Randomized Trial to Improve Body Composition and Micronutrient Status Among South African Children.

INTRODUCTION: Physical activity (PA) promotion combined with multimicronutrient supplementation (MMNS) among school-age children may reduce fat mass accrual and increase muscle mass through different mechanisms and so benefit child health. This study determined the efficacy of combined interventions on body composition among South African schoolchildren and determined if micronutrients mediate these effects. STUDY DESIGN: Longitudinal cluster randomized controlled trial of children followed from 2019 to 2021. Statistical analyses carried from 2022 to 2023. SETTING/PARTICIPANTS: A total of 1,304 children 6-12 years of age recruited from public schools in Gqeberha, South Africa. INTERVENTION: Children were randomized by classes to either: (a) a physical activity group (PA); (b) a MMNS group; (c) a physical activity + multimicronutrient supplementation group (PA + MMNS); and (d) a placebo control group. MAIN OUTCOME MEASURES: Trajectories of overall and truncal fat free mass (FFM) and fat mass (FM) estimates in modeled at 9 and 21 months using latent growth curve models (LGCM). Changes in micronutrient concentrations at 9 months from baseline. RESULTS: An increased FFM trajectory was found among children in the MMNS arm at 9 months (Beta 0.16, 95% CI = 0.12, 0.31). The PA and MMNS arms both had positive indirect effects on this trajectory at 9 months (Beta 0.66, 95% CI = 0.44, 0.88 and Beta 0.32 95% CI = 0.1 0.5, respectively) and similarly at 21 months when mediated by zinc concentration changes. A reduced FM trajectory was found among children in the PA promotion arm at 9 months when using this collection point as the referent intercept. This arm was inversely associated with the FM trajectory at 9 months when mediated by zinc changes. CONCLUSIONS: PA and MMNS promotion in school-based interventions directly contributed to reductions in FM and increased FFM among South African children and indirectly through changes in micronutrient status. TRIAL REGISTRATION: ISRCTN, ISRCTN29534081. Registered on August 9, 2018 Institutional review board: Ethikkommission Nordwest- und Zentralschweiz" (EKNZ, project number: Req-2018-00608). Date of approval: 2018.

Distribution and treatment needs of soil-transmitted helminthiasis in Bangladesh: A Bayesian geostatistical analysis of 2017-2020 national survey data.

BACKGROUND: In Bangladesh, preventive chemotherapy targeting soil-transmitted helminth (STH) infections in school-age children has been implemented since 2008. To evaluate the success of this strategy, surveys were conducted between 2017 and 2020 in 10 out of 64 districts. We estimate the geographic distribution of STH infections by species at high spatial resolution, identify risk factors, and estimate treatment needs at different population subgroups. METHODOLOGY: Bayesian geostatistical models were fitted to prevalence data of each STH species. Climatic, environmental, and socioeconomic predictors were extracted from satellite images, open-access, model-based databases, and demographic household surveys, and used to predict the prevalence of infection over a gridded surface at 1 x 1 km spatial resolution across the country, via Bayesian kriging. These estimates were combined with gridded population data to estimate the number of required treatments for different risk groups. PRINCIPAL FINDINGS: The population-adjusted prevalence of Ascaris lumbricoides, Trichuris trichiura, and hookworm across all ages is estimated at 9.9% (95% Bayesian credible interval: 8.0-13.0%), 4.3% (3.0-7.3%), and 0.6% (0.4-0.9%), respectively. There were 24 out of 64 districts with an estimated population-adjusted STH infection prevalence above 20%. The proportion of households with improved sanitation showed a statistically important, protective association for both, A. lumbricoides and T. trichiura prevalence. Precipitation in the driest month of the year was negatively associated with A. lumbricoides prevalence. High organic carbon concentration in the soil's fine earth fraction was related to a high hookworm prevalence. Furthermore, we estimated that 30.5 (27.2; 36.0) million dosages of anthelmintic treatments for school-age children were required per year in Bangladesh. CONCLUSIONS/SIGNIFICANCE: For each of the STH species, the prevalence was reduced by at least 80% since treatment was scaled up more than a decade ago. The current number of deworming dosages could be reduced by up to 61% if the treatment strategy was adapted to the local prevalence.

Accelerating the healing of hard-to-heal wounds with food supplements: nutritional analysis in the Côte d'Ivoire.

OBJECTIVE: Hard-to-heal wounds are an important, yet often neglected, public health issue in low- and middle-income countries (LMICs). Malnutrition has been identified as a risk factor for prolonged healing times. However, nutritional supplements are not routinely provided for patients with hard-to-heal wounds, and so this study aimed to investigate their benefits. METHOD: This 9-month study was conducted in the Taabo Health and Demographic Surveillance System in the south-central part of Côte d'Ivoire. Patients with wounds (≥30mm2) were recruited. Treatment was standardised for inpatients (72%) and outpatients (28%). There were three intervention groups: supplemented with soy; orange flesh sweet potato (OFSP); or both. Another group was included without supplement, serving as control. General linear models were employed to assess the effects of log initial wound size, type of wound, food treatment group, haemoglobin, sex, age, place of treatment and body mass index on the rate of wound closure. RESULTS: The cohort consisted of 56 patients, 41 of whom were placed in intervention groups, and the remainder as controls. Within the cohort, 37 (66%) patients suffered from Buruli ulcer, 15 (27%) from traumatic wounds and four (7%) from erysipelas. We found a significant effect (p=0.004) of diet supplemented with OFSP on the wound healing rate. CONCLUSION: OFSP is a nutritional rehabilitation supplement, characterised by a high content of beta-carotene and carbohydrates. It is associated with shortened wound healing times, reduced discomfort and reduced cost of wound care. Further research should investigate the effect of a diet rich in beta-carotene, in combination with standard medical care, on hard-to-heal wound healing in LMICs.

Improving coverage of antenatal iron and folic acid supplementation and malaria prophylaxis through targeted information and home deliveries in Côte d'Ivoire: a cluster randomised controlled trial.

INTRODUCTION: Coverage of antenatal iron and folic acid (IFA) supplementation and malaria chemoprophylaxis remains low in many low-income and middle-income settings. We assessed the effectiveness of personal information (INFO) sessions and personal information session plus home deliveries (INFO+DELIV) to increase coverage of IFA supplementation and intermittent preventive treatment in pregnancy (IPTp), and their effectiveness on postpartum anaemia and malaria infection. METHODS: We included 118 clusters randomised to a control (39), INFO (39) and INFO+DELIV (40) arm, in a trial conducted between 2020 and 2021 with pregnant women (age ≥15 years) in their first or second trimester of pregnancy in Taabo, Côte d'Ivoire. We used generalised linear regression models to assess intervention impact in postpartum anaemia and malaria parasitaemia, and displayed resulting estimates as prevalence ratios. RESULTS: Overall, 767 pregnant women were enrolled and 716 (93.3%) were followed up after delivery. Neither intervention had an impact on postpartum anaemia, with estimated adjusted prevalence ratios (aPRs) of 0.97 (95% CI 0.79 to 1.19, p=0.770) for INFO and 0.87 (95% CI 0.70 to 1.09, p=0.235) for INFO+DELIV. While INFO had no effect on malaria parasitaemia (aPR=0.95, 95% CI 0.39 to 2.31, p=0.915), INFO+DELIV reduced malaria parasitaemia by 83% (aPR=0.17, 95% CI 0.04 to 0.75, p=0.019). No improvements in antenatal care (ANC) coverage (aPR=1.05, 95% CI 0.81 to 1.36, p=0.692), IFA (aPR=2.00, 95% CI 0.89 to 4.46, p=0.093) and IPTp (aPR=1.03, 95% CI 0.87 to 1.21, p=0.728) compliance were found for INFO. INFO+DELIV increased ANC attendance (aPR=1.35, 95% CI 1.02 to 1.78, p=0.037) and compliance with IPTp (aPR=1.60, 95% CI 1.41 to 1.80, p<0.001) and IFA recommendations (aPR=7.06, 95% CI 3.68 to 13.51, p<0.001). CONCLUSIONS: INFO+DELIV can substantially increase compliance with IFA supplementation and improve malaria prevention. However, the increases in IFA supplementation are likely insufficient to address the prevalence of often severe anaemia in this population. TRIAL REGISTRATION NUMBER: NCT04250428.

Egg excretion indicators for the measurement of soil-transmitted helminth response to treatment.

BACKGROUND: Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments. METHODOLOGY: We built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14-21 and 22-45 days) after drug administration. PRINCIPAL FINDINGS: The 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14-21 days and 22-45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14-21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%. CONCLUSIONS/SIGNIFICANCE: Combining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections.

Evaluation of a Physical Activity and Multi-Micronutrient Intervention on Cognitive and Academic Performance in South African Primary Schoolchildren.

Executive functions (EFs) are essential for optimal academic development. Appropriate nutrition and physical activity (PA) have been shown to facilitate optimal cognitive development. Therefore, this study examined whether a 12-week school-based PA and multi-micronutrient supplementation (MMNS) intervention would improve cognitive and academic performance. A cluster-randomized controlled trial (RCT) was conducted. Children from four schools located in a peri-urban area of South Africa were randomly assigned to (i) PA + MMNS, (ii) PA + placebo, (iii) MMNS or (iv) placebo. Information processing and inhibitory control were measured with a computerized Flanker task. End-of-year results provided insight into academic achievement. Anthropometric measures were used to determine nutritional status. Data were analyzed with linear mixed-models, adjusting for baseline scores, school classes and age; 932 children (458 girls (49.1%), Mage (mean age) = 8.42 ± 1.94 years) completed baseline and post-intervention assessments. Cognitive performance improved among all four groups, with no significant group × time effects. For academic achievement, there was no significant interaction effect between the combined intervention group and placebo. We encourage future studies in this neglected area in order to determine the most optimal design of school-based nutrition and PA programs to enhance overall cognitive performance.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

Impact of a school-based health intervention program on body composition among South African primary schoolchildren: results from the KaziAfya cluster-randomized controlled trial.

BACKGROUND: The prevalence of overweight and obesity is increasing among African children potentially predisposing them to greater obesity and non-communicable diseases (NCDs) in adulthood. This risk may be higher among growth-impaired children who may have greater fat mass. Therefore, we examined the effects of school-based physical activity (PA) promotion and multi-micronutrient supplementation (MMNS) on body composition among South African children enrolled in a longitudinal school-based randomized controlled trial. METHODS: Children were cluster-randomized by class to one of four groups: (a) a physical activity group (PA), (b) a multi-micronutrient supplementation group (MMNS), (c) a physical activity + multi-micronutrient supplementation group (PA + MMNS), and (d) control group, and were being followed for 3 years. Linear random effects regression models with random intercepts for school classes tested the associations of each intervention arm with overall fat mass (FM), fat-free mass (FFM), truncal fat mass (TrFM), and truncal fat-free mass (TrFFM) at 9 months (T2) for boys and girls. These differences were then explored among children who differed in height velocity (HV). RESULTS: A total of 1304 children (614 girls, 667 boys) in twelve clusters were assessed at baseline and after 9 months follow-up (T2). At baseline, approximately 15% of children were classified as overweight or obese while approximately 38% of children were classified as mildly stunted or moderately/severely stunted. Among girls, promotion of PA was associated with reduced FM and TrFM at T2 while MMNS was associated with increased FFM. Children with reduced HV in the PA arm had reduced FM while children in the MMNS arm with lower HV had increased FM compared to children in the control arm. Similarly, children with lower HV in the MM and PA groups had reduced TrFM compared to children in the control arm. CONCLUSIONS: Our study suggests that the promotion of school-based physical activity programs and micronutrient supplementation can reduce childhood adiposity and so reduce the risk of obesity and chronic diseases later in adulthood. TRIAL REGISTRATION: ISRCTN, ISRCTN29534081 . Registered on August 9, 2018. The trial was designed, analyzed, and interpreted based on the CONSORT protocol (Additional file 1: CONSORT checklist for randomized trial).

Study protocol of a cluster randomized controlled trial of strategies to increase antenatal iron and folic acid supplementation and malaria prophylaxis in rural south-central Côte d'Ivoire.

BACKGROUND: Coverage of antenatal iron and folic acid supplementation (IFAS) and intermittent preventive treatment of malaria in pregnancy (IPTp) remains low in many countries. Evidence on the most effective ways to increase both IFASIPTp is mixed overall, with only few studies directly identifying cost-effective ways to increase coverage of both interventions. The proposed study aims to assess the cost, impact and relative cost-effectiveness of two complementary strategies of increasing IFAS and malaria chemoprophylaxis coverage among pregnant women relative to the current default system in a rural low-income setting of sub-Saharan Africa. METHODS/DESIGN: This study will be carried out in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire. This is a cluster-randomized trial targeting 720 consenting pregnant women aged ≥15 years. The 118 clusters constituting the Taabo HDSS monitoring area will be randomly allocated to one of the following three groups with equal probability: a control group, an information only group, and an information plus home delivery group. To assess the relative effectiveness of each strategy, we will conduct an endline survey within the first 2 weeks after delivery. The primary outcomes of the trial will be maternal post-partum anaemia and malaria infection. Anaemia will be assessed using HEMOCUE devices; malaria infections will be assessed using standard rapid diagnostic tests named CareStart™ Malaria Pf (HRP2) Ag RDT (Multi Kit with capped lancet and inverted cup specimen transfer device). Other outcomes will include self-reported adherence to supplementation and malaria chemoprophylaxis, as well as miscarriages, stillbirths and low birth weight deliveries. DISCUSSION: This study will assess the cost-effectiveness of two alternative strategies to increase antenatal IFAS and malaria chemoprophylaxis coverage among pregnant women in rural Côte d'Ivoire and similar settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04250428 ; Registered 31 January 2020.

The global progress of soil-transmitted helminthiases control in 2020 and World Health Organization targets for 2030.

Soil-transmitted helminth (STH) infections are the most widespread of the neglected tropical diseases, primarily affecting marginalized populations in low- and middle-income countries. More than one billion people are currently infected with STHs. For the control of these infections, the World Health Organization (WHO) recommends an integrated approach, which includes access to appropriate sanitation, hygiene education, and preventive chemotherapy (i.e., large-scale, periodic distribution of anthelmintic drugs). Since 2010, WHO has coordinated two large donations of benzimidazoles to endemic countries. Thus far, more than 3.3 billion benzimidazole tablets have been distributed in schools for the control of STH infections, resulting in an important reduction in STH-attributable morbidity in children, while additional tablets have been distributed for the control of lymphatic filariasis. This paper (i) summarizes the progress of global STH control between 2008 to 2018 (based on over 690 reports submitted by endemic countries to WHO); (ii) provides regional and country details on preventive chemotherapy coverage; and (iii) indicates the targets identified by WHO for the next decade and the tools that should be developed to attain these targets. The main message is that STH-attributable morbidity can be averted with evidence-informed program planning, implementation, and monitoring. Caution will still need to be exercised in stopping control programs to avoid any rebound of prevalence and loss of accrued morbidity gains. Over the next decade, with increased country leadership and multi-sector engagement, the goal of eliminating STH infections as a public health problem can be achieved.

Effects of school-based physical activity and multi-micronutrient supplementation intervention on growth, health and well-being of schoolchildren in three African countries: the KaziAfya cluster randomised controlled trial protocol with a 2 × 2 factorial design.

BACKGROUND: In low- and middle-income countries, infectious diseases remain a key public health issue. Additionally, non-communicable diseases are a rapidly growing public health problem that impose a considerable burden on population health. One way to address this dual disease burden, is to incorporate (lifestyle) health promotion measures within the education sector. In the planned study, we will (i) assess and compare physical activity, physical fitness, micronutrient status, body composition, infections with soil-transmitted helminths, Schistosoma mansoni, malaria, inflammatory and cardiovascular health risk markers, cognitive function, health-related quality of life, and sleep in schoolchildren in Côte d'Ivoire, South Africa and Tanzania. We will (ii) determine the bi- and multivariate associations between these variables and (iii) examine the effects of a school-based health intervention that consists of physical activity, multi-micronutrient supplementation, or both. METHODS: Assuming that no interaction occurs between the two interventions (physical activity and multi-micronutrient supplementation), the study is designed as a cluster-randomised, placebo-controlled trial with a 2 × 2 factorial design. Data will be obtained at three time points: at baseline and at 9 months and 21 months after the baseline assessment. In each country, 1320 primary schoolchildren from grades 1-4 will be recruited. In each school, classes will be randomly assigned to one of four interventions: (i) physical activity; (ii) multi-micronutrient supplementation; (iii) physical activity plus multi-micronutrient supplementation; and (iv) no intervention, which will serve as the control. A placebo product will be given to all children who do not receive multi-micronutrient supplementation. After obtaining written informed consent from the parents/guardians, the children will be subjected to anthropometric, clinical, parasitological and physiological assessments. Additionally, fitness tests will be performed, and children will be invited to wear an accelerometer device for 7 days to objectively assess their physical activity. Children infected with S. mansoni and soil-transmitted helminths will receive deworming drugs according to national policies. Health and nutrition education will be provided to the whole study population independently of the study arm allocation. DISCUSSION: The study builds on the experience and lessons of a previous study conducted in South Africa. It involves three African countries with different social-ecological contexts to investigate whether results are generalisable across the continent. TRIAL REGISTRATION: The study was registered on August 9, 2018, with ISRCTN. https://doi.org/10.1186/ISRCTN29534081.

Effects of a School-Based Health Intervention Program in Marginalized Communities of Port Elizabeth, South Africa (the KaziBantu Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: The burden of poverty-related infectious diseases remains high in low- and middle-income countries, while noncommunicable diseases (NCDs) are rapidly gaining importance. To address this dual disease burden, the KaziBantu project aims at improving and promoting health literacy as a means for a healthy and active lifestyle. The project implements a school-based health intervention package consisting of physical education, moving-to-music, and specific health and nutrition education lessons from the KaziKidz toolkit. It is complemented by the KaziHealth workplace health intervention program for teachers. OBJECTIVES: The aim of the KaziBantu project is to assess the effect of a school-based health intervention package on risk factors for NCDs, health behaviors, and psychosocial health in primary school children in disadvantaged communities in Port Elizabeth, South Africa. In addition, we aim to test a workplace health intervention for teachers. METHODS: A randomized controlled trial (RCT) will be conducted in 8 schools. Approximately 1000 grade 4 to grade 6 school children, aged 9 to 13 years, and approximately 60 teachers will be recruited during a baseline survey in early 2019. For school children, the study is designed as a 36-week, cluster RCT (KaziKidz intervention), whereas for teachers, a 24-week intervention phase (KaziHealth intervention) is planned. The intervention program consists of 3 main components; namely, (1) KaziKidz and KaziHealth teaching material, (2) workshops, and (3) teacher coaches. After randomization, 4 of the 8 schools will receive the education program, whereas the other schools will serve as the control group. Intervention schools will be further randomized to the different combinations of 2 additional intervention components: teacher workshops and teacher coaching. RESULTS: This study builds on previous experience and will generate new evidence on health intervention responses to NCD risk factors in school settings as a decision tool for future controlled studies that will enable comparisons among marginalized communities between South African and other African settings. CONCLUSIONS: The KaziKidz teaching material is a holistic educational and instructional tool designed for primary school teachers in low-resource settings, which is in line with South Africa's Curriculum and Assessment Policy Statement. The ready-to-use lessons and assessments within KaziKidz should facilitate the use and implementation of the teaching material. Furthermore, the KaziHealth interventions should empower teachers to take care of their health through knowledge gains regarding disease risk factors, physical activity, fitness, psychosocial health, and nutrition indicators. Teachers as role models will be able to promote better health behaviors and encourage a healthy and active lifestyle for children at school. We conjecture that improved health and well-being increase teachers' productivity with trickle-down effects on the children they teach and train. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 18485542; http://www.isrctn.com/ISRCTN18485542. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14097.

Geographical variation in the association of child, maternal and household health interventions with under-five mortality in Burkina Faso.

BACKGROUND: Over the past 15 years, scaling up of cost effective interventions resulted in a remarkable decline of under-five mortality rates (U5MR) in sub-Saharan Africa. However, the reduction shows considerable heterogeneity. We estimated the association of child, maternal, and household interventions with U5MR in Burkina Faso at national and subnational levels and identified the regions with least effective interventions. METHODS: Data on health-related interventions and U5MR were extracted from the Burkina Faso Demographic and Health Survey (DHS) 2010. Bayesian geostatistical proportional hazards models with a Weibull baseline hazard were fitted on the mortality outcome. Spatially varying coefficients were considered to assess the geographical variation in the association of the health interventions with U5MR. The analyses were adjusted for child, maternal, and household characteristics, as well as climatic and environmental factors. FINDINGS: The average U5MR was as high as 128 per 1000 ranging from 81 (region of Centre-Est) to 223 (region of Sahel). At national level, DPT3 immunization and baby post-natal check within 24 hours after birth had the most important association with U5MR (hazard rates ratio (HRR) = 0.89, 95% Bayesian credible interval (BCI): 0.86-0.98 and HRR = 0.89, 95% BCI: 0.86-0.92, respectively). At sub-national level, the most effective interventions are the skilled birth attendance, and improved drinking water, followed by baby post-natal check within 24 hours after birth, vitamin A supplementation, antenatal care visit and all-antigens immunization (including BCG, Polio3, DPT3, and measles immunization). Centre-Est, Sahel, and Sud-Ouest were the regions with the highest number of effective interventions. There was no intervention that had a statistically important association with child survival in the region of Hauts Bassins. INTERPRETATION: The geographical variation in the magnitude and statistical importance of the association between health interventions and U5MR raises the need to deliver and reinforce health interventions at a more granular level. Priority interventions are DPT3 immunization, skilled birth attendance, baby post-natal visits in the regions of Sud-Ouest, Sahel, and Hauts Bassins, respectively. Our methodology could be applied to other national surveys, as it allows an incisive, data-driven and specific decision-making approach to optimize the allocation of health interventions at subnational level.

Evaluation of integrated interventions layered on mass drug administration for urogenital schistosomiasis elimination: a cluster-randomised trial.

BACKGROUND: Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are targets set by WHO for 2025. Our aim was to assess biannual mass drug administration (MDA) applied alone or with complementary snail control or behaviour change interventions for the reduction of Schistosoma haematobium prevalence and infection intensity in children from Zanzibar and to compare the effect between the clusters. METHODS: In a 5-year repeated cross-sectional cluster-randomised trial, 90 shehias (small administrative regions; clusters) in Zanzibar eligible owing to available natural open freshwater bodies and public primary schools were randomly allocated (ratio 1:1:1) to receive one of three interventions: biannual MDA with praziquantel alone (arm 1) or in combination with snail control (arm 2), or behaviour change activities (arm 3). Neither participants nor field or laboratory personnel were blinded to the intervention arms. From 2012 to 2017, annually, a single urine sample was collected from approximately 100 children aged 9-12 years in the main public primary school of each shehia. The primary outcome was S haematobium infection prevalence and intensity in 9-12-year-old children after 5 years of follow-up. This study is completed and was registered with the ISRCTN, number 48837681. FINDINGS: The trial was done from Nov 1, 2011, through to Dec 31, 2017 and recruitment took place from Nov 2, 2011, until May 17, 2017. At baseline we enrolled 8278 participants, of whom 2899 (35%) were randomly allocated to arm 1, 2741 (33%) to arm 2, and 2638 (32%) to arm 3. 120 (4·2%) of 2853 in arm 1, 209 (7·8%) of 2688 in arm 2, and 167 (6·4%) of 2613 in arm 3 had S haematobium infections at baseline. Heavy infections (≥50 eggs per 10 mL of urine) were found in 126 (1·6%) of 8073 children at baseline. At the 5-year endline survey, 46 (1·4%) of 3184 in arm 1, 56 (1·7%) of 3217 (odds ratio [OR] 1·2 [95% CI 0·6-2·7] vs arm 1) in arm 2, and 58 (1·9%) of 3080 (1·3 [0·6-2·9]) in arm 3 had S haematobium infections. Heavy infections were detected in 33 (0·3%) of 9462 children. INTERPRETATION: Biannual MDA substantially reduced the S haematobium prevalence and infection intensity but was insufficient to interrupt transmission. Although snail control or behaviour change activities did not significantly boost the effect of MDA in our study, they might enhance interruption of transmission when tailored to focal endemicity and applied for a longer period. It is now necessary to focus on reducing prevalence in remaining hotspot areas and to introduce new methods of surveillance and public health response so that the important gains can be maintained and advanced. FUNDING: University of Georgia Research Foundation Inc and Bill & Melinda Gates Foundation.

Pregnancy-related morbidity and risk factors for fatal foetal outcomes in the Taabo health and demographic surveillance system, Côte d'Ivoire.

BACKGROUND: Reliable, population-based data on pregnancy-related morbidity and mortality, and risk factors for fatal foetal outcomes are scarce for low- and middle-income countries. Yet, such data are essential for understanding and improving maternal and neonatal health and wellbeing. METHODS: Within the 4-monthly surveillance rounds of the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire, all women of reproductive age identified to be pregnant between 2011 and 2014 were followed-up. A questionnaire pertaining to antenatal care, pregnancy-related morbidities, delivery circumstances, and birth outcome was administered to eligible women. Along with sociodemographic information retrieved from the Taabo HDSS repository, these data were subjected to penalized maximum likelihood logistic regression analysis, to determine risk factors for fatal foetal outcomes. RESULTS: A total of 2976 pregnancies were monitored of which 118 (4.0%) resulted in a fatal outcome. Risk factors identified by multivariable logistic regression analysis included sociodemographic factors of the expectant mother, such as residency in a rural area (adjusted odds ratio (aOR) = 2.87; 95% confidence interval (CI) 1.31-6.29) and poorest wealth tertile (aOR = 1.79; 95% CI 1.02-3.14), a history of miscarriage (aOR = 23.19; 95% CI 14.71-36.55), non-receipt of preventive treatment such as iron/folic acid supplementation (aOR = 3.15; 95% CI 1.71-5.80), only two doses of tetanus vaccination (aOR = 2.59; 95% CI 1.56-4.30), malaria during pregnancy (aOR = 1.94; 95% CI 1.21-3.11), preterm birth (aOR = 4.45; 95% CI 2.82-7.01), and delivery by caesarean section (aOR = 13.03; 95% CI 4.24-40.08) or by instrumental delivery (aOR = 5.05; 95% CI 1.50-16.96). Women who paid for delivery were at a significantly lower odds of a fatal foetal outcome (aOR = 0.39; 95% CI 0.25-0.74). CONCLUSIONS: We identified risk factors for fatal foetal outcomes in a mainly rural HDSS site of Côte d'Ivoire. Our findings call for public health action to improve access to, and use of, quality services of ante- and perinatal care.

Interrupting seasonal transmission of Schistosoma haematobium and control of soil-transmitted helminthiasis in northern and central Côte d'Ivoire: a SCORE study protocol.

BACKGROUND: To achieve a world free of schistosomiasis, the objective is to scale up control and elimination efforts in all endemic countries. Where interruption of transmission is considered feasible, countries are encouraged to implement a comprehensive intervention package, including preventive chemotherapy, information, education and communication (IEC), water, sanitation and hygiene (WASH), and snail control. In northern and central Côte d'Ivoire, transmission of Schistosoma haematobium is seasonal and elimination might be achieved. In a cluster-randomised trial, we will assess different treatment schemes to interrupt S. haematobium transmission and control soil-transmitted helminthiasis over a 3-year period. We will compare the impact of (i) arm A: annual mass drug administration (MDA) with praziquantel and albendazole before the peak schistosomiasis transmission season; (ii) arm B: annual MDA after the peak schistosomiasis transmission season; (iii) arm C: two yearly treatments before and after peak schistosomiasis transmission; and (iv) arm D: annual MDA before peak schistosomiasis transmission, coupled with chemical snail control using niclosamide. METHODS/DESIGN: The prevalence and intensity of S. haematobium and soil-transmitted helminth infections will be assessed using urine filtration and Kato-Katz thick smears, respectively, in six administrative regions in northern and central parts of Côte d'Ivoire. Once a year, urine and stool samples will be collected and examined from 50 children aged 5-8 years, 100 children aged 9-12 years and 50 adults aged 20-55 years in each of 60 selected villages. Changes in S. haematobium and soil-transmitted helminth prevalence and intensity will be assessed between years and stratified by intervention arm. In the 15 villages randomly assigned to intervention arm D, intermediate host snails will be collected three times per year, before niclosamide is applied to the selected freshwater bodies. The snail abundance and infection rates over time will allow drawing inference on the force of transmission. DISCUSSION: This cluster-randomised intervention trial will elucidate whether in an area with seasonal transmission, the four different treatment schemes can interrupt S. haematobium transmission and control soil-transmitted helminthiasis. Lessons learned will help to guide schistosomiasis control and elimination programmes elsewhere in Africa. TRIAL REGISTRATION: ISRCTN ISRCTN10926858 . Registered 21 December 2016. Retrospectively registered.

Shrinking risk profiles after deworming of children in Port Elizabeth, South Africa, with special reference to Ascaris lumbricoides and Trichuris trichiura.

Risk maps facilitate discussion among different stakeholders and provide a tool for spatial targeting of health interventions. We present maps documenting shrinking risk profiles after deworming with respect to soil-transmitted helminthiasis among schoolchildren from disadvantaged neighbourhoods in Port Elizabeth, South Africa. Children were examined for soil-transmitted helminth infections using duplicate Kato-Katz thick smears in March 2015, October 2015 and May 2016, and subsequently treated with albendazole after each survey. The mean infection intensities for Ascaris lumbricoides were 9,554 eggs per gram of stool (EPG) in March 2015, 4,317 EPG in October 2015 and 1,684 EPG in March 2016. The corresponding figures for Trichuris trichiura were 664 EPG, 331 EPG and 87 EPG. Repeated deworming shrank the risk of soil-transmitted helminthiasis, but should be complemented by other public health measures.

Iron Fortified Complementary Foods Containing a Mixture of Sodium Iron EDTA with Either Ferrous Fumarate or Ferric Pyrophosphate Reduce Iron Deficiency Anemia in 12- to 36-Month-Old Children in a Malaria Endemic Setting: A Secondary Analysis of a Cluster-Randomized Controlled Trial.

Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a nine-month cluster-randomized controlled trial conducted in south-central Côte d'Ivoire. 378 children aged 12-36 months were randomly assigned to no food intervention (n = 125; control group), CF fortified with 2 mg NaFeEDTA plus 3.8 mg FeFum for six days/week (n = 126; FeFum group), and CF fortified with 2 mg NaFeEDTA and 3.8 mg FePP for six days/week (n = 127; FePP group). The outcome measures were hemoglobin (Hb), plasma ferritin (PF), iron deficiency (PF < 30 µg/L), and anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for inflammation. The prevalence of Plasmodium falciparum infection and inflammation during the study were 44-66%, and 57-76%, respectively. There was a significant time by treatment interaction on IDA (p = 0.028) and a borderline significant time by treatment interaction on iron deficiency with or without anemia (p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total anemia. These data indicate that, despite the high endemicity of malaria and elevated inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of NaFeEDTA with FeFum or NaFeEDTA with FePP. However, there was no overall effect on anemia, suggesting most of the anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).