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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. [ABSTRACT FROM AUTHOR]

Background: Preventive chemotherapy is the current strategy to control soil-transmitted helminth infections (caused by Ascaris lumbricoides, hookworm, and Trichuris trichiura). But, to improve efficacy and avoid emerging resistance, new drugs are warranted. Tribendimidine has shown good anthelmintic efficacy and is therefore a frontrunner for monotherapy and combination chemotherapy.Methods: We did a randomised, controlled, single-blinded, non-inferiority trial on Pemba Island, Tanzania, and in Côte d'Ivoire. We recruited adolescents aged 15-18 years from four primary schools on Pemba, and school attendees and non-schoolers from two districts in Côte d'Ivoire. Only hookworm-positive participants were randomly assigned (1:1:1:1) to single, oral doses of tribendimidine 400 mg plus placebo (tribendimidine monotherapy), tribendimidine 400 mg plus ivermectin 200 μg/kg, tribendimidine 400 mg plus oxantel pamoate 25 mg/kg, or albendazole 400 mg plus oxantel pamoate 25 mg/kg. Randomisation was done via a computer-generated list in block sizes of four or eight. Participants were asked to provide two stool samples on 2 consecutive days at baseline and again 14-21 days at follow-up. The primary outcome was the difference in egg-reduction rates (ERRs; ie, the geometric mean reduction) in hookworm egg counts between treatment groups, measured by the Kato-Katz technique. Differences in coadministrated treatment groups were assessed for non-inferiority with a margin of -3% to albendazole plus oxantel pamoate based on the available-case population, analysed by intention to treat. Safety was assessed 3 h and 24 h after treatment. This study is registered with ISRCTN (number 14373201).Findings: Between July 26, and Dec 23, 2016, we treated 636 hookworm-positive participants, and outcome data were available for 601 participants (151 assigned to tribendimidine monotherapy, 154 to tribendimidine plus ivermectin, 148 to tribendimidine plus oxantel pamoate, and 148 to albendazole plus oxantel pamoate). Tribendimidine plus ivermectin was non-inferior to albendazole plus oxantel pamoate (ERRs 99·5% [95% CI 99·2-99·7] vs 96·0% [93·9-97·4]; difference 3·52 percentage points [2·05-5·65]). Likewise, tribendimidine plus oxantel pamoate was non-inferior to albendazole plus oxantel pamoate (ERRs 96·5% [95% CI 94·9 to 97·6] vs 96·0% [93·9 to 97·4]; difference 0·48 percentage points [-1·61 to 2·88]). 3 h after treatment, headache (n=50 [8%]) and vertigo (n=37 [6%]) were the most widely reported symptoms; 24 h after treatment, 50 (8%) patients reported vertigo and 41 (7%) reported headache. Mainly mild adverse events were reported with peak numbers (n=111 [18%]) at 24 h after treatment. Three participants had moderate adverse events 3 h after treatment: two (<1%) had vertigo and one (<1%) had headache, and two had moderate adverse events 24 h after treatment: one (<1%) had vomiting and one (<1%) had vomiting plus diarrhoea.Interpretation: Tribendimidine in combination with either ivermectin or oxantel pamoate had a similar, non-inferior efficacy profile as albendazole plus oxantel pamoate, hence tribendimidine will be a useful addition to the depleted anthelmintic drug armamentarium.Funding: Swiss National Science Foundation. [ABSTRACT FROM AUTHOR]

Background: Preventive chemotherapy with albendazole or mebendazole remains one of the cornerstones of soil-transmitted helminth control. However, these drugs are less effective against Trichuris trichiura. Combined ivermectin-albendazole is a promising treatment alternative, yet robust evidence is lacking. We aimed to demonstrate superiority of co-administered ivermectin-albendazole over albendazole monotherapy in three distinct epidemiological settings.Methods: We conducted a double-blind, parallel-group, phase 3, randomised controlled trial in community members aged 6-60 years infected with T trichiura in Côte d'Ivoire, Laos, and Pemba Island, Tanzania, between Sept 26, 2018, and June 29, 2020. Participants with at least 100 T trichiura eggs per g of stool at baseline were randomly assigned (1:1) using computer-generated randomisation sequences in varying blocks of four, six, and eight, stratified by baseline T trichiura infection intensity, to orally receive either a single dose of ivermectin (200 μg/kg) plus albendazole (400 mg) or albendazole (400 mg) plus placebo. Patients, field staff, and outcome assessors were masked to treatment assignment. The primary outcome was cure rate against T trichiura, defined as the proportion of participants with no eggs in their faeces 14-21 days after treatment, assessed by Kato-Katz thick smears, and analysed in the available-case population according to intention-to-treat principles. Safety was a secondary outcome and was assessed 3 h and 24 h after drug administration. The trial is registered at ClinicalTrials.gov, NCT03527732.Findings: Between Sept 13 and Dec 18, 2019, Jan 12 and April 5, 2019, and Sept 26 and Nov 5, 2018, 3737, 3694, and 1435 community members were screened for trial eligibility in Côte d'Ivoire, Laos, and Pemba Island, respectively. In Côte d'Ivoire, Laos, and Pemba Island, 256, 274, and 305 participants, respectively, were randomly assigned to the albendazole group, and 255, 275, and 308, respectively, to the ivermectin-albendazole group. Primary outcome data were available for 722 participants treated with albendazole and 733 treated with ivermectin-albendazole. Ivermectin-albendazole showed significantly higher cure rates against T trichiura than albendazole in Laos (66% [140 of 213]vs 8% [16 of 194]; difference 58 percentage points, 95% CI 50 to 65, p<0·0001) and Pemba Island (49% [140 of 288]vs 6% [18 of 293], 43 percentage points, 36 to 49, p<0·0001) but had similar efficacy in Côte d'Ivoire (14% [32 of 232]vs 10% [24 of 235], 4 percentage points, -2 to 10, p=0·24). No serious adverse events were reported; observed events were mostly classified as mild (95% [266 of 279] in the albendazole group and 91% [288 of 317] in the ivermectin-albendazole group), and all were transient in nature.Interpretation: Treatment with ivermectin-albendazole resulted in higher efficacy against trichuriasis than albendazole alone in Laos and Pemba Island but not in Côte d'Ivoire. We recommend implementation of this combination therapy for soil-transmitted helminth control in countries with high T trichiura prevalence and proven enhanced efficacy of this treatment, particularly where ivermectin is beneficial against other endemic helminthiases.Funding: Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity and low cardiorespiratory fitness (CRF) are independent cardiovascular risk factors among children, but have rarely been investigated concurrently in sub-Saharan Africa. The purpose of this study was to compare physical activity (PA) and CRF of primary schoolchildren living in Côte d'Ivoire (CI), South Africa (ZA), and Tanzania (TZ), to test sex- and age-related differences, and to examine whether PA and CRF are associated with each other. Methods: Baseline data from an ongoing cluster-randomized controlled trial were used, including 499 children from CI (Taabo, 49% girls, M = 8.0 ± 1.6 years), 1,074 children from ZA (Gqeberha, 49% girls, M = 8.3 ± 1.4 years), and 593 children from TZ (Ifakara, 51% girls, M = 9.4 ± 1.7 years). PA was assessed by accelerometry and CRF by a 20 m shuttle-run test. The data were analyzed using multi-/univariate analyses of variance and mixed linear models. Results: Most children met recommendations put forward by the World Health Organization for moderate-to-vigorous PA (MVPA) and achieved high CRF scores. In CI, 89.6% of the children met MVPA recommendations (boys: 91.7%, girls: 87.4%), whereas this rate was 76.9% in ZA (boys: 91.0%, girls: 62.4%), and 93.8% in TZ (boys: 95.5%, girls: 92.0%). Children from TZ had the highest CRF and MVPA levels, followed by children from CI and ZA. Boys had higher MVPA levels than girls, whereas girls engaged in more sedentary behavior. Sex differences were strongest in ZA. Sedentary behavior and MVPA were higher among older schoolchildren compared to their younger peers. Higher MVPA, but not sedentary behavior, was associated with better CRF. Conclusions: In all three settings, higher levels of MVPA were associated with higher CRF scores. Nevertheless, children living in the most urbanized setting (such as observed in ZA) were physically less active and had lower CRF than peers living in more rural areas (such as observed in CI and TZ). Particularly for girls, urbanization might increase the risk for insufficient MVPA, which may have negative effects on their CRF, thus negatively influencing health and well-being at later age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gerber, Ayekoé, Beckmann, Bonfoh, Kouassi, Gba, Traoré, Coulibaly, Daouda, du Randt, Finda, Minja, Gall, Mollel, Lang, Long, Masanja, Müller, Nqweniso, Okumu, Probst-Hensch, Pühse, Steinmann, Walter and Utzinger.)