Uganda National Institute of Public Health: Establishment and Experiences, 2013-2021.

Uganda is an ecological hot spot with porous borders that lies in several infectious disease transmission belts, making it prone to disease outbreaks. To prepare and respond to these public health threats and emergencies in a coordinated manner, Uganda established the Uganda National Institute of Public Health (UNIPH) in 2013.Using a step-by-step process, Uganda's Ministry of Health (MOH) crafted a strategy with a vision, mission, goal, and strategic objectives, and identified value additions and key enablers for success. A regulatory impact assessment was then conducted to inform the drafting of principles of the bill for legislation on the Institute.Despite not yet attaining legal status, the UNIPH has already achieved faster, smarter, and more efficient and effective prevention, detection, and response to public health emergencies. Successes include a more coordinated multisectoral, disciplined, and organized response to emergencies; appropriate, timely, and complete information receipt and sharing; a functional national lab sample and results transportation network that has enabled detection and confirmation of public health events within 48 hours of alert; appropriate response to a confirmed public health event in 24-48 hours; and real-time surveillance of endemic- and epidemic-prone diseases.In this article, we document success stories, lessons learned, and challenges encountered during the unique staged process used to develop the components of the UNIPH. The creation of an integrated disease control center has proven to yield better collaboration and synergies between different arms of epidemic preparedness and response.

African National Public Health Institutes Responses to COVID-19: Innovations, Systems Changes, and Challenges.

National public health institutes (NPHIs)-science-based governmental agencies typically part of, or closely aligned with, ministries of health-have played a critical part in many countries' responses to the COVID-19 pandemic. Through listening sessions with NPHI leadership, we captured the experiences of NPHIs in Africa. Our research was further supplemented by a review of the literature. To address issues related to COVID-19, NPHIs in Africa developed a variety of innovative approaches, such as working with the private sector to procure and manage vital supplies and address key information needs. Creative uses of technology, including virtual training and messaging from drones, contributed to sharing information and battling misinformation. Positive impacts of the pandemic response include increased laboratory capacity in many countries, modernized surveillance systems, and strengthened public-private partnerships; much of this enhanced capacity is expected to persist beyond the pandemic. However, several challenges remain, including the lack of staff trained in areas like bioinformatics (essential for genomic analysis) and the need for sustained relationships and data sharing between NPHIs and agencies not traditionally considered public health (eg, those related to border crossings), as well as the impact of the pandemic on prevention and control of non-COVID-19 conditions-both infectious and noncommunicable. Participants in the listening sessions also highlighted concerns about inequities in access to, and quality of, the public health services and clinical care with resultant disproportionate impact of the pandemic on certain populations. COVID-19 responses and challenges highlight the need for continued investment to strengthen NPHIs and public health infrastructure to address longstanding deficiencies and ensure preparedness for the next public health crisis.

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.

Schistosomiasis Consortium for Operational Research and Evaluation (SCORE): Its Foundations, Development, and Evolution.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research that would inform practices related to the control and elimination of schistosomiasis. This article traces SCORE's beginnings and underpinnings. These include an emphasis on openness and contributing to the development of a cohesive schistosomiasis control community, building linkages between researchers and national programs, and focusing on answering questions that will help Neglected Tropical Disease program managers to better control and eliminate schistosomiasis. It describes the development and implementation of SCORE's multiple projects. SCORE began by drawing on advice from a broad range of experts by holding wide-ranging meetings that informed the priorities and protocols for SCORE research. SCORE's major efforts included large, multicountry field studies comparing multiple strategies for mass drug administration with praziquantel, assessment of approaches to elimination, evaluation of a point-of-care assay for field mapping Schistosoma mansoni, and increasing the sensitivity of a laboratory-based diagnostic. SCORE also supported studies on morbidity due to schistosomiasis, quantification of vector snails and the detection of schistosome infections in snails, and changes in schistosome population genetics under praziquantel drug pressure. SCORE data and specimens are archived and will remain available for future research. Although much remains to be carried out, our hope is that through the already published articles and SCORE results described in this supplement, we will have provided a body of evidence to assist policy makers in the development of judicious guidelines for the control and elimination of schistosomiasis.

Circulating Anodic Antigen (CAA): A Highly Sensitive Diagnostic Biomarker to Detect Active Schistosoma Infections-Improvement and Use during SCORE.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato-Katz parasite egg-detection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications.

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.

The Schistosomiasis Consortium for Operational Research and Evaluation Rapid Answers Project: Systematic Reviews and Meta-Analysis to Provide Policy Recommendations Based on Available Evidence.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research to inform global health practices related to the control and elimination of schistosomiasis. The greatest part of the SCORE investment has been in multiyear, long-term efforts, including cluster-randomized trials of gaining and sustaining control of schistosomiasis, trials on elimination of schistosomiasis, and diagnostic test development and evaluation. In the course of planning and conducting SCORE studies, critical questions were raised that could be answered relatively quickly by collecting, collating, and synthesizing existing data. Through its Rapid Answers Project (RAP), the SCORE conducted seven systematic reviews, including four associated meta-analyses, on issues related to screening for schistosomiasis, enhancing mass drug administration, treatment impacts, and the efficacy of snail control for prevention of human schistosomiasis. This article summarizes the findings of the seven RAP reports and provides links to the studies and their supporting information.

SCORE Studies on the Impact of Drug Treatment on Morbidity due to Schistosoma mansoni and Schistosoma haematobium Infection.

The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis-better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE's larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE's Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children's infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity.

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.

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.

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.

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.

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.

National Public Health Institute Legal Framework: A Tool to Build Public Health Capacity.

As countries face public health emergencies, building public health capacity to prevent, detect, and respond to threats is a priority. In recent years, national public health institutes (NPHIs) have emerged to play a critical role in strengthening public health systems and to accelerate and achieve implementation of the International Health Regulations (IHR 2005). NPHIs are science-based government institutions that provide national leadership and expertise for the country's efforts to protect and improve health. Providing a Legal Framework for a National Public Health Institute is a recently released Africa CDC publication intended to support NPHI development throughout Africa. Here we present a legal mapping analysis of sampled legal domains for 5 countries, using the "Menu of Considerations for an NPHI Legal Framework." The analysis delineates the types of legal authorities countries may use to establish or enhance NPHIs and demonstrates how legal mapping can be used to review legal instruments for NPHIs. It also demonstrates variability among legal approaches countries take to establish and enable public health functions for NPHIs. This article examines how the legal framework and menu of considerations can help countries understand the nuances around creating and implementing the laws that will govern their organizations and how countries can better engage stakeholders to identify or address potential areas for opportunity where law may be used as a tool to strengthen public health infrastructure.

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.

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.

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.

Persistent Hotspots in Schistosomiasis Consortium for Operational Research and Evaluation Studies for Gaining and Sustaining Control of Schistosomiasis after Four Years of Mass Drug Administration of Praziquantel.

Control of schistosomiasis presently relies largely on preventive chemotherapy with praziquantel through mass drug administration (MDA) programs. The Schistosomiasis Consortium for Operational Research and Evaluation has concluded five studies in four countries (Côte d'Ivoire, Kenya, Mozambique, and Tanzania) to evaluate alternative approaches to MDA. Studies involved four intervention years, with final evaluation in the fifth year. Mass drug administration given annually or twice over 4 years reduced average prevalence and intensity of schistosome infections, but not all villages that were treated in the same way responded similarly. There are multiple ways by which responsiveness to MDA, or the lack thereof, could be measured. In the analyses presented here, we defined persistent hotspots (PHS) as villages that achieved less than 35% reduction in prevalence and/or less than 50% reduction in infection intensity after 4 years of either school-based or community-wide MDA, either annually or twice in 4 years. By this definition, at least 30% of villages in each of the five studies were PHSs. We found no consistent relationship between PHSs and the type or frequency of intervention, adequacy of reported MDA coverage, and prevalence or intensity of infection at baseline. New research is warranted to identify PHSs after just one or a few rounds of MDA, and new adaptive strategies need to be advanced and validated for turning PHSs into responder villages.

Use of the Staged Development Tool for Assessing, Planning, and Measuring Progress in the Development of National Public Health Institutes.

The Staged Development Tool (SDT) was created to help national public health institutes (NPHIs) assess their current capacity and develop roadmaps for achieving a higher level of functioning. This article discusses the current use of the SDT by national public health institutes to establish baseline capacity and inform strategic planning and its proposed use in a 3-step sequence for measuring the impact of capacity-building interventions over time. The article also includes descriptions of how national public health institutes have been using the SDT to assess their baseline capacity in management issues and core public health functions. The first use of the SDT by a national public health institute provides essential baseline information on their capacities and levels of functioning and plans for addressing gaps. By repeating the SDT after time for the plans to be implemented, the SDT can be used to evaluate changes in capacity and the effectiveness of the interventions made. Because the SDT is built to be complementary to existing assessments and public health strengthening tools and guidelines, implementing the SDT provides concrete, complementary information that can help countries achieve global health security goals and address current and future threats to public health.

Latent class analysis to evaluate performance of point-of-care CCA for low-intensity Schistosoma mansoni infections in Burundi.

BACKGROUND: Kato-Katz examination of stool smears is the field-standard method for detecting Schistosoma mansoni infection. However, Kato-Katz misses many active infections, especially of light intensity. Point-of-care circulating cathodic antigen (CCA) is an alternative field diagnostic that is more sensitive than Kato-Katz when intensity is low, but interpretation of CCA-trace results is unclear. To evaluate trace results, we tested urine and stool specimens from 398 pupils from eight schools in Burundi using four approaches: two in Burundi and two in a laboratory in Leiden, the Netherlands. In Burundi, we used Kato-Katz and point-of-care CCA (CCAB). In Leiden, we repeated the CCA (CCAL) and also used Up-Converting Phosphor Circulating Anodic Antigen (CAA). METHODS: We applied Bayesian latent class analyses (LCA), first considering CCA traces as negative and then as positive. We used the LCA output to estimate validity of the prevalence estimates of each test in comparison to the population-level infection prevalence and estimated the proportion of trace results that were likely true positives. RESULTS: Kato-Katz yielded the lowest prevalence (6.8%), and CCAB with trace considered positive yielded the highest (53.5%). There were many more trace results recorded by CCA in Burundi (32.4%) than in Leiden (2.3%). Estimated prevalence with CAA was 46.5%. LCA indicated that Kato-Katz had the lowest sensitivity: 15.9% [Bayesian Credible Interval (BCI): 9.2-23.5%] with CCA-trace considered negative and 15.0% with trace as positive (BCI: 9.6-21.4%), implying that Kato-Katz missed approximately 85% of infections. CCAB underestimated disease prevalence when trace was considered negative and overestimated disease prevalence when trace was considered positive, by approximately 12 percentage points each way, and CAA overestimated prevalence in both models. Our results suggest that approximately 52.2% (BCI: 37.8-5.8%) of the CCAB trace readings were true infections. CONCLUSIONS: Whether measured in the laboratory or the field, CCA outperformed Kato-Katz at the low infection intensities in Burundi. CCA with trace as negative likely missed many infections, whereas CCA with trace as positive overestimated prevalence. In the absence of a field-friendly gold standard diagnostic, the use of a variety of diagnostics with differing properties will become increasingly important as programs move towards elimination of schistosomiasis. It is clear that CCA is a valuable tool for the detection and mapping of S. mansoni infection in the field and CAA may be a valuable field tool in the future.