Journal Article > ResearchFull Text
BMC Nutr. 2019 July 1; Volume 5; DOI:10.1186/s40795-019-0298-3
Isanaka S, Kodish SR, Mamaty AA, Guindo O, Zeilani M, et al.
BMC Nutr. 2019 July 1; Volume 5; DOI:10.1186/s40795-019-0298-3
Background
In food insecure settings, it may be difficult for pregnant women to meet increased nutritional needs through traditional diets. A promising new strategy to fill nutrient gaps in pregnancy involves the provision of lipid-based nutrient supplements (LNS). We aimed to assess the acceptability and utilization of a 40 g LNS formulation (Epi-E) with increased micronutrient content relative to the recommended daily allowance among pregnant women in rural Niger.
Methods
We conducted a two-part, multi-methods study among pregnant women presenting to antenatal care in Madarounfa, Niger during two periods (Ramadan and non-Ramadan). Part 1 included two LNS test meals provided at the health center, and Part 2 included a 14-day home trial to simulate more realistic conditions outside of the health center. Open- and closed-ended questions were used to assess organoleptic properties of Epi-E using a 5-point hedonic scale after the test meals, as well as utilization and willingness to pay for Epi-E after the 14-day home trial.
Results
Participants consumed more than 90% of the test meal in both periods. Epi-E was rated highly in terms of overall liking, color, taste and smell during test meals in both periods (median 5/5 for all); only time, mode and frequency of consumption varied between Ramadan and non-Ramadan periods in observance of daily fasting during the holy month.
Conclusion
Epi- E, a 40 g LNS formulation with increased micronutrient content, was highly acceptable among pregnant women in rural Niger, and utilization was guided by household and individual considerations that varied by time period. This formulation can be further tested as a potential strategy to improve the nutritional status of pregnant women in this context.
In food insecure settings, it may be difficult for pregnant women to meet increased nutritional needs through traditional diets. A promising new strategy to fill nutrient gaps in pregnancy involves the provision of lipid-based nutrient supplements (LNS). We aimed to assess the acceptability and utilization of a 40 g LNS formulation (Epi-E) with increased micronutrient content relative to the recommended daily allowance among pregnant women in rural Niger.
Methods
We conducted a two-part, multi-methods study among pregnant women presenting to antenatal care in Madarounfa, Niger during two periods (Ramadan and non-Ramadan). Part 1 included two LNS test meals provided at the health center, and Part 2 included a 14-day home trial to simulate more realistic conditions outside of the health center. Open- and closed-ended questions were used to assess organoleptic properties of Epi-E using a 5-point hedonic scale after the test meals, as well as utilization and willingness to pay for Epi-E after the 14-day home trial.
Results
Participants consumed more than 90% of the test meal in both periods. Epi-E was rated highly in terms of overall liking, color, taste and smell during test meals in both periods (median 5/5 for all); only time, mode and frequency of consumption varied between Ramadan and non-Ramadan periods in observance of daily fasting during the holy month.
Conclusion
Epi- E, a 40 g LNS formulation with increased micronutrient content, was highly acceptable among pregnant women in rural Niger, and utilization was guided by household and individual considerations that varied by time period. This formulation can be further tested as a potential strategy to improve the nutritional status of pregnant women in this context.
Journal Article > ResearchFull Text
PLOS Med. 2021 August 10; Volume 18 (Issue 8); e1003720.; DOI:10.1371/journal.pmed.1003720
Isanaka S, Garba S, Plikaytis BD, McNeal MM, Guindo O, et al.
PLOS Med. 2021 August 10; Volume 18 (Issue 8); e1003720.; DOI:10.1371/journal.pmed.1003720
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.
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.
Journal Article > ResearchFull Text
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 2019 June 1
Chotsiri P, Denoeud-Ndam L, Baudin E, Guindo O, Diawara H, et al.
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 2019 June 1
Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub‐Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic‐pharmacodynamic study included 131 SAM and 266 non‐SAM children administered artemether‐lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit‐absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the pharmacokinetic model. Mid‐upper arm circumference (MUAC) was associated with decreased absorption of lumefantrine (25.4% decrease per 1 cm reduction). Risk of recurrent malaria episodes (i.e. reinfection) were characterised by an interval‐censored time‐to‐event model with a sigmoid EMAX‐model describing the effect of lumefantrine. SAM children were at risk of under‐exposure to lumefantrine and an increased risk of malaria reinfection compared to well‐nourished children. Research on optimised regimens should be considered for malaria treatment in malnourished children.
Conference Material > Video (talk)
Guindo O
Epicentre Scientific Day Paris 2020. 2020 September 24
Journal Article > ResearchFull Text
BMC Nutr. 2021 August 12; Volume 7(1) (Issue 47); DOI:10.1186/s40795-021-00448-w
Garba S, Salou H, Nackers F, Ayouba A, Guindo O, et al.
BMC Nutr. 2021 August 12; Volume 7(1) (Issue 47); DOI:10.1186/s40795-021-00448-w
BACKGROUND
The World Health Organization recommends the use of a weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC) as anthropometric criteria for the admission and discharge of young children for the community-based management of severe acute malnutrition. However, using MUAC as a single anthropometric criterion for admission and discharge in therapeutic nutritional programs may offer operational advantages to simplify admission processes at therapeutic nutritional centers and improve program coverage.
METHOD
This pragmatic, non-randomized, intervention study compared a standard outpatient nutritional program (n = 824) for the treatment of uncomplicated severe acute malnutrition using WHZ < - 3 and/or MUAC< 115 mm and/or bipedal edema for admission and discharge to a program (n = 1019) using MUAC as the sole anthropometric criterion for admission (MUAC< 120 mm) and discharge (MUAC ≥125 mm at two consecutive visits) in the Tahoua Region of Niger.
RESULTS
Compared to the standard program, the MUAC-only program discharged more children as recovered (70.1% vs. 51.6%; aOR 2.31, 95%CI 1.79-2.98) and fewer children as non-respondent or defaulters, based on respective program definitions. The risk of non-response was high in both programs. Three months post-discharge, children who were discharged after recovery in the MUAC-only program had lower WHZ and MUAC measures. Sixty-three children ineligible for the MUAC-only program but eligible for a standard program (MUAC ≥120 mm and WHZ < -3) were followed for twelve weeks and the anthropometric status of 69.8% of these children did not deteriorate (i.e. MUAC ≥120 mm) despite not immediately receiving treatment in the MUAC-only program.
CONCLUSION
The results from this study share the first operational experience of using MUAC as sole anthropometric criterion for admission and discharge in Niger and overall support the consideration for MUAC-only programming: the MUAC-only model of care was associated with a higher recovery and a lower defaulter rate than the standard program with very few children found to be excluded from treatment with an admission criterion of MUAC < 120 mm. Further consideration of the appropriate MUAC-based discharge criterion as it relates to an increased risk of non-response and adverse post-discharge outcomes would be prudent.
The World Health Organization recommends the use of a weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC) as anthropometric criteria for the admission and discharge of young children for the community-based management of severe acute malnutrition. However, using MUAC as a single anthropometric criterion for admission and discharge in therapeutic nutritional programs may offer operational advantages to simplify admission processes at therapeutic nutritional centers and improve program coverage.
METHOD
This pragmatic, non-randomized, intervention study compared a standard outpatient nutritional program (n = 824) for the treatment of uncomplicated severe acute malnutrition using WHZ < - 3 and/or MUAC< 115 mm and/or bipedal edema for admission and discharge to a program (n = 1019) using MUAC as the sole anthropometric criterion for admission (MUAC< 120 mm) and discharge (MUAC ≥125 mm at two consecutive visits) in the Tahoua Region of Niger.
RESULTS
Compared to the standard program, the MUAC-only program discharged more children as recovered (70.1% vs. 51.6%; aOR 2.31, 95%CI 1.79-2.98) and fewer children as non-respondent or defaulters, based on respective program definitions. The risk of non-response was high in both programs. Three months post-discharge, children who were discharged after recovery in the MUAC-only program had lower WHZ and MUAC measures. Sixty-three children ineligible for the MUAC-only program but eligible for a standard program (MUAC ≥120 mm and WHZ < -3) were followed for twelve weeks and the anthropometric status of 69.8% of these children did not deteriorate (i.e. MUAC ≥120 mm) despite not immediately receiving treatment in the MUAC-only program.
CONCLUSION
The results from this study share the first operational experience of using MUAC as sole anthropometric criterion for admission and discharge in Niger and overall support the consideration for MUAC-only programming: the MUAC-only model of care was associated with a higher recovery and a lower defaulter rate than the standard program with very few children found to be excluded from treatment with an admission criterion of MUAC < 120 mm. Further consideration of the appropriate MUAC-based discharge criterion as it relates to an increased risk of non-response and adverse post-discharge outcomes would be prudent.
Conference Material > Abstract
Idrissa AA, Atti S, Wasaulua RK, Kazadi S, Guindo O, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/wg9g-dq47
INTRODUCTION
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
Journal Article > ResearchFull Text
J R Soc Interface. 2020 August 26; Volume 17 (Issue 169); DOI:10.1098/rsif.2020.0480
Blake A, Djibo A, Guindo O, Bharti N
J R Soc Interface. 2020 August 26; Volume 17 (Issue 169); DOI:10.1098/rsif.2020.0480
Measles is a major cause of child mortality in sub-Saharan Africa. Current immunization strategies achieve low coverage in areas where transmission drivers differ substantially from those in high-income countries. A better understanding of measles transmission in areas with measles persistence will increase vaccination coverage and reduce ongoing transmission. We analysed weekly reported measles cases at the district level in Niger from 1995 to 2004 to identify underlying transmission mechanisms. We identified dominant periodicities and the associated spatial clustering patterns. We also investigated associations between reported measles cases and environmental drivers associated with human activities, particularly rainfall. The annual and 2-3-year periodicities dominated the reporting data spectrum. The annual periodicity was strong with contiguous spatial clustering, consistent with the latitudinal gradient of population density, and stable over time. The 2-3-year periodicities were weaker, unstable over time and had spatially fragmented clustering. The rainy season was associated with a lower risk of measles case reporting. The annual periodicity likely reflects seasonal agricultural labour migration, whereas the 2-3-year periodicity potentially results from multiple mechanisms such as reintroductions and vaccine coverage heterogeneity. Our findings suggest that improving vaccine coverage in seasonally mobile populations could reduce strong measles seasonality in Niger and across similar settings.
Journal Article > ResearchFull Text
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 2019 October 25; Volume 107 (Issue 5); 1179-1188.; DOI:10.1002/cpt.1707
Ding J, Coldiron ME, Assao B, Guindo O, Blessborn D, et al.
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 2019 October 25; Volume 107 (Issue 5); 1179-1188.; DOI:10.1002/cpt.1707
Poor adherence to seasonal malaria chemoprevention (SMC) might affect the protective effectiveness of SMC. Here, we evaluated the population pharmacokinetic properties of amodiaquine and its active metabolite, desethylamodiaquine, in children receiving SMC under directly observed ideal conditions (n = 136), and the adherence of SMC at an implementation phase in children participating in a case-control study to evaluate SMC effectiveness (n = 869). Amodiaquine and desethylamodiaquine concentration-time profiles were described simultaneously by two-compartment and three-compartment disposition models, respectively. The developed methodology to evaluate adherence showed a sensitivity of 65-71% when the first dose of SMC was directly observed and 71-73% when no doses were observed in a routine programmatic setting. Adherence simulations and measured desethylamodiaquine concentrations in the case-control children showed complete adherence (all doses taken) in < 20% of children. This result suggests that more efforts are needed urgently to improve the adherence to SMC among children in this area.
Journal Article > ResearchFull Text
PLOS Med. 2021 July 2; Volume 18 (Issue 7); e1003655.; DOI:10.1371/journal.pmed.1003655
Isanaka S, Langendorf C, McNeal MM, Meyer N, Plikaytis BD, et al.
PLOS Med. 2021 July 2; Volume 18 (Issue 7); e1003655.; DOI:10.1371/journal.pmed.1003655
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.
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.
Journal Article > ResearchFull Text
N Engl J Med. 2017 March 23; Volume 376 (Issue 12); 1121-1130.; DOI:10.1056/NEJMoa1609462
Isanaka S, Guindo O, Langendorf C, Matar Seck A, Plikaytis BD, et al.
N Engl J Med. 2017 March 23; Volume 376 (Issue 12); 1121-1130.; DOI:10.1056/NEJMoa1609462
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 .).
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 .).