Dataset Information

Maintaining Low Prevalence of Schistosoma mansoni: Modeling the Effect of Less Frequent Treatment.

ABSTRACT:

Background

The World Health Organization previously set goals of controlling morbidity due to schistosomiasis by 2020 and attaining elimination as a public health problem (EPHP) by 2025 (now adjusted to 2030 in the new neglected tropical diseases roadmap). As these milestones are reached, it is important that programs reassess their treatment strategies to either maintain these goals or progress from morbidity control to EPHP and ultimately to interruption of transmission. In this study, we consider different mass drug administration (MDA) strategies to maintain the goals.

Methods

We used 2 independently developed, individual-based stochastic models of schistosomiasis transmission to assess the optimal treatment strategy of a multiyear program to maintain the morbidity control and the EPHP goals.

Results

We found that, in moderate-prevalence settings, once the morbidity control and EPHP goals are reached it may be possible to maintain the goals using less frequent MDAs than those that are required to achieve the goals. On the other hand, in some high-transmission settings, if control efforts are reduced after achieving the goals, particularly the morbidity control goal, there is a high chance of recrudescence.

Conclusions

To reduce the risk of recrudescence after the goals are achieved, programs have to re-evaluate their strategies and decide to either maintain these goals with reduced efforts where feasible or continue with at least the same efforts required to reach the goals.

SUBMITTER: Ayabina D

PROVIDER: S-EPMC8201569 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model of Schistosoma mansoni infection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection. Parasitaemia was assessed by quantification of Schistosoma egg burden in liver tissues and morbidity was followed up by histological observation of liver lesions by microscopy and using biochemical measurement of liver transaminases. Immune responses were further determined by serum probing of schistosoma-specific antibodies, cytokines and quantification of liver cellular and soluble mediator responses by flow cytometry and ELISA, respectively. At similar ages and comparable gender distribution, groups of mice undergoing higher number of infections treatment cycles over a longer period, remained susceptible to reinfection by the parasite, as judged by the presence of eggs and the associated increasing pathology in the liver tissues. However, notably, there was a clear and significantly higher propensity to lower egg burden upon reinfection when compared to counterparts undergoing a lower number of infection-treatment cycles. This relative reduction of susceptibility to infection was paralleled by a more robust humoral response against parasite antigens, elevated serum IL-4 and liver cytokines. Of note, praziquantel treatment of infected mice left them at a higher baseline of serum IL-4, IgE and liver cytokines but lower CD4+ T cell -derived cytokines when compared to infected non-treated mice supporting an immunological treatment-induced advantage of previously infected mice over naïve mice and infected/not treated mice. Notably, repeated infection-treatment cycles did not preclude the infection-driven aggravation of collagen deposition in the livers over time and was corroborated by a more robust local production of inflammatory cytokines in the most exposed livers. Taken together, our data reveal that treatment of S. mansoni-infected hosts with praziquantel rewires the immune system to a conformation less permissive to subsequent reinfection in mice. Provided the data are translatable from mouse to human, our findings may provide mechanistic support to the potential benefits of more frequent MDAs in high transmission areas to allow rapid acquisition of protective immunity against reinfection.

Project description:IntroductionOffspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years.MethodsIn a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years.ResultsOf the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFN?, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not.ConclusionWe found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease.