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BackgroundArtesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.MethodsIndividual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites.ResultsForty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P

Introduction: In Senegal, the widespread use of vector control measures has resulted in a significant reduction in the malaria burden and led the country to consider the possibility of elimination. Given this shift and changing context, it is important to characterize the malaria burden across all age groups to guide decision-making on programmatic interventions to interrupt transmission and ultimately eradicate the disease. In Senegal, there is a lack of information on malaria prevalence among certain populations, particularly among adolescents and adults. This study sought to assess the magnitude of malaria infections in all age groups, as well as malaria associated factors in an area of persistent transmission in Senegal. Methods: A cross-sectional household survey was conducted in four health posts (Khossanto, Mamakhona, Diakhaling and Sambrambougou), of the health district of Saraya, in November 2021, among individuals over 6 months of age. Households were selected using multistage sampling. Consented participants were screened for malaria parasites by microscopic examination of blood smears, and hemoglobin levels were measured using the Hemocue HB 301TM analyzer. Socio-demographic information of the participants, household heads, household assets, and information on ownership and use of preventive measures were collected using a structured questionnaire. Weighted generalized mixed effects logistic regression model was used to identify factors associated with microscopically confirmed malaria infection. Results: A total of 1759 participants were enrolled in the study. Overall, about 21% of participants were classified as having Plasmodium infection; children aged 5–10 years old (26.6%), adolescents aged 10–19 years old (24.7%), and children under five years of age (20.5%) had higher rates of infection compared to adults (13.5%). Plasmodium falciparum accounted for 99.2% of the malaria infections, and most infections (69%) were asymptomatic. Around one-third of study participants had anemia (hemoglobin level <11.0 g/dl), with under five children bearing the highest burden (67.3%). Multivariate analysis showed that the odds of having a malaria infection were around 2 times higher among participants in Khossanto compared to Diakhaling (aOR = 1.84, 95% CI:1.06–3.20). Participants aged 5–9 years were more likely to have malaria infection compared to under five children (aOR = 1.40, 95% CI:1.02–1.91). Factors associated with anemia were P. falciparum infection (aOR = 1.36, p = 0.027), females (aOR = 2.16, p = 0.000), under-five age group (aOR = 13.01, p = 0.000). Conclusion: Malaria burden was considerable among adolescents and under ten children living in an area of persistent transmission, with adolescents more commonly presenting as asymptomatic. Interventions tailored to this specific group of the population are needed to better control the disease and reduce its burden. [ABSTRACT FROM AUTHOR]

Background: The Sud-Ouest region of Burkina Faso (especially the Bougouriba valley) has been historically problematic with respect to onchocerciasis control, with a recrudescence of infections after vector control carried out the WHO Onchocerciasis Control Programme was halted in 1989. After 1996, mass drug administration of ivermectin was instigated to control the recrudescence so that it would no longer constitute a public health problem. However, in 2010 WHO changed its recommended policy from control to elimination, and in 2013 biannual Community-Directed Treatment with Ivermectin (CDTI) was instigated. Epidemiological surveys were carried-out in 2011 and 2018 to determine whether CDTI was producing a decline in infection levels and progress towards elimination. Methodology/Principal findings: A cross-sectional study was conducted across 20 villages in four health districts in 2011 and 29 villages in 2018. Individuals aged five years and above were examined by skin-snip, and the prevalence and microfilarial load was determined for each village. In 2011, 75% of villages had some infections and 20% had prevalences >5%, with a mean prevalence across all villages of 2.63% (range 0.0–9.7%), and community microfilarial load ranging from 0 to 0.25 microfilariae per biopsy. In 2018, nine villages (= 31% of total) had some infections, with prevalences ranging from 0.41% to 3.54%, and a mean prevalence across all villages of 0.37%. Community microfilarial load ranged from 0 to 0.1. Amongst those people found to be microfilarial positive, 87% had a history of migration. Conclusions/significance: The endemicity of onchocerciasis infection in the Sud-Ouest region has declined to low levels and seems to be progressing towards elimination. Our findings indicated that biannual CDTI is having good effect, but it should continue for a number of years to ensure elimination of transmission. However, progress towards elimination has a troublesome history in this region, and it would be advisable to select more sentinel villages to have confidence in any future epidemiological and entomological surveys, especially Stop-MDA surveys. With positive individuals migrating between countries, cross-border collaboration needs more attention to ensure effective treatment for onchocerciasis elimination. Author summary: Onchocerciasis is a disease caused by infection with the parasitic nematode, Onchocerca volvulus, which is transmitted by blood-sucking blackflies, causing blindness, skin disease and epilepsy. The World Health Organization has listed the disease for elimination using the drug ivermectin, but the density of surveillance points necessary to ensure that elimination has been achieved throughout an area is not well understood. Most of Burkina Faso became free from onchocerciasis after the regular application of insecticides to the blackfly breeding sites from 1975 to 1989. However, the South-West Region suffered a speedy recrudescence, probably because an insufficient number of monitoring sites were not representative of the situation throughout the whole area and blackfly control was stopped prematurely. Mass distribution of ivermectin was introduced in 1996 to control the recrudescence and CDTI in 2013 to eliminate transmission. The objective of this study was to carry out epidemiological surveys in 2011 and 2018 to see if ivermectin is reducing human infections and eliminating the recrudescence. In 2011, 75% of villages still had some infections and the mean number of people infected across all villages was 2.63%. However, in 2018, only 31% of villages had any infections, with mean numbers infected across all villages of 0.37% showing that there is good progress towards elimination. [ABSTRACT FROM AUTHOR]

In children exposed to poor hygiene and sanitation, invasion of the gut by pathogenic microbes can result in a subclinical enteropathy termed "environmental enteric dysfunction" (EED) that contributes to undernutrition, growth faltering, and impaired organ development. EED may already be present by age 6–12 weeks; therefore, interventions that can be started early in life, and used alongside breastfeeding, are needed to prevent or ameliorate EED. A healthy gut microbiota is critical for intestinal development and repair, nutrient digestion and absorption, and resisting colonization or overgrowth by pathogens. However, its development can be impaired by several environmental factors. Dietary supplementation with pro-, pre-, or synbiotics may be a pragmatic and safe means of building the resilience of the developing gut microbiota against adverse environmental factors, thereby preventing EED. [ABSTRACT FROM AUTHOR]

Background Seasonal malaria chemoprevention (SMC) is recommended in the Sahel region of Africa for children under 5 years of age, for up to 4 months of the year. It may be appropriate to include older children, and to provide protection for more than 4 months. We evaluated the effectiveness of SMC using sulfadoxine-pyrimethamine plus amodiaquine given over 5 months to children under 10 years of age in Saraya district in south-east Senegal in 2011. Methods and findings Twenty-four villages, including 2,301 children aged 3-59 months and 2,245 aged 5-9 years, were randomised to receive SMC with community case management (CCM) (SMC villages) or CCM alone (control villages). In all villages, community health workers (CHWs) were trained to treat malaria cases with artemisinin combination therapy after testing with a rapid diagnostic test (RDT). In SMC villages, CHWs administered SMC to children aged 3 months to 9 years once a month for 5 months. The study was conducted from 27 July to 31 December 2011. The primary outcome was malaria (fever or history of fever with a positive RDT). The prevalence of anaemia and parasitaemia was measured in a survey at the end of the transmission season. Molecular markers associated with resistance to SMC drugs were analysed in samples from incident malaria cases and from children with parasitaemia in the survey. SMC was well tolerated with no serious adverse reactions. There were 1,472 RDT-confirmed malaria cases in the control villages and 270 in the SMC villages. Among children under 5 years of age, the rate difference was 110.8/1,000/month (95% CI 64.7, 156.8; p < 0.001) and among children 5-9 years of age, 101.3/1,000/month (95% CI 66.7, 136.0; p < 0.001). The mean haemoglobin concentration at the end of the transmission season was higher in SMC than control villages, by 6.5 g/l (95% CI 2.0, 11; p = 0.007) among children under 5 years of age, and by 5.2 g/l (95% CI 0.4, 9.9; p = 0.035) among children 5-9 years of age. The prevalence of parasitaemia was 18% in children under 5 years of age and 25% in children 5-9 years of age in the control villages, and 5.7% and 5.8%, respectively, in these 2 age groups in the SMC villages, with prevalence differences of 12.5% (95% CI 6.8%, 18.2%; p < 0.001) in children under 5 years of age and 19.3% (95% CI 8.3%, 30.2%; p < 0.001) in children 5-9 years of age. The pfdhps-540E mutation associated with clinical resistance to sulfadoxine-pyrimethamine was found in 0.8% of samples from malaria cases but not in the final survey. Twelve children died in the control group and 14 in the SMC group, a rate difference of 0.096/1,000 child-months (95% CI 0.99, 1.18; p = 0.895). Limitations of this study include that we were not able to obtain blood smears for microscopy for all suspected malaria cases, such that we had to rely on RDTs for confirmation, which may have included false positives. Conclusions In this study SMC for children under 10 years of age given over 5 months was feasible, well tolerated, and effective in preventing malaria episodes, and reduced the prevalence of parasitaemia and anaemia. SMC with CCM achieved high coverage and ensured children with malaria were promptly treated with artemether-lumefantrine. Trial registration www.clinicaltrials.gov NCT01449045., Author(s): Jean Louis A. Ndiaye 1,*, Youssoupha Ndiaye 2, Mamadou S. Ba 1, Babacar Faye 1, Maguette Ndiaye 1, Amadou Seck 1, Roger Tine 1, Pape Moussa Thior 2, Sharanjeet [...]