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[This corrects the article DOI: 10.1371/journal.pmed.1003923.].
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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.
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Desenvolvimento Infantil , Micronutrientes , Pré-Escolar , Suplementos Nutricionais , Feminino , Ácido Fólico , Humanos , Lactente , Ferro , Lipídeos/farmacologia , Micronutrientes/farmacologia , Níger , GravidezRESUMO
BACKGROUND: Community-based management of severe acute malnutrition (SAM) involves weekly or biweekly outpatient clinic visits for clinical surveillance and distribution of therapeutic foods. Distance to outpatient clinics and high opportunity costs for caregivers can represent major barriers to access. Reducing the frequency of outpatient visits while providing training to caregivers to recognize clinical danger signs at home between outpatient visits may increase acceptability, coverage, and public health impact of SAM treatment. We investigated the effectiveness of monthly clinic visits compared to the standard weekly follow-up in the outpatient treatment of uncomplicated SAM in northwestern Nigeria. METHODS AND FINDINGS: We conducted a cluster randomized crossover trial to test the noninferiority of nutritional recovery in children with uncomplicated SAM receiving monthly follow-up compared to the standard weekly schedule. From January 2018 to November 2019, 3,945 children aged 6 to 59 months were enrolled at 10 health centers (5 assigned to monthly follow-up and 5 assigned to weekly follow-up) in Sokoto, Nigeria. In total, 96% of children (n = 1,976 in the monthly follow-up group and 1,802 in the weekly follow-up group) were followed until program discharge, and 91% (n = 1,873 in the monthly follow-up group and 1,721 in the weekly follow-up group) were followed to 3 months postdischarge. The mean age at admission was 15.8 months (standard deviation [SD] 7.1), 2,097/3,945 (53.2%) were girls, and the mean midupper arm circumference (MUAC) at admission was 105.8 mm (SD 6.0). In a modified intention-to-treat analysis, the primary outcome of nutritional recovery, defined as having MUAC ≥125 mm on 2 consecutive visits, was analyzed using generalized linear models, with generalized estimating equations to account for clustering. Nutritional recovery was lower in the monthly follow-up group compared to the weekly group (1,036/1,976, 52.4% versus 1,059/1,802, 58.8%; risk difference: -6.8%), and noninferiority was not demonstrated (lower bound of the confidence interval [CI] was -11.5%, lower than the noninferiority margin of 10%). The proportion of children defaulting was lower in the monthly group than in the weekly group (109/1,976, 5.5% versus 151/1,802, 8.4%, p = 0.03). Three months postdischarge, children in the monthly group were less likely to relapse compared to those in the weekly group (58/976, 5.9% versus 78/1,005, 7.8%, p = 0.03), but cumulative mortality at 3 months postdischarge was higher in the monthly group (159/1,873, 8.5% versus 106/1,721, 6.2%, p < 0.001). Study results may depend on context-specific factors including baseline level of care and the clinical status of children presenting to health centers, and, thus, generalizability of these results may be limited. CONCLUSIONS: Where feasible, a weekly schedule of clinic visits should be preferred to maintain effectiveness of SAM treatment. Where geographic coverage of programs is low or frequent travel to outpatient clinics is difficult or impossible, a monthly schedule of visits may provide an alternative model to deliver treatment to those in need. Modifications to the outpatient follow-up schedule, for example, weekly clinic visits until initial weight gain has been achieved followed by monthly visits, could increase the effectiveness of the model and add flexibility for program delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03140904.
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Desnutrição , Desnutrição Aguda Grave , Assistência ao Convalescente , Criança , Estudos Cross-Over , Feminino , Seguimentos , Humanos , Lactente , Masculino , Desnutrição/diagnóstico , Nigéria/epidemiologia , Alta do PacienteRESUMO
BACKGROUND: Stocks of yellow fever vaccine are insufficient to cover exceptional demands for outbreak response. Fractional dosing has shown efficacy, but evidence is limited to the 17DD substrain vaccine. We assessed the immunogenicity and safety of one-fifth fractional dose compared with standard dose of four WHO-prequalified yellow fever vaccines produced from three substrains. METHODS: We did this randomised, double-blind, non-inferiority trial at research centres in Mbarara, Uganda, and Kilifi, Kenya. Eligible participants were aged 18-59 years, had no contraindications for vaccination, were not pregnant or lactating, had no history of yellow fever vaccination or infection, and did not require yellow fever vaccination for travel. Eligible participants were recruited from communities and randomly assigned to one of eight groups, corresponding to the four vaccines at standard or fractional dose. The vaccine was administered subcutaneously by nurses who were not masked to treatment, but participants and other study personnel were masked to vaccine allocation. The primary outcome was proportion of participants with seroconversion 28 days after vaccination. Seroconversion was defined as post-vaccination neutralising antibody titres at least 4 times pre-vaccination measurement measured by 50% plaque reduction neutralisation test (PRNT50). We defined non-inferiority as less than 10% decrease in seroconversion in fractional compared with standard dose groups 28 days after vaccination. The primary outcome was measured in the per-protocol population, and safety analyses included all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT02991495. FINDINGS: Between Nov 6, 2017, and Feb 21, 2018, 1029 participants were assessed for inclusion. 69 people were ineligible, and 960 participants were enrolled and randomly assigned to vaccine manufacturer and dose (120 to Bio-Manguinhos-Fiocruz standard dose, 120 to Bio-Manguinhos-Fiocruz fractional dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides standard dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides fractional dose, 120 to Institut Pasteur Dakar standard dose, 120 to Institut Pasteur Dakar fractional dose, 120 to Sanofi Pasteur standard dose, and 120 to Sanofi Pasteur fractional dose). 49 participants had detectable PRNT50 at baseline and 11 had missing PRNT50 results at baseline or 28 days. 900 were included in the per-protocol analysis. 959 participants were included in the safety analysis. The absolute difference in seroconversion between fractional and standard doses by vaccine was 1·71% (95% CI -2·60 to 5·28) for Bio-Manguinhos-Fiocruz, -0·90% (-4·24 to 3·13) for Chumakov Institute of Poliomyelitis and Viral Encephalitides, 1·82% (-2·75 to 5·39) for Institut Pasteur Dakar, and 0·0% (-3·32 to 3·29) for Sanofi Pasteur. Fractional doses from all four vaccines met the non-inferiority criterion. The most common treatment-related adverse events were headache (22·2%), fatigue (13·7%), myalgia (13·3%) and self-reported fever (9·0%). There were no study-vaccine related serious adverse events. INTERPRETATION: Fractional doses of all WHO-prequalified yellow fever vaccines were non-inferior to the standard dose in inducing seroconversion 28 days after vaccination, with no major safety concerns. These results support the use of fractional dosage in the general adult population for outbreak response in situations of vaccine shortage. FUNDING: The study was funded by Médecins Sans Frontières Foundation, Wellcome Trust (grant no. 092654), and the UK Department for International Development. Vaccines were donated in kind.
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Uso Off-Label , Vacina contra Febre Amarela/administração & dosagem , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Método Duplo-Cego , Feminino , Humanos , Quênia , Masculino , Soroconversão , Uganda , Febre Amarela/prevenção & controle , Vacina contra Febre Amarela/efeitos adversos , Vacina contra Febre Amarela/imunologiaRESUMO
BACKGROUND: Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. METHODS: We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase-polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. RESULTS: A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. CONCLUSIONS: Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.).
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Alanina/análogos & derivados , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Doença pelo Vírus Ebola/tratamento farmacológico , Ribonucleotídeos/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Adolescente , Adulto , Alanina/efeitos adversos , Alanina/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Antivirais/efeitos adversos , Criança , Pré-Escolar , República Democrática do Congo/epidemiologia , Surtos de Doenças , Ebolavirus/genética , Feminino , Doença pelo Vírus Ebola/mortalidade , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , RNA Viral/sangue , Ribonucleotídeos/efeitos adversos , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: In the outpatient management of severe wasting, routine antibiotic therapy is recommended for all children upon admission regardless of whether clinical signs of infection are present. Indicated antibiotic therapy, where antibiotics are provided only upon presentation of clinical signs of infection, may be considered for its potential to allow for more prudent antibiotic use and greater program coverage, reducing the risk of antibiotic resistance as well as costs and logistical burdens associated with treatment. We therefore conducted a cost-effectiveness analysis to measure the effects of indicated antibiotic therapy compared to routine antibiotic therapy in terms of incremental cost-per-life-year saved in Niger. METHODS: We used a cohort model to conduct a cost-effectiveness analysis from a healthcare system perspective to project and weigh the lifetime discounted costs and effects of indicated antibiotic therapy compared to routine antibiotic therapy in the treatment of uncomplicated severe wasting in children in Niger. We calculated incremental cost-effectiveness ratios (ICERs) in terms of treatment-related healthcare costs per discounted life-years saved (LYS), and conducted program coverage scenario and sensitivity analyses to assess model uncertainty. RESULTS: The ICER for indicated antibiotic therapy compared to routine antibiotic therapy was $8.5/LYS, which is under the cost-effectiveness threshold for Niger. The probability of the indicated strategy being optimal was 76.1% when program coverage was equal to coverage associated with routine therapy but was 100% likely to be optimal in probabilistic sensitivity analysis scenarios where indicated program coverage improved 5 percentage points. CONCLUSIONS: Indicated antibiotic therapy likely represents a cost-effective strategy, particularly if indicated treatment can result in expanded coverage. With the risk of increasing antibiotic resistance worldwide, antibiotic stewardship and simplified treatment protocols for severe wasting using indicated antibiotic therapy may represent good value for money in some low risk populations.
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This study aimed to quantify the burden of relapse following successful treatment for uncomplicated severe acute malnutrition (SAM) and to identify associated risk factors in rural Niger. We used data from 1490 children aged 6-59 months discharged as recovered from an outpatient nutritional programme for SAM and followed for up to 12 weeks after admission. Postdischarge SAM relapse was defined as weight-for-height Z-score <-3, mid-upper arm circumference (MUAC) <115 mm or bipedal oedema after having been discharged as recovered. Postdischarge hospitalisation was defined as admission to inpatient SAM treatment or hospitalisation for any cause after having been discharged as recovered. We used multivariate log-binomial models to identify independent risk factors. After programmatic discharge, 114 (8%) children relapsed to SAM and 89 (6%) were hospitalised. Factors associated with SAM relapse were discharge during the lean season (relative risk [RR] = 1.80 [95% confidence interval [CI] = 1.22-2.67]) and larger household size (RR = 1.56 [95% CI = 1.01-2.41]), whereas older child age (RR = 0.94 [95% CI = 0.88-1.00]), higher child MUAC at discharge (RR = 0.93 [95% CI = 0.87-1.00]) and maternal literacy (RR = 0.54 [95% CI = 0.29-0.98]) were protective factors. Discharge during the lean season (RR = 2.27 [95% CI = 1.46-3.51]) was independently associated with postdischarge hospitalisation. Future nutritional programmes in the context of Niger may consider modification of anthropometric discharge criteria or the provision of additional home support or follow-up during the lean season as potential interventions to prevent relapse. More research including postdischarge follow-up is needed to better understand the sustainability of treatment outcomes after discharge and the type of intervention that may best sustain recovery over time. Clinical Trial Registration: ClinicalTrials.gov number, NCT01613547.
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Desnutrição , Desnutrição Aguda Grave , Adolescente , Assistência ao Convalescente , Criança , Pré-Escolar , Doença Crônica , Humanos , Lactente , Níger/epidemiologia , Alta do Paciente , Recidiva , Fatores de Risco , Desnutrição Aguda Grave/terapiaRESUMO
[This corrects the article DOI: 10.1371/journal.pmed.1003720.].
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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.
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Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Imunogenicidade da Vacina , Ferro/administração & dosagem , Lipídeos/administração & dosagem , Micronutrientes/administração & dosagem , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Análise por Conglomerados , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Níger , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Vacinas Atenuadas/administração & dosagemRESUMO
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.
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Gastroenterite/prevenção & controle , Gastroenterite/virologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Pré-Escolar , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Programas de Imunização , Lactente , Masculino , Níger , Placebos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologiaRESUMO
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.
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Antimaláricos/administração & dosagem , Quimioprevenção/estatística & dados numéricos , Malária/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Malária/prevenção & controle , Masculino , Pessoa de Meia-Idade , Níger/epidemiologia , Prevalência , Estações do Ano , Adulto JovemRESUMO
BACKGROUND: Wasting and stunting, physical growth manifestations of child undernutrition, have historically been considered separately with distinct interventions at the program, policy, and financing levels despite similar risk factors, overlapping burdens and multiplicative risk of death when the conditions are concurrent. The aim of this study was to elucidate shared risk factors and the temporal relationship between wasting and stunting among children under 2 years of age in rural Niger. METHODS: From August 2014 to December 2019, anthropometric data were collected every 4 weeks from 6 to 8 weeks to 24 months of age for 6567 children comprising 139,529 visits in Madarounfa, Niger. Children were defined as wasted if they had a weight-for-length Z-score < - 2 and stunted if they had a length-for-age Z-score < - 2 using the 2006 World Health Organization child growth standards. Parental, child, and socioeconomic risk factors for wasting and stunting at 6 and 24 months of age and the relationship between episodes of wasting, stunting and concurrent wasting-stunting were assessed using general estimating equations. RESULTS: Half of children (50%) were female, and 8.3% were born low birthweight (< 2500 g). Overall, at 24 months of age, 14% of children were wasted, 80% were stunted and 12% were concurrently wasted-stunted. We found that maternal short stature, male sex, and low birthweight were risk factors for wasting and stunting at 6 and 24 months, whereas higher maternal body mass index and household wealth were protective factors. Wasting at 6 and 24 months was predicted by a prior episodes of wasting, stunting, and concurrent wasting-stunting. Stunting at 6 and 24 months was similarly predicted by prior episodes of stunting and concurrent wasting-stunting at any prior age but only by prior episodes of wasting after 6 months of age. CONCLUSIONS: These data support a complex and dynamic bi-directional relationship between wasting and stunting in young children in rural Niger and an important burden of concurrent wasting-stunting in this setting. Further research to better understand the inter-relationships and mechanisms between these two conditions is needed in order to develop and target interventions to promote child growth. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02145000 .
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Transtornos da Nutrição Infantil , Síndrome de Emaciação , Antropometria , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Transtornos do Crescimento/epidemiologia , Humanos , Lactente , Masculino , Níger/epidemiologia , Prevalência , Síndrome de Emaciação/epidemiologiaRESUMO
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 .).
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Gastroenterite/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus , Administração Oral , Animais , Bovinos , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/virologia , Humanos , Incidência , Lactente , Estimativa de Kaplan-Meier , Masculino , Níger , Rotavirus/isolamento & purificação , Vacinas contra Rotavirus/efeitos adversos , Vacinas contra Rotavirus/economia , Vacinas AtenuadasRESUMO
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.
Assuntos
Infecções por Enterobacteriaceae , Enterobacteriaceae , Amoxicilina , Antibacterianos/uso terapêutico , Pré-Escolar , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Lactente , Níger , beta-LactamasesRESUMO
Many factors can contribute to low coverage of treatment for severe acute malnutrition (SAM), and a limited number of health facilities and trained personnel can constrain the number of children that receive treatment. Alternative models of care that shift the responsibility for routine clinical and anthropometric surveillance from the health facility to the household could reduce the burden of care associated with frequent facility-based visits for both healthcare providers and caregivers. To assess the feasibility of shifting clinical surveillance to caregivers in the outpatient management of SAM, we conducted a pilot study to assess caregivers' understanding and retention of key concepts related to the surveillance of clinical danger signs and anthropometric measurement over a 28-day period. At the time of a child's admission to nutritional treatment, a study nurse provided a short training to groups of caregivers on two topics: (a) clinical danger signs in children with SAM that warrant facility-based care and (b) methods to measure and monitor their child's mid-upper arm circumference. Caregiver understanding was assessed using standardized questionnaires before training, immediately after training, and 28 days after training. Knowledge of most clinical danger signs (e.g., convulsions, edema, poor appetite, respiratory distress, and lethargy) was low (0-45%) before training but increased immediately after and was retained 28 days after training. Agreement between nurse-caregiver mid-upper arm circumference colour classifications was 77% (98/128) immediately after training and 80% after 28 days. These findings lend preliminary support to pursue further study of alternative models of care that allow for greater engagement of caregivers in the clinical and anthropometric surveillance of children with SAM.
Assuntos
Cuidadores/educação , Transtornos da Nutrição Infantil/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Assistência Domiciliar/educação , Desnutrição Aguda Grave/prevenção & controle , Adulto , Antropometria/métodos , Pré-Escolar , Estudos de Viabilidade , Feminino , Comportamento de Busca de Ajuda , Humanos , Lactente , Masculino , Monitorização Fisiológica/métodos , Níger/epidemiologia , Projetos PilotoRESUMO
Outpatient therapeutic feeding protocols for the treatment of uncomplicated severe acute malnutrition in children were initially based on weight gain data from inpatient settings and expert knowledge of the physiological requirements during recovery. However, weight gain and energy requirements from historic inpatient settings may differ from modern outpatient settings and therefore may not be appropriate to guide current therapeutic feeding protocols. We calculated the weight gain and average estimated total daily energy requirement of children successfully treated for uncomplicated severe acute malnutrition as outpatients in Niger (n = 790). Mean energy provided by six therapeutic feeding protocols was calculated and compared with average estimated energy requirements in the study population. Overall weight gain was 5.5 g·kg-1 ·day-1 among recovered children. Average energy requirements ranged from 92 to 110 kcal·kg-1 ·day-1 depending on the estimation approach. Two current therapeutic feeding protocols were found to provide an excess of energy after the first week of treatment in our study population, whereas four research protocols tended to provide less energy than the estimated requirement after the first week of treatment. Alternative feeding protocols have the potential to simplify and lead to important savings for programmes but should be evaluated to show adequacy to meet the energy needs of children under treatment, as well as feasibility and cost efficiency. Our findings rely on theoretical calculations based on several assumptions and should be confirmed in field studies.
Assuntos
Desnutrição , Desnutrição Aguda Grave , Criança , Fast Foods , Alimentos Fortificados , Humanos , Lactente , Desnutrição/terapia , Níger , Desnutrição Aguda Grave/terapia , Aumento de PesoRESUMO
BACKGROUND: Cholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (â¼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions. METHODS: We combined information on cholera incidence in sub-Saharan Africa (excluding Djibouti and Eritrea) from 2010 to 2016 from datasets from WHO, Médecins Sans Frontières, ProMED, ReliefWeb, ministries of health, and the scientific literature. We divided the study region into 20 kmâ×â20 km grid cells and modelled annual cholera incidence in each grid cell assuming a Poisson process adjusted for covariates and spatially correlated random effects. We combined these findings with data on population distribution to estimate the number of people living in areas of high cholera incidence (>1 case per 1000 people per year). We further estimated the reduction in cholera incidence that could be achieved by targeting cholera prevention and control interventions at areas of high cholera incidence. FINDINGS: We included 279 datasets covering 2283 locations in our analyses. In sub-Saharan Africa (excluding Djibouti and Eritrea), a mean of 141â918 cholera cases (95% credible interval [CrI] 141â538-146â505) were reported per year. 4·0% (95% CrI 1·7-16·8) of districts, home to 87·2 million people (95% CrI 60·3 million to 118·9 million), have high cholera incidence. By focusing on the highest incidence districts first, effective targeted interventions could eliminate 50% of the region's cholera by covering 35·3 million people (95% CrI 26·3 million to 62·0 million), which is less than 4% of the total population. INTERPRETATION: Although cholera occurs throughout sub-Saharan Africa, its highest incidence is concentrated in a small proportion of the continent. Prioritising high-risk areas could substantially increase the efficiency of cholera control programmes. FUNDING: The Bill & Melinda Gates Foundation.
Assuntos
Cólera/epidemiologia , Cólera/prevenção & controle , Vacinação/métodos , África Subsaariana/epidemiologia , Demografia , Humanos , Incidência , Cadeias de Markov , Vacinação em Massa , Densidade Demográfica , SaneamentoRESUMO
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.).
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Desnutrição Aguda Grave/tratamento farmacológico , Infecções Bacterianas/complicações , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Estado Nutricional , Prevalência , Desnutrição Aguda Grave/complicações , Desnutrição Aguda Grave/fisiopatologia , Falha de Tratamento , Aumento de Peso/efeitos dos fármacosRESUMO
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.
Assuntos
Antígenos de Protozoários/isolamento & purificação , Testes Diagnósticos de Rotina/estatística & dados numéricos , L-Lactato Desidrogenase/isolamento & purificação , Malária Falciparum/diagnóstico , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/isolamento & purificação , Quimioprevenção/estatística & dados numéricos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Níger , Estudos Prospectivos , Estações do AnoRESUMO
BACKGROUND: In low-resource settings, the lack of mental health professionals and cross-culturally validated screening instruments complicates mental health care delivery. This is especially the case for very young children. Here, we aimed to develop and cross-culturally validate a simple and rapid tool, the PSYCa 6-36, that can be administered by non-professionals to screen for psychological difficulties among children aged six to 36 months. METHODS: A primary validation of the PSYCa 6-36 was conducted in Kenya (n = 319 children aged 6 to 36 months; 2014), followed by additional validations in Kenya (n = 215; 2014) Cambodia (n = 189; 2015) and Uganda (n = 182; 2016). After informed consent, trained interviewers administered the PSYCa 6-36 to caregivers participating in the study. We assessed the psychometric properties of the PSYCa 6-36 and external validity was assessed by comparing the results of the PSYCa 6-36 against a clinical global impression severity [CGIS] score rated by an independent psychologist after a structured clinical interview with each participant. RESULTS: The PSYCa 6-36 showed satisfactory psychometric properties (Cronbach's alpha > 0.60 in Uganda and > 0.70 in Kenya and Cambodia), temporal stability (intra-class correlation coefficient [ICC] > 0.8), and inter-rater reliability (ICC from 0.6 in Uganda to 0.8 in Kenya). Psychologists identified psychological difficulties (CGIS score > 1) in 11 children (5.1%) in Kenya, 13 children (8.7%) in Cambodia and 15 (10.5%) in Uganda, with an area under the receiver operating characteristic curve of 0.65 in Uganda and 0.80 in Kenya and Cambodia. CONCLUSIONS: The PSYCa 6-36 allowed for rapid screening of psychological difficulties among children aged 6 to 36 months among the populations studied. Use of the tool also increased awareness of children's psychological difficulties and the importance of early recognition to prevent long-term consequences. The PSYCa 6-36 would benefit from further use and validation studies in popula`tions with higher prevalence of psychological difficulties.