VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center in 2023.

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) is a Bioinformatics Resource Center funded by the National Institutes of Health with additional funding from the Wellcome Trust. VEuPathDB supports >600 organisms that comprise invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Since 2004, VEuPathDB has analyzed omics data from the public domain using contemporary bioinformatic workflows, including orthology predictions via OrthoMCL, and integrated the analysis results with analysis tools, visualizations, and advanced search capabilities. The unique data mining platform coupled with >3000 pre-analyzed data sets facilitates the exploration of pertinent omics data in support of hypothesis driven research. Comparisons are easily made across data sets, data types and organisms. A Galaxy workspace offers the opportunity for the analysis of private large-scale datasets and for porting to VEuPathDB for comparisons with integrated data. The MapVEu tool provides a platform for exploration of spatially resolved data such as vector surveillance and insecticide resistance monitoring. To address the growing body of omics data and advances in laboratory techniques, VEuPathDB has added several new data types, searches and features, improved the Galaxy workspace environment, redesigned the MapVEu interface and updated the infrastructure to accommodate these changes.

Modeling Approaches to Predicting Persistent Hotspots in SCORE Studies for Gaining Control of Schistosomiasis Mansoni in Kenya and Tanzania.

BACKGROUND: Some villages, labeled "persistent hotspots (PHS)," fail to respond adequately in regard to prevalence and intensity of infection to mass drug administration (MDA) for schistosomiasis. Early identification of PHS, for example, before initiating or after 1 or 2 years of MDA could help guide programmatic decision making. METHODS: In a study with multiple rounds of MDA, data collected before the third MDA were used to predict PHS. We assessed 6 predictive approaches using data from before MDA and after 2 rounds of annual MDA from Kenya and Tanzania. RESULTS: Generalized linear models with variable selection possessed relatively stable performance compared with tree-based methods. Models applied to Kenya data alone or combined data from Kenya and Tanzania could reach over 80% predictive accuracy, whereas predicting PHS for Tanzania was challenging. Models developed from one country and validated in another failed to achieve satisfactory performance. Several Year-3 variables were identified as key predictors. CONCLUSIONS: Statistical models applied to Year-3 data could help predict PHS and guide program decisions, with infection intensity, prevalence of heavy infections (≥400 eggs/gram of feces), and total prevalence being particularly important factors. Additional studies including more variables and locations could help in developing generalizable models.

Developing web-based training for public health practitioners: what can we learn from a review of five disciplines?

During a time when governmental funding, resources and staff are decreasing and travel restrictions are increasing, attention to efficient methods of public health workforce training is essential. A literature review was conducted to inform the development and delivery of web-based trainings for public health practitioners. Literature was gathered and summarized from five disciplines: Information Technology, Health, Education, Business and Communications, following five research themes: benefits, barriers, retention, promotion and evaluation. As a result, a total of 138 articles relevant to web-based training design and implementation were identified. Key recommendations emerged, including the need to conduct formative research and evaluation, provide clear design and layout, concise content, interactivity, technical support, marketing and promotion and incentives. We conclude that there is limited application of web-based training in public health. This review offers an opportunity to learn from other disciplines. Web-based training methods may prove to be a key training strategy for reaching our public health workforce in the environment of limited resources.

SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and telomerase RNPs.

Assembly of H/ACA RNPs in yeast is aided by at least two accessory factors, Naf1p and Shq1p. Although the function of Naf1p and its human ortholog NAF1 has been delineated in detail, that of Shq1p and its putative human ortholog SHQ1 remains obscure. We demonstrate that SHQ1 indeed functions in the biogenesis of human H/ACA RNPs and we dissect its mechanism of action. Like NAF1, SHQ1 binds the major H/ACA core protein and pseudouridine synthase NAP57 (aka dyskerin) but precedes the assembly role of NAF1 at nascent H/ACA RNAs because the interaction of SHQ1 with NAP57 in vivo and in vitro precludes that of NAF1 and of the other H/ACA core proteins that are present at the sites of H/ACA RNA transcription. The N-terminal heat shock protein 20-like CS domain of SHQ1 is dispensable for NAP57 binding. Consistent with its role as an assembly factor, SHQ1 localizes to the nucleoplasm and is excluded from nucleoli and Cajal bodies, the sites of mature H/ACA RNPs. In an in vitro assembly system of functional H/ACA RNPs that is dependent on NAF1, excess recombinant SHQ1 interferes with assembly. Importantly, knockdown of cellular SHQ1 prevents accumulation of a newly synthesized H/ACA reporter RNA and generally reduces the levels of endogenous H/ACA RNAs including telomerase RNA. In summary, the sequential action of SHQ1 and NAF1 is required for functional assembly of H/ACA RNPs in vivo and in vitro. This step-wise process could serve as an efficient means of quality control during H/ACA RNP assembly.

Stepwise RNP assembly at the site of H/ACA RNA transcription in human cells.

Mammalian H/ACA RNPs are essential for ribosome biogenesis, premessenger RNA splicing, and telomere maintenance. These RNPs consist of four core proteins and one RNA, but it is not known how they assemble. By interrogating the site of H/ACA RNA transcription, we dissected their biogenesis in single cells and delineated the role of the non-core protein NAF1 in the process. NAF1 and all of the core proteins except GAR1 are recruited to the site of transcription. NAF1 binds one of the core proteins, NAP57, and shuttles between nucleus and cytoplasm. Both proteins are essential for stable H/ACA RNA accumulation. NAF1 and GAR1 bind NAP57 competitively, suggesting a sequential interaction. Our analyses indicate that NAF1 binds NAP57 and escorts it to the nascent H/ACA RNA and that GAR1 then replaces NAF1 to yield mature H/ACA RNPs in Cajal bodies and nucleoli.

Unprotected water sources and low latrine coverage are contributing factors to persistent hotspots for schistosomiasis in western Kenya.

BACKGROUND: Evidence indicates that whereas repeated rounds of mass drug administration (MDA) programs have reduced schistosomiasis prevalence to appreciable levels in some communities referred to here as responding villages (R). However, prevalence has remained high or less than anticipated in other areas referred to here as persistent hotspot villages (PHS). Using a cross-sectional quantitative approach, this study investigated the factors associated with sustained high Schistosoma mansoni prevalence in some villages despite repeated high annual treatment coverage in western Kenya. METHOD: Water contact sites selected based on observation of points where people consistently go to collect water, wash clothes, bathe, swim or play (young children), wash cars and harvest sand were mapped using hand-held smart phones on the Commcare platform. Quantitative cross-sectional surveys on behavioral characteristics were conducted using interviewer-based semi-structured questionnaires administered to assess water usage/contact patterns and open defecation. Questionnaires were administered to 15 households per village, 50 pupils per school and 1 head teacher per school. One stool and urine sample was collected from 50 school children aged 9-12 year old and 50 adults from both responding (R) and persistent hotspot (PHS) villages. Stool was analyzed by the Kato-Katz method for eggs of S. mansoni and soil-transmitted helminths. Urine samples were tested using the point-of-care circulating cathodic antigen (POC-CCA) test for detection of S. mansoni antigen. RESULTS: There was higher latrine coverage in R (n = 6) relative to PHS villages (n = 6) with only 33% of schools in the PHS villages meeting the WHO threshold for boy: latrine coverage ratio versus 83.3% in R, while no villages met the girl: latrine ratio requirement. A higher proportion of individuals accessed unprotected water sources for both bathing and drinking (68.5% for children and 89% for adults) in PHS relative to R villages. In addition, frequency of accessing water sources was higher in PHS villages, with swimming being the most frequent activity. As expected based upon selection criteria, both prevalence and intensity of S. mansoni were higher in the PHS relative to R villages (prevalence: 43.7% vs 20.2%; P < 0.001; intensity: 73.8 ± 200.6 vs 22.2 ± 96.0, P < 0.0001), respectively. CONCLUSION: Unprotected water sources and low latrine coverage are contributing factors to PHS for schistosomiasis in western Kenya. Efforts to increase provision of potable water and improvement in latrine infrastructure is recommended to augment control efforts in the PHS areas.

The nucleolar channel system of human endometrium is related to endoplasmic reticulum and R-rings.

The nucleolar channel system (NCS) is a well-established ultrastructural hallmark of the postovulation endometrium. Its transient presence has been associated with human fertility. Nevertheless, the biogenesis, composition, and function of these intranuclear membrane cisternae are unknown. Membrane systems with a striking ultrastructural resemblance to the NCS, termed R-rings, are induced in nuclei of tissue culture cells by overexpression of the central repeat domain of the nucleolar protein Nopp140. Here we provide a first molecular characterization of the NCS and compare the biogenesis of these two enigmatic organelles. Like the R-rings, the NCS consists of endoplasmic reticulum harboring the marker glucose-6-phosphatase. R-ring formation initiates at the nuclear envelope, apparently by a calcium-mediated Nopp140-membrane interaction, as supported by the calcium-binding ability of Nopp140, the inhibition of R-ring formation by calcium chelators, and the concentration of Nopp140 and complexed calcium in R-rings. Although biogenesis of the NCS may initiate similarly, the reduced presence of complexed calcium and Nopp140 suggests the involvement of additional factors.

Test, Treat, Track, Test, and Treat Active Surveillance toward Elimination of Schistosomiasis: A Feasibility Study.

We assessed the feasibility of using a test, treat, track, test, and treat (5T) active surveillance strategy to identify and treat individuals with schistosomiasis in three very low-prevalence villages in Kafr El Sheikh Governorate, Egypt. Primary index cases (PICs) were identified using the point-of-care circulating cathodic antigen (POC-CCA) assay in schools, in rural health units (retesting individuals with positive Kato-Katz examinations over the previous 6 months), and at potential water transmission sites identified by PICs and field observations. Primary cases identified potential second-generation cases-people with whom they shared water activities-who were then tracked, tested, and treated if infected. Those sharing water activities with second-generation cases were also tested. The yield of PICs from the three venues were 128 of 3,576 schoolchildren (3.6%), 42 of 696 in rural health units (6.0%), and 83 of 1,156 at water contact sites (7.2%). There were 118 second- and 19 third-generation cases identified. Persons testing positive were treated with praziquantel. Of 388 persons treated, 368 (94.8%) had posttreatment POC-CCA tests 3-4 weeks after treatment, and 81.8% (301) became negative. The 67 persons remaining positive had negative results after a second treatment. Therefore, all those found positive, treated, and followed up were negative following one or two treatments. Analysis of efforts as expressed in person-hours indicates that 4,459 person-hours were required for these 5T activities, with nearly 65% of that time spent carrying out interviews, treatments, and evaluations following treatment. The 5T strategy appears feasible and acceptable as programs move toward elimination.

The Schistosomiasis Consortium for Operational Research and Evaluation 2008-2020: Approaches, Experiences, Lessons, and Recommendations.

For the past 10 years, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), funded by the Bill & Melinda Gates Foundation, has been supporting operational research to provide a stronger evidence base for controlling and moving toward elimination of schistosomiasis. The SCORE portfolio was developed and implemented with engagement from many stakeholders and sectors. Particular efforts were made to include endemic country neglected tropical disease program managers. Examples of the challenges we encountered include the need to balance rigor (e.g., conducting large cluster-randomized trials) with ensuring relevance to real-world settings, allowing for local contexts while standardizing key study aspects, adjusting to evolving technologies, and incorporating changing technologies into multiyear studies. The Schistosomiasis Consortium for Operational Research and Evaluation's findings and data and the collected specimens will continue to be useful in the years to come. Our experiences and lessons learned can benefit both program managers and researchers conducting similar work in the future.

Challenges in Protocol Development and Interpretation of the Schistosomiasis Consortium for Operational Research and Evaluation Intervention Studies.

In 2010, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) began the design of randomized controlled trials to compare different strategies for praziquantel mass drug administration, whether for gaining or sustaining control of schistosomiasis or for approaching local elimination of Schistosoma transmission. The goal of this operational research was to expand the evidence base for policy-making for regional and national control of schistosomiasis in sub-Saharan Africa. Over the 10-year period of its research programs, as SCORE operational research projects were implemented, their scope and scale posed important challenges in terms of research performance and the final interpretation of their results. The SCORE projects yielded valuable data on program-level effectiveness and strengths and weaknesses in performance, but in most of the trials, a greater-than-expected variation in community-level responses to assigned schedules of mass drug administration meant that identification of a dominant control strategy was not possible. This article critically reviews the impact of SCORE's cluster randomized study design on performance and interpretation of large-scale operational research such as ours.

Evaluation, Validation, and Recognition of the Point-of-Care Circulating Cathodic Antigen, Urine-Based Assay for Mapping Schistosoma mansoni Infections.

Efforts to control Schistosoma mansoni infection depend on the ability of programs to effectively detect and quantify infection levels and adjust programmatic approaches based on these levels and program goals. One of the three major objectives of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has been to develop and/or evaluate tools that would assist Neglected Tropical Disease program managers in accomplishing this fundamental task. The advent of a widely available point-of-care (POC) assay to detect schistosome circulating cathodic antigen (CCA) in urine with a rapid diagnostic test (the POC-CCA) in 2008 led SCORE and others to conduct multiple evaluations of this assay, comparing it with the Kato-Katz (KK) stool microscopy assay-the standard used for more than 45 years. This article describes multiple SCORE-funded studies comparing the POC-CCA and KK assays, the pros and cons of these assays, the use of the POC-CCA assay for mapping of S. mansoni infections in areas across the spectrum of prevalence levels, and the validation and recognition that the POC-CCA, although not infallible, is a highly useful tool to detect low-intensity infections in low-to-moderate prevalence areas. Such an assay is critical, as control programs succeed in driving down prevalence and intensity and seek to either maintain control or move to elimination of transmission of S. mansoni.

Discovering, Defining, and Summarizing Persistent Hotspots in SCORE Studies.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) conducted large field studies on schistosomiasis control and elimination in Africa. All of these studies, carried out in low-, moderate-, and high-prevalence areas, resulted in a reduction in prevalence and intensity of Schistosoma infection after repeated mass drug administration (MDA). However, in all studies, there were locations that experienced minimal or no decline or even increased in prevalence and/or intensity. These areas are termed persistent hotspots (PHS). In SCORE studies in medium- to high-prevalence areas, at least 30% of study villages were PHS. There was no consistent relationship between PHS and the type or frequency of intervention, adequacy of reported MDA coverage, and prevalence or intensity of infection at baseline. In a series of small studies, factors that differed between PHS and villages that responded to repeated MDA as expected included sources of water for personal use, sanitation, and hygiene. SCORE studies comparing PHS with villages that responded to MDA suggest the potential for PHS to be identified after a few years of MDA. However, additional studies in different social-ecological settings are needed to develop generalizable approaches that program managers can use to identify and address PHS. This is essential if goals for schistosomiasis control and elimination are to be achieved.

Environmental Predictors of Schistosomiasis Persistent Hotspots following Mass Treatment with Praziquantel.

Schistosomiasis control programs rely heavily on mass drug administration (MDA) campaigns with praziquantel for preventative chemotherapy. Areas where the prevalence and/or intensity of schistosomiasis infection remains high even after several rounds of treatment, termed "persistent hotspots" (PHSs), have been identified in trials of MDA effectiveness conducted by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) in Kenya, Mozambique, Tanzania, and Côte d'Ivoire. In this analysis, we apply a previously developed set of criteria to classify the PHS status of 531 study villages from five SCORE trials. We then fit logistic regression models to data from SCORE and publically available georeferenced datasets to evaluate the influence of local environmental and population features, pre-intervention infection burden, and treatment scheduling on PHS status in each trial. The frequency of PHS in individual trials ranged from 35.3% to 71.6% in study villages. Significant relationships between PHS status and MDA frequency, distance to freshwater, rainfall, baseline schistosomiasis burden, elevation, land cover type, and village remoteness were each observed in at least one trial, although the strength and direction of these relationships was not always consistent among study sites. These findings suggest that PHSs are driven in part by environmental conditions that modify the risk and frequency of reinfection.

Evaluation of morbidity in Schistosoma mansoni-positive primary and secondary school children after four years of mass drug administration of praziquantel in western Kenya.

BACKGROUND: World Health Organization guidelines recommend preventive chemotherapy with praziquantel to control morbidity due to schistosomiasis. The primary aim of this cross-sectional study was to determine if 4 years of annual mass drug administration (MDA) in primary and secondary schools lowered potential markers of morbidity in infected children 1 year after the final MDA compared to infected children prior to initial MDA intervention. METHODS: Between 2012 and 2016 all students in two primary and three secondary schools within three kilometers of Lake Victoria in western Kenya received annual mass praziquantel administration. To evaluate potential changes in morbidity we measured height, weight, mid-upper arm circumference, hemoglobin levels, abdominal ultrasound, and quality of life in children in these schools. This study compared two cross-sectional samples of Schistosoma mansoni egg-positive children: one at baseline and one at year five, 1 year after the fourth annual MDA. Data were analyzed for all ages (6-18 years old) and stratified by primary (6-12 years old) and secondary (12-18 years old) school groups. RESULTS: The prevalence of multiple potential morbidity markers did not differ significantly between the egg-positive participants at baseline and those at 5 years by Mann Whitney nonparametric analysis and Fisher's exact test for continuous and categorical data, respectively. There was a small but significantly higher score in school-related quality of life assessment by year five compared to baseline by Mann Whitney analysis (P = 0.048) in 13-18 year olds where malaria-negative. However, anemia was not positively impacted by four annual rounds of MDA, but registered a significant negative outcome. CONCLUSIONS: We did not detect differences in morbidity markers measured in a population of those infected or re-infected after multiple MDA. This could have been due to their relative insensitivity or a failure of MDA to prevent morbidity among those who remain infected. High malaria transmission in this area and/or a lack of suitable methods to measure the more subtle functional morbidities caused by schistosomiasis could be a factor. Further research is needed to identify and develop well-defined, easily quantifiable S. mansoni morbidity markers for this age group.

Contributions of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) to Schistosomiasis Control and Elimination: Key Findings and Messages for Future Goals, Thresholds, and Operational Research.

Herein, we summarize what we consider are major contributions resulting from the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) program, including its key findings and key messages from those findings. Briefly, SCORE's key findings are as follows: i) biennial mass drug administration (MDA) with praziquantel can control schistosomiasis to moderate levels of prevalence; ii) MDA alone will not achieve elimination; iii) to attain and sustain control throughout endemic areas, persistent hotspots need to be identified following a minimal number of years of annual MDA and controlled through adaptive strategies; iv) annual MDA is more effective than biennial MDA in high-prevalence areas; v) the current World Health Organization thresholds for decision-making based on the prevalence of heavy infections should be redefined; and vi) point-of-care circulating cathodic antigen urine assays are useful for Schistosoma mansoni mapping in low-to-moderate prevalence areas. The data and specimens collected and curated through SCORE efforts will continue to be critical resource for future research. Besides providing useful information for program managers and revision of guidelines for schistosomiasis control and elimination, SCORE research and outcomes have identified additional questions that need to be answered as the schistosomiasis community continues to implement effective, evidence-based programs. An overarching contribution of SCORE has been increased cohesiveness within the schistosomiasis field-oriented community, thereby fostering new and productive collaborations. Based on SCORE's findings and experiences, we propose new approaches, thresholds, targets, and goals for control and elimination of schistosomiasis, and recommend research and evaluation activities to achieve these targets and goals.

SCORE Operational Research on Moving toward Interruption of Schistosomiasis Transmission.

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

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.

Developing competencies for training practitioners in evidence-based cancer control.

BACKGROUND: Competency-based education allows public health departments to better develop a workforce aimed at conducting evidence-based control cancer. METHODS: A 2-phased competency development process was conducted that systematically obtained input from practitioners in health departments and trainers in academe and community agencies (n = 60). RESULTS: Among the 26 competencies developed, 10 were rated at the beginner level, 12 were intermediate, and 4 were advanced. Community-level input competencies were seen as beginner level, whereas policy-related competencies were rated as advanced. CONCLUSION: Although adaptation to various audiences is needed, these competencies provide a foundation on which to build practitioner-focused training programs.

Five-Year Impact of Different Multi-Year Mass Drug Administration Strategies on Childhood Schistosoma mansoni-Associated Morbidity: A Combined Analysis from the Schistosomiasis Consortium for Operational Research and Evaluation Cohort Studies in the Lake Victoria Regions of Kenya and Tanzania.

The WHO recommends mass treatment with praziquantel as the primary approach for Schistosoma mansoni-related morbidity control in endemic populations. The Schistosomiasis Consortium for Operational Research and Evaluation implemented multi-country, cluster-randomized trials to compare effectiveness of community-wide and school-based treatment (SBT) regimens on prevalence and intensity of schistosomiasis. To assess the impact of two different treatment schedules on S. mansoni-associated morbidity in children, cohort studies were nested within the randomized trials conducted in villages in Kenya and Tanzania having baseline prevalence ≥ 25%. Children aged 7-8 years were enrolled at baseline and followed to ages 11-12 years. Infection intensity and odds of infection were reduced both in villages receiving four years of annual community-wide treatment (CWT) and those who received biennial SBT over 4 years. These regimens were also associated with reduced odds of undernutrition and reduced odds of portal vein dilation at follow-up. However, neither hemoglobin levels nor the prevalence of the rare abnormal pattern C liver scores on ultrasound improved. For the combined cohorts, growth stunting worsened in the areas receiving biennial SBT, and maximal oxygen uptake as estimated by fitness testing scores declined under both regimens. After adjusting for imbalance in starting prevalence between study arms, children in villages receiving annual CWT had significantly greater decreases in infection prevalence and intensity than those villages receiving biennial SBT. Although health-related quality-of-life scores improved in both study arms, children in the CWT villages gained significantly more. We conclude that programs using annual CWT are likely to achieve better overall S. mansoni morbidity control than those implementing only biennial SBT.