Betty Nabatte

Background: Schistosomiasis-related periportal fibrosis (PPF) diagnoses rely on point-of-care ultrasound imaging. Yet, the extent of agreement between sonographers, limitations of existing World Health Organization (WHO) protocols, and the applicability of ultrasound video remain poorly understood. Methods: In 2024, six sonographers performed ultrasound scans for 3302 participants aged 5–92 years within SchistoTrack, a community-based cohort in rural Uganda. We adapted and standardised the WHO Niamey protocol for the collection of curated ultrasound images of liver fibrosis patterns related to Schistosoma mansoni (ranging A–F) and liver ultrasound video sweeps. PPF was defined as patterns C–F. Images and videos were read for patterns of fibrosis by second sonographers who were blinded to field diagnoses. Second sonographers recorded their clinical confidence, the probe position and any ultrasound interference. Outcomes considered were simple agreement for individual patterns and agreement on whether any PPF pattern was present, using Cohen’s κ . The influence of participant characteristics and image quality factors was evaluated against agreement outcomes. Results: Abnormal liver fibrosis patterns (B–F) were identified in 32.8% (1082/3302) of participants, and among these 2074 images were read by a second sonographer from 1040 participants. The percentage agreement was 73.0% (1515/2074) for broad pattern categories. Severe fibrosis patterns had the least agreement; E and F patterns had κ = 0.430 and 0.149, respectively. The D pattern had the most agreement ( κ = 0.717). 94.0% of second sonographer readings were within one step of severity of the field diagnosis. Participant characteristics were not consistently associated with disagreement, though agreement clustered by the field sonographer. Clinical confidence, breathing/movement, fat interference and probe position were positively associated with disagreement. There was no agreement among the 1054 videos that were read by a second sonographer: κ = 0.001 for PPF agreement and ranged 0–0.062 for individual patterns. Conclusion: We have presented the largest diagnostic study of inter-sonographer agreement for schistosomal liver fibrosis patterns. Disagreement between adjacent patterns of liver fibrosis may indicate that the WHO Niamey protocol should be updated to capture a continuous progression of liver fibrosis rather than distinct patterns. The greatest disagreement was among severe patterns, which supports routine second reading to ensure life-threatening cases are prioritised and appropriately triaged.

Malaria and schistosomiasis are co-endemic across much of sub-Saharan Africa, yet it remains unclear whether co-infections reflect shared risk factors, unexplained biological determinants, or chance co-occurrence. We analysed data collected at recruitment from 4290 individuals aged 5–90 years across 52 villages in rural Uganda within the SchistoTrack cohort. A bivariate copula model was developed to separate shared and disease-specific associations from residual dependence. Prevalence was 41.47% for Schistosoma mansoni , 41.19% for Plasmodium falciparum , and 18.51% for co-infection. Prevalence overlapped in school-aged children with co-infection prevalence peaking at 13 years. Greater distance to a government health centre was the strongest shared determinant, apart from age, male gender and living in western districts, increasing the risk of both. Local water ecology influenced each pathogen in opposing directions. Fishing was associated with higher S. mansoni and co-infection risks, but not P. falciparum risk. A modelled scenario combining household drinking-water treatment, handwashing facilities and protected water sources with cessation of freshwater contact reduced co-infection prevalence by 32%. Our findings support integrated control around shared demographics and limited healthcare access and household water infrastructure, while highlighting the need for non-integrated approaches for ecological interventions aiming to reduce parasite-specific transmission determinants.

Schistosomiasis causes a complex, difficult to diagnose form of liver fibrosis with high rates of life-threatening morbidity in resource-poor settings where there are often no trained sonographers. Protocols for diagnosis of schistosomiasis-related liver fibrosis have focused on difficult-to-acquire and subjective ultrasound images dependent on extensive expertise. Here we present SchistoTrackVideoNet, the first deep learning-based video model trained on easy-to-acquire standardised ultrasound video sweeps for classification of schistosomiasis-related liver fibrosis. This video-based classification model was trained and evaluated on video sweeps from 2140 participants aged 5--87 years from three districts in rural Uganda. We tested the model at a clinically-relevant sensitivity threshold ($\geq$90\%) and achieved positive predictive values of 0.0968--0.5556 for diverse presentations of liver fibrosis. Our findings show potential for the use of easy-to-acquire video sweeps for diagnosis of schistosomiasis-related liver fibrosis and our model provides a proof-of-concept for deep learning applied to liver ultrasound video for diagnosis of schistosomiasis-related liver morbidity.

Liver fibrosis is a major cause of death in low- and middle-income country contexts. In rural, poor areas of sub-Saharan Africa, schistosomiasis is an underestimated cause of liver fibrosis. Despite the need for increased diagnostic capacity for schistosomiasis-related liver fibrosis, there are no automated, clinically-validated tools to diagnose schistosomiasis-related liver fibrosis. We present SchistoTrackNet which is, to our knowledge, the first deep learning-based model for distinguishing distinct presentations of schistosomiasis-related liver fibrosis of varying severity. Ultrasound images from 1533 participants aged 5–84 years from three districts in rural Uganda were used to train and evaluate the presented models. The models were evaluated by assessing failure cases and by comparing results with re-readings performed by sonographers experienced in diagnosis of schistosomiasis morbidity. Our models show potential to enable automated reading of ultrasound images for schistosomiasis-related liver fibrosis to allow large-scale surveillance of schistosomiasis morbidity and contribute towards the World Health Organization target to eliminate schistosomiasis as a public health problem.

Background: The role of gut inflammation for intestinal schistosomiasis remains poorly understood in chronically infected and repeatedly treated populations. Methods: We conducted a cross-sectional study nested in the SchistoTrack cohort within Pakwach district, Uganda. In 2024, 640 participants aged 6–85 years were examined for Schistosoma mansoni by Kato-Katz. Fecal calprotectin (fCal) concentration was measured by enzyme-linked immunosorbent assays. Fecal calprotectin was analyzed as binary outcomes (detectable, ≥100 µg/g, >250 µg/g) and natural log-transformed continuous values. Co-endemic infections (malaria, HIV, hepatitis B [HBV]) and sociodemographic covariates were investigated in logistic regressions with covariate selection. Results: 74.4% of participants had detectable fCal, 22.3% had fCal ≥100 µg/g, and 7% had fCal >250 µg/g. Schistosoma mansoni prevalence was 49.1%. Infection intensity was positively associated with all fCal outcomes (detectable: OR 1.20, ≥100 µg/g: OR 1.11, >250 µg/g: OR 1.26; continuous: β .06) while infection status was positively related to all but the continuous fCal outcome. HIV was associated with fCal ≥100 µg/g (OR 2.52), while malaria and HBV were uninformative. Conclusions: Schistosoma mansoni infections are characterized by persistent, clinically concerning levels of gut inflammation in chronically infected populations with repeated praziquantel treatment. Integration of fCal thresholds into clinical guidelines may improve management of schistosomiasis-related morbidity.

Background: Schistosomiasis causes substantial chronic morbidity in sub-Saharan Africa, yet case definitions, clinical management guidance, and health worker training for schistosomiasis-related morbidity remain limited. Methodology: We conducted a qualitative needs assessment for schistosomiasis morbidity management. Workshops were held over one day in each of Pakwach, Buliisa, and Mayuge Districts in Uganda in October 2024. 105 government health workers participated including clinicians, nurses, laboratory technicians, sonographers, and district health managers from health facilities at different levels of care. The workshops comprised six structured sessions: presentations on schistosomiasis burden in Uganda and the SchistoTrack cohort, a clinical case report by an expert clinician, an interactive session on patient case studies from the SchistoTrack cohort, mapping of patient pathways, anonymous participation and feedback, and demonstrations of schistosomiasis diagnosis. Workshop discussions were documented through notes taken in English and analysed using qualitative thematic analysis as per Braun and Clarke. Findings: Health workers demonstrated substantial gaps in understanding schistosomiasis case definitions, particularly in distinguishing current infection from chronic morbidity and in grading disease severity. Patient pathways for schistosomiasis morbidity management were fragmented and inconsistent, with weak triage, unclear referral and feedback mechanisms, and limited follow-up across facility levels. Health facilities lacked essential capacity and resources, including routine access to praziquantel outside mass drug administration, diagnostic reagents, functional ultrasound equipment, trained sonographers, and standardized training and reference tools. Collectively, these gaps contributed to inconsistent clinical decision-making and under-recognition of severe schistosomiasis-related morbidity. Conclusions: Integrating case management into routine health services through standardized case definitions, clearer patient pathways, and targeted practical training for health workers is essential to complement preventive chemotherapy and reduce preventable morbidity. The engagement framework and patient case studies used here can support needs-based assessments in other endemic settings to inform the development of context-appropriate clinical guidance and training programmes. Author summary: Schistosomiasis is a disease common in sub-Saharan Africa that can cause serious, lifelong health problems, even after the infection itself has been treated. While mass drug administration programmes have reduced infections, we found that health facilities are often not equipped to recognize or manage the chronic illness that remains after mass drug administration. In this study, we worked with government health workers in three rural districts of Uganda to understand their experiences, challenges, and training needs related to schistosomiasis morbidity. Through interactive workshops, we learned that many health workers struggle to distinguish between current infection and long-term organ damage, especially liver disease. Patient care pathways were often unclear, referrals were poorly coordinated, and essential tools, such as diagnostic supplies, ultrasound access, and routine availability of treatment, were frequently missing. These gaps make it difficult to identify severe cases early and provide consistent care. We show that strengthening routine health services through clearer case definitions, better training, and more coordinated patient pathways is essential to reduce preventable suffering from schistosomiasis. Our approach offers a practical way to support health systems in other endemic settings facing similar challenges.

Background: Schistosoma mansoni is a leading cause of hepatosplenic disease in sub-Saharan Africa. Yet, associations with current Schistosoma mansoni infections and hepatosplenic organometry remain unclear in the context of widespread mass drug administration and co-endemic infections. Methods: From January to February 2024, we conducted a community-based, cross-sectional study nested within the SchistoTrack cohort in three districts of Uganda. Liver and spleen dimensions were assessed via point-of-care B-mode ultrasound for 3121 individuals. Organ dimensions were classified using the standard deviations from height-standardized internal reference values derived from an infection-free population. Multinomial logistic regressions were run for children (5–17 years) and adults (18+ years) separately. Population attributable fractions (PAFs) were used to estimate the proportion of abnormal organometry statistically attributable to each infection. Key exposures were S. mansoni , malaria, human immunodeficiency virus (HIV), and hepatitis B virus (HBV) alongside a comprehensive set of social, biomedical, and other covariates controlled for. Results: Moderate-to-severe splenic enlargement was observed in 29.1% (438/1507) of children and 23.3% (376/1614) of adults. Among adults, 20.9% (337/1614) had left liver lobe enlargement and 18.8% (303/1614) had right liver lobe shrinkage. In children, severe splenic enlargement was statistically attributable to malaria (PAF 46.7%; Relative Risk Ratio (RRR) 3.96, 95% CI 2.64–5.92) and S. mansoni infection intensity (PAF 23.6%; RRR 1.12, 95% CI 1.04–1.20). In adults, S. mansoni intensity was associated with moderate left liver lobe enlargement (PAF 12.4%; RRR 1.11, 95% CI 1.04–1.18). In adults, HIV was associated with severe left liver lobe shrinkage (RRR 4.50, 95% CI 1.19–17.00) and severe splenomegaly (RRR 3.62, 95% CI 1.58–8.33), while HBV was associated only with severe left liver lobe shrinkage (RRR 2.54, 95% CI 1.07–6.03). Praziquantel treatment in the past year showed inconsistent associations and no clear protective pattern. Conclusion: Current S. mansoni infection intensity remains associated with splenomegaly in children despite controlling for concurrent malaria positivity, and with hepatomegaly in adults despite HIV and HBV associations.

Background: Schistosomiasis control relies on the continued effectiveness of praziquantel (PZQ), yet individual and spatial heterogeneity in PZQ efficacy in the context of repeated mass drug administration (MDA) remains poorly understood. This study aimed to identify individual and spatial determinants of PZQ efficacy against Schistosoma mansoni in rural Uganda. Methods: We studied 3870 participants aged 5–90 years from 52 villages in Pakwach, Buliisa, and Mayuge districts in Uganda. Participants were recruited to the SchistoTrack cohort in January–February of 2022 and 2023. Participants received PZQ and were followed up four to five weeks later to assess cure using Kato—Katz (KK) microscopy and point-of-care circulating cathodic antigen tests. Logistic regression models were used to identify predictors of cure, defined as egg reduction rates (ERR) of 100% or ERR ≥ 90%. We explored a comprehensive set of 18 sociodemographic, biomedical, water, sanitation, and hygiene, and spatial factors. Subgroup analyses were conducted for adults (aged 18–90) versus children (aged 5–17). Spatial autocorrelation in the outcome and model residuals was assessed using join count statistics and Moran’s I . Results: Of 3870 clinical participants, 3704 (95.7%) received PZQ, and 3395 of these had complete clinical data. Among the 3395 treated participants, 1406 (41.4%) were infected with S. mansoni at baseline. The overall cure rate (ERR of 100%) was 76.3%, ranging from 68.9% to 85.4% across districts. Higher odds of cure were associated with older age (OR 1.34) and lower baseline infection intensity (moderate/heavy vs light OR 0.39–0.61). Greater height was associated with lower odds of cure (OR 0.99), which was driven by adults. Compared with Mayuge district, participants in Western districts had lower odds of cure (OR 0.48–0.53). In children, greater distance to water sites with snail presence was linked to higher odds of cure (OR 1.05 per 100 m). Results were similar when defining cure as ERR ≥ 90% and when using POC-CCA outcomes. Spatial clustering of treatment outcomes was observed by district, but no residual spatial autocorrelation remained after accounting for district effects. Conclusions: Incorporating spatial analyses, refining dose assessment, and strengthening post-MDA monitoring may help maintain PZQ effectiveness and support sustainable schistosomiasis control efforts.

Background: There is limited data on trends in primary health care (PHC) access and utilisation in rural sub-Saharan Africa, with a particular lack of knowledge on disparities beyond geographic barriers. Methods: A cross-sectional study was conducted within the community-based cohort, SchistoTrack. 2191 households were randomly sampled from 52 rural villages in Pakwach, Buliisa, and Mayuge Districts in Uganda. All household members aged one year and older were surveyed between 2022-2024, resulting in 8038 individuals with baseline health access information. Key outcomes included any care sought within the month preceding the study, type of care sought, and usual source of care. Using logistic regressions with standard errors clustered by household and village, we examined a comprehensive and diverse set of medical, socioeconomic, and geographic determinants. Results: Only 8.2% (659/8038) of participants sought any care, with only 67.5% (445/659) of those participants seeking PHC. Having current symptoms, a previously diagnosed disease, older age, and being female were positively associated (Odds ratios (ORs) 1.02-2.85) with higher odds of seeking any care in the past month. Among participants who sought care, living in a Western district (Pakwach or Buliisa) was associated with higher odds (ORs 9.40-10.77) of seeking care from PHC centres than living in the Eastern study district (Mayuge). Current alcohol use among adults aged 20 years and older was associated with lower odds of seeking PHC (OR 0.43). Distance to a PHC centre and living in the Western districts were negatively (OR 0.72) and positively associated (ORs 4.70-5.64) with having PHC as the usual source of care for the household. Conclusions: Medical and demographic factors influenced the decision to seek any care, but PHC usage was largely determined by regional and spatial disparities suggesting different avenues for targeted interventions seeking to increase general health access vs PHC usage.