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Objective: To evaluate the efficacy of and resistance to mebendazole (500 mg) and levamisole (40 or 80 mg), alone or in combination, for the treatment of Ascaris lumbricoides, Trichuris trichiura and hookworm infections on Pemba Island - an area exposed to periodic school-based mebendazole treatment since 1994. Methods: A randomized, placebo-controlled trial was carried out in 914 children enrolled from the first and fifth grades of primary schools. Stool samples collected at baseline and 21 days after treatment were examined by the Kato-Katz technique to assess the prevalence and intensity of helminth infection. Findings: Efficacies of mebendazole and levamisole as single treatments against intestinal nematode infections were comparable with those in previous trials, but mebendazole treatment of hookworm infections gave significantly lower cure (7.6%) and egg reduction (52.1%) rates than reported in a study undertaken before the beginning of periodic chemotherapy (cure rate, 22.4%; egg reduction rate, 82.4%). Combined treatment with mebendazole and levamisole had a significantly higher efficacy against hookworm infections (cure rate, 26.1%; egg reduction rate, 88.7%) than either drug given alone. No difference in mebendazole efficacy was found in children who had been treated repeatedly compared with those who had not been treated previously. Conclusion: The overall efficacy of mebendazole against hookworm infections after periodic chemotherapy is reduced. The efficacy of benzimidazoles in chemotherapy-based control programmes should be monitored closely. Combined treatment with mebendazole and levamisole may be useful as a tool to delay the development of benzimidazole resistance.

In vivo depletion of C3 with cobra venom factor (CoF) was used to demonstrate the participation of complement in the innate immunity to S. mansoni and in the acquired immunity of both actively and passively immunized rats. Complement was shown to play an important role in innate immunity, being more involved later in larval migration (Days 8–13 post-infection) than at earlier times (Days - 1–3 and Days 3–8 post-infection). Furthermore, the specific component of immunity conferred by immune serum transferred at the lung-migration stage also required complement for optimal expression. This supports the notion that both innate and acquired immunity act not against the much studied early post-penetration stages, but primarily against the lung stages. Although decomplementation at earlier stages of parasite migration (up to 3 days post-infection) did cause some reduction of innate immunity, there was no evidence of any effect on the levels of resistance actively induced by exposure to irradiated cercariae. This suggests that, while complement may play a role in innate immunity during the skin-migration phase, specific complement-mediated attrition does not play a crucial role at this time. The situation was very different in the mouse model, since no involvement of complement in either innate or irradiated vaccine-induced immunity could be demonstrated within the first 15 days of infection. Thus, there appear to be phases in the parasite migration in rats, but not in mice, during which complement becomes a critical factor in both innate and acquired immunity to S. mansoni. [ABSTRACT FROM AUTHOR]

Sera from rabbits and rats vaccinated with highly irradiated cercariae of Schistosoma mansoni (VRabS, VRatS) were found to b¢ of substantially higher affinity than sera from CBA mice vaccinated four times (4 × CVMS), single sex sera (SSS) or chronic infection sera (CIS). In contrast, VRabS and SSS appeared to possess the highest titres of antibody, followed by CIS and VRatS, with 4 × CVMS displaying the lowest titre. Two mouse strains selectively bred for high-affinity (HA) or low-affinity (LA) antibody following vaccination were tested for their ability to resist a challenge infection. LA mice, which produce high titres of low-affinity antibody, manifested significantly more resistance than HA mice, which produce low titres of high-affinity antibody, immunoprecipitation studies demonstrated that sera from vaccinated LA mice (LVMS) recognized 125I-labelled schistosomular surface antigens more intensely than sera from vaccinated HA mice (HVMS). However, peritoneal macrophages from HA and LA mice in the presence of HVMS, LVMS or 4 × CVMS, and naive macrophages activated in vitro with interferon-gamma (IFN-γ)/lipopolysaccharide (LPS) mediated comparable levels of schistosomula killing in vitro. The experiments described here provide evidence that the titre of antibody rather than its affinity may be a more critical factor in the development of optimal immunity to S. mansoni. [ABSTRACT FROM AUTHOR]