Implementation and Outcomes of a Pilot Collaborative Surgical Hydrocele Training in Côte d'Ivoire.

Lymphatic filariasis (LF) is a neglected tropical disease that can cause hydrocele and its associated stigma, loss of economic productivity, and depression. Hydrocele surgery is an essential part of LF morbidity management but can be difficult for national programs to implement. To improve access to hydrocele surgeries in Côte d'Ivoire, we provided a WHO-certified surgical training for six surgical teams from five health districts in Côte d'Ivoire. We then evaluated the surgical outcomes and assessed the impact of hydrocele surgery on quality of life of hydrocelectomy patients. Preoperative and operative records were reviewed to describe baseline hydrocele characteristics and operative details. Postoperative interviews were conducted 4 to 6 months after surgical correction using a standardized questionnaire. Seventeen men underwent surgery during the training and were available for an interview at the 6-month visit. At the time of 6-month follow-up, 11/17 (64.7%) reported improvement in activities of daily living and reduction in difficulties with work, 8/17 (47.1%) reported an improved economic situation, 15/17 (88.2%) reported improved social interactions, and 15/16 (93.8%) reported improved sex life after surgical correction. Three patients (17.6%) had minor postoperative complications, but none required hospitalization. All 17 patients who were available for an interview were satisfied with their surgery. Surgical hydrocelectomy training in Côte d'Ivoire was well received and provided life-altering health improvements for participating patients across multiple domains of life. Support to scale up surgical capacity for this neglected problem is needed.

Synthesis of findings from the literature and a qualitative research study on the impacts of gender, disability, and ethnicity in Neglected Tropical Diseases programs.

INTRODUCTION: Act to End NTDs | West, a USAID-funded program that supports national governments to eliminate or control five neglected tropical diseases (NTDs) in West Africa including trachoma, lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminthiasis, conducted a gender and social inclusion analysis to determine how NTDs differentially impact various populations and how gender and social norms impact NTD programs to inform future programming. METHODS: The study used a mixed methods approach including a literature review; primary qualitative data collection; and monitoring data in Côte d'Ivoire, Sierra Leone, and Ghana. RESULTS: Women and girls face additional health risks from many NTDs compared to men and boys. In addition to differential health burden, the social and economic impacts of NTD-related disability or infertility can be particularly dire for women and girls. Men were somewhat less likely to participate in mass drug administration (MDAs) due to: lack of information about campaigns, lack of access due to work, and higher levels of mistrust of the government and concerns about side effects of the medicines. Pregnant and breastfeeding women were sometimes excluded by community drug distributors (CDDs) from certain types of MDAs for which they are eligible. Training participation rates for CDDs and supervisors were nearly universally higher for men than women, even though feedback on the effectiveness of female CDDs was overwhelmingly positive, and female CDDs often have more access to other women in conservative households. The role of a CDD can lead to career and social opportunities for women. However, challenges faced by CDDs were seen as a greater barrier for women, including transportation, safety, household responsibilities, lower education levels, and low or lack of wages. DISCUSSION: Programs to address NTDs can promote equity and improve programming by increasing women's participation as CDDs and providing financial compensation. Additionally, programs should prioritize inclusive training for CDDs, and inclusive messaging about MDA for communities.

High prevalence of trachomatous inflammation-follicular with no trachomatous trichiasis: can alternative indicators explain the epidemiology of trachoma in Côte d'Ivoire?

Baseline trachoma surveys in Côte d'Ivoire (2019) identified seven evaluation units (EUs) with a trachomatous inflammation-follicular (TF) prevalence ≥10%, but a trachomatous trichiasis (TT) prevalence in individuals ≥15 y of age below the elimination threshold (0.2%). Two of these EUs, Bondoukou 1 and Bangolo 2, were selected for a follow-up survey to understand the epidemiology of trachoma using additional indicators of Chlamydia trachomatis infection (DNA from conjunctival swabs) and exposure (anti-Pgp3 and Ct694 antibodies from dried blood spots [DBSs]). A two-stage cluster sampling methodology was used to select villages and households. All individuals 1-9 y of age from each selected household were recruited, graded for trachoma and had a conjunctival swab and DBS collected. Conjunctival swabs and DBSs were tested using Cepheid GeneXpert and a multiplex bead assay, respectively. The age-adjusted TF and infection prevalence in 1- to 9-year-olds was <1% and <0.3% in both EUs. Age-adjusted seroprevalence was 5.3% (95% confidence interval [CI] 1.5 to 15.6) in Bondoukou 1 and 8.2% (95% CI 4.3 to 13.7) in Bangolo 2. The seroconversion rate for Pgp3 was low, at 1.23 seroconversions/100 children/year (95% CI 0.78 to 1.75) in Bondoukou 1 and 1.91 (95% CI 1.58 to 2.24) in Bangolo 2. Similar results were seen for CT694. These infection, antibody and clinical data provide strong evidence that trachoma is not a public health problem in either EU.

Distinguishing recrudescence from reinfection in lymphatic filariasis: a genomics-based approach for monitoring worm burden.

Background: The Global Program to Eliminate Lymphatic Filariasis is the largest public health program based on mass drug administration (MDA). Despite decades of MDA, ongoing transmission in some countries remains a challenge. To optimize interventions, it is essential to differentiate between recrudescence (poor drug response and persistent infection) and new infections (ongoing transmission). Since adult filariae are inaccessible in humans, an approach that relies on genotyping the offspring microfilariae (mf) is required. Methods: We utilized Brugia malayi adults and mf obtained from gerbils with a known pedigree to develop and validate our whole-genome amplification and kinship analysis approach. We then sequenced the genomes of Wuchereria bancrofti mf from infected humans from Côte d'Ivoire (CDI), characterized the population genetic diversity, and made inferences about the adult breeders. We developed a whole-exome capture panel for W. bancrofti to enrich parasite nuclear DNA from lower-quality samples contaminated with host DNA. Results: We established a robust analysis pipeline using B. malayi adult and mf. We estimated the pre-treatment genetic diversity in W. bancrofti from 269 mf collected from 18 individuals, and further analyzed 1-year post-treatment samples of 74 mf from 4 individuals. By reconstructing and temporally tracking sibling relationships across pre- and post-treatment samples, we differentiated between new and established maternal families, suggesting reinfection in one subject and recrudescence in three subjects. Estimated reproductively active adult females ranged between 3 and 9 in the studied subjects. Hemizygosity of the male X-chromosome allowed for direct inference of haplotypes, facilitating robust maternal parentage inference, even when the genetic diversity was low. Population structure analysis revealed genetically distinct parasites among our CDI samples. Sequence composition and variant analysis of whole-exome libraries showed that the hybridization capture approach can effectively enrich parasite nuclear DNA and identify protein-coding variants with ∼95% genotype concordance rate. Conclusions: We have generated resources to facilitate development of field-deployable genotyping tools that can estimate worm burdens and monitor parasite populations. These tools are essential for the success of lymphatic filariasis MDA programs. With further expansion of the databases to include geographically diverse samples, we will be able to spatially track parasite movement associated with host/vector migration.

How well do coverage surveys and programmatically reported mass drug administration coverage match? Results from 214 mass drug administration campaigns in 15 countries, 2008-2017.

INTRODUCTION: Delivering preventive chemotherapy through mass drug administration (MDA) is a central approach in controlling or eliminating several neglected tropical diseases (NTDs). Treatment coverage, a primary indicator of MDA performance, can be measured through routinely reported programmatic data or population-based coverage evaluation surveys. Reported coverage is often the easiest and least expensive way to estimate coverage; however, it is prone to inaccuracies due to errors in data compilation and imprecise denominators, and in some cases measures treatments offered as opposed to treatments swallowed. OBJECTIVE: Analyses presented here aimed to understand (1) how often coverage calculated using routinely reported data and survey data would lead programme managers to make the same programmatic decisions; (2) the magnitude and direction of the difference between these two estimates, and (3) whether there is meaningful variation by region, age group or country. METHODS: We analysed and compared reported and surveyed treatment coverage data from 214 MDAs implemented between 2008 and 2017 in 15 countries in Africa, Asia and the Caribbean. Routinely reported treatment coverage was compiled using data reported by national NTD programmes to donors, either directly or via NTD implementing partners, following the implementation of a district-level MDA campaign; coverage was calculated by dividing the number of individuals treated by a population value, which is typically based on national census projections and occasionally community registers. Surveyed treatment coverage came from post-MDA community-based coverage evaluation surveys, which were conducted as per standardised WHO recommended methodology. RESULTS: Coverage estimates using routine reporting and surveys gave the same result in terms of whether the minimum coverage threshold was reached in 72% of the MDAs surveyed in the Africa region and in 52% in the Asia region. The reported coverage value was within ±10 percentage points of the surveyed coverage value in 58/124 of the surveyed MDAs in the Africa region and 19/77 in the Asia region. Concordance between routinely reported and surveyed coverage estimates was 64% for the total population and 72% for school-age children. The study data showed variation across countries in the number of surveys conducted as well as the frequency with which there was concordance between the two coverage estimates. CONCLUSIONS: Programme managers must grapple with making decisions based on imperfect information, balancing needs for accuracy with cost and available capacity. The study shows that for many of the MDAs surveyed, based on the concordance with respect to reaching the minimum coverage thresholds, the routinely reported data were accurate enough to make programmatic decisions. Where coverage surveys do show a need to improve accuracy of routinely reported results, NTD programme managers should use various tools and approaches to strengthen data quality in order to use data for decision-making to achieve NTD control and elimination goals.

Contextual determinants of mass drug administration performance: Modelling fourteen years of lymphatic filariasis treatments in West Africa.

BACKGROUND: Effective mass drug administration (MDA) is the cornerstone in the elimination of lymphatic filariasis (LF) and a critical component in combatting all neglected tropical diseases for which preventative chemotherapy is recommended (PC-NTDs). Despite its importance, MDA coverage, however defined, is rarely investigated systematically across time and geography. Most commonly, investigations into coverage react to unsatisfactory outcomes and tend to focus on a single year and health district. Such investigations omit more macro-level influences including sociological, environmental, and programmatic factors. The USAID NTD database contains measures of performance from thousands of district-level LF MDA campaigns across 14 years and 10 West African countries. Specifically, performance was measured as an MDA's epidemiological coverage, calculated as persons treated divided by persons at risk. This analysis aims to explain MDA coverage across time and geography in West Africa using sociological, environmental, and programmatic factors. METHODOLOGY: The analysis links epidemiological coverage data from 3,880 LF MDAs with contextual, non-NTD data via location (each MDA was specific to a health district) and time (MDA month, year). Contextual data included rainfall, temperature, violence or social unrest, COVID-19, the 2014 Ebola outbreak, road access/isolation, population density, observance of Ramadan, and the number of previously completed MDAs. PRINCIPAL FINDINGS: We fit a hierarchical linear regression model with coverage as the dependent variable and performed sensitivity analyses to confirm the selection of the explanatory factors. Above average rainfall, COVID-19, Ebola, violence and social unrest were all significantly associated with lower coverage. Years of prior experience in a district and above average temperature were significantly associated with higher coverage. CONCLUSIONS/SIGNIFICANCE: These generalized and context-focused findings supplement current literature on coverage dynamics and MDA performance. Findings may be used to quantify typically anecdotal considerations in MDA planning. The model and methodology are offered as a tool for further investigation.

Comparing antigenaemia- and microfilaraemia as criteria for stopping decisions in lymphatic filariasis elimination programmes in Africa.

BACKGROUND: Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires <2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole. METHODOLGY/PRINCIPAL FINDINGS: We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ population, and determined safe (>95% positive predictive value) thresholds for stopping MDA. The model captured trends in Mf and CFA prevalences reasonably well. Elimination cannot be predicted with sufficient certainty from CFA prevalence in 6-7-year olds. Resurgence may still occur if all children are antigen-negative, irrespective of the number tested. Mf-based criteria also show unfavourable results (PPV <95% or unpractically low threshold). CFA prevalences in the 5+ or 15+ population are the best predictors, and post-MDA threshold values for stopping MDA can be as high as 10% for 15+. These thresholds are robust for various alternative assumptions regarding baseline endemicity, biological parameters and sampling strategies. CONCLUSIONS/SIGNIFICANCE: For African areas with moderate to high pre-treatment Mf prevalence that have had 6 or more rounds of annual ivermectin/albendazole MDA with adequate coverage, we recommend to adopt a CFA threshold prevalence of 10% in adults (15+) for stopping MDA. This could be combined with Mf testing of CFA positives to ensure absence of a significant Mf reservoir for transmission.

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.

Global progress toward the elimination of active trachoma: an analysis of 38 countries.

BACKGROUND: Global elimination of trachoma as a public health problem was targeted for 2020. We reviewed progress towards the elimination of active trachoma by country and geographical group. METHODS: In this retrospective analysis of national survey and implementation data, all countries ever known to be endemic for trachoma that had either implemented at least one trachoma impact survey shown in the publicly available Trachoma Atlas, or are in Africa were invited to participate in this study. Scale-up was described according to the number of known endemic implementation units and mass drug administration implementation over time. The prevalence of active trachoma-follicular among children aged 1-9 years (TF1-9) from baseline, impact, and surveillance surveys was categorised and used to show programme progress towards reaching the elimination threshold (TF1-9 <5%) using dot maps, spaghetti plots, and boxplots. FINDINGS: We included data until Nov 10, 2021, for 38 countries, representing 2097 ever-endemic implementation units. Of these, 1923 (91·7%) have had mass drug administration. Of 1731 implementation units with a trachoma impact survey, the prevalence of TF1-9 had reduced by at least 50% in 1465 (84·6%) implementation units and 1182 (56·4%) of 2097 ever-endemic implementation units had reached the elimination threshold. 2 years after reaching a TF1-9 prevalence below 5%, most implementation units sustained this target; however, 58 (56·3%) of 103 implementation units in Ethiopia showed recrudescence. INTERPRETATION: Global elimination of trachoma as a public health problem by 2020 was not possible, but this finding masks the great progress achieved. Implementation units in high baseline categories and recrudescent TF1-9 might prolong the attainment of elimination of active trachoma. Elimination is delayed but, with an understanding of the patterns and timelines to reaching elimination targets and a commitment toward meeting future targets, global elimination can still be achieved by 2030. FUNDING: None.

Effectiveness of community-based burden estimation to achieve elimination of lymphatic filariasis: A comparative cross-sectional investigation in Côte d'Ivoire.

For lymphatic filariasis (LF) elimination, endemic countries must document the burden of LF morbidity (LFM). Community-based screening (CBS) is used to collect morbidity data, but evidence demonstrating its reliability is limited. Recent pilots of CBS for LFM alongside mass drug administration (MDA) in Côte d'Ivoire suggested low LFM prevalence (2.1-2.2 per 10,000). We estimated LFM prevalence in Bongouanou District, Côte d'Ivoire, using a comparative cross-sectional design. We compared CBS implemented independently of MDA, adapted from existing Ministry of Health protocols, to a population-based prevalence survey led by formally trained nurses. We evaluated the reliability of case identification, coverage, equity, and cost of CBS. CBS identified 87.4 cases of LFM per 10,000; the survey identified 47.5 (39.4-56.3; prevalence ratio [PR] 1.84; 95% CI 1.64-2.07). CBS identified 39.7 cases of suspect lymphoedema per 10,000; the survey confirmed 35.1 (29.2-41.5) filarial lymphoedema cases per 10,000 (PR 1.13 [0.98-1.31]). CBS identified 96.5 scrotal swellings per 10,000; the survey found 91.3 (83.2-99.8; PR 1.06 [0.93-1.21]); including 33.9 (27.7-38.8) filarial hydrocoele per 10,000 (PR of suspect to confirmed hydrocele 2.93 [2.46-3.55]). Positive predictive values for case identification through CBS were 65.0% (55.8-73.5%) for filarial lymphoedema; 93.7% (89.3-96.7%) for scrotal swellings; and 34.0% (27.3-41.2%) for filarial hydrocoele. Households of lower socioeconomic status and certain minority languages were at risk of exclusion. Direct financial costs were $0.17 per individual targeted and $69.62 per case confirmed. Our community-based approach to LFM burden estimation appears scalable and provided reliable prevalence estimates for LFM, scrotal swellings and LF-lymphoedema. The results represent a step-change improvement on CBS integrated with MDA, whilst remaining at programmatically feasible costs. Filarial hydrocoele cases were overestimated, attributable to the use of case definitions suitable for mass-screening by informal staff. Our findings are broadly applicable to countries aiming for LF elimination using CBS. The abstract is available in French in the S1 File.

Baseline and Impact of First-Year Intervention on Schistosoma haematobium Infection in Seasonal Transmission Foci in the Northern and Central Parts of Côte d'Ivoire.

In order to assess the impact of different control strategies against Schistosoma haematobium in seasonal transmission foci in Côte d'Ivoire, a three-year cluster randomized trial was implemented. The decrease in S. haematobium prevalence among children aged 9-12 years was the primary outcome. In the first step, an eligibility survey was conducted, subjecting 50 children aged 13-14 years to a single urine filtration. Sixty-four villages with a prevalence of S. haematobium of ≥4% were selected and randomly assigned to four intervention arms consisting of annual mass drug administration (MDA) before (arm 1) and after (arm 2) the peak transmission, biannual treatment with praziquantel before and after the peak transmission season (arm 3), and annual MDA before the peak transmission season, coupled with focal chemical snail control using molluscicides (arm 4). At baseline, we observed a prevalence of 24.8%, 10.1%, 13.9%, and 15.9% in study arms 1, 2, 3, and 4, respectively. One year after the first intervention, the prevalence decreased in all study arms by about two-thirds or more. The prevalence in arm 2 was lower than in arm 1 (3.5% vs. 8.1%), but the difference was not statistically significant (odds ratio (OR) = 0.42, 95% confidence interval (CI) = 0.10-1.80). After adjusting for baseline prevalence, arms 1 and 2 performed roughly similarly (adjusted odds ratio (aOR) = 1.03, 95% CI = 0.34-3.07). The prevalence in arms 3 and 4 (1.9% and 2.2%) were significantly lower compared to arm 1 in the unadjusted and the adjusted models (arm 3 vs. arm 1, OR = 0.22, 95% CI = 0.05-0.95, aOR = 0.19, 95% CI = 0.08-0.48; arm 4 vs. arm 1, OR = 0.26, 95% CI = 0.08-0.85, aOR = 0.23, 95% CI = 0.06-0.87). The initial intervention showed a significant impact on the prevalence of S. haematobium. It will be interesting to monitor the comparative impact of the different intervention arms and to determine whether the interruption of seasonal transmission of S. haematobium can be achieved in this epidemiological setting within three years.

Impact of annual and semi-annual mass drug administration for Lymphatic Filariasis and Onchocerciasis on Hookworm Infection in Côte d'Ivoire.

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual rounds of MDA with similar compliance. The effects of MDA using ivermectin (IVM, 0.2 mg/kg) combined with albendazole (ALB, 400 mg) on the prevalence and intensity of hookworm infection were evaluated in the Abengourou (annual MDA) and Akoupé (semi-annual MDA) health Districts in eastern Côte d'Ivoire from 2014 to 2017. A cross-sectional approach was used together with mixed logistic regression, and mixed linear models. Subjects were tested for STH using the Kato-Katz technique before the first round of MDA and 12, 24, and 36 months after the first round of MDA. The mean self-reported MDA compliance assessed during the survey was 65%, and no difference was observed between treatment areas. These results were confirmed by an independent coverage survey as recommended by WHO. Hookworm was the most prevalent STH species in both areas (23.9% vs 12.4%) and the prevalence of other STH species was less than 1%. The crude prevalence of hookworm dropped significantly, from 23.9% to 5.5% (p <0.001, 77% reduction) in the annual MDA treatment area and from 12.4% to 1.9% (p <0.001, 85% reduction) in the semi-annual treatment area. The average intensity of hookworm infection decreased in the annual MDA area (406.2 epg to 118.3 epg), but not in the semi-annual MDA area (804.9 epg to 875.0 epg). Moderate and heavy infections (1% and 1.3% at baseline) were reduced to 0% and 0.4% in the annual and semi-annual treatment areas, respectively. Using a mixed logistic regression model, and after adjusting for baseline prevalence, only the year 2 re-examination showed a difference in prevalence between treatments (OR: 2.26 [95% CI: 1.03, 4.98], p = 0.043). Analysis of intensity of hookworm infection indicated also that treatment differences varied by follow-up visit. In conclusion twelve months after the last treatment cycle, three annual and five semi-annual rounds of community-wide MDA with the combination of IVM and ALB showed strong, but similar impact on hookworm prevalence and intensity in eastern Côte d'Ivoire. Therefore, an annual MDA regimen seems to be an efficient strategy to control hookworm infection in endemic areas with low and moderate infection prevalence. Trial registration: The study was registered at ClinicalTrial.gov under the number NTC02032043.

Finding hotspots: development of an adaptive spatial sampling approach.

The identification of disease hotspots is an increasingly important public health problem. While geospatial modeling offers an opportunity to predict the locations of hotspots using suitable environmental and climatological data, little attention has been paid to optimizing the design of surveys used to inform such models. Here we introduce an adaptive sampling scheme optimized to identify hotspot locations where prevalence exceeds a relevant threshold. Our approach incorporates ideas from Bayesian optimization theory to adaptively select sample batches. We present an experimental simulation study based on survey data of schistosomiasis and lymphatic filariasis across four countries. Results across all scenarios explored show that adaptive sampling produces superior results and suggest that similar performance to random sampling can be achieved with a fraction of the sample size.

Lessons Learned in Conducting Mass Drug Administration for Schistosomiasis Control and Measuring Coverage in an Operational Research Setting.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries. To enhance relevance for routine practice, the MDA in these studies was coordinated by or closely aligned with national neglected tropical disease (NTD) control programs. The study protocol set minimum targets of at least 90% for coverage among children enrolled in schools and 75% for all school-age children. Over the 4 years of intervention, an estimated 3.5 million treatments were administered to study communities. By year 4, the median village coverage was at or above targets in all studies except that in Mozambique. However, there was often a wide variation behind these summary statistics, and all studies had several villages with very low or high coverage. In studies where coverage was estimated by comparing the number of people treated with the number eligible for treatment, denominator estimation was often problematic. The SCORE experiences in conducting these studies provide lessons for future efforts that attempt to implement strong research designs in real-world contexts. They also have potential applicability to country MDA campaigns against schistosomiasis and other NTDs, most of which are conducted with less logistical and financial support than was available for the SCORE study efforts.

Impact of Different Mass Drug Administration Strategies for Gaining and Sustaining Control of Schistosoma mansoni and Schistosoma haematobium Infection in Africa.

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation-funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local Schistosoma infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed.

Low transmission of Wuchereria bancrofti in cross-border districts of Côte d'Ivoire: A great step towards lymphatic filariasis elimination in West Africa.

BACKGROUND: Lymphatic filariasis (LF) is widely endemic in Côte d'Ivoire, and elimination as public health problem (EPHP) is based on annual mass drug administration (MDA) using ivermectin and albendazole. To guide EPHP efforts, we evaluated Wuchereria bancrofti infection indices among humans, and mosquito vectors after four rounds of MDA in four cross-border health districts of Côte d'Ivoire. METHODOLOGY: We monitored people and mosquitoes for W. bancrofti infections in the cross-border health districts of Aboisso, Bloléquin, Odienné and Ouangolodougou, Côte d'Ivoire. W. bancrofti circulating filarial antigen (CFA) was identified using filariasis test strips, and antigen-positive individuals were screened for microfilaremia. Moreover, filarial mosquito vectors were sampled using window exit traps and pyrethrum sprays, and identified morphologically at species level. Anopheles gambiae s.l. and Culex quinquefasciatus females were analyzed for W. bancrofti infection using polymerase chain reaction (PCR) technique. PRINCIPAL FINDINGS: Overall, we found a substantial decline in W. bancrofti infection indices after four rounds of MDA compared to pre-MDA baseline data. CFA prevalence fell from 3.38-5.50% during pre-MDA to 0.00-1.53% after MDA interventions. No subjects had detectable levels of CFA in Ouangolodougou. Moreover, post-MDA CFA prevalence was very low, and below the 1% elimination threshold in Aboisso (0.19%) and Odienné (0.49%). Conversely, CFA prevalence remained above 1% in Bloléquin (1.53%). W. bancrofti microfilariae (Mf) were not found in Aboisso, Bloléquin, and Ouangolodougou, except for Odienné with low prevalence (0.16%; n = 613) and microfilaremia of 32.0 Mf/mL. No An. gambiae s.l. and Cx. quinquefasciatus pools were infected with W. bancrofti in Bloléquin and Ouangolodougou, while they exhibited low infection rates in Aboisso (1% and 0.07%), and Odienné (0.08% and 0.08%), respectively. CONCLUSIONS: In cross-border areas of Côte d'Ivoire, LF infection indices in humans and mosquito vectors substantially declined after four rounds of MDA. CFA prevalence fell under the World Health Organization (WHO)-established threshold (1%) in Aboisso, Ouangolodougou and Odienné. Moreover, W. bancrofti prevalence in mosquitoes was lower than WHO-established threshold (2%) in all areas. This might suggest the interruption of W. bancrofti transmission, and possible MDA cessation. However, a formal transmission assessment survey (TAS) and molecular xenomonitoring in mosquito vectors should be implemented before eventual MDA cessation. However, MDA should pursue in Bloléquin where W. bancrofti infection prevalence remained above 1%. Our results provided important ramifications for LF control efforts towards EPHP in Côte d'Ivoire.

Efficacy of single versus four repeated doses of praziquantel against Schistosoma mansoni infection in school-aged children from Côte d'Ivoire based on Kato-Katz and POC-CCA: An open-label, randomised controlled trial (RePST).

BACKGROUND: Preventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d'Ivoire, using two different diagnostic tests. METHODS: An open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration. PRINCIPAL FINDINGS: During baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31-52%) in the standard treatment group and 86% (95% CI 75-92%) in the intense treatment group. Observed IRR was 72% (95% CI 55-83%) in the standard treatment group and 95% (95% CI 85-98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11-27%) and 36% (95% CI 26-46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events. CONCLUSION/SIGNIFICANCE: The observed CR using KK was significantly higher after four repeated treatments compared to a single treatment, without an increase in adverse events. Using POC-CCA, the observed CR was significantly lower than measured by KK, indicating that PZQ may be considerably less efficacious as concluded by KK. Our findings highlight the need for reliable and more accurate diagnostic tools, which are essential for monitoring treatment efficacy, identifying changes in transmission, and accurately quantifying the intensity of infection in distinct populations. In addition, the higher CR in the intense treatment group suggests that more focused and intense PZQ treatment can help to advance schistosomiasis control. TRIAL REGISTRATION: www.clinicaltrials.gov NCT02868385.

Gender and neglected tropical disease front-line workers: Data from 16 countries.

BACKGROUND: Delivery of preventive chemotherapy (PC) through mass drug administration (MDA) is used to control or eliminate five of the most common neglected tropical diseases (NTDs). The success of an MDA campaign relies on the ability of drug distributors and their supervisors-the NTD front-line workers-to reach populations at risk of NTDs. In the past, our understanding of the demographics of these workers has been limited, but with increased access to sex-disaggregated data, we begin to explore the implications of gender and sex for the success of NTD front-line workers. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed data collected by USAID-supported NTD projects from national NTD programs from fiscal years (FY) 2012-2017 to assess availability of sex-disaggregated data on the workforce. What we found was sex-disaggregated data on 2,984,908 trainees trained with financial support from the project. We then analyzed the percentage of males and females trained by job category, country, and fiscal year. During FY12, 59% of these data were disaggregated by sex, which increased to nearly 100% by FY15 and was sustained through FY17. In FY17, 43% of trainees were female, with just four countries reporting more females than males trained as drug distributors and three countries reporting more females than males trained as trainers/supervisors. Except for two countries, there were no clear trends over time in changes to the percent of females trained. CONCLUSIONS/SIGNIFICANCE: There has been a rapid increase in availability of sex-disaggregated data, but little increase in recruitment of female workers in countries included in this study. Women continue to be under-represented in the NTD workforce, and while there are often valid reasons for this distribution, we need to test this norm and better understand gender dynamics within NTD programs to increase equity.

Systems analysis-based assessment of post-treatment adverse events in lymphatic filariasis.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease, and the Global Program to Eliminate LF delivers mass drug administration (MDA) to 500 million people every year. Adverse events (AEs) are common after LF treatment. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the pathogenesis of AEs, we studied LF-patients from a treatment trial. Plasma levels of many filarial antigens increased post-treatment in individuals with AEs, and this is consistent with parasite death. Circulating immune complexes were not elevated in these participants, and the classical complement cascade was not activated. Multiple cytokines increased after treatment in persons with AEs. A transcriptomic analysis was performed for nine individuals with moderate systemic AEs and nine matched controls. Differential gene expression analysis identified a significant transcriptional signature associated with post-treatment AEs; 744 genes were upregulated. The transcriptional signature was enriched for TLR and NF-κB signaling. Increased expression of seven out of the top eight genes upregulated in persons with AEs were validated by qRT-PCR, including TLR2. CONCLUSIONS/SIGNIFICANCE: This is the first global study of changes in gene expression associated with AEs after treatment of lymphatic filariasis. Changes in cytokines were consistent with prior studies and with the RNAseq data. These results suggest that Wolbachia lipoprotein is involved in AE development, because it activates TLR2-TLR6 and downstream NF-κB. Additionally, LPS Binding Protein (LBP, which shuttles lipoproteins to TLR2) increased post-treatment in individuals with AEs. Improved understanding of the pathogenesis of AEs may lead to improved management, increased MDA compliance, and accelerated LF elimination.

Prevalence and Risk Factors for Schistosomiasis among Schoolchildren in two Settings of Côte d'Ivoire.

Schistosomiasis is a parasitic disease affecting more than 250 million people, primarily in sub-Saharan Africa. In Côte d'Ivoire both Schistosoma haematobium (causing urogenital schistosomiasis) and Schistosoma mansoni (causing intestinal schistosomiasis) co-exist. This study aimed to determine the prevalence of S. haematobium and S. mansoni and to identify risk factors among schoolchildren in the western and southern parts of Côte d'Ivoire. From January to April 2018, a cross-sectional study was carried out including 1187 schoolchildren aged 5-14 years. Urine samples were examined by a filtration method to identify and count S. haematobium eggs, while stool samples were subjected to duplicate Kato-Katz thick smears to quantify eggs of S. mansoni and soil-transmitted helminths. Data on sociodemographic, socioeconomic, and environmental factors were obtained using a pretested questionnaire. Multivariate logistic regression was employed to test for associations between variables. We found a prevalence of S. haematobium of 14.0% (166 of 1187 schoolchildren infected) and a prevalence of S. mansoni of 6.1% (66 of 1089 schoolchildren infected). In the southern part of Côte d'Ivoire, the prevalence of S. haematobium was 16.1% with a particularly high prevalence observed in Sikensi (35.6%), while S. mansoni was most prevalent in Agboville (11.2%). Swimming in open freshwater bodies was the main risk factor for S. haematobium infection (adjusted odds ratio (AOR) = 127.0, 95% confidence interval (CI): 25.0-634.0, p < 0.001). Fishing and washing clothes in open freshwater bodies were positively associated with S. haematobium and S. mansoni infection, respectively. Preventive chemotherapy using praziquantel should be combined with setting-specific information, education, and communication strategies in order to change children's behavior, thus avoiding contact with unprotected open freshwater.