Immunomodulation and Vaccines Programme, Medical Research Council-Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda.
Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.
Front Immunol. 2021 Mar 12;12:635869. doi: 10.3389/fimmu.2021.635869. eCollection 2021.
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 throughout the urinary system 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 persistently high infection intensities, but both "subtle" and 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 favor during times of PC implementation. Indeed, the focality and spatially-structured epidemiology of schistosomiasis, its transmission persistence and the morbidity induced, has long suggested that gene-environmental-interactions playing out at the host-parasite interface are crucial. Here we review 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 severe morbidity observed and the avenues and directions for future research currently underway within a new research and clinical trial programme (FibroScHot).
血吸虫病是第二大具有社会经济影响的人类寄生虫病，主要在非洲大陆造成高发病率和死亡率。对于肠道血吸虫病，严重的发病表现为门脉周围纤维化（PPF），肝脏内可见大片纤维化，超声下可见，可阻塞主门静脉导致门静脉高压（PHT），继发出腹水和侧支血管等并发症，最终导致死亡。对于尿路血吸虫病，严重的发病表现为整个泌尿系统和生殖器的病变，是鳞状细胞膀胱癌的明确病因。自 2003 年在乌干达启动以来，通过大规模药物治疗（MDA）给予吡喹酮（PZQ）的预防性化疗（PC）方案一直是撒哈拉以南非洲血吸虫病控制方案的前沿。然而，尽管取得了许多成功，但仍存在持续高传播率和发病率的“生物热点”（与“操作热点”不同）。在一些地区，未能控制血吸虫病会产生毁灭性后果，不仅持续存在高感染强度，而且“微妙”和严重的发病率仍然普遍存在。这些热点突出了需要重新审视严重发病及其机制的研究，这一主题在 PC 实施期间已不受关注。事实上，血吸虫病的局灶性和空间结构流行病学、其传播持久性和诱导的发病率，长期以来表明，在宿主-寄生虫界面发挥作用的基因-环境-相互作用至关重要。在这里，我们根据解释人类宿主中不同发病率的潜在寄生虫因素、宿主因素及其基因-环境相互作用的证据进行综述。然后，我们以乌干达阿尔贝蒂纳地区的曼氏血吸虫病为例，说明严重发病背后的因素以及目前在新的研究和临床试验方案（FibroScHot）中进行的未来研究的途径和方向。
