Evaluation of IFN-gamma and TNF-alpha as immunological markers of clinical outcome in cutaneous leishmaniasis

To evaluate if IFN-gamma and TNF-alpha levels could be used as markers of therapeutic response in cutaneous leishmaniasis, 54 patients with history of one ulcerated cutaneous lesion, with up to 30 days onset, were enrolled in the study. IFN-gammaand TNF-alpha were measured by ELISA in lymphocyte cultures supernatant before and 60 days after initiating therapy. Cure was considered to be a complete healing of lesion 60 days after treatment. IFN-gamma and TNF-alpha levels were similar in both groups of patients before therapy. There was a tendency to increase IFN-gamma levels in patients that were cured in 60 days, however the values did not reach statistical significance. In both groups of patients, TNF-alpha levels were similar before therapy and fell significantly after treatment, irrespective of cure or maintenance of active lesion.

Vaccination of C57BL/10 mice against cutaneous leishmaniasis using killed promastigotes of different strains and species of Leishmania

Antigenic extracts from five Leishmania stocks were used to vaccinate C57BL/10 mice. The Leishvacin® and PH8 monovalent vaccine yielded the highest IFN-gamma levels in the supernatants of spleen cell culture from vaccinated animals. Each single strain immunized group showed evidence of protective immunity six months after the challenge with promastigotes of Leishmania (Leishmania) amazonensis. No differences were detected between the vaccinated groups. It can be concluded that vaccines composed of single Leishmania stocks can provide protection to C57BL/10 mice against L. (L.) amazonensis infection.

An intermittent schedule is better than continuous regimen of antimonial therapy for cutaneous leishmaniasis in the municipality of Rio de Janeiro, Brazil

This study reviews a series of cutaneous leishmaniasis cases diagnosed and treated in outpatient units in the municipality of Rio de Janeiro, where the intermittent schedule of antimonial therapy was replaced by the continuous regimen. Both schedules were based on daily intramuscular injections of pentavalent antimonial. Forty-nine subjects received the intermittent regimen, consisting of three ten-day series alternated with ten-day rest intervals whereas seventy-one patients received the continuous regimen during 20 consecutive days. The study groups had similar composition regarding age, sex and clinical condition. The cure rate was significantly higher in the group receiving the intermittent schedule than in the group receiving continuous therapy (89.8% vs 63.3%). Moreover, loss to follow-up was significantly more frequent in the group receiving continuous therapy (19.7% vs 4.1% in the intermittent therapy). Under field conditions, the intermittent regimen provided higher effectiveness and adherence than the continuous schedule.

Predictors of an unsatisfactory response to pentavalent antimony in the treatment of American visceral leishmaniasis

Although treatment of visceral leishmaniasis with pentavalent antimony is usually successful, some patients require second-line drug therapy, most commonly with amphotericin B. To identify the clinical characteristics that predict an inadequate response to pentavalent antimony, a case-control study was undertaken in Teresina, Piaui, Brazil. Over a two-year period, there were 19 cases of VL in which the staff physicians of a hospital prescribed second-line therapy with amphotericin B after determining that treatment with pentavalent antimony had failed. The control group consisted of 97 patients that were successfully treated with pentavalent antimony. A chart review using univariate and multivariate analysis was performed. The cure rate was 90% with amphotericin B. The odds ratio for the prescription of amphotericin B was 10.2 for children less than one year old, compared with individuals aged over 10 years. Patients who presented coinfection had an OR of 7.1 while those on antibiotics had an OR of 2.8. These data support either undertaking a longer course of therapy with pentavalent antimony for children or using amphotericin B as a first-line agent for children and individuals with coinfections. It also suggests that chemoprophylaxis directed toward bacterial coinfection in small children with VL may be indicated.

Efficacy of azithromycin in the treatment of cutaneous leishmaniasis

The present open pilot study was conducted to assess the efficacy of azithromycin for the treatment of patients with cutaneous leishmaniasis in Araçuaí and Varzelândia, MG. Twenty-four patients with less of six months of disease evolution were treated after clinical examination, Montenegro test and a biopsy. The treatment schemes consisted of oral doses of 500 mg per day for 3, 5 and 10 days and of 1000 mg for two days. A clinical control was performed monthly and treatment cycles were repeated when necessary until full reepithelialization of the lesions. On the occasion of the final evaluation, 20 patients had completed the study and 17 of them (85%) were cured. The time to obtain a cure was 60 days ifor 6 (30%) patients, 90 days for 7 (35%), and 120 for 4 (20%). The three patients with treatment failure received a pentavalent antimonial for 20 days. No adverse reactions to the medication were observed and a 14 month follow-up did not show recurrence in any patient. These results suggest that azithromycin can be a good therapeutic option for the treatment of cutaneous leishmaniasis caused by Leishmania Viannia brasiliensis.

The presence of Lutzomyia longipalpis in a focus of American visceral leishmaniasis where the only proven vector is Lutzomyia cruzi. Corumbá, Mato Grosso do Sul State

The present communication reports the presence of Lutzomyia longipalpis in Corumbá, Mato Grosso do Sul, where the principal vector is Lutzomyia cruzi.

Using epidemiological survey data to infer geographic distributions of leishmaniasis vector species

An important aspect of tropical medicine is analysis of geographic aspects of risk of disease transmission, which for lack of detailed public health data must often be reduced to an understanding of the distributions of critical species such as vectors and reservoirs. We examine the applicability of a new technique, ecological niche modeling, to the challenge of understanding distributions of such species based on municipalities in the state of São Paulo in which a group of 5 Lutzomyia sandfly species have been recorded. The technique, when tested based on independent occurrence data, yielded highly significant predictions of species' distributions; minimum sample sizes for effective predictions were around 40 municipalities.

Canine rabies epidemiology in Araçatuba and neighborhood, Northwestern São Paulo State - Brazil

Epidemiological characteristics of canine rabies in the northwest region of São Paulo State (Araçatuba region), Brazil, from 1993 to 1997 are presented. Out of 1,984 dogs, a total of 351 (17.7%) were positive for rabies diagnosis; 89% (312/351) of these occurred in urban areas and 85% (266/312) of the urban positive cases were among owned dogs. The mean age of the rabid dogs was 34 months and 61% were male. Aggressive behavior was observed in 77% of rabid dogs, followed by lack of coordination and paralysis (42%) and 48% of these dogs were responsible biting people or other animals. Information about vaccination status was obtained from 182 records and 51% of rabid dogs were non-vaccinated. The number of unvaccinated rabid dogs indicates a low vaccination index and this factor added to the high dog/man ratio must have contributed to the canine rabies epizootic observed in the studied area.

Retrospective study of 151 patients with cutaneous leishmaniasis treated with meglumine antimoniate

We retrospectively analyzed a series of 151 cases of cutaneous leishmaniasis treated between 1967 and 1982. One-hundred-and-thirty-nine (92%) patients presented with active lesions and were treated with daily doses of meglumine antimoniate: 81 adults received a 5-ml vial IM and 58 children received 1 to 5ml. Forty-five (32.4%) patients underwent continuous treatment with meglumine antimoniate for 25 to 116 days without rest intervals, and 94 (67.6%) intermittent treatment with 2 to 5 series of meglumine antimoniate. Intermittent series could include schedules of daily IM applications for 10 to 25 days each and intervals varying from 10 to 60 days. Antimony dose was calculated for 66 (47.5%) patients and ranged from 3.9 to 28.7 Sb5+/kg/day. Of these, 35 patients received >10mg and 31 patients <10mg Sb5+/kg/day. Median time of healing was longer for lesions on the legs and feet - 67.5 days versus 48.7 days (p < 0.001) for other sites. However, there were no significant differences in the median time of healing between adults and children, intermittent and continuous regimens or high and low antimony doses. Fifty-one patients were reassessed 5 to 14 years after treatment and showed no evidence of disease. These results support further investigation (clinical trials) on treatment using low doses of antimony.

Phlebotomine sandflies in a focus of dermal leishmaniasis in the eastern region of the Brazilian State of Santa Catarina: preliminary results (Diptera: Psychodidae)

Due to the occurrence of cases of dermal leishmaniasis in the Municipality of Piçarras, in the East of the Brazilian State of Santa Catarina, collections of Phlebotomine sandflies by the use of CDC-like light traps were developed near the houses of the patients. Three species (Lutzomyia neivai, Lu. fischeri and Lu. ayrozai) were collected. Lu. neivai was predominant near the houses, and Lu. ayrozai was collected in a secondary forest in a nearby municipality (Navegantes). The novelty of this focus, the most southern one in the East of Brazil, underscores the need for more complete studies on the sandfly fauna.

Immunotherapy, immunochemotherapy and chemotherapy for American cutaneous leishmaniasis treatment

The first choice of treatment for American cutaneous leishmaniasis is the pentavalent antimonial drug. Although it has been shown that this treatment is mostly effective and indicated, some disadvantages should be taken into account such as side effects, long term treatment inconveniences and counter-indication for patients suffering from cardiopathy, nephropathy; yet, aging, pregnancy and other conditions. With the advent of the vaccine anti-American cutaneous leishmaniasis as a prophylactic measure, studies on therapy using the vaccine associated or not with other drugs have been performed by many investigators and it is currently among the alternative treatments and prevention measures for American cutaneous leishmaniasis. In conclusion, the association between antimony and vaccine (immunochemotherapy) showed the same cure rate when compared with the standard treatment (100%) and it was also able to reduce the salt volume in 17.9% and treatment length from 87 to 62 days, decreasing side effects.

An alternative antimonial schedule to be used in cutaneous leishmaniasis when high doses of antimony are undesirable

Despite more than half a century of use in leishmaniasis, antimony therapy still presents serious problems concerning dosage and toxicity. Low and high doses have been shown to be equally effective. In this paper, the feasibility of injecting one ampoule of meglumine antimoniate intramuscularly every other day until clinical cure is demonstrated, while studying a series of 40 cutaneous leishmaniasis cases. Total dose used varied from 1,822.5 to 12,150mg of pentavalent antimony and total time of treatment varied from 3 to 10 weeks, with 86% efficacy. Thirty-six out of the 40 patients are still on follow-up with a mean time of 10.7 ± 7 months and a median of 9 months. No relapse or mucosal lesions have been noted so far. The schedule showed good tolerance and easy application and its efficacy was comparable to the officially recommended WHO schedule. Therefore, such a schedule represents a valuable alternative for the cases with high toxicicity to antimony or daily injections are an obstacle to the treatment.

Phlebotominae sand flies associated with a tegumentary leishmaniasis outbreak, Tucumán Province, Argentina

The distribution of sand flies and cases of tegumentary leishmaniasis in the area surrounding JB Alberd city, and the proximities of Catamarca province were studied, after an increase of reported cases from JB Alberdi, Tucumán province, in 2003. Of 14 confirmed cases, 57% were females and 57% were less than 15 years old, suggesting peridomestic transmission. However, 86% of them lived close to the Marapa river forest gallery and related wooded areas. Over 1,013 sand flies were collected; Lutzomyia neivai (Pinto, 1926) was prevalent at all the sites (92.3%), while Lutzomyia migonei (França, 1920) (6.7%) and Lu. cortelezzii (Brèthes, 1923) (1%) were also found. The spatial distribution of Lu. neivai overlapped that of the cases, with higher abundance in microfocal hot spots close to the river in stable vegetated habitats or modified habitats with shadow and animal blood sources. The cumulative outcome of anthropic, ecological and climatic factors could have contributed to the onset of the outbreak.