Rapid and Comprehensive Screening for Urogenital and Gastrointestinal Schistosomiasis with Handheld Digital Microscopy Combined with Circulating Cathodic Antigen Testing.

Novel methods are required to aid the monitoring of schistosomiasis control and elimination initiatives through mass drug administration. Portable digital and mobile phone microscopy is a promising tool for this purpose. This cross-sectional study evaluated the diagnostic operating characteristics of a converted mobile phone microscope (the SchistoScope) for the detection of Schistosoma haematobium eggs, as determined by community-based field workers and expert microscopists, compared with a field gold standard of light microscopy. Three hundred sixty-five urine samples were evaluated by conventional light microscopy, with 49 (13.4%) positive for S. haematobium. Compared with light microscopy, the sensitivity and specificity of S. haematobium detection by field microscopists trained to use the SchistoScope were 26.5% (95% CI: 14.9-41.1%) and 98.4% (95% CI: 96.3-99.5%), respectively. The sensitivity and specificity of S. haematobium detection by expert microscopists using the SchistoScope was 74% (95% CI: 59.7-85.4%) and 98.1% (95% CI: 95.9-99.3%), respectively, compared with light microscopy. The sensitivity rose to 96.1% and 100% when evaluating for egg counts greater than five and 10 eggs per 10 mL, respectively. A point-of-care circulating cathodic anion (POC CCA) test was used to evaluate Schistosoma mansoni; however, there were too few positive samples to reliably comment on diagnostic characteristics. This study demonstrated that a "urine-only" approach to rapidly screen for schistosomiasis at the point of sample collection can be conducted with mobile phone microscopy (S. haematobium) coupled with POC CCA (S. mansoni). Such an approach may aid in streamlined schistosomiasis control and elimination initiatives.

Development of prediction models to identify hotspots of schistosomiasis in endemic regions to guide mass drug administration.

Schistosomiasis is a neglected tropical disease affecting over 150 million people. Hotspots of Schistosoma transmission-communities where infection prevalence does not decline adequately with mass drug administration-present a key challenge in eliminating schistosomiasis. Current approaches to identify hotspots require evaluation 2-5 y after a baseline survey and subsequent mass drug administration. Here, we develop statistical models to predict hotspots at baseline prior to treatment comparing three common hotspot definitions, using epidemiologic, survey-based, and remote sensing data. In a reanalysis of randomized trials in 589 communities in five endemic countries, a regression model predicts whether Schistosoma mansoni infection prevalence will exceed the WHO threshold of 10% in year 5 ("prevalence hotspot") with 86% sensitivity, 74% specificity, and 93% negative predictive value (NPV; assuming 30% hotspot prevalence), and a regression model for Schistosoma haematobium achieves 90% sensitivity, 90% specificity, and 96% NPV. A random forest model predicts whether S. mansoni moderate and heavy infection prevalence will exceed a public health goal of 1% in year 5 ("intensity hotspot") with 92% sensitivity, 79% specificity, and 96% NPV, and a boosted trees model for S. haematobium achieves 77% sensitivity, 95% specificity, and 91% NPV. Baseline prevalence is a top predictor in all models. Prediction is less accurate in countries not represented in training data and for a third hotspot definition based on relative prevalence reduction over time ("persistent hotspot"). These models may be a tool to prioritize high-risk communities for more frequent surveillance or intervention against schistosomiasis, but prediction of hotspots remains a challenge.

Effects of Climate Variability on Malaria Transmission in Southern Côte d'Ivoire, West Africa.

Malaria continues to be a major public health concern with a substantial burden in Africa. Even though it has been widely demonstrated that malaria transmission is climate-driven, there have been very few studies assessing the relationship between climate variables and malaria transmission in Côte d'Ivoire. We used the VECTRI model to predict malaria transmission in southern Côte d'Ivoire. First, we tested the suitability of VECTRI in modeling malaria transmission using ERA5 temperature data and ARC2 rainfall data. We then used the projected climatic data pertaining to 2030, 2050, and 2080 from a set of 14 simulations from the CORDEX-Africa database to compute VECTRI outputs. The entomological inoculation rate (EIR) from the VECTRI model was well correlated with the observed malaria cases from 2010 to 2019, including the peaks of malaria cases and the EIR. However, the correlation between the two parameters was not statistically significant. The VECTRI model predicted an increase in malaria transmissions in both scenarios (RCP8.5 and RCP4.5) for the time period 2030 to 2080. The monthly EIR for RCP8.5 was very high (1.74 to 1131.71 bites/person) compared to RCP4.5 (0.48 to 908 bites/person). These findings call for greater efforts to control malaria that take into account the impact of climatic factors.

Associations between soil-transmitted helminth infections and physical activity, physical fitness, and cardiovascular disease risk in primary schoolchildren from Gqeberha, South Africa.

BACKGROUND/AIM: School-aged children in low- and middle-income countries carry the highest burden of intestinal helminth infections, such as soil-transmitted helminths (STH). STH infections have been associated with negative consequences for child physical and cognitive development and wellbeing. With the epidemiological transition and rise in cardiovascular disease (CVD), studies have shown that helminth infections may influence glucose metabolism by preventing obesity. Thus, the aim of this study was to determine the association of STH infections in schoolchildren from Gqeberha, focusing on physical activity, physical fitness, and clustered CVD risk score. METHODS: This cross-sectional study involved 680 schoolchildren (356 girls and 324 boys; mean age 8.19 years, SD±1.4) from disadvantaged communities in Gqeberha (formerly, Port Elizabeth), South Africa. Stool samples were collected and examined for STH infections using the Kato-Katz method. Physical activity (accelerometer) and physical fitness (grip strength, 20 m shuttle run) were measured using standard procedures. Furthermore, anthropometry, blood pressure, as well as glycated haemoglobin and lipid profile from capillary blood samples were assessed. We employed one-way ANOVAs to identify the associations of STH infections in terms of species and infection intensity with physical activity, physical fitness, and clustered CVD risk score. RESULTS: We found a low STH infection prevalence (7.2%) in our study, with participants infected with at least one intestinal helminth species. In comparison to their non-infected peers, children infected with STH had lower mean grip strength scores, but higher mean VO2max estimation and higher levels of MVPA (p < .001). When considering type and intensity of infection, a positive association of A. lumbricoides infection and MVPA was found. In contrast, light T. trichiura-infected children had significantly lower grip strength scores compared to non and heavily-infected children. VO2max and MVPA were positively associated with light T. trichiura infection. No significant association between the clustered CVD risk score and infection with any STH species was evident. CONCLUSIONS: STH-infected children had lower grip strength scores than their non-infected peers, yet, achieved higher VO2max and MVPA scores. Our study highlights that the type and intensity of STH infection is relevant in understanding the disease burden of STH infections on children's health. The findings of our study must be interpreted cautiously due to the low infection rate, and more research is needed in samples with higher prevalence rates or case-control designs.

Efficacy and Safety of Moxidectin-Albendazole and Ivermectin-Albendazole Combination Therapy Compared to Albendazole Monotherapy in Adolescents and Adults Infected with Trichuris trichiura: A Randomized, Controlled Superiority Trial.

BACKGROUND: The currently recommended benzimidazole monotherapy is insufficiently effective to control infection with the soil-transmitted helminth Trichuris trichiura. Ivermectin-albendazole combination has shown promising, but setting-dependent efficacy, with therapeutic underperformance in Côte d'Ivoire. We evaluated whether moxidectin-albendazole could serve as an alternative to albendazole monotherapy in Côte d'Ivoire. METHODS: In this community-based, randomized, placebo-controlled, parallel-group superiority trial, individuals aged 12-60 years were screened for T. trichiura eggs in their stool using quadruplicate Kato-Katz thick smears. Diagnostically and clinically eligible participants were randomly assigned (1:1:1) to receive single oral doses of moxidectin (8 mg) and albendazole (400 mg), ivermectin (200 µg/kg) and albendazole (400 mg), or albendazole (400 mg) and placebo. The primary outcome was proportion cured, ie, cure rate (CR), assessed at 2-3 weeks post-treatment. Safety endpoints were assessed pre-treatment and at 3 and 24 hours post-treatment. RESULTS: For the 210 participants with primary outcome data, we observed CRs of 15.3% in the moxidectin-albendazole arm and 22.5% in the ivermectin-albendazole arm, which did not differ significantly from the CR of 13.4% in the albendazole arm (differences: 1.8%-points [95% confidence interval: -10.1 to 13.6] and 9.1%-points [-3.9 to 21.8], respectively). Most common adverse events were abdominal pain (range across arms: 11.9%-20.9%), headache (4.7%-14.3%), and itching (5.8%-13.1%), which were predominantly mild and transient. CONCLUSIONS: All therapies showed similar low efficacy in treating trichuriasis in Côte d'Ivoire. Alternative treatment options need to be evaluated, and further analyses should be conducted to understand the lack of enhanced activity of the combination therapies in Côte d'Ivoire. CLINICAL TRIALS REGISTRATION: NCT04726969.

Correction: A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication?

[This corrects the article DOI: 10.1371/journal.pntd.0009144.].

High Sensitivity of Mobile Phone Microscopy Screening for Schistosoma haematobium in Azaguié, Côte d'Ivoire.

Schistosomiasis infections continue to impact African settings disproportionately, and there is an urgent need for novel tools to evaluate infection control and elimination strategies at the community level. Mobile phone microscopes are portable and semiautomated devices with multiple applications for screening neglected tropical diseases. In a community-based schistosomiasis screening program in Azaguié, Côte d'Ivoire, mobile phone microscopy demonstrated a sensitivity of 85.7% (95% CI: 69.7-95.2%) and specificity of 93.3% (95% CI: 87.7-96.9%) for Schistosoma haematobium identification compared with conventional light microscopy, and 95% sensitivity (95% CI: 74.1-99.8%) with egg concentrations of five or more per 10 mL of urine. Mobile phone microscopy is a promising tool for schistosomiasis control and elimination efforts.

Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial).

BACKGROUND: Most studies assessing praziquantel (PZQ) efficacy have used relatively insensitive diagnostic methods, thereby overestimating cure rate (CR) and intensity reduction rate (IRR). To determine accurately PZQ efficacy, we employed more sensitive DNA and circulating antigen detection methods. METHODOLOGY: A sub-analysis was performed based on a previously published trial conducted in children from Côte d'Ivoire with a confirmed Schistosoma mansoni infection, who were randomly assigned to a standard (single dose of PZQ) or intense treatment group (4 repeated doses of PZQ at 2-week intervals). CR and IRR were estimated based on PCR detecting DNA in a single stool sample and the up-converting particle lateral flow (UCP-LF) test detecting circulating anodic antigen (CAA) in a single urine sample, and compared with traditional Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA). PRINCIPAL FINDINGS: Individuals positive by all diagnostic methods (i.e., KK, POC-CCA, PCR, and UCP-LF CAA) at baseline were included in the statistical analysis (n = 125). PCR showed a CR of 45% (95% confidence interval (CI) 32-59%) in the standard and 78% (95% CI 66-87%) in the intense treatment group, which is lower compared to the KK results (64%, 95% CI 52-75%) and 88%, 95% CI 78-93%). UCP-LF CAA showed a significantly lower CR in both groups, 16% (95% CI 11-24%) and 18% (95% CI 12-26%), even lower than observed by POC-CCA (31%, 95% CI 17-35% and 36%, 95% CI 26-47%). A substantial reduction in DNA and CAA-levels was observed after the first treatment, with no further decrease after additional treatment and no significant difference in IRR between treatment groups. CONCLUSION/SIGNIFICANCE: The efficacy of (repeated) PZQ treatment was overestimated when using egg-based diagnostics (i.e. KK and PCR). Quantitative worm-based diagnostics (i.e. POC-CCA and UCP-LF CAA) revealed that active Schistosoma infections are still present despite multiple treatments. These results stress the need for using accurate diagnostic tools to monitor different PZQ treatment strategies, in particular when moving toward elimination of schistosomiasis. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT02868385.

Dietary diversity in primary schoolchildren of south-central Côte d'Ivoire and risk factors for non-communicable diseases.

BACKGROUND: A balanced nutrition is important for children's physical and cognitive development; yet, remains a challenge in many parts of low- and middle-income countries (LMICs). Early detection of nutritional deficiency and metabolic syndrome in school-aged children is necessary to prevent non-communicable diseases (NCDs) in later life. This study aimed at obtaining baseline data on health, nutritional status, and metabolic markers of NCDs among primary schoolchildren in Côte d'Ivoire. METHODS: A cross-sectional survey was conducted among 620 children from 8 public primary schools located in the south-central part of Côte d'Ivoire. Underweight and overweight were defined as a body mass index (BMI; kg/m2) < 5th and 85th up to 95th percentile for sex and age, respectively. Dietary diversity of children was calculated based on a 24-hour recall conducted with the primary caretaker according to the guideline of Food and Agriculture Organization. Anaemia, malaria, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and blood glucose levels (HbA1c) were assessed, using capillary blood samples. Logistic models were performed to identify risk factors associated with overweight, HDL-C, LDL-C, and HbA1c. RESULTS: Among the 620 children (330 girls, 290 boys; Mage 8.0 (± 1.7) years), 530 children attended school in a semi-urban and 90 in a rural area. Around 60% of children had a medium dietary diversity score (DDS). Children in peri-urban areas consumed more cereals (80.2% vs. 63.3%, p < 0.05). Most children were normal weight (n = 496), whereas 3.9% of children classified as prediabetic, 5% were underweight, and 15% overweight. LDL-C and HDL-C levels of children were associated with age, high DDS, and moderate anaemia. A significant association was found between prediabetes and malaria infection, as well as medium and high DDS. Overweight was associated with malaria infection and moderate anaemia. CONCLUSION: Overweight, prediabetes, low HDL-C, malaria, and anaemia are the main concerns of children's health in Taabo. Our findings highlight interactions between infectious diseases, particularly malaria, and NCD risk factors. Monitoring NCD risk and infectious disease comorbidity in LMIC paediatric populations simultaneously is essential to better understand the dual diseases burden and apply early prevention measures.

Optimizing Implementation of Preventive Chemotherapy against Soil-Transmitted Helminthiasis and Intestinal Schistosomiasis Using High-Resolution Data: Field-Based Experiences from Côte d'Ivoire.

BACKGROUND: Despite efforts to control neglected tropical diseases (NTDs) using preventive chemotherapy (PC), soil-transmitted helminthiases and schistosomiasis remain widely prevalent in sub-Saharan Africa. The current PC regimen in endemic settings is defined based on health district-level prevalence. This work aims to highlight the need for high-resolution data when elimination, rather than morbidity control, is the targeted goal. METHODOLOGY: Cross-sectional parasitological surveys were conducted from July to August 2019 and from September to October 2019, respectively, across the entire Dabou and Jacqueville health districts in southern Côte d'Ivoire. From every village, 60 school-aged children (6-15 years) were randomly selected and invited to provide one fresh stool sample, whereof duplicate Kato-Katz thick smears were prepared and read by two independent technicians. PRINCIPAL FINDINGS: 4338 school-aged children from 77 villages were screened from the Dabou (n = 2174; 50.12%, 39 villages) and Jacqueville (n = 2164; 49.88%, 38 villages) health districts. The prevalence of any soil-transmitted helminth (STH) infection was 12.47% and 11.09% in the Dabou and Jacqueville health districts, respectively. Species-specific district-level prevalence remained below 10%, varying between 0.51% (hookworm in Jacqueville) and 9.06% (Trichuris trichiura in Dabou). However, when considering sub-districts or villages only, several STH infection hotspots (five sub-districts with ≥20% and four villages with more than 50% infected) were observed. Schistosoma mansoni infection was found in less than 1% of the examined children in each health district. CONCLUSIONS/SIGNIFICANCE: We conclude that keeping health district-level prevalence as a reference for PC implementation leaves many high-risk sub-districts or villages requiring PC (≥20% prevalence) untreated. To avoid maintaining those high-risk villages as STH reservoirs by skipping control interventions and jeopardizing the successes already achieved in STH control through PC during the past two decades, precision mapping is required. Further investigation is needed to assess cost-efficient approaches to implement small-scale disease surveillance.

Is grip strength linked to body composition and cardiovascular risk markers in primary schoolchildren? Cross-sectional data from three African countries.

OBJECTIVES: Muscular strength represents a specific component of health-related fitness. Hand grip strength (HGS) is used as an indicator for musculoskeletal fitness in children. HGS can also be used as a marker of cardiometabolic risk, but most available HGS data are derived from Western high-income countries. Therefore, this study examines whether HGS is associated with body composition and markers of cardiovascular risk in children from three sub-Saharan African countries. DESIGN: Cross-sectional study. SETTING: Public primary schools (grade 1-4) in Taabo (Côte d'Ivoire), Gqeberha (South Africa) and Ifakara (Tanzania). PARTICIPANTS: Data from 467 children from Côte d'Ivoire (210 boys, 257 girls), 864 children from South Africa (429 boys, 435 girls) and 695 children from Tanzania (334 boys, 361 girls) were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Body composition (assessed via bioelectrical impedance analysis) was the primary outcome. Cardiovascular risk markers were considered as secondary outcome. Blood pressure was measured with an oscillometric monitor, and blood markers (cholesterol, triglycerides, glycated haemoglobin) via Afinion point-of-care testing. HGS (independent variable) was assessed with a hydraulic hand dynamometer. Inferential statistics are based on mixed linear regressions and analyses of covariance. RESULTS: Across all study sites, higher HGS was associated with lower body fat, higher muscle mass and higher fat-free mass (p<0.001, 3.9%-10.0% explained variance), both in boys and girls. No consistent association was found between HGS and cardiovascular risk markers. CONCLUSIONS: HGS assessment is popular due to its simplicity, feasibility, practical utility and high reliability of measurements. This is one of the first HGS studies with children from sub-Saharan Africa. There is a great need for further studies to examine whether our findings can be replicated, to develop reference values for African children, to establish links to other health outcomes, and to explore whether HGS is associated with later development of cardiovascular risk markers. TRIAL REGISTRATION NUMBER: ISRCTN29534081.

Population genetic structure of Schistosoma haematobium and Schistosoma haematobium × Schistosoma bovis hybrids among school-aged children in Côte d'Ivoire.

While population genetics of Schistosoma haematobium have been investigated in West Africa, only scant data are available from Côte d'Ivoire. The purpose of this study was to analyze both genetic variability and genetic structure among S. haematobium populations and to quantify the frequency of S. haematobium × S. bovis hybrids in school-aged children in different parts of Côte d'Ivoire. Urine samples were subjected to a filtration method and examined microscopically for Schistosoma eggs in four sites in the western and southern parts of Côte d'Ivoire. A total of 2692 miracidia were collected individually and stored on Whatman® FTA cards. Of these, 2561 miracidia were successfully genotyped for species and hybrid identification using rapid diagnostic multiplex mitochondrial cox1 PCR and PCR Restriction Fragment Length Polymorphism (PCR-RFLP) analysis of the nuclear ITS2 region. From 2164 miracidia, 1966 (90.9%) were successfully genotyped using at least 10 nuclear microsatellite loci to investigate genetic diversity and population structure. Significant differences were found between sites in all genetic diversity indices and genotypic differentiation was observed between the site in the West and the three sites in the East. Analysis at the infrapopulation level revealed clustering of parasite genotypes within individual children, particularly in Duekoué (West) and Sikensi (East). Of the six possible cox1-ITS2 genetic profiles obtained from miracidia, S. bovis cox1 × S. haematobium ITS2 (42.0%) was the most commonly observed in the populations. We identified only 15 miracidia (0.7%) with an S. bovis cox1 × S. bovis ITS2 genotype. Our study provides new insights into the population genetics of S. haematobium and S. haematobium × S. bovis hybrids in humans in Côte d'Ivoire and we advocate for researching hybrid schistosomes in animals such as rodents and cattle in Côte d'Ivoire.

Title: Structuration génétique des populations de Schistosoma haematobium et des hybrides Schistosoma haematobium × Schistosoma bovis chez les enfants d'âge scolaire en Côte d'Ivoire. Abstract: Alors que la génétique des populations de Schistosoma haematobium a été étudiée en Afrique de l'Ouest, seules quelques données sont disponibles pour la Côte d'Ivoire. Le but de cette étude était d'analyser à la fois la variabilité génétique et la structure génétique des populations de S. haematobium et de quantifier la fréquence des hybrides S. haematobium × S. bovis chez les enfants d'âge scolaire dans différentes régions de la Côte d'Ivoire. Des échantillons d'urine ont été soumis à une méthode de filtration et examinés au microscope pour les œufs de Schistosoma dans quatre sites de l'ouest et du sud de la Côte d'Ivoire. Au total, 2 692 miracidia ont été collectés individuellement et stockés sur des cartes Whatman® FTA. Parmi ceux-ci, 2 561 miracidia ont été génotypés avec succès pour l'identification des espèces et des hybrides à l'aide de la PCR multiplex de diagnostic rapide du cox1 mitochondrial et d'une analyse du polymorphisme de longueur des fragments de restriction de PCR (PCR-RFLP) de la région ITS2 de l'ADN nucléaire. Sur 2 164 miracidia, 1 966 (90,9 %) ont été génotypés avec succès en utilisant au moins 10 loci microsatellites nucléaires pour étudier la diversité génétique et la structure de la population. Des différences significatives ont été trouvées entre les sites dans tous les indices de diversité génétique et une différenciation génotypique a été observée entre le site de l'Ouest et les trois sites de l'Est. L'analyse au niveau de l'infrapopulation a révélé un regroupement des génotypes de parasites au sein de chaque enfant, en particulier à Duekoué (Ouest) et Sikensi (Est). Parmi les six profils génétiques cox1-ITS2 possibles obtenus à partir de miracidia, S. bovis cox1 × S. haematobium ITS2 (42,0 %) était le plus fréquemment observé dans les populations. Nous avons identifié seulement 15 miracidia (0,7 %) avec un génotype S. bovis cox1 × S. bovis ITS2. Notre étude apporte de nouvelles connaissances sur la génétique des populations de S. haematobium et des hybrides S. haematobium × S. bovis chez l'homme en Côte d'Ivoire et nous plaidons pour la recherche de schistosomes hybrides chez les animaux (rongeurs et bovins) en Côte d'Ivoire.

Accuracy of a rapid diagnosis test, microscopy and loop-mediated isothermal amplification in the detection of asymptomatic Plasmodium infections in Korhogo, Northern Côte d'Ivoire.

BACKGROUND: Highly sensitive and accurate malaria diagnostic tools are essential to identify asymptomatic low parasitaemia infections. This study evaluated the performance of histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (RDTs), microscopy and loop-mediated isothermal amplification (LAMP) for the detection of asymptomatic Plasmodium spp. infections in Northern Côte d'Ivoire, using nested polymerase chain reaction (nPCR) as reference. METHODS: A household-based survey was carried out in July 2016, in the health district of Korhogo, involving 1011 adults without malaria symptom nor history of fever during the week before recruitment. The fresh capillary blood samples were collected to detect Plasmodium infections using on HRP-2-based RDTs, microscopy and LAMP and stored as dried blood spots (DBS). A subset of the DBS (247/1011, 24.4%) was randomly selected for nPCR analyses. Additionally, venous blood samples, according to LAMP result (45 LAMP positive and 65 LAMP negative) were collected among the included participants to perform the nested PCR used as the reference. RESULTS: The prevalence of asymptomatic Plasmodium spp. infections determined by RDT, microscopy, and LAMP were 4% (95% confidence interval (CI) 2.8-5.3), 5.2% (95% CI 3.9-6.6) and 18.8% (95% CI 16.4-21.2), respectively. Considering PCR on venous blood as reference, performed on 110 samples, the sensibility and specificity were, respectively, 17.8% (95% CI 6.1-29.4) and 100% for RDT, 20.0% (95% CI 7.8-32) and 100% for microscopy, and 93.3% (95% CI 85.7-100) and 95.4% (95% CI 92.2-100) for LAMP. CONCLUSION: In Northern Côte d'Ivoire, asymptomatic Plasmodium infection was found to be widely distributed as approximately one out of five study participants was found to be Plasmodium infected. LAMP appears currently to be the only available diagnostic method that can identify in the field this reservoir of infections and should be the method to consider for potential future active case detection interventions targeting elimination of these infections.

Point-of-Care Sample Preparation and Automated Quantitative Detection of Schistosoma haematobium Using Mobile Phone Microscopy.

Schistosoma haematobium continues to pose a significant public health burden despite ongoing global control efforts. One of several barriers to sustained control (and ultimately elimination) is the lack of access to highly sensitive diagnostic or screening tools that are inexpensive, rapid, and can be used at the point of sample collection. Here, we report an automated point-of-care diagnostic based on mobile phone microscopy that rapidly images and identifies S. haematobium eggs in urine samples. Parasite eggs are filtered from urine within a specialized, inexpensive cartridge that is then automatically imaged by the mobile phone microscope (the "SchistoScope"). Parasite eggs are captured at a constriction point in the tapered cartridge for easy imaging, and the automated quantification of eggs is obtained upon analysis of the images by an algorithm. We demonstrate S. haematobium egg detection with greater than 90% sensitivity and specificity using this device compared with the field gold standard of conventional filtration and microscopy. With simple sample preparation and image analysis on a mobile phone, the SchistoScope combines the diagnostic performance of conventional microscopy with the analytic performance of an expert technician. This portable device has the potential to provide rapid and quantitative diagnosis of S. haematobium to advance ongoing control efforts.

Pharmacokinetic modelling and simulation to optimize albendazole dosing in hookworm- or Trichuris trichiura-infected infants to adults.

BACKGROUND: Albendazole is the most commonly used drug in preventive chemotherapy programmes against soil-transmitted helminth (STH) infections, with the standard dose of 400 mg resulting in suboptimal clinical outcomes. Population pharmacokinetic (PK) models that could inform dosing strategies are not yet available. METHODS: A population pharmacokinetic model was developed based on micro-blood samples collected from 252 patients aged 2 to 65 years, infected with either hookworm or Trichuris trichiura and treated with albendazole doses ranging from of 200 to 800 mg. An exposure-response analysis was performed relating albendazole and its two metabolites to cure rates and egg reduction rates (ERR). Finally, model-based simulations were conducted to determine equivalent exposure coverage in infants to adults. RESULTS: A population PK model, with one distribution compartment for each compound and one peripheral compartment, following oral administration with a lag time, assuming first-order absorption and linear elimination, best described the concentration-time profiles. Clearance and volume parameters were scaled to body size (weight for albendazole and height for albendazole sulfoxide and sulfone). Dose proportionality was observed for the active metabolite, albendazole sulfoxide, but only in hookworm-infected individuals, with increasing exposure resulting in increased ERR. Exposure of sulfoxide was lowest in the tallest individuals. CONCLUSIONS: Pharmacometric simulations indicate that doses up to 800 mg could further increase albendazole efficacy in hookworm-infected adults, whereas the standard dose of 400 mg is sufficient in the youngest age cohorts. In the absence of evidence-based arguments for adjusting albendazole doses in T. trichiura-infected individuals, the search for new treatment options is further emphasized.

R-praziquantel integrated population pharmacokinetics in preschool- and school-aged African children infected with Schistosoma mansoni and S. haematobium and Lao adults infected with Opisthorchis viverrini.

Racemic praziquantel (PZQ) is the standard treatment for schistosomiasis and liver fluke infections (opisthorchiasis and clonorchiasis). The development of an optimal pediatric formulation and dose selection would benefit from a population pharmacokinetic (popPK) model. A popPK model was developed for R-PZQ, the active enantiomer of PZQ, in 664 subjects, 493 African children (2-15 years) infected with Schistosoma mansoni and S. haematobium, and 171 Lao adults (15-78 years) infected with Opisthorchis viverrini. Racemate tablets were administered as single doses of 20, 40 and 60 mg/kg in children and 30, 40 and 50 mg/kg in 129 adults, and as 3 × 25 mg/kg apart in 42 adults. Samples collected by the dried-blood-spot technique were assayed by LC-MS/MS. A two-compartment disposition model, with allometric scaling and dual first-order and transit absorption, was developed using Phoenix™ software. Inversely parallel functions of age described the apparent oral bioavailability (BA) and clearance maturation in children and ageing in adults. BA decreased slightly in children with dose increase, and by 35% in adults with multiple dosing. Crushing tablets for preschool-aged children increased the first-order absorption rate by 64%. The mean transit absorption time was 70% higher in children. A popPK model for R-PZQ integrated African children over 2 years of age with schistosomiasis and Lao adults with opisthorchiasis, and should be useful to support dose optimization in children. In vitro hepatic and intestinal metabolism data would help refining and validating the model in younger children as well as in target ethnic pediatric and adult groups.

Efficacy and safety of co-administered ivermectin and albendazole in school-aged children and adults infected with Trichuris trichiura in Côte d'Ivoire, Laos, and Pemba Island, Tanzania: a double-blind, parallel-group, phase 3, randomised controlled trial.

BACKGROUND: Preventive chemotherapy with albendazole or mebendazole remains one of the cornerstones of soil-transmitted helminth control. However, these drugs are less effective against Trichuris trichiura. Combined ivermectin-albendazole is a promising treatment alternative, yet robust evidence is lacking. We aimed to demonstrate superiority of co-administered ivermectin-albendazole over albendazole monotherapy in three distinct epidemiological settings. METHODS: We conducted a double-blind, parallel-group, phase 3, randomised controlled trial in community members aged 6-60 years infected with T trichiura in Côte d'Ivoire, Laos, and Pemba Island, Tanzania, between Sept 26, 2018, and June 29, 2020. Participants with at least 100 T trichiura eggs per g of stool at baseline were randomly assigned (1:1) using computer-generated randomisation sequences in varying blocks of four, six, and eight, stratified by baseline T trichiura infection intensity, to orally receive either a single dose of ivermectin (200 µg/kg) plus albendazole (400 mg) or albendazole (400 mg) plus placebo. Patients, field staff, and outcome assessors were masked to treatment assignment. The primary outcome was cure rate against T trichiura, defined as the proportion of participants with no eggs in their faeces 14-21 days after treatment, assessed by Kato-Katz thick smears, and analysed in the available-case population according to intention-to-treat principles. Safety was a secondary outcome and was assessed 3 h and 24 h after drug administration. The trial is registered at ClinicalTrials.gov, NCT03527732. FINDINGS: Between Sept 13 and Dec 18, 2019, Jan 12 and April 5, 2019, and Sept 26 and Nov 5, 2018, 3737, 3694, and 1435 community members were screened for trial eligibility in Côte d'Ivoire, Laos, and Pemba Island, respectively. In Côte d'Ivoire, Laos, and Pemba Island, 256, 274, and 305 participants, respectively, were randomly assigned to the albendazole group, and 255, 275, and 308, respectively, to the ivermectin-albendazole group. Primary outcome data were available for 722 participants treated with albendazole and 733 treated with ivermectin-albendazole. Ivermectin-albendazole showed significantly higher cure rates against T trichiura than albendazole in Laos (66% [140 of 213]vs 8% [16 of 194]; difference 58 percentage points, 95% CI 50 to 65, p<0·0001) and Pemba Island (49% [140 of 288]vs 6% [18 of 293], 43 percentage points, 36 to 49, p<0·0001) but had similar efficacy in Côte d'Ivoire (14% [32 of 232]vs 10% [24 of 235], 4 percentage points, -2 to 10, p=0·24). No serious adverse events were reported; observed events were mostly classified as mild (95% [266 of 279] in the albendazole group and 91% [288 of 317] in the ivermectin-albendazole group), and all were transient in nature. INTERPRETATION: Treatment with ivermectin-albendazole resulted in higher efficacy against trichuriasis than albendazole alone in Laos and Pemba Island but not in Côte d'Ivoire. We recommend implementation of this combination therapy for soil-transmitted helminth control in countries with high T trichiura prevalence and proven enhanced efficacy of this treatment, particularly where ivermectin is beneficial against other endemic helminthiases. FUNDING: Bill & Melinda Gates Foundation.