allopurinol and Leishmaniasis--Visceral

There is limited information about feline leishmaniosis (FeL) management in clinical practice. Leishmania infantum is the species of Leishmania most frequently reported in both dogs and cats in countries of the Mediterranean region (henceforth 'Mediterranean countries'), Central and South America, and Iran. This study was conducted to provide veterinary clinicians with an updated overview of evidence-based information on leishmaniosis in cats.. A review was performed using PubMed, Science Direct, Google Scholar and Web of Science. Case reports of FeL caused by L. infantum were sought for the period 1912 to 1 June 2021.. Sixty-three case reports are included in this review. Fifty-nine out of the 63 cats were from Europe, mostly from Mediterranean countries (88.9%). Most of them were domestic short-haired cats (90%) with a mean age of 7.9 years, and had access to the outdoors (77.3%). Sixty-six percent of the cats had comorbidities, of which feline immunodeficiency virus infection was the most frequent (37.7%). Dermatological lesions (69.8%) was the most frequent clinical sign, and hyperproteinemia (46.3%) the most frequent clinicopathological abnormality. Serology was the most performed diagnostic method (76.2%) and was positive for 93.7% of cats. Medical treatment was applied in 71.4% of cats, and allopurinol was the most used drug (74.4%). Survival time was greater for treated cats (520 days; 71.4% of cats) than non-treated cats (210 days; 25.4%).. The majority of the cats had comorbidities, of which feline immunodeficiency virus was the most frequent. Dermatological lesions were frequently reported, and systemic clinical signs and clinicopathological abnormalities were also common. Serology may be useful for the diagnosis of FeL in clinical practice, and a positive titer of ≥ 1/40 may be a useful cut-off for sick cats. The reported treatments and dosages varied, but there was a good clinical response and longer survival in most of the cats treated with allopurinol monotherapy.

Topics: Allopurinol; Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Leishmania infantum; Leishmaniasis; Leishmaniasis, Visceral

This article reviews essential topics of canine visceral leishmaniasis (CVL) due to Leishmania infantum infection. It focuses on the current serological and molecular diagnostic methods used in epidemiological research and veterinary clinics to diagnose CVL and includes new point-of-care (POC) tests under development. The efficacy of different treatment regimens on the clinical improvement and infectiousness of dogs is also addressed. In the last section, the review provides a critical appraisal of the effectiveness of different control measures that have been implemented to curb disease transmission.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Disease Reservoirs; Dog Diseases; Dogs; Leishmania infantum; Leishmaniasis, Visceral; Meglumine; Meglumine Antimoniate; Molecular Diagnostic Techniques; Organometallic Compounds; Phosphorylcholine; Point-of-Care Systems; Serologic Tests

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

Topics: Allopurinol; Amphotericin B; Antimony Sodium Gluconate; Humans; Leishmaniasis, Visceral; Pentamidine

Topics: Allopurinol; Amphotericin B; Antimony; Humans; Immunity, Cellular; Leishmaniasis, Visceral; Opportunistic Infections

Topics: Allopurinol; Amphotericin B; Antimony Sodium Gluconate; Child; Combined Modality Therapy; Humans; Ketoconazole; Leishmaniasis, Visceral; Pentamidine; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Splenectomy

Leishmaniasis are parasitic diseases in extension. They appear in new foci, because of important displacements of populations, and they affect immunocompromised patients (under chemotherapy, transplanted, or HIV infected). Study of 33 cases of leishmaniasis, 22 visceral and 11 cutaneous, at the Hôpital du Kremlin-Bicêtre, France, showed predominant contamination in Maghreb and in the south of France. In the case of Kala-Azar, fever (18 cases) and hepatosplenomegaly (19 cases) are frequent, and the serodiagnosis and the search of parasites by myelogram are always positive. In HIV-infected individuals, clinical signs are similar, but the serodiagnosis is less reliable. Evolution is bad in transplanted patients who must remain under immunosuppressive drugs. In the case of cutaneous leishmaniasis, diagnosis is based on local sample, while the serodiagnosis remains negative. Treatment is sometimes long, necessitating repeated treatments.

Topics: Allopurinol; Animals; Child, Preschool; Disease Reservoirs; Female; Global Health; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Meglumine; Pentamidine; Protozoan Vaccines

We report a case of visceral leishmaniasis in a 38-year-old renal transplant recipient living in an endemic country. Antimonial derivatives induced a rapid remission. A review of the literature disclosed 8 cases of this association with a fatal fulminant outcome in 5 cases. We suggest that the specific immunosuppression used in renal transplant patients might facilitate the development of a dormant infection and in these patients the misleading presentation may delay the diagnosis. Moreover special caution with treatment of leishmaniasis must be taken in renal transplant because of possible interactions between antimony compounds and ciclosporin metabolites. In renal transplant patients living in endemic countries, visceral leishmaniasis should be kept in mind as a potential cause of unexplained long-standing fever and considered as an opportunistic infection.

Topics: Adult; Allopurinol; Animals; Antimony; Antiprotozoal Agents; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Transplantation; Leishmania donovani; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Methylprednisolone; Muromonab-CD3; Organometallic Compounds

Topics: Allopurinol; Amidines; Animals; Antimony Sodium Gluconate; Gluconates; Glycolysis; Leishmania; Leishmaniasis, Visceral; Lipid Metabolism; Pentamidine

Pyrazolopyrimidines are purine analogues. These compounds are metabolized by the pathogenic hemoflagellates and other members of the family Trypanosomatidae as though they were purines. This metabolic sequence does not exist in man or other mammals. In the hemoflagellates, the pyrazolopyrimidine base, of which allopurinol is the paradigm, undergoes ribosylphosphorylation to the ribonucleotide. This ribonucleotide may remain as such or be aminated to the amino analogue and further converted to the aminopyrazolopyrimidine ribonucleoside triphosphate. The latter is incorporated into RNA. This metabolic sequence has been demonstrated in the genera Leishmania and Trypanosoma.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Aotus trivirgatus; Chagas Disease; Humans; Leishmania; Leishmaniasis, Visceral; Polyribosomes; Protein Biosynthesis; Ribonucleosides; RNA; Thionucleosides; Trypanosoma; Trypanosoma cruzi; Trypanosomiasis; Trypanosomiasis, African

Canine leishmaniosis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum with a wide spectrum of clinical signs, with cutaneous, ocular, renal and lymphoreactive conditions prevailing in the clinical setting. The immune system plays a pivotal role in the evolution of Leishmania infection and its response to antileishmanial treatment. Cytokines are important immune response mediators that are released by activated lymphocytes and less so by other immunocytes. In dogs with leishmaniosis, IFN-γ and IL-4 have been recognized as the main activators of cellular and humoral immunity, respectively. The objective of this study was to investigate intracellular IL-4 and IFN-γ expression by CD4 + and CD8 + lymphocytes in the peripheral blood of symptomatic dogs before and after combined antileishmanial treatment with miltefosine and allopurinol.. Postantileishmanial treatment CD4 + IL-4 + and CD8 + IL-4 + cell counts were significantly decreased, although no similar changes were observed in the comparisons made between the pre- and posttreatment CD4 + IFN-γ + and CD8 + IFN-γ + counts and ratios.. The findings indicate that IL-4 production by T cells may facilitate the symptomatic phase of CanL, whereas IFN-γ production by CD4 + and CD8 + cells may indicate its negligible role in the evolution of natural CanL and perhaps the equivocal positive influence of antileishmanial treatment.

Topics: Allopurinol; Animals; CD8-Positive T-Lymphocytes; Cross-Sectional Studies; Dog Diseases; Dogs; Interferon-gamma; Interleukin-4; Leishmania infantum; Leishmaniasis, Visceral

The aim of this 6-month, randomized, blinded, controlled clinical trial was to compare the efficacy and safety of aminosidine-allopurinol combination with that of meglumine antimoniate-allopurinol combination for the treatment of leishmaniosis in dogs without stage III or IV chronic kidney disease. Forty client-owned dogs were randomly assigned to group A [n = 20; aminosidine (15 mg/kg, subcutaneously, once daily, for 28 days) and allopurinol (10 mg/kg, per os, twice daily, for 6 months)] or group B [(n = 20; meglumine antimoniate (100 mg/kg SC, once daily, for 28 days) and allopurinol (10 mg/kg, per os, twice daily, for 6 months)]. Clinical and clinicopathological evaluations, parasitic load measurement (lymph node and bone marrow microscopy, bone marrow real-time PCR), specific serology and leishmanin skin test (LST) were performed at baseline (time 1) and after 14 (time 2), 28 (time 3), 60 (time 4) and 180 (time 5) days. Both treatments were safe and resulted in significant clinical and clinicopathological improvement, reduction of parasitic load and of indirect immunofluorescence antibody test (IFAT) titer and induction of positive LST. There was no significant difference between groups with regards to the primary outcome measures of the trial that included the proportion of dogs that presented severe treatment-related side effects, were cured and were parasitologically negative at time 5. However, some (proportion of dogs that presented no clinical signs, no hyperglobulinemia and negative serology at time 5) secondary outcome measures showed significant differences in favor of the meglumine antimoniate-allopurinol treatment arm. Treatment-related death occurred in one dog in each group, while injection site reactions appeared at a similar frequency in both groups. Due to the differences in some secondary outcome measures in association with the low power of this trial, it cannot be definitively concluded that the two treatments are equally effective. Therefore, the aminisodine-allopurinol combination cannot be proposed as a first-line treatment of CanL but rather as a second-line treatment that may be particularly useful to avoid repeated administration of meglumine antimoniate and in countries where the latter is not available or registered.

Topics: Allopurinol; Animals; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Injections, Subcutaneous; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine Antimoniate; Paromomycin; Trypanocidal Agents

Leishmaniasis is among the world's most neglected diseases. Dogs are the main reservoirs/hosts of Leishmania infantum, causative agent of both canine and human visceral leishmaniosis. Canine leishmaniasis (CanL) represents a public health problem as one of the most prevalent zoonotic diseases worldwide. Current therapeutics present drawbacks; thus, there is a need for more effective, safer, and cheaper drugs. The aim of this study was to evaluate and to compare the efficacy of oral administration of artesunate or meglumine antimoniate/allopurinol in dogs with clinical leishmaniasis. Forty-two dogs with naturally occurring clinical leishmaniasis were included in this open-label, simple randomized positive-control clinical field trial with 6 months of follow-up. Dogs received meglumine antimoniate 100 mg/kg/day and allopurinol 30 mg/kg/day for 28 days (control group, n = 26) or artesunate 25 mg/kg/day for 6 days (test group, n = 16). The animals were evaluated for their clinical evolution, parasite load (by qPCR) and humoral response at different time points: 0, 30, 90, and 180 days after treatment. Data analyses showed a significant improvement in both groups in clinical scores, parasitemia and antibody titers after treatment. Compared to the control group, the artesunate group showed significantly lower clinical score (P = 0.0001), lower parasitemia (P = 0.0001) and antibody titers after 6 months of follow-up. Compared to baseline values, a rapid, significant reduction (P < 0.012) in antibody levels, 2.28- versus 3.04-fold for the control versus artesunate groups, respectively, was observed 30 days after treatment. Antibody levels continued to decrease further in the artesunate group, where 58% of cases became seronegative at the 6-month follow-up. All qPCR-positive dogs were negative after treatment with artesunate, while 14.3% remained positive with the appearance of two new cases in the control group. Artesunate was well tolerated, and no side effects were recorded. Treatment failures were similar in both groups with 27.27% (6/22), including 18.18% (4/22) mortality in the control group, versus 26.66% (4/15), including 13.33% (2/15) mortality in the artesunate group. This is the first report showing the potential of artesunate in the treatment of dogs with clinical leishmaniasis. Artesunate showed higher efficacy than the current first-line treatment for CanL without any adverse effects. It could be a good alternative chemotherapy for CanL, and may be c

Topics: Allopurinol; Animals; Antiprotozoal Agents; Artesunate; Dog Diseases; Dogs; Female; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine Antimoniate; Parasite Load; Parasitemia; Zoonoses

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.

Topics: Allopurinol; Animals; Cochlea; Creatinine; Dog Diseases; Dogs; Double-Blind Method; Drug Combinations; Evoked Potentials, Auditory, Brain Stem; Female; Hearing; Hearing Loss; Injections, Subcutaneous; Kidney; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine Antimoniate; Neurologic Examination; Paromomycin; Random Allocation; Vestibule, Labyrinth

First-line treatment for canine leishmaniosis (CanL) is N-methylglucamine antimoniate (MGA) combined with allopurinol. However, in some dogs allopurinol may induce hyperxanthinuria leading to urolithiasis. Moreover, allopurinol resistance has recently been described in Leishmania infantum isolates from treated dogs with a relapse of the disease. Alternative treatments are thus needed. Since the type of host immune response strongly influences CanL progression and prognosis, dogs could benefit from treatments targeted at modulating such response, such as nucleotides and active hexose correlated compound (AHCC). The aim of this study was to evaluate the effects of an oral combination of nucleotides and AHCC in dogs with clinical leishmaniosis. Sixty-nine dogs with naturally-occurring clinical leishmaniosis were included in this multicenter, open-label, positively-controlled clinical trial and randomized to receive 10mg/kg allopurinol PO BID (allopurinol group) or 17mg/kg AHCC plus 32mg/kg nucleotides PO SID (supplement group) for 180 days. All dogs were also given 50mg/kg MGA SC BID during the first 28 days. At the time points 0, 30, and 180 days of the trial, dogs underwent a clinical examination, and blood, urine, and bone marrow samples were submitted for analytical tests. Final data analyses (allopurinol group: n=29; supplement group: n=24) revealed a significant improvement in both groups in clinical scores and ELISA-determined antibody titers after treatment. However, the supplement group showed a significantly lower clinical score (P=0.005) and significantly higher antibody titers (P=0.032) after 180 days, compared to the allopurinol group. RT-PCR parasite loads were reduced in groups (mean±SD supplement: 0.38±0.56 vs 5.23±18.9; allopurinol: 0.45±1.47 vs 3.09±8.36 parasites/ng of DNA), but there were no significant differences over time or between groups. During the study, 12 dogs in the allopurinol group developed xanthinuria (41%) compared to no dogs (0%) in the supplement group (P=0.000). Both treatments led to significantly increased CD4+/CD8+ ratio, and improvements in protein electrophoretic pattern and acute phase response. In conclusion, 6-month oral treatment with nucleotides and AHCC in addition to MGA showed similar efficacy to the current first-line treatment for CanL, without producing xanthinuria. This combination could be a good alternative to MGA-allopurinol combination treatment for CanL, especially for dogs suffering allopurinol-rel

Topics: Allopurinol; Animal Feed; Animals; Diet; Dog Diseases; Dogs; Female; Leishmaniasis, Visceral; Male; Nucleotides; Parasite Load; Polysaccharides

Topics: Allopurinol; Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Dog Diseases; Dogs; Doxycycline; Drug Combinations; Ehrlichia canis; Ehrlichiosis; Enzyme Inhibitors; Female; Hemostasis; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Platelet Aggregation; Treatment Outcome

Topics: Acute-Phase Proteins; Allopurinol; Animals; Dog Diseases; Dogs; Drug Administration Schedule; Enzyme Inhibitors; Leishmania infantum; Leishmaniasis, Visceral

Twenty-seven dogs infected naturally with Leishmania infantum were used in a randomised controlled trial to compare the clinical and parasitological efficacy of an oral treatment with a combination of metronidazole and spiramycin (13 dogs) with the efficacy of conventional treatment with meglumine antimonate and allopurinol (14 dogs) as controls. In the test group one dog had to be withdrawn from the treatment because it developed pemphigus foliaceus; 10 of the dogs were clinically responsive but none was cured parasitologically. In the control group four dogs were withdrawn from the treatment because of side effects; eight of the dogs were clinically responsive but none was cured parasitologically. The control group showed signs of improvement after an average of 30 days, whereas the test group did not show signs of improvement until after an average of 45 days.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Fluorescent Antibody Technique, Indirect; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Metronidazole; Polymerase Chain Reaction; Spiramycin; Treatment Outcome

A total of 95 clinically healthy and seronegative for Leishmania infantum dogs, residing an area highly endemic for canine leishmaniosis (CL) and living an outdoor life-style, were split into positive and negative groups, and then were randomly assigned to receive allopurinol (n=51; 20 mg/kg once daily), or placebo (n=44) for 1 week per month, from April to November. Forty per cent (38/95) of these dogs were not reexamined and retested at the end of the trial for reasons unrelated to CL. None of the remaining 57 dogs exhibited the symptomatic form of the disease at the end of the 1-year follow-up period. Of the 15 allopurinol-treated dogs that were non-infected (negative PCR and tissue smear microscopy) at the beginning of the trial, 6 (40% P=0.03) became PCR-positive, of which 3 became also seropositive, at the end of the observation period. In contrast, only 1 of 7 (14.3%) placebo-treated non-infected dogs became PCR positive at the same time point. Of the 19 allopurinol-treated dogs that were infected (PCR-positive) at the beginning of the trial, 18 (94.7%) remained PCR-positive and one (5.3%) seroconverted, at the end of the observation period. Of the 16 initially infected and placebo-treated dogs, 14 (87.5%) remained PCR positive, of which one (6.7%) also turned positive by tissue smear microscopy. Therefore, it is concluded that the use of allopurinol, at the daily dose of 20mg/kg, for 1 week per month, during the period of sandfly activity, does not prevent the infection of non-infected dogs by L. infantum, and, also, does not help in the elimination of the parasite from dogs with asymptomatic infections.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Double-Blind Method; Endemic Diseases; Female; Leishmania infantum; Leishmaniasis, Visceral; Male

To evaluate changes in serum concentrations of acute-phase proteins in dogs with leishmaniosis during short-term therapy in accordance with 2 treatment protocols and determine whether concentrations of acute-phase proteins could be used to monitor the initial response of dogs to treatment.. 12 dogs naturally infected with Leishmania infantum.. Dogs were allocated into 2 groups. Dogs of group 1 were treated by use of meglumine antimonate (100 mg/kg, SC, q 24 h) administered concurrently with allopurinol (15 mg/kg, PO, q 12 h) for 20 days and then with allopurinol alone at the same dosage for the subsequent 30 days. Dogs of group 2 were treated by administration of allopurinol alone (15 mg/kg, PO, q 12 h) for 60 days). Blood samples were obtained before and during treatment for measurement of serum concentrations of acute-phase proteins and determination of CBC counts, serum biochemical analyses, and electropherograms.. All dogs evaluated in the study had increased concentrations of C-reactive protein, haptoglobin, and ceruloplasmin at the time of diagnosis of leishmaniosis. Mean concentration of serum amyloid A before treatment was also increased, but some of the dogs had concentrations of serum amyloid A that were within the reference range. Concentrations of C-reactive protein and ceruloplasmin decreased significantly in all dogs at the end of the study period.. Measurement of concentrations of selected acute-phase proteins, such as C-reactive protein or ceruloplasmin, could be used to evaluate the initial response of dogs with leishmaniosis to treatment.

Topics: Acute-Phase Proteins; Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Administration Schedule; Drug Therapy, Combination; Female; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds

A randomized clinical trial of low dosage combination of pentamidine and allopurinol was carried out with objectives to assess the efficacy and toxicity as compared to full dosage of pentamidine in antimony unresponsive visceral leishmaniasis (VL) patients.. Using a randomized control clinical trial, a total of 158 antimony unresponsive patients of VL were randomly allocated into two treatment groups. Patients in one group (n=80) received half the dosage of pentamidine i.e. 2 mg/kg body weight by IM route on alternate day and allopurinol in dose of 15 mg/kg body weight in three divided dosages for 30 days; patients in the second group (n=78) received pentamidine in dose of 4 mg/kg body weight by IM route on alternate day for 15 injections in 30 days. The efficacy and safety of the two regimens were compared.. Apparent cure i.e. clinical and pathological cure at the end of therapy, in 78 (97.5%) and 67 (86%), and ultimate cure i.e. clinical and parasitological cure at the end of follow-up of six months, in 73 (91.25%) and 58 (74.35%) patients was observed in the combination regimen and single regimen group respectively. The difference of the ultimate cure between two groups of the patients was statistically significant (p < 0.01). In single regimen group, 11 (14%) patients showed primary unresponsiveness (with no response during treatment) and nine (13%) relapse (after six months of follow-up) respectively, where as in combination regimen group, two (2.5%) patients showed primary unresponsiveness and five (6.4%) relapse respectively. By the end of the treatment, the incidence of injection-related toxicity, such as rigor and fever, was same in both groups. No hyperglycemia was observed in combination therapy probably due to reduced dose of pentamidine and three patients in single regimen developed hyperglycemia and one of them developed irreversible hyperglycemia.. The study showed that the combination of pentamidine (half dose) and allopurinol is more effective in achieving ultimate cure with an added advantage of reduced toxicity in unresponsive cases as compared to full pentamidine dose.

Topics: Adolescent; Allopurinol; Antiprotozoal Agents; Chi-Square Distribution; Child; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Pentamidine

In 16 dogs, the diagnosis of canine leishmaniasis could be detected by direct microscopic identification, by determination of the antibody titre or by PCR method (peripheral blood/bone marrow). On the basis of the clinical and laboratory diagnostic results 9 cases of the cutaneous type and 7 dogs of the combined cutaneous-visceral type (+ mono- or polyarthritis, hepatopathy and/or renal insufficiency as well as occular manifestation) have been classified. Therapy was: GLUCANTIME in 6 dogs, allopurinol in 3 dogs as single agent, combination-therapy GLUCANTIME and allopurinol in 7 dogs. During GLUCANTIME-treatment the following adverse reactions could be observed: general weakness, reduced food intake up to anorexia, vomiting and diarrhoea. Laboratory parameters showed sporadically leucopenia or pancreatitis. Adverse reactions during allopurinol therapy were: vomitus/diarrhoea or urine concrements. One dog with GLUCANTIME therapy, 2 dogs with allopurinol as well as 2 dogs with combination therapy are clinically symptom-free at the moment (peripheral blood and bone marrow: PCR negative). The remaining 11 patients showed a good to very good improvement of the clinical symptoms. However, since the peripheral blood respectively the bone marrow continue to be PCR positive, relapses have to be expected in these dogs.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Female; Follow-Up Studies; Leishmania infantum; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Treatment Outcome

To assess the effectiveness of two regimens with allopurinol or pentavalent antimony as secondary prophylaxis for visceral leishmaniasis (VL) in human immunodeficiency virus (HIV)-infected patients.. Retrospective, nonrandomized, open trial.. A 1,000-bed academic tertiary institutional hospital in Barcelona.. Forty-six individuals over 14 years old with HIV infection, who recovered from an episode of VL between January 1988 and February 1995.. Twenty patients did not receive any prophylaxis, nine received 300 mg/8 h of allopurinol, and 17 received 850 mg once-a-month of pentavalent antimony. Patients were followed-up every 3 months, and the endpoint of study was relapse of VL.. Twenty-one patients had recurrent VL: 13 of 20 in the control group (65%), 5 of 9 in the allopurinol group (56%), and 3 of 17 in the antimonial group (18%). Kaplan-Meier estimates of the probability of remaining relapse-free at 12 months were 9% without prophylaxis (95% CI, 0-22%), 21% with allopurinol (95% CI, 0-51%), and 93% with antimonials (95% CI, 82-100%) (P < 0.001). Multivariate analysis showed that the only significant variables related to relapsing course of VL were assignment to the antimonial group, and the fact that the patient had experienced a previous episode of VL.. Pentavalent antimony given once a month is effective in the prevention of VL relapses in HIV-infected individuals. It is a low-cost treatment that proved to be well tolerated. Therefore, pentavalent antimony should be considered a suitable agent for secondary prophylaxis against VL.

Topics: Adult; Aged; Allopurinol; Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Data Interpretation, Statistical; Female; Follow-Up Studies; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Multivariate Analysis; Organometallic Compounds; Recurrence; Retrospective Studies; Time Factors

Topics: Allopurinol; Antimony Sodium Gluconate; Clinical Trials as Topic; Gluconates; Humans; Leishmaniasis, Visceral; Time Factors

Leishmania infantum is an intracellular protozoan parasite which is endemic in countries of the Mediterranean Basin. Leishmaniosis is increasingly diagnosed in non-endemic areas due to the relocation of dogs from endemic areas and the travel of dogs to and from these areas. The prognosis of leishmaniosis in these dogs may differ from that of those in endemic areas. The aims of this study were (1) to determine the Kaplan-Meier estimated survival time for dogs with leishmaniosis in the Netherlands (a non-endemic country), (2) to determine if clinicopathological variables at the time of diagnosis predicted the survival of these dogs, and (3) to evaluate the effect of a two-phase therapy protocol of allopurinol monotherapy followed by meglumine antimoniate and/or miltefosine in the case of incomplete remission or relapse.. The database of the Department of Clinical Sciences of Companion Animals of the Faculty of Veterinary Medicine, Utrecht University was investigated for leishmaniosis patients. Patient records were reviewed for signalment and clinicopathological data at the time of diagnosis. Only treatment-naive patients were included. Follow-up was performed during the study by phone contact and included treatment received and date and cause of death. Univariate analysis was performed using the Cox proportional hazards regression model.. The estimated median Kaplan-Meier survival time was 6.4 years. In the univariate analysis, increases in monocyte, plasma urea and creatinine concentrations, and urine protein to creatinine ratio were all significantly associated with decreased survival time. The majority of patients only received allopurinol monotherapy.. Canine leishmaniosis patients in our study population in the Netherlands, which is non-endemic for the disease, had an estimated Kaplan-Meier median survival time of 6.4 years, which is comparable to the outcome of other reported therapy protocols. Increased plasma urea and creatinine concentrations and monocyte concentration were statistically associated with an increased risk of death. We conclude that initial allopurinol monotherapy for 3 months should be effective in more than half of canine leishmaniosis cases, provided there is adequate follow-up, and that meglumine antimoniate or miltefosine therapy should be started as the second phase of the protocol in cases where remission is incomplete or there is a relapse.

Topics: Allopurinol; Animals; Creatinine; Dog Diseases; Dogs; Humans; Leishmania infantum; Leishmaniasis; Leishmaniasis, Visceral; Meglumine Antimoniate; Prognosis; Recurrence; Urea

Topics: Allopurinol; Animals; Antibodies, Monoclonal; CD4-Positive T-Lymphocytes; Dog Diseases; Dogs; Immunologic Factors; Immunotherapy; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Meglumine Antimoniate; Organometallic Compounds; Polyethylene Glycols; Receptors, Interleukin-10

Canine visceral leishmaniasis is an endemic zoonosis in Brazil. Dogs are the main hosts in urban environments. The treatment has gained popularity since the Brazilian government authorized miltefosine for canine treatment. The aim of this study was to investigate the clinical and parasitological impact of short-term treatment with miltefosine and allopurinol, alone and in combination. We evaluated the ability of pharmacotherapy to reduce clinical signs of disease, antibody levels using the indirect fluorescence antibody test (IFAT) and skin parasite load via qPCR after 28 days of treatment. The therapeutic protocols promoted a significant decline in clinical signs and in the skin parasite load in dogs (p < 0.01). We observed a moderate correlation between the skin parasite load and the clinical score in all three treatment groups (r > 0.5) Antibody levels did not decrease in this short period. It was concluded that the treatment with allopurinol reduced the number of parasites in the skin of dogs with visceral leishmaniasis in the short term. However, its efficiency is potentiated when associated with miltefosine.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Leishmania infantum; Leishmaniasis, Visceral; Phosphorylcholine

The purpose of the present study was to evaluate the efficacy of the treatment with a recombinant cysteine proteinase from Leishmania, rldccys1, associated with allopurinol or miltefosine on Leishmania (Leishmania) infantum chagasi-infected hamsters. Golden Syrian hamsters infected with L. (L.) infantum chagasi were treated with either miltefosine (46 mg/kg) or allopurinol (460 mg/kg) alone by oral route or associated with rldccys1 (150 µg/hamster) by subcutaneous route for 30 days. Infected hamsters were also treated with miltefosine (46 mg/kg) plus rldccys1 (150 µg/hamster) for 30 days (phase 1) followed by two additional doses of rldccys1 (250 µg/hamster) (phase 2). After the end of treatment, the animals were analyzed for parasite load, body weight, serum levels of immunoglobulins, cytokine expression, and drug toxicity. The data showed a significant decrease of parasite load in infected hamsters treated with allopurinol or miltefosine alone or associated with rldccys1, as well as in those treated with rldccys1 alone. Significantly lower levels of serum IgG were detected in hamsters treated with allopurinol plus rldccys1. The treatment with miltefosine associated with rldccys1 prevented relapse observed in animals treated with miltefosine alone. A significant loss of body weight was detected only in some hamsters treated with miltefosine for 1 month and deprived of this treatment for 15 days. There were no significant differences in transcript expression of IFN-γ and IL-10 in any of treated groups. Neither hepatotoxicity nor nephrotoxicity was observed among controls and treated groups. These findings open perspectives to further explore this immunochemotherapeutic schedule as an alternative for treatment of visceral leishmaniasis.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Body Weight; Cricetinae; Leishmania infantum; Leishmaniasis, Visceral; Mesocricetus; Phosphorylcholine

Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate.. In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated.. The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased.. The data indicates an increased L. infantum resistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number of L. infantum strains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated.

Topics: Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Resistance; Female; Leishmania infantum; Leishmaniasis, Visceral; Meglumine Antimoniate; Phosphorylcholine

Zoonotic visceral leishmaniasis by Leishmania infantum is a first-order pathology in canine veterinary clinics in endemic areas. Moreover, canine infections are considered the main reservoir for human disease; despite their importance in the control of the disease within a One Health approach, no scientometric study has been published. Aims of the study included analyzing the impact of canine leishmaniasis (CanL) on the scientific literature, drugs or combinations used, trends in the period from 2000 to 2020 and efficacy criteria employed.. A Web of Science (WOS)-based analysis of publications on CanL and chemotherapy of the disease in the period 2000-2020 was carried out using a stepwise methodology. Data were analyzed by year, geographical origin, chemical groups, drugs and combinations, and efficacy criteria.. Reports on CanL (n = 3324) represented < 16% of all publications on leishmaniasis (n = 20,968), and of these around 18% (n = 596) were related to chemotherapy. Publication records on CanL followed the distribution of the infection by L. infantum in endemic areas although Mediterranean countries were overrepresented in the reports on chemotherapy of CanL. Publications on the main antileishmanial drugs used in clinical practice showed a sustained tendency in the period analyzed. Pentavalent antimonials (Sb. Chemotherapy of CanL still relies on Sb

Topics: Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Combinations; Drug Therapy; Humans; Leishmania infantum; Leishmaniasis; Leishmaniasis, Visceral; Phosphorylcholine; Publications

Hypocobalaminemia in dogs is most commonly associated with gastrointestinal disorders leading to impaired absorption and utilization of cobalamin. The objectives of this study were to compare serum cobalamin concentrations between dogs with leishmaniosis and clinically healthy dogs, and to assess possible alterations of serum cobalamin concentrations in dogs with leishmaniosis at different timepoints during treatment. Fifty-five dogs with leishmaniosis and 129 clinically healthy dogs were prospectively enrolled. Diagnosis of leishmaniosis was based on clinical presentation, positive serology and microscopic detection of Leishmania amastigotes in lymph node aspiration smears. Twenty of the dogs with leishmaniosis were treated with a combination of meglumine antimonate and allopurinol for 28 days and serum cobalamin concentrations were measured in blood samples that were collected before initiation of treatment (timepoint 0) and on days 14 and 28. In order to estimate alterations of serum cobalamin concentrations during treatment, cobalamin concentrations were measured in blood samples from 20 out of 55 dogs with leishmaniosis at all timepoints. Serum cobalamin concentrations were significantly lower in dogs with leishmaniosis before treatment (median: 362 ng/L; IQR: 277-477 ng/L) compared to clinically healthy dogs (median: 470 ng/L; IQR: 367-632 ng/L; P = 0.0035). Serum cobalamin concentrations increased significantly in dogs with leishmaniosis on day 14 of treatment compared to timepoint 0 (P = 0.02). In the present study, serum cobalamin concentrations were significantly lower in dogs with leishmaniosis compared to clinically healthy dogs. In addition, there was an increase in serum cobalamin concentrations during treatment. The clinical significance of hypocobalaminemia in dogs with leishmaniosis remains to be determined.

Topics: Allopurinol; Animals; Dog Diseases; Dogs; Leishmania infantum; Leishmaniasis; Leishmaniasis, Visceral; Meglumine Antimoniate; Vitamin B 12

Topics: Allopurinol; Animals; Antimetabolites; Antiprotozoal Agents; Base Sequence; Cities; Colombia; DNA, Protozoan; Dog Diseases; Dogs; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine Antimoniate

Topics: Allopurinol; Animals; Antiprotozoal Agents; Cytokines; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Leishmaniasis, Visceral; Male; Phosphorylcholine

Leishmania infantum infection including treatment and follow up in domestic animals other than dogs and cats has not been described at this moment. This article describes the anti-Leishmania treatment and follow-up of a ferret (Mustela putorius furo) with leishmaniosis. A combined therapeutic protocol established for the patient, not yet approved for ferrets, was a combination of meglumine antimoniate plus allopurinol. A follow-up was established monthly during the first year in order to monitor the health condition of the patient. Six months after commencing allopurinol therapy, xanthine crystalluria was observed in urine sediment with no other urine alterations detected by urine analysis. The ferret worsened progressively with diarrhoea and weight loss after cohabiting with another ferret diagnosed with cryptosporidiosis. Cryptosporidium parvum was isolated in faecal samples from the patient detected by three different methods including Ziehl-Neelsen staining, a qualitative test to detection of C. parvum antigens and finally a specific molecular analysis to characterize the species. To the best of the authors´ knowledge, this is the first report providing information about anti-Leishmania protocol therapy used and follow-up in a domestic ferret with clinical leishmaniosis. Veterinarians practicing in endemic areas should be aware of this infection in ferrets at risk and their susceptibility especially when immunosuppressive conditions are present.

Topics: Allopurinol; Animals; Antiparasitic Agents; Drug Therapy, Combination; Female; Ferrets; Leishmania infantum; Leishmaniasis, Visceral; Meglumine Antimoniate; Trypanocidal Agents

This study examines correlations among serum proteins, clinical score, body weight and kidney function biomarkers after a standard treatment course (meglumine antimoniate plus allopurinol) in twelve Canine leishmaniosis (CanL) patients at the three times points pre treatment, after treatment and after the end of treatment. The laboratory variables measured were those used for the follow-up of sick dogs along with biomarkers of kidney function: glomerular filtration rate (GFR), creatinine (Cr), urea, calcium, inorganic phosphorus, urine specific gravity (USG) and urine protein to creatinine ratio (UPC). Arterial blood pressure (systolic blood pressure, SBP), clinical score (CS) and weight were also monitored over the study period. At Tp0, GFR was within the normal range in most dogs. Hyperfiltration was detected in three patients and hypofiltration in one. In dogs showing hyperfiltration, this factor remained in the non-azotemic range over the whole study period. After treatment normal filtration values were recovered. Meglumine antimoniate did not modify GFR or USG. A significant reduction in UPC was recorded. In all dogs, clinical scores improved. Negative correlation was found between GFR and Cr, UPC and albumin (Alb) and CS and Alb, while positive correlation was detected between UPC and total globulins (GlobT), CS and GlobT, UPC and total solids (TS), SBP and CS and SBP and UPC. Our findings indicate no impacts on kidney function of the treatment of CanL with meglumine antimoniate, as no effects were produced on GFR or USG. Treatment was effective and found to reduce UPC which could suggest improved glomerular injury.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Biomarkers; Creatinine; Dog Diseases; Dogs; Female; Glomerular Filtration Rate; Kidney Diseases; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine Antimoniate

The objective of this study was to compare changes in serum concentrations of acute phase proteins (APPs) and paraoxanase (PON-1) in response to two treatments in dogs with leishmaniosis (CanL). For this purpose, 20 dogs with CanL were assigned to two treatment groups: antimonial plus allopurinol (Group G, n=12) and miltefosine plus allopurinol (Group M, n=8). Serum concentrations of PON-1 and APPs including C-reactive protein, haptoglobin (Hp), ferritin (Ft) and albumin were monitored over a period of 3 months after treatment. At the beginning of the study (day 0), most of the dogs had APP abnormalities. None of the variables differed significantly between groups in the first or subsequent visits. There was a significantly higher reduction in serum Ft in Group G than in Group M from day 0 to day 30 (P=0.0085), and also from day 0 to day 90 (P=0.0214). There was a higher increase in serum PON-1 in Group G than in than Group M from day 0 to day 30 (P=0.0039), and also from day 0 to day 90 (P=0.0404). This is the first report of APPs in dogs with natural clinical leishmaniosis treated with miltefosine. There was faster resolution of serum APP concentrations in dogs treated with antimonials (P<0.05).

Topics: Acute-Phase Proteins; Allopurinol; Animals; Antiprotozoal Agents; Aryldialkylphosphatase; Dog Diseases; Dogs; Leishmania infantum; Leishmaniasis, Visceral; Meglumine Antimoniate; Phosphorylcholine

Leishmania infection in cats is being increasingly reported in endemic areas. Nevertheless, only a few clinical cases have been described in cats, and even fewer have provided information on the response to treatment and a proper follow-up. Here we report a case of feline leishmaniosis not associated with any other disease or co-infection and document its response to allopurinol treatment and long-term follow-up data.. A 6-year-old domestic shorthair female cat was referred for nodular blepharitis, mucocutaneous ulcerative lesions of the mouth and lymph node enlargement. The cat was moderately anaemic, hyperglobulinaemic and tested negative for feline leukaemia virus and feline immunodeficiency virus. Fine needle aspirates of nodules and mucocutaneous lesions showed the presence of numerous amastigote forms of Leishmania. Leishmania infection was further confirmed by serology (IFAT test, 1:640) and real-time PCR (RT-PCR) on blood and conjunctival swabs. The cat was treated with allopurinol (20 mg/kg SID), which was clinically effective, although the cat remained Leishmania-positive in serology and RT-PCR on blood and conjunctival swabs. Allopurinol treatment was interrupted after seven months because of the healing of all lesions and lack of compliance by the owner. After two years, the cat relapsed displaying almost the same clinical signs and clinicopathological alterations. On this occasion, the parasite was isolated by culture and identified as belonging to L. infantum. Allopurinol treatment was started again but was interrupted several times because of the itching side effect observed. The cat worsened progressively and died two months after the relapse without any chance to shift the treatment to another molecule (e.g. meglumineantimoniate or miltefosine).. Out of all documented cases of feline leishmanosis, the present case has the longest follow-up period and it is one of the few in which the parasite was isolated and identified. It further confirms the potential progression of Leishmania infection to disease in cats even in the absence of comorbidities. Veterinarians practicing in endemic areas should be aware of this susceptibility, properly include feline leishmaniosis in the differential diagnosis and propose preventative measures to those cats at risk.

Topics: Allopurinol; Animals; Cat Diseases; Cats; Female; Follow-Up Studies; Leishmania infantum; Leishmaniasis, Visceral; Treatment Outcome; Trypanocidal Agents

This report describes the first case of visceral leishmaniasis (VL) resistant to pentavalent antimonials and also the first use of combinational therapy in Iran. The patient was a two-year old boy, from a non-endemic area for leishmaniasis in northern Iran, presenting with pentavalent antimonial resistant VL. Additional treatment with conventional and liposomal amphotericin B was not effective. A complete cure was achieved following a three week treatment with liposomal amphotericin B (5 mg/kg/day for 5 days, then on the 14th and 21st days), allopurinol (25 mg/day for 5 days, then on the 14th and 21st days) and interferon gamma (50 μg/m

Topics: Allopurinol; Amphotericin B; Antiprotozoal Agents; Child, Preschool; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Interferon-gamma; Iran; Leishmaniasis, Visceral; Treatment Outcome

Hepatic fibropoiesis in canine visceral leishmaniasis (CVL) were evaluated by histological (morphometrical collagen deposition) and immunohistochemical assays characterizing alpha-actin (α-SMA), vimentin, calprotectin (L1 antigen), and TGF-β in 46 naturally infected dogs with Leishmania infantum treated with liposome-encapsulated meglumine antimoniate and allopurinol separately and in combination. Six treatment groups were defined: meglumine antimoniate encapsulated in nanometric liposomes (LMA), allopurinol (ALLOP); liposome-encapsulated meglumine antomoniate combined with allopurinol (LMA+ALLOP); empty liposomes (LEMP); empty liposomes combined with allopurinol (LEMP+ALLOP) and saline. Relative liver weight was lower in LMA, LMA+ALLOP, and ALLOP groups compared to the LEMP control. Significantly lower granulomatous chronic inflammatory reaction was seen in the ALLOP group compared to a control group. Calprotectin was lowest in liver of those dogs showing lower numbers of intralobular hepatic granulomas. Collagen deposits were significantly higher in LMA compared to ALLOP, LEMP+ALLOP, and Saline groups. LMA+ALLOP group collagen deposition was higher than dogs treated only with allopurinol. Immunohistochemical analysis showed significant higher α-SMA in hepatic stellate cells (HSCs), hepatic perisinusoidal cells, in control groups than LMA+ALLOP and LEMP+ALLOP. Alpha-actin and Vimentin positive cells were diffusely distributed throughout the liver parenchyma in the hepatic lobule, mainly in HSCs. Vimentin expression was significantly higher in the saline group than in the ALLOP group. Our data suggest that allopurinol inhibits HSC and results in lower collagen deposits in liver during CVL progression, as supported by the significantly lower expression of TGF-β in the ALLOP group compared to other groups. Results demonstrated that treatment with allopurinol inhibited chronic granulomatous inflammatory reaction and hepatic fibrosis in CVL.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Female; Gene Expression Regulation; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Liver; Liver Cirrhosis; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Random Allocation; Transforming Growth Factor beta; Vimentin

Some wild animals have been recognized as potential reservoirs of Leishmania infantum infection (e.g. carnivores, lagomorphs, rodents, etc.). Leishmania infantum was also identified infecting humans and lagomorphs (i.e. hares and rabbits) over the period of 2009-2016, with the latter acting as the main reservoirs involved in the human leishmaniosis outbreak in Madrid.. Two cases of clinical leishmaniosis are reported in orangutans (Pongo pygmaeus pygmaeus) housed at two different centres in Madrid. The first is the case of a 36-year-old male orangutan with severe weight loss and apathy. A complete blood count and biochemical profile revealed anaemia, neutropenia, hypoalbuminaemia and elevated transaminases. Hepato-splenomegaly was also observed. Four months later, due to worsening of clinical signs (mainly bilateral epistaxis), blood and bone marrow samples were collected. Amastigotes of L. infantum were detected in macrophages from a bone marrow aspirate and by specific polymerase chain reaction. The second case was a 34-year-old female orangutan with severe weight loss and apathy and no other apparent clinical signs. A complete blood count and biochemical profile revealed anaemia, pancytopenia and hypoalbuminaemia. Splenomegaly and pericardial effusion were also observed. As leishmaniosis was included in the differential diagnosis, both blood and bone marrow samples were collected. Leishmania infantum infection was confirmed by microscopy, molecular diagnosis and serology (immunofluorescence antibody test). Both animals were treated daily with oral miltefosine for 28 days; allopurinol was also given uninterruptedly in Case 2 for at least 6 months. During follow-up, though good clinical recovery was clear, a lack of parasitological cure was confirmed molecularly in both blood and bone marrow samples from the two orangutans. In both habitats, the presence of the sand fly vector identified as Phlebotomus perniciosus was confirmed.. To our knowledge, this is the first report of L. infantum infection in great apes and in the endangered species P. p. pygmaeus. We are presently looking for L. infantum in other non-human primates living in the same peri-urban areas. If detected, we will examine the impacts of this serious disease on these critically endangered species.

Topics: Allopurinol; Animals; Diagnosis, Differential; Disease Outbreaks; Endangered Species; Female; Leishmania infantum; Leishmaniasis, Visceral; Male; Phosphorylcholine; Pongo pygmaeus; Psychodidae; Spain

The aim of this study was to evaluate the possible changes in the concentration of anti-Leishmania antibodies in saliva samples from dogs with clinical leishmaniosis after short-term treatment. Twenty dogs with clinical signs and laboratory abnormalities compatible with canine leishmaniosis (CanL) were diagnosed and treated with a standard antimonial plus allopurinol therapy. The concentration of anti-Leishmania IgG2 and IgA antibodies in saliva was measured at the time of diagnosis (day 0) and after treatment (day 30) by time-resolved immunofluorometric assays (TR-IFMAs) and results were compared with those of serum. In addition, correlations between antibody concentrations in saliva and serum, clinical scores and selected laboratory analytes were calculated. TR-IFMA results were expressed as Units of Fluorometry for Leishmania (UFL). Most dogs that adequately responded to treatment (n = 17) showed a reduction of anti-Leishmania antibodies in saliva [median IgG2: from 678.0 (day 0) to 201.1 UFL (day 30), p < 0.0001; median IgA: from 91.3 (day 0) to 60.2 UFL (day 30), p < 0.01] in accordance with clinical improvement (p < 0.0001). However, two of these dogs showed an increase of anti-Leishmania antibodies in saliva. Among dogs that did not improve after one month of treatment (n = 3), two showed a reduction in serum and saliva antibodies. In these two dogs, clinical recovery was achieved after one additional month of treatment with allopurinol. The other dog that did not respond to treatment showed increases in the concentration of anti-Leishmania antibodies, both in saliva and serum, and did not adequately respond to an additional month of treatment with allopurinol. From this pilot study, it could be concluded that, despite the low number of dogs used, the measurement of anti-Leishmania IgG2 and IgA antibodies in saliva could have a potential use for treatment monitoring of CanL, provided that a sufficient amount of specific antibodies is present at diagnosis. This is because, especially in the case of IgG2, there is a high correlation between the saliva and serum concentrations, and the reduction of antibodies is generally in accordance with the clinical improvement. Further long-term studies with a larger population should be undertaken to confirm this potential.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antiprotozoal Agents; Dog Diseases; Dogs; Female; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Saliva

Leishmania infantum is one of the causative agents of visceral leishmaniasis (VL), a widespread, life-threatening disease. This parasite is responsible for the majority of human VL cases in Brazil, the Middle East, China, Central Asia and the Mediterranean basin. Its main reservoir are domestic dogs which, similar to human patients, may develop severe visceral disease and die if not treated. The drug allopurinol is used for the long-term maintenance of dogs with canine leishmaniasis. Following our report of allopurinol resistance in treated relapsed dogs, we investigated the mechanisms and markers of resistance to this drug. Whole genome sequencing (WGS) of clinical resistant and susceptible strains, and laboratory induced resistant parasites, was carried out in order to detect genetic changes associated with resistance. Significant gene copy number variation (CNV) was found between resistant and susceptible isolates at several loci, including a locus on chromosome 30 containing the genes LinJ.30.3550 through LinJ.30.3580. A reduction in copy number for LinJ.30.3560, encoding the S-adenosylmethionine synthetase (METK) gene, was found in two resistant clinical isolates and four induced resistant clonal strains. Using quantitative real time PCR, this reduction in METK copy number was also found in three additional resistant clinical isolates. Furthermore, inhibition of S-adenosylmethionine synthetase encoded by the METK gene in allopurinol susceptible strains resulted in increased allopurinol resistance, confirming its role in resistance to allopurinol. In conclusion, this study identified genetic changes associated with L. infantum resistance to allopurinol and the reduction in METK copy number identified may serve as a marker for resistance in dogs, and reduced protein activity correlated with increased allopurinol resistance.

Topics: Allopurinol; Animals; DNA Copy Number Variations; Dog Diseases; Dogs; Drug Resistance; Gene Dosage; Humans; Leishmania infantum; Leishmaniasis; Leishmaniasis, Visceral; Methionine Adenosyltransferase; Real-Time Polymerase Chain Reaction; Whole Genome Sequencing

Resistance to allopurinol in zoonotic canine leishmaniasis has been recently shown to be associated with disease relapse in naturally-infected dogs. However, information regarding the formation of resistance and its dynamics is lacking. This study describes the successful in-vitro induction of allopurinol resistance in Leishmania infantum cultured under increasing drug pressure. Allopurinol susceptibility and growth rate of induced parasites were monitored over 23 weeks and parasite clones were tested at selected time points and compared to their parental lines, both as promastigotes and as amastigotes. Allopurinol resistance was formed in strains from two parasite stocks producing a 20-fold rise in IC50 along three distinct growth phases. In addition, characteristic differential clustering of single nucleotide polymorphisms (SNP) was found in drug sensitive and resistant parasite clones. Results confirm that genetic polymorphism, as well as clonal heterogeneity, contribute to in-vitro resistance to allopurinol, which is likely to occur in natural infection.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Resistance; Inhibitory Concentration 50; Leishmania infantum; Leishmaniasis, Visceral; Polymorphism, Single Nucleotide

There is limited data regarding Leishmania infantum specific T cell mediated immunity in naturally infected sick dogs at the time of diagnosis and during anti-Leishmania treatment. Our aim was to investigate the kinetics of L. infantum specific IFN-γ production in dogs with leishmaniosis at the time of diagnosis and during treatment and to correlate it with specific L. infantum antibodies, blood parasitemia and clinicopathological findings. Thirty-four dogs were diagnosed with leishmaniosis based on physical examination, routine laboratory tests and L. infantum-specific antibody levels by quantitative ELISA. Heparinized whole blood was stimulated with L. infantum soluble antigen (LSA) and concanavalin A (ConA) and incubated for 5days. IFN-γ concentration was evaluated in supernatants of stimulated blood using a commercial sandwich ELISA. Leishmania real-time PCR was also performed for assessing blood parasitemia. Dogs were treated with meglumine antimoniate and allopurinol. Sixteen dogs were classified as IFN-γ non-producers after LSA stimulation (mean±SD: 0±0pg/mL) and 18 dogs as IFN-γ producers (mean±SD: 2885.3±4436.1pg/mL) at the time of diagnosis (P<0.0001). IFN-γ non-producers were classified in a more severe clinical staging than IFN-γ producers that presented a mild to moderate clinical staging (P=0.03). In the IFN-γ non-producer group, production of IFN-γ after LSA stimulation was significantly increased during treatment especially at day 365 (P=0.018) together with clinical improvement when compared with day 0. In contrast, IFN-γ producers maintained their IFN-γ production after LSA stimulation and no statistically significant changes were found during treatment follow-up. At diagnosis, IFN-γ non-producers showed a significantly higher blood parasitemia versus IFN-γ -producers (P=0.005). IFN-γ non-producers drastically reduced blood parasitemia to minimum values at day 365 when compared with day 0 (P=0.017). No significant differences were found at day 365 in blood parasitemia of IFN-γ producers compared to pre-treatment. At diagnosis, L. infantum specific antibodies were higher in IFN-γ non-producers than IFN-γ producers (P=0.014). A marked reduction of antibody levels was found at day 365 when compared with day 0 in IFN-γ non-producers (P=0.005) and producers (P=0.001). These results demonstrate that IFN-γ concentration increases with long-term anti-Leishmania treatment together with clinical improvement in dogs that do not produce IFN-γ at dia

Topics: Allopurinol; Animals; Dog Diseases; Dogs; Female; Interferon-gamma; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Trypanocidal Agents

Visceral leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs. Resistance of Leishmania strains from dogs to allopurinol has not been described before in clinical studies.. Following our observation of clinical disease relapse in dogs under allopurinol treatment, we tested susceptibility to allopurinol of L. infantum isolated from groups of dogs pre-treatment, treated in remission, and with disease relapse during treatment. Promastigote isolates obtained from four treated relapsed dogs (TR group) showed an average half maximal inhibitory concentration (IC50) of 996 μg/mL. A significantly lower IC50 (P = 0.01) was found for isolates from ten dogs before treatment (NT group, 200 μg/mL), as well as for five isolates obtained from treated dogs in remission (TA group, 268 μg/mL). Axenic amastigotes produced from isolates of the TR group also showed significantly higher (P = 0.002) IC50 compared to the NT group (1678 and 671 μg/mL, respectively). The lower sensitivity of intracellular amastigotes from the TR group relative to those from the NT group (P = 0.002) was confirmed using an infected macrophage model (6.3% and 20% growth inhibition, respectively at 300 μg/mL allopurinol).. This is the first study to demonstrate allopurinol resistance in L. infantum and to associate it with disease relapse in the canine host. These findings are of concern as allopurinol is the main drug used for long term control of the disease in dogs, and resistant L. infantum strains may enhance uncontrolled transmission to humans and to other dogs.

Topics: Allopurinol; Animals; Antimetabolites; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Resistance; Leishmania infantum; Leishmaniasis, Visceral

A 3-year-old Labrador Retriever originating from Spain was presented with a left-sided hind limb lameness for several months. The orthopedic examination revealed a pain response when palpating the left tarsal joint. Radiographic and computed tomographic studies showed polyostotic, aggressive osteolytic bone lesions with mild erosive arthritis. The diagnosis of canine leishmaniasis was confirmed by bone biopsy and the detection of the pathogen by PCR. Three weeks after initiation of therapy with allopurinol, the dog presented no signs of lameness. Eight months after start of therapy, radiographic examination revealed moderate regression of the osteolytic bone lesions.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Bone Diseases, Infectious; Dog Diseases; Dogs; Lameness, Animal; Leishmania infantum; Leishmaniasis, Visceral

Although dogs are the main reservoir for human Leishmania infantum infection, the disease has also been reported in other domestic and wild mammals. In 2011, a fatal case of naturally acquired leishmaniosis was described for the first time in a Bennett's wallaby (Macropus rufogriseus rufogriseus) kept in a wildlife park in Madrid (Spain). This study was designed to assess the infection status of twelve Bennett's wallabies in the same park one year after this incident. Phlebotomus perniciosus, the main vector of L. infantum in Spain, was screened for using sticky and Centers for Disease Control miniature light traps. L. infantum infection was confirmed by molecular diagnosis in four animals, but only one wallaby returned a positive serology result. The presence of the sand fly vector was also confirmed in this habitat. These results suggest that the first case of L. infantum in a wallaby in this park was not an isolated incident and stress the need for further work to determine the role of this parasite in the morbidity and mortality of these macropods. Madrid was recently the scene of an outbreak of human cutaneous and visceral leishmaniosis. Epidemiological studies have so far revealed the widespread presence of L. infantum infection in animals other than the dog. Our ongoing work suggests a risk of L. infantum infection not only among captive animals in Madrid, but also among threatened species or even species that are already extinct in the wild.

Topics: Allopurinol; Animals; Animals, Zoo; Female; Insect Vectors; Leishmania infantum; Leishmaniasis, Visceral; Macropodidae; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Psychodidae; Spain

A 5.5-year-old, intact male Rottweiler dog was admitted with a history of multifocal nodular tongue lesions which progressively deteriorated during the previous year. Physical examination revealed several reddish nodules with central depression on the surface of the tongue in an otherwise healthy dog. Clinicopathologic abnormalities included eosinophilia and hyperproteinemia. Lingual nodule cytopathology, histopathology, and immunohistochemistry revealed Leishmania spp. amastigotes and a severe granulomatous glossitis. The dog was also seroreactive to L infantum antigens by an indirect immunofluorescence assay. Clinical reevaluation 3 months after the institution of treatment with allopurinol and miltefosine indicated that the nodular lesions had completely regressed. In endemic areas, lingual nodular lesions may rarely be the sole clinical sign of canine leishmaniosis. Standard medical treatment may provide an excellent prognosis.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Therapy, Combination; Fluorescent Antibody Technique, Indirect; Glossitis; Immunohistochemistry; Leishmania infantum; Leishmaniasis, Visceral; Male; Phosphorylcholine; Tongue

Ferritin and paraoxonase-1 (PON-1) were measured in dogs experimentally infected by Leishmania infantum (during experimental infection and following treatment) and also in naturally-infected dogs which presented different degrees of proteinuria. Experimentally-infected dogs were monitored for 7 months post-infection, then treated for 3 months with allopurinol, and their response to therapy was followed for 11 additional months. Naturally-infected dogs were staged based on the urine protein/creatinine (UPC) ratio into three groups as follows: group 1 (non-proteinuric; UPC ratio: <0.2), group 2 (borderline proteinuric; UPC ratio: 0.2-0.5) and group 3 (proteinuric; UPC ratio>0.5). An increase in serum ferritin values and a decrease in PON-1 activity were observed 2 months after infection. Both analytes returned to preinfection values following treatment. Significantly higher concentrations of ferritin were observed in dogs classified as either borderline or proteinuric when compared with non-proteinuric dogs whereas serum PON-1 activity was decreased only in proteinuric dogs.

Topics: Allopurinol; Animals; Aryldialkylphosphatase; C-Reactive Protein; Creatinine; Dog Diseases; Dogs; Enzyme Inhibitors; Female; Ferritins; Leishmania infantum; Leishmaniasis, Visceral; Male; Prospective Studies; Statistics, Nonparametric

Hypothyroidism may predispose to the development of canine leishmaniosis or it may appear during the course of the latter due to infiltration and destruction of the thyroid gland by infected macrophages. The main purpose of this study was to evaluate thyroid function through measurement of serum total thyroxin (tT₄), free thyroxin (fT₄), and canine thyroid stimulating hormone (cTSH) concentrations in 36 dogs with leishmaniosis, before and after 2 and 4 weeks of treatment with allopurinol with or without meglumine antimonate. Before treatment 27/36 (75%) dogs had serum tT₄ concentrations below the lower limit of the reference interval but only 2 of them had concurrently serum fT₄ concentrations below the lower limit of the reference interval and none had increased serum cTSH concentrations. During treatment there were no significant changes in serum tT₄ or fT₄ concentrations, whereas a significant increase in serum cTSH was observed. Two dogs had decreased serum tT₄ and fT₄ but normal cTSH concentrations before treatment and two other dogs had decreased serum tT₄ and increased cTSH, but normal fT₄ concentrations during the treatment period. Although hypothyroidism could not be definitively excluded in these dogs it is considered unlikely based on their overall hormonal profile, clinical presentation, and response to treatment. Therefore, hypothyroidism does not appear to be an important predisposing disease or a frequent complication of canine leishmaniosis.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Hypothyroidism; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Thyrotropin; Thyroxine

Visceral leishmaniasis (VL) caused by parasites of Leishmania donovani complex is a severe human disease which often leads to death if left untreated. Domestic dogs are the main reservoir hosts for zoonotic human visceral infection caused by Leishmania infantum. In the absence of effective human and dog vaccines, the only feasible way to treat and control leishmaniasis is through the use of suitable medications. To know the drug susceptibility of human and canine Leishmania strains from Lisbon-Portugal, a study on a panel of strains was conducted by testing the susceptibility of promastigotes and intracellular amastigotes to the common drugs used in canine leishmaniasis (CanL) and human VL (meglumine antimoniate, amphotericin B, miltefosine and allopurinol). Although a high heterogeneity of susceptibilities was obtained to each drug on both axenic promastigote and intracellular amastigote assays, intracellular amastigotes system correlated better with treatment outcome. Parasites isolated from the refractory human case were the least susceptible to the drugs used highlighting that the emergence of cross-resistance to the drugs available for human therapy should not be neglected. Furthermore, parasites isolated from dogs showed low susceptibility to the main drugs used in CanL treatment. Our results focus the importance of reducing/avoiding the emergence and spread of resistant parasites in the canine and human populations, a factor that requires special consideration when dogs are treated using the same available anti-Leishmania drugs for human VL. In addition, efforts should be made in order to standardize the conditions used to test drug susceptibility (methodologies, drug formulations and media) in order to compare results between laboratories.

Topics: Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Deoxycholic Acid; Disease Reservoirs; Dog Diseases; Dogs; Drug Combinations; Humans; Immunocompetence; Immunocompromised Host; Inhibitory Concentration 50; Leishmania infantum; Leishmaniasis, Visceral; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Parasitic Sensitivity Tests; Phosphorylcholine

Despite the availability of different therapeutic options, canine visceral leishmaniosis (CVL) remains a challenging disease to treat. Recently miltefosine has been registered for use in dogs, and different studies have demonstrated its leishmanicidal effect. Moreover, it has been suggested that fluoroquinolones, compared to standard chemotherapeutic agents, could be an effective and pragmatic alternative to treat CVL. The efficacy of miltefosine and marbofloxacin alone or in combination with allopurinol against clinical strains of Leishmania infantum was assessed in vitro by incubating increasing concentrations of the drugs with a standard parasite inoculum. Miltefosine was significantly more efficacious than marbofloxacin (P < 0.05) against the two strains of L. infantum either alone or in combination with allopurinol. Both drugs were significantly (P < 0.05) more efficacious when associated with allopurinol than alone.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Synergism; Fluoroquinolones; Leishmania infantum; Leishmaniasis, Visceral; Phosphorylcholine

An innovative liposomal formulation of meglumine antimoniate (LMA) was recently reported to promote both long-term parasite suppression and reduction of infectivity to sand flies in dogs with visceral leishmaniasis. However, 5 months after treatment, parasites were still found in the bone marrow of all treated dogs. In order to improve treatment with LMA, the present study aimed to evaluate its efficacy in combination with allopurinol. Mongrel dogs naturally infected with Leishmania infantum were treated with six doses of LMA (6.5 mg Sb/kg of body weight/dose) given at 4-day intervals, plus allopurinol (20 mg/kg/24 h per os) for 140 days. Comparison was made with groups treated with LMA, allopurinol, empty liposomes plus allopurinol, empty liposomes, and saline. Dogs remained without treatment from day 140 to 200 after the start of treatment. The drug combination promoted both clinical improvement of dogs and significant reduction in the parasitic load in bone marrow and spleen on days 140 and 200 compared to these parameters in the pretreatment period. This is in contrast with the other protocols, which did not result in significant reduction of the bone marrow parasite load on day 200. Strikingly, the combined treatment, in contrast to the other regimens, induced negative quantitative PCR (qPCR) results in the liver of 100% of the dogs. Both xenodiagnosis and skin parasite determination by qPCR indicated that the drug combination was effective in blocking the transmission of skin parasites to sand flies. Based on all of the parasitological tests performed on day 200, 50% of the animals that received the combined treatment were considered cured.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dogs; Female; Leishmaniasis, Visceral; Liposomes; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds

Canine leishmaniosis (CanL) caused by Leishmania infantum is an endemic zoonosis in southern European countries. Infected dogs can present rare or atypical forms of the disease and diagnosis can be challenging. The present report describes a case of tongue nodules in a 3-year-old neutered female Labrador Retriever dog with leishmaniosis.. A fine needle aspiration of the lingual nodules revealed amastigote forms of Leishmania inside macrophages. Differential diagnosis ruled out neoplasia, calcinosis circumscripta, solar glossitis, vasculitis, amyloidosis, eosinophilic granulomas, chemical and electrical burns, uremic glossitis and autoimmune diseases. Combined therapy with antimoniate meglumine and allopurinol for 30 days resulted in the normalization of hematological and biochemical parameters. Two months after diagnosis and the beginning of treatment, a mild inflammatory infiltrate was observed by histopathology, but an anti-Leishmania immunofluorescence antibody test (IFAT) was negative as well as a PCR on both tongue lesions and a bone marrow aspirate. Seven months after diagnosis, the dog's general condition appeared good, there were no tongue lesions and a new IFAT was negative. Fifteen months after diagnosis this clinically favourable outcome continued.. The dog could have suffered a relapsing episode of CanL, but a new systemic or local infection cannot be excluded. Regular clinical re-evaluation should be maintained, as a future relapse can potentially occur. In conclusion, CanL should be considered in the differential diagnosis of nodular glossitis in dogs.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Leishmania infantum; Leishmaniasis, Visceral; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Tongue; Tongue Diseases

A female barbary lion (Panthera leo leo) from the Montpellier Zoological Park (France) showing colitis, epistaxis, and lameness with pad ulcers was positive by polymerase chain reaction (PCR) for Leishmania infantum. Further indirect immunofluorescence (IFAT) tests on the banked sera from all lions of the park detected another infected but asymptomatic female, which was confirmed by PCR on ethylenediaminetetraacetic acid (EDTA) blood sample. Leishmania infantum zymodeme MON-1 was cultured from EDTA bone marrow samples sampled from this second animal. The first female was successfully treated with marbofloxacine at 2 mg/kg s.i.d. for 28 days (Marbocyl, Vetoquinol 70204 Lure, France) and allopurinol at 30 mg/kg s.i.d. for 3 mo (Allopurinol Mylan, Mylan SAS, 69800 Saint-Priest, France) and then 1 wk/mo. Both positive animals were born at the Rabat Zoological Park, Morocco, and arrived together at Montpellier in 2003. The chronicity and source of this current infection are unknown since Morocco and southern France are well-known to be enzootic for leishmaniasis.

Topics: Allopurinol; Animals; Animals, Zoo; Antiprotozoal Agents; Drug Therapy, Combination; Female; Fluoroquinolones; Leishmania infantum; Leishmaniasis, Visceral; Lions

Acute phase proteins (APPs) have been proposed as useful markers for the diagnosis and monitoring of treatment of dogs infected by Leishmania infantum. However, the kinetics and behavior of these proteins in canine leishmaniasis is still unknown. The aim of this study was to monitor the kinetics of APPs in dogs experimentally infected with L. infantum, before, during and after therapy against canine leishmaniasis. Levels of serum haptoglobin, serum amyloid A and C-reactive protein from 6 infected beagles, positive by both PCR and parasite culture, were monitored for 7 months post-infection. The dogs were then treated for 3 months with allopurinol (20 mg mg/kg/day PO), and their response to therapy was followed for 11 additional months. Levels of Immunoglobulins G and M were recorded during these 21 months and compared. Experimental infection with L. infantum amastigotes induced an increase in all APPs studied which was statistically significant 2 months after infection for all proteins. Clinical recovery was accompanied by a significant decrease of all APPs 1 month after the beginning of treatment. However, differences were found between the APPs in both magnitude and duration of serum level elevations. The increase in total IgG and IgM was delayed in comparison to APPs and contrarily to the APPs, these immunoglobulins did not significantly decrease with treatment. In conclusion, the results of this study suggest that APPs could be used as early markers for disease as well as for monitoring the response to treatment in canine leishmaniasis.

Topics: Acute-Phase Proteins; Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Immunoglobulin G; Immunoglobulin M; Leishmaniasis, Visceral; Male

The goal of the present study was to characterize the semen quality of dogs naturally infected with Leishmaniachagasi, and treated with Allopurinol and Amphotericin B. Eight naturally infected and eight non-infected dogs were selected. Following semen collection, progressive motility, vigor, concentration and sperm morphology were evaluated. The seminal patterns in the treated animals were evaluated at the beginning (d0) and at days 30 (d30), 60 (d60) and 150 (d150) of treatment. The progressive motility at d0 (35.7+/-22.3%) was less than that of the control group (77.8+/-7.1%) (P<0.05). The vigor was similar to the control group throughout the treatment (P>0.05). The number of sperm/mL, sperm/ejaculate and sperm/kg of body weight was similar among groups (P>0.05). The percentages of normal spermatozoa of infected and treated animals were similar throughout the treatment and to the control group (69.1+/-8.7%) at d60 (37.5+/-11.2%) and d150 (48.3+/-10.8%) (P>0.05), but smaller at d0 (22.7+/-10.5%) and d30 (28.8+/-15.9%) (P<0.05). A greater percentage of acrosome damage was observed in the control group (3.1+/-2.3%) compared to the d60 (0.1+/-0.2%) (P<0.05). The infected dogs had a greater percentage of principal piece defects at d60 (37.0+/-6.3%) than the control group (16.8+/-7.3%) (P<0.05); and greater percentages of detached normal heads at d0 (28.7+/-19.7%) and d30 (18.5+/-18.5%) than the control group (0.4+/-0.5%) (P<0.05). This reduction in semen quality of the infected animals is suggestive of an epididymal dysfunction. Due to this poor semen quality, caution is recommended when using infected male dogs for reproductive purposes.

Topics: Acrosome; Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Epididymis; Leishmaniasis, Visceral; Male; Sperm Count; Sperm Motility; Spermatozoa; Testicular Diseases

Leishmune, the first licensed vaccine for prophylaxis against canine visceral leishmaniasis (CVL) and is also immunotherapeutic when used with double saponin adjuvant concentration. The Leishmune therapeutic vaccine was assessed for immunotherapy (IT) in 31 infected dogs and for immunochemotherapy (ICT) in combination with allopurinol or amphotericinB/allopurinol, in 35 dogs. Compared to infected untreated control dogs, at month 3, both treatments increased the proportion of dogs showing intradermal response to Leishmania antigen to a similar extent (from 8 to 67%, in the IT and to 76%, in the ICT groups), and conversely reduced from 100 to 38% (IT) and to 18% (ICT) the proportion of symptomatic cases, from 54 to 12% (IT) and to 15% (ICT) the proportion of parasite evidence in lymph nodes and from 48 to 19% (IT) and 12% (ICT) the proportion of deaths, indicating that the immunotherapy with enriched-Leishmune vaccine promotes the control of the clinical and parasitological signs of CVL rendering most dogs asymptomatic although PCR positive. By month 8, negative lymph node PCR results were obtained in 80% of the ICT-treated dogs, but only in 33% of the IT group (p=0.0253), suggesting that the combination of additional chemotherapy with Leishmune-enriched saponin vaccination abolished, not only the symptoms but also the latent infection condition, curing the dogs. The animals were followed up until 4.5 years after the beginning of the experiment and, compared to the untreated control group at month 3 (12/25 dogs; 48%), a decrease in the rate of CVL deaths was only seen after ICT treatment (7/35 dogs; 20%; 0.0273) but not after IT treatment (10/31 dogs; 32%; p=0.278), pointing out an additional advantage of the ICT treatment with the enriched-Leishmune in the control and cure of CVL.

Topics: Adjuvants, Immunologic; Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Therapy; Drug Therapy, Combination; Follow-Up Studies; Immunotherapy; Leishmaniasis, Visceral; Lymph Nodes; Protozoan Vaccines; Saponins; Survival Analysis; Treatment Outcome

Leishmaniasis is an infection caused by a protozoan parasite belonging to the genus Leishmania and transmitted by the Phlebotomus sandfly. We report a case of visceral leishmaniasis in a 49-year-old male renal transplant recipient, a resident of the western part of Tunisia, which is an endemic zone for the disease. Just before and after the transplantation, the patient resided in Tunis, which is non-endemic for leishmaniasis. Visceral leishmaniasis occurred eight years after renal transplantation, and the clinical picture was characterized by fever and pancytopenia. Leishmaniae were detected by bone marrow aspiration. Pentavalent antimonal was used for 28 days and was substituted by allopurinol (20 mg/kg per day). One year after the infection, the patient remains totally asymptomatic. Our report suggests that visceral leishmaniasis may complicate the clinical course of organ transplantation and can be fatal, particularly when untreated. Relapses may occur after completion of the apparently effective treatment. Allopurinol could be a solution to avoid these relapses.

Topics: Allopurinol; Bone Marrow Examination; Humans; Immunosuppressive Agents; Kidney Transplantation; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Time Factors; Treatment Outcome; Trypanocidal Agents; Tunisia

Visceral leishmaniosis is a life-threatening disease of medical, social and economic importance in endemic areas. It is an opportunistic infection in immunocompromised patients, including human immunodeficiency virus-positive subjects. Dogs are the main reservoir of Leishmania infantum. The aim of this study was to evaluate the efficacy of miltefosine and allopurinol for the control of human leishmaniosis using the dog as a model. The study included 28 sick dogs treated with miltefosine (2 mg/kg/day PO) administered concurrently with allopurinol (10 mg/kg/day, PO) for 30 days, and then with allopurinol alone, at the same dosage, for 1 year. Eight dogs (four of which relapsed) received a second cycle of miltefosine within 6 months of the first cycle. Efficacy was measured by real-time polymerase chain reaction assay on whole blood samples and lymph node aspirates, collected at baseline and every 3 months for 12 months. Of the total number of animals (28), two showed renal insufficiency and died after the start of therapy with miltefosine. Two other dogs presented some side effects to treatment, such as nausea, vomiting and reduction in white and red blood cell counts, and these animals were excluded from the follow-up. The results showed that the first cycle of therapy with miltefosine and allopurinol induced a drastic and progressive reduction of L. infantum load in lymph node aspirates but the second cycle did not eliminate the parasite.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Disease Models, Animal; Disease Reservoirs; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Humans; Leishmania infantum; Leishmaniasis, Visceral; Male; Phosphorylcholine; Recurrence; Treatment Outcome; Zoonoses

An adolescent with idiopathic CD4 lymphocytopenia suffered from 4 visceral leishmaniasis relapses despite appropriate treatment. CD8 lymphocytopenia and abnormal expansion of TCRalphabeta, CD4, CD8 cells were consistently detected together with reduced export of mature T cells from thymus. This novel form of idiopathic CD4 lymphocytopenia may predispose to multiple visceral leishmaniasis relapses.

Topics: Adolescent; Allopurinol; Amphotericin B; Antipruritics; Female; Humans; Immunophenotyping; Keratins; Leishmaniasis, Visceral; Lymph Nodes; Recurrence; T-Lymphocytopenia, Idiopathic CD4-Positive

Leishmaniasis from Leishmania infantum is a parasitary zoonotic disease and a serious problem to public health. Guidelines from Italian Health Authority (Istituto Superiore di Sanità) suggest to control the zoonotic visceral leishmaniasis canine reservoir in endemic areas using an association of preventive and therapeutic tools. Moreover, in literature there are no studies about the long term effects on the disease seroprevalence and incidence in relation to this "holistic" approach. Past research has considered the effects of the alternative employment of preventive or therapeutic treatment, usually for limited periods. In this retrospective study the patterns of seroprevalence and incidence of leishmaniasis in a dog shelter sited in an endemic area of Central Italy are described throughout a 4-year period. Both preventive spot-on tools (imidacloprid/permetrin) and therapeutic protocols based on antimonials and allopurinol were administered. The results showed a progressive reduction of prevalence and incidence of serological reactivity to L. infantum, corroborating the effectiveness of the treatment administered to the animals. Significant improvements from the beginning to the end of the 4-year period were reported, considering both prevalence and incidence. A very low rate of relapses (8% in a pool of 67 subjects positive since 2004; 10.2% among all subjects enrolled in the study) was achieved.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antiprotozoal Agents; Disease Reservoirs; Dog Diseases; Dogs; Endemic Diseases; Female; Imidazoles; Incidence; Italy; Leishmania infantum; Leishmaniasis, Visceral; Male; Neonicotinoids; Nitro Compounds; Permethrin; Retrospective Studies; Secondary Prevention; Seroepidemiologic Studies

In this study, we searched for a connection between Leishmania load and cytokine expression levels in the tissues of Leishmaniainfantum naturally infected dogs and the efficacy of treatment with miltefosine and allopurinol. To this purpose, we exploited a real-time PCR system to detect Leishmania load and the expression levels of IFN-gamma and IL-4 mRNAs at the time of diagnosis and during the follow up post-treatment. In particular, we measured the amount of parasites in blood and lymph node samples, while the expression levels of IFN-gamma and IL-4 cytokines were assessed in the blood of the animals. We employed different targeted real-time PCR assays on 20 naturally infected dogs with clinical signs. Three healthy dogs living in a non-endemic area were selected as negative controls. The overall results obtained demonstrate that the simultaneous evaluation of parasites and cytokine levels in different kinds of tissue might represent a reliable tool to evaluate the immune response, the efficacy of the therapy and to predict the relapses during the treatment.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Biomarkers; DNA, Protozoan; Dog Diseases; Dogs; Interferon-gamma; Interleukin-4; Leishmania infantum; Leishmaniasis, Visceral; Phosphorylcholine

Thirty dogs naturally infected with Leishmania infantum were studied in order to determine the effects of treatment on haemostatic function. The animals were divided randomly into two treatment groups: Group 1 received meglumine antimoniate and allopurinol; Group 2 dogs were given the same treatment plus prednisone. Ten healthy animals were used as untreated controls. Clinical examination and determination of platelet aggregation, coagulation factors and biochemical parameters were undertaken before treatment and after 15, 30 and 60 days. A significant improvement in platelet aggregation was detected after 60 days in Group 1, but only after 15 days in Group 2. In both treated groups, platelet aggregation was lower than in the control group at the end of the study. The results suggest that prednisone may be a useful tool in the treatment of haemostatic disorders during canine leishmaniosis. The potential benefits and risks due to the use of corticosteroids in the treatment of leishmaniosis are discussed.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Female; Homeostasis; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Platelet Aggregation; Prednisone; Random Allocation; Risk Assessment

We describe a 66-year-old woman hospitalized with fever, fatigue and hepatopathy. In her medical history arterial hypertension (treated with propranolol and lisinopril), diabetes mellitus type 2 (no treatment before admission) and a gout arthropathy were noted wherefore a therapy with allopurinol 300 mg per day has been started 4 months before. Liver biopsy revealed fibrin-ring granulomas, compatible with allopurinol-induced hepatitis. Because of persistence of high fever after stopping allopurinol, steroids (1 mg/kg) were started. Under this treatment, she developed pancytopenia and fever. The bone marrow aspiration revealed Leishmania infantum. A second liver biopsy showed amastigotes and a disappearance of the granulomas. The history revealed a travel to Malta 2 years earlier. Despite adequate treatment with liposomal amphotericin B the patient deteriorated and finally died in septic shock.

Topics: Aged; Allopurinol; Animals; Biopsy; Bone Marrow; Chemical and Drug Induced Liver Injury; Fatal Outcome; Female; Fibrin; Gout Suppressants; Granuloma; Humans; Leishmania infantum; Leishmaniasis, Visceral; Liver

The introduction of PCR has efficiently improved diagnosis of canine leishmaniasis. In order to provide a robust, efficient and reliable diagnostic method, a duplex PCR assay targeting the Leishmania infantum kDNA minicircle and the canine GAPDH gene as inner control was designed. Sensitivity of the assay reached 0.15 parasites/ml blood. Development, testing and application of this system on a group of 10 dogs during therapy administration (60 days) are also described. Six dogs (out of eight that have been showing a positive PCR result on peripheral blood during the study) were tested negative at day 62, indicating a reduction of parasitaemia at the end of the treatment period. All the animals had a positive PCR on lymph node aspirate both at the beginning and at the end of treatment. These findings seem to suggest that, in order to test therapy efficacy, PCR on whole blood could be a useful assay in dogs that have a positive PCR at the beginning of the treatment, while PCR positivity on lymph nodes lasts longer than the observation period during therapy administration. The presence of the GAPDH inner control band efficiently contributed to prevent false negatives, by highlighting samples affected by haemoglobin inhibition or inappropriate DNA isolation.

Topics: Allopurinol; Animals; Antiprotozoal Agents; DNA, Kinetoplast; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Leishmania infantum; Leishmaniasis, Visceral; Lymph Nodes; Lymphadenitis; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Parasitemia; Phosphoric Monoester Hydrolases; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity

Standard treatments for visceral leishmaniasis (antimonials, amphotericin B and pentamidine) pose several problems. Failure of antimonials or severe toxicity is particularly troublesome in patients with renal insufficiency. We report a case of visceral leishmaniasis and renal insufficiency successfully treated with fluconazole and allopurinol for 4 months.

Topics: Allopurinol; Antifungal Agents; Antimetabolites; Diabetic Nephropathies; Fluconazole; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Renal Insufficiency

Standard treatments for visceral leishmaniasis (antimonials, amphotericin B and pentamidine) pose several problems. Failure of antimonials or severe toxicity is particularly troublesome in patients with renal insufficiency. We report a case of visceral leishmaniaisis and renal insufficiency successfully treated with fluconazole and allopurinol for 4 months.

Topics: Allopurinol; Animals; Antimetabolites; Antiprotozoal Agents; Diabetic Nephropathies; Drug Therapy, Combination; Fluconazole; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Renal Insufficiency; Treatment Outcome

Seven dogs with parasitologically proven clinical visceral leishmaniosis (Leishmania infantum infection) were treated with a combination of allopurinol and sodium stibogluconate. The dogs received first orally 15 mg/kg of allopurinol every 12 h until the clinical signs improved, in the following 1 month period allopurinol at same dose and subcutaneously 30 mg/kg of sodium stibogluconate combination were given daily and at the end of the combined treatment, allopurinol was continued alone at the same dose till the end of 8 months. During the treatment period, dogs were supported by additional proteins, vitamins, and minerals. A long acting insecticide (collar or drop) was also used in order to prevent further parasite transmission. Follow-up was maintained by clinical, clinicopathological evaluation, and parasitological examination of lymph node, serology using the indirect immunofluorescent antibody test (IFAT). Before treatment commenced, the most important clinical signs were exfoliative dermatitis, ulcerations, peripheral lymhadenopathy, pale mucous membranes, weight loss, and ocular lesions. Clinicopathological findings included commonly anaemia, hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. Before the treatment, amastigotes were seen in six of the seven dogs by examination of lymph node aspiration, and IFAT-titers were positive in all dogs. At the end of 8 months treatment, remission of clinical signs, restoration to normal of clinicopathological abnormalities were noticed. Lymph node aspiration was performed on three out of the seven dogs at the end of the treatment because of the very small sizes of the lymph nodes, and no amastigotes were observed. Although the mean IFAT-titer of the dogs were significantly (P < 0.001) lower compared with pretreatment, IFAT-titers of dogs were still positive. No relapses occurred during treatment period and a 6-24-month duration after the end of therapy. Based on the above results, long-term use of allopurinol combined with sodium stibogluconate together with support treatment concluded to have enough therapeutic efficacies in the treatment of dogs with visceral leishmaniosis. Observations of the cases for possible relapses were still going on and insecticide application was carefully carrying on in order preventing a possible re-infection.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antimetabolites; Antimony Sodium Gluconate; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Fluorescent Antibody Technique, Indirect; Leishmania infantum; Leishmaniasis, Visceral; Lymph Nodes; Male

In this study, different types of tissue sampling for PCR-based diagnosis and follow-up of canine visceral leishmaniosis were compared. Skin, whole blood and lymph node samples were collected from 95 naturally infected dogs living in South Italy, where the disease is endemic. Twenty-nine of these 95 dogs, treated with meglumine administered concurrently with allopurinol for 30 days, and then with allopurinol alone, were monitored during a period of 2 years. The DNA extracted from the clinical specimens was amplified by PCR using as target DNA a 116-bp fragment in the constant region of the kinetoplast DNA minicircle. PCR analysis was more sensitive than indirect immunofluorescence antibody test in detecting Leishmania infection in symptomatic dogs: 99% of lymph node samples resulted positive, whereas 94% of blood samples and 95% of skin samples gave a positive result. PCR analysis of samples from dogs followed up 2 years showed that: (1) all subjects resulted positive in at least one of the three types of samples; (2) all time the dogs had a relapse, PCR resulted positive in all three types of samples; (3) when dogs were apparently healthy, PCR analysis was positive on skin and lymph node samples, but not always on blood samples. Since lymph node sampling is invasive and sometimes difficult in healthy asymptomatic dogs, our results suggest that, independently from the presence or not of cutaneous lesions, skin biopsy represents a good substratum for PCR-based diagnosis and follow-up of canine visceral leishmaniosis.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Biopsy; DNA, Mitochondrial; DNA, Protozoan; Dog Diseases; Dogs; Female; Fluorescent Antibody Technique, Indirect; Leishmania infantum; Leishmaniasis, Visceral; Lymph Nodes; Male; Meglumine; Polymerase Chain Reaction; Skin Diseases, Parasitic

Fourteen dogs naturally infected with Leishmania infantum and treated with allopurinol were monitored clinically and serologically with immunofluorescent antibody test (IFAT, amastigotes and promastigotes), enzyme linked-immunosorbent-assay (ELISA, IgG1 and IgG2) and Western blotting (WB). In all dogs therapy lead to clinical improvement together with decreasing specific antibodies in IFAT, ELISA and WB, demonstrating the usefulness of serology for follow-up. Although IgG1 and IgG2 varied considerably between individual animals, IgG2 of all dogs was predominantly in both ELISA and WB. This suggests the value of monitoring the IgG2 response (especially against 29 and 67 kDa antigens) in the follow-up of treated dogs.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Blotting, Western; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Direct; Follow-Up Studies; Host-Parasite Interactions; Immunoglobulin G; Leishmania infantum; Leishmaniasis, Visceral; Treatment Outcome

Reported herein for the first time in the literature is the case of a 41-yr-old woman who developed a tumor lysis-like syndrome, consisting of hyperkalemia, hyperphosphatemia, hyperuricemia, and acute renal insufficiency, soon after the initiation of chemotherapy for severe visceral leishmaniasis with liposomal amphotericin B. Allopurinol therapy, together with iv fluid administration and urine alkalization, resulted in full recovery of the metabolic abnormalities. Awareness of this condition can lead to prophylactic treatment as well as the early recognition and management of susceptible patients.

Topics: Adult; Allopurinol; Amphotericin B; Antimetabolites; Antiprotozoal Agents; Female; Fluid Therapy; Humans; Hydrogen-Ion Concentration; Leishmaniasis, Visceral; Tumor Lysis Syndrome; Urine

The expression of IgG, IgG1 and IgG2 specific antibodies for Leishmania infantum was studied in five groups of dogs in Catalonia (Spain): I, 99 asymptomatic dogs (infected and uninfected) from a highly endemic area for leishmaniosis; II, 139 untreated dogs with clinically patent leishmaniosis; III, 11 naturally infected asymptomatic dogs monitored for up to 5 years since they were found seropositive to Leishmania antigen and without treatment; IV, 25 naturally infected dogs with clinically patent leishmaniosis and treated with either meglumine antimoniate and allopurinol or allopurinol alone and V, six experimentally infected dogs, treated with meglumine antimoniate and controlled for 5 years. The levels (ELISA units) of IgG, IgG1 and IgG2 in asymptomatic dogs (group I) were very variable (24+/-33, 32+/-31 and 26+/-31, respectively), and, as expected, lower than in ill dogs (group II) (168+/-34, 84+/-71 and 172+/-31, respectively). In both groups, the correlation between IgG and IgG2 levels (r=0.95, P<0.001 in group I and r=0.63, P<0.001 in group II) was higher than between IgG and IgG1 levels (r=0.01, P>0.05 in group I and r=0.31, P<0.001 in group II). In group III, IgG and IgG2 expression increased during infection, while IgG1 expression remained the same. In dogs of group IV, IgG levels after 1 year of treatment decreased more in responsive (mean values, 163+/-42 before treatment (b.t.) and 100+/-36 after treatment (a.t.)) than in unresponsive dogs (158+/-29 b.t. and 124+/-51 a.t.), especially for IgG1 (94+/-89 b.t. and 20+/-21 a.t. in responsive dogs and 35+/-25 b.t. and 22+/-13 a.t. in unresponsive dogs) rather than for IgG2 (156+/-16 b.t. and 114+/-45 a.t. in responsive and 151+/-11 b.t. and 125+/-36 a.t. in unresponsive dogs). Similar results were observed in the evolution of experimentally infected animals after consecutive and specific treatments. Overall results show the great variation in Leishmania-specific IgG1 expression in asymptomatic and symptomatic dogs, their lack of correlation with that of IgG2 and chemotherapy is more effective in dogs with initially high expression of IgG1.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antibody Specificity; Antiprotozoal Agents; Dog Diseases; Dogs; Endemic Diseases; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Immunoglobulin G; Leishmania infantum; Leishmaniasis, Visceral; Longitudinal Studies; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Seroepidemiologic Studies; Spain

Pentavalent antimony is still the drug of choice in the treatment of visceral leishmaniasis. Pantavalent antimony can cause a wide range of adverse effects, the most serious of which are cardiotoxicity and hepatotoxicity. Acute pancreatitis is a rarely reported adverse effect. An infant who developed pancreatitis during meglumine antimoniate treatment for visceral leishmaniasis and who was successfully treated with a combination of allopurinol and ketoconazole is reported.

Topics: Acute Disease; Allopurinol; Antiprotozoal Agents; Child, Preschool; Humans; Ketoconazole; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pancreatitis

Specific serum antibody levels in Leishmania infantum-infected dogs treated with a combination of glucantime and allopurinol were estimated by indirect immunofluorescence and Western blotting. The sensitivity of Western blot was greater than that obtained with immunofluorescence titration. In general, both diagnostic methods concurred with the post-treatment clinical status of the animals. Clinical improvement of successfully treated dogs was related to lower immunofluorescence titers and simpler and/or less reactive immunodetection patterns in Western blotting. The recognition, by infected dogs, of certain low molecular weight antigens, particularly one of approximately 26 kDa, was restricted to pretreatment samples and a single animal in relapse thus apparently constituting an active infection marker.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antiprotozoal Agents; Blotting, Western; Disease Progression; Dog Diseases; Dogs; Enzyme Inhibitors; Fluorescent Antibody Technique, Indirect; Leishmania infantum; Leishmaniasis, Visceral; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Sensitivity and Specificity; Treatment Outcome

A comparison of an indirect immunofluorescence test using promastigotes (IFATp) or cultured amastigotes (IFATa) in the diagnosis and follow-up of canine leishmaniasis caused by Leishmania infantum was carried out. Results obtained with both diagnostic methods were in good agreement although the IFATa titration was more sensitive than the currently used IFATp without losing specificity. The higher sensitivity of the amastigote-based IFAT resulted in an earlier diagnosis in the absence of clinical signs. Both methods showed comparable results for monitoring the clinical evolution of naturally infected and treated (meglumine antimoniate plus allopurinol) dogs.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antimetabolites; Antimony; Dog Diseases; Dogs; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Leishmania infantum; Leishmaniasis, Visceral

Topics: Aged; Allopurinol; Antiprotozoal Agents; Drug Therapy, Combination; Humans; Ketoconazole; Kidney Transplantation; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds

Topics: Allopurinol; Animals; Antimony; Antiprotozoal Agents; Dog Diseases; Dogs; Follow-Up Studies; Leishmania infantum; Leishmaniasis, Visceral; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Regression Analysis; Serum Albumin; Serum Globulins; Time Factors

A study has been performed to investigate the usefulness of the polymerase chain reaction (PCR) for both the diagnosis and the follow-up after treatment of canine leishmaniosis (CaL). Blood samples (PBL) and/or bone marrow aspirates (BM) could be examined in a total of 18 confirmed cases of primary CaL. PBL was PCR-positive in 87%, whereas the BM was found to be positive in all cases (n=14) tested. PBL and BM from a total of 13 patients were submitted to PCR examinations after meglumine antimoniate (Glucantime) treatment. Only one dog showed a negative PCR after 2 treatment cycles (days 1-2: 50 mg/kg bw; days 3-10: 100 mg/kg bw). Examination of the PBL and BM after 15 months remained further PCR negative. All other dogs, from which four were pretreated with allopurinol up to 5 weeks, continued to be positive (92%) at least in the BM. Ten dogs could be monitored by means of the PCR after allopurinol treatment (2 x 10 mg/kg/bw/day/) either as a monodrug therapy in seven or as a successive combination with Glucantime in three cases. Two out of three dogs which showed good clinical improvement after daily administration for five weeks were likewise PCR negative in both the PBL and the BM. The four other dogs remained positive after the single therapy with allopurinol up to 5 weeks. A further three dogs were treated with allopurinol for 5 weeks, 6 and 20 month, respectively, after being clinically cured with Glucantime. Two of them were PCR negative in the PBL and BM after 5 weeks and 20 month, respectively. The results presented suggest that longterm treatment with allopurinol has some therapeutic benefit in CaL especially when administered following treatment with the pentavalent antimonial Glucantime.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Follow-Up Studies; Humans; Leishmania; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Polymerase Chain Reaction; Sensitivity and Specificity; Species Specificity

The transmission of visceral leishmaniasis (VL) in the absence of its natural vector, the sandfly, is considered exceptional. This report describes VL in a 12-month-old dog which had never been in an area in which VL is endemic but was born in the Netherlands from a bitch that had been infected in Spain. Although the mode of transmission, via the placenta or otherwise, is unknown, it can be concluded that bitches with VL can be a source of infection for their pups, even in a sandfly-free non-endemic area. The dog was successfully treated with allopurinol.

Topics: Allopurinol; Animals; Antimetabolites; Dog Diseases; Dogs; Female; Infectious Disease Transmission, Vertical; Leishmaniasis, Visceral; Male; Netherlands

Visceral leishmaniasis (VL) is endemic in Sicily. Although it is a notifiable disease, there is evidence that the actual number of cases is higher than that reported. In 1987, a regional reference center for active surveillance of VL was established and it recorded a total of 284 cases through 1995, a mean of 31.5 cases/year and about four-fold more than previously reported. Of the 284 cases, 150 (53%) were children (< or = 14 years of age), and of the 134 adults, 39 (29%) were coinfected with human immunodeficiency virus (HIV). The commonest viscerotropic zymodeme of Leishmania infantum, MON 1, was identified in 40 (93%) of 43 HIV-negative and eight (57%) of 14 HIV-positive patients. Among 280 patients evaluated (i.e., all HIV-negative and 35 of 39 HIV-positive subjects), 254 (91%) were treated with meglumine antimoniate alone or in combination with other drugs; 23 (8%) received allopurinol or amphotericin B, either conventional or in liposomal form; and three terminally ill patients were not treated. Among the 245 HIV-negative patients, 236 (96%) were successfully cured, while nine (4%) (seven adults) died during the course of antimonial treatment. None of the 35 HIV-positive patients was definitively cured, although mortality was apparently associated with other opportunistic infections.

Topics: Adolescent; Adult; Age Distribution; Aged; Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Child; Child, Preschool; Cohort Studies; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Recurrence; Sex Distribution; Sicily

To analyze the clinical features, yield of the diagnostic techniques, and therapeutic response of HIV-associated visceral leishmaniasis (VL), and compare the initial episodes to the relapses.. Forty-one episodes of leishmaniasis visceral, diagnosed in 31 HIV-positive patients between 1st February 1992 and 31st January 1996 were reviewed.. The prevalence of VL in HIV-positive patients in our center was 4.2%. Fifty-eight percent of the patients had AIDS prior to the diagnosis of VL. Fever was more frequent in the initial episodes than in the relapses (90.3% versus 60%; p < 0.05; OR: 6.2; IC 95%: 0.8-51.5), splenomegaly was more frequent in the relapses (100% versus 71%; p = 0.05). The diagnostic delay was longer in the initial episodes (27.2 +/- 22.7 versus 5 +/- 4.8 days; p < 0.05). The diagnostic yield of bone marrow biopsy was 82.1%, of liver biopsy 72.7% and of splenic fine-needle aspiration 87.5%. The indirect immunofluorescence test for Leishmania antibodies was positive in 5.9% of cases. Therapeutic failure occurred in 47.6% of patients treated with antimonials and 3.3% of patients treated with amphotericin B. Those patients who received secondary prophylaxis had less relapses than those who did not (17.6% versus 66.7%; p < 0.05; OR: 0.11; IC 95%: 0.01-1.28). Of the 31 patients, twenty-six (83.8%) died, and in none of them was the cause of the death directly related to LV.. HIV-associated VL manifests clinically in a similar fashion to the immunocompetent's disease. It appears in advanced immunosuppression phases, behaving like other AIDS-defining illnesses. In spite of a good therapeutic response the relapse rate is high.

Topics: Adult; AIDS-Related Opportunistic Infections; Allopurinol; Amphotericin B; Antiprotozoal Agents; Drug Therapy, Combination; Female; HIV-1; Humans; Leishmaniasis, Visceral; Male; Prevalence; Recurrence; Spain

The experience with 52 episodes of visceral leishmaniasis diagnosed in 43 patients is reported. The most common symptoms were fever (81%), splenomegaly (65%), hepatomegaly (63%), and pancytopenia (73%). In 79% of the patients, CD4+ cell counts were < 100 cells/mm3. Prior or simultaneous diagnosis of AIDS was made in 29 (67%) patients. Diagnosis was considered fortuitous in 19% of the episodes. In 27% of the episodes, the diagnosis was made on the basis of demonstration of parasites outside the reticuloendothelial system, chiefly blood (7 cases) and gastrointestinal mucosa (5 cases). Parasites were frequently observed or cultured from blood (22/37 episodes) or the digestive tract (8/9 episodes). High antimony doses were more effective than low doses in achieving clinical or parasitological cure (rate of cure, 80% vs. 40%, p = 0.11). Severe toxicity was observed in six (11.7%) of the 51 treated episodes. Severe AIDS-related diseases [odds ratio (OR) 10, p < 0.05] and CD4+ counts (OR 12, p < 0.05) were independent factors for early death. Prophylaxis with monthly pentamidine was not useful in reducing relapses of visceral leishmaniasis.

Topics: AIDS-Related Opportunistic Infections; Allopurinol; Amebicides; Amphotericin B; Analysis of Variance; Anti-HIV Agents; Antimetabolites; Antimony; Antiprotozoal Agents; Blood; Bone Marrow; CD4-Positive T-Lymphocytes; Cerebrospinal Fluid; Didanosine; Digestive System; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatic Encephalopathy; HIV; Humans; Intestinal Mucosa; Leishmaniasis, Visceral; Lymphocyte Count; Male; Myocarditis; Neutrophils; Pancreatitis; Pentamidine; Renal Insufficiency; Spain; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adult; Allopurinol; Antifungal Agents; Antimetabolites; Bone Marrow; Drug Therapy, Combination; Enzyme Inhibitors; Female; Fluconazole; Humans; Immunocompromised Host; Kidney Transplantation; Leishmaniasis, Visceral; Male

Visceral leishmaniosis was diagnosed in a working sled dog on the basis of history, clinical signs, and identification of amastigotes in a skin biopsy specimen. Allopurinol was administered as sole treatment for the disease. The drug was given for 9 months, and, during this time, clinical signs of disease resolved. Laboratory abnormalities had resolved by 12 months after diagnosis and 3 months after treatment. The dog has been without medications for 19 months and remains free of clinical signs, has sired 2 litters, and functions well as lead sled dog for a team.

Topics: Administration, Oral; Allopurinol; Animals; Antimetabolites; Biopsy, Needle; Cold Temperature; Dog Diseases; Dogs; Leishmaniasis, Visceral; Lymph Nodes; Male; Skin; Spain; Yukon Territory

Topics: Adolescent; Allopurinol; Antimetabolites; Antiprotozoal Agents; Child; Female; Follow-Up Studies; Humans; Hypopigmentation; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Remission Induction

Topics: Allopurinol; Animals; Antimetabolites; Dog Diseases; Dogs; Leishmaniasis, Visceral; Recurrence

Topics: Adult; Allopurinol; Antiprotozoal Agents; Follow-Up Studies; Humans; Immunosuppression Therapy; Kidney Transplantation; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Recurrence; Splenectomy; Splenomegaly; Time Factors

Topics: Allopurinol; Animals; Dog Diseases; Dogs; Leishmaniasis, Visceral; Male

Frequent relapses after treatment for visceral leishmaniasis and apparent parasitological cure is not commonly reported. Seven year old boy who relapsed four times with clinical and parasitological evidence of the disease at each two months follow-up period is presented. He had Leishimania donovani Kenya strain. After treatment, review would be after two months, six months and twelve months periods. Splenic aspirates were routinely done weekly and on the last day of each treatment. The drugs administered for varying periods included intravenous sodium stibogluconate 20 mg/kg daily, P20 in combination with allopurinol 21 mg/kg three times daily, and Pentamidine 4 mg/kg three times weekly and antituberculous drugs. The presence of abundant extra cellular leishmania donovani bodies in the bone marrow and possible pulmonary tuberculosis might have precipitated the frequent relapses. It is not clear which of the drugs effected the cure. It was observed that inspite of prolonged antileishmanial drug administration no side effects were noted.

Topics: Allopurinol; Animals; Antimetabolites; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Humans; Leishmania donovani; Leishmaniasis, Visceral; Male; Pentamidine; Recurrence

The changes in the titres of anti-leishmania antibodies in 25 dogs with leishmaniasis were studied by using a Dot-ELISA technique while they were being treated with N-methylglucamine and allopurinol. When the diagnosis of leishmaniasis was established, 21 of the dogs had positive titres (1:800 or higher), and after treatment, 15 of them still had high titres, in most cases the same as at the point of the diagnosis. In four dogs the titres decreased, and were less than the cut-off value in two cases nine months after treatment. Only four dogs had titres less than the cut-off value when they were diagnosed, but one month later the titres in all four dogs had reached the cut-off value. There was no correlation between the serological titres and the severity of the clinical signs. It is concluded that the Dot-ELISA is a sensitive method for the diagnosis of canine leishmaniasis but is not satisfactory for monitoring the clinical development of the disease.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Dog Diseases; Dogs; Drug Monitoring; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Sensitivity and Specificity

Topics: Allopurinol; Animals; Dog Diseases; Dogs; Leishmaniasis, Visceral

Topics: Adult; AIDS-Related Opportunistic Infections; Allopurinol; Animals; Anti-Infective Agents; Antimetabolites; Humans; Itraconazole; Leishmania; Leishmaniasis, Visceral; Male

128 untreated cases of Kala-azar were divided in 4 equal groups of 32, Group A was treated with Sodium Stibogluconate (SSG) in the dose of 20 mg/kg/body wt. for 30 days. Group B was treated SSG plus allopurinol in the dose of 20 mg/kg/body wt. orally in divided dosage for 30 days. Group C received SSG plus Ketoconazole 600 mg orally in divided dosage for 30 days. Group D in addition to SSG also received levamisole in single oral daily dose of 13 mg/kg/body wt. for 30 days. Response of Group B, C and D was compared to Group A. Results from this study revealed combination of allopurinol with SSG to be statistically not superior to SSG alone.

Topics: Adult; Allopurinol; Antimony Sodium Gluconate; Antiprotozoal Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Ketoconazole; Leishmaniasis, Visceral; Levamisole; Male

Sixty-five patients, 51 males and 14 females, with clinical and parasitological evidence of visceral leishmaniasis were initially treated as follows: 44.6% were on intravenous sodium stibogluconate (pentostam) 20 mg/kg/d for 30 days, 35.4% was on a combination of pentostam as above and allopurinol 21 mg/kg/d in three divided doses for 30 days while 20% was on pentostam 10 mg/kg thrice/d intravenously for 10 days. All patients were parasitologically negative by the end of their respective treatment regimen. All patients were reviewed at 2 months, 6 months, and 12 months periods in order to evaluate the relapse rates and optimal follow-up period. Thirteen patients (20%) relapsed at 2 months and one patient (1.5%) relapsed at 6 months follow-up periods respectively. There was no relapse between 6 months and 12 months follow-up period. The mean liver and spleen sizes in responders showed a dramatic reduction at 2 months follow-up and thereafter a gradual reduction occurred in the next 10 months. Weight gain continued throughout the year. Apart from platelet count which showed a sustained high level from discharge to 12 months follow-up, the peripheral blood indices stabilized from 2 months follow-up. Relapses were retreated until parasitologically negative twice and then followed up, for a period of 12 months. At follow-up the liver and spleen sizes reduced gradually in the next 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aftercare; Allopurinol; Antimony Sodium Gluconate; Child; Child, Preschool; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Leishmaniasis, Visceral; Male; Middle Aged; Recurrence; Treatment Outcome

We report on 11 patients with HIV infection and visceral leishmaniasis and who were treated with meglumine antimoniate plus allopurinol for 3 weeks (six patients) or 4 weeks (five patients). Clinical and parasitological cures were achieved in four of the five patients treated for 4 weeks and in one of the six patients treated for 3 weeks. Only one patient developed a severe maculopapular rash. Allopurinol plus meglumine antimoniate was found to be a safe combination of drugs for the treatment of visceral leishmaniasis in patients infected with HIV. The optimal length of this treatment is unknown but a course of at least 4 weeks' duration would appear to be necessary for obtaining parasitological cure in most cases.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Allopurinol; Antiprotozoal Agents; Drug Therapy, Combination; Female; HIV Infections; Humans; Injections, Intramuscular; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pilot Projects

A case of a renal transplant recipient who developed pancreatitis during stibogluconate treatment for visceral leishmaniasis and who was successfully treated with a combination of allopurinol and ketoconazole is reported. The features of this case are compared with those of the three previously reported cases of pancreatitis during stibogluconate treatment. Complete cure was achieved during the follow-up period of 15 months. If stibogluconate is used for treatment of renal transplant recipients, we advise extreme caution with close observation and combination therapy to be considered instead.

Topics: Adult; Allopurinol; Antimony Sodium Gluconate; Drug Therapy, Combination; Female; Humans; Ketoconazole; Kidney Transplantation; Leishmaniasis, Visceral; Pancreatitis

We previously reported the effectiveness of trans-aconitic acid (TAA) as an antileishmanial compound. Inhibitory effects of TAA along with other antileishmanial compounds on transformation and in vitro multiplication in macrophage cultures of Leishmania donovani have been assessed. The efficacy of TAA in combined chemotherapy of experimental visceral leishmaniasis has also been evaluated along with those of commonly used antileishmanial compounds such as sodium stibogluconate, pentamidine, and allopurinol. TAA (2 mM) inhibited transformation of L. donovani amastigotes to promastigotes by 95.2%, whereas in combination with pentamidine (5 micrograms/ml), allopurinol (10 micrograms/ml), and sodium stibogluconate (50 micrograms of Sb per ml), it inhibited transformation by about 100, 99, and 98.5%, respectively. Sodium stibogluconate (20 micrograms of Sb per ml), pentamidine (2 micrograms/ml), and allopurinol (5 micrograms/ml) suppressed the amastigote burden in peritoneal macrophage cultures from BALB/c mice by 32.6, 56.1, and 46.3%, respectively. When these three drugs were used along with TAA (5 mM), the parasite loads were reduced by 100, 100, and 88.1%, respectively. TAA (5 mM) alone suppressed the amastigote burden by 59.5%. In experimental visceral leishmaniasis in hamsters (1-month model), TAA at a dose of 200 mg/kg of body weight per day suppressed the spleen parasite load by 73.5%, and TAA in combination with sodium stibogluconate (50 mg of Sb per kg per day), pentamidine (8 mg/kg/day), and allopurinol (15 mg/kg/day) inhibited the spleen parasite load by 98, 98.9, and 97%, respectively. Individually, these three drugs inhibited the parasite load by 35, 20, and 22%, respectively. TAA (400 mg/kg/day) inhibited the spleen parasite load by 99.8%, but an inhibitory effect of approximately 100% was noted when TAA was supplemented with an antileishmanial drug. TAA was administered in experimental animals through oral, intraperitoneal, and intramuscular routes; the intramuscular route was most effective.

Topics: Aconitic Acid; Allopurinol; Animals; Antimony Sodium Gluconate; Cells, Cultured; Cricetinae; Drug Therapy, Combination; In Vitro Techniques; Leishmania donovani; Leishmaniasis, Visceral; Liver; Macrophages; Mesocricetus; Mice; Mice, Inbred BALB C; Pentamidine; Spleen; Stereoisomerism

Although human visceral leishmaniasis (VL) is a notifiable disease in Italy, there is evidence that the actual number of cases is far higher than that notified. A programme for active surveillance of VL in the 14 Italian endemic regions was launched by the Istituto Superiore di Sanità. We report data collected during a 3-year period of active surveillance in Campania, a south Tyrrhenian region covering 4.5% of the Italian territory. Out of 120 clinically suspected cases referred to medical and diagnostic references centres, there were 52 confirmed VL cases (17.3/year), i.e. 10-fold more than previously notified. Most of the infection sites were in rural areas or peripheral districts of towns in hilly parts of Naples province. An epidemic cluster of 10 cases was identified in a microfocus of Caserta province. The biochemical analysis of 23 Leishmania stocks showed a zymodeme composition indicating Campania as an old and well-established focus of VL. The data obtained emphasize that the present notification system for VL in Italy is inadequate.

Topics: Adolescent; Adult; Allopurinol; Animals; Antiprotozoal Agents; Child; Child, Preschool; Disease Outbreaks; Female; Humans; Infant; Infant, Newborn; Isoenzymes; Italy; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Population Surveillance; Seasons; Skin Tests

Topics: Allopurinol; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Humans; Infant; Leishmaniasis, Visceral; Meglumine; Recurrence

To investigate the epidemiological, clinical and biological features of visceral leishmaniasis (VL) in patients with HIV-1 infection.. Retrospective study.. Three university hospitals in southern Spain.. Forty-seven adult patients with VL and HIV-1 infection diagnosed between January 1986 and November 1991.. Forty-five out of the 47 (96%) cases were diagnosed in the last 2 years. Fever (87%), hepatomegaly (74%), splenomegaly (72%) and pancytopenia (77%) were the most common presenting features. Most patients (79%) were strongly immunocompromised when VL was diagnosed, and were in stage IV of the Centers for Disease Control classification; 87% had a CD4 lymphocyte count < 200 x 10(6)/l. However, VL was the first severe infection diagnosed in 10 cases. Significant titres (> 1:40) of antileishmanial antibodies were detected by indirect immunofluorescence in five out of 16 (31%) cases only. Clinical response to the therapy was difficult to assess. Microbiological response was achieved in only 38% of the patients evaluated.. Leishmaniasis is a relatively common infection in HIV-1-infected individuals in southern Spain. Its clinical picture is quite uniform and it can be the first opportunistic infection in individuals with HIV-1. In endemic areas, a high index of clinical suspicion should be maintained in order to avoid underdiagnosis of leishmaniasis.. Physicians examined the records of 47 adults with visceral leishmaniasis (VL) and HIV-1 infection who were patients at 3 urban teaching hospitals in the Andalucia region in southern Spain between January 1986 and November 1991. They wanted to identify the clinical, biological, and epidemiological features of VL in HIV-1 positive patients. 96% of the cases were diagnosed with both infections during the last 2 years of the study period and 79% between January and November 1991. All the patients had risk factors for HIV infection (65.9% IV drug use, 21.3% sexual contact, and 12.8% blood transfusion). 70% exhibited the classic symptoms of VL (fever, enlarged liver and spleen, and depressed counts of blood cells). Most patients were already very immunocompromised when VL was diagnosed. 87% had a total lymphocyte count of less than 1000 x 1 million/1 and a CD4 lymphocyte count of less than 200 x 1 million/1. In fact, 66% had full blown AIDS prior to diagnosis of VL. VL was the first severe infection in 10 cases. 68% also suffered from opportunistic infections, especially candidiasis, extrapulmonary tuberculosis, and Pneumocystis carinii pneumonia. Microscopic examination of Leishmania amastiogotes in tissue samples led to a diagnosis in 94% of cases, isolation of motile amastigotes in culture of bone marrow aspirate in 2%, and microscopic and culture in 4%. Just 46% completed a full course of treatment (pentavalent antimony, allopurinol, and/or pentamidine). Only 38% had a microbiological response. Immunofluorescence detected sizeable titers (1:40) of antileishmanial antibodies in just 31% of cases. 17% experienced clear clinical improvement. Physicians in endemic areas should consider VL in every HIV-1 infected patient with fever, hepatosplenomegaly, or hematological abnormalities to avoid underdiagnosis of leishmaniasis.

Topics: Adult; AIDS-Related Opportunistic Infections; Allopurinol; Antiprotozoal Agents; CD4-Positive T-Lymphocytes; Female; HIV-1; Hospitals, University; Humans; Leishmaniasis, Visceral; Leukocyte Count; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pentamidine; Retrospective Studies; Spain; Treatment Outcome

Topics: Adult; Allopurinol; Heroin Dependence; HIV Infections; Humans; Leishmaniasis, Visceral; Male

Topics: Acquired Immunodeficiency Syndrome; Adult; Allopurinol; Antiprotozoal Agents; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Prognosis

Topics: Acquired Immunodeficiency Syndrome; Adult; Allopurinol; Humans; Leishmaniasis, Visceral; Male

Topics: Allopurinol; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Tests; Infant; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Sorbitol

The dose of orally administered 9-deazainosine calculated to suppress 50% of Leishmania donovani amastigotes in hamster livers was 19 mg/kg (body weight) per day; 96 to 99% of Leishmania organisms were eliminated from the liver and spleen of squirrel monkeys by 50 mg/kg per day. Because these activities were greater than that of the experimental clinical agent allopurinol and comparable to that of the classical agent parenteral pentavalent antimony, 9-deazainosine should be considered for clinical development for visceral leishmaniasis.

Topics: Administration, Oral; Allopurinol; Animals; Cricetinae; Formycins; Guanosine; Injections, Intramuscular; Inosine; Leishmania donovani; Leishmaniasis, Visceral; Liver; Male; Meglumine; Meglumine Antimoniate; Mesocricetus; Organometallic Compounds; Saimiri; Spleen

Five patients with long-standing visceral leishmaniasis who were unresponsive to sodium stibogluconate, 20 mg antimony/kg body-weight once or twice daily, were treated for 14 to 54 days with a combination of sodium stibogluconate at the same dose plus allopurinol at a dose of 20 mg/kg body-weight per day in three divided doses. This combination was safe and effective. Negative splenic aspirate smears were obtained from all patients within 19 days, and none has relapsed in at least 12 months of follow-up.

Topics: Adolescent; Allopurinol; Antimony Sodium Gluconate; Child; Drug Resistance; Drug Therapy, Combination; Female; Gluconates; Humans; Leishmaniasis, Visceral; Male; Spleen

Pentavalent antimony (Sbv) compounds have been used in the treatment of kala azar for over 60 years. Their introduction was preceded by the use, for a few years, of SbIII compounds, especially tartar emetic. Although the exact usage of Sbv varies from country to country, with correct use, cure rates of over 90% can, in most countries, be expected. There is little problem with toxicity, though occasional unexplained deaths that do not appear to be directly due to Sbv do occur during treatment. The main second line drugs, pentamidine and amphotericin, are less effective and relatively toxic. Other second line treatments that have been used in resistant kala azar in Kenya include allopurinol, diminazene aceturate, and Sbv liposomes. Splenectomy has been used as a last resort.

Topics: Allopurinol; Amidines; Amphotericin B; Analgesics; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antiprotozoal Agents; Blood Transfusion; Child; Humans; Kenya; Leishmaniasis, Visceral; Male; Splenectomy

Allopurinol and allopurinol ribonucleoside tested in vitro and in vivo for activity against Leishmania donovani. Activity in vitro was low against the amastigote form of this parasite with ED50 values of the order of 54 and 96 microM and 86 and 213 microM respectively for the two compounds. In vivo inhibition of up to 47% was achieved with allopurinol ribonucleoside given in the drinking water. However, low blood levels were found in the mouse relative to those in man. Low in vivo activity was also seen with allopurinol ribonucleoside against L. major and other species of Leishmania causing cutaneous lesions. The metabolism of allopurinol ribonucleoside in aldehyde oxidase deficient mice (inbred strains DBA/1, DBA/2) resembled that of man, but the antileishmanial activity remained low. Other compounds, formycin B, sinefungin and the lepidine WR6026 were highly active against mice infected with L. donovani or L. major.

Topics: Adenosine; Allopurinol; Aminoquinolines; Animals; Antiprotozoal Agents; Cricetinae; Female; Formycins; Leishmania; Leishmaniasis; Leishmaniasis, Visceral; Macrophages; Mice; Mice, Inbred Strains; Ribonucleosides; Thionucleosides

Topics: Allopurinol; Antimony Sodium Gluconate; Humans; Leishmaniasis, Visceral; Pentamidine

Sixty four Kenyan patients with visceral leishmaniasis were treated with sodium stibogluconate (Pentostam) (40 patients) or various combinations of Pentostam and allopurinol (24 patients). Three patients, initially considered cured after Pentostam, relapsed but responded to further treatment. Sixty two were cured and two patients died. The treatment and the clinical, haematological and parasitological response to treatment are described in detail. If follow up is impossible or unlikely it is advised to continue treatment until parasitological cure is obtained. Prolonged courses of Pentostam, which were required in some patients, resulted in cures and apparently were non toxic. Consideration is to be given to extended treatment with Pentostam before more toxic drugs such as pentamidine and amphotericin B are given.

Topics: Adolescent; Allopurinol; Antimony Sodium Gluconate; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Gluconates; Humans; Kenya; Leishmaniasis, Visceral; Male; Middle Aged; Recurrence

Allopurinol, at doses of 300 to 1,200 mg per day for at least 14 days, was tested on 17 hospital patients with confirmed kala-azar. 14 of these were considered "cured" on clinical grounds and eight of these were confirmed by the absence of amastigotes in the bone marrow. Four were not examined parasitologically and two remained infected. Before further clinical trials of allopurinol are undertaken it is important to assess the role of its metabolites.

Topics: Adolescent; Adult; Allopurinol; Child; Female; Humans; Leishmaniasis, Visceral; Male; Middle Aged

Leishmania donovani, the causative agent of visceral leishmaniasis, infects macrophages (M phi ) of susceptible vertebrates. Immunologically activated M phi are leishmanicidal, but the mechanisms involved in the killing process are not well defined. We sought to investigate the role of reactive oxygen intermediates in the killing of L. donovani. Both the free-swimming promastigote and the intracellular amastigote forms were found to be susceptible to killing in vitro by hydrogen peroxide and other oxygen intermediates. Upon phagocytosis by mouse peritoneal M phi, promastigotes elicited a significantly stronger respiratory burst compared with amastigotes as measured by release of superoxide anion. Although amastigotes do not elicit a strong burst of M phi oxidative metabolism during the initial phagocytic event, immunologically activated M phi that acquired leishmanicidal capacity could be triggered to release substantial amounts of H2O2. Hence, the development of leishmanicidal capacity was correlated temporally with enhanced H2O2 generation by the M phi. In contrast, M phi that lost their ability to release significant amounts of H2O2 after several days in culture were unable to eliminate their parasite burden. Catalase markedly inhibited the elimination of amastigotes by lymphokine-stimulated M phi. In toto, the results implicate reactive oxygen intermediates in killing of the tissue form of L. donovani by its host cell, the mononuclear phagocyte.

Topics: Animals; Catalase; Cricetinae; Cytotoxicity, Immunologic; Female; Hydrogen Peroxide; Leishmaniasis, Visceral; Lymphokines; Macrophage Activation; Macrophages; Mice; Mice, Inbred C57BL; Oxygen; Peroxidase; Phagocytosis; Superoxides; Xanthine Oxidase

Allopurinol was used in the treatment of 10 patients with kala-azar. Of six patients who had previously failed to respond satisfactorily to Pentostam, "cures" were achieved in four. However, it was necessary to add Pentostam to the allopurinol in one, and another relapsed after apparent "cure" but again responded to allopurinol. The response of four patients who had had no previous treatment for kala-azar was less satisfactory.

Topics: Adolescent; Adult; Allopurinol; Antimony Sodium Gluconate; Child; Child, Preschool; Female; Hemoglobins; Humans; Leishmaniasis, Visceral; Male; Spleen