by intralesional and intravenous SSG (Pentostam, GlaxoSmithKline) between 2004 and 2006 was performed, for cases referred to a tertiary care university-affiliated medical centre in Israel. Intralesional SSG was injected at 0.5 mL per lesion (50 mg). Treatment was repeated every 2-3 weeks for a total of 12 weeks. Intravenous SSG was administered at a dose of 20 mg/kg for 10-20 days.. Thirty-three cases of cutaneous leishmaniasis were treated with intralesional SSG during the study period. The patients consist of 26 males and 7 females, mostly Israeli military personnel, and there were a total of 93 lesions. Within 3 months from treatment onset, 91% (30/33) had completed healing of the cutaneous lesions after an average of 3 treatments (range 1-6). Side-effects were mild and were mostly pain during injection, with two patients developing mild local site reaction after the injection.. Intralesional SSG treatment is safe, effective and well tolerated with minimal side-effects.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged; Retrospective Studies

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Belize; Fingers; Hand Dermatoses; Humans; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Military Personnel; Skin Transplantation; Travel; Young Adult

25 years old HIV-positive farmer on Anti-retroviral therapy from North Ethiopia with PKDL occurring as IRIS is reported. He developed popular and nodular lesions on the face, chest and arms (Grade II severe PKDL) one month after anti-retroviral therapy initiation, who had history of therapy for visceral leishmaniasis (VL) one year back. PKDL manifesting as IRIS after ART initiation in previously treated case for VL was among the few reported case in the world. The case is presented and discussed with the few available review literatures.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antimony Sodium Gluconate; HIV Seropositivity; Humans; Immune Reconstitution Inflammatory Syndrome; Leishmaniasis; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male

Topics: Adult; Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Biopsy; Female; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Middle Aged; Phosphorylcholine; Pregnancy; Treatment Outcome

The present work aimed to determine the risk factors, lesion pattern and effective therapy of emerging ZCL in Sirte-Libya. The study was carried out on 163 patients referred to health centers of Al-Gadaheya and Al-Hisha villages in the years 2006 & 2007. Methods consisted of a predesigned questionnaire (personal and demographic data), clinical examination of lesions, and parasitological examination by slit smear, treatment and follow up. Results showed an annual incidence of 0.95%, with onset peak during autumn months. Important local risk factors included: increased occupational exposure of farmers and construction worker to infection from fat sand rat burrows, facilitated by lack of prevention knowledge and prophylactic measures; close association of bad-ventilated animal shelters to houses, and increased soil moisture by warm spring ponds. The majority of lesions were multiple (73%) located on legs, arms, and face 66.8%, 52.1% and 41.1%. Most lesions were active 1-2 month duration and 1-3 cm size, ulcerative type (77.3%), and papulo-nodular (21.5%). Giemsa slit smear proved quite reliable for active lesions, confirmed 79.5% of lesions. The majority of lesions (60.1%) were treated by intra-lesional Pentostam. Systemic route was restricted to facial, over-joint, multiple or large lesions producing, good response in 31.9%. Cryotherapy and oral Fluconazole gave satisfactory response in 5.5% & 2.5% of cases.

Topics: Adolescent; Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Cryotherapy; Disease Reservoirs; Female; Fluconazole; Humans; Incidence; Leishmaniasis, Cutaneous; Libya; Male; Occupational Diseases; Rats; Risk Factors; Seasons; Young Adult

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Iraq; Leishmaniasis, Cutaneous; Lip Diseases; Male; Military Personnel; United States

Treatment for cutaneous leishmaniasis (CL) with standard pentavalent antimonial therapy is hampered by cumbersome administration, toxicity, and potential failure. Knowledge of factors influencing treatment outcome is essential for successful management.. A case-control study of incident cases was performed with patients experiencing their first CL episode. The standard treatment for CL for these patients was 20 mg/kg/day of sodium stibogluconate for 20 days. Clinical and epidemiological data were recorded, and parasite isolates were species typed. Patients were followed up for 6 months to assess treatment outcome. Clinical cure was defined as complete wound closure and re-epithelization without inflammation or infiltration; new lesions, wound reopening, or signs of activity were classified as treatment failure. Descriptive, bivariate, and logistic regression analyses were performed.. One hundred twenty-seven patients were recruited; 63 (49.6%) were infected with Leishmania (Viannia) peruviana, 29 (22.8%) were infected with Leishmania (Viannia) braziliensis, 27 (21.3%) were infected with Leishmania (Viannia) guyanensis, and 8 (6.3%) were infected with other species. Only patients infected with the 3 most common species were selected for risk-factor analysis (n=119). Final failure rate at 6 months was 24.4% (95% confidence interval [CI], 16.5%-32.1%), with 96% of failures occurring within the first 3 months of follow-up assessment. Risk factors for treatment failure identified in the final multivariate model were age (per year, odds ratio [OR], 0.95; 95% CI, 0.92-0.99; P=.017), stay of <72 months in area of disease acquisition (OR, 30.45; 95% CI, 2.38-389.25; P=.009), duration of disease <5 weeks (OR, 4.39; 95% CI, 1.12-17.23; P=.034), additional lesion (per lesion, OR, 2.06; 95% CI, 1.3-3.28; P=.002), infection with L. (V.) peruviana (OR, 9.85; 95% CI, 1.01-95.65; P=.049), and infection with L. (V.) braziliensis (OR, 22.36; 95% CI, 1.89-263.96; P=.014).. The identification of parasite species and clinical risk factors for antimonial treatment failure should lead to an improved management of CL in patients in Peru.

Topics: Adolescent; Adult; Age Factors; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Case-Control Studies; Child; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Peru; Prospective Studies; Risk Factors; Treatment Failure

Sodium stibogluconate has been associated with the reactivation of varicella zoster virus (VZV) in otherwise healthy adults who receive the drug as treatment for cutaneous leishmaniasis. Ten patients receiving daily sodium stibogluconate underwent phlebotomy at baseline and at day 10. Flow cytometry-based immunophenotyping, VZV-specific IgG levels, and lymphocyte proliferative responses and intracellular cytokine secretion to VZV, cytomegalovirus, tetanus toxoid, superantigen, and mitogens were performed at both time points. The absolute number of total leukocytes, total lymphocytes, and lymphocyte subsets decreased overall without predilection for any particular subset of lymphocytes, such that the percentage of the total lymphocyte population for each lymphocyte subset did not change significantly (except for a marginal increase in percentage of cytotoxic T cells). Antibodies to VZV were measured in seven patients before and after treatment, and did not change. Lymphocyte proliferative responses to VZV and other antigens and mitogens did not change from baseline. The mechanism for the increased rate of VZV reactivation after treatment with sodium stibogluconate remains undefined.

Topics: Adult; Antigens, Viral; Antimony Sodium Gluconate; Antiprotozoal Agents; CD4-Positive T-Lymphocytes; Herpesvirus 3, Human; Humans; Interferon-gamma; Interleukin-2; Leishmaniasis, Cutaneous

New World cutaneous leishmaniasis among Israeli travelers is mostly acquired in the Amazon Basin of Bolivia where Leishmania viannia (V.) braziliensis is endemic. Treatment with systemic pentavalent antimonial compounds is effective in achieving clinical cure in only 75% of cases. In this study, we assessed liposomal amphotericin B (AmBisome) as an alternative treatment for cutaneous L (V.) braziliensis infection.. A prospective evaluation was performed for cutaneous leishmaniasis due to L (V.) braziliensis, proven by polymerase chain reaction. A 3-mg/kg AmBisome dose was given for 5 consecutive days, and a sixth dose on day 10, all in an outpatient setting. This therapy was compared with a series of historical patients who were treated with sodium stibogluconate (SSG).. Seven consecutive patients, 5 males and 2 females, received AmBisome treatment. All were returned travelers infected in Bolivia; their mean age was 23.1 years; 5 had failed to respond to a full course of SSG; two had a primary lesion; none had mucosal lesions. All achieved complete clinical cure within less than 1 month. Mean follow-up of 12 months revealed no relapses. Side effects were mild, and none had to terminate treatment prematurely. Comparison of AmBisome to SSG treatment shows that the former is safer, with fewer recurrence rates. Additionally, the expense of the total care with AmBisome is less than with SSG: 45% less if SSG was given in an inpatient setting; 15% less when SSG was given in an outpatient setting.. This was a nonrandomized study, with relatively few patients.. AmBisome treatment for L (V.) braziliensis appears to be effective, better tolerated, and to have more cost benefit in countries where hospital-care costs are significant.

Topics: Adult; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Prospective Studies; Risk Assessment; Severity of Illness Index; Skin Diseases, Infectious; Treatment Outcome

Patients with certain diseases appear to be at greater risk of developing adverse drug interactions, either because of the disease state itself or the drugs used to treat it. The effects of streptozotocin-induced diabetes and/or cutaneous Leishmania major infection on the pharmacokinetics of antimony (SbV) have now been investigated, in hamsters treated with sodium stibogluconate (Pentostam). The animals were randomly divided into five groups, each of 20 hamsters, known as D (for diabetes without leishmaniasis), DL (diabetes induced prior to the leishmaniasis), L (leishmaniasis without diabetes), LD (diabetes induced after leishmanial infection) and C (the control group, of animals with neither diabetes nor leishmaniasis). After its diabetes and/or leishmaniasis (if any) was established, each animal was given an intramuscular dose of sodium stibogluconate (80 mg/kg) each day for 3 weeks. Blood samples were collected after the first or last doses, to allow the pharmacokinetic parameters of SbV after single and multiple dosing to be compared. Although the between-dose interval (24 h) was more than 10 times longer than the terminal elimination rate constant (t1/2) at steady state, there was a significant increase in the mean peak SbV concentration (Cmax), as the result of multiple dosing, in all five groups (P<0.001 for each). The hamsters with diabetes showed the least accumulation of SbV in their blood, whether or not they were infected with L. major. In the non-diabetic animals of groups L and C, the apparent total clearance of SbV (CL/F) was decreased by multiple dosing, being, respectively, 34.5% and 23.0% lower after the 21st dose than after the first. An increase in urine volume was the reason for the significant increase in CL/F in group D (P<0.001), and this offset the decrease in CL/F seen in the L group, resulting in no change in CL/F in the animals of the DL group. Three weeks of antileishmanial treatment produced no significant reductions in the leishmanial lesions on the parasite-inoculated foot-pads of the hamsters in the L or DL groups but such reductions were detected in the animals of the LD group (P<0.001). In conclusion, it appears that the administration of SbV over a few weeks may cause renal toxicity and, in clinical use, should therefore be accompanied by the regular monitoring of renal function. A cautious increase in SbV dosing may be necessary for the effective treatment of L. major (and perhaps other species of Leishmania) in diab

Topics: Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Cricetinae; Diabetes Mellitus, Experimental; Drug Administration Routes; Female; Leishmaniasis, Cutaneous; Male

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Cicatrix; Facial Dermatoses; France; Humans; Leishmania infantum; Leishmaniasis, Cutaneous; Male

Cutaneous leishmaniasis is an established disease in Sri Lanka. The majority of cases have been reported from the North-Central Province, with the southern parts of the country considered less affected. However, during 2004, when the services of a dermatologist were available, a considerable number of patients were referred from the Southern Province, which formed the basis for this study. The clinical pattern, detailed geographical distribution within the Southern Province and periodicity of the cases were studied over a period of 12 months. Of the 113 patients diagnosed, the highest number was within the 10-19 years age group. Most patients were from densely populated rural areas around Matara, a large town within this province. There was a notable increase in the number of cases presenting during February-March and August-September, which are periods following monsoonal rains. Exposed areas of the skin were commonly affected, with the majority of patients having single lesions. Females and males were equally affected. This is in contrast to our previous findings in the North-Central Province where the majority of patients were male soldiers with multiple lesions.

Topics: Adolescent; Adult; Age Distribution; Aged; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged; Retrospective Studies; Sri Lanka

Cutaneous leishmaniasis (CL) is a major health problem in endemic areas of Iran. The pentavalent antimony (SbV) based drug Glucantime is the first line of treatment for CL in Iran, but recently SbV-resistant Leishmania tropica isolates derived from unresponsive patients were reported. We show in this study that these resistant parasites are cross-resistant to the other SbV-containing drug Pentostam and at least for one isolate also to amphotericin B. However, these resistant isolates were shown to be sensitive to miltefosine and paromomycin. The latter two drugs could thus be useful alternatives for the treatment of leishmaniasis in Iran even for SbV-resistant isolates.

Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Resistance; Humans; Iran; Leishmania tropica; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Parasitic Sensitivity Tests; Paromomycin; Phosphorylcholine

A 50 year-old man, a United States resident, presented in Texas with a violaceous non-ulcerating lesion, involving the entire lower eyelid. The patient had traveled to a jungle area of Belize several hours drive from the capital city. Leishmania mexicana was isolated. The lesion only partially resolved after an initial course of sodium stibogluconate, requiring retreatment. At two years of follow-up, there was no relapse. The parasite isolated from the patient caused a progressive, non-ulcerating lesion in an experimental mouse footpad infection. This is an unusual case of cutaneous leishmaniasis in a traveler. Travelers must be educated about personal protective measures to prevent exotic infections acquired during travel.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Belize; Eyelid Diseases; Humans; Leishmania mexicana; Leishmaniasis, Cutaneous; Male; Middle Aged; Travel; Treatment Outcome

We present a 42-year-old man who was admitted with worsening of his general condition and facial skin lesions. He had previously been diagnosed with HIV infection and visceral leishmaniasis (VL). Diagnostic work-up revealed a new relapse of VL paralleled by the diagnosis of post-kala-azar dermal leishmaniasis (PKDL). The patient was treated with IV liposomal amphotericin B as well as sodium stibogluconate followed by oral hexadecylphosphocholine (miltefosine) over a period of 9 months. PKDL lesions began to disappear after 8 months of treatment. In addition, severe and relapsing VL so far remains in remission. This case demonstrates successful treatment of PKDL and relapsing VL in a Western European patient with HIV infection.

Topics: Adult; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Europe; Germany; HIV Infections; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Liposomes; Male; Phosphorylcholine; Recurrence; Treatment Outcome

Use of parenteral pentavalent antimonials to treat leishmaniasis is associated with a range of cardiological, biochemical and haematological adverse effects. The most serious of these is the development of ventricular tachyarrhythmias associated with prolongation of the electrocardiographic rate-corrected QT interval (QTc). Whereas some studies have reported that serious cardiological and biochemical adverse effects are common and often require treatment interruption or discontinuation, others have reported the drugs to be well tolerated. We conducted a detailed retrospective analysis of adverse events among British returned travellers (n=65) with New World cutaneous or mucosal leishmaniasis who received i.v. sodium stibogluconate (SbV) for >or=21 days. The mean+/-SEM QTc progressively increased from 389+/-3.1 msec to 404+/-2.9 msec during 3 weeks of treatment and the QTc reached the threshold for potential cardiac toxicity among 6 (10%) patients during the third week of treatment. Marked QTc prolongation and ventricular tachyarrhythmias occurred in one elderly patient with hypokalaemia and pre-existing cardiovascular morbidity. Although increased serum concentrations of amylase and hepatic transaminases were observed among 67% and 85% of patients respectively, none developed clinical pancreatitis or hepatitis and treatment modification was not required. SbV can be used safely in this population with adequate monitoring and the need for treatment interruption is uncommon. Identification of factors before and during treatment that may increase the risk of QTc prolongation and arrhythmias is important.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimony Sodium Gluconate; Antiprotozoal Agents; Arrhythmias, Cardiac; Electrocardiography; Female; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Middle Aged; Retrospective Studies; Travel

We report the case of a patient with Indian post-kala-azar dermal leishmaniasis (PKDL) who failed to show any response to 2 months' treatment with sodium stibogluconate. Six months later he was treated with oral miltefosine on a compassionate basis as an off-label indication. Miltefosine was given 100mg daily in divided doses for an initial 8 weeks. Due to insufficient response, the treatment was extended up to a total of 12 weeks. The patient showed an excellent response to treatment, and after 12 months of follow-up there was complete healing of all cutaneous lesions. Oral miltefosine appears to be an important alternative for the treatment of PKDL in India and confirmatory studies in controlled clinical trials are needed.

Topics: Administration, Oral; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Injections, Intravenous; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Phosphorylcholine; Treatment Outcome

By injecting uninfected rabbits intradermally with one of the test compounds or the isotonic saline (0.9% NaCl) used as a control, the possible mechanisms of the indirect action of some drugs used intralesionally in the treatment of human cutaneous leishmaniasis [sodium stibogluconate, 2% zinc sulphate, and hypertonic (7% NaCL) saline] were explored. The 24 injected rabbits (six for the control and six for each test compound) were followed up for 30 days, both macroscopically, with checks for erythema and increases in skin thickness, and microscopically, with the histopathological examination of sections of biopsies from the injection sites. Although the microscopy revealed inflammatory-cell infiltration, beginning with eosinophils, followed by lymphocytes and finally by the proliferation of fibroblasts, at all of the injection sites, these changes were most intense with the sodium stibogluconate and 2% zinc sulphate, less marked with the hypertonic saline, and minimal and relatively short-lived with the isotonic saline. Presumably as a result of their metal content, sodium stibogluconate and zinc sulphate each probably induce tissue damage and, subsequently, severe inflammatory changes. The antileishmanial activity of hypertonic saline, however, may be entirely attributable to its osmotic effects.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cell Count; Eosinophils; Erythema; Female; Fibroblasts; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Leukocyte Count; Lymphocytes; Male; Rabbits; Saline Solution, Hypertonic; Skin; Zinc Sulfate

Sodium stibogluconate (Pentostam(R); GlaxoSmithKline) is a pentavalent antimonial compound used in the treatment of leishmaniasis, which has an association with reactivation of varicella zoster virus (VZV). We report the first known case of an immunocompetent adult who developed VZV aseptic meningitis and dermatomal herpes zoster during treatment with sodium stibogluconate.

Topics: Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Diagnosis, Differential; Encephalitis, Varicella Zoster; Herpes Zoster; Humans; Leishmania major; Leishmaniasis, Cutaneous; Male; Skin Diseases, Viral

Topics: Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Diagnosis, Differential; Humans; Infusions, Intravenous; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Remote Consultation; Skin Ulcer

Individuals with visceral leishmaniasis, or kala azar (KA) and individuals with post-KA dermal leishmaniasis (PKDL) are considered to be reservoirs of transmission of Leishmania donovani in India. When intracellular amastigotes were used to assess the natural susceptibility that PKDL isolates and KA isolates have to sodium antimony gluconate (SAG), the mean ED(50) was found to be 12.0+/-2.49 and 11.0+/-1.38 microg/mL, respectively; and there was a significant correlation with the clinical response (r rank=0.99). All KA isolates, as well as a significant proportion (55%) of PKDL isolates from high-endemicity zones, were resistant to SAG. The median ED(50) for SAG-resistant PKDL isolates (20.0 microg/mL) was significantly higher (P<.05) than that for SAG-resistant KA isolates (15.7 microg/mL). SAG-resistant PKDL isolates may contribute to KA's increased refractoriness to SAG, via anthroponotic transmission of SAG-resistant strains.

Topics: Adolescent; Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Disease Reservoirs; Disease Transmission, Infectious; Drug Resistance; Endemic Diseases; Female; Humans; India; Insect Vectors; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Mice; Middle Aged; Rhodamine 123

Weaknesses in the multistep process of admixture preparation and administration resulted in a patient with cutaneous leishmaniasis (CL) receiving a 10-fold intravenous (IV) overdose of Pentostam (sodium stibogluconalte), a rarely used drug.. A review of this adverse event resulted in five recommendations: (1) Provide staffing continuity among pharmacists and pharmacy technicians preparing and nurses administering the admixture; (2) Take time to ensure thorough and deliberative consideration ofquestions or concerns about admixture preparation; (3) Use due diligence in performing double checks of admixture calculations; (4) Know the drug and seek clarification when appropriate; and (5) Examine label information carefully. PROGRESS UPDATE: Two changes were made to improve patientsafety. First, a form was developed to accompany the preparation of complex IV drugs, including chemoltherapy solutions and nonformulary IV admixtures; the form is consistently used. Second, the pharmacy service developed information sheets for 12 high-risk drugs frequently used in IV admixtures.. The medical center had processes in place to prevent medication errors, yet an error occurred nonetheless. Weaknesses were identified in staff communication, quality assurance checks, and product labeling. Also, nurses and pharmacists had less than adequate information about new or unusually dosed medications.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Compounding; Drug Labeling; Forms and Records Control; Humans; Infusions, Intravenous; Leishmaniasis, Cutaneous; Male; Medication Errors; Medication Systems, Hospital; Organizational Case Studies; Pharmacy Service, Hospital; Safety Management

Leishmania species that occur within different geographical areas may cause different clinical manifestations, virulence and drug sensitivity. Patients/Methods. All patients with a clinical diagnosis of cutaneous leishmaniasis seen at the Hospital for Tropical Diseases from 1997 to 2000 were identified and clinical details recorded onto a database, with emphasis on clinical presentation, risk factors, travel history and laboratory diagnosis.. Forty-two patients were identified, 23 of whom had travelled to New World and 19 to Old World countries. Clinical presentation typically consisted of a single nodule with ulceration. In 50% infection was caused by L. (Viannia) braziliensis. PCR was performed in specimens from 34 patients and species identification was possible in 32 cases (sensitivity 94%), the two PCR negative patients had amastigotes demonstrated by histology and culture. Patients were treated with established therapies. Seventy one percent were cured by treatment, 12% had a spontaneous cure, 7% were lost to follow-up and the remaining 10% required a second-line therapy. No relapses were reported during a mean follow-up period of 27 months.. Our study highlights the need for comprehensive investigations and the advantages of PCR in the diagnosis of patients with suspected leishmaniasis in non-endemic regions of the world.

Topics: Adolescent; Adult; Aged; Animals; Antifungal Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Databases, Factual; England; Female; Global Health; Humans; Ketoconazole; Leishmania; Leishmaniasis, Cutaneous; Male; Middle Aged; Polymerase Chain Reaction; Risk Factors; Skin; Travel; Treatment Outcome

Human cutaneous leishmaniasis (CL) and mucous leishmaniasis (ML) are highly endemic in Isiboro Secure Park, which lies in the Bolivian department of Cochabamba--an area where branded meglumine antimoniate (Glucantime) is expensive and poorly distributed. The safety and efficacy of generic sodium stibogluconate (SSG), from Albert David Ltd, was therefore explored, in CL and ML cases from the park, who were treated with 20 mg/kg.day for 20 and 30 days, respectively. A questionnaire recording adverse effects was completed by a physician in each treatment centre. Efficacy of treatment was assessed at the end of treatment and at follow-ups 1 month and 3, 6 and 12 months later. Overall, 146 patients completed treatment with SSG in 2003-2004. No fatalities or severe adverse effects were reported but mild to moderate adverse effects were noted in 41 (28%) of the patients. The incidence of adverse effects was significantly higher among the cases of ML than among the cases of CL. Of the 86 patients with CL who completed 6 months of follow-up, 81 (94.2%) were considered to have been clinically cured; a comparable cohort of 69 CL cases who had been treated with Glucantime in 2001-2002 showed a similar frequency of clinical cure (90%). Generic SSG was shown to be safe and efficacious for the treatment of tegumentary leishmaniasis in Bolivia. Being several times cheaper than Glucantime, it could contribute to improving the access of CL and ML patients to treatment, not only in Bolivia but also in other countries of Latin America.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Bolivia; Drugs, Generic; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Treatment Outcome

A 50 year-old man, a United States resident, presented in Texas with a violaceous non-ulcerating lesion, involving the entire lower eyelid. The patient had traveled to a jungle area of Belize several hours drive from the capital city. Leishmania mexicana was isolated. The lesion only partially resolved after an initial course of sodium stibogluconate, requiring retreatment. At two years of follow-up, there was no relapse. The parasite isolated from the patient caused a progressive, non-ulcerating lesion in an experimental mouse footpad infection. This is an unusual case of cutaneous leishmaniasis in a traveler. Travelers must be educated about personal protective measures to prevent exotic infections acquired during travel.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Belize; Eyelid Diseases; Humans; Itraconazole; Leishmania mexicana; Leishmaniasis, Cutaneous; Male; Middle Aged; Travel

Studies on in vitro skin permeation and in vivo anti-leishmanial activity in mice experimentally infected with Leishmania (Leishmania) major pointed out to the potential of a new paromomycin (PA) formulation (hydrophilic gel) for treatment of cutaneous leishmaniasis (CL). In this study, the activity of this formulation was evaluated in animals experimentally infected by Leishmania species that prevail in the New World. PA gel activity was compared to antimony treatment, since it is still the first choice treatment to the different clinical forms of leishmaniasis. The topical treatment activity with 10% PA gel in BALB/c mice infected by Leishmania (Leishmania) amazonensis was higher than that observed for parenteral antimony treatment, while the efficacy of these two regimes in hamsters infected by Leishmania (Viannia) braziliensis was similar. These results suggest that this formulation could be suitable for clinical studies and may represent an alternative novel formulation for topical treatment of CL.

Topics: Administration, Topical; Animals; Antimony Sodium Gluconate; Cricetinae; Female; Gels; Injections, Intramuscular; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Meglumine; Meglumine Antimoniate; Mice; Mice, Inbred BALB C; Organometallic Compounds; Paromomycin; Random Allocation; Statistics, Nonparametric

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmania braziliensis; Leishmaniasis, Cutaneous; Military Personnel

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Injections, Intramuscular; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Middle Aged

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmaniasis; Leishmaniasis, Cutaneous; Male; Sri Lanka

A new focus of localised cutaneous leishmaniasis has emerged along the Satluj River valley in the mountainous region of north west Himachal Pradesh. The main endemic region extends from Pooh subdivision of Kinnaur district to Kumarsain subdivision of Shimla district with adjoining Nirmand subdivision of Kullu District comprising 86 villages. The climate of the affected areas varies from temperate to subtropical. A total of 285 cases were recorded from 1988 to January, 2005. The age of these patients varied from 10 months to 75 years, with 63 children (<12Years), and a male to female ratio of 1: 0.9. The duration of disease was 15 days to 48 months with majority (85%) presenting between 1-6 months. The number of lesions varied from 1-8, and were mostly seen on exposed parts of the body. Morphologically, lesions were asymptomatic, dry, nodular or crusted nodulo-ulcerative plaques. Tissue smear positivity for amastigotes was 43%. The characterization of 14 strains of these Leishmania revealed presence of both Leishmania tropica (n=3) and Leishmania donovani (n=11). Identification of the 42 sandflies collected from the peridomestic environment of the patients, revealed Phlebotomus longiductus - 29, P. major 8, P. kandelaki 2, while 2 remained unidentified. The patients were treated with intralesional sodium stibogluconate and majority showed excellent response.

Topics: Adolescent; Adult; Aged; Animals; Antimony Sodium Gluconate; Child; Child, Preschool; Female; Humans; India; Infant; Leishmania donovani; Leishmania tropica; Leishmaniasis, Cutaneous; Male; Middle Aged; Schistosomicides

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Azure Stains; Biopsy; Humans; Leg Ulcer; Leishmania; Leishmaniasis, Cutaneous; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Travel

The aim of this study was to evaluate the epidemiology of cutaneous leishmaniasis in the Eastern Province of Saudi Arabia. In addition, the clinical spectrum of the disease was evaluated.. This is a retrospective study of cutaneous leishmania cases from 1956 to 2002.. In the study period, there were 1862 patients with cutaneous leishmaniasis in the Saudi Aramco health care system. The disease is more prevalent in the Al-Hasa Oasis (Eastern Province of Saudi Arabia) and affects males and females equally. Cutaneous leishmaniasis follows a seasonal distribution in parallel with the known activity of the sandfly. The majority (76%) of cases occurred in patients < 15 years of age and the disease affected the extremities more frequently than the face. Seventy-one percent of patients presented with a single lesion and 27% presented with two lesions. Ulcerative cutaneous leishmaniasis was the predominant morphology (89%).. Cutaneous leishmaniasis attained epidemic proportions in 1973 and subsequently declined and reached a plateau in the mid-1980s. Skin involvement is the major clinical picture, with no evidence of dissemination or viscerotropic syndrome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Humans; Infant; Leishmania tropica; Leishmaniasis, Cutaneous; Male; Middle Aged; Retrospective Studies; Saudi Arabia

Topics: Afghanistan; Antimony Sodium Gluconate; Antiprotozoal Agents; Bedding and Linens; Emergency Medical Services; Health Education; Humans; Incidence; International Cooperation; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pesticides; Refugees

Topics: Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Iraq; Leishmania major; Leishmaniasis, Cutaneous; Male; Military Personnel; Neck; United States

The pentavalent antimonial compounds Glucantime and Pentostam are the first line drugs used in anti-Leishmania treatment. However, no in vivo studies have compared the efficacy and toxicity of these drugs where host variability has been controlled. Biochemical studies of Leishmania have detected differences between the two drugs with regard to DNA topoisomerase I inhibition, a phenomenon that possibly impacts treatment efficacy. To evaluate the clinical efficacy, hamsters were infected intradermally in the right hind foot with 10(6) promastigotes of a wild type or luciferase-transfected Leishmania panamensis. At three weeks post-inoculation, the animals were treated intramuscularly with either Glucantime or Pentostam (30, 60 or 120 mg SbV/kg per day for 20 days). To evaluate parasitological efficacy a luminometry assay was standardized for quantitation of amastigotes in hamster tissues. To evaluate toxicity, hamsters were treated intramuscularly with Glucantime or Pentostam (120, 160 or 240 mg SbV/kg per day for 20 days). Animals inoculated with either of the parasite strains and treated with either drug, showed a similar rate of lesion reduction, as compared to untreated controls (p<0.01). Parasite burden was also comparable, and no significant differences were found in the cure rate. No renal or hepatic alterations occurred as evidenced by normal serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and amylase. Hamsters treated with 120 mg SbV/kg per day for 20 days or higher doses of Pentostam showed macro- and microscopic signs of inflammation at the site of injection. These effects were absent in the animals treated with Glucantime. The results confirmed clinical observations regarding the similar efficacy of the two drugs, as well as the higher local toxicity of Pentostam.

Topics: Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Cricetinae; Disease Models, Animal; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Belize; Humans; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Middle Aged; Polymerase Chain Reaction; Travel

It would be very useful to have a more effective and more rapid method available for the treatment of cutaneous leishmaniasis (CL). The main aim of the present, Iranian study, was to see if the combination of cryotherapy and intralesional injections with meglumine antimoniate (C + MA) would be more effective than the injections given alone (MA) or the combination of cryotherapy plus intralesional sodium stibogluconate (C + SS). Forty patients (with 67 lesions) were treated with C + MA, another 40 (with 65 lesions) were treated with C + SS and 100 patients (with 180 lesions) were treated with MA. Follow-up for 6 months after the final treatment indicated that 89.5% of the lesions treated with C + MA, 92.3% of those treated with C + SS but only 50% of the lesions treated with MA only were completely cured. The frequencies of cure in the two cryotherapy groups were similar, both being significantly higher than that in the MA group (P < 0.05). The combination of cryotherapy with intralesional injections of meglumine antimoniate or sodium stibogluconate, which is much more effective than the use of intralesional meglumine antimoniate alone, should be promoted.

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Combined Modality Therapy; Cryotherapy; Female; Humans; Infant; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Treatment Outcome

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Diagnosis, Differential; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Mouth Diseases

Post-kala-azar dermal leishmaniasis (PKDL) is condition characterized by non-ulcerative lesions of the skin caused by Leishmania donovani that is usually seen after the completion of treatment of kala-azar (visceral leishmaniasis). We document the first case report of PKDL in Nepal.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Female; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Nepal

In recent years, New World cutaneous leishmaniasis has been seen at a higher incidence among returning Israeli travelers. Leishmania braziliensis and related species cause unsightly cutaneous lesions possibly complicated with a mucosal disease. A total of 12 patients with New World cutaneous leishmaniasis were treated in our clinic, 11 of whom (92%) acquired the disease in the Bolivian Amazon Basin. Five (42%) had regional lymphadenopathy in addition to cutaneous lesions. Polymerase chain reaction was performed for 8 patients to identify the causative Leishmania species. In all, 9 patients (75%) were cured by a single course, and 3 (25%) after an additional course of intravenous sodium stibogluconate. The treatment was well tolerated clinically. Laboratory abnormalities, mainly elevation of liver enzymes (58%), were reversible. We concluded that polymerase chain reaction is a useful tool in establishing the species diagnosis of leishmaniasis and that sodium stibogluconate appears to be a safe and effective treatment for L braziliensis infection.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Female; Humans; Leishmaniasis, Cutaneous; Male; Polymerase Chain Reaction; Travel

Three weeks after returning from a trip to Guatemala, a 33-year-old man developed two ulcers with indurated edges on his right leg and painful lymph nodes in the right groin. His general condition was not impaired.. Histological examination revealed cellular infiltrates of the corium by lymphocytes and plasma cells, always accompanied by epithelial cells and multinuclear giant cells. Special stainings were unable to detect pathogens but Leishmania brasiliensis was identified using PCR. The Leishmania culture remained negative.. After 7-day intravenous therapy with 20 mg/kg/d pentostam (pentavalent antimonial compound), the patient developed gastrointestinal complaints, coupled with a marked elevation of transaminases. Therapy was discontinued until the transaminase values normalized, then continued in reduced dosage (12 mg/kg body weight) for 23 days. The ulcers and lymphadenitis healed under this therapy.. The diagnosis of American cutaneous Leishmaniasis may be complicated by the relative lack of pathogens in the lesions. PCR diagnosis are very helpful here. The therapy must be systemic owing to the danger of progression to mucocutaneous Leishmaniasis. The standard therapeutic pentostam has, however, a high rate of side effects and administration is exclusively intravenous.

Topics: Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Biopsy; DNA, Protozoan; Genotype; Guatemala; Humans; Injections, Intravenous; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Polymerase Chain Reaction; Skin; Time Factors; Travel

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Facial Dermatoses; Female; Humans; Itraconazole; Leishmaniasis, Cutaneous; Middle Aged; Treatment Outcome

We present 3 cases of American cutaneous leishmaniasis occurring in soldiers of a unit of US Army Rangers who parachuted into the jungles of Panama. Shortly after returning to the United States, these 3 soldiers each developed a crusted, indurated papule, which slowly enlarged during the following 6 weeks. Routine microscopy of skin biopsies revealed a dermal granulomatous inflammation and a predominantly lymphoid infiltrate. Numerous histiocytes contained small oval organisms with bar-shaped paranuclear kinetoplasts, morphologically consistent with leishmanial parasites. Cultures grew Leishmaniasis brasiliensis, subspecies panamensis. The soldiers were treated with intravenous pentavalent antimonial therapy daily for 20 days with good clinical improvement. Epidemics of leishmaniasis occur periodically in tropical regions of the world, and leishmaniasis has emerged in new settings, for example, as an acquired immunodeficiency syndrome-associated opportunistic infection. With an increasingly mobile society, it is important to be familiar with the clinical and histopathologic appearance of conditions such as leishmaniasis, which are common in tropical and subtropical regions and are increasingly significant in other regions of the world.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Injections, Intravenous; Leishmania braziliensis; Leishmaniasis, Cutaneous; Military Personnel; Panama; Skin

This study aims to evaluate the in vitro and in vivo leishmanicidal activity of lapachol, a naphthoquinone found in the seeds and heartwood of certain tropical plants, and to compare its efficacy with a reference drug, sodium stibogluconate (Pentostam(R)). These compounds (0.0125-4.0 mg/mL) were evaluated in vitro against intracellular amastigotes of Leishmania (Viannia) braziliensis (LVb), then tested in an animal model (hamster) to try to reproduce the leishmanicidal activity. In vitro, lapachol exhibited an anti-amastigote effect, whereas in vivo it did not prevent the development of LVb-induced lesions at an oral dose of 300 mg/kg/day for 42 days. Pentostam(R) demonstrated a significant anti-amastigote effect in vitro for LVb and apparent clinical cure in vivo (60 mg/kg/day). However, it could not completely eradicate parasites from the tissues of infected animals. The observation that lapachol exerts leishmanicidal activity in vitro without offering significant protection against LVb-infected lesions in hamsters suggests that lapachol in vivo might possibly inhibit the microbicidal functioning of macrophages. Alternatively, it might be transformed into an inactive metabolite(s) or neutralized, losing its leishmanicidal activity. It is also possible that an optimal and sustained plasma level of the drug could not be achieved at the dose used in this study.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cricetinae; Disease Models, Animal; Female; Leishmania braziliensis; Leishmaniasis, Cutaneous; Macrophages, Peritoneal; Male; Mesocricetus; Mice; Naphthoquinones; Plants, Medicinal

We report 20 patients who contracted cutaneous leishmaniasis in Central and South America, 18 of them in Belize. The diagnosis was confirmed by the polymerase chain reaction (PCR) in 79% of those tested; the corresponding figure for histology was 62%, touch smear 46%, and culture 11%. Results of PCR can be falsely positive, so treatment should not be based on PCR alone. Of the 20 cases 18 were healed 6 weeks after intravenous sodium stibogluconate 20 mg/kg per day for 20 days. We present a management protocol.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Medical Records; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Treatment Outcome

Topics: Adolescent; Antimony Sodium Gluconate; Antiprotozoal Agents; Biopsy; Diagnosis, Differential; Emigration and Immigration; Facial Dermatoses; Humans; Leishmaniasis, Cutaneous; Male; Mexico; Physical Examination; Texas

With the increasing numbers of travelers and immigrants coming to the United States from tropical areas where Leishmaniasis is endemic, it is important to be familiar with its common cutaneous manifestations. Leishmaniasis is a parasitic infection caused by the obligate intracellular protozoa Leishmania and is transmitted by the bite of the sandfly. It can appear as a nonhealing lesion on exposed skin in patients and is often misdiagnosed, delaying treatment. We present two cases of patients who presented to the Emergency Department with chronic, nonhealing ulcers that were ultimately found to have Leishmaniasis.

Topics: Adult; Antimony Sodium Gluconate; Diagnosis, Differential; Emergency Service, Hospital; Female; Humans; Leishmaniasis, Cutaneous; Los Angeles; Male; Schistosomicides; Skin Ulcer; Travel

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male

We describe a patient with very late recurring leishmaniasis recidivans from whom lesional biopsy samples were obtained during and after topical steroid treatment that demonstrated the ability of the host to contain the parasite in the absence of therapy. Combination therapy with intralesional sodium stibogluconate and oral itraconazole was successful and immunologic data suggest that both CD4(+) and CD8(+) T cell subsets had roles in this disease process.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Itraconazole; Leishmania; Leishmaniasis, Cutaneous; Male; Middle Aged; Recurrence; Steroids; Time Factors

Topics: Adolescent; Antimony Sodium Gluconate; Antiprotozoal Agents; Costa Rica; Female; Humans; Leishmaniasis, Cutaneous; Travel

Neopterin, a product of gamma-interferon-activated macrophages, was measured in sera from 28 patients (12 patients with cutaneous leishmaniasis and 16 patients with visceral leishmaniasis) to determine the utility as a marker of disease activity and therapeutic efficacy. Patients originated from Kenya (n=5) and from the Academic Medical Center, Amsterdam, The Netherlands (n=23). In seven patients follow-up sera after treatment were available. Two patients at the time of diagnosis of visceral leishmaniasis were co-infected with HIV. The 12 patients with cutaneous leishmaniasis had serum neopterin levels below the upper limit of the normal range. All 16 patients with visceral leishmaniasis had elevated levels of serum neopterin before treatment. In six out of seven patients with visceral leishmaniasis followed during treatment neopterin levels decreased to values below the upper limit of the normal range (10 nmol l(-1)). Sequential measurements of serum neopterin levels may be useful for monitoring therapeutic efficacy in patients with visceral leishmaniasis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; HIV Infections; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Middle Aged; Neopterin; Pentamidine; Treatment Outcome

The incidence of leishmaniasis is increasing globally due to population and environmental changes. Ease of worldwide travel and immigrant populations means that the UK surgeon is more likely to encounter cutaneous lesions. Two cases are presented and treatment options discussed.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Carcinoma, Basal Cell; Child; Cryotherapy; Facial Dermatoses; Female; Humans; Leishmaniasis, Cutaneous; Middle Aged; Skin Neoplasms

Post-kala-azar dermal leishmaniasis (PKDL) is a common complication following kala-azar (visceral leishmaniasis). In a prospective study in a village in the endemic area for kala-azar in the Sudan, 105 of 183 (57%) kala-azar patients developed PKDL. There was a significantly higher PKDL rate (69%) in those who received inadequate and irregular treatment of kala-azar than in those who were treated with stibogluconate 20 mg kg-1 daily for 15 days (35%). The group of patients who developed PKDL did not differ from those who did not develop PKDL with regard to age and sex distribution, reduction in spleen size, and conversion in the leishmanin skin test (LST). In a clinical study, 416 PKDL patients were analysed and divided according to grade of severity. Severe PKDL was more frequent in younger age groups (P < 0.001); there was an inverse correlation between grade and conversion in the LST (P < 0.01). In 16% of patients tested, parasites were demonstrated in inguinal lymph node or bone marrow aspirates, indicating still visceral disease (para-kala-azar dermal leishmaniasis); there was no correlation between the presence of parasites and grade of severity. Conversion rates in the LST were lower than in those who did not have demonstrable parasites (11% and 37%, respectively; P < 0.01). In the absence of reliable and practical diagnostic tests, PKDL may be diagnosed on clinical grounds and differentiated from other conditions, of which miliaria rubra was the most common. Differentiation from leprosy was most difficult.

Topics: Adolescent; Adult; Age Factors; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Diagnosis, Differential; Endemic Diseases; Female; Humans; Infant; Infant, Newborn; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Sudan

Topics: Afghanistan; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Facial Dermatoses; Female; Humans; Leishmaniasis, Cutaneous; Lip Diseases; London

Topics: Aged; Animals; Antibodies, Protozoan; Antimony Sodium Gluconate; Antiprotozoal Agents; Biopsy; Diagnosis, Differential; Endemic Diseases; Female; Humans; Injections, Intravenous; Italy; Leishmania infantum; Leishmaniasis, Cutaneous; Skin

Cutaneous leishmaniasis (CL) is not common in South-East Asia and often presents as a granulomatous plaque on the exposed areas, with a high index of suspicion required for diagnosis. Two such cases were seen at the National Skin Centre recently, and both were Gurkha men with a history of travel to Belize. They were treated with intravenous sodium stibogluconate with success. A discussion on CL and its management follows.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Belize; Biopsy, Needle; Ear, External; Hospitalization; Hospitals, Urban; Humans; Injections, Intravenous; Leishmaniasis, Cutaneous; Male; Singapore; Travel

A quantitative colorimetric assay using the oxidation-reduction indicator Alamar Blue was developed to measure cytotoxicity of compounds against the protozoan parasite Leishmania. Absorbance increased linearly with the plating density of promastigotes of L. major MRHO/IR/76 vaccine strain up to at least 2.5 x 10(6) cells/ml when parasites were incubated for 72 h in the presence of 10% Alamar Blue. The 50% effective dose values of common drugs (amphotericin B, pentostam and paromomycin) obtained by this assay were in the same range as previously determined by other methods. The Alamar Blue assay permits a simple, reproducible and reliable method for screening antileishmanial drugs.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Colorimetry; Coloring Agents; Leishmania major; Leishmaniasis, Cutaneous; Oxazines; Oxidation-Reduction; Parasitic Sensitivity Tests; Paromomycin; Reproducibility of Results; Xanthenes

A Leishmania donovani species-specific monoclonal antibody (monoclonal antibody D2) was evaluated for its diagnostic and prognostic potential by a competitive enzyme-linked immunosorbent assay (C-ELISA) in sera from Indian patients with visceral leishmaniasis (VL) and seven patients with post-kala-azar dermal leishmaniasis (PKDL). These results were compared with those obtained by microscopy with Giemsa-stained tissue smears and a direct enzyme-linked immunosorbent assay (direct ELISA) with crude parasite antigen. Of 121 patients with clinically diagnosed VL examined, 103 (85.1%) were positive and 11 (9.1%) were negative by all three methods. An additional 7 (5.8%) who were negative by microscopy were positive by both C-ELISA and direct ELISA. Seven PKDL patients were also examined and were found to be positive by all three methods. Analysis of the chemotherapeutic response to sodium antimony gluconate of these 110 serologically positive VL patients showed that 57 (51.8%) were drug responsive and 53 (48.2%) were drug resistant. The C-ELISA with sera from 20 longitudinally monitored VL patients before and after chemotherapy showed a significant decrease in percent inhibition of monoclonal antibody D2 in drug-responsive patients. However, in drug-unresponsive patients, the percent inhibition of D2 was unchanged or was slightly increased. Our results therefore indicate (i) the applicability of L. donovani species-specific monoclonal antibody D2 for sensitive and specific serodiagnosis by C-ELISA, (ii) that the C-ELISA is more sensitive than microscopy, especially for early diagnosis, (iii) that L. donovani is still the main causative agent of VL, irrespective of the chemotherapeutic response, and (iv) that the C-ELISA can be used to evaluate the success of drug treatment.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Protozoan; Antimony Sodium Gluconate; Antiprotozoal Agents; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Humans; India; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Leprosy; Malaria; Prognosis; Tuberculosis

Cutaneous infection with Leishmania braziliensis complex requires treatment with parenteral pentavalent antimonials to prevent development of mucocutaneous leishmaniasis. Patients with imported disease are usually managed in hospital because of concerns over drug toxicity. This study describes the clinical features and outcome of infection treated in the UK in an out-patient setting. Thirteen marines (aged 19-35 years) who acquired leishmaniasis in Belize were studied prospectively. Three had at least two lesions (0. 6-3 cm diameter), eight had regional lymphadenopathy and one had localized painless lymphatic thickening. Histology for amastigotes and PCR for Leishmania braziliensis complex was positive in all. Culture was positive in six. Patients received 1.5-2 g (mean 1.7 g) (20 mg/kg) sodium stibogluconate intravenously daily for 20 days. All developed transient musculoskeletal symptoms and asymptomatic hepatitis. Eleven developed biochemical pancreatitis, and one thrombocytopenia. Three developed transient ECG changes and one herpes zoster. There were four device-related infections, two requiring hospitalization (one required surgical drainage of an abscess). All lesions re-epithelialized. A total of 250 bed-days were saved over a 67-day period. These results indicate that in selected patients, out-patient therapy for cutaneous leishmaniasis with parenteral high-dose sodium stibogluconate may be appropriate, provided there is adequate monitoring of therapy.

Topics: Adult; Ambulatory Care; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Infusions, Intravenous; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Self Administration; Treatment Outcome

Only a few cases of Post-kala-azar dermal leishmaniasis have been reported in Japan, especially recently. We describe a case of a 32-year-old woman who developed rose-colored nodules on her forearms two years after Kala-azar. A skin biopsy specimen from a nodule revealed not only granulomatous changes but also many amastigotes of Leishmania donovani in macrophages. Rose-colored nodules were also distributed on her face and neck. Treatment with antimony compound was very effective.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Biopsy, Needle; Disease-Free Survival; Face; Female; Humans; Japan; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral

Cutaneous South American leishmaniasis is caused by several species of leishmaniasis. Lack of appropriate treatment may lead to mucocutaneous leishmaniasis, mainly with L. b. braziliensis and L. b. panamensis.. To describe the clinical findings of Israeli travelers infected with cutaneous South American leishmaniasis and to draw attention to this problem.. Ten patients were interviewed, examined and treated.. Twenty-two lesions of cutaneous leishmaniasis were found, all in exposed areas. Patients were seen by an average three physicians (range 1-6) before the final diagnosis was confirmed by direct smear, after an average period of 125 days (range 88-270 days). Treatment with Pentostam was started after an average period of 134 days (range 94-275 days). All lesions healed completely, but with scarring.. Travelers to endemic areas, as well as physicians, should be instructed about the potential risks and the clinical manifestations of cutaneous and mucocutaneous South American leishmaniasis. Such awareness will prevent undue delay in diagnosis and treatment.

Topics: Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Female; Headache; Humans; Israel; Leg Ulcer; Leishmania mexicana; Leishmaniasis, Cutaneous; Liver; Liver Function Tests; Male; Meglumine; Meglumine Antimoniate; Muscle Weakness; Muscular Diseases; Organometallic Compounds; Pain; Retrospective Studies; Skin; South America; Travel; Weight Loss

Post-kala-azar dermal leishmaniasis can present as hypopigmented macules, erythematous to skin-coloured papules, nodules and photosensitive butterfly erythema on the face. We present a patient with disseminated annular lesions of post-kala-azar dermal leishamaniasis. The patient was treated with daily intravenous injections of sodium antimony gluconate for 120 days at a dose of 20 mg/kg body weight with complete clearance of lesions.

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Skin

A 24-year old German man was complaining of painful ulcers with infiltration of the lips without alteration of the oral mucosa and swelling of the regional lymph nodes. Three months earlier he had visited Israel, Italy, Romania and Bulgaria. He was treated with penicillin, doxycyclin, ciprofloxacin, itraconazole and prednisolone after detection of Candida spec. and staphylococci in another town without any effect. The smear and biopsy were sent to the Robert Koch Institute Berlin. Giemsa stain by phase contrast light microscopy with oil immersion showed extracellular amastigote leishmaniae with clearly stained kinetoplasts. Leishmania major could be detected by PCR investigation. The IgE was elevated, other investigations of the blood and from the lips were inconspicuous. The ulcers healed promptly under the treatment with Pentostam (antimony derivative) 0,1 ml/kg body weight i.m. for 12 days and 15% Paromomycin ointment.

Topics: Adult; Amebicides; Animals; Antimony Sodium Gluconate; Candidiasis; Diagnosis, Differential; Diagnostic Errors; Humans; Immunoglobulin E; Leishmania major; Leishmaniasis, Cutaneous; Lip Diseases; Male; Mouth Mucosa; Ointments; Paromomycin; Polymerase Chain Reaction

Treatment of nonhealing forms of human leishmaniasis with antimonial drugs in combination with gamma interferon (IFN-gamma) may promote healing more effectively than conventional drug therapy. Although the natures of immune responses in patients prior to treatment are often unclear, it is generally assumed that such therapy also promotes a switch from a Th2-type response to a dominant Th1-type response. We have examined the efficacy of IFN-gamma therapy, in combination with drug therapy, to promote healing and a Th2-to-Th1 switch in highly susceptible BALB/c mice infected with Leishmania major. Short-term treatment with the antileishmanial drug sodium stibogluconate failed to significantly alter the course of disease or the immune response when it was given during the third and fourth weeks of infection. IFN-gamma therapy, administered over the same time period, also failed to induce cure or a Th1 dominant response. In contrast, mice treated with a combination of drug and IFN-gamma therapy resolved their infections and developed Th1-type responses. However, administration of an antibody to interleukin 12 (IL-12) reversed the therapeutic effects of therapy with drug plus IFN-gamma, suggesting that IFN-gamma promotes cure through an IL-12-dependent mechanism. Analysis of mRNA levels within parasitized lesions suggests that drug treatment plus IFN-gamma treatment, in addition to reducing parasite numbers, results in reduced levels of IL-4, IL-10, and transforming growth factor beta transcripts but increased levels of transcripts of the p40 chain of IL-12 and inducible nitric oxide synthase, which catalyzes the production of nitric oxide. Together, these results suggest that such immunotherapy may promote the development of a protective Th1-type response in susceptible mice by a mechanism which involves both suppression of regulatory cytokines and enhancement of IL-12 and nitric oxide production.

Topics: Animals; Antibodies, Protozoan; Antimony Sodium Gluconate; Antiprotozoal Agents; Chronic Disease; Immunoglobulin G; Interferon-gamma; Interleukin-12; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Transforming Growth Factor beta

Cutaneous leishmaniasis is a protozoal disease transmitted by sandflies. It is endemic across the desert of the Middle East to Afghanistan and Africa. This paper reviews the findings in 148 expatriates with cutaneous leishmaniasis seen in Arar, northern Saudi Arabia, during a five year period. Cutaneous leishmaniasis was seen in all age groups. Farm workers, labourers and military personnel stationed in the region during the Gulf war were most affected. There was a seasonal variation with maximum incidence between November and January. The lesions were commonly multiple, the number of lesions per patient ranged from one to twelve. 18% of the lesions were located on the face, 34% on the upper extremity, 42% on the lower extremity and six per cent on other sites. The average duration of the lesions before diagnosis was two months. The most common complications were secondary bacterial skin infection (pyoderma and cellulitis) and residual scarring. The response to sodium stibogluconate was good. There has been a gradual reduction in the number of cases from a peak of 64 in 1991 to twelve in 1995. As compared to studies in the indigenous population, cutaneous leishmaniasis tends to be more frequent and server in expatriates from non endemic areas. There is a need for increased awareness of this disorder, especially in the home countries of these expatriates.

Topics: Adolescent; Adult; Age Distribution; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Emigration and Immigration; Humans; Incidence; Leishmaniasis, Cutaneous; Middle Aged; Saudi Arabia; Seasons; Travel

Little is known about the influence of host factors on successful chemotherapy in leishmaniasis. Although successfully treated patients will convert from a delayed-type hypersensitivity (DTH)-negative to a DTH-positive state, the importance of the immune status of the host before treatment remains largely unexplored. In experimental murine cutaneous leishmaniasis, it was found that increased polarization towards a Th2 cytokine profile before the onset of drug therapy leads to an increased frequency of relapse after treatment. Whereas >50% of mice with established Leishmania major infections were cured when treated with the antileishmanial drug sodium stibogluconate, <10% of mice were cured when the animals had been pretreated with anti-interferon-gamma antibody to polarize the response toward a Th2 cytokine pattern before therapy. With successful drug therapy, cytokine profiles were found to switch from a Th2 to Th1 pattern, and resistance to reinfection was observed.

Topics: Animals; Antibodies, Protozoan; Antimony Sodium Gluconate; Antiprotozoal Agents; Hypersensitivity, Delayed; Immunoglobulin Isotypes; Interferon-gamma; Leishmania major; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; T-Lymphocytes; Th1 Cells; Th2 Cells

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged; Peripheral Nervous System Diseases

Various therapeutic modalities have been used for treating cutaneous leishmaniasis. Intralesional pentavalent antimonial injection is one of the effective therapeutic modalities. In this study, the efficacy of three different intralesional schedules with sodium stibogluconate have been investigated.. Ninety-six patients with 129 lesions were entered into the study, all with confirmed diagnosis of cutaneous leishmaniasis. The lesions were treated with three different schedules, including daily, alternate day, and weekly interlesional injections of sodium stibogluconate. The clinical response was then compared to arrive at the most effective schedule.. The clinical responses (complete and partial cure) were 67%, 97%, and 91% for the daily, alternate-day, and weekly schedules, respectively. Lesions with either partial cure or failure of treatment were injected weekly with the same medication until complete cure had been achieved. The final overall success rate of complete cure was 99.2%.. Alternate day or weekly intralesional treatment of cutaneous leishmaniasis with sodium stibogluconate are more effective than daily treatments.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Injections, Intradermal; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Remission Induction; Treatment Outcome

The pathology of cutaneous leishmaniasis (CL) caused by Leishmania major zymodeme LON 1 in the Sudan was compared with that caused by L. major zymodeme LON 4 in Saudi Arabia and with that already described for L. tropica infections in Iran and for localized CL in the New World. The lesions were classified according to Ridley's five histological types. Most of the lesions in the Sudan and Saudi Arabia were of types B and C, characterized, respectively, by diffuse macrophage necrosis and focalized necrosis. B was the most common type in Nicaragua and Guyana whereas responses of types A (in which there are heavily parasitized macrophages without necrosis) and D (reactive tuberculoid) were the most frequent in Iran. The type-E response, which is similar to D but with virtual absence of plasma cells, was uncommon in all areas. The type-D reaction is a chronic relapsing disease when associated with L. tropica but not when associated with L. major. The major differences in the pathology of CL in different geographical areas most probably relate to differences in the Leishmania species involved. Minor differences, however, not only occur between patients from the same area but may also occur, with time, in the same patient. Detailed comparison between areas is therefore difficult; lesions on one patient may heal asynchronously and show different histological types at any point in time and rebiopsy from the same lesion during healing reveals changes from one histological type to another.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmania major; Leishmania tropica; Leishmaniasis, Cutaneous; Necrosis; Saudi Arabia; Skin; Sudan

We report on 4 cases of post-kala-azar dermal leishmaniasis (PKDL). History of kala-azar was available in all 4 patients. Slit-skin smears (SSS) for leishmania donovani (LD) bodies were negative in all 4. In 3 patients hypopigmented lesions were present over the face. Papules and nodules over his lips, tongue, scrotum and dactylitis were some unusual features observed in 1 patient. Histopathological examination showed LD bodies in 2 patients; histopathology was nonspecific in the other 2. All the patients were treated with sodium stibogluconate, 20 mg/kg/day. Infiltrated papules and nodules had subsided by 3 months, while hypopigmented macules took longer to improve. In 3 patients there had previously been a misdiagnosis as leprosy sufferers and they had been treated with antileprosy drugs. Clinical and histopathological differences between PKDL and leprosy are discussed.

Topics: Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Diagnosis, Differential; Female; Humans; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Leprosy; Male

Studies with Leishmania donovani in the mouse have demonstrated that an intact T cell compartment is required for effective anti-leishmanial therapy using pentavalent antimony compounds such as Pentostam (sodium stibogluconate), suggesting that the in vivo efficacy of drug treatment is at least partially immune-based. Similarly, Leishmania-infected, immunodeficient human patients including those with acquired immunodeficiency syndrome (AIDS) generally relapse following therapy with antimonials. However, sodium stibogluconate is directly parasiticidal in vitro, in the absence of T cells or T cell products. Using a model of a cutaneous form of leishmaniasis, in which susceptible BALB/c mice were infected with Leishmania major, we investigated whether the antileishmanial activity of the drug demonstrated a requirement for interferon-gamma (IFN-gamma), a cytokine produced during a T helper cell type 1 (Th1) immune response and known to contribute to resistance to infection, and whether drug therapy affected the nature of the antileishmanial response. Lesion development was suppressed in mice treated from the onset of infection with sodium stibogluconate alone, and in animals treated with sodium stibogluconate plus a neutralizing anti-IFN-gamma antibody, and tissue parasite burdens were approximately 10,000-fold less at the end of therapy in both groups compared with controls. Lesion development was similarly suppressed in mice with established lesions treated with either sodium stibogluconate alone, or sodium stibogluconate plus anti-IFN-gamma antibody. The production of IFN-gamma by cells from infected animals was somewhat increased immediately following therapy with sodium stibogluconate, an effect that was not long-lasting, while interleukin-4 (IL-4) production was not affected by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibodies, Monoclonal; Antimony Sodium Gluconate; Cytokines; Immunoglobulin E; Injections, Intramuscular; Interferon-gamma; Leishmania major; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Th1 Cells

The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absorption spectrophotometry after an appropriate dilution with Triton X-100. The 24-hr urine was also collected and analyzed similarly. The blood concentration-time data conformed to the one-compartment open model with mean and (SEM) of the apparent first-order rate constants for absorption (ka) and elimination (kd) of 1.71 (0.15) and 0.391 (0.016) hr-1, respectively. The maximum concentration of Sb achieved was 8.77 (0.39) mg/L and the peak time was 1.34 (0.09) hr. The total body clearance (TBC) and the volume of distribution (Vd) were 17.67 (1.38) L/hr and 45.7 (2.6) L, respectively, assuming a complete absorption. The fraction of dose of Sb excreted in the urine was 0.80 (0.07) and the renal clearance was 12.7 (1.16) L/hr. The frequency distribution pattern of the area-under-the-curve (AUC) appears to be bimodal and separates patients into those with low exposure to Sb (AUC = 11.7-29.04 mg.hr/L) (i.e., rapid eliminators) and those with high exposure to Sb (AUC = 31.5-49.1 mg.hr/L) (i.e., slow eliminators). This may explain the variability observed in the response to treatment of leishmaniasis with sodium stibogluconate.

Topics: Absorption; Adult; Antimony; Antimony Sodium Gluconate; Humans; Individuality; Injections, Intramuscular; Leishmaniasis, Cutaneous; Male; Middle Aged; Therapeutic Equivalency; Tissue Distribution

Successful treatment in allergic, autoimmune, and infectious diseases often requires altering the nature of a detrimental immune response mediated by a particular CD4+ T helper (Th) cell subset. While several factors contribute to the development of CD4+ Th1 and Th2 cells, the requirements for switching an established response are not understood. Here we use infection with Leishmania major as a model to investigate those requirements. We report that treatment with interleukin 12 (IL-12), in combination with the antimony-based leishmanicidal drug Pentostam, induces healing in L. major-infected mice and that healing is associated with a switch from a Th2 to a Th1 response. The data suggest that decreasing antigen levels may be required for IL-12 to inhibit a Th2 response and enhance a Th1 response. These observations are important for treatment of nonhealing forms of human leishmaniasis and also demonstrate that in a chronic infectious disease an inappropriate Th2 response can be switched to an effective Th1 response.

Topics: Animals; Antimony Sodium Gluconate; Base Sequence; Cells, Cultured; Cytokines; Drug Therapy, Combination; Female; Interleukin-12; Leishmaniasis, Cutaneous; Lymph Nodes; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Molecular Sequence Data; RNA, Messenger; Spleen; T-Lymphocytes, Helper-Inducer; Th1 Cells; Th2 Cells

We examined in this study the pharmacokinetics of Sb in the affected skin and normal skin of patients treated with sodium stibogluconate for cutaneous leishmaniasis and compared the results with those for the blood. The procedure was fully explained, and a written consent was obtained from each of nine patients. After a dose of sodium stibogluconate equivalent to 600 mg of Sb was administered intramuscularly, small skin biopsies were collected under local anesthesia at different time intervals from the circumferences of the lesions and simultaneously from normal skin. Antimony was measured in these biopsies after suitable ashing and processing by flameless atomic absorption spectrophotometry. The means (with standard errors of the means in parentheses) of the peak concentration, time to peak concentration, area under the curve, half-life, and mean residence time in lesions were 5.02 (1.43) micrograms/g, 2.1 (0.4) h, 32.8 (6.1) micrograms.h/g, 6.88 (0.54) h, and 10.4 (1.2) h, respectively, and those in normal skin were 6.56 (2.01) micrograms/g, 2.6 (0.8) h, 44.0 (15.8) micrograms.h/g, 5.44 (0.83) h, and 8.08 (1.34) h, respectively. There was no significant difference in any of these parameters between lesions and normal skin, whereas the differences in peak concentration, half-life, and mean residence time between lesions and whole blood were significant (P < or = 0.05). The penetration of Sb into skin, either affected or normal, as measured by the skin/blood area under the curve ratio appears to be complete, but the disposition is slow compared with that from the blood.

Topics: Adult; Antimony; Antimony Sodium Gluconate; Half-Life; Humans; Leishmaniasis, Cutaneous; Male; Skin

One hundred and fifty-eight lesions of acute cutaneous leishmaniasis in 70 patients were treated with hypertonic sodium chloride solution "HSCS" (88 lesions) or sodium stibogluconate (50 lesions); 20 lesions were left untreated as controls. The injections were given at 7-10 day intervals, and patients were followed-up for 42 days. "HSCS" was shown to be a very effective local therapy (96.05% cure rate) and was as effective as local sodium stibogluconate (96.42% cure rate). With both types of therapy, most lesions needed only one injection. Mild improvement was noticed 7-10 days after the first injection, and the cure was complete within 2-6 weeks (mean 4 weeks) of follow-up. None of the control lesions showed a cure within the six weeks follow-up. The mechanisms of action of both "HSCS" and sodium stibogluconate probably involve interference with the osmotic pressure of the cell cytoplasm of the parasites and lesional tissues. Scarring was either absent or minimal following healing of the treated lesions with both types of treatment. Post-inflammatory hyperpigmentation was observed in all patients. We strongly recommend intralesional "HSCS" as a cheap, safe, and effective local method for treating cutaneous leishmaniasis.

Topics: Adolescent; Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Cicatrix; Cytoplasm; Female; Follow-Up Studies; Humans; Hyperpigmentation; Injections, Intralesional; Leishmania; Leishmaniasis, Cutaneous; Male; Middle Aged; Osmotic Pressure; Remission Induction; Saline Solution, Hypertonic

Topics: Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Facial Dermatoses; Humans; Injections; Leishmaniasis, Cutaneous; Male; Travel

A total of 17 Leishmania isolates, 6 of them isolated from antimony-resistant patients, were collected in the Sudan and tested for their sensitivity to sodium stibogluconate (Pentostam) as promastigotes. Six of those isolates were tested as amastigotes infecting a murine macrophage cell line. The results indicated that the conventional promastigote screening assay did not correlate with the clinical picture, whereas the amastigote/macrophage system produced results that pertained to the in vivo responses to the drug. A laboratory-generated resistant strain of L. major was adapted to grow at a high concentration of Pentostam (1000 micrograms/ml) as promastigotes but was quite sensitive to the drug at much lower concentrations in the amastigote/(macrophage system (20 micrograms/ml), thus suggesting that Pentostam's inhibitory action is mediated through the macrophage rather than through a direct toxic effect exerted on the parasite.

Topics: Animals; Antimony Sodium Gluconate; Cell Line; Drug Resistance; Humans; Leishmania donovani; Leishmania major; Leishmaniasis; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Macrophages; Mice; Sudan

The pentavalent antimonial sodium stibogluconate is the mainstay of anti-leishmanial therapy. Sodium stibogluconate is less cardiotoxic than antimony and the trivalent derivatives, but has been associated with dose-related electrocardiographic changes. The effect of the currently-used regimen of sodium stibogluconate (20 mg/kg/day for 20 days) on cardiac function is uncertain. We studied 12 soldiers, mean age 24 years, with proven cutaneous leishmaniasis treated with this regimen. There were no significant changes in echocardiographic indices of left ventricular systolic or diastolic function during treatment. Indices of myocardial electrical stability (heart-rate variability and episodes of overt supraventricular and ventricular arrhythmias) were unchanged, but there was a reversible decrease in T-wave amplitude during treatment. Systolic and diastolic blood pressure fell and the heart rate increased during treatment. This regimen of sodium stibogluconate does not measurably impair left ventricular systolic or diastolic function. Minor T-wave changes occur during treatment, but there is no increase in arrhythmia frequency or change in heart-rate variability. In most young fit patients, this regimen has no cardiac side-effects. However, idiosyncratic reactions cannot be excluded, and patients with malnutrition, impaired renal function or pre-existing heart disease may be more sensitive to any cardiotoxic properties of sodium stibogluconate.

Topics: Adult; Antimony Sodium Gluconate; Blood Pressure; Creatine Kinase; Electrocardiography; Humans; L-Lactate Dehydrogenase; Leishmaniasis, Cutaneous; Male; Military Personnel; Myocardium; Prospective Studies; Ventricular Function, Left

Whereas most inbred mouse strains mount a protective Th1 helper T-cell response following infection with Leishmania major, an ineffective Th2 response develops in BALB/c mice, leading to the development of disseminated, ultimately fatal disease. Interleukin-4 (IL-4) production is required for the initiation of the Th2 response, though little is known about the requirements for the long-term maintenance of this response. In order to investigate the role of the expanding parasite population on the Th2 response, mice infected for 2 weeks with L. major, which exhibited a Th2-like cytokine profile, were treated with a leishmanicidal agent (Pentostam) and/or various doses of anti-IL-4 antibody. Untreated mice, mice treated with Pentostam alone, or mice treated with 2.5 mg of anti-IL-4 antibody given at days 13 and 21 of infection developed progressive disease. However, in 8 of 10 mice treated with this dose of anti-IL-4 antibody plus Pentostam lesion development was arrested and lesions were either controlled or eventually healed. Healing was associated with the production of high levels of gamma interferon by spleen cells, and low levels of immunoglobulin E in serum compared with levels for control animals, indicating that a Th1-like response had developed in mice receiving both treatments. Thus, depletion of IL-4 only in combination with a reduction in the parasite burden allowed the expression of a Th1 response. When the dose of anti-IL-4 antibody was increased to 5 mg per injection, all mice treated with this dose of antibody, with or without Pentostam therapy, healed. However, combined therapy with Pentostam in mice treated with this dose of antibody had an additional protective effect. As expected, a Th1 response developed in mice treated with this dose of anti-IL-4 antibody with or without combined therapy with Pentostam, whereas a Th2 response developed in control mice. Thus, a significant effect on the course of disease is noted when mice with established L. major infections are treated with anti-IL-4 antibody in combination with Pentostam, suggesting that the combined effect of inhibiting IL-4 and reducing the parasite burden has a dramatic effect on the development of resistance to L. major.

Topics: Animals; Antibodies, Protozoan; Antimony Sodium Gluconate; Cytokines; Immunity, Cellular; Immunoglobulin E; Interleukin-4; Leishmania major; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Th1 Cells; Treatment Outcome

Visceral leishmaniasis (VL) is endemic in several areas in the Sudan. The disease is associated with depressed cellular immunity. Tinea versicolor is a normal commensal of the skin which can become pathogenic particularly in patients with depressed cell-mediated immunity. Patients with VL have a high prevalence of tinea versicolor.. One hundred and thirty patients with parasitologic confirmation of VL were screened for tinea versicolor infection. In the suspected cases the diagnosis was made by demonstrating the fungal hyphae and spores in skin scrapings. All patients were treated with sodium stibogluconate.. Of the 130 patients with VL, 10.8% were found to have severe tinea versicolor. The fungal infection developed or became worse with the start of VL. After successful treatment of VL, the tinea lesions disappeared completely or decreased in severity.. Depressed cell-mediated immunity that is a feature of VL is the probable underlying cause for fungal infection. Tinea infection during the course of VL is to be distinguished from lesions of post-kala-azar dermal leishmaniasis.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Child; Diagnosis, Differential; Facial Dermatoses; Female; Follow-Up Studies; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Opportunistic Infections; Remission Induction; Sudan; Time Factors; Tinea Versicolor

To characterize the exposures and practices of U.S. travelers who acquired cutaneous leishmaniasis in the Americas and to highlight problems they encountered in seeking medical care from U.S. physicians.. A retrospective review of Centers for Disease Control and Prevention Drug Service records and a telephone survey of patients.. Fifty-nine civilian U.S. travelers with American cutaneous leishmaniasis for whom the Drug Service released sodium stibogluconate between 1 January 1985 and 30 April 1990; 58 travelers (98%) were interviewed.. Travel destination, exposure duration, knowledge about leishmaniasis, and time from noticing skin lesions to release of drug.. Overall, travelers acquired leishmaniasis in as many as 14 countries; 33 of 59 travelers (56%) were infected in Mexico or Central America. Twenty-seven travelers (46%) were conducting field studies and 23 (39%) were tourists, visitors, or tour guides. At least 15 persons (26% of the 58 interviewed travelers) were in forested areas for 1 week or less; at least 6 of these persons had a maximum exposure of 2 days. Ten persons (17%) were home at least 1 month before they noticed skin lesions. Patients consulted from one to seven physicians (mean, 2.1 physicians) before leishmaniasis was diagnosed. Overall, the median time from noticing lesions to the release of drug was 112 days (range, 13 to 1022 days); however, the median was only 55 days for 13 patients (22%) unusually knowledgeable about leishmaniasis and was a maximum of 60 days for 16 patients (28%) (including 7 of the 13 unusually knowledgeable patients) who generally consulted physicians exceptionally knowledgeable about infectious and tropical diseases.. Travelers to forested areas in Mexico and Central and South America and their physicians need to be educated about the risk for acquiring leishmaniasis even during short stays, as well as about effective preventive measures; and appropriate medical management [corrected].

Topics: Adolescent; Adult; Americas; Antimony Sodium Gluconate; Child; Child, Preschool; Cluster Analysis; Female; Health Knowledge, Attitudes, Practice; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged; Retrospective Studies; Time Factors; Travel; United States

The medical records of 306 British soldiers in whom a clinical diagnosis of cutaneous leishmaniasis had been made following a tour of duty in Belize were analysed. Parasitological confirmation of the diagnosis was established in 187 cases; leishmania were cultured in 117 cases and Leishman-Donovan bodies were identified histologically in a further 70 cases. Leishmania braziliensis braziliensis was identified in 78 cases and Leishmania mexicana mexicana in a further 29 cases. Seventy-one per cent of patients had a single lesion which, in most cases, occurred on the exposed extremities. The mean diameter of the ulcers was 14.4 mm. Treatment with sodium stibogluconate was effective. Two regimens were used, consisting of either 600-800 mg daily given initially for 10 days, or 600 mg b.d. given initially for 14 days. Of those allocated to the lower dose regimen 48.5% were cured after the initial 10-day course, and ultimately the ulcers of 93% of patients healed following more prolonged treatment at this dose. Of those allocated to the higher dose regimen 63.9% were cured after the initial 14-day course and ultimately the ulcers of all patients healed after more prolonged treatment at this dose. A transient leucopenia and a rise in liver enzymes were noted during treatment, and these changes were dose-dependent. No cases of mucocutaneous leishmaniasis were encountered.

Topics: Adult; Animals; Antimony Sodium Gluconate; Belize; Drug Administration Schedule; Follow-Up Studies; Humans; Leishmania braziliensis; Leishmania mexicana; Leishmaniasis, Cutaneous; Male; Military Personnel; United Kingdom

Simple cutaneous leishmaniasis (CL), which is endemic in several areas of Israel, is usually caused by Leishmania major. CL, which is caused by replication of parasites within dermal macrophages, is self-limited and almost always confined to the skin. We recently encountered two cases of CL in which skin defenses were breached and lesions appeared in subcutaneous locations. In one case, abnormal cell-mediated immune function was detected. The purpose of this article is to present these data and to comment on the immunological aspects of leishmaniasis.

Topics: Adult; Aged; Antimony Sodium Gluconate; Female; Humans; Leishmaniasis, Cutaneous; Male; Skin

Post-kala-azar dermal leishmaniasis is a condition peculiarly confined to the Indian subcontinent.. The clinical features and investigations in 18 patients of post-kala-azar dermal leishmaniasis were studied.. There was a polymorphic picture from hypopigmented macules to nodules and plaques. Mucous membranes were affected in five, the lips and glans penis being the most frequent sites. Histopathologically, a rich dermal infiltrate was seen in indurated lesions and in macules; it was confined to perivascular foci in the upper dermis. Leishman-Donovan bodies were seen in 16.. The lesions cleared in 4 to 5 months after treatment with sodium antimony gluconate intramuscularly 20 mg/kg/day up to a maximum of 1 g/day. The drug was well tolerated.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Biopsy; Child; Diagnostic Tests, Routine; Female; Follow-Up Studies; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Middle Aged; Skin

Topics: Adult; Antimony Sodium Gluconate; Female; Granuloma; Humans; Leishmaniasis, Cutaneous; Nose; Nose Diseases; Postoperative Complications

Topics: Adult; Antimony Sodium Gluconate; Female; Humans; India; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral

A 27-year-old woman who acquired cutaneous leishmaniasis in Central America was inadvertently treated with 10 times the intended daily dose of the pentavalent antimonial compound sodium stibogluconate (Pentostam): 8500 mg (143 mg/kg) instead of 850 mg. The patient felt "wiped out" during the 4-h infusion of the drug. After the mistake in dosing was discovered, she was vigorously hydrated and carefully monitored in an intensive care unit for greater than 48 h. Her vital signs were stable, and no arrhythmias were noted. Her alanine aminotransferase level rose briefly to 2.4 times the upper limit of normal, and her white blood cell count briefly fell 43% to a low of 3700/microliter. Her skin lesions subsequently healed without further therapy. Although sodium stibogluconate has been associated with a variety of side effects, in this case, a single high dose of the drug was tolerated without serious toxicity.

Topics: Adult; Animals; Antimony Sodium Gluconate; Drug Overdose; Female; Fluid Therapy; Humans; Infusions, Intravenous; Leishmania braziliensis; Leishmaniasis, Cutaneous

We report that in vitro sensitivity to pentavalent antimony (Sb5) of 35 Leishmania isolates as determined by the semiautomated microdilution technique (SAMT) showed an 89% and 86% correlation with clinical outcome after Pentostam and Glucantime treatment, respectively. These results suggest that in over 85% of the cases, the clinical outcome of treatment (cure or failure) could have been predicted by using the SAMT technique. Furthermore, the results clearly indicate that drug resistance is a problem, and that at least in some instances, failure to respond to treatment is due to the parasite as well as patient factors. Strains from Sb5-treated patients with American cutaneous and mucocutaneous disease who fail at least one complete course of Pentostam are as highly nonresponsive to this drug as laboratory-proven drug-resistant Leishmania strains. It was determined that some Leishmania isolates are innately less susceptible to Sb5 than others, and that moderate resistance to Sb5 exists in nature. A 10- and 17-fold increase was detected in the 50% inhibitory concentration (IC50) of Sb5 for L. mexicana and L. braziliensis isolates after subcurative treatment of the patients, when compared with the mean IC50 of seven and six isolates from the same endemic areas in Guatemala and Peru, respectively. Thus, we have correlated subcurative treatment to a decrease in drug sensitivity in at least these two cases. Collectively, these results indicate that under Sb5 pressure from undermedication, the parasites inherently most drug resistant are favored. The degree of resistance of a strain to antimony in association with host-specific factors will determine whether the clinical response to treatment with this drug is a total cure or a partial response followed by relapse(s), and possibly secondary unresponsiveness resulting in total resistance to antimony. It is evident from our in vitro test data that the SAMT is an extremely powerful and highly accurate technique for the prediction and determination of drug sensitivity of leishmanial isolates, as well as a means to screen for anti-leishmanial agents.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Resistance; Humans; Leishmania; Leishmania braziliensis; Leishmania mexicana; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds

Cutaneous leishmaniasis (CL) is a skin disease encountered in the East Mediterranean Region including Egypt. In this paper, it was intended to throw some light on the clinical picture of six parasitologically proven human CL. Also, the results of treating three cases of them with Pontostam or Cryosurgery. The whole results were discussed.

Topics: Adult; Antimony Sodium Gluconate; Chemotherapy, Adjuvant; Child, Preschool; Cryosurgery; Egypt; Female; Follow-Up Studies; Humans; Infant; Leishmaniasis, Cutaneous; Male; Middle Aged

This paper reports two indigenous cases of cutaneous leishmaniasis for the first time in Kafr Shokr, Qualyobia Governorate. One of the two cases was misdiagnosed as cutaneous tuberculosis (primary complex) and was kept on TB treatment, but with no clinical improvement. The two patients were successfully treated with sodium stibogluconate (pentostam).

Topics: Adult; Antimony Sodium Gluconate; Egypt; Female; Humans; Infant; Leishmaniasis, Cutaneous

Post kala-azar dermal leishmaniasis (PKDL) occurs occasionally after successful cure of visceral leishmaniasis. Twelve patients with diagnosis consistent with PKDL were seen at Clinical Research Centre from 1981 to 1985. Clinical presentation ranged from macular hypopigmented lesion to generalized nodular lesions. All lesions cleared either by self-cure or by treatment with sodium stibogluconate.

Topics: Antimony Sodium Gluconate; Female; Humans; Kenya; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Time Factors

Topics: Antimony; Antimony Sodium Gluconate; Enzyme Inhibitors; Humans; Leishmaniasis; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; United States