antimony-sodium-gluconate and Leishmaniasis

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

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

Leishmaniasis is an infectious disease caused by Leishmania protozoa, transmitted by the bite of phlebotomine sandflies. It causes a spectrum of clinical syndromes, of which the most common are cutaneous and visceral leishmaniasis. Clinical presentation is highly variable and is dependent on multiple factors, such as Leishmania species and patient characteristics (including immune competence). The relationship between these variables is poorly understood, and there is no single, evidence-based treatment for the disease. Currently management focuses on identification of the species, but this requires specialist tests which are often unavailable, particularly on military operations. Leishmaniasis is of particular relevance to military medical personnel as it is endemic in many tropical and sub-tropical regions of the world, including Belize, Iraq and Afghanistan where UK Armed Forces may be deployed. It can present a potentially serious threat to military personnel deployed in endemic areas due to the possibility of long-term sequelae of infection.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Diagnosis, Differential; Endemic Diseases; Humans; Insecticide-Treated Bednets; Leishmaniasis; Military Medicine; Occupational Diseases; United Kingdom

The control of Leishmania infection relies primarily on chemotherapy till date. Resistance to pentavalent antimonials, which have been the recommended drugs to treat cutaneous and visceral leishmaniasis, is now widespread in Indian subcontinents. New drug formulations like amphotericin B, its lipid formulations, and miltefosine have shown great efficacy to treat leishmaniasis but their high cost and therapeutic complications limit their usefulness. In addition, irregular and inappropriate uses of these second line drugs in endemic regions like state of Bihar, India threaten resistance development in the parasite. In context to the limited drug options and unavailability of either preventive or prophylactic candidates, there is a pressing need to develop true antileishmanial drugs to reduce the disease burden of this debilitating endemic disease. Notwithstanding significant progress of leishmanial research during last few decades, identification and characterization of novel drugs and drug targets are far from satisfactory. This review will initially describe current drug regimens and later will provide an overview on few important biochemical and enzymatic machineries that could be utilized as putative drug targets for generation of true antileishmanial drugs.

Topics: Aminoquinolines; Amphotericin B; Antigens, Protozoan; Antimony Sodium Gluconate; Antiprotozoal Agents; Caspase Inhibitors; Cyclin-Dependent Kinases; Drug Discovery; Enzyme Inhibitors; Folic Acid Antagonists; Humans; Leishmaniasis; Macrophages; Microbodies; Mitogen-Activated Protein Kinase Kinases; Paromomycin; Pentamidine; Phosphorylcholine; Polyamines; Protease Inhibitors; Sterols; Sulfhydryl Compounds; Topoisomerase Inhibitors

Pentavalent antimonials are the first-line drugs for treatment of the major tropical disease leishmaniasis. However, their use is limited by the need for daily parenteral administration, their severe side effects and treatment failures. As leishmaniasis belongs to the group of neglected diseases, the improvement of old drugs through new delivery approaches has more support than the development of new chemical entities.. The review covers, from 1977 to the present, the progress achieved towards pharmaceutically acceptable liposome-based formulations of antimonials, identification of specific ligands for improved targeting of infected macrophages and new approaches for oral and topical delivery of antimonial drugs.. Insights into the most promising delivery strategies to improve antimonial therapy and the chemical basis and future directions for achieving innovative orally and topically effective formulations.. The development of drug delivery strategies for the old pentavalent antimonials is a still growing and promising field, with expected innovations in the near future from improved knowledge of antimony chemistry.

Topics: Administration, Oral; Administration, Topical; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Delivery Systems; Humans; Leishmaniasis; Liposomes; Meglumine; Meglumine Antimoniate; Organometallic Compounds

We report a rare UK case of laryngeal leishmaniasis, mimicking laryngeal candidiasis, associated with long term steroid inhaler use.. Case report and review of the world literature concerning leishmaniasis.. Laryngeal leishmaniasis is a protozoal infection which is rare in the Western world. It is becoming more common, however, with increased foreign travel. The disease can be difficult to diagnose histologically, and diagnosis is often delayed because of its rarity. It can mimic malignant laryngeal disease, and patients may therefore be subjected to significant and inappropriate treatment interventions.. A diagnosis of leishmaniasis should be considered if initial treatment for persistent hoarseness is ineffective, particularly in a patient who is at low risk of malignancy.

Topics: Anti-Asthmatic Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Candidiasis, Oral; Diagnosis, Differential; Hoarseness; Humans; Laryngoscopy; Leishmaniasis; Male; Middle Aged; Time Factors; Treatment Outcome

Leishmania are protozoan parasites distributed worldwide. About 1.5-2.0 million cases are reported in the world annually from this disease and the death toll is estimated to be 57,000. Along with Brazil, Sudan and Bangladesh, India contributes to 90 per cent of the global burden of visceral leishmaniasis (VL). The absence of effective vaccines and vector control programmes, makes chemotherapy the most widely used tool against leishmaniasis. Chemotherapy based on pentavalent antimonials has been used for more than 50 years and remains the mainstay for treatment of leishmaniasis. Clinical resistance to pentavalent antimonials, in the form of sodium antimony gluconate (SAG), has become a major problem in the treatment of kala-azar (visceral leishmaniasis) in India. The mechanism of resistance is unclear in these clinical isolates although a lot of work has been carried out with Leishmania mutants selected in vitro by step-wise increasing drug concentration using the antimony related metal arsenic and more recently sodium antimony gluconate. We for the first time, investigated the molecular aspect of drug resistance in clinically confirmed sodium antimony gluconate resistant field isolates and found that the parasite evaded cytotoxic effects of therapy by enhanced efflux of drugs through overexpressed membrane proteins belonging to the superfamily of ABC (ATP-binding cassette) transporters. Additionally, our study also points towards cell surface changes in resistant isolates.

Topics: Animals; Antimony Sodium Gluconate; Drug Resistance; Humans; Leishmania donovani; Leishmaniasis; Models, Biological

In multicellular organisms, cellular growth and development can be controlled by programmed cell death (PCD), which is defined by a sequence of regulated events. However, PCD is thought to have evolved not only to regulate growth and development in multicellular organisms but also to have a functional role in the biology of unicellular organisms. In protozoan parasites and in other unicellular organisms, features of PCD similar to those in multicellular organisms have been reported, suggesting some commonality in the PCD pathway between unicellular and multicellular organisms. However, more extensive studies are needed to fully characterise the PCD pathway and to define the factors that control PCD in the unicellular organisms. The understanding of the PCD pathway in unicellular organisms could delineate the evolutionary origin of this pathway. Further characterisation of the PCD pathway in the unicellular parasites could provide information regarding their pathogenesis, which could be exploited to target new drugs to limit their growth and treat the disease they cause.

Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Apoptosis; Bacteria; Dinoflagellida; Eukaryota; Leishmania; Leishmaniasis; Life Cycle Stages; Plasmodium; Trypanosoma; Yeasts

The leishmaniases consist of cutaneous, mucosal, and visceral syndromes. The classic treatment is with pentavalent antimonials. The disadvantages of the antimonials are their requirement for intramuscular or intravenous injection each day for 20-28 days, their toxicity, and the recent development of resistance in regions such as India. Amphotericin B is a potent secondary agent, but is also compromised by its parenteral nature and toxicity. Clinical investigation of treatment agents from January 2000 to January 2003 is reviewed to determine if there are new agents that can be used.. A large number of pilot studies on visceral and cutaneous leishmaniasis have been performed. There can be more confidence in the visceral studies because visceral disease is incurable if untreated, and because large numbers of patients have been treated in highly endemic regions such as India. There is less confidence in pilot studies of the cutaneous disease, because most are uncontrolled, and there is a variable, and often high, cure rate without treatment.. Liposomal amphotericin B, which is injected infrequently and is easily tolerated, is virtually 100% effective for Indian visceral disease at a total dose of 15 mg/kg and is 90% effective at a dose of 5-10 mg/kg. The oral agent, miltefosine, is more than 95% effective for Indian visceral disease. Fluconazole treatment for 6 weeks speeds up the already-rapid cure rate of cutaneous disease due to Leishmania major.

Topics: Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Clinical Trials as Topic; Fluconazole; Humans; Leishmaniasis; Paromomycin; Pentamidine; Phosphorylcholine

Treatment of leishmaniasis is far from satisfactory: all antileishmanial drugs are toxic and most have to be used parenterally for prolonged periods, especially for visceral leishmaniasis. In recent years, there has been a steady erosion in the efficacy of pentavalent antimony to cure visceral leishmaniasis in Bihar, India. In addition, several new antileishmanial formulations have become available.. Through the publication of three studies from Africa, generic sodium stibogluconate, which is a fraction of the price of the branded drug Pentostam, has proven to be equivalent to Pentostam both in terms of safety and efficacy. The first oral drug, miltefosine, has been approved for treating visceral leishmaniasis in India, and preliminary reports of its efficacy against cutaneous leishmaniasis have been published. Interesting studies on successful low/single dose treatment of Indian visceral leishmaniasis with liposomal amphotericin B have been published. Several trials using different approaches towards treating cutaneous leishmaniasis are also reviewed. The results of clinical trials of two oral compounds are reported - fluconazole in treating cutaneous leishmaniasis was found to be safe and effective, whereas sitamaquine (WR6026) for visceral leishmaniasis was found to be toxic with poor efficacy.. Generic stibogluconate enables the cost effective treatment of all forms of leishmaniasis as it remains the most important antileishmanial drug in most parts of the world. In India, successful single dose AmBisome for visceral leishmaniasis makes therapy simple and enables mass treatment, provided the drug cost is brought down. For cutaneous leishmaniasis, two new oral drugs, fluconazole and miltefosine, provide wider options to the clinician.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Resistance; Humans; India; Leishmania; Leishmaniasis

The literature on the leishmaniases in the Sudan is reviewed with an emphasis on clinical aspects and on literature related to the recent outbreaks in the south and east of the country. The numbers of cases of subclinical infection and post-kala azar dermal leishmaniasis in the recent outbreaks are remarkable. New diagnostic techniques have been introduced and evaluated, notably the direct agglutination test and polymerase chain reaction technology. The latter gives very promising results and further research into application of the technique is warranted. Treatment with pentavalent antimony is still satisfactory. The reservoir host has not been identified definitely.

Topics: Agglutination Tests; Antimony Sodium Gluconate; Antiprotozoal Agents; Disease Outbreaks; Humans; Leishmaniasis; Polymerase Chain Reaction; Sudan

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Diagnosis, Differential; Humans; Insect Vectors; Leishmaniasis; Psychodidae

Leishmanial infections include three major clinical syndromes: visceral, cutaneous, and mucosal leishmaniasis. Visceral leishmaniasis, usually due to Leishmania donovani, has received increasing attention in the United States because of the growing number of cases seen in AIDS patients and the occurrence of viscerotropic L. tropica disease among Persian Gulf war participants. Cutaneous leishmaniasis is a relatively benign disease caused by L. Mexicana and L. (Viannia) species in the New World, and L. major, L. tropica, and L. aethiopica in the Old World. Many of these cutaneous lesions are self-healing, and treatment recommendations vary and continue to undergo evolution and study. Mucosal disease, caused by Leishmania (V.) braziliensis, is difficult to diagnose as well as to treat. A practical approach to the clinical presentation, diagnostic measures, and some treatment options of these syndromes is presented in relation to specific case studies.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Child, Preschool; Female; Humans; Leishmania; Leishmaniasis; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Protozoan Vaccines; Vaccination

Topics: Anti-Bacterial Agents; Antimony Sodium Gluconate; Cryosurgery; Hot Temperature; Humans; Leishmaniasis

Topics: Allopurinol; Aminoquinolines; Antimony; Antimony Sodium Gluconate; Cryosurgery; Humans; Leishmaniasis; Leishmaniasis, Mucocutaneous; Levamisole; Liposomes; Meglumine; Meglumine Antimoniate; Metronidazole; Nifurtimox; Organometallic Compounds; Phenothiazines; Rifampin

This review outlines the present knowledge of American cutaneous leishmaniasis, a disease which, owing to the increase in international travel, is being seen with increasing frequency in Europe and North America. A knowledge of this disease is of particular importance to the military medical officer as in recent years approximately one-hundred and fifty cases of leishmaniasis have been seen in British troops who have served in Belize. Leishmania braziliensis sp. have been isolated from a number of these cases. Organisms of this complex had not previously been recorded in Belize and the Army Medical Services are therefore in a unique position to study this disease, as well as having a responsibility to ensure its correct management.

Topics: Antimony; Antimony Sodium Gluconate; Antiparasitic Agents; Antiprotozoal Agents; Belize; Central America; Diagnosis, Differential; Humans; Leishmaniasis; Meglumine; Military Medicine; Skin Diseases, Parasitic; South America; United Kingdom

Topics: Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Disease Models, Animal; Glycolipids; Humans; Leishmaniasis; Leishmaniasis, Visceral; Liposomes; Lysosomes; Malaria; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Primaquine; Protozoan Infections; Trypanosomiasis

The efficacy and toxicity of sodium stibogluconate (SSG) at a dosage of 20 mg/(kg.d) for either 20 days (for cutaneous disease) or 28 days (for visceral, mucosal, or viscerotropic disease) in the treatment of leishmaniasis is reported. Ninety-six U.S. Department of Defense health care beneficiaries with parasitologically confirmed leishmaniasis were prospectively followed for 1 year. One patient was infected with human immunodeficiency virus; otherwise, comorbidity was absent. Clinical cure occurred in 91% of 83 cases of cutaneous disease and 93% of 13 cases of visceral/viscerotropic disease. Adverse effects were common and necessitated interruption of treatment in 28% of cases, but they were generally reversible. These included arthralgias and myalgias (58%), pancreatitis (97%), transaminitis (67%), headache (22%), hematologic suppression (44%), and rash (9%). No subsequent mucosal leishmaniasis was identified, and there were no deaths attributable to SSG or leishmaniasis.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Headache; Humans; Injections, Intravenous; Leishmaniasis; Male; Middle Aged; Military Personnel; Pancreatitis; Treatment Outcome

Pentavalent antimony has been considered to be the standard treatment for leishmaniasis, but more recently, the orally administrable agent allopurinol ribonucleoside has been the subject of several clinical trials. In this study, these two agents were evaluated in patients with Ecuadorian cutaneous leishmaniasis. Patients were randomly assigned to the two treatment groups. The mean reduction in lesion size for the 28 patients treated with Pentostam (20 mg Sb/kg/day intramuscularly for 20 days) was 61%, 23%, and 11% after one, two, and three weeks, respectively. There was a wide range in the individual values, and some lesions markedly enlarged in the first week of therapy. An initially healed lesion was defined as one that had greater than 80% re-epithelialized by the 1.5-month post-treatment followup. All Pentostam patients demonstrated this degree of lesion resolution (100% initial healing rate), but one patient showed evidence of relapse at the three month followup resulting in a 96% complete healing rate for the 12 month observation period. Patients in the untreated control group demonstrated a strikingly high rate of healing with 9 of 12 patients having re-epithelialized all lesions after 1.5 months observation (75% initial healing rate). The mean reduction in lesion size for the untreated patients was 56%, 29%, and 25% after one, two, and three weeks, respectively. Twenty-one patients received allopurinol ribonucleoside (1,500 mg QID) plus probenecid (500 mg QID) for 28 days. Lesions in nine of these patients were healed at the time of the 1.5 month followup (41% healing rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Allopurinol; Antimony Sodium Gluconate; Antiprotozoal Agents; Ecuador; Humans; Leishmaniasis; Ribonucleosides

The classic agent for cutaneous leishmaniasis is pentavalent antimony. However, there are no reports of the efficacy of antimony versus placebo or of the efficacy of any alternative therapy versus either antimony or placebo. In the present report, the oral antifungal agent ketoconazole (600 mg/day for 28 days) was compared to a recommended regimen of intramuscular Pentostam (20 mg antimony/kg, with a maximum of 850 mg antimony/day, for 20 days) in a randomized study of the treatment of Panamanian cutaneous leishmaniasis due to Leishmania braziliensis panamensis. A separate group of patients with this disease was administered placebo.. Ketoconazole clinically cured 16 of 21 (76%) patients. The lesions on nine patients healed by 1 month after therapy, and the lesions healed by 3 months after therapy on the other seven patients. Side effects were limited to a 27% incidence of mild, reversible hepatocellular enzyme elevation and an asymptomatic, reversible, approximately 70% decrease in serum testosterone in all patients. Pentostam cured 13 of 19 (68%) patients; the lesions on seven patients healed by the end of therapy, and the lesions on four other patients healed by 1 month after the end of therapy. Side effects were a 47% incidence of mild, reversible hepatocellular enzyme elevation and the morbidity due to 20 intramuscular injections in almost all patients. The placebo group of 11 patients had a 0% cure rate. By 1 month after therapy, all placebo-treated patients demonstrated new lesions or one lesion that was 23% to 875% larger than before therapy.. Both ketoconazole and Pentostam were more effective than placebo against L. braziliensis panamensis cutaneous leishmaniasis. Oral ketoconazole is comparable in efficacy to this parenteral Pentostam regimen and can be recommended as initial treatment for this disease.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Gluconates; Humans; Ketoconazole; Leishmaniasis; Male; Middle Aged; Randomized Controlled Trials as Topic; Testosterone

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Child; Child, Preschool; Female; Gluconates; Humans; Leishmaniasis; Leishmaniasis, Visceral; Male; Middle Aged

40 patients with American cutaneous leishmaniasis caused primarily by Leishmania braziliensis panamensis were treated with sodium stibogluconate in a double-blind, randomised controlled trial. Nine weeks after starting treatment, all 19 patients treated with 20 mg Sb/kg per day for twenty days were cured but 5 of 21 patients treated with 10 mg Sb/kg per day for twenty days had persistent active disease (p less than 0.05). Both treatment regimens were well tolerated and they were associated with a similar incidence of reversible toxic effects. Existing recommendations for therapy of American cutaneous leishmaniasis with sodium stibogluconate are inadequate for some patients, and higher doses are both safe and efficacious.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Clinical Trials as Topic; Double-Blind Method; Follow-Up Studies; Gluconates; Humans; Joint Diseases; Leishmania braziliensis; Leishmania donovani; Leishmaniasis; Male; Military Personnel; Random Allocation; Safety

Thirty-six patients with American cutaneous leishmaniasis were randomized to receive intravenous sodium stibogluconate for 10 days at a dose of 600 mg antimony (Sb) per day by one of three schedules: once daily by rapid infusion (A), by continuous 24 hr infusion (B), or in divided doses every eight hours by rapid infusion (C). Patients not cured after initial treatment were rerandomized to one of the other treatment schedules. An additional 19 patients who were not part of the randomized study received standard (STD) sodium stibogluconate treatment (600 mg Sb once daily by rapid infusion for 10 days, identical with schedule A). In the randomized study, the overall cure rate after the first course of treatment was 64%, but was higher for schedule A (100%) than for B (50%) or C (42%) (P less than 0.01). Considering all courses of treatment, schedule A was more effective (94%) than B (53%) or C (43%) (P less than 0.01). Paradoxically, patients in group A had a higher cure rate than patients in group STD (42% after the first course of treatment and 51% when all courses of treatment were considered). Side effects were mild and well tolerated. Total side effects were more frequent in groups B + C (52%) than A + STD (23%) due to an increased incidence of subjective complaints (26% vs. 10%, P less than 0.05) in patients receiving other than once daily rapid infusion. We conclude that giving the same total amount of sodium stibogluconate in three divided doses or by continuous infusion offers no advantage over standard, once daily treatment of American cutaneous leishmaniasis.

Topics: Antimony Sodium Gluconate; Clinical Trials as Topic; Drug Administration Schedule; Gluconates; Humans; Infusions, Parenteral; Leishmania; Leishmaniasis; Random Allocation

Leishmaniasis, an infectious disease, manifests itself mostly in two forms, cutaneous leishmaniasis (CL) and, a more severe and potentially deadly form, visceral leishmaniasis (VL). The current control strategy for leishmaniasis relies on chemotherapy drugs such as sodium antimony gluconate (SAG) and meglumine antimoniate (MA). However, all these chemotherapy compounds have poor efficacy, and they are associated with toxicity and other adverse effects, as well as drug resistance. While research in vaccine development for leishmaniasis is continuously progressing, no vaccine is currently available. However, some experimental vaccines such as LEISH-F1+MPL-SE (

Topics: Antimony Sodium Gluconate; Humans; Leishmaniasis; Leishmaniasis, Visceral; Meglumine Antimoniate; Models, Biological; Vaccines

Topical drug delivery against cutaneous leishmaniasis (CL) signifies an effective alternate for improving the availability and reducing the toxicity associated with the parenteral administration of conventional sodium stibogluconate (SSG) injection. The basic aim of the study was to develop nano-deformable liposomes (NDLs) for the dermal delivery of SSG against CL. NDLs were formulated by a modified thin film hydration method and optimized via Box-Behnken statistical design. The physicochemical properties of SSG-NDLs were established in terms of vesicle size (195.1 nm), polydispersity index (0.158), zeta potential (-32.8 mV), and entrapment efficiency (35.26%). Moreover, deformability index, in vitro release, and macrophage uptake studies were also accomplished. SSG-NDLs were entrapped within Carbopol gel network for the ease of skin application. The ex vivo skin permeation study revealed that SSG-NDLs gel provided 10-fold higher skin retention towards the deeper skin layers, attained without use of classical permeation enhancers. Moreover, in vivo skin irritation and histopathological studies verified safety of the topically applied formulation. Interestingly, the cytotoxic potential of SSG-NDLs (1.3 mg/ml) was higher than plain SSG (1.65 mg/ml). The anti-leishmanial activity on intramacrophage amastigote model of Leishmania tropica showed that IC

Topics: Administration, Topical; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Dose-Response Relationship, Drug; Drug Delivery Systems; Female; Leishmaniasis; Liposomes; Macrophages; Mice; Mice, Inbred BALB C; Nanoparticles; Organ Culture Techniques; Rats; Skin Absorption; Treatment Outcome

Some novel heteroretinoid-bisbenzylidine ketone hybrids have been synthesized and evaluated for their in vitro antileishmanial activity against intramacrophagic amastigotes of Leishmania donovani. Among all the nine synthetic compounds, five compounds (7c, 7d and 7f-h) have shown significant (less than 7μM) activity against intramacrophagic amastigotes. The IC50 values of these compounds were found better than the reference drugs sodium stibogluconate (SSG) and miltefosine. This study helped us in identifying the new class of compounds that could be exploited as potent antileishmanial agents.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cell Survival; Cells, Cultured; Chlorocebus aethiops; Inhibitory Concentration 50; Ketones; Leishmania donovani; Leishmaniasis; Macrophages; Mice; Molecular Structure; Parasitic Sensitivity Tests; Phosphorylcholine; Retinoids; Structure-Activity Relationship; Vero Cells

In the Brazilian Amazon, American tegumentary leishmaniasis (ATL) is endemic and presents a wide spectrum of clinical manifestations due, in part, to the circulation of at least seven Leishmania species. Few reports of Leishmania (Viannia) naiffi infection suggest that its occurrence is uncommon and the reported cases present a benign clinical course and a good response to treatment. This study aimed to strengthen the clinical and epidemiological importance of L. (V.) naiffi in the Amazon Region (Manaus, state of Amazonas) and to report therapeutic failure in patients infected with this species. Thirty Leishmania spp samples isolated from cutaneous lesions were characterised by multilocus enzyme electrophoresis. As expected, the most common species was Leishmania (V.) guyanensis (20 cases). However, a relevant number of L. (V.) naiffi patients (8 cases) was observed, thus demonstrating that this species is not uncommon in the region. No patient infected with L. (V.) naiffi evolved to spontaneous cure until the start of treatment, which indicated that this species may not have a self-limiting nature. In addition, two of the patients experienced a poor response to antimonial or pentamidine therapy. Thus, either ATL cases due to L. (V.) naiffi cannot be as uncommon as previously thought or this species is currently expanding in this region.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Brazil; Demography; Electrophoresis; Geography; Humans; Leishmania; Leishmaniasis; Male; Middle Aged; Pentamidine; Population Density; Rainforest; Rare Diseases; Remission, Spontaneous; Skin; Treatment Failure; Young Adult

Leishmaniasis is caused by Leishmania protozoa. It is widely present in more than 88 countries worldwide, resulting in up to 80,000 deaths annually. Leishmaniasis occurs as visceral, cutaneous, or mucocutaneous variants. Mucosal involvement can occur secondarily to the cutaneous or visceral varieties. However, primary mucosal leishmaniasis (PML) occurs without any present or past cutaneous and or visceral disease. It is extremely rare, and its diagnosis may present a serious challenge. It may be difficult to differentiate it from granulomatous conditions like tuberculosis, sarcoidosis, leprosy, fungal infections, Wegener's granuloma, and neoplasms. Here, we present a case of PML in Saudi Arabia.

Topics: Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmaniasis; Male; Mucous Membrane; Otorhinolaryngologic Diseases; Saudi Arabia

Several plant products have been tested and found to possess antileishmanial activity. The present study was undertaken to establish whether methanolic extract of Allium sativum Linn has antileishmanial activity in comparison to standard drugs.. Methanolic extract of A. sativum bulbs was screened for in vitro and in vivo antileishmanial activity against Leishmania major strain (NLB 145) and L. donovani strain (NLB 065). Pentostam and Amphotericin B were used as standard drugs. BALB/c mice and golden hamsters (Mesocricetus auratus) were used in in vivo studies on L. major and L. donovani respectively.. The extract exhibited very low cytotoxicity (IC50 >450 μg/ml) against Vero cells. The extract had significantly better (p <0.001) leishmanicidal activity against both species (IC50 34.22 μg/ml to L. major, 37.41 μg/ml to L. donovani) than Pentostam. However, the activity was significantly lower (p <0.001) than that of Amphotericin B against both the species. At a concentration of 250 μg/ml, the extract induced the production of 60 μM of nitric oxide, a ten-fold up-regulation in activated macrophages. The multiplication indices for L. major amastigotes treated in 100 μg/ml were significantly different (p <0.05). Treatment with the extract, daily for 28 days led to a significant reduction (p <0.05) in footpad swelling in BALB/c mice; similar activity noticed in the treatment with standard drugs. The Leishman-Donovan Units (LDU) for the extract treated animals were significantly higher (p <0.05) than those of standard drugs, but lower compared to the negative control.. Since the mechanism of action for the methanolic extract is apparently immunomodulatory, garlic compounds could be purified and tried as complementary medicine in the management of leishmaniases.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Chlorocebus aethiops; Cricetinae; Disease Models, Animal; Garlic; Humans; Leishmania donovani; Leishmania major; Leishmaniasis; Mesocricetus; Methanol; Mice; Mice, Inbred BALB C; Plant Extracts; Vero Cells

This study aimed to identify differentially overexpressed membrane-enriched as well as cytosolic proteins in SAG sensitive and resistant clinical strains of L. donovani isolated from VL patients which are involved in the drug resistance mechanism.. The proteins in the membrane-enriched as well as cytosolic fractions of drug-sensitive as well as drug-resistant clinical isolates were separated using two-dimensional gel electrophoresis and overexpressed identified protein spots of interest were excised and analysed using MALDI-TOF/TOF.. Six out of 12 overexpressed proteins were identified in the membrane-enriched fraction of the SAG resistant strain of L. donovani whereas 14 out of 18 spots were identified in the cytosolic fraction as compared with the SAG sensitive strain. The major proteins in the membrane-enriched fraction were ABC transporter, HSP-83, GPI protein transamidase, cysteine-leucine rich protein and 60S ribosomal protein L23a whereas in the cytosolic fraction proliferative cell nuclear antigen (PCNA), proteasome alpha 5 subunit, carboxypeptidase, HSP-70, enolase, fructose-1,6-bisphosphate aldolase, tubulin-beta chain have been identified. Most of these proteins have been reported as potential drug targets, except 60S ribosomal protein L23a and PCNA which have not been reported to date for their possible involvement in drug resistance against VL.. This study for the first time provided a cumulative proteomic analysis of proteins overexpressed in drug resistant clinical isolates of L. donovani indicating their possible role in antimony resistance of the parasite. Identified proteins provide a vast field to be exploited for novel treatment strategies against VL such as cloning and overexpression of these targets to produce recombinant therapeutic/prophylactic proteins.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Cytosol; Electrophoresis, Gel, Two-Dimensional; Humans; Leishmania donovani; Leishmaniasis; Membrane Proteins; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Topics: Aged; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Biopsy; Chronic Disease; Dermatitis, Atopic; Facial Dermatoses; Female; Humans; Leishmania donovani; Leishmania infantum; Leishmaniasis; Treatment Outcome

A set of flavonoids from Consolida oliveriana, kaempferol (1), quercetin (2), trifolin (3), and acetyl hyperoside (5) and their O-acetyl derivatives (1a, 2a, 3a), and octa-O-acetylhyperoside (4) showed leishmanicidal activity against promastigote as well as amastigote forms of Leishmania spp. The cellular proliferation, metabolic, and ultrastructural studies showed that the acetylated compounds 2a, 3a, and 4 were highly active against Leishmania (V.) peruviana, while 2a as well as 4 were effective against Leishmania (V.) braziliensis. These compounds were not cytotoxic and are effective at similar concentrations up to or lower than the reference drugs (pentostam and glucantim).

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Female; Flavonoids; Galactosides; Kaempferols; Leishmania; Leishmaniasis; Meglumine; Meglumine Antimoniate; Molecular Structure; Organometallic Compounds; Ranunculaceae; Rats; Rats, Inbred Strains; Turkey

The in vitro susceptibilities of the reference strain Leishmania donovani MHOM/ET/67/L82 to sodium stibogluconate, amphotericin B, miltefosine, and the experimental compound PX-6518 were determined for extracellular log-phase promastigotes, established axenic amastigotes, fresh spleen-derived amastigotes, and intracellular amastigotes in primary mouse peritoneal macrophages. Susceptibility to amphotericin B did not differ across the various axenic models (50% inhibitory concentrations [IC50], 0.6 to 0.7 microM), and amphotericin B showed slightly higher potency against intracellular amastigotes (IC50, 0.1 to 0.4 microM). A similar trend was observed for miltefosine, with comparable efficacies against the extracellular (IC50, 0.4 to 3.8 microM) and intracellular (IC50, 0.9 to 4.3 microM) stages. Sodium stibogluconate, used either as Pentostam or as a crystalline substance, was inactive against all axenic stages (IC50, >64 microg SbV/ml) but showed good efficacy against intracellular amastigotes (IC50, 22 to 28 microg SbV/ml); the crystalline substance was about two to three times more potent (IC50, 9 to 11 microg SbV/ml). The activity profile of PX-6518 was comparable to that of sodium stibogluconate, but at a much higher potency (IC50, 0.1 microg/ml). In conclusion, the differential susceptibility determines which in vitro models are appropriate for either drug screening or resistance monitoring of clinical field isolates. Despite the more complex and labor-intensive protocol, the current results support the intracellular amastigote model as the gold standard for in vitro Leishmania drug discovery research and for evaluation of the resistance of field strains, since it also includes host cell-mediated effects. Axenic systems can be recommended only for compounds for which no cellular mechanisms are involved, for example, amphotericin B and miltefosine.

Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cells, Cultured; Inhibitory Concentration 50; Leishmania donovani; Leishmaniasis; Mice; Microscopy, Electron, Transmission; Parasitic Sensitivity Tests; Phosphorylcholine; Saponins; Triterpenes

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

Diagnostic material from patients with leishmaniasis is generally available as promastigotes, and proper testing for susceptibility to first-line drugs by the intracellular amastigote assay is frequently hampered by the poor infectivity of the promastigotes for the macrophage host cell. Several conditions for optimization of the in vitro metacyclogenesis and cell infectivity of Leishmania donovani, L. guyanensis, and L. braziliensis field strains obtained from patients receiving standard antimony medication were investigated. Triggering log-phase promastigotes to become amastigote-like by increasing the temperature or acidifying the culture medium was not successful. Adequate metacyclogenesis and the highest levels of macrophage infection were obtained after 5-day-old late-log-phase promastigote cultures were preconditioned at 25 degrees C to pH 5.4 for 24 h in Schneider's medium prior to infection. The susceptibility assay with primary peritoneal mouse macrophages included pentavalent antimony (Sb(V); sodium stibogluconate), trivalent antimony (Sb(III); potassium antimonyl tartrate), miltefosine, and the experimental drug PX-6518. All strains were sensitive to miltefosine (50% inhibitory concentration [IC(50)] < 10 microM) and PX-6518 (IC(50) < 2 microg/ml) but showed distinct susceptibility to Sb(V) and/or Sb(III), depending on whether they were derived from cured, relapse, or nonresponder patients. Within the available set of Leishmania species and strains, simultaneous Sb(V)-Sb(III) resistance was clearly associated with treatment failure; however, a larger set of isolates is still needed to judge the predictive value of Sb(V)-Sb(III) susceptibility profiling on treatment outcome. In conclusion, the proposed conditioning protocol further contributes toward a more standardized laboratory model for evaluation of the drug sensitivities of field isolates.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cells, Cultured; Flow Cytometry; Leishmania; Leishmaniasis; Macrophages, Peritoneal; Mice; Microscopy; Parasitic Sensitivity Tests; Phosphorylcholine; Saponins; Temperature; Triterpenes

High-performance liquid chromatography (HPLC), mass spectrometry (MS), and computational chemistry has been applied to resolve the composition and structure of the Sb species present in dilutions of Pentostam, a first-line treatment drug against Leishmania parasites. Using HPLC-inductively coupled plasma-MS and electrospray-MS, it was shown that the original drug consists of large Sb(V)-glyconate complexes of polymeric nature that degrade upon dilution. In dilution solution, the drug is a mixture of noncomplexed Sb(V), large polymeric complexes as well as several low molecular mass Sb(V)-glyconate complexes of various stoichiometry (1:1, 1:2, 1:3, 2:2, 2:3, 2:4, 3:3, 3:4). The 1:1 complex became the most abundant low molecular mass Sb(V) complex with dilution time. A novel mixed-mode chromatographic system was applied in order to separate complexes of various stoichiometry and isomers. Density functional theory was used to study the structure of the 1:1 Sb-gluconate complex with three or four solvent molecules bound. By computing the structures and the free energies of the various possible isomers in aqueous solvation models, the most likely structures of the species were deduced. Importantly, 6-coordination is always preferred over 5-coordination, and the species commonly adopt conformations involving tris-coordination of deprotonated hydroxyl groups from gluconate.

Topics: Antimony Sodium Gluconate; Chromatography, High Pressure Liquid; Drug Stability; Leishmaniasis; Mass Spectrometry; Molecular Conformation; Molecular Weight; Pharmaceutical Preparations; Solutions

Leishmaniasis is an important opportunistic disease among patients infected with human immunodeficiency virus (HIV)-1. The pentavalent antimony compound sodium stibogluconate is a drug of choice for the treatment of leishmaniasis. Because sodium stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and such inhibitors can promote HIV-1 replication, we tested the effect of this compound on virus gene expression. Using pseudotyped reporter viruses and fully infectious laboratory-adapted and clinical strains of HIV-1, we report that sodium stibogluconate induces an increase in HIV-1 transcription and virus replication in primary CD4(+) T cells and in thymic histocultures. This activation is a slow process and appears to involve the transcription factors nuclear factor- kappa B and activator protein 1, as well as the Syk, Jun, and mitogen-activated protein kinase/extracellular signal-related kinase signal-transduction pathways. In addition, the effect seems to be partly mediated by a soluble factor. Altogether, these findings might reveal clinical implications for the treatment of leishmaniasis in HIV-1-infected patients.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; CD4-Positive T-Lymphocytes; Cells, Cultured; HIV-1; Humans; Leishmaniasis; Leukocytes, Mononuclear; Organ Culture Techniques; Thymus Gland; Transcription, Genetic; Viral Proteins; Virus Replication

Rocco Jemma was the greatest Italian paediatrician, because he left the greatest signs in history. The most important amongst his achievements is certainly the foundation of the Rocco Jemma School which spread all over Italy and provided the greatest number of paediatric teachers who reached excellence levels. He was, among all the presidents of the Italian Society of Paediatrics, the one who was in office for the longest time. The therapy of leishmaniosis, based on antimonial derivatives formulated by Jemma, is still used and respected today.

Topics: Antimony; Antimony Sodium Gluconate; Child; History, 19th Century; History, 20th Century; Humans; Injections, Intravenous; Italy; Leishmaniasis; Pediatrics; Societies, Medical

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

In spite of the extensive use of pentavalent antimony chemotherapy, the mechanism of its anti-leishmania action is still not clear. Here, we report the interactions of Sb(V), including the clinically used drug stibogluconate, with guanosine 5'-monophosphate (5'-GMP) and guanosine 5'-diphospho-d-mannose (5'-GDP-mannose) in aqueous solution. The deprotonated hydroxyl groups (-OH) of the ribose ring are shown to be the binding site for Sb(V), probably via chelation. Both mono- and bis-adducts were formed as determined by NMR, high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS), and both of them are stable in the pH range of 4 to around 9.5. The formation of the mono-adduct (k(1)=1.67x10(-3) and 3.43x10(-3) mM(-1) min(-1) for Sb(5'-GMP) and Sb(5'-GDP-mannose), respectively, at 298 K) was 10-fold faster than that of the bis-adduct (k(2)=0.16x10(-3) and 0.21x10(-3) mM(-1) min(-1), for Sb(5'-GMP)(2) and Sb(5'-GDP-mannose)(2), respectively), and the mono-adduct was the major species in solution with the [bis-adduct]/[mono-adduct]<0.5. The reactions of stibogluconate with 5'-GMP and 5'-GDP-mannose were slower than that of antimonate under similar conditions.

Topics: Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Chromatography, High Pressure Liquid; Guanosine Diphosphate Mannose; Guanosine Monophosphate; Humans; In Vitro Techniques; Kinetics; Leishmania; Leishmaniasis; Magnetic Resonance Spectroscopy; Spectrometry, Mass, Electrospray Ionization

Despite extensive use of antimonial compounds in the treatment of leishmaniasis, their mode of action remains uncertain. Here we show that trivalent antimony (Sb(III)) interferes with trypanothione metabolism in drug-sensitive Leishmania parasites by two inherently distinct mechanisms. First, Sb(III) decreases thiol buffering capacity by inducing rapid efflux of intracellular trypanothione and glutathione in approximately equimolar amounts. Second, Sb(III) inhibits trypanothione reductase in intact cells resulting in accumulation of the disulfide forms of trypanothione and glutathione. These two mechanisms combine to profoundly compromise the thiol redox potential in both amastigote and promastigote stages of the life cycle. Furthermore, we demonstrate that sodium stibogluconate, a pentavalent antimonial used clinically for the treatment for leishmaniasis, induces similar effects on thiol redox metabolism in axenically cultured amastigotes. These observations suggest ways in which current antimony therapies could be improved, overcoming the growing problem of antimony resistance.

Topics: Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Cells, Cultured; Cricetinae; Disulfides; Drug Resistance; Humans; Leishmania donovani; Leishmaniasis; Mesocricetus; Oxidation-Reduction; Sulfhydryl Compounds

We present a 35 years-old man with fever related leishmania infection as the first complication of a previously undiagnosed cirrhosis. Diagnosis of leishmaniasis is often complicated. Clinical and therapeutical aspects are commented.

Topics: Adult; Animals; Antibodies, Protozoan; Antimony Sodium Gluconate; Humans; Leishmania; Leishmaniasis; Liver Cirrhosis; Liver Diseases, Parasitic; Male; Treatment Outcome

Visceral leishmaniasis is a parasitic disease endemic in the Mediterranean Basin, including Malta. Finnish-type congenital nephrotic syndrome is an autosomal recessive condition that presents in the first 3 months of life with heavy proteinuria, hypoalbuminemia with secondary edema, and hyperlipidemia. We present an infant with congenital nephrotic syndrome who had had unilateral nephrectomy and who also developed visceral leishmaniasis. He was successfully cleared of the infection by the administration of sodium stibogluconate, with no deterioration of renal function or other complications.

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Infant; Leishmaniasis; Male; Nephrotic Syndrome; Viscera

Topics: Anemia; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Dermatitis; Diagnosis, Differential; Dog Diseases; Dogs; Fatal Outcome; Finland; Histocytochemistry; Leishmania infantum; Leishmaniasis; Macrophages; Male; Microscopy, Electron; Spain; Tongue; Tongue Neoplasms

Leishmaniasis is a chronic parasitic protozoal disease transmitted by sandfly vectors and is endemic in some regions of South America, Asia, Africa and Mediterranean countries. This case report describes a British patient who presented with oral mucosal leishmaniasis and in whom it was also the first sign of HIV disease. We believe it is the first reported case of isolated oral mucosal leishmaniasis as a presenting feature of otherwise unknown HIV infection.

Topics: Animals; Anti-HIV Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; HIV Infections; HIV Seropositivity; Humans; Leishmaniasis; Male; Middle Aged; Mouth Diseases

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

Topics: Adult; AIDS-Related Opportunistic Infections; Antimony Sodium Gluconate; Humans; Immunocompetence; Leishmaniasis; Male; Pancreatitis

We tested the World Health Organization (WHO) recommended treatment for mucosal leishmaniasis in 16 Panamanians with disease due to Leishmania braziliensis panamensis. Disease was mild in this population because it was limited to the nasal mucosa and only one patient had septal perforation. The patients were administered 20 mg antimony (in the form of Pentostam) per kg intravenously each day for 28 days. Ten patients completed therapy and were cured at 12 month follow-up. Three patients completed therapy, healed their lesions, but relapsed at the six or 12 month follow-up. Three patients terminated therapy prematurely because of liver enzyme elevations in conjunction with either EKG abnormalities or musculoskeletal complaints; none of these patients were healed. This study indicates that in patients with mild mucosal leishmaniasis, the WHO regimen is curative in 77% patients who complete treatment and in 63% of all patients.

Topics: Adult; Aged; Antimony Sodium Gluconate; Female; Humans; Leishmaniasis; Leishmaniasis, Mucocutaneous; Male; Middle Aged; Nasal Mucosa; Nasal Septum; Recurrence

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Biopsy; Female; Humans; Isoniazid; Ketoconazole; Leishmaniasis; Levamisole; Male; Rifampin; Ultraviolet Therapy

In a retrospective study the data concerning 49 patients with cutaneous leishmaniasis were analysed. The group included 39 patients seen in Amsterdam in the period 1979-1988 in the Royal Institute for the Tropics and the University Medical Centre and 10 patients seen in the University Hospital of Leiden in the period 1970-1982. Mediterranean countries, especially Spain, were important sources of infection. In 26 patients, one skin lesion was found. All but one of the patients had (papulo)nodules, nodules with central scab formation and/or ulcerative skin lesions. In most cases the lesions were localized on the face and extremities, one patient had a mucosal lesion of the nose, three had sporotrichoid extension and six, lymphadenitis. For demonstration of the parasite, aspiration, smear, biopsy and culture were used with varying frequencies. The biopsy and culture methods contributed most to the diagnosis. The treatment in 22 patients consisted in parenteral administration of sodium stibogluconate while 13 received primary cryotherapy. In addition, four patients were subjected to cryotherapy because of a recurrence after, or side effects of the treatment with sodium stibogluconate. In three patients, spontaneous healing was awaited. Owing to incomplete follow-up, the ultimate condition was not known of all patients; the skin lesions treated with cryotherapy all healed. In case of nodular and ulcerative skin lesions in a person who has lived in the (sub)tropics, cutaneous leishmaniasis should be considered; the geographical anamnesis is of great importance in this respect.

Topics: Adult; Animals; Antimony Sodium Gluconate; Child; Humans; Leishmania; Leishmaniasis; Travel

A complicated case of ACL, which showed feverish and widely disseminated ulcers over the face was successfully treated with systemic antibiotic and pentostam as intralesional injections.

Topics: Antimony Sodium Gluconate; Humans; Leishmaniasis; Male; Middle Aged; Saudi Arabia

Fifty three (30 male and 23 female), previously untreated, patients with post kala-azar dermal leishmaniasis (PKDL) were treated with sodium stibogluconate, at the dose of 20 mg/kg/bw/d/im/(with a maximum of 8.5 ml) for 120 days (or more, if necessary). All the patients were followed up for 12 months. The patients were assessed after 40 days and thereafter at an interval of 20 days. The mean age of onset was 24 yr, maximum number of patients developed the disease within 3 yr of apparent cure of kala-azar. Maximum number of patients sought treatment within 5 yr of the onset of PKDL. The disease affected the face (98%), trunk (83%), upper limb (72%), lower limb (40%), genetalia (6%), and mucus membrane of the tongue 40%. The lesions observed were nodules (19%), papules (30%), and hypopigmented (45%) and reddish macules (7%). The parasites could be demonstrated in the nodules (100%), papules (69%) and macules (59%). The response to treatment started in 72 per cent of patients in the first 20 days and in 40 days in all patients. All the nodules and papules disappeared in 120 days, and the macules within 200 days. The side effects of treatment noted were changes in S T and T in electrocardiogram (7%), arthralgia (11%), allergic rash (7%), swelling at the site of injection (5%), neuralgia (4%) and metalic taste (6%). The S T and T changes reverted to normal when the drug was discontinued for 20 days. Arthralgia improved with indomethacin. The higher dosages and longer course of treatment were well tolerated and resulted in a cure in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Child; Child, Preschool; Female; Gluconates; Humans; Infant; Leishmaniasis; Leishmaniasis, Visceral; Male; Middle Aged

Cutaneous leishmaniasis is a parasitic infection which is especially endemic in the southern parts of Europe, in several regions of Africa, and in South and Central America. Whether treatment is necessary or not depends on the virulence of the germ, the infection's localization, and the host's immunological reaction. Because of the high rate of recidivation and the large number of undesirable side-effects of systemic chemotherapy of localized cutaneous leishmaniasis, several methods of local therapy have been tested. This case report demonstrates one of several approaches to the local treatment of this disease. Despite progress in this field, cutaneous leishmaniasis will continue to be a considerable medical and sociopolitical problem, because successful treatments in under-developed countries must be highly efficient, cost little, be easy to administer, and have a low rate of undesirable side-effects.

Topics: Administration, Topical; Adult; Antimony Sodium Gluconate; Ear Cartilage; Ear, External; Humans; Leishmaniasis; Male; Recurrence; Ulcer

Quantitative in vitro drug sensitivity of 32 Leishmania isolates (16 from patients failing pentavalent antimony [SbV] therapy) was determined using a radiorespirometric microtechnique (RAM). Of 30 isolates with histories, 22 (73%) RAM tests agreed with patient history; the remaining 8 (27%) did not. There was no difference in RAM drug sensitivity: clinical correlation between 15 isolates tested blindly and 15 with known clinical history (4 did not agree with clinical history in both). Test sensitivity appeared to be limited only by the sensitivity of the Leishmania to SbV and could be detected at 2 micrograms/ml Sb (about 10% of serum drug level). An isolate from a patient with untreated self-healing cutaneous disease was drug resistant. Using RAM, parasite drug sensitivity can be quantified apart from patient physiologic and immunologic variables intrinsic to clinical data. Potency differed a maximum of 100% (weight% Sb:weight% Sb) among drug lots and also between Glucantime and Pentostam. Potency changes between drug lots were not explainable based on Sb content or test-to-test variability. This microtest offers a rapid method for evaluating the drug sensitivity of patient isolates and for determining of the activity of pentavalent antimonials and other candidate anti-leishmanials prior to the initiation of therapy.

Topics: Adenosine; Animals; Antimony Sodium Gluconate; Drug Resistance; Eflornithine; Leishmania; Leishmaniasis; Meglumine; Meglumine Antimoniate; Organometallic Compounds

Topics: Antimony Sodium Gluconate; Drug Therapy, Combination; Humans; Leishmaniasis; Male; Middle Aged; Pentamidine

Antimony unresponsiveness in mucocutaneous and visceral leishmaniasis is a serious clinical problem. Information on the mechanisms and characteristics of drug resistance in parasites that suggest chemotherapeutic strategies to overcome resistance is of practical importance. We developed nine lines of Leishmania resistant to drugs, the major emphasis being on pentavalent antimony (Sb) complexed to carbohydrate in the form of sodium stibogluconate (Pentostam), one of the only two antileishmanial agents with a clearly favorable therapeutic index. Resistance to Pentostam (33- to 212-fold increase) was obtained in promastigotes of Leishmania in vitro by exposure to gradually increasing concentrations of drug over several passages. Resistance to Sb was found to be either stable or unstable. Stable resistance to Sb required (greater than 3) exposures of the initial sensitive clones to Pentostam and tended to stabilize with increased time under pressure. In general, resistance obtained in a clone after only a few (less than or equal to 3) step treatments was low and unstable. Differences in the susceptibility to Pentostam were found between strains isolated from patients with American cutaneous leishmaniasis. In addition, natural isolates of Leishmania from patients represented a heterogeneous population of parasites as demonstrated by a biphasic concentration response to Sb (typical of mixed population dynamics) and by marked differences in susceptibility to Pentostam among clones prepared from single isolates. These results suggest that the emergence of parasite resistance to antimonial treatment is a potential risk of inadequate dose therapy.

Topics: Animals; Antimony Sodium Gluconate; Dose-Response Relationship, Drug; Drug Resistance; Gluconates; Humans; Leishmania; Leishmania braziliensis; Leishmania mexicana; Leishmaniasis

Topics: Adult; Antimony Sodium Gluconate; Biopsy; Diagnosis, Differential; Ear Diseases; Ear, External; Humans; Leishmaniasis; Male

Topics: Antimony Sodium Gluconate; Humans; Leishmaniasis; Meglumine

Topics: Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Humans; Leishmaniasis; Meglumine; Meglumine Antimoniate; Organometallic Compounds

Cutaneous leishmaniasis (CL.) caused by L. major or L. tropica is endemic in many countries in the Middle East particularly Saudi Arabia. The disease is characterized by spontaneous healing and sterilizing immunity. However, medical treatment is always indicated particularly those due to L. tropica to reduce the reservoir of infection. In this study parasitologically proven patients with CL. were treated with Pentostam (57) or Cryosurgery (38). Both gave satisfactory results. However, the disadvantages of each line were discussed. There is a need for a drug which is cheaper, less toxic, safe, more effective and more easily administered than those currently available.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Child; Child, Preschool; Cryosurgery; Female; Gluconates; Humans; Infant; Leishmaniasis; Male

We describe an in vitro microtest which is quantitative, rapid, and readily applicable to parasites isolated from all major forms of human leishmaniasis. It is based on drug-mediated inhibition of promastigote catabolism of a battery of simple 14C-substrates to 14CO2. Each test requires less than 1 microCi. The test is conducted in a serum-free, chemically defined medium containing 120 micrograms protein/ml, minimizing the possible interference of drug: serum protein interaction. Prior adaptation is not necessary to cultivate "difficult-to-grow" species. Leishmania sensitivity to pentavalent antimonials is detectable at micrograms levels below concentrations achievable in patients' sera.

Topics: Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Culture Media; Gluconates; Humans; Least-Squares Analysis; Leishmania; Leishmaniasis; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Regression Analysis; Sorbitol; Time Factors

BALB/c mice were infected with Leishmania mexicana amazonensis and/or Plasmodium yoelii in order to determine the impact of multiple parasitic infection on the efficacy of chemotherapeutic agents. Uninfected, P. yoelii-infected, L.m. amazonensis-infected, and L.m. amazonensis and P. yoelii-infected mice were inoculated with cimetidine (80 mg kg-1 day-1) or pentostam (200 mg kg-1 day-1) once a day for an initial 20-day period, and once a week thereafter. Leishmania mexicana amazonensis lesion development and P. yoelii parasitaemia were the criteria used to assay disease severity. Mice infected with both P. yoelii and L.m. amazonensis developed more severe disease than did animals infected with either parasite alone. Cimetidine and pentostam each slowed the development of L.m. amazonensis in animals infected with only that parasite and in animals infected with both P. yoelli and L.m. amazonensis. However, mice treated with pentostam developed more severe P. yoelii infections than did control animals, whereas cimetidine significantly reduced P. yoelii parasitaemia in all instances.

Topics: Animals; Antimony Sodium Gluconate; Cimetidine; Female; Gluconates; Leishmania mexicana; Leishmaniasis; Malaria; Mice; Mice, Inbred BALB C; Plasmodium yoelii

The anti-leishmanial activity of ivermectin, pentostam or combination of pentostam with either levamisole or thymic extract was tested against Leishmania donovani infection in hamsters and mice. In vitro peritoneal macrophage-parasite interaction, the effect of splenic cells on the interaction of macrophages and parasites, spleen weight, parasite burden in spleen tissue as well as the antibody titers using micro-ELISA were used as parameters for evaluating the efficacy of these chemotherapeutic regimens. Treatment with ivermectin and immunoenhancement with pentostam combined with levamisole gave best results in both animal models. Furthermore, regimens used in this work were all active in reducing phagocytosis of promastigotes by macrophages in vitro.

Topics: Adjuvants, Immunologic; Animals; Antimony Sodium Gluconate; Cricetinae; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Gluconates; In Vitro Techniques; Ivermectin; Leishmania donovani; Leishmaniasis; Levamisole; Macrophages; Male; Mice; Mice, Inbred BALB C; Organ Size; Spleen; Thymus Extracts

Topics: Adult; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Gluconates; Humans; Injections, Intradermal; Leishmaniasis; Male; Organometallic Compounds; Succimer; Sulfhydryl Compounds

Cell-mediated immune (CMI) response and the concurrent clinical events were studied longitudinally before, during and after treatment in 24 kala-azar (KA) and ten post-kala-azar dermal leishmaniasis (PKADL) patients for a period of six months. The status of specific CMI response was estimated by in vitro tests, viz. lymphocyte transformation and leucocyte migration inhibition in response to L. donovani antigen. The generalized CMI response was assessed by lymphocyte transformation in the presence of mitogen (phytohaemagglutinin) and quantitation of the circulatory T-lymphocyte population. To measure the drug response, the extent of clinical improvement following treatment was used as a yardstick. The results showed that suppression of the CMI response was both specific and generalized in nature during the active stage of KA; but in PKADL, unlike in KA, suppression of the CMI response was found to be associated only at the specific level. With administration of the drug (sodium antimony gluconate), the immunosuppression was gradually eliminated with concomitant clinical improvement in both KA and PKADL patients, although the latter took a longer period of time and a larger amount of drugs compared to the former.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Cell Migration Inhibition; Child; Female; Humans; Leishmaniasis; Leishmaniasis, Visceral; Leukocyte Count; Leukocytes; Lymphocyte Activation; Male; T-Lymphocytes

To facilitate studies on the effect of chemotherapeutic agents on the host-parasite interaction in leishmaniasis, we have developed an experimental model for infecting mouse peritoneal macrophages in culture with recently-isolated Leishmania donovani promastigotes. As the drug action is often dependent on concentration, the distribution of sodium stibogluconate, which is the commonly used drug for treatment of leishmaniasis, was studied in various parts of the macrophages by energy dispersive X-ray microanalysis. The drug was found to accumulate in secondary lysosomes. The ultrastructural examination, using TEM and SEM, of macrophages, whose secondary lysosomes had been preloaded with gold particles, showed that leishmania parasites are phagocytosed and finally located in secondary lysosomes. Using flameless atomic absorption spectrophotometry, the concentration of Mn, Fe and Cu in promastigotes of Leishmania donovani, Leishmania aethiopica, Leishmania crithidia, Leishmania major and their culture media was estimated. Of the three transition metals, the parasites accumulated only Mn from the medium, which they may use in a primitive defense mechanism against reactive oxygen metabolites produced by macrophages during the respiratory burst associated with phagocytosis.

Topics: Animals; Antimony Sodium Gluconate; Cells, Cultured; Disease Models, Animal; Electron Probe Microanalysis; Female; Gluconates; Gold; Leishmania; Leishmaniasis; Leishmaniasis, Visceral; Lysosomes; Macrophages; Male; Metals; Mice; Microscopy, Electron; Microscopy, Electron, Scanning; Specimen Handling; Spectrophotometry, Atomic

One hundred and thirty lesions of cutaneous leishmaniasis in 60 patients were treated with intralesional injections of Pentostam and 30 lesions were left untreated as controls. The injections were given at 8-day intervals and the patients followed-up for 42 days. One hundred and four lesions (80%) needed one injection only, 20 (15.4%) needed two and six (4.6%) needed three injections. One hundred and twenty three of the treated lesions (94.6%) showed a good clinical response with complete healing or marked improvement within the follow-up period. None of the control lesions showed marked improvement or complete healing. Scarring was minimal or absent following healing of treated lesions. The only side-effect was some localized pain following the injection. We recommend intralesional Pentostam as a safe and effective method of treating acute cutaneous leishmaniasis.

Topics: Acute Disease; Adolescent; Adult; Antimony Sodium Gluconate; Child; Female; Gluconates; Humans; Injections; Leishmaniasis; Male; Middle Aged

Topics: Animals; Antimony Sodium Gluconate; Cimetidine; Deoxyguanosine; Drug Therapy, Combination; Immunotherapy; Leishmaniasis; Mice; Mice, Inbred BALB C

Furazolidone and nitrofurazone showed in vitro activity against amastigotes of Leishmania donovani, L. enriettii and L. major in macrophages, at concentrations which were also toxic to the macrophages. A low grade of activity was observed against L. donovani infections in BALB/c mice by furazolidone but not with nitrofurazone. Nitrofurazone, in two concentrations, was not active when applied to the lesions of cutaneous leishmaniasis due to L. enriettii (guinea-pig infection) or L. major strain P (BALB/c mouse infection). After systemic administration to BALB/c mice infected with L. major strain JISH 252 clone 1, low-grade activity was observed at the highest level tested.

Topics: Animals; Antimony Sodium Gluconate; Furazolidone; Guinea Pigs; Leishmania; Leishmania donovani; Leishmania mexicana; Leishmania tropica; Leishmaniasis; Macrophages; Mice; Mice, Inbred BALB C; Nitrofurazone

Topics: Antimony Sodium Gluconate; Gluconates; Humans; Injections, Jet; Leishmaniasis

Topics: Adult; Antimony Sodium Gluconate; Drug Evaluation; Female; Gluconates; Humans; Immunologic Techniques; Leishmaniasis; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Random Allocation; Sorbitol

We report the case of a patient who acquired cutaneous leishmaniasis in Israel, with multiple lesions on the face and wrists. The diagnosis was made several months after the onset of disease. We observed large multiple ulcers, which at first responded to sodium stibogluconate (600 mg daily for 2 weeks). After initially decreasing in size, the lesions remained unchanged. Several weeks later clinical exacerbation of the cutaneous leishmaniasis was observed. Fearing late complications on the upper eyelid, we administered two 2-week courses of ketoconazole, 800 mg daily. The early and rapid improvement achieved indicates that ketoconazole was successful in this case of cutaneous leishmaniasis.

Topics: Aged; Animals; Antimony Sodium Gluconate; Drug Resistance; Gluconates; Humans; Ketoconazole; Leishmania tropica; Leishmaniasis; Male

The case of a 15-year-old boy with recurrent cutaneous leishmaniasis is reported. Species identification was based on results of serotyping and isoenzyme analysis. The patient did not respond to rifampin combined with isoniazid or to ketoconazole. Subsequent therapy with systemic sodium antimony gluconate resulted in complete regression of the lesions.

Topics: Adolescent; Antimony Sodium Gluconate; Facial Dermatoses; Gluconates; Humans; Injections, Intramuscular; Leishmaniasis; Male; Recurrence

Topics: Antimony Sodium Gluconate; Diagnosis, Differential; Humans; Kenya; Leishmaniasis; Leishmaniasis, Visceral; Male; Middle Aged; Time Factors

In major American textbooks of dermatology and medicine the use of intralesional sodium stibogluconate (Pentostam) in the treatment of cutaneous leishmaniasis is not mentioned. In this brief informal communication I have summarized personal experience with this effective treatment modality.

Topics: Adolescent; Adult; Aged; Antimony Sodium Gluconate; Child; Child, Preschool; Gluconates; Humans; Infant; Injections; Leishmaniasis; Middle Aged

Topics: Adult; Antimony; Antimony Sodium Gluconate; Gluconates; Humans; Leishmaniasis; Male; Organometallic Compounds; Succimer; Sulfhydryl Compounds

Sodium stibogluconate although potentially cardiotoxic is the drug of choice for Kalaazar and cutaneous leishmaniasis due to Leishmania braziliensis. Increasing use of this drug in the British Army has necessitated a formal evaluation of its cardiac side-effects. Consequently a detailed study of the cardiac effects of sodium stibogluconate was undertaken in 22 male soldiers using for the first time modern non-invasive techniques. Intravenous sodium stibogluconate 600 mg daily for 10 days did not affect blood pressure, heart rate, left ventricular contractile function or rhythm. Electrocardiography showed a reversible reduction of T wave amplitude.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Echocardiography; Electrocardiography; Gluconates; Heart; Heart Rate; Humans; Leishmaniasis; Male; Monitoring, Physiologic

Serial electrocardiograms (ECGs) were obtained during 65 courses of sodium stibogluconate treatment in 59 Kenyan patients with leishmaniasis (56 visceral and 3 cutaneous). ECG abnormalities developed during 54% of the treatment courses. The frequency with which abnormalities occurred was related to the total daily dose of antimony (Sb), increasing from 2/9 patients treated with 10 mg Sb/kg/d to 25/48 treated with 20-30 mg Sb/kg/d and 8/8 treated with 40-60 mg Sb/kg/d. The frequency with which ECG abnormalities developed was also related to the duration of treatment, increasing from 11/65 patients after 7 days to 18/44 after 15 days, 26/39 after 30 days and 11/12 after 60 days. ECG abnormalities were similar to those previously described during treatment with trivalent antimonial drugs, the most common being flattening and/or inversion of T waves. Prolongation of the corrected QT interval occurred in 13 patients, all of whom were treated for more than 30 days or with more than 20 mg Sb/kg/d. One patient died suddenly during the fourth week of treatment with 60 mg Sb/kg/d, and 2 patients died of measles after 9 or 10 days of treatment with 30 mg Sb/kg/d. QT prolongation and a concave ST segment developed in all 3 patients who died. We conclude that minor ECG abnormalities are common when sodium stibogluconate is used at doses above 20 mg Sb/kg/d for more than 15 days, and that life-threatening arrhythmias may occur if very high doses are used.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Arrhythmias, Cardiac; Child; Dose-Response Relationship, Drug; Electrocardiography; Gluconates; Heart Rate; Humans; Leishmaniasis; Leishmaniasis, Visceral; Male; Middle Aged

Treatment of visceral and cutaneous leishmaniasis rests on pentavalent antimonial drugs. However, side effects are often a problem and resistance may emerge. N-methyl-glucamine given for kala-azar induced hematologic or hepatic toxicity in three patients and failed in two. Four patients with cutaneous leishmaniasis recovered but two exhibited adverse side effects. Sodium stibo-gluconate failed in one of three kala-azar patients and in one of two patients with cutaneous leishmaniasis. The effects of these two drugs are discussed, as well as indications of pentamidine and splenectomy.

Topics: Adolescent; Adult; Antimony; Antimony Sodium Gluconate; Child; Child, Preschool; Female; Gluconates; Humans; Infant; Leishmaniasis; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pentamidine; Splenectomy

This epidemic of kala-azar in Bihar, India, started from a small block and gradually spread to almost all of North Bihar. Vaishali was the district most affected, with the highest incidence rate of 5.9 per thousand in 1978. The epidemic spread more to the east than to the west. In 1977 there were 100,000 cases of kala-azar in Bihar and in Vaishali district the death rate was 28.7% of affected cases. It took five years to control the epidemic. 750 parasitologically confirmed cases of kala-azar were studied. The male:female ratio was 5.5:1. 63.4% of cases were aged 10 to 29 years. Clinical features were classical. Sodium stibogluconate, used as a first line drug, was effective in 92.6% of cases. By increasing the course of antimonial therapy from 10 to 20 days the relapse rate was reduced to 0.5% compared with 15% in the previous epidemic. Kala-azar patients who also had tuberculosis were treated with the antimonial and antituberculosis drugs concurrently and all cases recovered. 86 cases unresponsive to sodium stibogluconate were given pentamidine, which was effective in 93.4%. Side effects with sodium stibogluconate were minimal, but were common and serious with pentamidine. The need for a safer drug effective in cases which do not respond to antimony was very evident. 20 cases of post kala-azar dermal leishmaniasis (PKDL) were reviewed: two had no previous previous history of kala-azar. The relapse rate was higher in PKDL than in kala-azar.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Child; Child, Preschool; Disease Outbreaks; Female; Humans; India; Infant; Infant, Newborn; Leishmaniasis; Leishmaniasis, Visceral; Male; Middle Aged; Pentamidine

Local heat treatment was tested and found effective in three patients with diffuse cutaneous leishmaniasis (DCL), a form of disease poorly responsive to the usual chemotherapy. A water bath that circulated water through a pad wrapped around the lesion provided a temperature of 39 degrees C to 41 degrees C for a cumulative time of at least 20 hours, over a period of several days. In the DCL patients beneficial effect of heat treatment was documented by pre- and post-treatment biopsies and cultures. Several other patients with ordinary cutaneous leishmaniasis did not respond to the same form of treatment. It was concluded that different strains and/or species of leishmanial parasites vary in their sensitivity to elevated temperature. While local heat treatment may be curative in certain cases of cutaneous leishmaniasis, such therapy is still experimental and should be monitored by quantitative parasitological studies to document its usefulness.

Topics: Adolescent; Adult; Amphotericin B; Animals; Antimony Sodium Gluconate; Biopsy; Child, Preschool; Female; Hot Temperature; Humans; Leishmaniasis; Male; Middle Aged

Topics: Adult; Antimony Sodium Gluconate; Female; Gluconates; Humans; Leishmaniasis; Middle Aged; Netherlands; Nose

Orally administered allopurinol at 50 mg/kg for 21 days showed pronounced antileishmanial activity against experimentally induced lesions of Leishmania braziliensis panamensis on the nose of Panamanian Aotus trivirgatus monkeys, with complete healing in 4 of 5, although parasitologic cure was achieved in only 2 of 5. The same total daily dose of drug, given in a divided dose twice daily, resulted in complete healing in all 5, and parasitologic cure in 4 of 5 animals. Standard treatment controls receiving 40 mg/kg of antimony stibogluconate intramuscularly for 15 days showed healing in 4 of 5 monkeys. It is not known if a similar level of effectiveness would result with this dose of allopurinol in humans, since Aotus may have a different pattern of metabolic conversion of the drug to the more active riboside.

Topics: Administration, Oral; Allopurinol; Animals; Antimony Sodium Gluconate; Aotus trivirgatus; Drug Evaluation, Preclinical; Female; Leishmaniasis; Male

Metronidazole has been claimed in several earlier reports to be active in human cases of leishmaniasis and trypanosomiasis. Its efficacy against the protozoa causing these diseases was tested in hamsters infected with Leishmania mexicana or L. donovani, and in mice infected with Trypanosoma brucei brucei. In separate experiments, hamsters were either inoculated intradermally into the nose with 5 million amastigotes of L. mexicana or intracardially with 10-30 million amastigotes of L. donovani, and mice were infected intraperitoneally with 30 million T. b. brucei. Metronidazole was administered in four oral doses on alternate days for a total of 375 mg/kg to hamsters and 500 mg/kg to mice. Sodium stibogluconate (Pentostam) served as a positive control. In hamsters the extent of infection was assessed by the appearance of flagellates in blood agar cultures of nose and spleen, by counting amastigotes in nose and liver impression smears, and by measuring the size of nose lesions. Ultrastructure of nose lesions before and after treatment with metronidazole or Pentostam was also evaluated. Infection in mice was assessed by the extent of parasitemia and/or survival to 30 days. In no case did metronidazole-treated animals differ from untreated controls. Metronidazole shows no activity against experimental infections of leishmaniasis or trypanosomiasis in these animal models.

Topics: Animals; Antimony Sodium Gluconate; Cricetinae; Leishmaniasis; Leishmaniasis, Visceral; Mesocricetus; Metronidazole; Mice; Microscopy, Electron; Nose; Pentamidine; Trypanosoma brucei brucei; Trypanosomiasis, African

Thirty-five golden hamsters infected with Leishmania donovani were treated with Pentostam and followed up to determine the effect of treatment on the development of secondary amyloidosis. Seventy untreated golden hamsters infected with L. donovani were followed up as controls to determine the pattern of development of secondary amyloidosis. Amyloid developed in all animals treated and untreated. The treatment significantly prolonged the survival time, but did not inhibit the development of renal amyloid in animals shown by biopsy to be free from renal amyloid at the time of treatment. When amyloid was present in kidney at the time of treatment it progressed invariably to renal failure.

Topics: Amyloidosis; Animals; Antimony Sodium Gluconate; Cricetinae; Kidney Diseases; Leishmaniasis; Mesocricetus

Cutaneous leishmaniasis caused by Leishmania aethiopica usually responds poorly to conventional doses of pentavalent antimonial drugs. We treated three patients with cutaneous leishmaniasis acquired in Kenya, presumed or documented to be caused by L. aethiopica, with intravenous sodium stibogluconate, 18 to 20 mg Sb/kg body-weight twice daily for 30 days. All patients had a good response to treatment, with disappearance of parasites from skin smears and cultures after 14 to 27 days, clinical healing of the lesions, and no recurrence during a three to 18-month follow-up. Side effects of treatment were minor. We conclude that this high dose sodium stibogluconate regimen is safe and effective for treating cutaneous leishmaniasis caused by L. aethiopica in Kenya.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Drug Administration Schedule; Follow-Up Studies; Gluconates; Humans; Kenya; Leishmaniasis; Male

Two cases of leishmaniasis recidivans of twenty years' duration were treated intravenously with sodium stibogluconate (Pentostam) with good results. Before treatment, histologic examination of a biopsy specimen revealed many Leishman-Donovan (LD) bodies. After treatment, repeated biopsies done in one of the cases revealed only scar tissue. We recommended treatment with sodium stibogluconate in cases of leishmaniasis recidivans, although an ideal treatment for this condition still does not exist.

Topics: Adult; Anti-Bacterial Agents; Antimony; Antimony Sodium Gluconate; Gluconates; Humans; Leishmaniasis; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Recurrence

Topics: Animals; Antimony Sodium Gluconate; Gluconates; Injections, Intravenous; Injections, Subcutaneous; Leishmaniasis; Liposomes; Mice

Clinically achievable concentrations of the three major antileishmanial drugs in use--pentavalent antimony, pentamidine, and amphotericin B--eliminated 90%--100% of the mammalian forms (amastigotes) of Leishmania tropica and Leishmania donovani from in vitro infected human monocyte-derived macrophages. This is apparently the first report of in vitro susceptibility of Leishmania to pentavalent antimony or to pentamidine. The insensitivity of insect forms (promastigotes) multiplying in cell-free media to thee drugs suggests that amastigotes are more sensitive than promastigotes to these antileishmanial agents. Alternatively, macrophages may concentrate or metabolize the drugs to increase their toxicity. In contrast, amphotericin B was toxic to both amastigotes and promastigotes. The sensitivities of Leishmania within human monocyte-derived macrophages in vitro to clinically achievable concentration of antileishmanial agents suggests that this model may be useful for investigation of mechanisms of sensitivity and resistance of antimicrobial agents against Leishmania.

Topics: Amidines; Amphotericin B; Antimony Sodium Gluconate; Gluconates; Humans; Leishmaniasis; Macrophages; Pentamidine

Topics: Antimony Sodium Gluconate; Emigration and Immigration; Finland; Humans; Leishmaniasis

A Peace Corps volunteer in Senegal, West Africa contracted cutaneous leishmaniasis which had several noteworthy features. One of the three presenting cutaneous ulcers was associated with subcutaneous nodules and viable organisms were recovered from healing lesions after multiple courses of treatment, including amphotericin B. Yet, the patient was found to exhibit both humoral and cell mediated features of normal immunologic responsiveness. Ultimately, clinical and parasitological cure occurred. The patient's organism was found to produce lesions in the foot pads of mice.

Topics: Adult; Amphotericin B; Antibodies; Antimony Sodium Gluconate; Humans; Immunity, Cellular; Leishmaniasis; Male; Wound Healing

Topics: Aminoquinolines; Amphotericin B; Animals; Antimony Sodium Gluconate; Disease Models, Animal; Female; Leishmaniasis; Metronidazole; Mice; Mice, Inbred BALB C; Senegal; Wound Healing

A series of 31 patients presenting with skin lesions with positive smears for leishmania parasites were treated with sodium stibogluconate (each ml of injection containing the equivalent of 100 mg pentavalent antimony). The drug was administered either intramuscularly at a dosage of 6 ml daily for at least 10 days or infiltrated around the lesion (maximum 2 ml per lesion) at weekly intervals for 3 to 4 consecutive weeks. Twenty-four (77%) of the patients were assessed as showing a successful response, with parasites absent from the smear and the lesions healing at the end of treatment. Poor results, however, were reported in 5 of the 16 patients treated solely by infiltration. Follow-up of a few patients at 3 months showed that the healing process was prompt and little disfiguration was produced, lesions on the trunk tending to heal more quickly than those on the face.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Child; Female; Gluconates; Humans; Leishmaniasis; Male; Middle Aged; Syria

Topics: Adult; Antimony Sodium Gluconate; Electrocardiography; Gluconates; Humans; Leishmaniasis; Male

Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.

Topics: Animals; Antimony; Antimony Sodium Gluconate; Cricetinae; Disease Models, Animal; Gluconates; Leishmaniasis; Liposomes; Liver; Meglumine; Pharmaceutical Vehicles; Phospholipids; Structure-Activity Relationship; Surface Properties

Topics: Antimony Sodium Gluconate; Gluconates; Humans; Leishmaniasis; Male; Middle Aged

Topics: Antimony; Antimony Sodium Gluconate; Humans; Leishmaniasis; Leishmaniasis, Mucocutaneous; Metronidazole; Pentamidine

Topics: Animals; Antimony Sodium Gluconate; Gluconates; Guinea Pigs; Immunity; Leishmaniasis; Time Factors

Topics: Antimony Sodium Gluconate; Cell Division; Humans; Leishmania; Leishmaniasis; Leishmaniasis, Mucocutaneous; Leishmaniasis, Visceral

American leishmaniasis that is acquired in Panama may appear clinically as a sporotrichoid eruption. When leisons reminiscent of sporotrichosis are encountered, a careful history of the patient's travels should be made, as well as a search for the organism of leischmaniasis in tissue smears, histopathological sections, and cultured media. We report the case of an American soldier stationed in Panama who had developed an ulcer on the dorsum of his right wrist, and nodules on his right forearm that were arranged in a linear pattern. The initial clinical impression was that of sporotrichosis, but on careful study of the patient's history, and after other appropriate investigations were made, it was discovered that the patient had leishmaniasis.

Topics: Adult; Antimony Sodium Gluconate; Diagnosis, Differential; Electrocardiography; Erythromycin; Heart; Humans; Leishmaniasis; Male; Sporotrichosis

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

Topics: Antimony; Antimony Sodium Gluconate; Filariasis; Humans; Leishmaniasis; Sodium

Topics: Antimony; Antimony Sodium Gluconate; Asian People; Humans; Leishmaniasis; Leishmaniasis, Visceral; Sodium

Topics: Antimony; Antimony Sodium Gluconate; Humans; Leishmaniasis; Sodium

Topics: Antimony; Antimony Sodium Gluconate; Humans; Leishmaniasis

Topics: Antimony; Antimony Sodium Gluconate; Humans; Leishmaniasis; Sodium

Topics: Antimony; Antimony Sodium Gluconate; Asian People; Humans; Leishmaniasis; Leishmaniasis, Visceral; Sodium

Topics: Antimony Sodium Gluconate; Enzyme Inhibitors; Humans; Leishmaniasis

Topics: Antimony Sodium Gluconate; Humans; Leishmaniasis

Topics: Antimony; Antimony Sodium Gluconate; Humans; Leishmaniasis; Sodium

Topics: Antimony; Antimony Sodium Gluconate; Gluconates; Humans; Leishmaniasis; Leishmaniasis, Visceral; Sodium; Stomach