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.

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

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

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.

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.

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 .).