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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.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.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.Compared with IFA, MMS and MQ-LNS had no effect on child LAZ, WAZ, or WLZ at 24 mo of age (P0.05). 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.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.

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.

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., Sheila Isanaka and co-workers study nutrient supplementation and infants’ immune responses to rotavirus vaccination., Author summary Why was this study done? The World Health Organization recommends that all children be vaccinated against rotavirus, the most common cause of severe childhood diarrhea and a major cause of morbidity and mortality worldwide. Two oral rotavirus vaccines have been shown to be highly efficacious against childhood diarrhea in high- and middle-income countries (85%–98%), but, virtually, all trials in sub-Saharan Africa and South Asia have shown lower immune response and much lower efficacy (40%–64%), leaving many children unprotected. As the development of the immune cells that support vaccine response specifically depend on an adequate supply of micronutrients, nutritional supplementation has been considered as a potential adjunctive intervention to improve oral vaccine performance. What did the researchers do and find? 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. This study found no effect of the type of prenatal nutrient supplementation on immune response in this setting; however, the immune response appeared to vary by previous exposure to rotavirus. What do these findings mean? To improve the oral vaccine immunogenicity gap between low- and high-income countries, a more complete understanding of the factors influencing immunogenicity and a reliable correlate of protection are needed. Without improvement in oral vaccine performance, alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings.

S U M M A R Y: 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.

BackgroundHealthcare-associated infections pose a major, yet often preventable risk to patient safety. Poor hand hygiene among healthcare personnel and unsanitary hospital environments may contribute to this risk in low-income settings. We aimed to describe hand hygiene behaviour and environmental contamination by season in a rural, sub-Saharan African hospital setting.MethodsWe conducted a concurrent triangulation mixed-methods study combining three types of data at a hospital in Madarounfa, Niger. Hand hygiene observations among healthcare personnel during two seasons contributed quantitative data describing hand hygiene frequency and its variability in relation to seasonal changes in caseload. Semistructured interviews with healthcare personnel contributed qualitative data on knowledge, attitudes and barriers to hand hygiene. Biweekly environmental samples evaluated microbial contamination from October 2016 to December 2017. Triangulation identified convergences, complements and contradictions across results.ResultsHand hygiene compliance, or the proportion of actions (handrubbing or handwashing) performed out of all actions required, was low (11% during non-peak and 36% during peak caseload seasons). Interviews with healthcare personnel suggesting good general knowledge of hand hygiene contradicted the low hand hygiene compliance. However, compliance by healthcare activity was convergent with poor knowledge of precise hand hygiene steps and the motivation to prevent personal acquisition of infection identified during interviews. Contamination of environmental samples with gram-negative bacilli was high (45%), with the highest rates of contamination observed during the peak caseload season.ConclusionLow hand hygiene compliance coupled with high contamination rates of hospital environments may increase the risk of hospital-acquired infections in sub-Saharan African settings.

Using quantitative PCR diagnostics in a phase 3 clinical trial of Rotasiil in Niger, we identified Shigella, Cryptosporidium, rotavirus, and heat-stabile toxin-producing Escherichia coli to be the top 4 leading etiologies of moderate-to-severe diarrhea in children 0-2 years of age., 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.

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 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.

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., Sheila Isanaka and co-workers report extended follow-up of a rotavirus vaccine trial in Niger., Author summary Why was this study done? The World Health Organization (WHO) recommends rotavirus vaccine use in all countries, but several questions remain for countries that have not yet implemented rotavirus vaccination or are weighing different vaccine options. In resource-limited settings, where rotavirus vaccine delivery has important cost implications, evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We previously reported on the efficacy and safety of Rotasiil (Serum Institute of India, Pune, India), a heat-stable, affordable oral rotavirus vaccine that was WHO prequalified in 2018, against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger. What did the researchers do and find? In the present analysis, we assessed the extended and strain-specific vaccine efficacy of Rotasiil in children up to 24 months of age. Rotasiil provided protection against SRVGE in infants through an extended follow-up period and against a changing pattern of rotavirus strains during the 2-year efficacy period. What do these findings mean? Vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, and can be expected to greatly reduce the burden of rotavirus disease.

Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa.We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3.Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception.Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).

Background Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative. Methods A prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3–28 October, 2017) and during the low transmission season (28 January–31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season. Results In the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1–63.8) for the pLDH test and 57.4% (95% CI 51.5–63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1–71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3–95.0) for the pLDH test and 85.8% (95% CI 79.3–90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9–66.8) for the pLDH test and 61.9% (55.0–68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention. Conclusions The low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.

ObjectivesRoutine amoxicillin for children with uncomplicated severe acute malnutrition raises concerns of increasing antibiotic resistance. We performed an ancillary study nested within a double-blind, placebo-controlled trial in Niger testing the role of routine 7 day amoxicillin therapy in nutritional recovery of children 6 to 59 months of age with uncomplicated severe acute malnutrition.MethodsWe screened 472 children for rectal carriage of ESBL-producing Enterobacteriaceae (ESBL-E) as well as their household siblings under 5 years old, at baseline and Week 1 (W1) and Week 4 (W4) after start of therapy, and characterized strains by WGS. ClinicalTrials.gov: NCT01613547.ResultsCarriage in index children at baseline was similar in the amoxicillin and the placebo groups (33.8% versus 27.9%, P = 0.17). However, acquisition of ESBL-E in index children at W1 was higher in the amoxicillin group than in the placebo group (53.7% versus 32.2%, adjusted risk ratio = 2.29, P = 0.001). Among 209 index and sibling households possibly exposed to ESBL-E transmission, 16 (7.7%) had paired strains differing by ≤10 SNPs, suggesting a high probability of transmission. This was more frequent in households from the amoxicillin group than from the placebo group [11.5% (12/104) versus 3.8% (4/105), P = 0.04].ConclusionsAmong children exposed to amoxicillin, ESBL-E colonization was more frequent and the risk of transmission to siblings higher. Routine amoxicillin should be carefully balanced with the risks associated with ESBL-E colonization.

Background In Niger, malaria transmission is markedly seasonal with most of the disease burden occurring in children during the rainy season. Seasonal malaria chemoprevention (SMC) with amodiaquine plus sulfadoxine– pyrimethamine (AQ + SP) is recommended in the country to be administered monthly just before and during the rainy season. Moreover, clinical decisions on use of SP for intermittent preventive treatment in pregnancy (IPTp) now depend upon the validated molecular markers for SP resistance in Plasmodium falciparum observed in the local parasite population. However, little is known about molecular markers of resistance for either SP or AQ in the south of Niger. To address this question, clinical samples which met clinical and biological criteria, were collected in Gabi, Madarounfa district, Maradi region, Niger in 2011–2012 (before SMC implementation). Molecular markers of resistance to pyrimethamine (pfdhfr), sulfadoxine (pfdhps) and amodiaquine (pfmdr1) were assessed by DNA sequencing. Results Prior to SMC implementation, the samples showed a high proportion of clinical samples that carried the pfdhfr 51I/59R/108N haplotype associated with resistance to pyrimethamine and pfdhps 436A/F/H and 437G mutations associated with reduced susceptibility to sulfadoxine. In contrast mutations in codons 581G, and 613S in the pfdhps gene, and in pfmdr1, 86Y, 184Y, 1042D and 1246Y associated with resistance to amodiaquine, were less frequently observed. Importantly, pfdhfr I164L and pfdhps K540E mutations shown to be the most clinically relevant markers for high level clinical resistance to SP were not detected in Gabi. Conclusion Although parasites with genotypes associated with the highest levels of resistance to AQ + SP are not yet common in this setting, their importance for deployment of SMC and IPTp dictates that monitoring of these markers of resistance should accompany these interventions. This study also highlights the parasite heterogeneity within a small spatial area and the need to use caution when extrapolating results from surveys of molecular markers of resistance in a single site to inform regional policy decisions.

Background Antibiotic prophylaxis for contacts of meningitis cases is not recommended during outbreaks in the African meningitis belt. We assessed the effectiveness of single-dose oral ciprofloxacin administered to household contacts and in village-wide distributions on the overall attack rate (AR) in an outbreak of meningococcal meningitis. Methods and findings In this 3-arm, open-label, cluster-randomized trial during a meningococcal meningitis outbreak in Madarounfa District, Niger, villages notifying a suspected case were randomly assigned (1:1:1) to standard care (the control arm), single-dose oral ciprofloxacin for household contacts within 24 hours of case notification, or village-wide distribution of ciprofloxacin within 72 hours of first case notification. The primary outcome was the overall AR of suspected meningitis after inclusion. A random sample of 20 participating villages was enrolled to document any changes in fecal carriage prevalence of ciprofloxacin-resistant and extended-spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae before and after the intervention. Between April 22 and May 18, 2017, 49 villages were included: 17 to the control arm, 17 to household prophylaxis, and 15 to village-wide prophylaxis. A total of 248 cases were notified in the study after the index cases. The AR was 451 per 100,000 persons in the control arm, 386 per 100,000 persons in the household prophylaxis arm (t test versus control p = 0.68), and 190 per 100,000 persons in the village-wide prophylaxis arm (t test versus control p = 0.032). The adjusted AR ratio between the household prophylaxis arm and the control arm was 0.94 (95% CI 0.52–1.73, p = 0.85), and the adjusted AR ratio between the village-wide prophylaxis arm and the control arm was 0.40 (95% CI 0.19‒0.87, p = 0.022). No adverse events were notified. Baseline carriage prevalence of ciprofloxacin-resistant Enterobacteriaceae was 95% and of ESBL-producing Enterobacteriaceae was >90%, and did not change post-intervention. One limitation of the study was the small number of cerebrospinal fluid samples sent for confirmatory testing. Conclusions Village-wide distribution of single-dose oral ciprofloxacin within 72 hours of case notification reduced overall meningitis AR. Distributions of ciprofloxacin could be an effective tool in future meningitis outbreak responses, but further studies investigating length of protection, effectiveness in urban settings, and potential impact on antimicrobial resistance patterns should be carried out. Trial registration ClinicalTrials.gov NCT02724046

Background: In nutritional crises, large-scale preventive distributions of specialized nutritious foods are recommended to prevent acute and chronic malnutrition in young children. Among the available specialized nutritious foods, the World Food Programme and UNICEF recommend lipid-based nutrient supplements (LNSs) and Super Cereal Plus (SC+). Although the effectiveness of short-term distributions for prevention of severe acute malnutrition (SAM) is well documented, evidence for long-term strategies and the role of distribution of specialized nutritious foods for prevention of stunting is weaker. Objective: The objective of this study was to compare long-term supplementation of LNSs and SC+ on the incidence of acute malnutrition and stunting in young children. Methods: We conducted two 15-mo-long supplementation interventions with the use of LNSs (500 kcal/d) and SC+ (810 kcal/d) and half rations during 5 mo of the nonlean season, for the prevention of acute malnutrition and stunting in children aged 6–23 mo. The study was designed as a prospective cohort in 11 villages in Madarounfa, Niger. We compared the incidence of acute malnutrition and stunting with the use of Cox proportional hazards models and report on sharing and use of these food supplements. Results: Characteristics of children at baseline were similar across groups. A total of 1967 children were included in the analysis (845 in the SC+ group and 1122 in the LNS group). No significant differences in the incidence of moderate acute malnutrition (SC+ compared with LNS: adjusted HR: 0.79; 95% CI: 0.61, 1.02) or SAM (HR: 0.84; 95% CI: 0.52, 1.34) were found. No difference in the incidence of stunting (HR: 1.08; 95% CI: 0.95, 1.24) or severe stunting (HR: 0.94; 95% CI: 0.71, 1.22) over the follow-up period were found. Conclusions: These findings in young children in Niger suggest that both products should be considered when planning preventive distributions and choice of long-term supplementation should be guided by context-specific factors such as acceptability, cost, and operational feasibility, among others. Additional research is essential to improving child health. The study was registered at clinicaltrials.gov as NCT01828814. J Nutr 2015;145:2596–603.

International audience; OBJECTIVE:We conducted a parallel evaluation of the diagnostic accuracy of VIKIA® Rota-Adeno, a rapid diagnostic test (RDT) and Premier™ Rotaclone® an enzyme immunoassay (EIA) using reverse transcription polymerase chain reaction (RT-PCR) as the reference standard. The study was part of a rotavirus surveillance project in Niger.RESULTS:The sensitivity of both tests was 80.7%. After exclusion of one indeterminate result by visual reading, the specificity of the Premier™ Rotaclone® was 100% by visual or optical density readings and that of VIKIA® Rota-Adeno test was 95.5%. Inter-reader agreement was excellent for both tests (kappa = 1). Our results showed almost similar performance of the EIA and RDT when compared to RT-PCR. Hence, the VIKIA® Rota-Adeno could be a good alternative for use in peripheral health centres where laboratory capacity is limited.

ObjectiveThe current qualitative study aimed to identify gender, social and cultural influences on the management and use of unconditional cash transfers as part of a prospective intervention study in Niger.DesignIn February to March 2012, focus group discussions and semi-structured individual interviews were conducted with female caregivers of children aged 6 to 23 months who received unconditional cash transfers. Discussion and interview transcripts were analysed using content thematic analysis.SettingThe study was conducted in the Madarounfa district in Maradi region of Niger.SubjectsAmong forty-eight intervention villages, fourteen were selected for the qualitative study. Participants were randomly selected from eligible households.ResultsIn total, 124 women participated in focus group discussions or interviews. The majority reported giving the cash transfer to the male head of household who primarily managed cash at the household level. Women reported using a portion of the money to purchase foods for the target child. Feeding the household was the primary use of the cash transfer, followed by health care, clothing, gifts or ceremonies.ConclusionsGender, social and cultural norms influenced management and usage of the cash transfer at the household level. The results highlight the importance of integrating gender-sensitive indicators into interventions. Information and awareness sessions should be an integral component of large-scale distributions with a special emphasis on gender equality and the importance of women’s empowerment to improve agriculture and family health.

International audience; Knowledge of rotavirus epidemiology is necessary to make informed decisions about vaccine introduction and to evaluate vaccine impact. During April 2010-March 2012, rotavirus surveillance was conducted among 9,745 children 80% of isolates during the second year. Hospitalization and death rates and severe dehydration among rotavirus case-patients did not differ during the 2 years. The emergence of G12P[8] warrants close attention to the characteristics of associated epidemics and possible prevention measures.

Background Epidemics of meningococcal meningitis are common in the “African meningitis belt.” Current response strategies include reactive vaccination campaigns, which are often organized too late to have maximal impact. A novel strain of Neisseria meningitidis serogroup C has been circulating in recent years, and vaccine supplies are limited. An evaluation of chemoprophylaxis with single-dose ciprofloxacin for household contacts of meningitis cases has therefore been recommended. Methods/design A three-arm cluster-randomized trial has been designed for implementation during a meningococcal meningitis epidemic in a health district in Niger in which at least two Health Zones (HZs) have met the weekly epidemic threshold. The primary outcome is the incidence (attack rate) of meningitis during the epidemic. Villages will be randomized in a 1:1:1 ratio to one of three different arms: standard care, household-level prophylaxis, or village-wide prophylaxis. After study launch, when a case of meningococcal meningitis is identified in an HZ, the first reported case from a village will trigger the inclusion and randomization of the village. Household-level prophylaxis with single-dose ciprofloxacin will be offered in the home to all household members within 24 hours of the notification of the case, and village-wide distributions will occur within 72 hours of the notification of the case. The sample size necessary to detect differences between each of the two intervention arms and the standard care arm will be set after 4 weeks of data collection, in order to quantify multiple variables that could be particular to a given area. The primary analysis will compare attack rates at the end of the epidemic in each of the three arms. A nested sub-study will assess the effects of ciprofloxacin prophylaxis on the prevalence of ciprofloxacin-resistant enterobacteriaceae. A total of 200 participants in the standard care arm and 200 in the village-wide prophylaxis arm will provide stool samples at days 0, 7, and 28 following their village’s inclusion in the study. Discussion An innovative trial is proposed for implementation during an epidemic that will assess the impact of a novel strategy for meningitis outbreak response. In parallel, we will describe potential negative effects of the intervention. Trial registration ClinicalTrials.gov, NCT02724046. Registered on 15 March 2016. Last updated on 13 June 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2028-y) contains supplementary material, which is available to authorized users.

Strategies for preventing undernutrition comprise a range of interventions, including education, provision of complementary food and cash transfer. Here, we compared monthly distributions of two different lipid‐based nutrient supplements (LNS), large‐quantity LNS (LNS‐LQ) and medium‐quantity LNS (LNS‐MQ) for 15 months on prevention of undernutrition among children 6 to 23 months. Both groups also received cash transfer for the first 5 months of the intervention. We conducted a prospective intervention study in Maradi, Niger, between August 2011 and October 2012. Six and 11 villages were randomly allocated to LNS‐LQ/Cash and LNS‐MQ/Cash, respectively. Children measuring 60–80 cm were enrolled in the respective groups and followed up monthly. Poisson regression was used to assess differences between interventions and adjust for baseline characteristics, intervention periods and child‐feeding practices. The analysis included 2586 children (1081 in the LNS‐LQ/Cash group and 1505 in the LNS‐MQ/Cash group). This study suggests that provision of LNS‐LQ (reference) or LNS‐MQ had, overall, similar effect on incidence of severe acute malnutrition (RR = 0.97; 95% CI: 0.67–1.40; P = 0.88), moderate acute malnutrition (RR = 1.20; 95% CI: 0.97–1.48; P = 0.08), severe stunting (RR = 0.94; 95% CI: 0.70–1.26; P = 0.69), moderate stunting (RR = 0.95; 95% CI: 0.76–1.19; P = 0.67) and mortality (RR = 0.83; 95% CI: 0.41–1.65; P = 0.59). Compared with LNS‐LQ, LNS‐MQ showed a greater protective effect on moderate acute malnutrition among children with good dietary adequacy: RR = 0.72; 95% CI: 0.56–0.94; P = 0.01. These results highlight the need to design context‐specific programmes. Provision of LNS‐LQ might be more appropriate when food insecurity is high, while when food security is better, distribution of LNS‐MQ might be more appropriate.

International audience; BACKGROUND:Although rotavirus is the leading cause of severe diarrhea among children in sub-Saharan Africa, better knowledge of circulating enteric pathogenic bacteria and their antimicrobial resistance is crucial for prevention and treatment strategies.METHODOLOGY/PRINCIPAL FINDINGS:As a part of rotavirus gastroenteritis surveillance in Maradi, Niger, we performed stool culture on a sub-population of children under 5 with moderate-to-severe diarrhea between April 2010 and March 2012. Campylobacter, Shigella and Salmonella were sought with conventional culture and biochemical methods. Shigella and Salmonella were serotyped by slide agglutination. Enteropathogenic Escherichia coli (EPEC) were screened by slide agglutination with EPEC O-typing antisera and confirmed by detection of virulence genes. Antimicrobial susceptibility was determined by disk diffusion. We enrolled 4020 children, including 230 with bloody diarrhea. At least one pathogenic bacterium was found in 28.0% of children with watery diarrhea and 42.2% with bloody diarrhea. Mixed infections were found in 10.3% of children. EPEC, Salmonella and Campylobacter spp. were similarly frequent in children with watery diarrhea (11.1%, 9.2% and 11.4% respectively) and Shigella spp. were the most frequent among children with bloody diarrhea (22.1%). The most frequent Shigella serogroup was S. flexneri (69/122, 56.5%). The most frequent Salmonella serotypes were Typhimurimum (71/355, 20.0%), Enteritidis (56/355, 15.8%) and Corvallis (46/355, 13.0%). The majority of putative EPEC isolates was confirmed to be EPEC (90/111, 81.1%). More than half of all Enterobacteriaceae were resistant to amoxicillin and co-trimoxazole. Around 13% (46/360) Salmonella exhibited an extended-spectrum beta-lactamase phenotype.CONCLUSIONS:This study provides updated information on enteric bacteria diversity and antibiotic resistance in the Sahel region, where such data are scarce. Whether they are or not the causative agent of diarrhea, bacterial infections and their antibiotic resistance profiles should be closely monitored in countries like Niger where childhood malnutrition pre-disposes to severe and invasive infections.

Céline Langendorf and colleagues conducted a pragmatic intervention study in Niger to assess whether distributions of supplementary foods in addition to household support by cash transfer effectively reduced malnutrition in children aged 6 to 23 months. Please see later in the article for the Editors' Summary, Background Finding the most appropriate strategy for the prevention of moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) in young children is essential in countries like Niger with annual “hunger gaps.” Options for large-scale prevention include distribution of supplementary foods, such as fortified-blended foods or lipid-based nutrient supplements (LNSs) with or without household support (cash or food transfer). To date, there has been no direct controlled comparison between these strategies leading to debate concerning their effectiveness. We compared the effectiveness of seven preventive strategies—including distribution of nutritious supplementary foods, with or without additional household support (family food ration or cash transfer), and cash transfer only—on the incidence of SAM and MAM among children aged 6–23 months over a 5-month period, partly overlapping the hunger gap, in Maradi region, Niger. We hypothesized that distributions of supplementary foods would more effectively reduce the incidence of acute malnutrition than distributions of household support by cash transfer. Methods and Findings We conducted a prospective intervention study in 48 rural villages located within 15 km of a health center supported by Forum Santé Niger (FORSANI)/Médecins Sans Frontières in Madarounfa. Seven groups of villages (five to 11 villages) were allocated to different strategies of monthly distributions targeting households including at least one child measuring 60 cm–80 cm (at any time during the study period whatever their nutritional status): three groups received high-quantity LNS (HQ-LNS) or medium-quantity LNS (MQ-LNS) or Super Cereal Plus (SC+) with cash (€38/month [US$52/month]); one group received SC+ and family food ration; two groups received HQ-LNS or SC+ only; one group received cash only (€43/month [US$59/month]). Children 60 cm–80 cm of participating households were assessed at each monthly distribution from August to December 2011. Primary endpoints were SAM (weight-for-length Z-score [WLZ], Editors' Summary Background Good nutrition during childhood is essential for health and survival. Undernourished children are more susceptible to infection and are more likely to die from common ailments such as diarrhoea than well-nourished children. Malnutrition can be chronic or acute. Chronic (long-term) malnutrition causes stunting. A stunted child has a low height for his or her age when compared to the World Health Organization Child Growth Standards, which chart the growth of a reference population. By contrast, acute malnutrition causes wasting. A wasted child has a low weight for his or her height. Acute malnutrition, which is responsible for more than 800,000 deaths among children under 5 years old every year (12.6% of all deaths in this age group), often follows earthquakes or other emergencies but also occurs in countries such as Niger that regularly experience a “hunger gap,” a shortage of food in the months before the annual harvest. Interventions designed to prevent acute malnutrition include distributions of supplementary food such as lipid-based nutrient supplements (LNS) and fortified cereal products (for example, super cereal plus [SC+]) targeting children and household support in the form of food or cash transfers, which allow households to buy their own food. Why Was This Study Done? Governments and donor agencies need to know which preventative strategy is most effective, particularly among children under 2 years old who are most vulnerable to acute malnutrition. Here, the researchers compare the effectiveness of seven preventative strategies—including the distribution of nutritious supplementary foods with and without additional household support (food or cash transfer) and cash transfer alone—on the incidence (occurrence) of moderate and severe acute malnutrition among children aged 6–23 months living in 48 villages in the Madarounfa district of Niger between August and December, 2011. Niger regularly experiences a hunger gap between June and October; 12.9% of the population of the Madarounfa district was at risk of severe food insecurity at the time of the study. What Did the Researchers Do and Find? The researchers allocated the villages to receive high or medium quantity LNS plus cash, SC+ plus cash or a family food ration, high quantity LNS only, SC+ only, or cash only; the cash transfer was sufficient to meet the energy needs of an average household. The interventions were distributed once a month to households that included at least one child measuring 60–80 cm in length at any time during the study period (length is used as a proxy for age when the precise age of children is unknown). Eligible children in each participating household were assessed for moderate and severe acute malnutrition as defined by the World Health Organization by measuring their weight, length, and mid-upper arm circumference at each distribution. The incidence of moderate acute malnutrition was about twice as high among children who received the cash-only intervention as among those who received any of the food supplement plus cash. For example, the incidence of moderate acute malnutrition was 3.33 cases per 100 child-months among children who received the SC+ plus cash intervention but 7.97 cases per 100 child-months among those who received the cash-only intervention. Moreover, the incidence of severe acute malnutrition was about three times higher among the children who received the SC+ only intervention than among those who received the SC+ plus cash intervention. What Do These Findings Mean? These findings suggest that, in this region of Niger, interventions that combined the distribution of supplementary food and a cash transfer prevented acute malnutrition more effectively than strategies that relied on cash transfer or supplementary food distribution alone. Unmeasured differences between the groups that affect the incidence of malnutrition may be responsible for some of the differences between intervention groups, and the incidences of malnutrition may have been different if the study period had covered the whole hunger gap. Moreover, these findings may not be generalizable to other regions of Niger or to other countries that experience an annual hunger gap. Despite these limitations, which highlight the need for further research into the effectiveness of nutritional interventions, these findings suggest that the distribution of supplementary foods to young children in conjunction with household support should remain an important part of nutritional interventions during the hunger gap and other emergencies. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001714. This study is further discussed in a PLOS Medicine Perspective by Marco Kerac and Andrew Seal More information about this prospective intervention study is available from ClinicalTrials.gov The charity UNICEF, which protects the rights of children and young people around the world, provides detailed statistics on child undernutrition; it has detailed information about malnutrition and the humanitarian situation in Niger; a 2012 article on malnutrition among children in Niger includes a personal story about a child with severe acute malnutrition in Maradi The World Health Organization Child Growth Standards are available (in several languages) The United Nations Millennium Development Goals provides information on ongoing world efforts to reduce hunger and child mortality The World Food Programme is the world's largest humanitarian agency fighting hunger worldwide; its website provides information about malnutrition in Niger, including a visual presentation on wide-scale targeted food distribution in the country “Starved for Attention” is an international multimedia campaign launched in 2010 by Médecins Sans Frontiéres (MSF) and the VII Photo agency to rewrite the story of childhood malnutrition; information about MSF's work in Niger to tackle malnutrition is available

Few studies have looked at consumption of Ready-to-Use-Supplementary-Foods (RUSFs) during a nutritional emergency. Here, we describe the use and acceptability of RUSF within households in four districts of the region of Maradi, Niger during large scale preventive distributions with RUSF in 2010 targeted at children 6–35 months of age. Our study comprised both quantitative and qualitative components to collect detailed information and to allow in-depth interviews. We performed a cross-sectional survey in 16 villages between two monthly distributions of RUSF (October–November 2010). All households with at least one child who received RUSF were included and a total of 1842 caregivers were interviewed using a structured questionnaire. Focus groups and individual interviews of 128 caregivers were conducted in eight of the selected villages. On average, 24.7% of households reported any sharing of RUSF within the household. Sharing practices outside the household remained rare. Most of the sharing reported occurred among children under 5 years of age living in the household. On average, 91% of caregivers in all districts rated the child’s appreciation of the products as good or very good. Program planning may need to explicitly accounting for the sharing of products among children under 5 within household.