title: Predicted impact of mass drug administration on the development of protective immunity against Schistosoma haematobium.
abstract: 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.
authors: Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors: Kate M
authors: KM
authors: Mitchell
authors: Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors: Francisca
authors: F
authors: Mutapi
authors: Department of Biochemistry, University of Zimbabwe, Harare, Zimbabwe; College of Health Sciences, University of KwaZulu Natal, Durban, South Africa.
authors: Takafira
authors: T
authors: Mduluza
authors: National Institute of Health Research, Harare, Zimbabwe.
authors: Nicholas
authors: N
authors: Midzi
authors: Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors: Nicholas J
authors: NJ
authors: Savill
authors: Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors: Mark E J
authors: ME
authors: Woolhouse
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D000909:Antibodies, Helminth / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003625:Data Collection; D004358:Drug Therapy / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010270:Parasite Egg Count; D011223:Praziquantel / Q000627:therapeutic use*; D012548:Schistosoma haematobium / Q000187:drug effects* / Q000276:immunology*; D012553:Schistosomiasis haematobia / Q000188:drug therapy* / Q000276:immunology* / Q000635:transmission; D055815:Young Adult
chemical_list: D000871:Anthelmintics; D000909:Antibodies, Helminth; D011223:Praziquantel