Amadou Garba

Schistosomes experience many populational selection pressures but their sexual and reproductive biology are unusually dynamic and particularly special. If given sufficient opportunity, certain schistosome species can hybridize and give rise to progeny that have either abrupt genomic changes or exhibit more gradual genetic introgressions. The importance and impact of such short- and long-term dynamics were discussed and debated in February 2025 at The Royal Society, with the 12 resultant papers elaborated upon here. Schistosomes were discovered just under 175 years ago and continue to attract global attention, being interlinked in several dimensions of the Sustainable Development Goals. Adult schistosomes are dioecious helminths and parasitize a wide range of mammals; hundreds of millions of people, and innumerable livestock, have schistosomiasis. This disease raises their medical and veterinary importance, notwithstanding their detrimental economic impact. Once their lifecycle was elucidated, involving certain freshwater snail species, public health interventions could be waged. Attack points were developed, with health education and safe water hygiene applied, sometimes with local snail control, but effective constraint was only achieved once praziquantel, a relatively low-cost anthelminthic medicine, was procured then administered at scale. As praziquantel is active against adult worms alone, protective effects are short-term and retreatment is required. This article is part of the Science+ meeting issue ‘Parasite evolution and impact in action: exploring the importance and control of hybrid schistosomes’.

WHO promotes the implementation of a comprehensive strategy to control and eliminate schistosomiasis through preventive chemotherapy, snail control, clean water supply, improved sanitation, behaviour change interventions, and environmental management. The transmission of schistosomiasis involves infected definitive hosts (humans or animals) excreting eggs that hatch (miracidia), which infect freshwater snail vectors (also referred to as intermediate snail hosts) living in marshlands, ponds, lakes, rivers, or irrigation canals. Infective larvae (cercariae) develop within the snail, which, when released, may infect humans and/or animals in contact with the water. Snail control aims to interrupt the transmission cycle of the disease by removing the vector snails and, by so doing, indirectly improves the impact of the preventive chemotherapy by reducing reinfection. Snail control was, for many years, the only strategy for the prevention of schistosomiasis before preventive chemotherapy became the primary intervention. Snails can be controlled through various methods: environmental control, biological control, and chemical control. The chemical control of snails has proven to be the most effective method to interrupt the transmission of schistosomiasis. The current review aims to describe the vector snails of human schistosomiasis, present the chemicals and strategies for the control of snails, the challenges with the implementation, and the future needs. Snail control can play a key role in reducing schistosomiasis transmission and, thus, complements other interventions for disease control. There is a need to develop new molluscicide products or new formulations and methods of applications for existing molluscicides that would target snail vectors more specifically.

Female genital schistosomiasis (FGS) is a complication of Schistosoma haematobium infection, and imposes a health burden whose magnitude is not fully explored. It is estimated that up to 56 million women in sub-Saharan Africa have FGS, and almost 20 million more cases will occur in the next decade unless infected girls are treated. Schistosomiasis is reported throughout the year in South Africa in areas known to be endemic, but there is no control programme. We analyze five actions for both a better understanding of the burden of FGS and reducing its prevalence in Africa, namely: (1) schistosomiasis prevention by establishing a formal control programme and increasing access to treatment, (2) introducing FGS screening, (3) providing knowledge to health care workers and communities, (4) vector control, and (5) water, sanitation, and hygiene. Schistosomiasis is focal in South Africa, with most localities moderately affected (prevalence between 10% and 50%), and some pockets that are high risk (more than 50% prevalence). However, in order to progress towards elimination, the five actions are yet to be implemented in addition to the current (and only) control strategy of case-by-case treatment. The main challenge that South Africa faces is a lack of access to WHO-accredited donated medication for mass drug administration. The establishment of a formal and funded programme would address these issues and begin the implementation of the recommended actions.

Hybridization of infectious agents is a major emerging public and veterinary health concern at the interface of evolution, epidemiology, and control. Whilst evidence of the extent of hybridization amongst parasites is increasing, their impact on morbidity remains largely unknown. This may be predicted to be particularly pertinent where parasites of animals with contrasting pathogenicity viably hybridize with human parasites. Recent research has revealed that viable zoonotic hybrids between human urogenital Schistosoma haematobium with intestinal Schistosoma species of livestock, notably Schistosoma bovis, can be highly prevalent across Africa and beyond. Examining human populations in Senegal, we found increased hepatic but decreased urogenital morbidity, and reduced improvement following treatment with praziquantel, in those infected with zoonotic hybrids compared to non-hybrids. Our results have implications for effective monitoring and evaluation of control programmes, and demonstrate for the first time the potential impact of parasite hybridizations on host morbidity.

Background Tests for diagnosing schistosomiasis in areas where prevalence is low due to control programme of the disease should be suffiently sensitive to detect the residual disease. If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use. Objectives To compare sensitivity and specificity of new tests, especially rapid diagnostic tests (RDTs), with regard to a certain reference test. Methods We searched the electronic databases Pubmed, EMBASE, the Cochrane Library and LILACS up to February 2021. Furthermore we searched results from the previous meta-analyses. We included studies that used microscopy as the reference standard: for S. haematobium, microscopy of urine prepared by filtration, centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool by Kato-Katz thick smear. Two review authors independently extracted data, assessed quality of the data using QUADAS-2, and performed meta-analysis where appropriate. Grading of evidence was done with the GRADE methodology by using GradePro. Using the variability of test thresholds, we used a bayesian bivariate random-effects summary receiver operating characteristic model for all eligible tests. We investigated heterogeneity, and carried out sensitivity analyses where possible. Results for sensitivity and specificity are presented as percentages with 95% confidence intervals (CI). Results The review gathered 203 articles stating a diagnostic test for the diagnosis of S. haematobium and S. mansoni out of which 114 entered the analyses. Microscopy of Urine filtration or Kato-Katz smears were used as the reference standard. Compared with Kato-Katz smears, AWE-SEA ELISA (Se=94%; Sp=64%) is comparable to CCA1 (Se=87%; Sp=60%). IgG ELISA (Se=93%; Sp=68%) has also a very good ability to detect true positive as well as CAA cassette (Se=73%; Sp=68%). For S. haematobium, proteinuria (Se=59%; Sp=83%) and haematuria (Se=74%; Sp=87%) reagent strips showed reasonably high specificities with a considerably better sensitivity for the haematuria test. There are interesting promising new diagnostic tests that were tested in field studies. However prevalences of the locations where these studies took place are variable and there are no specific study with a high number of patients in areas with low level of schistosomiasis infection.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries. To enhance relevance for routine practice, the MDA in these studies was coordinated by or closely aligned with national neglected tropical disease (NTD) control programs. The study protocol set minimum targets of at least 90% for coverage among children enrolled in schools and 75% for all school-age children. Over the 4 years of intervention, an estimated 3.5 million treatments were administered to study communities. By year 4, the median village coverage was at or above targets in all studies except that in Mozambique. However, there was often a wide variation behind these summary statistics, and all studies had several villages with very low or high coverage. In studies where coverage was estimated by comparing the number of people treated with the number eligible for treatment, denominator estimation was often problematic. The SCORE experiences in conducting these studies provide lessons for future efforts that attempt to implement strong research designs in real-world contexts. They also have potential applicability to country MDA campaigns against schistosomiasis and other NTDs, most of which are conducted with less logistical and financial support than was available for the SCORE study efforts.

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation–funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local Schistosoma infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed.

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 . AUTHOR SUMMARY: It has been argued that drug resistance is unlikely to spread rapidly in helminth parasites infecting humans. This is based, at least in part, on the premise that resistance mutations are rare or absent within populations prior to treatment, and take a long time to reach appreciable frequencies because helminth parasite generation time is long. This argument is critically dependent on the starting frequency of resistance alleles – if high levels of “standing variation” for resistance are present prior to deployment of treatment, resistance may spread rapidly. We examined frequencies of oxamniquine resistance alleles present in Schistosoma mansoni from Africa and the Middle East where oxamniquine has seen minimal use. We found that oxamniquine resistance alleles are widespread in the Old World, ranging from 4.29% in the Middle East to 14.91% in East African parasite populations. Furthermore, we show that resistance alleles from West African and the Caribbean schistosomes share a common origin, suggesting that these alleles travelled to the New World with S. mansoni during the transatlantic slave trade. Together, these results demonstrate extensive standing variation for oxamniquine resistance. Our results have important implications for both drug treatment policies and drug development efforts, and demonstrate the power of molecular surveillance approaches for guiding helminth control.

Intestinal schistosomiasis due to Schistosoma mansoni was first reported in Oman in 1979. We describe the trend in parasitological and serological prevalence of human infection with S. mansoni in the endemic area over the period 1982–2014, and the compliance of data generated by the national monitoring and evaluation system with schistosomiasis elimination criteria set by the Ministry of Health of Oman. Parasitological and serological assessments were carried out on population (mainly children) living in the area at risk for schistosomiasis in Dhofar, the country’s only endemic Governorate, for a period of over 30 years. Kato-Katz thick smear and Indirect Haemagglutination Assay were the techniques employed. Data indicate a progressive decline in prevalence of S. mansoni throughout the 1980s and the 1990s, a recrudescence in the early 2000s, and a more marked decrease following the implementation of six rounds of mass treatment with praziquantel from 2007 to 2013. Latest parasitological prevalence (2011) was 0%, while latest serological prevalence (2014) was 0.11%. Transmission of schistosomiasis has reached very low levels in Oman. Elimination criteria established by the Ministry of Health of Oman (parasitological prevalence ≤ 1% and serological prevalence ≤ 5%) have been met since 2008. Further investigations are required to assess whether interruption of transmission has been achieved in some or all foci, in view of the establishment of a formal verification process under the auspices of WHO.