Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: a retrospective metagenomic analysis of a placebo-controlled trial.

BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition. METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of those 161 children, on the basis of anthropometric measures, for follow-up 2 years later (Sept 28 to Oct 27, 2015). Children provided faecal samples at baseline, week 1, week 4, week 8, week 12, and, for those in the 2-year follow-up cohort, week 104. We conducted metagenomic sequencing followed by microbiome and resistome profiling of faecal samples. 38 children without severe acute malnutrition and six children with severe acute malnutrition matching the baseline ages of the original cohort were used as reference controls. FINDINGS: In the 12-week follow-up group, amoxicillin led to an immediate decrease in gut microbiome richness from 37·6 species (95% CI 32·6-42·7) and Shannon diversity index (SDI) 2·18 (95% CI 1·97-2·39) at baseline to 27·7 species (95% CI 22·9-32·6) species and SDI 1·55 (95% CI 1·35-1·75) at week 1. Amoxicillin increased gut antibiotic resistance gene abundance to 6044 reads per kilobase million (95% CI 4704-7384) at week 1, up from 4800 (3391-6208) at baseline, which returned to baseline 3 weeks later. 35 children were included in the 2-year follow-up; the amoxicillin-treated children (n=22) had increased number of species in the gut microbiome compared with placebo-treated children (n=13; 60·7 [95% CI 54·7-66·6] vs 36·9 [29·4-44·3]). Amoxicillin-treated children had increased Prevotella spp and decreased Bifidobacterium spp relative to age-matched placebo-treated children, indicating a more mature, adult-like microbiome. INTERPRETATION: Amoxicillin treatment led to acute but not sustained increases in antimicrobial resistance genes and improved gut microbiome maturation 2 years after severe acute malnutrition treatment. FUNDING: Bill & Melinda Gates Foundation; Médecins sans Frontières Operational Center Paris; National Institute of Allergy and Infectious Diseases; National Institute of General Medical Sciences; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Edward Mallinckrodt Jr Foundation; Doris Duke Foundation.

Practices and challenges related to antibiotic use in paediatric treatment in hospitals and health centres in Niger and Uganda: a mixed methods study.

BACKGROUND: Antibiotic resistance is a significant public health problem and is responsible for high mortality in children and new-borns. Strengthening the rational use of antibiotics and improving the quality and access to existing antibiotics are important factors in the fight against antibiotic resistance. This study aims to provide knowledge on the use of antibiotics in children in resource-limited countries in order to identify problems and possible avenues for improvement of antibiotics use. METHODS: We conducted a retrospective study in July 2020 and collected quantitative clinical and therapeutic data on antibiotic prescriptions between January and December 2019 in 4 hospitals or health centres in both Uganda and Niger, respectively from January to December 2019. Semi-structured interviews and focus groups were conducted among healthcare personnel and carers for children under 17 years of age, respectively. RESULTS: A total of 1,622 children in Uganda and 660 children in Niger (mean age of 3.9 years (SD 4.43)) who received at least one antibiotic were included in the study. In hospital settings, 98.4 to 100% of children prescribed at least one antibiotic received at least one injectable antibiotic. Most hospitalized children received more than one antibiotic in both Uganda (52.1%) and Niger (71.1%). According to the WHO-AWaRe index, the proportion of prescriptions of antibiotics belonging to the Watch category was 21.8% (432/1982) in Uganda and 32.0% (371/1158) in Niger. No antibiotics from the Reserve category were prescribed. Health care provider's prescribing practices are rarely guided by microbiological analyses. Prescribers are faced with numerous constraints, such as lack of standard national guidelines, unavailability of essential antibiotics at the level of hospital pharmacies, the limited financial means of the families, and pressure to prescribe antibiotics from caregivers as well as from drug company representatives. The quality of some antibiotics provided by the National Medical Stores to the public and private hospitals has been questioned by some health professionals. Self-medication is a widespread practice for the antibiotic treatment of children for economic and access reasons. CONCLUSION: The study findings indicate that an intersection of policy, institutional norms and practices including individual caregiver or health provider factors, influence antibiotic prescription, administration and dispensing practices.

Faecal carriage of extended-spectrum ß-lactamase-producing Escherichia coli in a remote region of Niger.

OBJECTIVE: Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger. METHODS: Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads. RESULTS: Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome. CONCLUSIONS: Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.

Validation of Three MicroScan® Antimicrobial Susceptibility Testing Plates Designed for Low-Resource Settings.

Easy and robust antimicrobial susceptibility testing (AST) methods are essential in clinical bacteriology laboratories (CBL) in low-resource settings (LRS). We evaluated the Beckman Coulter MicroScan lyophilized broth microdilution panel designed to support Médecins Sans Frontières (MSF) CBL activity in difficult settings, in particular with the Mini-Lab. We evaluated the custom-designed MSF MicroScan Gram-pos microplate (MICPOS1) for Staphylococcus and Enterococcus species, MSF MicroScan Gram-neg microplate (MICNEG1) for Gram-negative bacilli, and MSF MicroScan Fastidious microplate (MICFAST1) for Streptococci and Haemophilus species using 387 isolates from routine CBLs from LRS against the reference methods. Results showed that, for all selected antibiotics on the three panels, the proportion of the category agreement was above 90% and the proportion of major and very major errors was below 3%, as per ISO standards. The use of the Prompt inoculation system was found to increase the MIC and the major error rate for some antibiotics when testing Staphylococci. The readability of the manufacturer's user manual was considered challenging for low-skilled staff. The inoculations and readings of the panels were estimated as easy to use. In conclusion, the three MSF MicroScan MIC panels performed well against clinical isolates from LRS and provided a convenient, robust, and standardized AST method for use in CBL in LRS.

Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial.

BACKGROUND: It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials. METHODS AND FINDINGS: We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron-folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: -0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: -0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: -0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: -0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: -0.22, 0.44; p = 0.53) or motor scores (SMD: -0.04; 95% CI: -0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages. CONCLUSIONS: There was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.

Risk of community- and hospital-acquired bacteremia and profile of antibiotic resistance in children hospitalized with severe acute malnutrition in Niger.

OBJECTIVE: To estimate the prevalence and antibiotic resistance profile of community- and hospital-acquired bacteremia among hospitalized children with severe acute malnutrition in Niger. METHODS: A descriptive, longitudinal study was conducted in an intensive nutritional rehabilitation center in Madarounfa, Niger. Children aged 6 to 59 months admitted for inpatient treatment of complicated severe acute malnutrition (n=2187) had blood specimens drawn at admission to assess prevalence of community-acquired bacteremia. Subsequent specimens were drawn per physician discretion to assess incidence of hospital-acquired bacteremia. Antibiotic susceptibility testing was performed on positive blood cultures. RESULTS: The prevalence of community-acquired bacteremia at admission was at least 9.1% (95% confidence interval [CI]: 8.1, 10.4%), with non-typhoid Salmonella identified in over half (57.8%) of cases. The cumulative incidence of hospital-acquired bacteremia was estimated at 1.2% (95% CI: 0.8, 1.7%), among which the most common organisms were Klebsiella pneumoniae (19.4%), Acinetobacter baumannii (16.1%), Enterococcus faecalis (12.9%), and Escherichia coli (12.9%). In community-acquired bacteremia, 58% cases were resistant to amoxicillin-clavulanate; 100% of hospital-acquired bacteremia cases were resistant to amoxicillin and amoxicillin-clavulanate. Mortality risk was elevated among children with hospital-acquired bacteremia (risk ratio [RR] = 9.32) and community-acquired bacteremia (RR = 2.67). CONCLUSION: Bacteremia was a significant contributor to mortality. Antibiotic resistance poses a challenge to effective clinical management of severe acute malnutrition.

Prenatal supplementation with multiple micronutrient supplements or medium-quantity lipid-based nutrient supplements has limited effects on child growth up to 24 months in rural Niger: a secondary analysis of a cluster randomized trial.

BACKGROUND: Prenatal multiple micronutrient supplementation (MMS) and lipid-based nutrient supplementation (LNS) can improve birth outcomes relative to iron-folic acid supplementation (IFA); however, effects on child postnatal growth remain unclear. OBJECTIVES: The aim was to compare the effect of prenatal MMS, medium-quantity LNS (MQ-LNS), and IFA on child growth up to 2 y of age. METHODS: We conducted a cluster randomized controlled trial of prenatal nutritional supplementation in Madarounfa, Niger. Villages were randomly assigned for pregnant women to receive IFA (17 villages, 1105 women), MMS (18 villages, 1083 women) or MQ-LNS (18 villages, 1144 women). Pregnant women received nutritional supplements weekly until delivery, and children were followed up monthly from 6-8 wk to 24 mo of age. We assessed the effect of prenatal MMS and MQ-LNS compared with IFA and the effect of prenatal MMS compared with MQ-LNS on child length-for-age z scores (LAZ), weight-for-age z scores (WAZ), and weight-for-length z scores (WLZ) at 24 mo of age using generalized linear models. In secondary analyses, we used mixed-effects models to assess the trajectories of anthropometric z scores longitudinally from 6-8 wk to 24 mo. RESULTS: Compared with IFA, MMS and MQ-LNS had no effect on child LAZ, WAZ, or WLZ at 24 mo of age (P > 0.05). Children in the MQ-LNS arm had significantly higher mid-upper arm circumference at 24 mo than children in the MMS arm: mean difference 0.50 cm (95% CI 0.10, 0.91 cm). WAZ and WLZ trajectories were more negative in the MQ-LNS arm compared with IFA and MMS, with lower z scores from 14 to 20 mo of age. However, WAZ and WLZ trajectories converged after 20 mo of age, and there were no differences by 24 mo of age. CONCLUSIONS: Prenatal MMS and MQ-LNS had limited effect on anthropometric measures of child growth up to 24 mo of age as compared with IFA in rural Niger.

Correction: Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

[This corrects the article DOI: 10.1371/journal.pmed.1003720.].

Prevalence of malaria in an area receiving seasonal malaria chemoprevention in Niger.

BACKGROUND: Malaria transmission is highly seasonal in Niger. Despite the introduction of seasonal malaria chemoprevention (SMC) in the Magaria District, malaria incidence remains high, and the epidemiology of malaria in the community is not well-understood. METHODS: Four cross-sectional, household-based malaria prevalence surveys were performed in the Magaria District of Niger between October 2016 and February 2018. Two occurred during the peak malaria season and two during the low malaria season. Individuals in each of three age strata (3-59 months, 5-9 years, and 10 years and above) were sampled in randomly-selected households. Capillary blood was collected by fingerprick, thick and thin blood films were examined. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 396 households during the high-season surveys and 266 households during the low-season surveys. RESULTS: Prevalence of parasitaemia was highest in children aged 5-9 years during all four surveys, ranging between 53.6% (95%CI 48.8-63.6) in February 2018 and 73.2% (66.2-79.2) in September 2017. Prevalence of parasitaemia among children aged 3-59 months ranged between 39.6% (33.2-46.4) in February 2018 and 51.9% (45.1-58.6) in October 2016. Parasite density was highest in children aged 3-59 months during all four surveys, and was higher in high season surveys than in low season surveys among all participants. The prevalence of gametocytaemia in children aged 3-59 months ranged between 9.9% (6.5-14.8) in February 2018 and 19.3% (14.6-25.2) in October 2016. The prevalence of gametocytaemia in children aged 5-9 years ranged between 6.3% (3.5-11.1) in February 2018 and 18.5% (12.7-26.1) in October 2016. CONCLUSIONS: Asymptomatic malaria infection is highly prevalent in this area, even during the season with low incidence of clinical malaria. The high prevalence of parasitaemia in children aged 5-9 years warrants considering their inclusion in SMC programmes in this context.

An exploratory qualitative study of caregivers' knowledge, perceptions and practices related to hospital hygiene in rural Niger.

BACKGROUND: The risk of healthcare-associated infections is exacerbated by poor hygiene practices in health care facilities and can contribute to increased patient morbidity and mortality. In low-income settings, caregivers play a key role in maintaining proper hygiene during inpatient stays. We aimed to explore caregivers' knowledge, perceptions and practices related to hospital hygiene in a rural, sub-Saharan African setting. METHODS: We conducted an exploratory qualitative study among caregivers of children admitted to an inpatient therapeutic feeding center in Madarounfa, Niger. Individual interviews with 28 caregivers of hospitalized children were conducted to explore their knowledge, perceptions and practices of hygiene in the health facility. FINDINGS: Caregivers described a broad understanding of hygiene and reported knowledge of its importance in the hospital, particularly to prevent disease transmission and protect child health. Hygiene was perceived as a collective rather than individual responsibility. Caregivers reported on the poor hygiene practice of others and cited a lack of space and hygiene materials as barriers to correct hygiene practice. Caregivers described educational sessions and informal sharing with other caregivers as tools to gain knowledge and improve practice. CONCLUSION: This exploratory study is unique in describing the perspective of caregivers in a low-resource hospital setting, a group often underrepresented when designing health interventions to improve hospital hygiene. Our findings suggest a strong knowledge of hospital hygiene among caregivers in this setting, with positive perception of its importance in health promotion. Poor individual practice was reported but may be improved through additional education and provision of hygiene materials.

Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger.

BACKGROUND: High-resolution data on the etiology of childhood diarrhea in countries with the highest burden and mortality remain sparse and are needed to inform burden estimates and prioritize interventions. METHODS: We tested stool specimens collected between October 2014 and December 2017 from children under 2 years of age from the per-protocol population of a placebo-controlled clinical trial of a bovine rotavirus pentavalent vaccine (Rotasiil) in Niger. We tested 1729 episodes of moderate-to-severe diarrhea (Vesikari score ≥ 7) using quantitative PCR and estimated pathogen-specific burdens by age, season, severity, and trial intervention arm. RESULTS: The 4 pathogens with the highest attributable incidence of diarrhea were Shigella (7.2 attributable episodes per 100 child-years; 95% confidence interval: 5.2, 9.7), Cryptosporidium (6.5; 5.8, 7.2), rotavirus (6.4; 5.9, 6.7), and heat-stabile toxin-producing enterotoxigenic Escherichia coli (ST-ETEC) (6.2; 3.1, 7.7). Cryptosporidium was the leading etiology of severe diarrhea (Vesikari score ≥ 11) and diarrhea requiring hospitalization. Shigella was the leading etiology of diarrhea in children 12-23 months of age but also had a substantial burden in the first year of life, with 60.5% of episodes of severe shigellosis occurring in infants. Shigella, Cryptosporidium, and ST-ETEC incidence peaked during the warmer and wetter period and coincided with peak all-cause diarrhea incidence. CONCLUSIONS: In this high-burden setting, the leading diarrheal pathogens were Shigella, Cryptosporidium, rotavirus, and ST-ETEC, and each was disproportionately seen in infants. Vaccine development should target these pathogens, and the impact of vaccine schedule on diarrhea burden in the youngest children will need to be considered.

Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

BACKGROUND: Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. METHODS AND FINDINGS: We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron-folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6-8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. CONCLUSIONS: This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.

Performance of six rapid diagnostic tests for SARS-CoV-2 antigen detection and implications for practical use.

BACKGROUND: Direct detection of SARS-CoV-2 viral proteins in nasopharyngeal swabs using lateral flow immunoassays is a simple, fast and cheap approach to diagnose the infection. AIMS AND METHODS: The performance of 6 SARS-CoV-2 antigen rapid diagnostic tests has been assessed in 634 hospitalized patients or outpatients including 297 patients found to be positive for SARS-CoV-2 RNA by means of RT-PCR and 337 patients presumed to be SARS-CoV-2 RNA-negative. RESULTS: The specificity of SARS-CoV-2 RDTs was generally high (398.5%). One assay had a lower specificity of 93.2%. The overall sensitivity of the 6 RDTs was variable, from 32.3% to 61.7%. Sensitivity correlated with the delay of sampling after the onset of symptoms and the viral load estimated by the Ct value in RT-PCR. Four out of 6 RDTs tested achieved sensitivities 380% when clinical specimens were collected during the first 3 days following symptom onset or with a Ct value ≤25. CONCLUSIONS: The present study shows that SARS-CoV-2 antigen can be easily and reliably detected by RDTs. These tests are easy and rapid to perform. However, the specificity and sensitivity of COVID-19 antigen RDTs may widely vary across different tests and must therefore be carefully evaluated before releasing these assays for realworld applications.

Rotavirus vaccine efficacy up to 2 years of age and against diverse circulating rotavirus strains in Niger: Extended follow-up of a randomized controlled trial.

BACKGROUND: Rotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger. METHODS AND FINDINGS: From August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy. CONCLUSIONS: Rotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.

AMR in low-resource settings: Médecins Sans Frontières bridges surveillance gaps by developing a turnkey solution, the Mini-Lab.

BACKGROUND: In low- and middle-income countries (LMICs), data related to antimicrobial resistance (AMR) are often inconsistently collected. Humanitarian, private and non-governmental medical organizations (NGOs), working with or in parallel to public medical systems, are sometimes present in these contexts. Yet, what is the role of NGOs in the fight against AMR, and how can they contribute to AMR data collection in contexts where reporting is scarce? How can context-adapted, high-quality clinical bacteriology be implemented in remote, challenging and underserved areas of the world? OBJECTIVES: The aim was to provide an overview of AMR data collection challenges in LMICs and describe one initiative, the Mini-Lab project developed by Médecins Sans Frontières (MSF), that attempts to partially address them. SOURCES: We conducted a literature review using PubMed and Google scholar databases to identify peer-reviewed research and grey literature from publicly available reports and websites. CONTENT: We address the necessity of and difficulties related to obtaining AMR data in LMICs, as well as the role that actors outside of public medical systems can play in the collection of this information. We then describe how the Mini-Lab can provide simplified bacteriological diagnosis and AMR surveillance in challenging settings. IMPLICATIONS: NGOs are responsible for a large amount of healthcare provision in some very low-resourced contexts. As a result, they also have a role in AMR control, including bacteriological diagnosis and the collection of AMR-related data. Actors outside the public medical system can actively contribute to implementing and adapting clinical bacteriology in LMICs and can help improve AMR surveillance and data collection.

Performance and operational feasibility of antigen and antibody rapid diagnostic tests for COVID-19 in symptomatic and asymptomatic patients in Cameroon: a clinical, prospective, diagnostic accuracy study.

BACKGROUND: Real-time PCR is recommended to detect SARS-CoV-2 infection. However, PCR availability is restricted in most countries. Rapid diagnostic tests are considered acceptable alternatives, but data are lacking on their performance. We assessed the performance of four antibody-based rapid diagnostic tests and one antigen-based rapid diagnostic test for detecting SARS-CoV-2 infection in the community in Cameroon. METHODS: In this clinical, prospective, diagnostic accuracy study, we enrolled individuals aged at least 21 years who were either symptomatic and suspected of having COVID-19 or asymptomatic and presented for screening. We tested peripheral blood for SARS-CoV-2 antibodies using the Innovita (Biological Technology; Beijing, China), Wondfo (Guangzhou Wondfo Biotech; Guangzhou, China), SD Biosensor (SD Biosensor; Gyeonggi-do, South Korea), and Runkun tests (Runkun Pharmaceutical; Hunan, China), and nasopharyngeal swabs for SARS-CoV-2 antigen using the SD Biosensor test. Antigen rapid diagnostic tests were compared with Abbott PCR testing (Abbott; Abbott Park, IL, USA), and antibody rapid diagnostic tests were compared with Biomerieux immunoassays (Biomerieux; Marcy l'Etoile, France). We retrospectively tested two diagnostic algorithms that incorporated rapid diagnostic tests for symptomatic and asymptomatic patients using simulation modelling. FINDINGS: 1195 participants were enrolled in the study. 347 (29%) tested SARS-CoV-2 PCR-positive, 223 (19%) rapid diagnostic test antigen-positive, and 478 (40%) rapid diagnostic test antibody-positive. Antigen-based rapid diagnostic test sensitivity was 80·0% (95% CI 71·0-88·0) in the first 7 days after symptom onset, but antibody-based rapid diagnostic tests had only 26·8% sensitivity (18·3-36·8). Antibody rapid diagnostic test sensitivity increased to 76·4% (70·1-82·0) 14 days after symptom onset. Among asymptomatic participants, the sensitivity of antigen-based and antibody-based rapid diagnostic tests were 37·0% (27·0-48·0) and 50·7% (42·2-59·1), respectively. Cohen's κ showed substantial agreement between Wondfo antibody rapid diagnostic test and gold-standard ELISA (κ=0·76; sensitivity 0·98) and between Biosensor and ELISA (κ=0·60; sensitivity 0·94). Innovita (κ=0·47; sensitivity 0·93) and Runkun (κ=0·43; sensitivity 0·76) showed moderate agreement. An antigen-based retrospective algorithm applied to symptomatic patients showed 94·0% sensitivity and 91·0% specificity in the first 7 days after symptom onset. For asymptomatic participants, the algorithm showed a sensitivity of 34% (95% CI 23·0-44·0) and a specificity of 92·0% (88·0-96·0). INTERPRETATION: Rapid diagnostic tests had good overall sensitivity for diagnosing SARS-CoV-2 infection. Rapid diagnostic tests could be incorporated into efficient testing algorithms as an alternative to PCR to decrease diagnostic delays and onward viral transmission. FUNDING: Médecins Sans Frontières WACA and Médecins Sans Frontières OCG. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Evaluating 10 Commercially Available SARS-CoV-2 Rapid Serological Tests by Use of the STARD (Standards for Reporting of Diagnostic Accuracy Studies) Method.

Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially available SARS-CoV-2 rapid serological tests using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) methodology. Two hundred fifty serum samples from 159 PCR-confirmed SARS-CoV-2 patients (collected 0 to 32 days after the onset of symptoms) were tested with rapid serological tests. Control serum samples (n = 254) were retrieved from pre-coronavirus disease (COVID) periods from patients with other coronavirus infections (n = 11), positivity for rheumatoid factors (n = 3), IgG/IgM hyperglobulinemia (n = 9), malaria (n = 5), or no documented viral infection (n = 226). All samples were tested using rapid lateral flow immunoassays (LFIAs) from 10 manufacturers. Only four tests achieved ≥98% specificity, with the specificities ranging from 75.7% to 99.2%. The sensitivities varied by the day of sample collection after the onset of symptoms, from 31.7% to 55.4% (days 0 to 9), 65.9% to 92.9% (days 10 to 14), and 81.0% to 95.2% (>14 days). Only three of the tests evaluated met French health authorities' thresholds for SARS-CoV-2 serological tests (≥90% sensitivity and ≥98% specificity). Overall, the performances varied greatly between tests, with only one-third meeting acceptable specificity and sensitivity thresholds. Knowledge of the analytical performances of these tests will allow clinicians and, most importantly, laboratorians to use them with more confidence; could help determine the general population's immunological status; and may help diagnose some patients with false-negative real-time reverse transcription-PCR (RT-PCR) results.

Intrahousehold management and use of nutritional supplements during the hunger gap in Maradi region, Niger: a qualitative study.

BACKGROUND: Nutritional supplements are used for preventing and treating childhood malnutrition. While there is a growing body of evidence on product efficacy, less emphasis has been placed on how they are perceived and used at the household level. Here, we report on the intrahousehold management of three different supplements (Ready to Use Supplementary food (RUSF), medium quantity lipid-based nutrient supplements (LNS-MQ) and Super Cereal Plus (SC+)) in the region of Maradi (Niger). The main objective of this study was to describe the use, consumption and perception of the three different nutritional products at the household level. METHODS: The study was conducted in the Madarounfa district in the region of Maradi (February - March 2012). Female caregivers were purposely selected from eligible households and invited to participate. Data were collected through focus group discussion and interviews and were analyzed using thematic content analysis. RESULTS: In total, 114 caregivers participated. Three major themes were initially identified and included preparation and conservation; consumption and sharing practices as well as perception of impact. The data showed good acceptance at the household level including perceived benefits for the target children, health improvement, prevention of illness and malnutrition. Sharing and gifting at both household and community level were also reported. CONCLUSIONS: Caregivers displayed positive perceptions toward the investigated supplements. Patterns of actual management should be considered in the design, implementation, monitoring and evaluation of future programs.

Adherence and Population Pharmacokinetic Properties of Amodiaquine When Used for Seasonal Malaria Chemoprevention in African Children.

Poor adherence to seasonal malaria chemoprevention (SMC) might affect the protective effectiveness of SMC. Here, we evaluated the population pharmacokinetic properties of amodiaquine and its active metabolite, desethylamodiaquine, in children receiving SMC under directly observed ideal conditions (n = 136), and the adherence of SMC at an implementation phase in children participating in a case-control study to evaluate SMC effectiveness (n = 869). Amodiaquine and desethylamodiaquine concentration-time profiles were described simultaneously by two-compartment and three-compartment disposition models, respectively. The developed methodology to evaluate adherence showed a sensitivity of 65-71% when the first dose of SMC was directly observed and 71-73% when no doses were observed in a routine programmatic setting. Adherence simulations and measured desethylamodiaquine concentrations in the case-control children showed complete adherence (all doses taken) in < 20% of children. This result suggests that more efforts are needed urgently to improve the adherence to SMC among children in this area.