Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Epidemiology of helminth infections: implications for parasite control programmes, a South African perspective. Chagas disease vector control through different intervention modalities in endemic localities of Paraguay. Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense: a randomised trial. Praziquantel in the treatment of mixed S. haematobium and S. mansoni infections. The impact of Schistosoma haematobium infection and of praziquantel treatment on the growth of primary school children in Bertoua, Cameroon. Comparison of four nitroimidazole compounds for treatment of symptomatic amoebiasis in Kenya. Therapeutic evaluation of two different dose regimens of praziquantel in a recent Schistosoma mansoni focus in Northern Senegal. Immunization with SPf66 and subsequent infection with homologous and heterologous Plasmodium falciparum parasites.
Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection.
                Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection.
                Minor side-effects requiring no specific medication were recorded in a small proportion of individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001).
                The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy. To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal. To assess the South African government's parasite control policy.
                The study recruited 268 school children, aged 8 to 10, and randomly allocated them into treatment and placebo groups (treatment consisted of a single dose of albendazole (400 mg) and praziquantel (40 mg/kg)). Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline (prior to treatment) and 16 weeks post treatment. Two weeks after treatment prevalence and intensity were again measured for an approximate 50% sub-sample of the children to investigate efficacy of treatment. An analysis of the South African government's policies concerning parasite control is assessed in the light of these epidemiological findings.
                Low levels of both stunting and wasting were observed throughout the study (approximately 10% and 1%, respectively), but did not vary significantly across either treatment group or time period (P >0.50). At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5%, Trichuris trichiura 51.9% and Schistosoma haematobium 22.3%. These prevalences declined significantly to 4.7% (P <0.0005), 38.0% (P < 0.03), and 3.3% (P < 0.0002), respectively, 16 weeks post treatment. The majority of infections observed at baseline were of light intensity, namely A. lumbricoides (50%), T. trichiura (80%) and S. haematobium (100%), and following treatment these levels were reduced significantly (P <0.0001, P< 0.05 and P < 0.005, respectively). The levels of both prevalence and intensity in the untreated group remained constant. The cure rates over the first two weeks of the study were found to be 94.4% for A. lumbricoides, 40% for T. trichiura and 72.2% for S. haematobium.
                The benefits of targeted, school-based treatment in reducing the prevalence and intensity of infection supports the South African government's focus of using school-based interventions as part of an integrated parasite control programme. These strategies and programmes are consistent with recommendations of the World Health Organization (WHO) and The United Nations Children's Fund (UNICEF). In a field study carried out in three rural communities in Paraguay in a zone endemic for Chagas disease, we implemented three different vector control interventions--spraying, housing improvement, and a combination of spraying plus housing improvement--which effectively reduced the triatomine infestation. The reduction of triatomine infestation was 100% (47/47) in the combined intervention community, whereas in the community where housing improvement was carried out it was 96.4% (53/55). In the community where fumigation alone was used, the impact was 97.6% (40/41) in terms of domiciliary infestation. In all the houses where an intervention was made, an 18-month follow-up showed reinfestation rates of less than 10%. A serological survey of the population in the pre- and post-intervention periods revealed a shift in positive cases towards older age groups, but no significant differences were observed. The rate of seroconversion was 1.3% (three new cases) in the community with housing improvement only, but none of these cases could have resulted from vector transmission. The most cost-effective intervention was insecticide spraying, which during a 21-month follow-up period had a high impact on triatomine infestation and cost US$ 29 per house as opposed to US$ 700 per house for housing improvement. African trypanosomiasis is a fatal disease caused by protozoan parasites of the species Trypanosoma brucei. The disease has reached epidemic dimensions in various countries of central Africa. Treatment of the second stage is long and complicated, and is hampered by severe adverse reactions to the first-line drug, melarsoprol. Despite these problems, melarsoprol is likely to remain the drug of choice for the next decade. We therefore did a randomised trial comparing the standard treatment schedule with a new, concise regimen.
                The safety and efficacy of the new schedule were assessed in patients presenting to a hospital in Kwanza Norte, Angola with sleeping sickness. The control group followed the 26-day standard Angolan schedule of three series of four daily injections of melarsoprol at doses increasing from 1.2 to 3.6 mg/kg within each series, with a 7-day interval between series. The new treatment schedule comprised 10 daily injections of 2.2 mg/kg. Primary outcomes assessed were elimination of parasites, deaths attributed to treatment, and rate of encephalopathy. Analysis was by intention to treat.
                Of 767 patients with second-stage disease, 500 were enrolled: 250 were assigned the standard schedule, and 250 the new schedule. 40 patients on the standard schedule and 47 on the new schedule had adverse events which resulted in treatment disruption or withdrawal. 50 patients on the standard regimen deviated or withdrew from treatment, compared with two on the new regimen. Parasitological cure 24 h after treatment was 100% in both groups; there were six deaths (all due to encephalopathy) 30 days after treatment in each group. The number of patients with encephalopathic syndromes was also the same in each group (14). Skin reactions were more common with the new treatment, but all could be resolved by additional medication or withdrawal of treatment.
                Considering the economic and practical advantages of the new 10-day schedule over the standard 26-day treatment schedule, and the similarity of treatment outcome, the new schedule is a useful alternative to the present standard, especially in epidemic situations and in locations with limited resources. A randomized single blind stratified study involving 153 patients with mixed S. mansoni and S. haematobium infection showed that 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) is effective in giving high cure rates in each infection separately, 66% (64 patients) and 77% (94 patients), respectively. The complete clearance of both infections (i.e., no eggs whether dead or alive) 6 months after treatment was 29% (43 patients). The side effects of the drug were minimal and transient, the most common being gastrointestinal ones. The assessment of the objective tolerability by clinical, haematological and biochemical tests showed also that the drug was very safe. It is thus concluded that the drug is a promising useful tool in the control of schistosomiasis in general and the treatment of the individual. Our objective was to determine in a Cameroonian school population the effect of mild to moderate S. haematobium infection intensity on growth and development of children before and 6 months after praziquantel treatment. Previous studies have yielded contradictory results. Children from Bertoua schools were divided into four study groups: heavily infected (> 500 eggs 10 ml-1), moderately infected (1-499 eggs 10 ml-1) treated with praziquantel, a similar group treated with placebo, and an uninfected control group. Anthropometric measures--height for age per cent median (HAPM), and weight for age per cent median (WAPM)--were significantly higher among the uninfected children. Stepwise regression analysis showed that S. haematobium and Ascaris infections were the strongest predictors of the HAPM with hookworm and malaria infections playing a lesser role. Post treatment comparison of the praziquantel treatment group and the placebo group showed no significant differences for the anthropometric indicators except for mid-arm circumference. Longer observations of growth after treatment as well as monitoring of the rate of reinfection would be necessary to understand better the effect of S. haematobium on growth. Four antiamoebic drugs currently used in many Kenyan hospitals and health centres were compared for their efficacy on symptomatic luminal amoebiasis in Kiambu, Kilifi, and Machakos hospitals during this study. The drugs were; the brand metronidazole (Flagyl, May & Baker, Kenya Ltd.), the generic metronidazole (Metrozol, Cosmos Ltd., Nairobi, Kenya), the brand tinidazole (Fasigyn, Pfizer Laboratories Ltd.) and the generic tinidazole (Tynazole Laboratory and Allied Equipments, Kenya Ltd). Clinical cure was achieved in all individuals receiving any of the four drugs. Parasitological cure was better for those receiving either Flagyl or Fasigyn, than those receiving the generic counterparts. Both parasitological and clinical cures were achieved in about 50% of all those who received either Flagyl or Fasigyn. It appears that Flagyl and Fasigyn are not as efficacious as previously reported but are still much better than their generic counterparts for the treatment of symptomatic Entamoeba histolytica infections. A therapeutic trial, involving 130 Schistosoma mansoni-infected children, with no previous history of antischistosomal treatment, was carried out to evaluate the efficacy of two different dose regimens of praziquantel. The study was carried out because low cure rates were described in this recently established (1990) S. mansoni focus in northern Senegal, following treatment with a standard dosage of 40 mg/kg. The subjects were randomly allocated into two groups: one group (1) received 40 mg/kg in one oral dose, the other group (2) was treated with two oral doses of 30 mg/kg at a 6-hr interval. Parasitologic examination and circulating anodic antigen (CAA) detection were performed before, 10 days, three, six, and 21 weeks after chemotherapy. No significant differences in cure rates were found between the two groups. Six weeks after treatment, 34% and 44% of the individuals were found to be stool negative in group 1 and group 2, respectively. However, only 10-15% became completely negative according to the serum CAA antigen assay. Mean egg counts were reduced by 99% in both groups. Antigen detection confirmed the parasitologic results. Fewer side effects were observed in the group treated with 2 x 30 mg/kg, which may be explained by split dosage administration. Our study shows that the low cure rates observed in this area could not be improved by using a higher dosage of praziquantel. In an area of intense transmission, a malaria vaccine could reduce infection due to the parasite types represented in the vaccine, but have no detectable effect on the overall frequency of infection if it did not protect against infection with heterologous parasites. These studies were performed to determine whether immunization with SPf66 decreased infection with homologous parasites containing the 11 amino acid peptide from merozoite surface protein-1 (MSP-1) in SPf66, or increased infection due to heterologous parasites containing heterologous (alternative) MSP-1 sequences. Based on this 11 amino acid peptide (YSLFQKEKMVL), three forward primers (S,Q,V) were designed to amplify the MSP-1 sequence present in SPf66, and 3 additional forward primers (G,H,I) to amplify the alternative MSP-1 sequence (YGLFHKEKMIL). This strategy was validated by polymerase chain reaction (PCR) amplification and dideoxy sequencing with 14 cloned laboratory isolates, which demonstrated that each primer amplified one MSP-1 sequence or the other, but not both. The technique was then used to examine filter paper blots from an SPf66 vaccine study of 69 subjects in Saradidi, Kenya. In that study, the prevalence of infection with YSLFQKEKMVL or YGLFHKEKMIL type parasites was unaffected by immunization with SPf66 (based on PCR amplification with the S, Q, V, G, H and I primers, respectively). These results suggest that immunization with SPf66 does not produce a selective effect in vivo. They demonstrate a molecular method to test for selection in vivo as an indirect measure of vaccine efficacy.
Despite major public health importance, trypanocidal·therapy for chronic asymptomatic T. cruzi infection has been tested in few, small size RCTs which were designed to assess parasitic-related, but not clinical outcomes. Therefore, the potential of trypanocidal therapy to prevent Chagas' disease among asymptomatic, chronically infected subjects is promising, but remains to be evaluated. Trypanocidal therapy, particularly nitroimidazolic derivatives given to children or adults with positive xenodiagnosis improve parasite-related outcomes. The large contrast between the burden of Chagas disease and the existing evidence on its prevention points the need to test these or newer agents in more and larger RCTs that include clinical endpoints.