Schistosoma Transmission in a Dynamic Seasonal Environment and its Impact on the Effectiveness of Disease Control.

BACKGROUND: A seasonal transmission environment including seasonal variation of snail population density and human-snail contact patterns can affect the dynamics of Schistosoma infection and the success of control interventions. In projecting control outcomes, conventional modeling approaches have often ignored seasonality by using simplified intermediate-host modeling, or by restricting seasonal effects through use of yearly averaging. METHODS: We used mathematical analysis and numerical simulation to estimate the impact of seasonality on disease dynamics and control outcomes, and to evaluate whether seasonal averaging or intermediate-host reduction can provide reliable predictions of control outcomes. We also examined whether seasonality could be used as leverage in creation of effective control strategies. RESULTS: We found models that used seasonal averaging could grossly overestimate infection burden and underestimate control outcomes in highly seasonal environments. We showed that proper intraseasonal timing of control measures could make marked improvement on the long-term burden reduction for Schistosoma transmission control, and we identified the optimal timing for each intervention. Seasonal snail control, implemented alone, was less effective than mass drug administration, but could provide additive impact in reaching control and elimination targets. CONCLUSIONS: Seasonal variation makes Schistosoma transmission less sustainable and easier to control than predicted by earlier modeling studies.

Enabling precision medicine via standard communication of HTS provenance, analysis, and results.

A personalized approach based on a patient's or pathogen's unique genomic sequence is the foundation of precision medicine. Genomic findings must be robust and reproducible, and experimental data capture should adhere to findable, accessible, interoperable, and reusable (FAIR) guiding principles. Moreover, effective precision medicine requires standardized reporting that extends beyond wet-lab procedures to computational methods. The BioCompute framework (https://w3id.org/biocompute/1.3.0) enables standardized reporting of genomic sequence data provenance, including provenance domain, usability domain, execution domain, verification kit, and error domain. This framework facilitates communication and promotes interoperability. Bioinformatics computation instances that employ the BioCompute framework are easily relayed, repeated if needed, and compared by scientists, regulators, test developers, and clinicians. Easing the burden of performing the aforementioned tasks greatly extends the range of practical application. Large clinical trials, precision medicine, and regulatory submissions require a set of agreed upon standards that ensures efficient communication and documentation of genomic analyses. The BioCompute paradigm and the resulting BioCompute Objects (BCOs) offer that standard and are freely accessible as a GitHub organization (https://github.com/biocompute-objects) following the "Open-Stand.org principles for collaborative open standards development." With high-throughput sequencing (HTS) studies communicated using a BCO, regulatory agencies (e.g., Food and Drug Administration [FDA]), diagnostic test developers, researchers, and clinicians can expand collaboration to drive innovation in precision medicine, potentially decreasing the time and cost associated with next-generation sequencing workflow exchange, reporting, and regulatory reviews.

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA.

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.

Achieving Elimination as a Public Health Problem for Schistosoma mansoni and S. haematobium: When Is Community-Wide Treatment Required?

The World Health Organization (WHO) has set elimination as a public health problem (EPHP) as a goal for schistosomiasis. As the WHO treatment guidelines for schistosomiasis are currently under revision, we investigate whether school-based or community-wide treatment strategies are required for achieving the EPHP goal. In low- to moderate-transmission settings with good school enrolment, we find that school-based treatment is sufficient for achieving EPHP. However, community-wide treatment is projected to be necessary in certain high-transmission settings as well as settings with low school enrolment. Hence, the optimal treatment strategy depends on setting-specific factors such as the species present, prevalence prior to treatment, and the age profile of infection.

Factors associated with early childhood stunted growth in a 2012-2015 birth cohort monitored in the rural Msambweni area of coastal Kenya: a cross-sectional study.

BACKGROUND: Chronic malnutrition, often measured as stunted growth, is an understudied global health problem. Though poor nutritional intake has been linked to stunted growth, there is evidence suggesting environmental exposures may have a significant role in its occurrence. Here, we characterize the non-nutritional prenatal and postnatal factors that contribute to early childhood stunted growth in rural coastal Kenya. METHODS: Overall, 232 women and 244 children from a 2012-2015 maternal-child cohort in Msambweni, Kenya were included. Women were tested for parasitic infections during the prenatal period and at the time of delivery. Children were tested for parasitic infections and assessed for stunted growth using height-for-age Z-scores (HAZ) at 6-month intervals after birth. Socioeconomic status (SES) was evaluated using both a simplified water, asset, maternal education, and income (WAMI) index and a principal component analysis (PCA) asset score. Multivariate logistic regression analysis was used to determine the relative influence of prenatal and postnatal factors on the occurrence of stunted growth. RESULTS: Of the 244 children (ages 6-37 months), 60 (25%) were stunted at the study endpoint. 179 mothers (77%) had at least one parasitic infection during pregnancy and 94 children (38%) had at least one parasitic infection during the study period. There was no significant association between maternal parasitic infection and child stunted growth (p = 1.00). SES as determined using the WAMI index was not associated with HAZ in linear regression analysis (p = 0.307), however, the PCA asset score was (p = 0.048). Multivariate logistic regression analysis identified low birth weight (AOR: 3.24, 95% CI: [1.38, 7.57]) and child parasitic infectious disease burden (AOR: 1.41, 95% CI: [1.05, 1.95]) as independent predictors of stunted growth, though no significant association was identified with PCA asset score (AOR: 0.98, 95% CI: [0.88, 1.10]). CONCLUSIONS: Stunted growth remains highly prevalent in rural Kenya, with low birth weight and child parasitic infectious disease burden demonstrated to be significantly associated with this indicator of chronic malnutrition. These results emphasize the multifaceted nature of stunted growth and the need to address both the prenatal and postnatal environmental factors that contribute to this problem.

Cord Blood Antiparasite Interleukin 10 as a Risk Marker for Compromised Vaccine Immunogenicity in Early Childhood.

Background: Antenatal exposure to parasites can affect infants' subsequent responses to vaccination. The present study investigated how maternal prenatal infections and newborns' antiparasite cytokine profiles relate to immunoglobulin G (IgG) responses to standard vaccination during infancy. Methods: A total of 450 Kenyan women were tested for parasitic infections during pregnancy. Their newborns' responses to Plasmodium falciparum, schistosome, and filaria antigens were assessed in cord blood lymphocytes. Following standard neonatal vaccination, this infant cohort was followed biannually to age 30 months for measurement of circulating IgG levels against Haemophilus influenzae b (Hib), diphtheria toxoid (DT), hepatitis B virus (HBV), and tetanus toxoid. Results: Trajectories of postvaccination IgG levels were classified by functional principal component (PC) analysis to assess each child's response profile. Two main components, PC1, reflecting height of response over time, and PC2, reflecting crossover from high to low responses or from low to high responses, were identified. Cord blood cytokine responses to schistosome and filarial antigens showed a significant association between augmented antihelminth interleukin 10 and reduced antibody levels, particularly to DT and HBV, and a more rapid postvaccination decline in circulating IgG levels against Hib. Conclusion: Antenatal sensitization to schistosomiasis or filariasis and related production of antiparasite interleukin 10 at birth are associated with reduced antivaccine IgG levels in infancy, with possibly impaired protection.

Are We on Our Way to Achieving the 2020 Goals for Schistosomiasis Morbidity Control Using Current World Health Organization Guidelines?

Background: Schistosomiasis remains an endemic parasitic disease affecting millions of people around the world. The World Health Organization (WHO) has set goals of controlling morbidity to be reached by 2020, along with elimination as a public health problem in certain regions by 2025. Mathematical models of parasite transmission and treatment impact have been developed to assist in controlling the morbidity caused by schistosomiasis. These models can inform and guide implementation policy for mass drug administration programs, and help design monitoring and evaluation activities. Methods: We use these models to predict whether the guidelines set by the WHO are on track for achieving their 2020 goal for the control of morbidity, specifically for Schistosoma mansoni. We examine whether programmatic adaptations; namely increases in treatment coverage and/or expansion to adult inclusion in treatment, will improve the likelihood of reaching the WHO goals. Results: We find that in low-prevalence settings, the goals are likely to be attainable under current WHO guidelines, but in moderate to high-prevalence settings, the goals are less likely to be achieved unless treatment coverage is increased and expanded to at least 85% for school-aged children and 40% for adults. Conclusions: To improve the likelihood of reaching the WHO goals, programmatic adaptations are required, particularly for moderate- to high-prevalence settings. Furthermore, improvements in adherence to treatment, potential development of candidate vaccines, and enhanced snail control and WASH (water, sanitation, and hygiene) measures will all assist in achieving the goals.

Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies. METHODS: In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. RESULTS: At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory. CONCLUSIONS: Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis. TRIAL REGISTRATION: These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 .

One hundred years of neglect in paediatric schistosomiasis.

Early in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel - PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts.

Gaining and sustaining schistosomiasis control: study protocol and baseline data prior to different treatment strategies in five African countries.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study. METHODS: Beginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies. RESULTS: These studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control. CONCLUSIONS: We expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community. TRIAL REGISTRATION: The trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114 , ISRCTN14849830 , ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 and ISRCTN32045736 ).

Human schistosomiasis.

Human schistosomiasis--or bilharzia--is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination.

Use of prospective hospital surveillance data to define spatiotemporal heterogeneity of malaria risk in coastal Kenya.

BACKGROUND: Malaria in coastal Kenya shows spatial heterogeneity and seasonality, which are important factors to account for when planning an effective control system. Routinely collected data at health facilities can be used as a cost-effective method to acquire information on malaria risk for large areas. Here, data collected at one specific hospital in coastal Kenya were used to assess the ability of such passive surveillance to capture spatiotemporal heterogeneity of malaria and effectiveness of an augmented control system. METHODS: Fever cases were tested for malaria at Msambweni sub-County Referral Hospital, Kwale County, Kenya, from October 2012 to March 2015. Remote sensing data were used to classify the development level of each monitored community and to identify the presence of rice fields nearby. An entomological study was performed to acquire data on the seasonality of malaria vectors in the study area. Rainfall data were obtained from a weather station located in proximity of the study area. Spatial analysis was applied to investigate spatial patterns of malarial and non-malarial fever cases. A space-time Bayesian model was performed to evaluate risk factors and identify locations at high malaria risk. Vector seasonality was analysed using a generalized additive mixed model (GAMM). RESULTS: Among the 25,779 tested febrile cases, 28.7 % were positive for Plasmodium infection. Malarial and non-malarial fever cases showed a marked spatial heterogeneity. High risk of malaria was linked to patient age, community development level and presence of rice fields. The peak of malaria prevalence was recorded close to rainy seasons, which correspond to periods of high vector abundance. Results from the Bayesian model identified areas with significantly high malaria risk. The model also showed that the low prevalence of malaria recorded during late 2012 and early 2013 was associated with a large-scale bed net distribution initiative in the study area during mid-2012. CONCLUSIONS: The results indicate that the use of passive surveillance was an effective method to detect spatiotemporal patterns of malaria risk in coastal Kenya. Furthermore, it was possible to estimate the impact of extensive bed net distribution on malaria prevalence among local fever cases over time. Passive surveillance based on georeferenced malaria testing is an important tool that control agencies can use to improve the effectiveness of interventions targeting malaria (and other causes of fever) in such high-risk locations.

RNA helicase signaling is critical for type i interferon production and protection against Rift Valley fever virus during mucosal challenge.

Rift Valley fever virus (RVFV) is an emerging RNA virus with devastating economic and social consequences. Clinically, RVFV induces a gamut of symptoms ranging from febrile illness to retinitis, hepatic necrosis, hemorrhagic fever, and death. It is known that type I interferon (IFN) responses can be protective against severe pathology; however, it is unknown which innate immune receptor pathways are crucial for mounting this response. Using both in vitro assays and in vivo mucosal mouse challenge, we demonstrate here that RNA helicases are critical for IFN production by immune cells and that signaling through the helicase adaptor molecule MAVS (mitochondrial antiviral signaling) is protective against mortality and more subtle pathology during RVFV infection. In addition, we demonstrate that Toll-like-receptor-mediated signaling is not involved in IFN production, further emphasizing the importance of the RNA cellular helicases in type I IFN responses to RVFV.

Communicating computational workflows in a regulatory environment.

The volume of nucleic acid sequence data has exploded recently, amplifying the challenge of transforming data into meaningful information. Processing data can require an increasingly complex ecosystem of customized tools, which increases difficulty in communicating analyses in an understandable way yet is of sufficient detail to enable informed decisions or repeats. This can be of particular interest to institutions and companies communicating computations in a regulatory environment. BioCompute Objects (BCOs; an instance of pipeline documentation that conforms to the IEEE 2791-2020 standard) were developed as a standardized mechanism for analysis reporting. A suite of BCOs is presented, representing interconnected elements of a computation modeled after those that might be found in a regulatory submission but are shared publicly - in this case a pipeline designed to identify viral contaminants in biological manufacturing, such as for vaccines.

Physical condition and maintenance of mosquito bed nets in Kwale County, coastal Kenya.

BACKGROUND: Despite the extensive ownership and use of insecticide-treated nets (ITNs) over the last decade, the effective lifespan of these nets, especially their physical integrity, under true operational conditions is not well-understood. Usefulness of nets declines primarily due to physical damage or loss of insecticidal activity. METHODS: A community based cross-sectional survey was used to determine the physical condition and to identify predictors of poor physical condition for bed nets owned by individuals from communities in Kwale County, coastal Kenya. A proportionate hole index (pHI) was used as a standard measure, and the cut-offs for an 'effective net' (offer substantial protection against mosquito bites) and 'ineffective nets' (offer little or no protection against mosquito bites) were determined (pHI ≤88 (about ≤500 cm2 of holes surface area) and pHI of >88 (≥500 cm2 of holes surface area), respectively). RESULTS: The vast majority (78%) of the surveyed nets had some holes. The median pHI was 92 (range: 1-2,980). Overall, half of the nets were categorized as 'effective nets' or 'serviceable nets'. Physical deterioration of nets was associated with higher use and washing frequency. Young children and older children were found to use ineffective bed nets significantly more often than infants, while the physical integrity of nets owned by pregnant women was similar to those owned by infants. Estuarine environment inhabitants owned nets with the worst physical condition, while nets owned by the coastal slope inhabitants were in fairly good physical condition. The results suggest that bed nets are optimally utilized when they are new and physically intact. Thereafter, bed net utilization decreases gradually with increasing physical deterioration, with most net owners withdrawing physically damaged nets from routine use.This withdrawal commonly happens following 1.5 years of use, making bed net use the most important predictor of physical integrity. On average, the nets were washed twice within six months prior to the survey. Washing frequency was significantly influenced by the bed net colour and bed net age. Lack of knowledge on reasons for net retreatment and the retreatment procedure was evident, while net repair was minimal and did not seem to improve the physical condition of the nets. The "catch-up" bed net distribution strategies are sufficient for ensuring adequate ownership and utilization of 'effective nets' in the targeted groups, but bi-annual mass distribution is necessary to provide similar ownership and utilization for the other groups not targeted by "catch-up" strategies. CONCLUSIONS: Monitoring and maintenance strategies that will deliver locally appropriate education messages on net washing and repair will enhance the effectiveness of malaria control programmes, and further research to assess ineffective nets need is needed.

Monitoring malaria vector control interventions: effectiveness of five different adult mosquito sampling methods.

Long-term success of ongoing malaria control efforts based on mosquito bed nets (long-lasting insecticidal net) and indoor residual spraying is dependent on continuous monitoring of mosquito vectors, and thus on effective mosquito sampling tools. The objective of our study was to identify the most efficient mosquito sampling tool(s) for routine vector surveillance for malaria and lymphatic filariasis transmission in coastal Kenya. We evaluated relative efficacy of five collection methods--light traps associated with a person sleeping under a net, pyrethrum spray catches, Prokopack aspirator, clay pots, and urine-baited traps--in four villages representing three ecological settings along the south coast of Kenya. Of the five methods, light traps were the most efficient for collecting female Anopheles gambiae s.l. (Giles) (Diptera: Culicidae) and Anopheles funestus (Giles) (Diptera: Culicidae) mosquitoes, whereas the Prokopack aspirator was most efficient in collecting Culex quinquefasciatus (Say) (Diptera: Culicidae) and other culicines. With the low vector densities here, and across much of sub-Saharan Africa, wherever malaria interventions, long-lasting insecticidal nets, and/or indoor residual spraying are in place, the use of a single mosquito collection method will not be sufficient to achieve a representative sample of mosquito population structure. Light traps will remain a relevant tool for host-seeking mosquitoes, especially in the absence of human landing catches. For a fair representation of the indoor mosquito population, light traps will have to be supplemented with aspirator use, which has potential for routine monitoring of indoor resting mosquitoes, and can substitute the more labor-intensive and intrusive pyrethrum spray catches. There are still no sufficiently efficient mosquito collection methods for sampling outdoor mosquitoes, particularly those that are bloodfed.

A 14-year follow-up of ultrasound-detected urinary tract pathology associated with urogenital schistosomiasis in women living in the Msambweni region of coastal Kenya.

BACKGROUND: Complications of urogenital schistosomiasis include acute inflammatory and chronic fibrotic changes within the urogenital tract. Disease burden of this neglected tropical disease is often underestimated, as only active, urine egg-patent Schistosoma infection is formally considered. Previous studies have focussed on short-term effects of praziquantel treatment on urinary tract pathology, demonstrating that acute inflammation is reversible. However, the reversibility of chronic changes is less well studied. METHODS: Our study compared, at two time points 14 y apart, urine egg-patent infection and urinary tract pathology in a cohort of women living in a highly endemic area having intermittent praziquantel treatment(s). In 2014 we matched 93 women to their findings in a previous study in 2000. RESULTS: Between 2000 and 2014 the rate of egg-patent infection decreased from 34% (95% confidence interval [CI] 25 to 44) to 9% (95% CI 3 to 14). However, urinary tract pathology increased from 15% (95% CI 8 to 22) to 19% (95% CI 11 to 27), with the greatest increase seen in bladder thickening and shape abnormality. CONCLUSIONS: Despite praziquantel treatment, fibrosis from chronic schistosomiasis outlasts the presence of active infection, continuing to cause lasting morbidity. We suggest that future efforts to eliminate persistent morbidity attributable to schistosomiasis should include intensified disease management.

Detection of acute dengue virus infection, with and without concurrent malaria infection, in a cohort of febrile children in Kenya, 2014-2019, by clinicians or machine learning algorithms.

Poor access to diagnostic testing in resource limited settings restricts surveillance for emerging infections, such as dengue virus (DENV), to clinician suspicion, based on history and exam observations alone. We investigated the ability of machine learning to detect DENV based solely on data available at the clinic visit. We extracted symptom and physical exam data from 6,208 pediatric febrile illness visits to Kenyan public health clinics from 2014-2019 and created a dataset with 113 clinical features. Malaria testing was available at the clinic site. DENV testing was performed afterwards. We randomly sampled 70% of the dataset to develop DENV and malaria prediction models using boosted logistic regression, decision trees and random forests, support vector machines, naïve Bayes, and neural networks with 10-fold cross validation, tuned to maximize accuracy. 30% of the dataset was reserved to validate the models. 485 subjects (7.8%) had DENV, and 3,145 subjects (50.7%) had malaria. 220 (3.5%) subjects had co-infection with both DENV and malaria. In the validation dataset, clinician accuracy for diagnosis of malaria was high (82% accuracy, 85% sensitivity, 80% specificity). Accuracy of the models for predicting malaria diagnosis ranged from 53-69% (35-94% sensitivity, 11-80% specificity). In contrast, clinicians detected only 21 of 145 cases of DENV (80% accuracy, 14% sensitivity, 85% specificity). Of the six models, only logistic regression identified any DENV case (8 cases, 91% accuracy, 5.5% sensitivity, 98% specificity). Without diagnostic testing, interpretation of clinical findings by humans or machines cannot detect DENV at 8% prevalence. Access to point-of-care diagnostic tests must be prioritized to address global inequities in emerging infections surveillance.