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.

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.].

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.

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.

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.

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.

Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 .).

Increased risk of acquisition and transmission of ESBL-producing Enterobacteriaceae in malnourished children exposed to amoxicillin.

OBJECTIVES: Routine 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. METHODS: We 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. RESULTS: Carriage 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]. CONCLUSIONS: Among 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.

Routine Amoxicillin for Uncomplicated Severe Acute Malnutrition in Children.

BACKGROUND: High-quality evidence supporting a community-based treatment protocol for children with severe acute malnutrition, including routine antibiotic use at admission to a nutritional treatment program, remains limited. In view of the costs and consequences of emerging resistance associated with routine antibiotic use, more evidence is required to support this practice. METHODS: In a double-blind, placebo-controlled trial in Niger, we randomly assigned children who were 6 to 59 months of age and had uncomplicated severe acute malnutrition to receive amoxicillin or placebo for 7 days. The primary outcome was nutritional recovery at or before week 8. RESULTS: A total of 2412 children underwent randomization, and 2399 children were included in the analysis. Nutritional recovery occurred in 65.9% of children in the amoxicillin group (790 of 1199) and in 62.7% of children in the placebo group (752 of 1200). There was no significant difference in the likelihood of nutritional recovery (risk ratio for amoxicillin vs. placebo, 1.05; 95% confidence interval [CI], 0.99 to 1.12; P=0.10). In secondary analyses, amoxicillin decreased the risk of transfer to inpatient care by 14% (26.4% in the amoxicillin group vs. 30.7% in the placebo group; risk ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02). CONCLUSIONS: We found no benefit of routine antibiotic use with respect to nutritional recovery from uncomplicated severe acute malnutrition in Niger. In regions with adequate infrastructure for surveillance and management of complications, health care facilities could consider eliminating the routine use of antibiotics in protocols for the treatment of uncomplicated severe acute malnutrition. (Funded by Médecins sans Frontières Operational Center Paris; ClinicalTrials.gov number, NCT01613547.).

Evaluation of OMNIgene Sputum and Ethanol Reagent for Preservation of Sputum Prior to Xpert and Culture Testing in Uganda.

Xpert MTB/RIF (Xpert) and culture are the most reliable methods for tuberculosis diagnosis but are still poorly accessible in many low-resource countries. We aimed to assess the effects of OMNIgene Sputum (OM-S) and ethanol in preserving sputum for Xpert and OM-S for mycobacterial growth indicator tube (MGIT) testing over periods of 15 and 8 days, respectively. Sputum samples were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on days 0, 7, and 15 without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days. Totals of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using day 0 as a reference, untreated samples stored for 7 and 15 days showed concordances of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordances were 46/48 (95.8%) and 47/48 (97.9%), while those of ethanol were 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordances between untreated and OM-S-treated samples were 21/41 (51.2%) at day 0 and 21/44 (47.7%) at day 8. In conclusion, Xpert equally detected tuberculosis in OM-S-treated and untreated samples up to 15 days but showed slightly lower detection in ethanol-treated samples. Among OM-S-treated samples, MGIT positivity was significantly lower than in untreated samples at both time points.

Dual screen and confirm rapid test does not reduce overtreatment of syphilis in pregnant women living in a non-venereal treponematoses endemic region: a field evaluation among antenatal care attendees in Burkina Faso.

OBJECTIVES: In resource-limited settings, screening pregnant women for syphilis using rapid diagnostic tests (RDTs) is a key tool in the prevention of congenital syphilis. However, most syphilis RDTs detect only treponemal antibodies (T-RDT), meaning antibiotics may be provided unnecessarily to previously treated pregnant women, particularly in non-venereal treponematoses endemic regions. We estimated the potential reduction in overtreatment when comparing T-RDT (SD Bioline) to a newer rapid test (Dual Path Platform (DPP) Screen and Confirm Assay, Chembio) detecting both treponemal and non-treponemal antibodies. METHODS: Pregnant women in Déou, Burkina Faso, screened for syphilis during antenatal care (ANC) visits were prospectively enrolled in the study after providing consent. DPP and T-RDT tests were performed on whole blood specimens. Plasma was tested in an international reference laboratory by Treponema pallidum passive particle agglutination (TPPA) and quantitative rapid plasma reagin (RPR). Presumptive active syphilis was defined as a result that was both TPPA and RPR reactive. RESULTS: Of the 242 pregnant women included in the study, 91 (37.6%) had presumptive active syphilis and 19.0% had RPR titres ≥8. DPP testing did not reduce the number of pregnant women who would have been overtreated compared with T-RDT (0.0% vs 2.5%; p=0.218) and had a higher proportion of underdiagnosis (48.4% vs 2.2%; p<0.001). Seven women with high RPR titres ≥8 would not have received treatment had only DPP testing been used. CONCLUSION: In the first evaluation comparing DPP with traditional screening methods in pregnant women, we saw no reduction in unnecessarily treated syphilis and an underestimation of those needing treatment. High seroprevalence in the population may indicate the presence of other treponemal infections in the area, and further study of DPP in a variety of Sahelian and other contexts is warranted.

Clinical diagnostic evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria in an area receiving seasonal malaria chemoprevention in Niger.

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.

Post-traumatic osteomyelitis in Middle East war-wounded civilians: resistance to first-line antibiotics in selected bacteria over the decade 2006-2016.

BACKGROUND: War-wounded civilians in Middle East countries are at risk of post-traumatic osteomyelitis (PTO). We aimed to describe and compare the bacterial etiology and proportion of first-line antibiotics resistant bacteria (FLAR) among PTO cases in civilians from Syria, Iraq and Yemen admitted to the reconstructive surgical program of Médecins Sans Frontières (MSF) in Amman, Jordan, and to identify risk factors for developing PTO with FLAR bacteria. METHODS: We retrospectively analyzed the laboratory database of the MSF program. Inclusion criteria were: patients from Iraq, Yemen or Syria, admitted to the Amman MSF program between October 2006 and December 2016, with at least one bone biopsy sample culture result. Only bone samples taken during first orthopedic surgery were included in the analysis. To assess factors associated with FLAR infection, logistic regression was used to estimate odds ratio (ORs) and 95% confidence intervals (CI). RESULTS: 558 (76.7%) among 727 patients included had ≥1 positive culture results. 318 were from Iraq, 140 from Syria and 100 from Yemen. Median time since injury was 19 months [IQR 8-40]. Among the 732 different bacterial isolates, we identified 228 Enterobacteriaceae (31.5%), 193 Staphylococcus aureus (26.3%), 99 Pseudomonas aeruginosa (13.5%), and 21 Acinetobacter baumanii (2.8%). Three hundred and sixty four isolates were FLAR: 86.2% of Enterobacteriaceae, 53.4% of Pseudomonas aeruginosa, 60.5% of S. aureus and 45% of Acinetobacter baumannii. There was no difference in bacterial etiology or proportion of FLAR according to the country of origin. In multivariate analysis, a FLAR infection was associated with an infection of the lower extremity, with a time since the injury ≤12 months compared with time > 30 months and with more than 3 previous surgeries. CONCLUSIONS: Enterobacteriaceae were frequently involved in PTO in war wounded civilians from Iraq, Yemen and Syria between 2006 and 2016. Proportion of FLAR was high, particularly among Enterobacteriaceae, regardless of country of origin.

Measles seroprevalence after reactive vaccination campaigns during the 2015 measles outbreak in four health zones of the former Katanga Province, Democratic Republic of Congo.

BACKGROUND: Measles continues to circulate in the Democratic Republic of Congo, and the country suffered from several important outbreaks over the last 5 years. Despite a large outbreak starting in the former province of Katanga in 2010 and the resulting immunization activities, another outbreak occurred in 2015 in this same region. We conducted measles seroprevalence surveys in four health zones (HZ) in the former Katanga Province in order to assess the immunity against measles in children 6 months to 14 years after the 2015 outbreak. METHODS: We conducted multi-stage cluster surveys stratified by age group in four HZs, Kayamba, Malemba-Nkulu, Fungurume, and Manono. The age groups were 6-11 months, 12-59 months, and 5-14 years in Kayamba and Malemba-Nkulu, 6-59 months and 5-14 years in Manono and Fungurume. The serological status was measured on dried capillary blood spots collected systematically along with vaccination status (including routine Extended Program of Immunization (EPI), and supplementary immunization activities (SIAs)) and previous self-reported history of suspected measles. RESULTS: Overall seroprevalence against measles was 82.7% in Kayamba, 97.6% in Malemba-Nkulu, 83.2% in Manono, and 74.4% in Fungurume, and it increased with age in all HZs. It was 70.7 and 93.8% in children 12-59 months in Kayamba and Malemba-Nkulu, and 49.8 and 64.7% in children 6-59 months in Fungurume and Manono. The EPI coverage was low but varied across HZ. The accumulation of any type of vaccination against measles resulted in an overall vaccine coverage (VC) of at least 85% in children 12-59 months in Kayamba and Malemba-Nkulu, 86.1 and 74.8% in children 6-59 months in Fungurume and Manono. Previous measles infection in 2015-early 2016 was more frequently reported in children aged 12-59 months or 6-59 months (depending on the HZ). CONCLUSION: The measured seroprevalence was consistent with the events that occurred in these HZs over the past few years. Measles seroprevalence might prove a valuable source of information to help adjust the timing of future SIAs and prioritizing support to the EPI in this region as long as the VC does not reach a level high enough to efficiently prevent epidemic flare-ups.

Single-dose oral ciprofloxacin prophylaxis as a response to a meningococcal meningitis epidemic in the African meningitis belt: A 3-arm, open-label, cluster-randomized trial.

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.

Molecular markers of resistance to amodiaquine plus sulfadoxine-pyrimethamine in an area with seasonal malaria chemoprevention in south central Niger.

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. CONCLUSIONS: 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.

Intermittent preventive treatment for malaria among children in a refugee camp in Northern Uganda: lessons learned.

Northern Uganda hosts a large population of refugees from South Sudan, and malaria is one of the major health problems in the area. In 2015, intermittent preventive treatment for malaria (IPTc) was implemented in two refugee camps among children aged 6 months to 14 years. Three distributions of dihydroartemisinin-piperaquine (DP) were conducted at 8-week intervals. The first dose was directly administered at IPTc distribution sites and the second and third doses were given to caregivers to administer at home. A multi-faceted evaluation was implemented, including coverage surveys, malaria prevalence surveys, reinforced surveillance, and pharmacovigilance. Programme coverage exceeded 90% during all three distributions with a total of 40,611 participants. Compared to same period during the previous year (only available data), the incidence of malaria in the target populations was reduced (IRR 0.73, 95% CI 0.69-0.77 among children under 5 years old; IRR 0.70, 95% CI 0.67-0.72 among children aged 5-14 years). Among those not targeted for intervention, the incidence between the 2 years increased (IRR 1.49, 95% CI 1.42-1.56). Cross-sectional surveys showed a prevalence of parasitaemia (microscopy or PCR) of 12.9-16.4% (95% CI 12.6-19.3) during the intervention, with the highest prevalence among children aged 5-14 years, but with a large increase 8 weeks after the final distribution. A total of 57 adverse events were reported during the intervention period, including one severe adverse event (death from varicella). Adverse events were of mild to moderate severity, and were mainly dermatologic and gastrointestinal. This is the first documentation of an IPTc programme in a refugee camp. The positive impact of DP on the incidence of malaria, together with its favourable safety profile, should lead to further use of IPTc in similar settings. Expanding coverage groups and decreasing intervals between distributions might provide more benefit, but would need to be balanced with the operational implications of a broader, more frequent distribution schedule.

The gender, social and cultural influences on the management and use of unconditional cash transfers in Niger: a qualitative study.

OBJECTIVE: The 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. DESIGN: In 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. SETTING: The study was conducted in the Madarounfa district in Maradi region of Niger. SUBJECTS: Among forty-eight intervention villages, fourteen were selected for the qualitative study. Participants were randomly selected from eligible households. RESULTS: In 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. CONCLUSIONS: Gender, 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.

Effect of ready-to-use foods for preventing child undernutrition in Niger: analysis of a prospective intervention study over 15 months of follow-up.

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.

Preventive Effects of Long-Term Supplementation with 2 Nutritious Food Supplements in Young Children in Niger.

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.