Age-group associations of schistosomiasis prevalence from trial data, Côte d'Ivoire, Kenya and the United Republic of Tanzania.

Objective: To determine if the prevalence of schistosomiasis in children aged 9-12 years is associated with the prevalence in 5-8-year-olds and adults after preventive chemotherapy in schools or the community. Methods: We combined data from four community-randomized, preventive chemotherapy trials in treatment-naïve populations in Côte d'Ivoire, Kenya and the United Republic of Tanzania during 2010-2016 according to the number of praziquantel treatments and the delivery method. Schistosoma mansoni infection was sought on two slides prepared from each participant's first stool using the Kato-Katz technique. We assessed associations between S. mansoni prevalence in 9-12-year-olds and 5-8-year-olds and adults in the community before and after treatment using Bayesian regression models. Findings: Stool samples from 47 985 5-8-year-olds, 81 077 9-12-year-olds and 20 492 adults were analysed. We found associations between the prevalence in 9-12-year-olds and that in 5-8-year-olds and adults after preventive treatment, even when only school-age children were treated. When the prevalence in 9-12-year-olds was under 10%, the prevalence in 5-8-year-olds was consistently under 10%. When the prevalence in 9-12-year-olds was under 50%, the prevalence in adults after two or four rounds of preventive chemotherapy was 10%-15% lower than before chemotherapy. Post-chemotherapy age-group associations were consistent with pre-chemotherapy associations in this analysis and previous studies. Conclusion: The prevalence of S. mansoni infection in 9-12-year-olds was associated with the prevalence in other age groups and could be used to guide community treatment decisions.

Spatio-temporal variability in transmission risk of human schistosomes and animal trematodes in a seasonally desiccating East African landscape.

Different populations of hosts and parasites experience distinct seasonality in environmental factors, depending on local-scale biotic and abiotic factors. This can lead to highly heterogeneous disease outcomes across host ranges. Variable seasonality characterizes urogenital schistosomiasis, a neglected tropical disease caused by parasitic trematodes (Schistosoma haematobium). Their intermediate hosts are aquatic Bulinus snails that are highly adapted to extreme rainfall seasonality, undergoing prolonged dormancy yearly. While Bulinus snails have a remarkable capacity for rebounding following dormancy, we investigated the extent to which parasite survival within snails is diminished. We conducted an investigation of seasonal snail schistosome dynamics in 109 ponds of variable ephemerality in Tanzania from August 2021 to July 2022. First, we found that ponds have two synchronized peaks of schistosome infection prevalence and observed cercariae, though of lower magnitude in the fully desiccating than non-desiccating ponds. Second, we evaluated total yearly schistosome prevalence across an ephemerality gradient, finding ponds with intermediate ephemerality to have the highest infection rates. We also investigated dynamics of non-schistosome trematodes, which lacked synonymity with schistosome patterns. We found peak schistosome transmission risk at intermediate pond ephemerality, thus the impacts of anticipated increases in landscape desiccation could result in increases or decreases in transmission risk with global change.

Spatiotemporal variability in transmission risk of human schistosomes and animal trematodes in a seasonally desiccating East African landscape.

Different populations of hosts and parasites experience distinct seasonality in environmental factors, depending on local-scale biotic and abiotic factors. This can lead to highly heterogenous disease outcomes across host ranges. Variable seasonality characterizes urogenital schistosomiasis, a neglected tropical disease caused by parasitic trematodes (Schistosoma haematobium). Their intermediate hosts are aquatic Bulinus snails that are highly adapted to extreme rainfall seasonality, undergoing dormancy for up to seven months yearly. While Bulinus snails have a remarkable capacity for rebounding following dormancy, parasite survival within snails is greatly diminished. We conducted a year-round investigation of seasonal snail-schistosome dynamics in 109 ponds of variable ephemerality in Tanzania. First, we found that ponds have two synchronized peaks of schistosome infection prevalence and cercariae release, though of lower magnitude in the fully desiccating ponds than non-desiccating ponds. Second, we evaluated total yearly prevalence across a gradient of an ephemerality, finding ponds with intermediate ephemerality to have the highest infection rates. We also investigated dynamics of non-schistosome trematodes, which lacked synonymity with schistosome patterns. We found peak schistosome transmission risk at intermediate pond ephemerality, thus the impacts of anticipated increases in landscape desiccation could result in increases or decreases in transmission risk with global change.

Test-Treat-Track-Test-Treat Strategy for Control of Schistosomiasis in Two Low-Prevalence Villages in Northwestern Tanzania.

Mass drug administration of praziquantel becomes a less attractive strategy for elimination of schistosomiasis in low-prevalence areas due to cost implications and low treatment compliance. We aimed to determine the feasibility of a Test-Treat-Track-Test-Treat (5T) strategy in two low-prevalence villages; the 5T strategy has been successfully implemented in diseases such as malaria. A total of 200 school children aged 6-12 years were randomly selected from two schools and tested for Schistosoma mansoni infection using the point-of-care circulating cathodic antigen test. Schistosoma mansoni-positive children, referred to as first-generation cases (FGCs), were tracked and treated including up to five members of their families. Second-generation cases, identified by the FGCs as their close, non-relative contacts, were also tracked, tested, and treated, including up to five members of their families. The prevalence of schistosomiasis among screened FGCs was 16.5% (33/200) in both villages. Twenty-four FGCs were included in the study. Prevalence among 94 contacts of FGCs was 46.8% (44/94). The proportion was higher in Muda than Bulunga village (61.2% versus 31.1%, χ2 = 10.6611, P = 0.005). Prevalence among SGCs and their contacts was 37.5% (9/24) and 47.1% (49/104), respectively. Overall, the 5T strategy identified 102 additional cases out of 222 tracked from FGCs, 95% of whom were treated, at a total time of 52 hours. Our data demonstrate the potential of the 5T strategy in identifying and treating additional cases in the community and hence its practicality in schistosomiasis control in low-prevalence settings at relatively low time and resources investment.

The trend of schistosomiasis related bladder cancer in the lake zone, Tanzania: a retrospective review over 10 years period.

INTRODUCTION: Bladder cancer is a possible outcome of chronic urinary schistosomiasis in many endemic countries. In Tanzania, the Lake Victoria area is one of the areas with the highest prevalence of urinary schistosomiasis and higher incidences of squamous cell carcinoma (SCC) of the urinary bladder. A previous study in the area over one decade (2001-2010) showed SCC to be common in patients aged below 50 years. With various prevention and intervention programs there are likely to be notable changes in schistosomiasis-related urinary bladder cancer, which is currently unknown. Updated information on the status of SCC in this area will be useful for giving an insights into efficacy of control interventions implemented and help guide the initiation of new ones. Therefore, this study was done to determine the current trend of schistosomiasis-related bladder cancer in lake zone, Tanzania. METHODS: This was a descriptive retrospective study of histologically confirmed urinary bladder cancer cases diagnosed at the Pathology Department of Bugando Medical Centre over 10 years period. The patient files and histopathology reports were retrieved and information was extracted. Data were analyzed using Chi-square and student t-test. RESULTS: A total of 481 patients were diagnosed with urinary bladder cancer during the study period whereby, 52.6% were males and 47.4% were females. The mean age regardless of histological type of cancer was 55 ± 14.2 years. The SCC was the commonest histological type accounting for 57.0%, followed by transitional cell carcinoma 37.6%, and 5.4% were adenocarcinomas. The Schistosoma haematobium eggs were observed in 25.2% and were commonly associated with SCC (p = 0.001). Poorly differentiated cancers were observed mostly in females (58.6%) compared to males (41.4%) (p = 0.003). Muscular invasion of the urinary bladder by cancer was observed in 11.4% of the patients, and this was significantly higher in non-squamous than in squamous cancers (p = 0.034). CONCLUSION: Schistosomiasis-related cancers of the urinary bladder in the Lake zone of Tanzania is still a problem. Schistosoma haematobium eggs were associated with SCC type indicating the persistence of infection in the area. This calls for more efforts on preventive and intervention programs to reduce the burden of urinary bladder cancer in the lake zone.

Urogenital schistosomiasis among pre-school and school aged children in four districts of north western Tanzania after 15 years of mass drug administration: Geographical prevalence, risk factors and performance of haematuria reagent strips.

BACKGROUND: Urogenital schistosomiasis remains as a public health problem in Tanzania and for the past 15 years, mass drug administration (MDA) targeting primary school children has remained as the mainstay for its control. However, after multiple rounds of MDA in highly risk groups, there are no data on the current status of Schistosoma haematobium in known endemic areas. Furthermore, the performance of commonly used diagnostic test, the urine reagent strips is not known after the decline in prevalence and intensities of infection following repeated rounds of treatment. Thus, after 15 of national MDA, there is a need to review the strategy and infection diagnostic tools available to inform the next stage of schistosomiasis control in the country. METHODS/FINDINGS: A analytical cross-sectional study was conducted between October and November, 2019 among pre-school (3-5years old) and school aged children (6-17 years old) living in four (4) districts with low (<10%) and moderate (10%-<50%) endemicity for schistosomiasis as per WHO classification at the start of the national control programme in 2005/06, with mean prevalence of 20.7%. A total of 20,389 children from 88 randomly selected primary schools participated in the study. A questionnaire was used to record demographic information. A single urine sample was obtained from each participant and visually examined for macrohaematuria, tested with a dipstick for micro-haematuria, to determine blood in urine; a marker of schistosome related morbidity and a proxy of infection. Infection intensity was determined by parasitological examination of the urine sample for S. haematobium eggs. Overall, mean infection prevalence was 7.4% (95%CI: 7.0-7.7, 1514/20,389) and geometric mean infection intensity was 15.8eggs/10mls. Both infection prevalence (5.9% versus 9%, P<0.001) and intensity (t = -6.9256, P<0.001) were significantly higher in males compared to females respectively. Light and heavy infections were detected in 82.3% and 17.7% of the positive children respectively. The prevalence of macrohaematuria was 0.3% and that of microhaematuria was 9.3% (95%CI:8.9-9.7). The sensitivity and specificity of the urine reagent strip were 78% (95%CI: 76.1-79.9) and 99.8% (95%CI: 99.7-99.9). Having light (P<0.001) and heavy infection intensities (P<0.001) and living in the study districts increased the odd of having microhaematuria. Predictors of S. haematobium infection were being male (P<0.003), microhaematuria (P<0.001), and living in the three study districts (P<0.001) compared to living at Nzega district. CONCLUSION: The findings provide an updated geographical prevalence which gives an insight on the planning and implementation of MDA. Comparing with the earlier mapping survey at the start of the national wide mass drug administration, the prevalence of S. haematobium infection have significantly declined. This partly could be attributed to repeated rounds of mass drug administration. The urine reagent strips remain as a useful adjunct diagnostic test for rapid monitoring of urogenital schistosomiasis in areas with low and high prevalence. Based on prevalence levels and with some schools having no detectable infections, review of the current blanket mass drug administration is recommended.

A novel theatre-based behaviour change approach for influencing community uptake of schistosomiasis control measures.

BACKGROUND: Appropriate behaviour change with regard to safe water contact practices will facilitate the elimination of schistosomiasis as a public health concern. Various approaches to effecting this change have been trialled in the field but with limited sustainable outcomes. Our case study assessed the effectiveness of a novel theatre-based behaviour change technique (BCT), in combination with cohort awareness raising and capacity training intervention workshops. METHODOLOGY: Our study was carried out in four rural communities in the Mwanza region of Tanzania and in the semi-urban town of Kemise, Ethiopia. We adapted the Risk, Attitude, Norms, Ability and Self-regulation (RANAS) framework and four phases using a mixed methods approach. Participatory project phase engagement and qualitative formative data were used to guide the design of an acceptable, holistic intervention. Initial baseline (BL) data were collected using quantitative questionnaire surveys with 804 participants in Tanzania and 617 in Ethiopia, followed by the theatre-based BCT and capacity training intervention workshops. A post-intervention (PI) survey was carried out after 6 months, with a participant return rate of 65% in Tanzania and 60% in Ethiopia. RESULTS: The intervention achieved a significant improvement in the knowledge of schistosomiasis transmission being associated with poorly managed sanitation and risky water contact. Participants in Tanzania increased their uptake of preventive chemotherapy (males: BL, 56%; PI, 73%, females: BL, 43%; PI, 50%). There was a significant increase in the selection of sanitation (Tanzania: BL, 13%; PI, 21%, Ethiopia: BL, 63%; PI, 90%), safe water and avoiding/minimising contact with infested waters as prevention methods in Tanzania and Ethiopia. Some of the participants in Tanzania followed on from the study by building their own latrines. CONCLUSIONS: This study showed that substantial positive behaviour changes in schistosomiasis control can be achieved using theatre-based BCT intervention and disease awareness training. With the appropriate sensitisation, education and stakeholder engagement approaches, community members were more open to minimising risk-associated contact with contaminated water sources and were mobilised to implement preventive measures.

Defining elimination as a public health problem for schistosomiasis control programmes: beyond prevalence of heavy-intensity infections.

WHO's 2021-30 road map for neglected tropical diseases (NTDs) outlines disease-specific and cross-cutting targets for the control, elimination, and eradication of NTDs in affected countries. For schistosomiasis, the criterion for elimination as a public health problem (EPHP) is defined as less than 1% prevalence of heavy-intensity infections (ie, ≥50 Schistosoma haematobium eggs per 10 mL of urine or ≥400 Schistosoma mansoni eggs per g of stool). However, we believe the evidence supporting this definition of EPHP is inadequate and the shifting distribution of schistosomiasis morbidity towards more subtle, rather than severe, morbidity in the face of large-scale control programmes requires guidelines to be adapted. In this Viewpoint, we outline the need for more accurate measures to develop a robust evidence-based monitoring and evaluation framework for schistosomiasis. Such a framework is crucial for achieving the goal of widespread EPHP of schistosomiasis and to meet the WHO road map targets. We encourage use of overall prevalence of schistosome infection (instead of the prevalence of heavy-intensity infections), development of species-dependent and age-dependent morbidity markers, and construction of a standardised monitoring and evaluation protocol.

Specific Nucleic AcId Ligation for the detection of Schistosomes: SNAILS.

Schistosomiasis, also known as bilharzia or snail fever, is a debilitating neglected tropical disease (NTD), caused by parasitic trematode flatworms of the genus Schistosoma, that has an annual mortality rate of 280,000 people in sub-Saharan Africa alone. Schistosomiasis is transmitted via contact with water bodies that are home to the intermediate host snail which shed the infective cercariae into the water. Schistosome lifecycles are complex, and while not all schistosome species cause human disease, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform evidence-based local environmental, food security and health systems policy making. Crucially, schistosomiasis disproportionally affects low- and middle-income (LMIC) countries and for that reason, environmental screening of water bodies for schistosomes may aid with the targeting of water, sanitation, and hygiene (WASH) interventions and preventive chemotherapy to regions at highest risk of schistosomiasis transmission, and to monitor the effectiveness of such interventions at reducing the risk over time. To this end, we developed a DNA-based biosensor termed Specific Nucleic AcId Ligation for the detection of Schistosomes or 'SNAILS'. Here we show that 'SNAILS' enables species-specific detection from genomic DNA (gDNA) samples that were collected from the field in endemic areas.

"Using the same hand": The complex local perceptions of integrated one health based interventions in East Africa.

BACKGROUND: Neglected Tropical Diseases (NTDs) such as soil transmitted helminths (STH) and human rabies represent a significant burden to health in East Africa. Control and elimination remains extremely challenging, particularly in remote communities. Novel approaches, such as One Health based integrated interventions, are gaining prominence, yet there is more to be learned about the ways in which social determinants affect such programmes. METHODOLOGY: In 2015 a mixed method qualitative study was conducted in northern Tanzania to determine community perceptions towards integrated delivery of two distinct healthcare interventions: treatment of children for STH and dog vaccination for rabies. In order to assess the effectiveness of the integrated approach, villages were randomly allocated to one of three intervention arms: i) Arm A received integrated mass drug administration (MDA) for STH and mass dog rabies vaccination (MDRV); ii) Arm B received MDA only; iii) Arm C received MDRV only. PRINCIPLE FINDINGS: Integrated interventions were looked upon favourably by communities with respondents in all arms stating that they were more likely to either get their dogs vaccinated if child deworming was delivered at the same time and vice versa. Participants appreciated integrated interventions, due to time and cost savings and increased access to essential health care. Analysis of qualitative data allowed deeper exploration of responses, revealing why people appreciated these benefits as well as constraints and barriers to participation in integrated programmes. CONCLUSIONS/SIGNIFICANCE: An interdisciplinary One Health approach that incorporates qualitative social science can provide key insights into complex local perceptions for integrated health service delivery for STH and human rabies. This includes providing insights into how interventions can be improved while acknowledging and addressing critical issues around awareness, participation and underlying health disparities in remote pastoralist communities.

Genomic analysis of a parasite invasion: Colonization of the Americas by the blood fluke Schistosoma mansoni.

Schistosoma mansoni, a snail-borne, blood fluke that infects humans, was introduced into the Americas from Africa during the Trans-Atlantic slave trade. As this parasite shows strong specificity to the snail intermediate host, we expected that adaptation to South American Biomphalaria spp. snails would result in population bottlenecks and strong signatures of selection. We scored 475,081 single nucleotide variants in 143 S. mansoni from the Americas (Brazil, Guadeloupe and Puerto Rico) and Africa (Cameroon, Niger, Senegal, Tanzania, and Uganda), and used these data to ask: (i) Was there a population bottleneck during colonization? (ii) Can we identify signatures of selection associated with colonization? (iii) What were the source populations for colonizing parasites? We found a 2.4- to 2.9-fold reduction in diversity and much slower decay in linkage disequilibrium (LD) in parasites from East to West Africa. However, we observed similar nuclear diversity and LD in West Africa and Brazil, suggesting no strong bottlenecks and limited barriers to colonization. We identified five genome regions showing selection in the Americas, compared with three in West Africa and none in East Africa, which we speculate may reflect adaptation during colonization. Finally, we infer that unsampled populations from central African regions between Benin and Angola, with contributions from Niger, are probably the major source(s) for Brazilian S. mansoni. The absence of a bottleneck suggests that this is a rare case of a serendipitous invasion, where S. mansoni parasites were pre-adapted to the Americas and able to establish with relative ease.

Transmission potential of human schistosomes can be driven by resource competition among snail intermediate hosts.

Predicting and disrupting transmission of human parasites from wildlife hosts or vectors remains challenging because ecological interactions can influence their epidemiological traits. Human schistosomes, parasitic flatworms that cycle between freshwater snails and humans, typify this challenge. Human exposure risk, given water contact, is driven by the production of free-living cercariae by snail populations. Conventional epidemiological models and management focus on the density of infected snails under the assumption that all snails are equally infectious. However, individual-level experiments contradict this assumption, showing increased production of schistosome cercariae with greater access to food resources. We built bioenergetics theory to predict how resource competition among snails drives the temporal dynamics of transmission potential to humans and tested these predictions with experimental epidemics and demonstrated consistency with field observations. This resource-explicit approach predicted an intense pulse of transmission potential when snail populations grow from low densities, i.e., when per capita access to resources is greatest, due to the resource-dependence of cercarial production. The experiment confirmed this prediction, identifying a strong effect of infected host size and the biomass of competitors on per capita cercarial production. A field survey of 109 waterbodies also found that per capita cercarial production decreased as competitor biomass increased. Further quantification of snail densities, sizes, cercarial production, and resources in diverse transmission sites is needed to assess the epidemiological importance of resource competition and support snail-based disruption of schistosome transmission. More broadly, this work illustrates how resource competition can sever the correspondence between infectious host density and transmission potential.

Genetic analysis of praziquantel response in schistosome parasites implicates a transient receptor potential channel.

Mass drug administration with praziquantel (PZQ) monotherapy is considered the mainstay for control and elimination of the parasites causing schistosomiasis in humans. This drug shows imperfect cure rates in the field, and parasites showing reduced PZQ response can be selected in the laboratory, but the extent of resistance in Schistosoma mansoni populations is unknown. We examined the genetic basis of the variation in response in a PZQ-selected S. mansoni population (SmLE-PZQ-R) in which 35% of the parasitic worms survive high-dose PZQ (73 micrograms per milliliter) treatment. We used genome-wide association to map loci underlying PZQ response and identified a transient receptor potential (Sm.TRPMPZQ) channel (Smp_246790) within the major chromosome 3 peak that is activated by nanomolar concentrations of PZQ. The PZQ response showed recessive inheritance and marker-assisted selection of parasites at a single Sm.TRPMPZQ SNP that produced populations of PZQ-enriched resistant (PZQ-ER) and PZQ-enriched sensitive (PZQ-ES) parasites, exhibiting >377-fold difference in PZQ response. The PZQ-ER parasites survived treatment in rodents at higher frequencies compared with PZQ-ES, and resistant parasites exhibited 2.25-fold lower expression of Sm.TRPMPZQ relative to sensitive parasites. Specific chemical blockers of Sm.TRPMPZQ enhanced PZQ resistance, whereas Sm.TRPMPZQ activators increased sensitivity. We surveyed Sm.TRPMPZQ sequence variations in 259 parasites from different global sites and identified one nonsense mutation that resulted in a truncated protein with no PZQ binding site. Our results demonstrate that Sm.TRPMPZQ underlies variation in PZQ responses in S. mansoni and provides an approach for monitoring emerging PZQ-resistant alleles in schistosome elimination programs.

Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania.

Studies on pharmacogenetics of praziquantel (PZQ) and its relevance on plasma drug concentrations and schistosomiasis treatment outcomes are lacking. We investigated the effect of pharmacogenetics variations of PZQ on plasma drug levels and schistosomiasis treatment outcomes among infected Tanzanian school-aged children. A total of 340 Schistosoma mansoni infected children were enrolled and treated with single-dose PZQ. Stool samples analysis was done by thick smear Kato-Katz technique, and treatment efficacy was assessed at 3-weeks post-treatment. Safety was assessed within 4 h after PZQ intake. Plasma samples were collected at 4 h post-dose, and PZQ and trans-4-OH-PZQ concentrations were quantified using UPLCMS/MS. Genotyping for CYP3A4*1B, CYP3A5 (*3, *6, *7), CYP2C19 (*2, *3, *17), and CYP2C9 (*2, *3) were done by Real-Time PCR. The median age (range) of the study participants was 12 years (7-17). There was a significant association of CYP2C19 genotypes with PZQ concentrations and its metabolic ratio (trans-4-OH-PZQ/PZQ). PZQ concentration was significantly higher among CYP2C19 (*2, *3) carriers than CYP2C19 *1/*1 and CYP2C19 *17 carriers (ultra-rapid metabolizers) (p = 0.04). The metabolic ratio was significantly higher among CYP2C19*17 carriers than CYP2C19 (*2, *3) carriers (p = 0.01). No significant effect of CYP3A4, CYP3A5, CYP2C19, and CYP2C9 genotypes on treatment efficacy or adverse events were observed. Baseline infection intensity and CYP3A5 genotype were significant predictors of treatment associated-adverse events. In conclusion, CYP2C19 genotype significantly affects plasma PZQ concentration and its metabolic ratio. For the first time, we report the importance of pharmacogenetic variation for the treatment of schistosomiasis, a neglected tropical disease.

Optimal single sampling time-point for monitoring of praziquantel exposure in children.

Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC-MS/MS). The correlation between area under the plasma concentration-time curve from 0 to 8 h (AUC8) and plasma concentrations at each specific sampling time-point was determined by Pearson's correlation coefficient (r2). The median age (range) of the study population was 12.5 years (10-17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC8 for both total praziquantel (r2 = 0.81, p < 0.001) and S-praziquantel (r2 = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC8 (r2 = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer.

Hand hygiene intervention to optimise soil-transmitted helminth infection control among primary school children: the Mikono Safi cluster randomised controlled trial in northwestern Tanzania.

BACKGROUND: Soil-transmitted helminth (STH) infections are highly prevalent in resource-limited countries. We assessed the effect of a combination intervention aiming to enhance handwashing with soap on STH reinfection following mass drug administration among primary school children in Kagera region, Northwestern Tanzania. METHODS: We conducted a cluster randomised trial in sixteen primary schools with known high STH prevalence. Schools were randomly assigned in a 1:1 ratio to either receive the intervention or continue with routine health education. The intervention included teacher-led classroom teaching, parental engagement sessions, environmental modifications and improved handwashing stations. The evaluation involved two cross-sectional surveys in a representative sample of students, with the end-line survey conducted 12 months after the baseline survey. The primary outcome was the combined prevalence of Ascaris lumbricoides and Trichuris trichiura infections at the end-line survey. Secondary outcomes included reported handwashing behaviour, the prevalence and intensity of individual STHs, and hand contamination with STH ova and coliform bacteria. End-line STH prevalence and intensity were adjusted for baseline differences of potential confounders. RESULTS: At the end-line survey, 3081 school children (1566 from intervention schools and 1515 from control schools) provided interview data and stool specimens. More school children in the intervention group reported the use of water and soap during handwashing compared to school children in the control group (58% vs. 35%; aOR=1.76, 95%CI 1.28-2.43, p=0.001). The combined prevalence of A. lumbricoides and T. trichiura infections was 39% in both trial arms (aOR = 1.19; 95%CI 0.74-1.91). The prevalence of A. lumbricoides was 15% in the intervention and 17% in the control arm (aOR =1.24, 95%CI 0.59-2.59) and that of T. trichiura was 31% in both arms (aOR=1.17, 95%CI 0.73-1.88). No significant differences were found for STH infection intensity in both the main study and the hand contamination sub-study. CONCLUSIONS: The intervention was effective in increasing reported handwashing behaviour at school, but failed to show a similar effect in the home. The intervention had no effect on STH infection, possibly due to infection in the home environment, other transmission routes such as contaminated water or food or limited changes in school children's handwashing behaviour. TRIAL REGISTRATION: The trial was registered on June 21, 2017, by the International Standard Randomised Controlled Trial Number ( ISRCTN45013173) .

Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment of Schistosoma mansoni Infection.

Praziquantel (PZQ) and dihydroartemisinin-piperaquine (DHP) combination recently showed superior effectiveness than PZQ alone to treat intestinal schistosomiasis. In this follow-up study, we investigated the effect of DHP co-administration on the pharmacokinetics of PZQ and its enantiomers among 64 Schistosoma mansoni infected children treated with PZQ alone (n = 32) or PZQ + DHP combination (n = 32). Plasma samples collected at 0, 1, 2, 4, 6, and 8 h post-dose were quantified using UPLCMS/MS. The geometric mean (GM) of AUCs for total PZQ, R-PZQ and S-PZQ were significantly higher among children who received PZQ + DHP than PZQ alone. The geometric mean ratio (GMR) and (90% CI) of AUC0-∞ for PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 2.18 (1.27, 3.76), 3.98 (2.27, 7.0) and 1.86 (1.06, 3.28), respectively. The GMR and (90% CI) of AUC0-8 for total PZQ, R-PZQ, and S-PZQ were 1.73 (1.12, 2.69), 2.94 (1.75, 4.92), and 1.50 (0.97, 2.31), respectively. The GM of Cmax for total PZQ, R-PZQ and S-PZQ were significantly higher among those who received PZQ + DHP than PZQ alone. The GMR (90% CI) of Cmax of PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 1.75 (1.15, 2.65), 3.08 (1.91, 4.96), and 1.50 (1.0, 2.25%), respectively. The 90% CI of the GMRs for both AUCs and Cmax for total PZQ, R-PZQ, and S-PZQ were outside the acceptable 0.80-1.25 range, indicating that the two treatment arms were not bioequivalent. DHP co-administration significantly increases systemic PZQ exposure, and this may contribute to increased effectiveness of PZQ + DHP combination therapy than PZQ alone to treat schistosomiasis.

Hand hygiene intervention to optimize helminth infection control: Design and baseline results of Mikono Safi-An ongoing school-based cluster-randomised controlled trial in NW Tanzania.

INTRODUCTION: Soil transmitted helminths (STH) can affect over 50% of children in some parts of Tanzania. Control measures involve annual deworming campaigns in schools, but re-infection is rapid. This paper presents the design and baseline survey results of an ongoing school-based cluster-randomised controlled trial in Kagera region, NW Tanzania. The trial aims to determine whether the effect of routine deworming on the prevalence of Ascaris lumbricoides and Trichuris trichiura infections among school aged children can be sustained when combined with a behaviour change intervention promoting handwashing with water and soap. METHODS: As part of the trial, a total of 16 schools were randomised to receive the intervention (N = 8) or as controls (N = 8). Randomisation was stratified per district and restricted to ensure pre-trial STH prevalence was balanced between study arms. The combination intervention to be tested comprises class-room based teacher-led health education, improvement of handwash stations, coloured nudges to facilitate handwashing and parental engagement sessions. The impact evaluation involves two cross-sectional surveys conducted at baseline and endline. The objectives of the baseline survey were: (i) to confirm whether the deworming campaign was successful, and identify and treat students still infected about 2 weeks after deworming, (ii) to document any baseline differences in STH prevalence between trial arms, and (iii) to assess handwashing behaviours, and access to water and sanitation at school and home. We randomly sampled 35 students per class in Grades 1-6 (an average of 200 children per school), stratified to ensure equal representation between genders. Assenting students were interviewed using a structured questionnaire and asked to provide a stool specimen. RESULTS: Results of the baseline survey conducted about 2 weeks after deworming shows balanced demographic and STH prevalence data across trial arms. We observed a low prevalence of ascariasis (< 5%) as expected; however, the prevalence of trichuriasis was still about 35% in both arms. CONCLUSION: The randomisation procedure was successful in achieving a balanced distribution of demographic characteristics and helminth infections between trial arms. The intervention is being rolled out. The current deworming treatment regimen may need to be revised with regards to the treatment of trichuriasis.