Said Mohammed Ali

Background: The human gastrointestinal microbiota plays a crucial role in immune modulation, metabolism, and pathogen resistance. Soil-transmitted helminth (STH) infections, including Trichuris trichiura (whipworm), significantly alter gut microbial composition, yet the extent and functional consequences of these changes remain underexplored across different geographical regions. This study investigates the taxonomic and functional impacts of T. trichiura on gut microbiota in three endemic regions - Côte d’Ivoire, Laos, and Tanzania - using a unified high-resolution metagenomic sequencing approach. Results: This study reveals extensive gut microbiota disruptions linked to T. trichiura infection, with both regional and cross-country patterns. A core signature found across all study sites includes depletion of Faecalibacterium prausnitzii and Eubacterium rectale (Short-chain fatty acids (SCFA) producers) and enrichment of mucin-degrading bacteria ( Ruminococcus , Bacteroides ), alongside increased host-derived carbohydrate metabolism. Infection destabilized microbial networks, characterized by reduced connectivity and clustering, with opportunistic taxa such as Segatella copri emerging as network hubs across regions, indicating a shared ecological response. Both taxonomic and functional disruptions exhibited a combination of conserved and region-specific patterns; for example, whereas certain taxa, such as Prevotella and Streptococcus , showed notable geographic variability, specific functional changes, such as SCFA depletion and mucin degradation, were consistently observed across sites. These conserved functional changes suggest that T. trichiura imposes similar metabolic pressures on the gut microbiome across populations, potentially affecting host nutrient availability and immune responses in a predictable manner. Discussion and Conclusion: This study provides robust evidence that T. trichiura infection induces significant and consistent microbiome alterations across diverse populations. The depletion of SCFA-producing bacteria and the enrichment of mucin-degrading taxa, along with corresponding metabolic pathways, imply compromised gut barrier integrity, providing insights into the complex inflammatory processes associated with this helminth infection. Additionally, these microbiome differences could play a critical role in facilitating parasite persistence and reinfection, which remain major challenges limiting the efficacy of global control strategies. Our findings highlight the potential of microbiome-targeted interventions, such as probiotic supplementation or dietary modifications, to mitigate the health impacts of T. trichiura infections by restoring microbial homeostasis.

Background/Objectives: Despite efforts within the framework of the Sustainable Development Goal to end malnutrition by 2030, malnutrition and soil-transmitted helminth infections persist in sub-Saharan Africa. A significant barrier to success is the inadequate understanding of effective intervention methods. Most research on the gut microbiota’s role in health has been conducted in developed countries, leaving a critical gap in knowledge regarding low-income populations. This study addresses this gap by expanding research on the gut microbiota of underprivileged populations to help tackle these public health challenges. Methods: We employed 16S rDNA sequencing to assess the bacterial gut microbiota composition of 60 children (mean age: 26.63 ± 6.36 months) and their 58 mothers (mean age: 30.03 ± 6.31 years) in Pemba, with a focus on helminth infection and nutritional status. Results: Our differential abundance analysis identified bacterial taxa that were significantly negatively associated with both helminth infections and malnutrition, highlighting the potential for microbiota-directed interventions to address these health issues simultaneously. Notably, we identified Akkermansia, Blautia, Dorea, and Odoribacter as promising probiotic candidates for such interventions. In stunted children, positive co-occurrences were observed between Lactobacillus, Prevotella, and Bacteroides, while Escherichia/Shigella displayed negative co-abundance relationships with short-chain fatty acid (SCFA) producers in the gut microbiota. These findings suggest that administering Lactobacillus and SCFA-producing probiotics to children may foster the growth of beneficial bacteria like Prevotella and Bacteroides while reducing the relative abundance of Escherichia/Shigella, potentially enhancing overall health. Conclusions: This study underscores the importance of microbiota-directed interventions in children and women of reproductive age as promising strategies, alongside established approaches, for combating helminth infections and malnutrition in vulnerable populations.

We estimated the financial costs of different interventions against urogenital schistosomiasis, implemented by the Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project, on Pemba and Unguja islands, Tanzania. We used available data on project activities, resources used, and costs reported in the accounting information systems of ZEST partners. The costs were estimated for all the activities related to snail control, behavior change interventions, the impact assessment surveys, and management of the whole program. Costs are presented in US$ for the full duration of the ZEST project from 2011/2012 to 2017. The total financial costs of implementing snail control activities over 5 years, excluding the costs for donated Bayluscide, were US$55,796 on Pemba and US$73,581 on Unguja, mainly driven by personnel costs. The total financial costs of implementing behavior change activities were US$109,165 on Pemba and US$155,828 on Unguja, with costs for personnel accounting for 47% on Pemba and 69% on Unguja. Costs of implementing biannual mass drug administration refer to the estimated 2.4 million treatments provided on Pemba over 4 years (2013-2016), and do not include the costs of donated praziquantel. The total cost per provided treatment was, on average, US$0.21. This study showed the value of exploiting administrative data to estimate costs of major global health interventions. It also provides an evidence base for financial costs and main cost drivers of implementing multiple combinations of intervention sets that inform decisions regarding the feasibility and affordability of implementing schistosomiasis control and elimination strategies.

Accurate diagnosis of urogenital schistosomiasis is crucial for disease surveillance and control. Routine diagnostic methods, however, lack sensitivity when assessing patients with low levels of infection still able to maintain pathogen transmission. Therefore, there is a need for highly sensitive diagnostic tools that can be used at the point-of-care in endemic areas. Recombinase polymerase amplification (RPA) is a rapid and sensitive diagnostic tool that has been used to diagnose several pathogens at the point-of-care. Here, the analytical performance of a previously developed RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic region was assessed using commercially synthesised S. haematobium Dra1 copies and laboratory-prepared samples spiked with S. haematobium eggs. Clinical performance was also assessed by comparing diagnostic outcomes with that of a reference diagnostic standard, urine-egg microscopy. The RT-ShDra1-RPA was able to detect 1 × 10¹ copies of commercially synthesised Dra1 DNA as well as one S. haematobium egg within laboratory-spiked ddH₂O samples. When compared with urine-egg microscopy, the overall sensitivity and specificity of the RT-ShDra1-RPA assay was 93.7% (±88.7–96.9) and 100% (±69.1–100), respectively. Positive and negative predictive values were 100% (±97.5–100) and 50% (±27.2–72.8), respectively. The RT-ShDra1-RPA therefore shows promise as a rapid and highly sensitive diagnostic tool able to diagnose urogenital schistosomiasis at the point-of-care.

Background: Efforts to control and eliminate schistosomiasis have accelerated over the past decade. As parasite burden, associated morbidity and egg excretion decrease, diagnosis with standard parasitological methods becomes harder. We assessed the robustness and performance of a real-time PCR (qPCR) approach in comparison with urine filtration microscopy and reagent strip testing for the diagnosis of Schistosoma haematobium infections of different intensities. Methods: The robustness of DNA isolation and qPCR was validated in eight laboratories from Europe and Africa. Subsequently, 792 urine samples collected during cross-sectional surveys of the Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project in 2012–2017 were examined with qPCR in 2018. Diagnostic sensitivity of the qPCR was calculated at different infection intensity categories, using urine filtration microscopy as reference test. Spearman’s rank correlation between Ct-values and S. haematobium egg counts was assessed and Ct-value percentiles for infection intensity categories determined. Results: S. haematobium Dra1 DNA-positive samples were identified correctly in all eight laboratories. Examination of urine samples from Zanzibar revealed Dra1 DNA in 26.8% (212/792) by qPCR, S. haematobium eggs in 13.3% (105/792) by urine filtration, and microhaematuria in 13.8% (109/792) by reagent strips. Sensitivity of the qPCR increased with augmenting egg counts: 80.6% (29/36) for counts between 1 and 4 eggs, 83.3% (15/18) for counts between 5 and 9 eggs, 100% (23/23) for counts between 10 and 49 eggs, and 96.4% (27/28) for counts of 50+ eggs. There was a significant negative correlation between Ct-values and egg counts (Spearman’s rho = − 0.49, P < 0.001). Seventy-five percent of the Ct-values were ≥ 33 in the egg-negative category, < 31 in the light intensity category, and < 24 in the heavy intensity category. Conclusions: While the sensitivity of the qPCR was ~ 80% for very light intensity infections (egg counts < 10), in general, the Dra1 based qPCR assay detected twice as many S. haematobium infections compared with classical parasitological tests. The qPCR is hence a sensitive, urine-based approach for S. haematobium diagnosis that can be used for impact assessment of schistosomiasis elimination programmes, individual diagnosis, and in improved format also for verification and certification of elimination. Trial registration: ISRCTN, ISRCTN48837681. Registered 05 September 2012 - Retrospectively registered.

Schistosomiasis, a neglected tropical disease of medical and veterinary importance, transmitted through specific freshwater snail intermediate hosts, is targeted for elimination in several endemic regions in sub-Saharan Africa. Multi-disciplinary methods are required for both human and environmental diagnostics to certify schistosomiasis elimination when eventually reached. Molecular xenomonitoring protocols, a DNA-based detection method for screening disease vectors, have been developed and trialed for parasites transmitted by hematophagous insects, such as filarial worms and trypanosomes, yet few have been extensively trialed or proven reliable for the intermediate host snails transmitting schistosomes. Here, previously published universal and Schistosoma-specific internal transcribed spacer (ITS) rDNA primers were adapted into a triplex PCR primer assay that allowed for simple, robust, and rapid detection of Schistosoma haematobium and Schistosoma bovis in Bulinus snails. We showed this two-step protocol could sensitively detect DNA of a single larval schistosome from experimentally infected snails and demonstrate its functionality for detecting S. haematobium infections in wild-caught snails from Zanzibar. Such surveillance tools are a necessity for succeeding in and certifying the 2030 control and elimination goals set by the World Health Organization.

As part of its diverse portfolio, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) included two cluster-randomized trials evaluating interventions that could potentially lead to interruption of schistosomiasis transmission (elimination) in areas of Africa with low prevalence and intensity of infection. These studies, conducted in Zanzibar and Cote d'Ivoire, demonstrated that multiyear mass drug administration (MDA) with praziquantel failed to interrupt the transmission of urogenital schistosomiasis, even when provided biannually and/or supplemented by small-scale implementation of additional interventions. Other SCORE activities related to elimination included a feasibility and acceptability assessment of test-treat-track-test-treat (T5) strategies and mathematical modeling. Future evaluations of interventions to eliminate schistosomiasis should recognize the difficulties inherent in conducting randomized controlled trials on elimination and in measuring small changes where baseline prevalence is low. Highly sensitive and specific diagnostic tests for use in very low-prevalence areas for schistosomiasis are not routinely available, which complicates accurate measurement of infection rates and assessment of changes resulting from interventions in these settings. Although not encountered in these two studies, as prevalence and intensity decrease, political and community commitment to population-wide MDA may decrease. Because of this potential problem, SCORE developed and funded the T5 strategy implemented in Egypt, Kenya, and Tanzania. It is likely that focal MDA campaigns, along with more targeted approaches, including a T5 strategy and snail control, will need to be supplemented with the provision of clean water and sanitation and behavior change communications to achieve interruption of schistosome transmission.

Recent research calls for distinguishing whether the failure to comply with World Health Organisation hand hygiene guidelines is driven by omitting to rub/wash hands, or subsequently recontamination of clean hands or gloves prior to a procedure. This study examined the determinants of these two behaviours. Across the 10 highest-volume labour wards in Zanzibar, we observed 103 birth attendants across 779 hand hygiene opportunities before aseptic procedures (time-and-motion methods). They were then interviewed using a structured cross-sectional survey. We used mixed-effect multivariable logistic regressions to investigate the independent association of candidate determinants with hand rubbing/washing and avoiding glove recontamination. After controlling for confounders, we found that availability of single-use material to dry hands (OR:2.9; CI:1.58–5.14), a higher workload (OR:29.4; CI:12.9–67.0), more knowledge about hand hygiene (OR:1.89; CI:1.02–3.49), and an environment with more reminders from colleagues (OR:1.20; CI:0.98–1.46) were associated with more hand rubbing/washing. Only the length of time elapsed since donning gloves (OR:4.5; CI:2.5–8.0) was associated with avoiding glove recontamination. We identified multiple determinants of hand washing/rubbing. Only time elapsed since washing/rubbing was reliably associated with avoiding glove recontamination. In this setting, these two behaviours require different interventions. Future studies should measure them separately.

Background: In clinical research, obtaining informed consent from participants is an ethical and legal requirement. Conveying the information concerning the study can be done using multiple methods yet this step commonly relies exclusively on the informed consent form alone. While this is legal, it does not ensure the participant’s true comprehension. New effective methods of conveying consent information should be tested. In this study we compared the effect of different methods on the knowledge of caregivers of participants of a clinical trial on Pemba Island, Tanzania.Methods: A total of 254 caregivers were assigned to receive (i) a pamphlet (n = 63), (ii) an oral information session (n = 62) or (iii) a pamphlet and an oral information session (n = 64) about the clinical trial procedures, their rights, benefits and potential risks. Their post-intervention knowledge was assessed using a questionnaire. One group of caregivers had not received any information when they were interviewed (n = 65).Results: In contrast to the pamphlet, attending an information session significantly increased caregivers’ knowledge for some of the questions. Most of these questions were either related to the parasite (hookworm) or to the trial design (study procedures).Conclusions: In conclusion, within our trial on Pemba Island, a pamphlet was found to not be a good form of conveying clinical trial information while an oral information session improved knowledge. Not all caregivers attending an information session responded correctly to all questions; therefore, better forms of communicating information need to be found to achieve a truly informed consent.

Soil-transmitted helminthiasis affects almost 2 billion people worldwide in tropical climates. Preventive chemotherapy, using the benzimidazoles (albendazole and mebendazole) is the current main recommended control strategy. Nevertheless, there is limited efficacy of these drugs against hookworm infection and, to a greater extent, against trichuriasis. We describe a protocol for a trial investigating the efficacy and safety of the co-administration of ivermectin and albendazole against trichuriasis. A double-blind, placebo-controlled randomized controlled trial will be conducted in three countries (Côte d’Ivoire, Tanzania and Lao PDR) with the aim to determine the efficacy, safety and extended effects of co-administered ivermectin and albendazole compared to standard albendazole monotherapy. We will enroll 600 participants aged 6–60 years in each setting. The primary outcome is cure rate (CR) against Trichuris trichiura infection as assessed by Kato-Katz 14–21 days after treatment. Secondary outcomes include CRs against concomitant soil-transmitted helminth (STH) infections (Ascaris lumbricoides, hookworm and Strongyloides stercoralis) and egg reduction rates (ERRs) against STH at 14–21 days, 180 days and 360 days. Tolerability of treatment, infection status assessed by polymerase chain reaction (PCR), and potential benefits of deworming on nutritional and morbidity indicators will be assessed. The primary analysis will include an available-case set and use logistic regression models adjusted for age, sex and weight. This trial will provide robust results on the efficacy and safety of co-administration of ivermectin and albendazole with the aim to better inform WHO recommendations on control of STHs. Furthermore, secondary and explanatory outcomes will provide direct evidence on the extended effects of combination therapy and insight on the relationship between nutrition and morbidity parameters and infection status and intensity. NCT03527732 (date assigned: 17 May 2018).