Rotavirus vaccines for severe rotavirus gastroenteritis in Africa

Registration and administrative information (PROSPERO field set)

Extracted values, and where each came from

One row per extracted value. Every row carries the value, the verbatim sentence it was read from, a resolvable link to the source, and whether the number was read or derived. Where any of those is absent the row says so rather than omitting the value.

References

Included studies

• — https://clinicaltrials.gov/study/NCT00241644
• — https://clinicaltrials.gov/study/NCT00362648
• — https://clinicaltrials.gov/study/NCT02145000

Regulatory documents

Methods and guidance

Sources

Visual abstract

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: d53ddd2dd7d78487), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — visual-abstract.eps, 4 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — visual-abstract.tiff, 27,685 KB.

Projected from the canonical object, so it carries the same k, the same pooled estimate and the same interval as the paper and cannot drift from them. The interval is drawn to scale against the no-difference line, which it EXCLUDES: 0.347 to 0.704, with no difference at 1.

Risk of bias

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Only the vector format is offered for this figure, by choice: it is line art — discrete marks, glyphs and labels — which SVG reproduces exactly at any size, so a raster would add weight without adding fidelity. The build was able to rasterise; it was asked not to.

Not drawn, because there is nothing to draw it from.

GOSH

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: dd33d4f986f7c7c5), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — gosh.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — gosh.tiff, 5,537 KB.

Deliberately not drawn. Every subset meta-analysis of 3 trials is 7 points; a cloud that small cannot show the multimodality GOSH exists to reveal, and a reader would take the picture as evidence of its absence.

Trial-sequential analysis

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 25ed9800fdf56614), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — tsa.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — tsa.tiff, 6,665 KB.

TSA boundaries depend entirely on a target information size that must be pre-specified. This review's protocol registers none, so any boundary drawn here would be a parameter chosen after seeing the data -- which is the practice TSA exists to protect against.

Meta-regression

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 2316b730fa24744e), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — bubble.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — bubble.tiff, 5,537 KB.

The protocol pre-specifies no moderator, and at k = 3 a meta-regression would be fitted on 3 points. Not drawn rather than drawn with a caveat: a bubble plot invites reading a slope, and there is no slope here that any reader should read.

Summary of findings

1. No GRADE assessment or reconciliation record is held in this object, so the certainty of this evidence has not been rated. This is recorded as a declared departure under Cochrane Handbook §III.3.4.1: the review reports a pooled estimate for which no certainty assessment was made. Rating it here would require two assessors and an adjudicator, and a rating produced by neither is not a GRADE assessment whatever letter it carries.
2. Read this beside `whether the estimand was established`. That flag records that every contributing trial measures the same quantity. It records nothing about what that quantity was measured against -- whether the comparators are of one kind, whether each comparison was randomised, whether it was concurrent. The two questions were never separated. Named as P48 in PAGE-STANDARD.md v1.21.0 and swept by scripts/audit_mixed_contrast_pools.py.

Reproducibility artifact

This page CANNOT be rebuilt from what is recorded here: no canonical object is recorded and no registered commit is recorded. Each figure on the Analysis tab downloads as an SVG carrying exactly the values shown.

Other recorded qualifications

Statements this review records about the limits of what it establishes, which are not shown elsewhere on this page. They are reproduced from the object verbatim and are not summarised.

Paper

Each statement below cites the record it came from; those sources are listed at the end of every section. Where the record holds nothing, the section says so by name rather than being left out, so a procedure that was not carried out can be told from one that simply was never mentioned.

Title

Rotavirus vaccines for severe rotavirus gastroenteritis in Africa¹

Abstract

Question. In Rotavirus vaccines for severe rotavirus gastroenteritis in Africa, what do the contributing trials show?¹

Methods. estimates were pooled under a random-effects model with the REML (restricted maximum likelihood) estimator.²

Results. Multiple trial-declared outcomes: Number of Subjects With Severe Rotavirus Gastroenteritis (rv ge) Caused by the Circulating Wild-type Rotavirus Strain | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third D: odds ratio 0.494 (0.347 to 0.704) across 3 trials; 1 of these pooled outcome(s) carries a stated qualification -- a referral or a recorded finding -- given in full in Results and not reproduced here; and no statistical heterogeneity was detected (I-squared 57.6%).³

Introduction

Background. This review asks: In Rotavirus vaccines for severe rotavirus gastroenteritis in Africa, what do the contributing trials show? It pools 3 randomised trials. The outcome pooled is Multiple trial-declared outcomes: Number of Subjects With Severe Rotavirus Gastroenteritis (rv ge) Caused by the Circulating Wild-type Rotavirus Strain | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third D.¹

Methods — search

Primary trials. No bibliographic search for primary trials was run. The 3 included trials were identified by reading named registrations on the dates recorded on each entry. The basis on which this object was verified is not recorded. What this object does not claim is not recorded. The bar this object had to clear is not recorded. Published syntheses. PubMed E-utilities esearch + esummary, executed 2026-08-21. Query as executed: (rotavirus[tiab] and vaccine*[tiab] and (Africa*[tiab] OR "sub-Saharan"[tiab] OR "low-income"[tiab] OR "developing"[tiab])) and (meta-analysis[pt] OR "systematic review"[pt] OR meta-analysis[tiab] OR "pooled"[tiab] OR Cochrane[tiab]). It matched 70 record(s), of which 70 were retrieved and 70 read; 1 appraised.¹

Methods — eligibility criteria

not recorded on the page this object was extracted from¹

Methods — synthesis

For multiple trial-declared outcomes: Number of Subjects With Severe Rotavirus Gastroenteritis (rv ge) Caused by the Circulating Wild-type Rotavirus Strain | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third D, a random-effects model was fitted with the REML (restricted maximum likelihood) estimator.¹

Results

The pooled odds ratio for multiple trial-declared outcomes: Number of Subjects With Severe Rotavirus Gastroenteritis (rv ge) Caused by the Circulating Wild-type Rotavirus Strain | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third D was 0.494 (0.347 to 0.704) across 3 trials.¹

Noted on this pool. Read this beside the estimate. The unadjusted interval is OR 0.4941 (0.3466 to 0.7045) and excludes no effect. This project's hartung-knapp interval at k = 3 IS 0.2268 TO 1.0764, on t = 4.3027 with 2 degrees of freedom, and it includes no effect. The house rule already requires the adjusted interval to be shown beside the unadjusted one where k is small; on this pool the two disagree about the conclusion. A published individual-level analysis argues this kind of estimate is biased toward the null by the setting it was measured in. Amin et al., American Journal of Epidemiology 2025 (PMID 39745811), pooled 83,592 infants across 23 countries from monovalent rotavirus vaccine trials. Efficacy against severe rotavirus gastroenteritis appeared to vary from 10% to 100% between countries; after adjusting for local exposure magnitude, all but two countries fell between 80% and 86%. High-burden settings -- which include the African settings pooled here -- are where the unadjusted estimates are lowest. Stated so the caution is not discounted. At k = 2 the t critical value is 12.7062 and almost no effect survives the adjustment, so a crossing there is weak evidence. Here k = 3 and t IS 4.3027, which is a far less demanding test. There is also real spread: tau-squared 0.0557, Q 4.7195 on 2 df, I-squared 56.97%. The crossing is driven by disagreement between the trials, not by the correction being brutal at tiny k. That analysis held the vaccine class constant (monovalent) and modelled the setting. This pool combines Rotarix, RotaTeq and Rotasiil -- three different vaccines -- and pools across settings. The two designs answer different questions and theirs isolates a cause. Their 80-86% and this pool's ~51% are not two estimates of one quantity: one is exposure-adjusted single-vaccine efficacy, the other is unadjusted multi-vaccine. The finding is about design, not about a number being wrong. The stored estimate is not changed. Withdrawing or restating a published number is a content decision. What has been done is to put the adjusted interval where a reader meets the number. Read this beside the estimate. The three trials administered three different vaccines, verified against their registrations on 2026-08-21: NCT00241644 gave Rotarix, a monovalent human vaccine; NCT00362648 gave RotaTeq, a pentavalent human-bovine reassortant; NCT02145000 gave BRV-PV, a pentavalent bovine vaccine. They differ in valency, in strain origin and in manufacturer. A single pooled odds ratio across them estimates the average effect of three products, not the effect of a rotavirus vaccine, and a reader deciding about one product cannot take this number as its efficacy. I-squared is 57.6%, which is consistent with that and does not establish it. The stored point is 0.4940987113879037 on an interval running from 0.347 to 0.704. Fifteen of those sixteen digits are noise: the interval is 0.36 wide, so the estimate is not determined beyond the second decimal place. Reporting it at sixteen figures asserts a precision the data cannot carry, and it is the same defect as a displayed value the engine could not compute -- a number saying more than its evidence. The value is not rounded here, because it is a published number; what is recorded is that it should be read as 0.49 (0.35 to 0.70).²

The trials' results were moderately consistent with one another: I-squared, the share of the variation between them that is more than chance alone would produce, was 57.6%; the estimated variance of the true effects between trials (tau-squared) was 0.0572, the heterogeneity test statistic Q was 4.72, on degrees of freedom 2.³

The grounds for pooling are recorded as: The extractor recovered a pooled result from this page, so the page pooled these trials. Whether they should have been pooled is not established by conversion - several pages in this corpus pooled harm with efficacy, or distinct agents, and their estimates were withdrawn for that reason. Where a later pool on this page rests on the same grounds, they are not restated.⁴

The full model output for every pooled outcome -- the call, the estimator, the heterogeneity statistics and the back-transformed interval -- is stored verbatim on this review object at `results.by_outcome.<outcome>.r_output.verbatim`. It is not reproduced as an Extended data section in this article; an earlier version of this sentence said it was, and no such section exists.⁵

Comparison with published syntheses

Published syntheses were identified as follows. PubMed E-utilities, executed 2026-08-21. Query, counts and per-record disposition in ssot/rotavirus-vaccine-africa-review/appraisal/the screen of published syntheses.json.¹

Limitations

What this review does not give a clinician: the number of events in each arm, any absolute effect or number needed to treat and any measure of harm. A relative effect cannot be turned into the benefit or the risk facing one patient without them, so this review can support a judgement about what these trials found and not a judgement about what to do.¹

Software availability

Analyses were computed under R 4.6.0 with metafor 5.0.1.¹

Reporting guidelines

This review reports against PRISMA 2020. A screening record is held on this object and the flow it supports is shown in the Methods. The completed PRISMA checklist and FLOW diagram are not held here: the venue requires them deposited in an approved repository with a DOI cited in the Data Availability Statement, and minting that DOI is an author action rather than a build step.¹

Note on registration

No PROSPERO registration or protocol record is held on this object. That is not the same as knowing this review was not registered, and neither claim is made. It is recorded here as an absence so that a reader does not have to infer it from silence.¹

References

Figures

Trial characteristics

Not reported in this record

The items below were not written because the record does not hold what they would be composed from. They are named here so that an absence is not mistaken for an omission.