Predicted Impact of Mass Drug Administration on the Development of Protective Immunity against Schistosoma haematobium.

Mitchell, Kate M.; Mutapi, Francisca; Mduluza, Takafira; Midzi, Nicholas; Savill, Nicholas J.; Woolhouse, Mark E. J.

Previous studies suggest that protective immunity against Schistosoma haematobium is primarily stimulated by antigens from dying worms. Praziquantel treatment kills adult worms, boosting antigen exposure and protective antibody levels. Current schistosomiasis control efforts use repeated mass drug administration (MDA) of praziquantel to reduce morbidity, and may also reduce transmission. The long-term impact of MDA upon protective immunity, and subsequent effects on infection dynamics, are not known. A stochastic individual-based model describing levels of S. haematobium worm burden, egg output and protective parasite-specific antibody, which has previously been fitted to cross-sectional and short-term post-treatment egg count and antibody patterns, was used to predict dynamics of measured egg output and antibody during and after a 5-year MDA campaign. Different treatment schedules based on current World Health Organisation recommendations as well as different assumptions about reductions in transmission were investigated. We found that antibody levels were initially boosted by MDA, but declined below pre-intervention levels during or after MDA if protective immunity was short-lived. Following cessation of MDA, our models predicted that measured egg counts could sometimes overshoot pre-intervention levels, even if MDA had had no effect on transmission. With no reduction in transmission, this overshoot occurred if protective immunity was short-lived. This implies that disease burden may temporarily increase following discontinuation of treatment, even in the absence of any reduction in the overall transmission rate. If MDA was additionally assumed to reduce transmission, a larger overshoot was seen across a wide range of parameter combinations, including those with longer-lived protective immunity. MDA may reduce population levels of immunity to urogenital schistosomiasis in the long-term (3–10 years), particularly if transmission is reduced. If MDA is stopped while S. haematobium is still being transmitted, large rebounds (up to a doubling) in egg counts could occur. Author Summary: Urogenital schistosomiasis, caused by schistosome blood flukes, infects more than 100 million people in sub-Saharan Africa. Current control efforts involve regularly treating all school-aged children with the drug praziquantel, which kills schistosome worms. Earlier work by our group suggests that protective immunity against schistosomes is mainly stimulated by dying worms, and that in the short term, praziquantel treatment boosts immunity through killing worms. The longer-term impact upon the development of protective immunity is unknown. In this paper, we used a mathematical model which was able to replicate short-term patterns of infection and antibody to predict the long-term changes in antibody and infection levels that would occur during and after a 5-year treatment programme. We found that the longevity of protective immunity was particularly influential. Short-lived protective immunity was associated with levels of protective antibody declining below pre-treatment levels in the long term, and also with an increase in measured infection levels (eggs in urine) to peak above pre-treatment levels after the treatment programme finished. Antibody declines and infection peaks post-treatment were also predicted if treatment programmes reduced schistosome transmission. These results highlight the possible negative consequences of ceasing mass treatment programmes once they have commenced.

SUB-Saharan Africa; SCHISTOSOMA haematobium; WORLD Health Organization; DRUG administration; DRUG development; IMMUNITY; HERD immunity

PLoS Neglected Tropical Diseases, 2014, Vol 8, Issue 7, p1

1935-2727

Academic Journal

10.1371/journal.pntd.0003059