Intestinal and urinary schistosomiasis dynamics in sub-Saharan Africa

Schistosomiasis is a chronic infection by a digean trematode of the genus Schistosoma. More than 207 million people are infected with this parasite, of which 120 million are symptomatic. There are two main species infecting humans in sub-Saharan Africa: Schistosoma haematobium and S. mansoni, both occur in areas with similar socio-economic and environmental conditions and often have matching distribution patterns. The principle aims of the research presented in this thesis were to further our understanding of schistosome population genetics, associated human host morbidity and chemotherapeutic treatment of schistosomes in relation to mixed species infections. Structured sampling of parasites and/or host traits from school-aged children at baseline and post Mass Drug Administration (MDA) in Niger and Kenya were performed. The results presented provided evidence for S. haematobium - S. mansoni interactions and their impact on the human host and on the parasite population. In Kenya coinfections had lower S. haematobium related morbidity relative to single S. haematobium infections pre and post MDA. Additionally parasite infra-populations from coinfected children had higher genetic diversity levels compared to single infected children in mixed infection foci. In Niger, an impact of MDA on the population genetics of S. mansoni was detected in one mixed infection village, characterised as a noticeable bottleneck effect, but not in the other. There was no apparent impact of MDA on the population genetics of S. haematobium. Conversely, in Kenya, a significant impact of MDA on both species was detected, with a bottleneck effect occurring on the S. haematobium population and conversely, an increase in genetic diversity in the S. mansoni population. The results of this thesis are discussed in terms of their implications on schistosome epidemiology and evolution, and in relation to the control of schistosomiasis in sub-Saharan Africa

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial.

Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0-19.7%) and 2.7% (range: 0-26.5%) in Unguja, and 8.9% (range: 0-31.8%) and 5.5% (range: 0-23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03-2.03). Decreasing adult age (OR: 1.04; CI: 1.02-1.06), being born in Pemba (OR: 1.48; CI: 1.02-2.13) or Tanzania (OR: 2.36; CI: 1.16-4.78), and use of freshwater (OR: 2.15; CI: 1.53-3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved

Schistosomiasis and water resources development in Africa: a scoping review and multi-case evaluation of associated snail control

Background Water resources development (WRD), specifically infrastructural man-made water bodies such as dams and irrigation schemes, are built to improve water supply, provide energy, and enhance food security. However, dams and irrigation schemes may lead to a dramatic increase in the prevalence of schistosomiasis. Methodology/Principal findings We conducted a scoping review of WRD impacts on schistosomiasis transmission risk in Africa using electronic databases including Scopus, Web of Science, and grey literature. From 1483 retrieved records, we assessed 186 full-text papers and identified 122 articles covering 54 dams and irrigation schemes in 32 African countries. We found that, although the relationship between WRD and schistosomiasis transmission risk is well-documented in the scientific literature, the vast majority of the approximately 1,600 medium- to large-sized dams currently operating in endemic regions of Africa lack before-and-after prevalence data necessary to evaluate their actual impact on schistosomiasis transmission. Our analysis revealed that rigorous epidemiological data to assess WRD’s effects exist for only 11 dams across 9 countries. Additionally, only a limited number of studies provided information on schistosomiasis control methods, surveillance, or monitoring for WRD. Few countries have implemented engineering and biological snail control measures, some of which have proven effective, enabling us to identify successful interventions employed at various stages of the WRD lifecycle. Lastly, to assess these measures in detail, we selected case studies from Africa that illustrate the success and challenges of schistosomiasis control with regard to WRD, thus gaining insights of the global relevance of lessons learnt for the future development of water resources. Conclusions/Significance Our analysis highlighted that an integrated and coordinated approach is vital for the successful control of schistosomiasis transmission risk associated with Water Resources Development. We provide key recommendations which could be adopted by the Continental Africa Water Investment Programme (AIP) with the ultimate goal of decreasing prevalence and moving towards elimination.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) Impact Acceleration Award block grant allocation to Cranfield University (grant # EP/X525534/1 to MNS).Belmont Collaborative Forum on Climate, Environment and Health; NSF grant # 2522282, NSF grant #DEB – 2011179)PLOS Neglected Tropical Disease

The impact of single versus mixed schistosome species infections on liver, spleen and bladder morbidity within Malian children pre- and post-praziquantel treatment

Abstract Background: In the developing world co-infections and polyparasitism within humans appear to be the rule rather than the exception, be it any combination of inter-specific and/or inter- and intra-Genera mixed infections. Mixed infections might generate synergistic or antagonistic interactions and thereby clinically affect individuals and/or impact parasite epidemiology. Methods: The current study uniquely assesses both Schistosoma mansoni- and Schistosoma haematobium-related morbidity of the liver and the bladder as assessed by ultrasound as well as spleen and liver morbidity through clinical exams. The impact of praziquantel (PZQ) treatment on such potential inter-specific schistosome interactions and resulting morbidity using uniquely detailed longitudinal data (pre- and one year post-PZQ treatment) arising from the National Schistosomiasis Control Program in three areas of Mali: Ségou, Koulikoro and Bamako, is also evaluated. At baseline, data were collected from up to 2196 children (aged 7-14 years), 844 of which were infected with S. haematobium only, 124 with S. mansoni only and 477 with both. Follow-up data were collected from up to 1265 children. Results: Results suggested lower liver morbidity in mixed compared to single S. mansoni infections and higher bladder morbidity in mixed compared to single S. haematobium infections. Single S. haematobium or S. mansoni infections were also associated with liver and spleen morbidity whilst only single S. haematobium infections were associated with bladder morbidity in these children (light S. haematobium infection OR: 4.3, p < 0.001 and heavy S. haematobium infection OR: 19, p < 0.001). PZQ treatment contributed to the regression of some of the forms of such morbidities. Conclusions: Whilst the precise biological mechanisms for these observations remain to be ascertained, the results illustrate the importance of considering mixed species infections in any analyses of parasite-induced morbidity, including that for the proposed Disability Adjusted Life Years (DALYs) revised estimates of schistosomiasis morbidity

A systematic literature review of schistosomiasis in urban and peri-urban settings.

BACKGROUND: Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and belongs to the neglected tropical diseases. The disease has been reported in 78 countries, with around 290.8 million people in need of treatment in 2018. Schistosomiasis is predominantly considered a rural disease with a subsequent focus of research and control activities in rural settings. Over the past decades, occurrence and even expansion of schistosomiasis foci in peri-urban and urban settings have increasingly been observed. Rural-urban migration in low- and middle-income countries and subsequent rapid and unplanned urbanization are thought to explain these observations. Fifty-five percent (55%) of the world population is already estimated to live in urban areas, with a projected increase to 68% by 2050. In light of rapid urbanization and the efforts to control morbidity and ultimately achieve elimination of schistosomiasis, it is important to deepen our understanding of the occurrence, prevalence, and transmission of schistosomiasis in urban and peri-urban settings. A systematic literature review looking at urban and peri-urban schistosomiasis was therefore carried out as a first step to address the research and mapping gap. METHODOLOGY: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic computer-aided literature review was carried out using PubMed, ScienceDirect, and the World Health Organization Database in November 2019, which was updated in March 2020. Only papers for which at least the abstract was available in English were used. Relevant publications were screened, duplicates were removed, guidelines for eligibility were applied, and eligible studies were reviewed. Studies looking at human Schistosoma infections, prevalence, and intensity of infection in urban and peri-urban settings were included as well as those focusing on the intermediate host snails. PRINCIPAL FINDINGS: A total of 248 publications met the inclusion criteria. The selected studies confirm that schistosomiasis is prevalent in peri-urban and urban areas in the countries assessed. Earlier studies report higher prevalence levels in urban settings compared to data extracted from more recent publications, yet the challenge of migration, rapid uncontrolled urbanization, and resulting poor living conditions highlight the potential for continuous or even newly established transmission to take place. CONCLUSIONS: The review indicates that schistosomiasis has long existed in urban and peri-urban areas and remains a public health problem. There is, however, a challenge of comparability of settings due to the lack of a clear definition of what constitutes urban and peri-urban. There is a pressing need for improved monitoring of schistosomiasis in urban communities and consideration of treatment strategies

Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa

Analyses of the population genetic structure of schistosomes under the “Schistosomiasis Consortium for Operational Research and Evaluation” (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent “biological hotspot” sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general

“Female Genital Schistosomiasis: Translational Challenges and Opportunities”: Outputs and actions from a consultative, collaborative and translational workshop.

Female genital schistosomiasis (FGS) is a chronic disease manifestation of the waterborne parasitic infection Schistosoma haematobium that affects up to 56 million women and girls, predominantly in sub-Saharan Africa. Starting from early childhood, this stigmatizing gynaecological condition is caused by the presence of Schistosoma eggs and associated toxins within the genital tract. Schistosoma haematobium typically causes debilitating urogenital symptoms, mostly as a consequence of inflammation, which includes bleeding, discharge and lower abdominal pelvic pain. Chronic complications of FGS include adverse sexual and reproductive health and rights outcomes such as infertility, ectopic pregnancy and miscarriage. FGS is associated with prevalent human immunodeficiency virus and may increase the susceptibility of women to high-risk human papillomavirus infection. Across SSA, and even in clinics outside endemic areas, the lack of awareness and available resources among both healthcare professionals and the public means FGS is underreported, misdiagnosed and inadequately treated. Several studies have highlighted research needs and priorities in FGS, including better training, accessible and accurate diagnostic tools, and treatment guidelines. On 6 September, 2024, LifeArc, the Global Schistosomiasis Alliance and partners from the BILGENSA Research Network (Genital Bilharzia in Southern Africa) convened a consultative, collaborative and translational workshop: ‘Female Genital Schistosomiasis: Translational Challenges and Opportunities’. Its ambition was to identify practical solutions that could address these research needs and drive appropriate actions towards progress in tackling FGS. Here, we present the outcomes of that workshop – a series of discrete translational actions to better galvanize the community and research funders

Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29–14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate OXA deployment. We conclude that standing variation for OXA resistance is widespread in S. mansoni

The first BILGENSA Research Network workshop in Zambia: identifying research priorities, challenges and needs in genital bilharzia in Southern Africa [version 1; peer review: 1 approved, 3 approved with reservations]

Female genital schistosomiasis (FGS) and male genital schistosomiasis (MGS) are gender-specific manifestations of urogenital schistosomiasis. Morbidity is a consequence of prolonged inflammation in the human genital tract caused by the entrapped eggs of the waterborne parasite, Schistosoma (S.) haematobium. Both diseases affect the sexual and reproductive health (SRH) of millions of people globally, especially in sub-Sahara Africa (SSA). Awareness and knowledge of these diseases is largely absent among affected communities and healthcare workers in endemic countries. Accurate burden of FGS and MGS disease estimates, single and combined, are absent, mostly due to the absence of standardized methods for individual or population-based screening and diagnosis. In addition, there are disparities in country-specific FGS and MGS knowledge, research and implementation approaches, and diagnosis and treatment. There are currently no WHO guidelines to inform practice. The BILGENSA (Genital Bilharzia in Southern Africa) Research Network aimed to create a collaborative multidisciplinary network to advance clinical research of FGS and MGS across Southern African endemic countries. The workshop was held in Lusaka, Zambia over two days in November 2022. Over 150 researchers and stakeholders from different schistosomiasis endemic settings attended. Attendees identified challenges and research priorities around FGS and MGS from their respective countries. Key research themes identified across settings included: 1) To increase the knowledge about the local burden of FGS and MGS; 2) To raise awareness among local communities and healthcare workers; 3) To develop effective and scalable guidelines for disease diagnosis and management; 4) To understand the effect of treatment interventions on disease progression, and 5) To integrate FGS and MGS within other existing sexual and reproductive health (SRH) services. In its first meeting, the BILGENSA Network set forth a common research agenda across S. haematobium endemic countries for the control of FGS and MGS