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Fundamentals: American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania., Objectives: To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis., Methods: 185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment., Results: No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1% for pentamidine and 55.5% for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7%) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40%) patients, especially arthralgia (20.3%) in the meglumine group, and pain (35.1%) or induration (10.8%) at the site of injection in the pentamidine group., Conclusion: Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches.

Introduction: The therapeutic arsenal against cutaneous leishmaniasis is very limited. Pentavalent antimonial compounds have been the drugs of choice for treatment of this disease for over 50 years. Despite their effectiveness, these drugs require daily injections, have many side effects and present prolonged healing time., Objective: To carry out a systematic literature review on the advances in the treatment of cutaneous leishmaniasis in the new world in the last ten years., Methods: We conducted an electronic search on the Pubmed and LILACS database as well as on the SciELO electronic library in June 2009. The search words in English were: "cutaneous", "leishmaniasis" and "treatment". We included only randomized, double-blind and placebo controlled trials. We used the Jadad scale to assess the quality of the selected studies., Results: According to the inclusion and exclusion criteria, only eight articles were selected. The drugs evaluated in the selected studies were glucantime®, miltefosine, immunotherapy, imiquimod, rhGM-CSF and pentoxifylline, and paromomycin., Conclusion: Although cutaneous leishmaniasis is a major public health issue, the published data on the use of new drugs for the treatment of cutaneous leishmaniasis in Brazil are still quite limited.

Introduction: Visceral leishmaniasis is a public health problem, with lethality reaching 10%. The recommended drug treatment is methylglucamine antimoniate. This study aimed to evaluate drug use for cases of visceral leishmaniasis treated at the Infectology Clinic of the Campo Grande University Hospital Center, State of Mato Grosso do Sul., Methods: To collect data, we examined the medical records of 76 patients with a diagnosis of visceral leishmaniasis treated at this Infectology Clinic., Results: The medical files of 76 patients (56 men and 20 women; 28.9%) showed comorbidities. The first choice drug for 88.2% of the patients was N-methylglucamine antimoniate, with a fatal outcome for 18.4%. Survival analysis showed a statistically significant difference between patients with and without comorbidities (p <0.0001) and with comorbidities who used Glucantime (p < 0.0009). The fatality rate of 18.4% indicates the low efficiency of the healthcare measures used., Conclusions: The results suggest that the prognosis becomes poor when associated with the presence of comorbidities, and that the treatment needs to be carefully administered to minimize mortality.

Introduction: Visceral leishmaniasis is a systemic infectious disease of broad geographical distribution, characterized by high potential for lethality. With the purpose of contributing towards reducing mortality and helping healthcare professionals in clinical management of patients with this disease, this paper aimed to investigate the clinical and laboratory characteristics of cases with a fatal outcome in hospitals in Campo Grande, Mato Grosso do Sul, between 2003 and 2008., Methods: Fifty-five medical files on patients who died due to visceral leishmaniasis were analyzed., Results: Among the 55 patients studied, 37 were from the municipality of Campo Grande; 41 (74.5%) were males; and age over 40 years predominated. The patients presented with fever in 89.1% of the cases. The duration of the illness from the onset of symptoms to hospitalization was 78.2 days on average. Leukopenia was seen in 85.5% of the patients. Comorbidities were present in 39 (70.9%) patients; malnutrition and alcoholism were the most frequent of these. Confirmation of the diagnosis occurred on average 6.7 days after admission. Pentavalent antimoniate was the drug most used, and 87.5% of the patients presented some type of adverse reaction. Bacterial infections occurred in 36 patients and were one of the causes of death in 27 (49%)., Conclusions: The data showed that early identification of these clinical and laboratory characteristics, at the time when patients are first attended, is extremely important for reducing mortality through instituting efficient therapeutic and prophylactic measures.

The therapeutic effect of and adverse events associated with topical use of 10% paromomycin gel on cutaneous leishmaniasis are described. Fifteen patients with cutaneous leishmaniasis fulfilled the following inclusion criteria: contraindication for the use of meglumine antimoniate, positive Montenegro skin test and up to four ulcerated lesions. The formula was prescribed twice a day for 20 days. Fourteen patients were available for the therapeutic outcome evaluation. The cure rate was 21.4% (3/14); 50% improved as far as complete epithelialization; and the failure rate was 28.6%. Nine patients who did not initially present cure were retreated. Eight received a new series of topical paromomycin and one was treated with meglumine antimoniate. Two patients did not receive any new treatment and had continuous slow improvement. Five out of the eight patients retreated with topical paromomycin achieved clinical cure, and three presented failure, including one patient who had shown any improvement with the first treatment. For 53.3% of the patients, the adverse events were mild and local and never led to treatment suspension.

The results from a field study on autochthonous visceral leishmaniasis on the island of São Luís are presented. This study started in 2004 and finished in 2006 and had the aim of ascertaining the determinant epidemiological and clinical characteristics of this endemic disease. Two hundred ninety nine autochthonous cases were analyzed, of which 83.6% were children younger than 9 years old and 54.1% were male. The disease occurred in all months of the year, with a peak in June. The coefficient of incidence decreased from 46.1 to 35.2 cases per 100,000 inhabitants over the years studied. The diagnosis was confirmed by laboratory tests in 93.3% of the cases. The treatment of choice was based on N-methylglucamine, with a cure rate of 96.1%. The mean lethality rate was 3.7%. Because of the absence of systematic control actions, the authors propose the creation of a specific program to be developed by the municipalities under the coordination of the State Department of Health.

Unlabelled: Twenty-five mice were infected with Leishmania amazonensis and treated with glucamine and oral miltefosine. The criteria used were pad measurements and investigations of amastigotes and cultures after treatment., Measurements: miltefosine 2.43 mm and glucamine 3.46 mm (p: 0.05). Miltefosine smears and cultures were negative. Glucamine produced two positive smears and the cultures were positive (p < 0.05). Miltefosine was similar to or better than glucamine.

Objectives: Evaluate the effect of Meglumine Antimoniate on maternal-fetal transference in F1 generations (offspring of dams exposed to the drug), and embryotoxicity in F2 generations., Methods: Female Swiss mice were treated with daily s.c. injection of Meglumine Antimoniate (100mgSb v/kg bw/day) from day 7 until day 12 of pregnancy. The control group received only the vehicle (distilled water). After birth of offspring (F1 generation), 59 females were examined daily for determination of the estral cycle. When the cycle estrus was determined, males were mated with 18 females of the same lineage. On day 18 of pregnancy, females were euthanasied in a chamber of CO2 and after incision of the abdomen, the uterus was exposed. Then, resorptions as well as living and dead fetuses were evaluated, also the number of embryo/fetal implantation sites. Fetuses and their placenta were weighted to calculate the placental index. Three placentas of each litter were separated for microscopic analysis., Results: Administration of the Meglumine Antimoniate did not interfere in the estral cycle of the treated group, since it did not alter the precoital interval and fertility index. Placenta alterations were not observed in the F2 generations., Conclusion: Meglumine Antimoniate did not interfere in the reproductive performance, after chronic exposition of dams. Data suggest that there is a gradual elimination of Meglumine Antimoniate by the maternal organism without damaging the future offspring.

This study, realized from October 2000 to January 2003 describes the clinical epidemiological characteristics of visceral leishmaniasis in Três Lagoas, Mato Grosso do Sul State, Brazil. A total of 149 cases were confirmed, with a predominance of the male gender (71.1%). The principal age group was aged 0 to 4 years old (42%). The clinical picture included fever (97.3%), esplenomegaly (85.9%) and anemia (75.8%). Associated infections were seen in 32 patients (21.5%), pneumonia being most common. Changes registered in the laboratory included a median hemoglobin level of 8mg/dl and 3,100 leucocytes/mm(3). Bone marrow smears were positive in 90.6% of patients. Of the 97.9% patients treated, 78.2% used pentavalent antimony. Mortalities occurred in 8% of cases, half of these with associated infection. Taken together, these data suggest changes in the physiographical occurrence of visceral leishmaniasis in this locality, with expansion and urbanization of the disease, requiring greater attention for early diagnosis and treatment.

We investigated factors associated with treatment failure in the treatment of cutaneous leishmaniasis with meglumine antimony in a reference service in Mato Grosso State. A retrospective cohort of 151 patients with cutaneous leishmaniasis was built using medical records. The incidence of therapeutic failure was 47% (IC95%=39.2%-55%). Antimoniate doses below 10 mg/kg/day (RR=1.8; IC95: 1.1-3.0), previous leishmaniasis treatment (RR=1.7; IC95: 1.3-2.4), 3 or more skin lesions (RR=1.9; IC95: 1.4-2.5), incomplete treatment (RR=1.9; IC95: 1.3-2.6) and body weight above 68 kg (RR=1.7; IC95: 1.1-2.5) were associated with therapeutic failure. After adjustment, therapeutic failure was associated with having 3 or more cutaneous lesions (OR=4.6; IC95%=1.2-17.4), reports of previous leishmaniasis treatment (OR=4.5; IC95%=1.1-17.5), body weight above 68 kg (OR=4.3; IC95=1.5-11.9) and incomplete treatment schedule (OR=12.5; IC95%=2.1-75.4), although body weight is possibly associated with treatment failure due to the limitation of the maximum daily dose. These results help to identify patients at risk of treatment failure of cutaneous leishmaniasis with antimony therapy.

Nine cases of American tegumentary leishmaniasis were reported at a Training Military Unit located in Bela Vista City, State of Mato Grosso do Sul. Parasites obtained from lesions of six patients were isolated in culture media followed by identification, through isoenzymes analysis, as being Leishmania amazonensis. This is the first evidence of the presence of the parasite in Mato Grosso do Sul.

The aim of work was to study the epidemiology of American tegumentary leishmaniasis in a military training unit situated in Zona da Mata region of Pernambuco State. Between 2002 and 2003 twenty-three cases were notified by clinical exam, detection and/or isolation of parasite and Montenegro skin test. Seven stocks of Leishmania (Viannia) braziliensis were obtained from patients, identified by a panel of specific monoclonal antibodies and isoenzymatic electrophoresis profiles. An epidemiologic survey on prevalence of infection was carried out by Montenegro skin test in the population that underwent training activities during the same period, out of which 25.3% were identified as positive. These results in association with previous data from this area, shows the maintenance of a primary transmission cycle and the occurrence of periodical outbreaks after training activities in local areas of remnant Atlantic rain forest.

The authors report a case of mucocutaneous leishmaniasis in a 45-year-old patient who was unsuccessfully treated with pentavalent antimonial for 30 days. After 10 days from the initial treatment and before starting a new therapeutic regimen with the same drug the patient died due to sudden cardiac arrest.

Seventy-nine patients with cutaneous leishmaniasis were included in this study. The experimental group (n = 38) was treated with pentamidine isothionate in a dose of 4mg/kg/day on alternate days, for one week. The control group (n = 41) was treated with N-methylglucamine in a dose of 20mgSbV/kg/day for 20 days. Twenty-one isolates were identified using monoclonal antibody technique. We characterized Leishmania (Viannia) braziliensis, most frequently. There was a cure rate of 71.05% of the patients in the experimental group and 73.17% in the control group (p = 0.47). We found a statistical significance regarding frequency of ECG alterations between the experimental and control group (p<0.05). In our study pentamidine was as effective as antimonial for the treatment of american cutaneous leishmaniasis. It proved to be a safer drug considering heart toxicity. Moreover, it requires less time to complete the treatment.

This randomized, single blind clinical trial was performed to compare the efficacy and toxicity of BP88 Sodium Stibogluconate (SS) to Glucantime(R) (N-methyl-glucamine), (GL). Sixty-three patients were randomly assigned to one of two groups: 32 patients were treated with GL and 3l patients were treated with SS. Both groups received 15mg Sb+5/kg/day for 20 days. Toxicity was evaluated through EKG, urea, creatinine, AST, ALT, alkaline phosphatase, amylase, and lipase, assessed before treatment, on day 10 and day 20 of treatment and 90 days after treatment. In the group treated with GL, 81% (26/32) of patients were cured compared to 77% (24/31) in the SS group. Five (16%) patients relapsed in the GL group compared to 6 (19%) in the SS group. One patient in each group did not respond to treatment. AST, ALT, amylase, and lipase were more elevated in the SS group (p < 0.05). In conclusion, the efficacy of both treatments was similar although there was more toxicity in the ES group.

Efficacy and safety of meglumine antimoniate and sodium stibogluconate BP 88R were compared in cutaneous leishmaniasis treatment in Corte de Pedra, Bahia, an endemic area of leishmaniasis due to Leishmania (Viannia) braziliensis. An open trial was developed with one hundred twenty seven patients who were diagnosed based on clinical criteria and Montenegro's skin test. Fifty eight patients were treated with meglumine antimoniate and 69 received sodium stibogluconate. Both groups received 20 mg/Sbv/kg/day for 20 days. Patients were followed every ten days during treatment and every month thereafter for three months. Sixty two percent patients cured with meglumine antimoniate and 55% cured with sodium stibogluconate (p = 0.42). Headache was more frequent during the first half of treatment in patients receiving sodium stibogluconate (p = 0.026). During the second half, patients treated with sodium stibogluconate showed a greater frequency of myalgia/arthralgia (p = 0.004) and abdominal pain/anorexia (p = 0.004). Three patients treated with sodium stibogluconate had severe side effects.

The authors report a case of a 89 years-old woman with mucocutaneous leishmaniasis and previous diabetes mellitus and high blood pressure, who had been treated with allopurinol for 10 months without healing of lesions. Afterwards, she has been treated with meglumine antimonate, "glucantime" for 4 days, with a total dose 2,380 mg of Sbv, but developed cardiac side effects and hypokalemia, hence the treatment was withdrawn. However, this patient developed total clinical regression of lesions, in spite of she has been received low dose of this drug.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.

Visceral leishmaniasis (kala-azar) was definitively an important disease of the state of Maranhão, Brasil since 1982. Since of then, many authors have been working with this topic in spite of reports. Nevertheless, the aspects of diagnosis, treatment an control of cure went through still hard worried the authors have been studying the disease, that came at São Luís Island since of the destabilization of the ecotopes of Lutzomya longipalpis, most important sandflies bites. After 1993 the constatation of cases with bad response to pentavalent antimonial (Glucantime) comes to add the other worries. This actual trial accost the disease and conclude about an existence of failures to Glucantime being important to have much vigilance in the diagnosis, treatment and control of cure of the patients.

We treated six patients with mucosal leishmaniasis who failed to respond to glucantime (20 mg/kg/day) with ambisome (2-5 grams total dose). The daily dose was 2-3 mg/kg/day given for a minimum of 20 days. After 26-38 months of follow up, five patients were clinically cured. One relapsed after six months. No side effects of therapy were observed apart from headache after infection. Ambisome is a therapeutic option for patients with mucosal leishmaniasis unresponsive to antimonials.

From September to November 1994. 21 patients with active mucosal leishmaniasis were treated with aminosidine sulphate 16 mg/kg/day by intramuscular injection for 20 days. They were principally adult male agricultural workers. Thirteen patients had not received specific treatment and eight had failed to respond to Glucantime therapy. Diagnosis was based on clinical and epidemiological observations, a search for the parasite, leishmanin skin sensitivity and indirect fluorescent antibody serological tests. Sixty seven percent of patients had leishmania parasites isolated from inoculated hamsters or visualized in imprints or histopathological sections. The mean follow-up period was 12.6 months. All patients completed treatment. Side effects were pain at the injection site (86%); mild proteinuria (24%), elevated serum creatinine (.5%) and subclinical bearing loss in one of two patients who did audiometric tests. Clinical cure was achieved in 48% and the accumulated relapse rate was 29% (4/14).

Skin ulcers by Leishmania (Viannia) braziliensis are often deep and irregular and are difficult to measure by just the skin surface transverse and longitudinal diameters. The proposal is to mould the cavity, after local asepsis with fresh water plus soap, with a gelatinous plastic which contains silence, potassium alginate, calcium sulphate, magnesium oxide commercialized under the name of jeltrate (Dentsply Laboratory), by solving 9.5g of jeltrate in 20ml of fresh water and applying the gel on the ulcer which solidifies in 5 minutes. This mould is then filled with a self polymerising acrylic and its volume measured either by weight (by using an analytical balance)-technique 1-or by water displacement by applying Archimeds'principle-technique 2. We show data in a field trial before and after 20 days treatment in 20 patients using three different schedules as follows: 7 received pentamidine isethionate, 7 patients received aminosidine sulphate and 6 received meglumine antimoniate. The results point out that there was a uniform reduction of ulcer volume occurred during this period in the three groups, in both technique. Regarding the therapeutic schedules we are sure that there was a significant statistical difference between the three schedules using the T Student Test, which showed that aminostdine sulphate produced a better volume reduction of the ulcer than the other drugs. Serial moulds reflect clinical billing and are a permanent record. We conclude that the measure of the volume of the skin ulceration can be useful in the therapeutic evaluation, as a practical and cheap procedure, and may be used in field trials.

During the period October 1992 to July 1995 we measured the osmolarity and pH of ampoules of meglumine antimoniate (glucantime) from lot 9206L-004 (manufactured by Rhodia Farma Ltd, of São Paulo, SP, Brazil) maintained in three temperature conditions namely 4 degrees C, 37 degrees C and ambiental. Although we observed statistically significant differences in osmolarity between samples, the limited number of measurements and the variation of this property in ampoules maintained at the same temperature were obstacles to obtain definitive conclusions. Such a variation was not found with pH. Assuming these parameters could reflect structural changes in the pentavalent antimony molecule, clearly further better controlled experiments are indicated.

With the aim of comparing the therapeutic efficacy, tolerability and toxicity of meglumine antimoniate, aminosidine sulphate and pentamidine isethionate, a field study was conducted on randomized treatment of patients with primary cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis (L(V)b), in Corte de Pedra, BA, from October 1992 up to January 1993. Forty six patients were treated and distributed into three groups, two with 15 and one with 16 subjects. All patients were submitted to clinical examination, histopathological and immunological investigations, as diagnostic criterium. All patients were treated by intramuscular route. Group 1 received pentamidine 4 mg/kg/every 2 days, for 8 applications; Group 2 received aminosidine 20 mg/kg/day, for 20 days, and Group 3 received meglumine 10 mg Sbv/kg/day, for 20 days. Failure of therapy was defined as ulceration of the skin lesion four months after treatment. Such failure occurred in five cases as follows: two cases in patients of group 1 one case in patients of group 2, and two cases in group 3, after the first year of follow up. In the evaluation after three years we reviewed fifteen patients, five in each group; except for one in Group 3, all of them were cured. Statistical significance of the results between the three schedules used was not verified.

A grave kala-azar infection in a 14 years old boy is described. The leishmanial infection failed to respond to ten interrupted courses of glucantime of variable duration (14-56 days) at a dose of 20mg Sb5/kg/day. However a favorable response occurred to intramuscular aminosidine sulphate (20mg/kg/day) for 20 days. This same regimen was repeated 20 days later. After the first treatment splenic puncture parasite density fell from 50 amastigotes per oil immersion field to 3 amastigotes in 10 fields. A further splenic puncture 7 months after treatment was negative. The marked hepatoesplenomegaly gradually resolved over 26 months follow up and he gained 13 kilograms in weight. After aminosidine sulphate therapy his Montenegro reaction become positive and his lymphocytes responded to leishmania antigens.

Two patients, with cervical lymphadenopathies and a presumptive diagnosis of lymphoma or scrofula, were submitted to biopsies of the affected lymph nodes. Unexpectedly, the histological picture revealed a necrotic-granulomatous reaction and the presence of leishmania (amastigotes) in some vacuolated macrophages. The patients were from different endemic areas of leishmaniasis in Brazil, and had no perceptible cutaneous or mucosal lesions. Later, however, one of them developed such lesions, probably as an effect of a treatment for toxoplasmosis. These findings support the idea that the agents of the disease, once in the host organism, would invade the organs of the phagocytic-mononuclear system, there remaining for a long time, maybe for the rest of the host life. Eventually, under the action of several factors, that could modify the host resistance, the parasites migrate to the skin or the mucosal membranes, causing secondary or reactivating lesions.

We have evaluated, in a retrospective manner, three chemotherapeutic schemes with meglumine antomoniate (Glucantime) use in the treatment of 43 autochthonous cases of visceral leishmaniasis in children in the age-group of 1-12 years old, during the period 1985-1990. Of the 43 cases, 28 (group A) were treated with 40mg/SbV/kg given IV at intervals of 48 hours, in courses of 15 applications (scheme I); 8 (group B) were treated with 40 mg/SbV/kg given IV daily during 15 days (scheme II), and 7 (group C) were treated with 20 mg/SbV/kg given IV daily during 15 days (scheme III). With the criteria for cure based essentially on clinical examination, we admitted that the scheme III would be the preferred for these reasons: a) it produces the same cure-rate as those schemes which use double this dosage, b) in relation to positive results it is less expensive, c) the scheme can be used for more extended periods, with less risk of toxic effects, and d) there has till now been no evidence of the development of resistance to treatment using this scheme, at least in our particular area of study (Pará).

American cutaneous leishmaniasis has shown an endemic character in areas of North-North-west Paraná State, which were populated in 40's, where residual forests persist with intense modifications. The infection has been found mainly in males, but was found also in females and children and in many individuals of a same family. 513 cases of cutaneous leishmaniasis notified to SUCAM by clinical diagnosis were investigated. Treatment was begun with Glucantime at State Health Centers or at SUCAM. Of 513 treated patients 260 (50.67%) were considered clinically cured. The remaining 253 (49.33%) abandoned treatment. The quantity of Glucantime supplied to the patients varied from 10 vials to more than 200, with or without intervals during the treatment. Two hundred and seventeen (85.46%) patients among 260 received from 10 to 75 vials. The occurrence of leishmaniasis in 163 (31.75%) women and in 34 (6.62%) children, of both sexes, up to 10 years old, suggests domiciliary transmission. It's not known if the 253 (49.33%) individuals who abandoned the treatment recovered. This high number shows the necessity of better knowledge of the consequences that can occur due to incomplete treatment.

The authors report one case of leishmaniasis in a 60 year old patient who developed renal failure after treatment with Glucantime. With the interruption of these drug the patient recovered her normal renal function, and a new treatment with Amphotericin B was tried with complete cicatrization of the lesions.