Stunting (low height-for-age > 2 s.d. below the WHO child growth standards median) is a key indicator of chronic malnutrition and is influenced by poor nutrition, infections, chronic inflammation and impaired gut health. In sub-Saharan Africa, stunting frequently occurs in regions where schistosomiasis is endemic. Our previous research in Zimbabwean preschool children (≤ 5 years) found that Schistosoma haematobium infection alone could account for up to one-third of stunting cases. Using epidemiological, gut microbiome and metabolomic analyses, we investigated how this parasitic infection contributes to poor growth. Infected children showed significantly altered gut microbiome profiles compared to uninfected peers, indicating potential microbiome disruption linked to disease and impaired development. Metabolomic profiling revealed that S. haematobium infection elevated energy- and purine-related metabolites, reflecting metabolic stress associated with malnutrition. Early treatment with praziquantel did not significantly alter the microbiome but did restore normal metabolic profiles, aligning with observed catch-up growth. Here, we synthesize findings from our studies and others to highlight opportunities for intervention and key research gaps, supporting the inclusion of praziquantel in early health programmes and integrated strategies combining treatment with nutrition. Further research, particularly longitudinal studies, is needed to confirm causality and optimize child health outcomes in endemic areas. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.

Disease epidemiology during the COVID-19 pandemic differed greatly across the globe. In contrast to early pandemic predictions, Africa recorded the fewest SARS-CoV-2 related hospitalizations and deaths. Hypotheses proposed to explain this paradox include underreporting, age demographics, climate, national mitigation strategies, lifestyle factors, pre-existing cross-reactive protection, and host genetic determinants. This traditional, narrative review evaluates these hypotheses investigated in the published literature, and highlights knowledge gaps which limit our understanding and obscure validation of potential explanations. It also discusses how responses to vaccines, the primary intervention sought to control infectious disease outbreaks, may vary both within the African population and across other continents. Potential explanations in the literature include pre-existing immunity, poor nutrition, immune modulating co-infections, comorbidities, microbiome composition, genetic polymorphisms, and demographic factors. Previous studies have shown that pre-existing (infection-derived) immunity or cross-reactive immune responses can augment vaccine-elicited positive responses and can protect against reinfection in a way similar to immunization. Conversely, there are also studies showing that prior immunity interferes with the efficacy of new vaccines through mechanisms like original antigenic sin and immune imprinting. Thus, there is need for more immunology studies to understand the relative contribution of pre-existing cross-reactive immune responses to the epidemiology of new pathogens. These studies are particularly essential to understand the differences between pandemic preparedness and population vulnerability, as well as to inform vaccine development and vaccine effectiveness monitoring studies. SARS-CoV-2 serves as an important case study to understand heterogeneity between and within populations in immune responses to both the pathogen and to vaccination. This understanding is crucial in informing vaccine research and development aimed at supporting the 100-day mission for when the next pandemic threat emerges.

Background: We set out to estimate the community-level exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Ghana. Methods: Phased seroprevalence studies of 2729 participants at selected locations across Ghana were conducted. Phase I (August 2020) sampled 1305 individuals at major markets/lorry stations, shopping malls, hospitals and research institutions involved in coronavirus disease 2019 (COVID-19) work. The study utilized a lateral flow rapid diagnostic test (RDT) which detected IgM and IgG antibodies against SARS-CoV-2 nucleocapsid protein. Results: During Phase I, 252/1305 (19%) tested positive for IgM or IgG or both. Exposure was significantly higher at markets/lorry stations (26.9%) compared to malls (9.4%), with 41–60-year group demonstrating highest seropositivity (27.2%). Exposure was higher in participants with no formal education (26.2%) than those with tertiary education (13.1%); and higher in informally employed workers (24.0%) than those in the formal sector (15.0%). Results from phases II and III, in October and December 2020 respectively, implied either reduced transmissions or loss of antibody expression in some participants. The Upper East region showed the lowest seropositivity (2%). Phase IV, in February 2021, showed doubled seropositivity in the upper income bracket (26.2%) since August 2020, reflective of Ghana’s second wave of symptomatic COVID-19 cases. This suggested that high transmission rates had overcome the initial socioeconomic stratification of exposure risk. Reflective of second wave hospitalisation trends, the 21-40 age group demonstrated modal seropositivity (24.9) in Phase IV whilst 40-60 years and 60+ previously demonstrated highest prevalence. Conclusions: Overall, the data indicates higher COVID-19 seroprevalence than officially acknowledged, likely implying a considerably lower-case fatality rate than the current national figure of 0.84%. The data also suggests that COVID-19 is predominantly asymptomatic COVID-19 in Ghana. The observed trends mimic clinical trends of infection and imply that the methodology used was appropriate.

Helminths have co-evolved with humans and developed sophisticated mechanisms to manipulate the host immune system, allowing them to persist for years. During chronic disease, helminths typically shift immune responses toward a Th2 profile-supporting antibody production and tissue repair-while suppressing Th1/Th17 responses that are crucial for combating viruses and intracellular pathogens. Additionally, they elevate regulatory T cells and anti-inflammatory cytokines such as IL-10 and TGF-β, dampening inflammation, compromising host immunity to other infections, and, in some cases, reducing vaccine efficacy. Further, both experimental and clinical studies have shown that anthelminthic treatment can reverse parasite host immunomodulation. However, there is evidence that helminth-induced immune changes may persist months after parasite clearance. With the widespread rollout of preventive chemotherapy via mass drug administration (MDA) across the continent, many African populations have now received at least one round of deworming treatment. This raises critical questions about the nature, persistence, and public health significance of anthelminthic treatment-related immunological shifts in endemic settings with repeated exposures. In Africa, which bears a disproportionate share of the global helminth burden, there is growing interest in how these factors shape immune responses. In this review, we summarise current knowledge and key research gaps regarding mechanisms that contribute to immune variation in helminth-endemic populations and the broader implications for disease control, vaccine response, and health policy in endemic settings.

BackgroundNeglected tropical diseases (NTDs) are a group of 21 diseases affecting approximately 1.5 billion people globally. Significant progress has been made in their control: by March 2024, 50 countries had eliminated at least one NTD, with 13 of these countries eliminating at least two. Togo achieved the highest milestone, having eliminated four. The eight NTDs eliminated in at least one country are Guinea worm disease, human African trypanosomiasis, lymphatic filariasis, onchocerciasis, rabies, trachoma, visceral leishmaniasis and yaws. We reviewed elimination efforts of these 50 countries to identify factors underlying their successes and failures to generate a blueprint to inform the acceleration of NTD elimination.Methodology/principal findingsWe conducted a review of published and grey literature and extracted and recorded data on various features of the elimination programmes, including the durations and organisers of elimination efforts, interventions, strategies including mainstreaming into other health services, partnerships involved, and details of historical failed control efforts. These data were synthesised to generate a blueprint for NTD elimination. Key features of successful NTD elimination included country ownership, dedicated elimination efforts, and use of a combination of strategies. Most elimination programmes targeted one NTD at a time, while fewer utilised integrated approaches. Elimination required at least two decades of sustained efforts and partnerships between the endemic country and international stakeholders. Failure in historical efforts was frequently a result of sociopolitical instability, insufficient resources, deprioritisation, lack of effective interventions, or lax implementation of interventions.Conclusions/significanceAccelerating NTD elimination requires sustained, intense, and multisectoral approaches. In addition, mainstreaming within the health system, improved cross-cutting One Health strategies including water, sanitation and hygiene, and sustained financing are critical for elimination. While this study provides valuable insights, limitations due to documentation gaps and secondary sources highlight the need for improved data reporting and future research to strengthen elimination frameworks.

Urogenital schistosomiasis is contracted from the Schistosoma haematobium parasite and is treated with the drug praziquantel (PZQ). Despite MDA interventions, persistent hotspots (PHS) of S. haematobium infection have been identified in multiple schistosome endemic African countries but have yet to be characterised in Zimbabwe. This study assessed long-term infection persistence and variability in praziquantel (PZQ) efficacy among school-aged children (6-15 years) in 29 districts of Zimbabwe, using data from MDAs conducted between 2012 and 2017. Metrics included infection prevalence, mean egg count, and treatment efficacy indicators. Two hotspot definitions were applied: (i) prevalence-based persistent hotspots (PPHS), identified by limited reduction or rebound in prevalence; and (ii) efficacy-based persistent hotspots (EPHS), defined by cure rates below 70%. Statistical comparisons between hotspot and non-hotspot ("responder") districts used regression models, Fisher's exact test and Mann-Whitney U tests. Analyses revealed four PPHS and six EPHS. PPHS districts exhibited significantly higher baseline prevalence and infection intensity compared with responders (P = 0.043), a pattern not observed for EPHS. Greater distance from freshwater sources was associated with EPHS occurrence (P = 0.016), although this appeared to be an indirect effect of initially high infection intensities. Lower treatment frequency correlated with increased hotspot occurrence, but the relationship was not statistically significant for either hotspot category. Other investigated factors including treatment coverage, timing of drug administration and ecological suitability for intermediate host snails showed no significant association with hotspot status. The elevated initial prevalence and infection intensity in PPHS suggest these indicators could be used for early hotspot identification, enabling targeted adjustments in intervention strategies. The findings underscore the limitations of relying solely on preventive chemotherapy in high-transmission settings. Integrating complementary measures such as water, sanitation and hygiene (WASH) interventions and snail control may improve outcomes, particularly in hotspot areas. In conclusion, the persistence of S. haematobium hotspots in Zimbabwe highlights the need for adaptive, integrated control approaches aligned with the WHO's 2030 roadmap. Monitoring baseline epidemiological indicators could facilitate earlier detection of persistent transmission foci, guiding more effective and sustainable schistosomiasis control.

Significant progress has been made in controlling neglected tropical diseases (NTDs). As of July 2025, 57 countries have eliminated at least one NTD as a public health problem or with interruption of transmission. Nonetheless, progress has not been uniform across the spectrum of NTD health service delivery. Comparatively, less progress has been made in managing chronic disease. Less than 15% of the 178 NTD-endemic countries currently have guidelines, protocols, or policies dedicated to the management of disabilities and secondary health problems resulting from widespread NTDs in their countries. To provide comprehensive health services to people living with chronic NTD diseases, there is a need to understand the impact of these diseases on the daily lives of affected people, health system shortcomings in providing treatment and management, and policy gaps. As part of a larger study, we conducted inclusive consultative workshops involving people suffering from NTD-related chronic diseases, disability, and disfigurement, health workers, policy makers, and NTDs researchers from Sudan, Tanzania, and Zimbabwe. Through this, we co-produced an NTD-affected voices-led roadmap to inform health service provision for NTD-affected people. The roadmap made 5 calls to action directed at different groups: affected voices, health workers, policy makers, ministries of health, and development partners. Responding to these calls through the actionable roadmap will improve the management of NTD-related disease including complications, disfigurement, and disability.

BACKGROUND:Neglected tropical diseases (NTDs) affect about 1.7 billion people worldwide, with the highest burden in sub-Saharan Africa. While global initiatives have reduced infection prevalence, the chronic impacts of NTDs, including morbidity, disability, and disfigurement, remain severely neglected, perpetuating poverty, social exclusion, and mental health challenges. This study aimed to identify gaps in care and management for individuals living with chronic NTD-related disabilities and to validate the situational analysis findings through participatory workshops. METHODOLOGY/PRINCIPAL FINDINGS:A mixed-methods approach was employed, comprising a situational analysis of national policies, healthcare services, and control strategies across the World Health Organization (WHO) African Region, complemented by participatory workshops, including focus group discussions (FGDs) and in-depth interviews (IDIs) with affected individuals and stakeholders, in Zimbabwe and Tanzania. Qualitative data were thematically analysed to capture key challenges, including healthcare access barriers, stigma, and gaps in care and management. The situational analysis revealed critical gaps in chronic NTD care, including lack of comprehensive policies for NTD disability management, fragmented health services, limited access to rehabilitation and mental health support, and where available at all, weak integration of morbidity management into national health systems. Findings from FGDs and IDIs corroborated these findings, highlighting barriers to healthcare access, policy deficiencies, socioeconomic burden, deep-rooted stigma, and psychological distress. Participants emphasised the urgency of integrating chronic care into national health systems, strengthening service delivery, and ensuring financial protection. CONCLUSIONS/SIGNIFICANCE:Current NTD programs prioritise infection control and disease elimination while neglecting long-term disability management. To ensure end-to-end health service provision, it is imperative to integrate morbidity management, disability support, psychosocial support, and rehabilitation into existing healthcare frameworks, informed directly by the voices of those affected. Ultimately, by bridging the gaps between policy, healthcare, and community engagement, and mainstreaming NTD morbidity management, we can ensure that individuals affected by NTDs receive comprehensive, long-term support, and that progress in disease control translates into sustained improvements in well-being.

Female genital schistosomiasis (FGS) is a neglected manifestation of Schistosoma haematobium infection, affecting an estimated 56 million women in sub-Saharan Africa. It is characterized by lesions in the genital tract, leading to symptoms like pain, infertility and an increased risk of HIV transmission. Despite its prevalence, FGS remains underdiagnosed and underreported due to limited awareness and diagnostic capabilities. Current knowledge emphasizes the need for integrated approaches combining diagnosis, treatment with praziquantel and education. There are ongoing efforts to integrate FGS services into women's sexual and reproductive services, yet to date many African countries lack programmatic guidance to achieve this. More comprehensive integration and mainstreaming of FGS prevention, control and treatment across various sectors is needed to ensure intersectoral collaboration and financing of programmes. This review examines the various intervention tools currently available to achieve FGS integration in health systems. These include water, sanitation and hygiene improvements, environmental management, health education and inclusion of preschool-aged children in national schistosomiasis control programmes. Highlighted are also the required diagnostic and therapeutic tools, preventive interventions, effective policy and sustainable funding, all integral to achieving comprehensive FGS mainstreaming.

INTRODUCTION:Praziquantel (PZQ) is commonly used to treat schistosomiasis; however, there is considerable interindividual variability in its efficacy, partly because of genetic variation. Data on this relationship is scarce across Africa - where schistosomiasis is prevalent. This study aimed to investigate the pharmacokinetic/pharmacodynamic and pharmacogenetic relationship between PZQ and its metabolites in a Zimbabwean population infected with Schistosoma haematobium by leveraging dried blood spots (DBS) and mass spectrometry (MS). METHODS:DBS were obtained from 38 Zimbabwean participants on PZQ treatment at four-time points (0.5, 1.5, 2.5, and 4 h). We compared two extraction methods for recovering PZQ and its metabolites from the DBS cards and performed MS analysis to determine the concentrations. A random forest model was used to determine whether CYP1A2 , CYP2C9 , CYP2C19 , CYP2D6 , CYP3A4 , and CYP3A5 known variants were predictive of PZQ efficacy. The relationships between PZQ/metabolite concentration, metabolite ratio, and drug exposure with genotype were determined using a one-way analysis of variance. RESULTS:An acetonitrile and water (4 : 1) mixture was determined to be optimal for recovering PZQ and its metabolites from the DBS cards. Subsequent MS analysis identified PZQ and six metabolite compounds - including phase 1 metabolites (-2H)-O-PZQ, O2-PZQ, and 4-OH-PZQ. Pooled MS sampling was comparable to individual MS sampling for determining pharmacokinetic profiles at the 2.5 and 4-h time points. The (-2H)-O-PZQ and O2-PZQ metabolites had significantly higher concentrations in participants with CYP2C9*1/*9 and *9/*9 versus those with CYP2C9*1/*1. CYP1A2 rs2069514-A (formerly *1C ) and rs762551-A ( CYP1A2*30 ; formerly *1F ) were observed to alter PZQ pharmacokinetic profiles; however, differences in analyte concentrations across the corresponding genotypes were NS. CONCLUSION:We show that low-cost microsampling using DBS and MS is feasible for detecting and quantifying PZQ and its metabolites. Furthermore, our pharmacogenetics analysis elucidates the impact of known cytochrome P450 variants on PZQ drug response in an African setting.

Neglected tropical diseases affect more than a billion people worldwide, cause ill health and perpetuate cycles of poverty. Behavioural change can help, particularly through hygiene. But to achieve this we first need to understand the complex circumstances that mean hygiene is not always prioritized.

BackgroundMetabolomics approaches are indispensable tools in infection biomarker discovery efforts as they shed light on the underlying pathophysiological mechanisms of disease. In this study, we analysed plasma metabolites that can be used as biomarkers of urogenital schistosomiasis in pre-school aged children below the age of five.MethodsA case-control study was conducted involving 82 pre-school aged children that were age- and sex-matched. Urine samples were collected for three consecutive days to detect S. haematobium infection using urine filtration. Blood samples were also collected and processed to obtain plasma. Beckman Coulter AU480 chemistry analyser and commercial metabolite kits were used for profiling biomarkers in plasma samples. Descriptive statistics and MetaboAnalyst tool, were used for metabolite analysis. For the determination of diagnostic efficiency of plasma biomarkers, the area under the curve (AUC) was calculated from receiver operating characteristic curves at 95% CI.ResultsSuccinic acid, glucose-6-phosphate, phosphatidylcholine, alanine and creatinine levels in plasma were significantly associated with urogenital schistosomiasis (p<0.005) at the population level. Significant increase in concentration at 1.5-fold change (FC) threshold was highest for glucose-6-phosphate with FC value of 2.02 followed by creatinine, albumin and phosphatidylcholine. Creatinine was significantly downregulated with a FC value of 1.98. Of the six dysregulated metabolic pathways, glucose and sucrose metabolism were predominantly affected. Glucose-6-phosphate had the highest AUC (0.81), sensitivity (88.85%) and specificity (90.37%). Phosphatidylcholine and succinic acid also had AUC values greater than 0.7.ConclusionUrogenital schistosomiasis affects the energy-related metabolic pathways in pre-school aged children. Glucose-6-phosphate was identified as a potential indicator of infection at the population level. Furthermore, we recommend intensive validation of schistosome metabolite biomarkers.

Strongyloidiasis is a soil-transmitted helminthiasis that is estimated to affect 300–600 million people across Asia, Africa, South and central America, and the Pacific. This neglected parasitic disease is most known for its ability to persist as a lifelong infection due to autoinfection and its risk of hyperinfection and disseminated disease during immunosuppression, which has a more than 60% case fatality. Despite the large global burden of strongyloidiasis, there have been no large-scale public health programmes or WHO guidelines directed towards its control and elimination. However, over the past decade, key scientific and policy changes along with requests from endemic countries have led to WHO incorporating strongyloidiasis into its 2021–30 roadmap and public health targets for control and elimination of neglected tropical diseases. In 2024, WHO published its first guideline on public health control of strongyloidiasis with a single recommendation: in endemic settings with a Strongyloides stercoralis infection prevalence of 5% or higher (measured either with Baermann or agar plate culture from stool specimens), WHO conditionally recommends mass drug administration with single-dose ivermectin (200 μg/kg; oral therapy) in all age groups from 5 years and older to reduce strongyloidiasis. This Review, written by the 2023–24 strongyloidiasis guidelines development group along with WHO colleagues and international experts, presents a summary of the recently published WHO guideline recommendation for strongyloidiasis, and the supporting evidence, considerations for public health implementation, and future research needs.

ObjectivesThe widespread adoption of self-testing for SARS-CoV-2 has proven effective in curbing the virus’ spread, particularly in Western countries. However, significant knowledge gaps persist regarding the feasibility, acceptance and factors influencing the uptake of self-testing in low-resource areas, notably rural Africa. Our aim was to assess the willingness and capability of rural Zimbabwean participants to self-diagnose COVID-19 using rapid lateral flow tests (LFTs) and adhere to post-positive test guidelines. Additionally, we aimed to identify barriers to self-testing uptake and reasons for non-compliance with follow-up actions.Design and settingWe conducted a cross-sectional survey in Shamva District, Zimbabwe.ParticipantsA total of 120 villagers aged 18 years and above participated. We employed a questionnaire to gather data on participants' attitudes towards self-testing for SARS-CoV-2 using LFTs, along with their knowledge, attitudes and practices regarding COVID-19.Primary outcomesincluded the likelihood of self-testing, the ability and accuracy of self-testing, adherence to post-test guidelines and socio-demographic factors influencing these responses.ResultsAmong the 120 participants, 108 (90%) expressed willingness to use LFTs for self-testing. The subset unwilling to self-test belonged to a religious sect historically opposed to Western medicine. All self-tests yielded valid results, as confirmed by the appearance of control lines on the LFT. Participants demonstrated the ability to interpret their results accurately without assistance and expressed willingness to adhere to post-test guidelines. Questionnaire responses indicated a preference for self-testing due to its ease, lack of pain, convenience and confidentiality. Moreover, participants exhibited a high level of knowledge about COVID-19.ConclusionThis study underscores the acceptability and feasibility of SARS-CoV-2 LFT self-testing in rural settings, suggesting its potential as an additional public health measure for epidemics and pandemics in low-resource areas.

BACKGROUND:Early diagnosis of urogenital schistosomiasis is key to its control and elimination. The current gold standard microscopic examination techniques lack sensitivity in detecting light Schistosomiasis infections in pre-school aged children thus it is urgent to develop diagnostic tools that may be integrated into control programs. In this study, we evaluated the diagnostic performance of urine metabolite biomarkers using a chemical reagent strip in the detection of S. haematobium infection in pre-school aged children. METHODS:A case-control study was conducted involving 82 pre-school aged children that were age and sex matched. Urine samples were collected for 3 consecutive days and were evaluated using urine filtration gold techniques as the gold standard method. The samples were simultaneously measured for metabolite biomarkers specifically haematuria, proteins, ketones, nitrites, glucose, bilirubin and urobilinogen using chemical reagent strips. Pearson correlation test was used to measure the relationship between S. haematobium infection and the urine metabolite biomarkers. RESULTS:The diagnostic performance of urine biomarkers were correlated with the microscopic examination urine filtration technique. Haematuria (r = 0.592, p = 0.0001) and proteinuria (r = 0.448, p = 0.0001) were correlated to S. haematobium infection. Negative correlations with p > 0.05 were recorded for ketones and urobilinogen. Highest sensitivity was 65.9 % (CI, 49.4 - 79.9) for haematuria whilst protein (albumin) biomarker had a lower specificity value of 43.9 % (28.5 - 60.3). Inversely, highest sensitivity was 87.8 % (73.8 - 95.9) for proteinuria whilst haematuria had a lower sensitivity value of 82.9 % (67.9 - 92.8). The positive predictive values ranged from 57.7 % (41.6 - 72.2) to 79.4 % (65.5 - 88.7) whereas negative predictive values ranged from 70.8 % (60.8 - 79.2) to 52.0 % (48.7 - 55.3). With respect to diagnostic efficiency, haematuria had a fair diagnostic performance with an area under the curve of 0.76 followed by proteinuria with proteinuria whilst the remaining metabolites fail discriminating ability with an area under the curve of <0.5. CONCLUSION:Although haematuria and protein biomarkers in urine are moderately sensitive and specific, they are important morbidity indicators of urogenital schistosomiasis in pre-school aged that may be utilised during screening in schistosomiasis control programs. We recommend comprehensive analysis of biomarkers using metabolomics techniques to identify novel urine biomarkers.

The World Health Organization calls for schistosomiasis endemic countries to regularly monitor the efficacy of Praziquantel (PZQ) drug, the only antischistosomal drug used for four decades in Tanzania. In response to that call, the current study investigated the efficacy of single dose of PZQ against Schistosoma haematobium during the high transmission season and further assessed, the sensitivity and specificity of urine reagent strips before and after treatment. The study recruited a total of 2,498 -children aged (4 -17 years old) who provided a single urine sample that was visually examined for macro-haematuria, then using urine dipstick and urine filtration technique for microhaematuria and the presence of S. haematobium eggs. The baseline prevalence of S. haematobium eggs positive based on urine filtration test was 29.2%(95%CI:27.5-31.0) and that of microhaematuria was 43.1% (95%CI:41.1-45.0). Of the infected participants, 40.9%(95%CI:37.4-44.6) had a heavy intensity of infection and the geometrical mean intensity (GMI) of infection was 33.7 eggs/10mls of urine. A single dose of PZQ reduced the prevalence of infection to 16.2%, the GMI of infection to 18.8eggs/10mls of urine and that of microhaematuria to 27.9%. Cure rate and egg reduction rates (ERR) were 83.8% and 44.3% respectively. At baseline, the sensitivity and specificity of the urine reagent strips were 59.7% and 93.8%, whereas at post-treatment they were 16.7% and 93.6%. When PZQ drug is administered during the high transmission season, its efficacy in term of ERR is poor. The urine reagent strips had low sensitivity but high specificity at pre-and-post PZQ treatment.