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Assessment of allopurinol plus meglumine antimoniate in the treatment of visceral leishmaniasis in patients infected with HIV.
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.
Visceral leishmaniasis in clinical practice.
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Evaluation of a specific immunochemotherapy for the treatment of canine visceral leishmaniasis.
The efficacy of specific immunochemotherapy against Leishmania infantum infection in dog was studied. The effects on transmission of the disease, as well as the cellular and humoral immune response were examined. The treated animals showed a significant reduction in the infection rates that were detected in Phlebotomus perniciosus females fed on the dog. The humoral immune response, assayed with an indirect immunofluorescence antibody test (IFAT), did not show significant variations under the influence of the therapy. The characterisation of the peripheral blood mononuclear cells (PBMC) using flow cytometry indicated a significant increase in the proportion of T lymphocytes, especially of CD4/TcR(alpha)(beta)(+) and CD4/CD45RA(+) cells, without showing evidence for modifications in the other leukocyte subsets. Cellular lymphoproliferation studies indicated a lack of a specific response to soluble leishmanial antigen (SLA), but the non-specific lymphoproliferative capacity assayed with phytohemagglutinin (PHA) was maintained.
Specific IgG1 and IgG2 antibody and lymphocyte subset levels in naturally Leishmania infantum-infected treated and untreated dogs.
Peripheral blood lymphocyte subpopulations and specific IgG1 and IgG2 antibody levels were studied in 14 dogs naturally infected with Leishmania infantum using flow cytometry and ELISA. Six dogs (Group 1) were asymptomatic, and received no treatment. Samples from this group were collected from D0 to D180. The other eight dogs (Group 2) showed clinical symptoms, and were treated with Glucantime (from D0 to D40), with samples being collected from D0 to D90. Twenty-two healthy dogs were used as a control group (Group 3). The results demonstrated changes in the lymphocyte subsets, as well as a decrease in humoral and cellular immunity, in the infected dogs. Analysis of the B-cell populations of Groups 1 and 2 showed a striking reduction in the number of CD21+ cells. There was also a reduction in the CD5+, CD4+ and CD8+ T-cell populations. Drug therapy was found to partly restore the lost immunity, essentially the cell-mediated immunity. Both IgG1- and IgG2- specific antibodies were detected in sera from the fourteen infected dogs, but the IgG2 subclass appeared to be predominant. A significant decrease in the level of IgG2 antibodies was observed in treated and untreated dogs.
[Circumscribed and confluent papular rash in the trunk and hands in a male patient infected with the human immunodeficiency virus].
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Meglumine antimoniate, amiodarone and torsades de pointes: a case report.
Pentavalent antimonial drugs used for the treatment of leishmaniasis have been associated with sudden deaths, probably due to the development of ventricular tachyarrhythmias. Prolongation of the QT interval and ventricular tachyarrhymias have been described in patients on amiodarone therapy. We report a case of recurrent torsades de pointes following treatment with pentavalent antimonial drugs and amiodarone.
Leishmania infantum-specific IgG, IgG1 and IgG2 antibody responses in healthy and ill dogs from endemic areas. Evolution in the course of infection and after treatment.
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.
Serological and parasitological follow-up in dogs experimentally infected with Leishmania infantum and treated with meglumine antimoniate.
Six healthy beagle dogs were infected with Leishmania infantum (MCAN/ES/92/BCN-83/MON-1) by intravenous inoculation of 5 x 10(7) promastigotes and two others were used as controls. When animals showed clinical signs of disease at 29, 37, 41 and 45 weeks post-infection (p.i.), they were treated with meglumine antimoniate (20.4 mg Sb/kg/12 h) subcutaneously for two periods of 10 days each. Sera were tested periodically for Leishmania antibodies by Dot-ELISA, ELISA and Western blot (WB). Aspirates of popliteal lymph node (PLN), peripheral blood sample (PB) and healthy skin were cultured in NNN and Schneider's medium. PLNs were positive between 8 and 20 weeks p.i. and in one animal PB was positive 6 weeks p.i. Samples of healthy skin, obtained before treatment, were also positive. Dot-ELISA and ELISA detected specific antibodies at an early stage between 4 and 12 weeks p.i and surpassed the cut-off between 16-24 weeks p.i., while the WB was positive between 10-19 weeks p.i. The pattern of bands revealed during the first stages of infection was variable and only in two cases did the positivity start with bands of low molecular weight (12-14 kD); the number of bands increased until 15-24 weeks p.i., after which sera revealed a complete pattern of bands, from 12 to 85 kD, in the antigen of Leishmania. After treatment the clinical improvement of the animals was accompanied by a decrease in antibody titers (Dot-ELISA and ELISA) although the parasites remained in the PLN. This was reflected in the WB by a decrease in the intensity of bands, especially those in the region of 12-30 kD. A new increase in the antibody levels between 3 and 5 months after terminating the therapy was detected in the WB by a restoration of the initial complete pattern of bands.
Evaluation of the immune response in visceral leishmaniasis.
Detection of parasites in culture or by microscopy is still necessary to make diagnosis of visceral leishmaniasis (VL). Serological methods still need assessment, as they are quick but not very sensitive, especially in immunosuppressed subjects. This paper compares the results obtained with three serological methods (indirect immunofluorescence test (IFAT), direct agglutination test (DAT), and enzyme-linked immunosorbent assay (ELISA) and the specific cell-mediated immune response, evaluated as proliferation and IFN-gamma production by peripheral blood lymphocytes (PBL) following stimulation with heat-killed L. infantum promastigotes. PBL and sera were obtained from 10 healthy donors, 3 VL patients in acute phase, and 3 patients recovering after two glucantim treatment courses. No false positive results were observed with the serological methods. IFAT can be considered the most sensitive and best suited for follow-up, as it allowed a good discrimination between the acute and remission phase. DAT did not discriminate between healthy donors and remission-phase patients, whereas ELISA is unsuited for follow-up, as it did not show any significant difference between remission- and acute-phase patients. Assessment of the cellular response is not recommended for making a diagnosis, because false positive results are frequent. However, a strong cellular response in a patient stands for a successful treatment. IFN-gamma titration is preferable to the proliferation test, because it gives earlier results and does not require the use of radioactive isotopes.
[Visceral leishmaniasis in an immunocompetent subject, acquired in the Pyrenees region].
INTRODUCTION: Visceral leishmaniasis can develop in immunocompetent subjects exposed to a risk of infestation during physical activities outdoors. CASE: A 35-year-old woman was hospitalized for impaired health status with fever, hepatomegaly, splenomegaly, and pancytopenia, which worsened during her stay. Leishmaniasis was finally diagnosed, based on serologic testing and the finding of Leishmania infantum in the sternal aspiration. Eight months earlier, she had spent two weeks at a lake in the Pyrenees. Treatment with meglumine antimoniate was efficacious. COMMENTS: This case is original because of the extent of the organomegaly and its onset after vacation in an area far from those where it is thought to be endemic.
[Visceral leishmaniasis: new drugs].
The standard treatment of visceral leishmaniasis is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug. Moreover, antimony unresponsiveness is increasing, both in immunocompetent and in immunosuppressed patients. Amphotericin B is a polyene macrolide antibiotic that binds to sterols in cell membranes. It is the most active antileishmanial agent in use. Its infusion-related and renal toxicity may be reduced by lipid-based delivery. Liposomal amphotericin B (Ambisome) seems to be less toxic than other amphotericin B lipid formulations (Amphocil, Amphotec). Optimal drug regimens of Ambisome vary from one geographical area to another. In the Mediterranean Basin, a total dose of 18 to 24 mg/kg is safe and effective. Shortening the duration of treatment without decreasing the total dose (i.e., 10 mg/kg/day for 2 days) seems promising to reduce the global cost of the therapy.
[Chronic visceral leishmaniasis during chemotherapy for metastatic osteosarcoma].
UNLABELLED: Leishmaniasis refers to a spectrum of diseases caused by Leishmania. Clinically, three types of leishmaniasis can be distinguished: the cutaneous, mucous and visceral leishmaniasis, the latter being caused by Leishmania donovani. CASE REPORT: An 11-year-old Thai, living in Belgium for 6 years, had surgery for a vertebral osteosarcoma with pulmonary metastases, followed by polychemotherapy, then pulmonary metastasectomy. During a post-chemotherapy bone marrow aplasia, febrile episode with a general condition impairment was noted and first treated by broad-spectrum antibiotherapy, then by amphotericin B, in the absence of any accurate etiology. The outcome first was favorable. Nevertheless, 7 months later, the visceral leishmaniasis diagnosis was made because of the recurrence of the same symptoms. Classical treatments by antimony derivatives (Glucantim), then liposomal amphotericin (Ambisome) proved to be inefficient. A liposomal amphotericin-gamma interferon association suppressed the symptoms without eradicating the parasite. The patient was given a maintenance therapy based on liposomal amphotericin. CONCLUSION: The stubborn and recurring nature of this chronic visceral leismaniosis can be due to the immune deficit inherent in the polychemotherapy performed in order to treat the metastatic osteosarcoma which currently is in first full remission.
[Treatment of infantile visceral leishmaniasis].
Visceral leishmaniasis is an endemic disease in the Mediterranean Basin. Children are one of the targets of the infection. Treatment usually requires parenteral injections of pentavalent antimony (Glucantime or Pentostam), but the high frequency of adverse events and the occurrence of primary or secondary resistance cases limit the use of these medications. Diamidines (Pentacarinat) or amphotericin B derivatives are alternatives to antimony. Unfortunately, pharmacokinetics and optimal dosage of diamidines are not well-known, and numerous adverse events are described. Liposomal preparations of amphotericin B enhance its efficiency and tolerance, and the duration of treatment may be reduced to 5 days. Moreover, primary resistance to amphotericin B is not described in immunocompetent children. Allopurinol associated with antimony seems no more efficient than antimony alone. Aminosidine is not evaluated.
Visceral leishmaniasis: a lingual presentation in a patient with HIV infection.
The term leishmaniasis covers a series of illnesses caused by the protozoan Leishmania; depending on the patient's immune response, the particular species of the protozoan, and the geography, the condition may manifest itself as cutaneous, mucocutaneous, or visceral disease. Visceral leishmaniasis has often been found as a co-infection associated with the human immunodeficiency virus, particularly in the region of the western Mediterranean. We report the case of an HIV-infected patient with a history of treated laryngeal leishmaniasis who subsequently appeared for treatment with a tumorous lesion on the dorsum of the tongue that was caused by Leishmania infection.
Pediatric visceral leishmaniasis in Albania.
OBJECTIVE: Visceral leishmaniasis (VL) in children is endemic in southern Europe but has not been previously reported from Albania. This prospective study reports the clinical and laboratory findings in 50 children with visceral leishmaniasis, the value of a direct agglutination test (DAT), and the result of treatment with meglumine antimonate. MATERIALS AND METHODS: Sera obtained from 50 children with VL confirmed by bone marrow examination, 40 household contacts, and 30 hospitalized children with other infections were examined using DAT. RESULTS: Clinical features included fever (100%), hepatosplenomegaly (100%), pallor (100%), weight loss (98%), vomiting (68%), diarrhea (32%), and bleeding disorders (8%). Laboratory findings were anemia (94%), neutropenia (85%), hypergammaglobulinemia (70%), and thrombocytopenia (22%). Thirty children who developed secondary bacterial infections had significantly lower hemoglobin and neutrophil counts (P<0.0001). Direct agglutination test had a sensitivity of 98%, a specificity of 100%, and a positive predictive value of 100%. One child with severe generalized bleeding died within 48 hours of admission before receiving treatment. CONCLUSION: The direct agglutination test was highly valuable in diagnosis of VL in this series. Meglumine antimonate was an effective therapeutic agent. Post-treatment bone marrow examination confirmed recovery in all patients. There were no relapses of VL during one-year follow up.
Emergency initiative to reduce leishmaniasis in Afghanistan.
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The epidemiology and surveillance of visceral leishmaniasis in the Campania region of Italy. The value of zymodeme typing.
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.