Priority knowledge gaps for schistosomiasis research and development in the World Health Organization Africa Region

Abstract

Schistosomiasis, also known as bilharzia, is a widespread neglected tropical disease (NTD) in Africa, with more significant research and development (R&D) challenges and gaps compared to other preventive chemotherapy NTDs (PC-NTDs) like onchocerciasis, lymphatic filariasis, and trachoma. In response to this challenge, some global initiatives have advocated for bridging this gap, focusing on coordinated engagement with research donors. In this opinion article we highlight key R&D priorities for combating schistosomiasis in the WHO Africa region. These include defining morbidity indicators, expanding prevention, and developing innovative diagnostics, treatments, and public health strategies like test-and-treat. We emphasize integrating efforts with broader health campaigns, assessing zoonotic transmission through One Health, and using environmental surveillance tools like xenomonitoring and eDNA. We stress the need to study climate and environmental impacts on transmission, zoonotic transmission, schistosome hybridization, and snail ecology, advancing snail control, and developing vaccines, while calling for new treatments beyond praziquantel, addressing drug resistance, and improving access for children and remote populations. Further, operational research should refine hotspot interventions, enhance water, sanitation and hygiene integration, and address socio-cultural barriers. Lastly, sustainable funding and global collaboration are vital to achieve 2030 NTD Roadmap goals.

Graphical Abstract

Background

Schistosomiasis also known as bilharzia, caused by parasitic trematodes of the genus Schistosoma is one of the most widespread neglected tropical diseases (NTDs) in the African region, but also significantly one of those lagging behind in terms research and development (R&D), compared to other NTDs prioritized under the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN), including onchocerciasis, lymphatic filariasis, and trachoma [1]. Various global collaborative initiatives have been established in the past decade to propel R&D for NTDs including schistosomiasis. These include the formation of the ESPEN https://espen.afro.who.int/, the NTD NGO Network (NNN)—https://www.ntd-ngonetwork.org/ to coordinate the work of organizations engaged in the fight against NTDs, and other NTD-related alliances; and the establishment of the Coalition for Operational Research on NTDs https://www.cor-ntd.org/ as a leading scientific body focused on NTDs which is contributing to funding research in resource limited settings. In the Africa region the African Research Network for Neglected Tropical Diseases (ARNTD) https://arntd.org/ has been building capacity among young and mid-career researchers. Notably, it is the formation of the Global Schistosomiasis Alliance (GSA) https://www.eliminateschisto.org/ which has helped bring a specific focus to schistosomiasis thus closing the gap between it and other NTDs in terms of R&D.

Building on previous advocacy on schistosomiasis control and research gaps [2,3,4,5], The NTD Roadmap 2030 identifies several research gaps and needs for schistosomiasis, emphasizing the importance of comprehensive strategies to meet 2030 targets [6]. Key actions include defining morbidity indicators, extending preventive chemotherapy (PC) to all population groups in need, implementing targeted snail control, and developing new diagnostic tests and interventions, including alternatives to praziquantel [6]. The roadmap highlights the need for improved scientific understanding, particularly regarding transmission pathways, specific snail species, zoonotic reservoirs, and the spectrum of morbidities associated with the disease. It calls for developing standardized, sensitive diagnostics for various settings and uses, including surveillance and clinical use, and creating a biorepository for diagnostic development. Additionally, the roadmap suggests operational research to refine current strategies, including micro-targeting of interventions, exploring new medicines, and promoting WASH and behavioural change interventions. The Roadmap 2030 also underscores the importance of cross-sectoral governance and sufficient resource allocation, including domestic financing and health care capacity strengthening for R&D in this area. Addressing these knowledge gaps requires global solidarity and coordinated efforts among researchers, communities, public health professionals, governments, funders and international organizations. Increased funding, enhanced surveillance, and innovative research are essential to fill these gaps and move closer to the control and eventual elimination of schistosomiasis in Africa.

Responding to the NTD roadmap call [6], there is currently increased research on schistosomiasis in the WHO Africa Region. At the end of 2023, published research work from the Africa region on preventive chemotherapy [7,8,9,10,11] focused on efficacy of praziquantel [the drug of choice for schistosomiasis[7], evaluation of within-country schistosomiasis strategies [8], strategies to improve treatment compliance in the context of the new WHO schistosomiasis guidelines 2022 [9,10,11], and challenges and perspectives on implementing the new schistosomiasis guidelines [12, 13]. Much research focused on diagnostics [14,15,16,17,18], finding new serologic methods [15,16,17], alternative diagnostics to Kato-Katz and urine microscopy [18, 19], use of deep learning systems and artificial intelligence to enhance diagnostic tools [20,21,22] and diagnostics for female genital schistosomiasis (FGS) [17]. Reported mapping surveys [23,24,25] focused on precision mapping for community-level data and identification of transmission in new areas [24,25,26]. Much research was conducted on schistosomiasis morbidity including FGS [27,28,29,30,31,32,33,34,35,36,37,38,39,40], with most of the work focusing on diagnostics and prevalence surveys for FGS [27,28,29,30,31,32,33,34,35,36], integration of FGS into health systems [34,35,36,37], co-morbidities [38,39,40] and awareness of FGS among health care professionals [39, 40] and patients [41]. Deeper appreciation of the complexity of schistosomiasis transmission at the nexus of humans, animals and environment contributed to increased research on the One Health approach for schistosomiasis in 2023 [41]. There was continued research into intermediate snail hosts [42, 43]. With a new paediatric formulation at the verge of unveiling by the Paediatric Praziquantel Consortium, research into reaching paediatric populations [44] will provide valuable data towards implementation of treatments in this population. This opinion piece synthesizes recent evidence to identify and highlight the critical R&D gaps that must be addressed to advance schistosomiasis control and elimination efforts in the WHO African Region, to inform future strategies and prioritize areas for action to accelerate progress toward the 2030 targets.

Main text

Methodological approach

Leading schistosomiasis researchers in the WHO Africa Region reviewed the progress made by national schistosomiasis programmes in the World Health Organization Africa Region, as presented in the ESPEN portal, based on data shared by the national programmes with WHO, and published publicly on the portal (https://espen.afro.who.int). While some actions and tools are required throughout the control and elimination programme, different phases of the control and elimination programme require specific actions and tools. Thus, knowledge gaps were identified based on the programme phase of WHO AFRO countries as presented in the WHO schistosomiasis and soil-transmitted helminthiasis (STH) monitoring and evaluation (M&E) framework [45, 46] (Fig. 1). We classified the countries (Table 1) according to the programme phases outlined in Fig. 1. This progress was based on implementation of preventive chemotherapy as follows: nascent programmes as those with less than 3 annual PC rounds; maturing programmes as those that have conducted between 3–5 annual PC rounds with sub-optimal coverage; and mature programmes as those that have consistently conducted more than 5 annual PC rounds, with or without impact assessment. For the next categories, countries under elimination as public health problem (EPHP) are those that have attained elimination of schistosomiasis as a public health problem at national level as defined in the WHO NTD roadmap 2021–2030 (currently defined as < 1% proportion of heavy intensity infections), while those in sustaining EPHP phase are countries that have been validated for EPHP status by the WHO. Elimination of transmission is achieved when transmission of infections is fully interrupted in humans and other zoonotic reservoirs, defined as “Zero autochthonous incidence in humans for at least 5 consecutive years” and is followed by the post elimination surveillance phase. Despite ongoing control efforts and R&D progress, schistosomiasis remains a significant public health issue in many parts of Africa. We then considered significant knowledge gaps in each programme phase (Table 2) and in cross-cutting areas (Table 3).

Fig. 1

Phases of schistosomiasis control and elimination programmes. *To be conducted in selected areas (with suspected high transmission of schistosomiasis infection) after at least 2 years of PC, however, there is need to clearly define hotspots currently defined as “an area that demonstrates a < 1/3 reduction in prevalence of Schistosoma spp. infection between an initial survey (with prevalence ≥ 10%) and a follow up survey conducted after at least 2 years of preventive chemotherapy with effective (≥ 75%) treatment coverage” [42]. **After a country has been validated for EPHP, post-validation surveillance is recommended. However, surveillance is also recommended in any implementation unit that has reduced the frequency of PC distribution or achieved the EPHP target. EPHP elimination as public health problem, PC preventive chemotherapy

Table 1 Programmatic phases for countries in the WHO Africa Region. EPHP elimination of schistosomiasis as a public health problem

Table 2 Overview of knowledge gaps in the Africa region categorized by control programme status. WASH water, sanitation, and hygiene

Table 3 Overview of knowledge gaps in the Africa region categorized by cross-cutting areas. WASH water, sanitation, and hygiene, FGS female genital schistosomiasis; NTD neglected tropical diseases

Nascent programmes

Key knowledge gaps during this phase are the need for identifying potential transmission sites, disease distribution and prevalence data, and co-endemicity with other diseases for which integration of interventions is feasible. Precise, up-to-date data on the distribution and prevalence of schistosomiasis are lacking in many areas in the WHO Africa Region. This gap hinders effective targeting of control measures and resource allocation, especially in nascent programmes such as those of South Africa and Equatorial Guinea, the two countries in the WHO Africa Region currently classified in this category. Innovative approaches towards filling disease prevalence gaps are needed to enable progress. While development and deployment of rapid, sensitive, and specific diagnostic tools for both acute and chronic schistosomiasis are needed at all phases of the programme, having these in place for starting programmes sets an appreciable baseline dataset for appropriate policy decisions on timely treatment, and accurate assessment of control programmes in the continued monitoring and evaluation framework.

Maturing programmes

For countries falling in this category, MDA interventions are started but not up to scale or are irregular. These countries include Angola, Botswana, Central African Republic, Chad, Congo, Gabon, Guinea-Bissau, Nigeria, South Sudan, and Zambia. While the countries are at different levels of maturing their programmes, operational research is needed in these countries to inform scale up and to optimize treatment coverage.

Mature programmes

Neglected tropical diseases programmes in these countries have fully scaled up mass drug administration (MDA) to all endemic areas. Reaching populations in hard-to-reach areas is a priority, as well as ensuring high treatment coverage, and managing morbidity in adults. This involves extending preventive chemotherapy to all populations in need, ensuring access to essential NTD medicines, and implementing targeted snail control with updated guidelines. It also includes the continuation of micro-mapping and targeting to identify and treat affected populations accurately. Programmatic knowledge gaps in this phase include morbidity surveys, identifying morbidity markers and innovating for morbidity management; as well as social science studies on reaching hard to reach populations and understanding reasons for low coverage and existence of persistent hotspots (Fig. 1). There is a need for more research on the integration of schistosomiasis control with other NTD control programs and broader public health interventions to enhance efficiency and outcomes as elimination programmes mature, to facilitate their mainstreaming into routing health services. Furthermore, drug efficacy and resistance become a major concern with widespread annual MDAs. Continued monitoring of the efficacy of praziquantel, the primary drug used for schistosomiasis treatment, is necessary, particularly in the face of potential drug resistance. There is a need for research on new therapeutic agents and treatment strategies including strategies to increase therapeutic coverage to all population groups in need, and access to new paediatric formulations of praziquantel. In addition, once the primary objective of scaling up treatments to all in need is reached, residual disease morbidity and management becomes a priority. Greater understanding of the long-term health impacts of chronic schistosomiasis, including its contribution to anaemia, malnutrition, subfertility, cancer and cognitive impairment, and establishing a clear and measurable indicator to effectively assess the morbidity caused by schistosomiasis, is needed, including the gap in knowledge regarding the most effective strategies for managing and reducing morbidity. The impact of co-infections such as between schistosomiasis and malaria, HIV/AIDS, and helminth infections, are not well understood, even though such co-infections can influence disease severity, immune responses, and the effectiveness of treatment.

Further research is needed to come up with strategies for non-responding areas and hotspots. There is a need to understand contributing factors such as; high baseline prevalence and/or intensity [47], possible reduction in drug effectiveness [48], low treatment coverage (< 75%), environmental factors [49], high abundance of intermediate snail hosts [50, 51], low participation in MDA [52], reservoir hosts [53, 54], human behaviour [55, 56], inadequate water, sanitation, and hygiene [WASH] infrastructures and access [57, 58], and other intrinsic drivers such as human [59] and parasite genetics [60, 61].

Elimination as a Public Health Problem Phase and sustaining EPHP status

Programmes that have conducted more than five years of high coverage annual MDA (> 75% community coverage) should conduct impact assessments to set a new baseline and consider adjusting treatment strategies if needed. Better understanding and deeper insights into how human behaviour, cultural practices, and how socioeconomic factors influence exposure to infection and disease outcomes is crucial for designing culturally sensitive and effective intervention strategies. Assessment of WASH coverage and its promotion as well as water resource development is critical during this phase.

Elimination of transmission and post-elimination surveillance

To achieve elimination of transmission, snail control in persistent hotspots and high transmission areas as well as elimination of zoonotic schistosomiasis is required. In this regard it is important to study hybridization and efficacy of praziquantel on such hybrids. Schistosomiasis transmission is intricately linked to specific freshwater snails that serve as intermediate hosts for the parasites. There is a need for more detailed understanding of snail ecology, including factors that influence snail distribution, population dynamics, and interactions with the schistosome parasites to inform improved, targeted control approaches. During this phase the effects of environmental changes, such as climate change, water resource development [e.g., dams, irrigation], and land use changes, on schistosomiasis transmission should be monitored and their effects mitigated. These changes can alter habitats and the ecology of snail populations, potentially affecting disease transmission patterns, and research into these factors is needed as is the development of surveillance methodologies to monitor for the emergence and/or reemergence of schistosomiasis in previously clear areas. There is a need to develop and launch safer, cheaper, and effective snail control technology, mitigating environmental impacts. Furthermore, understanding zoonotic transmission and interventions to address zoonotic reservoirs can help achieve elimination of transmission. Another area that requires attention at this phase is vaccine development for both humans and animals to prevent reinfection and sustain elimination of transmission [62]. Despite significant research efforts over the decades including promising candidate vaccines such as rSh28GST (aka Bilhvax), Sm‐TSP‐2 (S. mansoni tetraspanin 2), Sm‐p80 (S. mansoni calpain), and Sm14 [63, 64], and radiation‐attenuated [RA] cercariae vaccine [65, 66], there is currently no vaccine available for schistosomiasis. Mathematical modelling shows that even a partly protective vaccine would play a role in reducing schistosome infections and hinder transmission [67]. Continued research to identify viable vaccine targets and develop effective vaccines is a critical knowledge gap.

Cross-cutting scientific advances and research gaps

Preventing chemotherapy

The development of chemotherapy for schistosomiasis has faced significant challenges. Early treatments like arsenic-containing salvarsan and antimony potassium tartrate were highly toxic, and while praziquantel, introduced in 1982, is effective against adult schistosomes, it does not target younger forms and raises concerns about resistance with repeated mass treatments. The slow development of new drugs and lack of combination therapies limit options. Preventive chemotherapy coverage remains inadequate due to reinfections from untreated reservoirs and reliance on drug donations, which pose sustainability challenges. Urgent research is needed to address possible emergence of resistance, improve surveillance, and develop alternative medicines. Efforts should include evaluating preventive chemotherapy for all populations, refining access and distribution models, implementing targeted snail control, and addressing.

Schistosomiasis diagnostics

Schistosomiasis diagnostics face significant challenges due to inadequate tools with low sensitivity and specificity. The WHO NTD roadmap highlights the need for standardized point-of-care diagnostics. Diagnosing S. haematobium is hindered by the lack of a suitable animal model to correlate egg excretion with worm burden, while S. mansoni and S. japonicum diagnostics struggle with detecting light infections using Kato-Katz. Promising advancements include detecting glycoproteins and parasite DNA, but biomarker studies are needed for better targets. General challenges include reliance on surrogate measures, outdated calibration data, and biological factors affecting egg excretion. Improved, sensitive, and practical diagnostic methods are essential for better disease detection and control.

Urogenital schistosomiasis and morbidity

Significant progress has been made in understanding and managing urogenital schistosomiasis, particularly FGS, caused mainly by S. haematobium. FGS is characterized by egg deposition in the female genital tract, leading to symptoms like lesions, pain, bleeding, increased HIV risk, subfertility, and poor birth outcomes. Diagnosis lacks a "gold standard" and relies on identifying eggs in biopsies, with advances in polymerase chain reaction (PCR) testing and antigen detection showing promise [32, 68,69,70]. Praziquantel remains the primary treatment, with research ongoing into its efficacy, timing, and frequency specifically for FGS. Integrated care approaches combining treatment with reproductive health services and menstrual hygiene initiatives are critical [70,71,72]. Key research areas include raising awareness, developing scalable diagnostic and management guidelines, and understanding treatment effects on disease progression [73, 74]. The psychosocial aspects, including stigma and mental health impacts, require attention, alongside evaluations of FGS's association with HIV and its economic and health implications [74]. Male genital schistosomiasis (MGS) and its health impact also demand further study [75].

Schistosomiasis pathology

Research on schistosomiasis pathology faces significant gaps. Key areas include understanding historical disease impact, shifting transmission dynamics due to factors like population growth and irrigation, and the immunological mechanisms triggered by schistosome eggs in host tissues. More studies are needed on severe pathology in S. mansoni infections, genetic influences, and repeated exposures, as well as the pathogenesis of S. haematobium, including its role in bladder cancer, genital schistosomiasis, and viral susceptibility. Low-level infections and their role in transmission dynamics require attention. The urgency of eradication is heightened by the disease's severe health impacts, such as fibrosis hindering detection. The NTD Roadmap highlights the need for measurable indicators to assess schistosomiasis morbidity effectively.

One Health approach

The One Health approach, integrating human, animal, and environmental health, can advance schistosomiasis control by improving understanding of ecological factors affecting snail populations and environmental management practices like habitat modification and sanitation. Integrated surveillance systems for humans and snails are needed for more effective interventions. However, critical gaps remain in understanding zoonotic transmission, wildlife reservoirs, and the impact of human activities like agriculture and dam construction on disease prevalence. Climate change's influence on transmission dynamics also requires further study. Multidisciplinary collaboration across epidemiology, veterinary science, environmental science, and public health is essential to address these gaps and strengthen One Health strategies for schistosomiasis control.

Treating paediatric populations

Recent advancements in paediatric schistosomiasis treatment include the development of a child-friendly formulation of praziquantel (arpraziquantel, arPZQ), addressing issues with the original large, bitter tablets [75]. This breakthrough, led by the Pediatric Praziquantel Consortium, offers smaller, palatable tablets for easier ingestion. Despite approval by the European Medicines Agency, research is needed to implement arPZQ in endemic regions effectively. Additionally, gaps remain in understanding schistosomiasis's long-term effects on children's growth, cognitive development, fertility, and interactions with malnutrition and other childhood conditions, which may complicate recovery.

Snail intermediate host

Research on schistosome species and their snail hosts highlights key gaps. The WHO schistosomiasis guidelines 2022 [48] support environmentally friendly snail control, yet improved, cost-effective technologies are needed. Africa hosts five human-infecting species, including S. mansoni, S. haematobium, S. rodhaini, S. intercalatum, S. guineensis [61]. Molecular studies reveal hybridization between human and animal schistosomes, influencing adaptation and evolution, with notable cases in East and West Africa [76,77,78,79,80]. Hybrids between S. haematobium and S. bovis in Corsica raise concerns about wildlife reservoirs. DNA barcoding has enhanced snail classification, but compatibility mechanisms between schistosomes and snails remain unclear. Progress in using plant-based molluscicides, like Phytolacca dodecandra, offers promise [80]. Further, technologies like eDNA for detecting snail habitats and manipulating snail microbiomes should be explored. Understanding snail immune responses and miracidia-host interactions also remains critical [81,82,83,84].

Operational research to improve effective WASH and behaviour interventions for prevention

Many African countries affected by schistosomiasis are still far from meeting WASH targets. Despite infrastructure improvements, some community members will continue to use natural water sources. Focal snail control, along with health education and behaviour change, can help ensure safe water use with a clear understanding of the risks. Endemic areas may need safe washing facilities at key water contact points. Operational research is essential to guide WASH and behaviour change interventions, ensuring they are effective, sustainable, and tailored to local contexts. This includes examining water treatment, sanitation, and safe water access, as well as testing community-led sanitation initiatives. Research should evaluate the cost-effectiveness of these interventions, the role of community engagement, and environmental factors in disease transmission. Additionally, studies should focus on the governance structures that support effective WASH, ensuring integration with broader health programs and achieving long-term disease prevention.

Impact of climate change on schistosomiasis

Addressing the impact of climate change on schistosomiasis requires a multifaceted research approach. This includes developing localized climate models to predict environmental changes affecting snail habitats and the Schistosoma lifecycle. Research must investigate snail vector ecology, including how water condition changes influence parasite hosting. For example, while laboratory studies show heat pulses can make resistant Biomphalaria glabrata susceptible to S. mansoni [81], recent findings reveal minimal heat shock effects on infection prevalence in B. glabrata and B. sudanica and no impact on infection intensity [84]. Even small effects, however, can significantly influence transmission dynamics and public health [79]. Rising temperatures may enable transmission in new areas beyond current control programs, threatening the 2021–2030 Roadmap goals. Research should examine Schistosoma adaptation and range expansion while assessing human behaviour and socioeconomic shifts on transmission. Integrated surveillance, including environmental DNA (eDNA) technology, is critical for monitoring and predicting outbreaks. An interdisciplinary approach blending climatology, ecology, and public health is essential to evaluate and adapt control measures effectively under changing climate conditions.

Modelling for decision making in schistosomiasis

Current models [85, 86] for schistosomiasis elimination have gaps in understanding transmission dynamics, infection heterogeneity, and the impact of climate change. Models should incorporate WASH interventions, assess drug resistance risks and treatment efficacy, and evaluate the disease's socio-economic effects. Effective elimination programs rely on health system capacity, vector control, co-infection management, and robust surveillance systems for outbreak detection and response. To optimize strategies, models must simulate surveillance and response while integrating environmental, biological, socio-economic, and health system factors. Addressing these modelling gaps is critical for informing comprehensive approaches to schistosomiasis elimination.

Ensuring sufficient resources for schistosomiasis R&D

Investment in research and development is essential to advance understanding, develop innovative strategies, and address challenges like the threat of drug resistance in schistosomiasis control. Advocacy with policymakers, donors, and the private sector, alongside demonstrating the socioeconomic benefits of elimination, can drive critical support. Cross-sectoral governance and sustainable funding are vital, requiring collaboration across WASH, agriculture, environmental management, and animal health to address the parasite's lifecycle. Significant gaps remain in fostering collaboration, aligning priorities, and designing effective, localized interventions. Coordinated efforts in cross sectoral governance and resource mobilization will be crucial for achieving sustainable schistosomiasis elimination.

Conclusions

The fight against schistosomiasis in the WHO Africa Region urgently requires addressing significant R&D gaps and operational challenges. Key knowledge gaps include the need for innovative diagnostics to replace low-sensitivity methods, better morbidity indicators, and new treatment strategies to improve access and address the threat of drug resistance. Operational research is vital to refine interventions in non-responsive areas, optimize WASH integration, and address behavioural and socio-economic barriers to treatment. Critical gaps also exist in understanding zoonotic transmission, schistosome species hybridization, and snail host ecology. Additionally, there is limited evidence on how climate change, environmental modifications, and cultural practices influence transmission in fast changing ecological settings. The lack of robust cross-sectoral governance frameworks and sustainable financing further hampers coordinated efforts across WASH, animal health, agriculture, and environmental management. A concerted effort by researchers, governments, funders, and international organizations is needed to prioritize and invest in these areas. Strengthened collaboration and resource allocation are essential to meet the 2030 NTD Roadmap targets, eliminate schistosomiasis as a public health threat, and achieve sustainable disease transmission interruption.