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

Isanaka, Sheila; Guindo, Ousmane; Langendorf, Céline; Seck, Amadou; Plikaytis, Brian D.; Sayinzoga-Makombe, Nathan; McNeal, Monica; Meyer, Nicole; Adéhossi, Eric; Djibo, Ali; Jochum, Bruno; Grais, Rebecca F.

doi:10.1056/nejmoa1609462

Cited by 144 publications

(155 citation statements)

References 39 publications

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“…Similarly, the Lewis-negative phenotype is significantly more common in parts of Africa (reaching >30% in some populations) than in Caucasians (4-6%) [83]. Thus, an impaired replicative capacity of P [8] strains combined with the high prevalence of P [6] genotypes in Lewis-negative individuals, as reported in Burkina Faso [78], would be consistent with observed discrepancies in rotavirus vaccine efficacy.…”

Section: Histo Blood Group Antigenssupporting

confidence: 63%

“…Binding to HBGA occurs through the VP8* domain of protein VP4 [76,77]. To date, 47 VP4 (P) genotypes have been identified, of which P [4], P [6] and P [8] are most common. A recent systematic review based on studies in France, Vietnam, the USA and Burkina Faso documented a 27-fold increase in susceptibility to P [8] rotavirus in secretors versus nonsecretors, but showed no association between secretor status and susceptibility to P [4] or P [6] genotypes [75].…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

“…To date, 47 VP4 (P) genotypes have been identified, of which P [4], P [6] and P [8] are most common. A recent systematic review based on studies in France, Vietnam, the USA and Burkina Faso documented a 27-fold increase in susceptibility to P [8] rotavirus in secretors versus nonsecretors, but showed no association between secretor status and susceptibility to P [4] or P [6] genotypes [75]. In Burkina Faso, no Lewis-negative secretors (expressing H type 1 antigen) were infected with P [8] strains, despite making up 25% of the study population [78], suggesting that the infectivity of P [8] strains may be dependent on both secretor and Lewis status.…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

“…Currently licensed oral vaccines include live-attenuated poliovirus vaccines containing one, two or three serotypes, live-attenuated rotavirus vaccines (Rotarix R , RotaTeq R , Lanzhou lamb rotavirus vaccine [China only] and Rotavac R [India only]), live-attenuated cholera vaccine (CVD 103-HgR or Vaxchora TM ), inactivated cholera vaccines (Dukoral R and Shanchol R ) and live-attenuated typhoid vaccine (Ty21a). Other oral vaccines are in development, including those against Shigella, enterotoxigenic E. coli, Campylobacter and Clostridium difficile, as well as several novel rotavirus vaccine candidates (including the human neonatal vaccine RV3-BB [5] and an oral bovine pentavalent vaccine [6]). …”

mentioning

confidence: 99%

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Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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Oral vaccines are less immunogenic when given to infants in low-income compared with high-income countries, limiting their potential public health impact. Here, we review factors that might contribute to this phenomenon, including transplacental antibodies, breastfeeding, histo blood group antigens, enteric pathogens, malnutrition, microbiota dysbiosis and environmental enteropathy. We highlight several clear risk factors for vaccine failure, such as the inhibitory effect of enteroviruses on oral poliovirus vaccine. We also highlight the ambiguous and at times contradictory nature of the available evidence, which undoubtedly reflects the complex and interconnected nature of the factors involved. Mechanisms responsible for diminished immunogenicity may be specific to each oral vaccine. Interventions aiming to improve vaccine performance may need to reflect the diversity of these mechanisms. Enteric pathogens are a substantial threat to public health. This threat takes many forms, from the toxin-producing bacteria (e.g., Vibrio cholerae) and flagellated protozoa (e.g., Giardia lamblia) that colonize the mucosal surface of the small intestine to the enteroviruses that are capable of spreading via the bloodstream to the CNS, causing acute flaccid paralysis (e.g., poliovirus). Each year, enteric pathogens cause hundreds of millions of cases of diarrhea and approximately 800,000 deaths, the vast majority of which occur among children in low-income countries [1]. The most common causes of childhood diarrheal morbidity include rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli and Shigella [2].Vaccines against enteric pathogens are important tools for mitigating this disease burden. Oral vaccines offer several distinct benefits compared with parenteral vaccines. They can be produced in large quantities at relatively low cost, are easy to administer and have the capacity to induce local immunity in the intestinal mucosa, thereby protecting vaccinated individuals against subsequent infection and -by blocking onward transmission -enhancing herd immunity [3,4]. Currently licensed oral vaccines include live-attenuated poliovirus vaccines containing one, two or three serotypes, live-attenuated rotavirus vaccines (Rotarix R , RotaTeq R , Lanzhou lamb rotavirus vaccine [China only] and Rotavac R [India only]), live-attenuated cholera vaccine (CVD 103-HgR or Vaxchora TM ), inactivated cholera vaccines (Dukoral R and Shanchol R ) and live-attenuated typhoid vaccine (Ty21a). Other oral vaccines are in development, including those against Shigella, enterotoxigenic E. coli, Campylobacter and Clostridium difficile, as well as several novel rotavirus vaccine candidates (including the human neonatal vaccine RV3-BB [5] and an oral bovine pentavalent vaccine [6]).Yet oral vaccines have an Achilles' heel -their immunogenicity and efficacy is impaired in low-income countries that experience the greatest burden of enteric disease (Box 1). For example, Rotarix has a 1-year protective efficacy against severe rotavirus-associated gas...

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Section: Histo Blood Group Antigenssupporting

confidence: 63%

Section: Genetic Risk Factorsmentioning

confidence: 99%

Section: Genetic Risk Factorsmentioning

confidence: 99%

mentioning

confidence: 99%

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Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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“…Recently [20] estimated that 3 doses of vaccine had 66.7% efficacy against severe RVGE among children in Niger. Though we do not explicitly account for 3 doses of vaccine, we can calculate the effective seroconversion rate for our model above that would yield this observed efficacy after a complete sequence of doses.…”

Section: A21 Projections Based On Vaccine Efficacy From a Recent Studymentioning

confidence: 99%

An ensemble approach to predicting the impact of vaccination on rotavirus disease in Niger

Park

Goldstein

Haran

et al. 2017

Vaccine

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Recently developed vaccines provide a new way of controlling rotavirus in sub-Saharan Africa.Models for the transmission dynamics of rotavirus are critical both for estimating current burden from imperfect surveillance and for assessing potential effects of vaccine intervention strategies.We examine rotavirus infection in the Maradi area in southern Niger using hospital surveillance data provided by Epicentre collected over two years. Additionally, a cluster survey of households in the region allows us to estimate the proportion of children with diarrhea who consulted at a health structure. Model fit and future projections are necessarily particular to a given model; thus, where there are competing models for the underlying epidemiology an ensemble approach can account for that uncertainty. We compare our results across several variants of Susceptible-Infectious-Recovered (SIR) compartmental models to quantify the impact of modeling assumptions on our estimates. Model-specific parameters are estimated by Bayesian inference using Markov chain Monte Carlo. We then use Bayesian model averaging to generate ensemble estimates of the current dynamics, including estimates of R0, the burden of infection in the region, as well as the impact of vaccination on both the short-term dynamics and the long-term reduction of rotavirus incidence under varying levels of coverage. The ensemble of models predicts that the current burden of severe rotavirus disease is 2.9 to 4.1% of the population each year and that a 2-dose vaccine schedule achieving 70% coverage could reduce burden by 37-43%.

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Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances

Orkin

Gill

Ghersi

et al. 2021

JAMA

194

185

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for the CONSERVE Group IMPORTANCE Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete.OBJECTIVE As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances. EVIDENCE A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders.FINDINGS The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses.CONCLUSIONS AND RELEVANCE CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.

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

Abstract: 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 .).

Cited by 144 publications

References 39 publications

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

An ensemble approach to predicting the impact of vaccination on rotavirus disease in Niger

Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances

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