Reduction of morbidity in hepatosplenic Schistosomiasis mansoni after treatment with praziquantel: a long term study

Forty-two with hepatosplenic patients treated with praziquantel and followed up for 5 years. One half of the patients received a single 30 mg/kg dose and the other half, two doses of 25 mg/kg given 4 hrs apart. According to Hoffman and Kato-Katz stool exams, an 83.3% cure rate, was observed after twelve months. Stool egg counts in cases of incomplete cure were greatly reduced. Liver function, as assessed by serum levels of aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase activities as well as albumin and gamma globulin showed marked improvement after one year. Hepatomegaly was reduced in 81.0% of patients and splenomegaly in 78.8%. Spleen regression was complete in 15.1% of the total, and in 18.5% of those with compensated hepatosplenic disease. As a result of these observations, the authors recomend early treatment with anti-schistosomal medication, either oxamniquine or praziquantel, to halt progression of disease and reduce splenomegaly.

Biochemical behavior of Trypanosoma cruzi strains isolated from mice submitted to specific chemotherapy

To investigate the influence of chemotherapy on the biochemical beha vior of Trypanosoma cruzi strains, three groups of mice were infected with one of three strains of T. cruzi of different biological and isoenzymic patterns (Peruvian, 21 SF and Colombian strains). Each group was subdivided into subgroups: 1 - treated with nifurtimox; 2 - treated with benznidazole and 3 - untreated infected controls. At the end of treatment, that lasted for 90 days, xenodiagnosis, sub inoculation of blood into new born mice and haemoculture were performed as tests of cure. From the positive tests, 22 samples of T. cruzi were isolated from all subgroups. Electrophoretic analysis of the isoenzymes PGM, GP1, ALAT and AS AT failed to show any difference between parasite strains isolated from treated and untreated mice, which indicates that no detectable clonal selection or parasite genetic markers alterations concerning the isoenzymes analysed have been determined by treatment with drugs of recognized antiparasitic effect, suggesting stability of the phenotypic characteristics of the three biological types of T. cruzi strains.

Control of parasitic infections among school children in the peri-urban area of Botucatu, São Paulo, Brazil

Tide prevalence of intestinal parasitosis ivas investigated in a primaiy school located in Rubiâo Júnior, a peri-urban district of Botucatu, São Paulo slate, Brazil, in order to assess the effect of treatment and practical measures of prophylaxis in the control of parasitic infections among 7-to- 18-year-old school children of a low socio-economic status. The first series of parasitological examinations included 219 school children, ef which 123 (56.1 %) were found to be infected with one or more parasite species. Eighty- four children canying pathogenic parasites were submitted to various anti-parasitic treatment schedules. We re-evaluated 15 (89 %) students after 4 to 6 months post- chemotherapy. The results indicate that the combination of treatment with prophylactic measures has been successful in the control of parasitic infections, since reinfection rates were generally low (< 5-3 %), except for Giardia lamblia infections (18.6 %), and a marked reduction oti the prevalence rates was obsewed with a significant percentage of cure (> 73-1 %) in children infected with most parasite species. The reasons for the apparent failure in the control of infections caused by Hymenolepis nana and Strongyloides stercoralis are discussed.

Histopathology of human American cutaneous leishmaniasis before and after treatment

Chemical therapy for the treatment of leishmaniasis is still inadequate, and a number of drugs and therapeutic programs are being tested. Besides treatment, the ultimate goal is an effective cure, and histopathological analyses of the lesion cicatrices constitute an important measure of treatment success, or otherwise, in this respect. In this paper, we describe histopathological patterns in cases of American cutaneous leishmaniasis in 32 patients from the municipality of Caratinga, Minas Gerais, Brazil, before and after treatment with the following therapeutic methodos: l) leishvacin + glucantime; 2) leishvacin + BCG associated with glucantime; 3) glucantime; 4) leishvacin + BCG. Lesion fragments were collected from all patients by biopsy prior to, and approximately 30 days after, each treatment which resulted in a clinical diagnosis of cure. Following the analysis of slides, the preparations were described from a histopathological point of view and grouped taking into account the prevalence or significance of the characteristic elements. This process resulted in the following classification: 1. exsudative reaction (ER); 2. exsudative giant cell reaction (EGCR); 3. exsudative productive reaction (EPR); 4. exsudative productive giant cell reaction (EPGCR); 5. exsudative productive necrotic reaction (EPNR); 6. necrotic exsudative reaction (NER); 7. productive exsudative reaction (PER), 8. productive giant cell reaction (PGCR); 9. productive exsudative giant cell reaction (PEGCR); 10. productive exsudative giant cell granulomatous reaction (PEGCGR); 11. productive reaction (PR) and 12. productive cicatricial (cure) reaction (PCR). After this analysis, it was noted that clinical cure did not always coincide with histopathological cure.

Experimental treatment with sodium stibogluconate of hamsters infected with Leishmania (Leishmania) chagasi and Leishmania (Leishmania) amazonensis

The present paper reports the experimental treatment of hamsters infected with Leishmania chagasi and Leishmania amazonensis with sodium stibogluconate (20mg/kg/day x 20 days). Only with L. chagasi did the treatment result in the complete elimination of parasites from the spleen. However, no parasitological cure was achieved in hamsters infected with L. amazonensis.

Therapeutic trial in experimental tegumentary leishmaniasis caused by Leishmania (Leishmania) amazonensis. A comparative study between mefloquine and aminosidine

One hundred and eighty-two male inbred C57/BL/6 mice were infected with 3 x 106 Leishmania (Leishmania) amazonensis promastigotes of the MHOM/BR/PH8 strain by means of a subcutaneous injection in the right ear. The animals were separated in three groups: 1) oral mefloquine hydrochloride treatment (16mg/kg/day/10 days), 2) intramuscular aminosidine (Paromomycin®) treatment (20mg/kg/20 days) and 3) control. Twenty six mice of each treated group were sacrificed, one at the end of treatment (nine weeks after inoculation), and one six weeks later (fifteen weeks after inoculation). Control Group animals were sacrificed at weeks six, nine and fifteen after inoculation. There was no significant difference between Group 1 (mefloquine) and Group 3 (control) subjects. Group 2 animals (aminosidine) presented the smallest differences of all, both at the end of the treatment and six weeks later. The histopato-logical parameters have shown the following findings: a) there was no significant difference between the mefloquine treated group and the control group; the group treated with aminosidine showed fewer of vacuolated macrophages than the control group, at week 9 (end of treatment). b) both at the end of treatment and six weeks later, evaluation of tissue necrosis and tissue fibrosis revealed no differences between the treated groups. It was found that six weeks after the end of treatment, mice in the control group presented significantly more severe degrees of fibrosis than mice in the other groups. It can be concluded that mefloquine showed limited therapeutic effect in this experimental model, whereas aminosidine had a significant effect. Nevertheless, neither of them resulted in cure of the lesions.

QBC® for the diagnosis of human and canine american visceral leishmaniasis: preliminary data

"Quantitative Buffy Coat" (QBC®) is a direct and fast fluorescent method used for the identification of blood parasites. Since Leishmania chagasi circulates in blood, we decided to test it in American visceral leishmaniasis (AVL). Bone marrow (BM) and peripheral blood (PB) of 49 persons and PB of 31 dogs were analyzed. QBC® was positive in BM of 11/11 patients with AVL and in 1/6 patients with other diseases. Amastigotes were identified in PB of 18/22 patients with AVL and in none without AVL. The test was positive in 30 out of the 31 seropositive dogs and in 28/28 dogs with Leishmania identified in other tissues. QBC® is a promising method for diagnosis of human AVL, and possibly for the exam of PB of patients with AVL/AIDS, for the control of the cure and for the identification of asymptomatic carriers. Because it is fast and easy to collect and execute, QBC® should be evaluated for programs of reservoir control.

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.

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.

Sensitivity of polymerase chain reaction for detection of known aliquots of Trypanosoma cruzi in the blood of mice: an in vitro study

To evaluate the sensitivity of polymerase chain reaction (PCR) to reveal known number of trypomastigote in the blood of mice, three separate experiments were done. First: To eight samples of 500mul of normal mice blood, one aliquot of 1, 2, 3, 4, 5, 10, and 50 trypomastigotes respectively, were added. Second and third: 10 aliquots with 1 and 10 with 2 trypomastigotes were added to samples of 500mul of normal mice blood. Positive control: 500mul of blood containing 100,000 trypomastigotes. For kDNA minicircles amplification by PCR the primers:S35 and S36 were used. PCR revealed products of 330 b.p in the positive controls. When only one sample with the aliquots of 1 or 2 trypomastigotes was examined, results were negative; results were positive with aliquots of 3 to 50 trypomastigotes. In the 2nd and 3rd experiments, 9/10 aliquots with one parasite and 9/10 with 2 trypomastigotes were positive revealing a high sensitivity of this reaction. In conclusion, the presence of one single parasite in 500mul of blood, is enough for a positive PCR. This method could be used as a complement to the various parasitological cure tests in treated mice, when low volumes of blood are individually examined.

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.

Trypanosoma cruzi: susceptibility to chemotherapy with benznidazole of clones isolated from the highly resistant Colombian strain

The present investigation was performed to evaluate the susceptibility of seven clones isolated from the highly resistant Colombian strains, prototype of Biodeme Type III. Seven clones previously obtained, showed a phenotypic homogeneity and high similarity with the parental strain. Eight groups of 30 mice were inoculated with one of seven clones or the parental strain; 20 were treated with benznidazole (100mg/kg/day) and 10 were untreated controls. Cure evaluations were done by parasitological and serological tests and PCR. Cure rates varied from 0% (null) to 16.7%. Correlation between positivity of parasitological and serological tests with positive PCR reached 37%. The results demonstrated the high resistance of the clones, suggesting the predominance of a highly resistant principal clone in this strain. The findings apparently indicate that the possibility of cure is minimal for patients infected with this biodeme; a fact that could affect the control of Chagas' disease through treatment of chronically infected people.

Response to chemotherapy with benznidazole of clones isolated from the 21SF strain of Trypanosoma cruzi (biodeme Type II, Trypanosoma cruzi II)

Susceptibility to chemotherapy with benznidazole was investigated of 5 clones isolated from the 21 SF strain (biodeme Type II, Trypanosoma cruzi II). Swiss mice were infected with the parental strain for each clone and submitted to chemotherapy with benznidazole (100mg/kg/day during 90 days). Treatment determined negativity of the parasitemia. Cure rates were evaluated by parasitological cure tests. Serology was evaluated for treated animals (titers from negative to 1:640) and untreated controls (1:160 to 1:640). Cure rates varied from 30 to 100% for the 5 clones, and were 25% for the parental strain. Results suggested that the variability of response to treatment of the clonal populations of Trypanosoma cruzi II strains is responsible for the high variation in the response to chemotherapy with benznidazole and nifurtimox by strains of this biodeme.

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.