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Schistosoma mansoni reinfection: Analysis of risk factors by classification and regression tree (CART) modeling.

ABSTRACT: Praziquantel (PZQ) is an effective chemotherapy for schistosomiasis mansoni and a mainstay for its control and potential elimination. However, it does not prevent against reinfection, which can occur rapidly in areas with active transmission. A guide to ranking the risk factors for Schistosoma mansoni reinfection would greatly contribute to prioritizing resources and focusing prevention and control measures to prevent rapid reinfection. The objective of the current study was to explore the relationship among the socioeconomic, demographic, and epidemiological factors that can influence reinfection by S. mansoni one year after successful treatment with PZQ in school-aged children in Northeastern Minas Gerais state Brazil. Parasitological, socioeconomic, demographic, and water contact information were surveyed in 506 S. mansoni-infected individuals, aged 6 to 15 years, resident in these endemic areas. Eligible individuals were treated with PZQ until they were determined to be negative by the absence of S. mansoni eggs in the feces on two consecutive days of Kato-Katz fecal thick smear. These individuals were surveyed again 12 months from the date of successful treatment with PZQ. A classification and regression tree modeling (CART) was then used to explore the relationship between socioeconomic, demographic, and epidemiological variables and their reinfection status. The most important risk factor identified for S. mansoni reinfection was their "heavy" infection at baseline. Additional analyses, excluding heavy infection status, showed that lower socioeconomic status and a lower level of education of the household head were also most important risk factors for S. mansoni reinfection. Our results provide an important contribution toward the control and possible elimination of schistosomiasis by identifying three major risk factors that can be used for targeted treatment and monitoring of reinfection. We suggest that control measures that target heavily infected children in the most economically disadvantaged households would be most beneficial to maintain the success of mass chemotherapy campaigns.

SUBMITTER: Gazzinelli A

PROVIDER: S-EPMC5558968 | 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.

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Schistosoma mansoni reinfection: Analysis of risk factors by classification and regression tree (CART) modeling.

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