AUTHOR=Mawa Patrice A. , Kincaid-Smith Julien , Tukahebwa Edridah M. , Webster Joanne P. , Wilson Shona 

TITLE=Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.635869

DOI=10.3389/fimmu.2021.635869

ISSN=1664-3224

ABSTRACT=Schistosomiasis is the second most important human parasitic disease in terms of socioeconomic impact, causing great morbidity and mortality, predominantly across the African continent. For intestinal schistosomiasis, severe morbidity manifests as periportal fibrosis (PPF) in which large tracts of macro-fibrosis of the liver, visible by ultrasound, can occlude the main portal vein leading to portal hypertension (PHT), sequelae such as ascites and collateral vasculature, and ultimately fatalities.  For urogenital schistosomiasis, severe morbidity manifests as pathology to the urinary tract and genitals, and is a definitive cause of squamous cell bladder carcinoma. Preventative chemotherapy (PC) programmes, delivered through mass drug administration (MDA) of praziquantel (PZQ), have been at the forefront of schistosomiasis control programmes in sub-Saharan Africa since their commencement in Uganda in 2003. However, despite many successes, ‘biological hotspots’ (as distinct from ‘operational hotspots) of both persistent high transmission and morbidity remain. In some areas, this failure to gain control of schistosomiasis has devastating consequences, with not only infection and “subtle” morbidities, but severe morbidity remaining prevalent. These hotspots highlight the requirement to revisit research into severe morbidity and its mechanisms, a topic that has been out of favour during times of PC implementation. Indeed, the focality and spatially-structured epidemiology of schistosomiasis, its transmission persistence and morbidity induced, has long suggested that gene-environmental-interactions playing out at the host-parasite interface are crucial. Here we review, the evidence of potential unique parasite factors, host factors, and their gene-environmental interactions in terms of explaining differential morbidity profiles in the human host.  We then take the situation of schistosomiasis mansoni within the Albertine region of Uganda as a case study in terms of elucidating the factors behind the unique severe morbidity observed to date and the avenues and directly for future research currently underway within a new research and clinical trial programme (FibroScHot).