Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin-piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial.
Barsosio HC, Madanitsa M, Ondieki ED, Dodd J, Onyango ED, Otieno K, Wang D, Hill J, Mwapasa V, Phiri KS, Maleta K, Taegtmeyer M, Kariuki S, Schmiegelow C, Gutman JR, Ter Kuile FO
- DOI
- 10.1016/S0140-6736(23)02631-4
- Record issued
- 2026-08-10
- Engine
- 7.29.0
- Exported
- 2026-09-22
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/779f1403-6c3c-481b-a32d-efa63c75144f is authoritative.
How this rating was calculated
- ReportingEthical approvals partially met−0.25★
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run on this paper: the pass that reads its reported means did not complete. No reported mean was checked for arithmetic impossibility.
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
The paper presents a well-designed and reported randomised controlled trial with strong methodological rigor. The main weaknesses are the absence of an explicit regulatory compliance statement (e.g., Declaration of Helsinki) and a missing reference to the CONSORT reporting guideline, both minor reporting gaps. The study's statistical analyses are sound, and data availability is adequately addressed.
Both independent reviewers (AI) agreed on all dimension statuses, with minor checklist-level disagreements on biological variables (sex justification) and statistical analysis (assumptions verification). The copyedit pass identified three minor issues. The statistics verification found 8/8 recomputed tests consistent, and no citation integrity issues were flagged.
Numerical inconsistencies
None foundValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
Checked — nothing surfaced.
Recomputed 8 tests: 8 consistent, 0 inconsistent; 6 recomputed directly from the reported test statistics, 2 via agent-written checks.
- CONSISTENTreported p < .001 · recomputed p = <.001Recomputed risk ratio 0.45 (95% CI 0.30–0.67), reported p=0.0001
“risk ratio 0.45, 95% CI 0.30–0.67; p=0.0001”
Taken as given: 0.30–0.67 is a two-sided 95% confidence interval for the risk ratio of 0.45, not a range, an IQR, or a different interval level; the risk ratio is a RATIO measure, so the interval is symmetric on the log scale; p=0.0001 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(0.45, 0.3, 0.67, 1) - CONSISTENTreported p < .001 · recomputed p = <.001Recomputed RR 0.45 (95% CI 0.30–0.67), reported p=0.0001
“RR 0.45, 95% CI 0.30–0.67; p=0.0001”
Taken as given: 0.30–0.67 is a two-sided 95% confidence interval for the RR of 0.45, not a range, an IQR, or a different interval level; the RR is a RATIO measure, so the interval is symmetric on the log scale; p=0.0001 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(0.45, 0.3, 0.67, 1) - CONSISTENTreported p = .056 · recomputed p = .058Recomputed IRR 0.29 (95% CI 0.08–1.03), reported p=0.056
“IRR 0.29 [95% CI 0.08–1.03], p=0.056”
Taken as given: 0.08–1.03 is a two-sided 95% confidence interval for the IRR of 0.29, not a range, an IQR, or a different interval level; the IRR is a RATIO measure, so the interval is symmetric on the log scale; p=0.056 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(0.29, 0.08, 1.03, 1) - CONSISTENTreported p = .002 · recomputed p = .003Recomputed RR 0.37 (95% CI 0.19–0.70), reported p=0.0023
“RR 0.37, 95% CI 0.19–0.70, p=0.0023”
Taken as given: 0.19–0.70 is a two-sided 95% confidence interval for the RR of 0.37, not a range, an IQR, or a different interval level; the RR is a RATIO measure, so the interval is symmetric on the log scale; p=0.0023 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(0.37, 0.19, 0.7, 1) - CONSISTENTreported p = .004 · recomputed p = .003Recomputed RR 0.62 (95% CI 0.45–0.85), reported p=0.0036
“RR 0.62, 95% CI 0.45–0.85, p=0.0036”
Taken as given: 0.45–0.85 is a two-sided 95% confidence interval for the RR of 0.62, not a range, an IQR, or a different interval level; the RR is a RATIO measure, so the interval is symmetric on the log scale; p=0.0036 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(0.62, 0.45, 0.85, 1) - CONSISTENTreported p = .390 · recomputed p = .394Recomputed RR 1.33 (95% CI 0.69–2.56), reported p=0.39
“RR 1.33, 95% CI 0.69–2.56, p=0.39”
Taken as given: 0.69–2.56 is a two-sided 95% confidence interval for the RR of 1.33, not a range, an IQR, or a different interval level; the RR is a RATIO measure, so the interval is symmetric on the log scale; p=0.39 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(1.33, 0.69, 2.56, 1) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1Incidence rate ratio (IRR 0.32, 95% CI 0.22-0.47, p<0.0001) for all malaria episodes.
“The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the cotrimoxazole plus dihydroartemisinin–piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22–0·47, p<0·0001).”
Taken as given: The CI is a two-sided 95% confidence interval.; The p-value is two-sided for the null hypothesis IRR=1.; The ratio is analysed on the log scale.Method: Recomputed two-sided p from the reported IRR and 95% CI using pCI with log=1.How we recomputed it: pCI(0.32,0.22,0.47,1) - CONSISTENTreported p = .021 · recomputed p = .018Reviewer 1Active placental malaria risk ratio (RR 0.23, 95% CI 0.07-0.80, p=0.021).
“risk of active placental malaria detected by histology was also lower in the co-trimoxazole plus dihydroartemisinin–piperaquine group (RR 0·23, 0·07–0·80, p=0·021)”
Taken as given: The CI is a two-sided 95% confidence interval.; The p-value is two-sided for the null hypothesis RR=1.; The ratio is analysed on the log scale.Method: Recomputed two-sided p from the reported RR and 95% CI using pCI with log=1.How we recomputed it: pCI(0.23,0.07,0.80,1)
Overstated conclusions
1 finding · worst lowConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Conclusions only partially backed by the presented evidenceAssessed
9 major claims checked against the paper's own evidence: all adequately supported.
- partialReviewers 1, 2The risk of adverse pregnancy outcomes did not differ between groups.No significant differences were observed, but the paper itself cautions that the study was underpowered for birth outcomes and that confidence intervals were wide, so the flat wording somewhat overstates the certainty of 'no difference'.Evidence: Composite adverse pregnancy outcome RR 0·93 (95% CI 0·74–1·16); Discussion states 'the study was not powered to address adverse pregnancy outcomes, and the results were too imprecise to provide assurances'.
“The risk of adverse pregnancy outcomes did not differ between groups.”
DiscussionFind in source - supportedReviewer 1Addition of monthly intermittent preventive treatment with dihydroartemisinin–piperaquine to daily co-trimoxazole substantially improves malaria chemoprevention and should be considered for policy.The primary and key secondary efficacy analyses directly back the claim, with a large, significant reduction in malaria infection and comparable safety.Evidence: Primary endpoint RR 0·45 (95% CI 0·30–0·67, p=0·0001); incidence IRR 0·32 (95% CI 0·22–0·47, p<0·0001); SAE rates similar between groups.
“Addition of monthly intermittent preventive treatment with dihydroartemisinin–piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy.”
InterpretationFind in source - supportedReviewer 1The cumulative risk of any malaria infection during pregnancy or delivery was lower in the DHA-PPQ plus co-trimoxazole group than in the placebo plus co-trimoxazole group.Directly demonstrated by the cumulative risk analysis with a significant risk ratio.Evidence: 31/443 women vs 70/452 women; RR 0·45 (95% CI 0·30–0·67, p=0·0001).
“The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin–piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30–0·67; p=0·0001).”
AbstractFind in source - supportedReviewer 1Both regimens were well tolerated.Safety endpoints show similar serious adverse event rates and only mild, transient nausea; QTc changes were asymptomatic.Evidence: Maternal SAE rate 17.7 vs 17.8 per 100 person-years; no participant had QTc >500 ms; nausea 7% vs 3%.
“Both regimens were well tolerated.”
ResultsFind in source - supportedReviewer 1The efficacy of dihydroartemisinin–piperaquine is retained in pregnant women on dolutegravir-based cART.The trial's efficacy findings, together with the cited pharmacokinetic study in 13 Malawian women, support retained efficacy on dolutegravir.Evidence: Significant malaria reduction in the trial; prior PK study showed piperaquine exposure similar to that in pregnant/non-pregnant women without HIV.
By contrast with women on efavirenz-based cART, a known inducer of CYP3A4, which metabolises piperaquine, our findings suggest that the efficacy of dihydroartemisinin–piperaquine is retained in pregnant women on dolutegravir.
Discussionreviewer’s wording - supportedReviewer 1Monthly IPTp with DHA-PPQ combined with daily co-trimoxazole in women with HIV on dolutegravir is as effective as IPTp with DHA-PPQ alone in women without HIV.The paper's indirect comparison with six completed trials in HIV-negative women shows similar effect sizes, supporting the 'as effective' suggestion, though the comparison is cross-trial.Evidence: Six completed trials in HIV-negative women: reductions in clinical malaria IRR 0·32, any malaria at delivery RR 0·39, active placental malaria RR 0·29.
“These findings suggest that monthly IPTp with dihydroartemisinin–piperaquine, when combined with daily co-trimoxazole in women with HIV on dolutegravir-based cART, is as effective in preventing malaria infections as IPTp with dihydroartemisinin–piperaquine alone in women without HIV.”
DiscussionFind in source - supportedReviewer 2Addition of monthly IPTp with DHA-PPQ to daily co-trimoxazole substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART.The primary endpoint shows a significant reduction in malaria infection (RR 0.45, 95% CI 0.30-0.67, p=0.0001), supporting the claim.Evidence: Primary endpoint: cumulative risk 7% vs 15%, RR 0.45, p=0.0001.
“The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin–piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30–0·67; p=0·0001).”
Figure 2Find in source - supportedReviewer 2The combination of co-trimoxazole plus dihydroartemisinin–piperaquine was well tolerated.Safety data show similar serious adverse events between groups, and nausea was mild and transient.Evidence: Table 3: similar SAE rates, nausea 7% vs 3% but mild.
Both regimens were well tolerated. Overall, two (<1%) of 446 women in the co-trimoxazole plus dihydroartemisinin–piperaquine group and three (1%) of 455 women in the co-trimoxazole plus placebo group vomited within 30 min of an initial dose...
Table 3reviewer’s wording - supportedReviewer 2The incidence of serious adverse events was similar between groups in mothers and infants.SAE rates per 100 person-years are nearly identical in mothers and infants.Evidence: Table 3: mothers 17.7 vs 17.8, infants 45.4 vs 40.2.
The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin–piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]).
Table 3reviewer’s wording
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
1 finding · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Ethics/consent reporting incompleteAssessed
The Introduction and 'Research in context' section cite prior trials of IPTp with mefloquine, the inconclusive Ugandan pilot of DHA-PPQ in efavirenz-based cART, and pharmacokinetic studies showing an efavirenz interaction, explicitly acknowledging weaknesses such as poor tolerability and drug–drug interactions. The premise is that antifolate resistance threatens co-trimoxazole and that dolutegravir-based cART avoids the prior interaction, directly motivating the trial. All three sub-criteria are adequately covered.
“IPTp with dihydroartemisinin–piperaquine has only been assessed in a small trial of 200 pregnant women living with HIV receiving efavirenz-based cART in Uganda. The study was inconclusive.”
“Unlike efavirenz, no clinically relevant drug–drug interactions have been seen between dihydroartemisinin–piperaquine and dolutegravir in pregnancy.”
“Currently, high-level resistance of Plasmodium falciparum to sulfadoxine–pyrimethamine in east and southern Africa threatens the antimalarial efficacy of daily co-trimoxazole because both are sulfa-based antifolate drugs with similar antimalarial modes of action.”
“Unlike efavirenz, no clinically relevant drug–drug interactions have been seen between dihydroartemisinin–piperaquine and dolutegravir in pregnancy.”
Randomisation was computer-generated, permuted-block, stratified by site and HIV status; the unit of randomisation was the individual participant. Masking covered participants, investigators, laboratory staff, and data analysts, with placebo tablets identical in appearance. Power was explicitly calculated for 80% power to detect a 50% reduction, requiring 898 participants. Eligibility criteria are detailed, and the analysis approach is pre-specified with modified ITT, per-protocol, and safety populations plus non-responder imputation sensitivity analysis. Bench-oriented criteria such as replicate distinction, wet-lab controls, and internal replication are not applicable to a human RCT.
“Balanced randomisation was done using computer-generated permuted block randomisation stratified by site and HIV status (women diagnosed with HIV before enrolment as documented in their existing health records [ie, known positive] vs newly diagnosed).”
“All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment.”
“The study was designed to achieve 80% power to detect a 50% reduction in the cumulative incidence of Plasmodium infection from 12% in the co-trimoxazole plus placebo group to 6% in the co-trimoxazole plus dihydroartemisinin–piperaquine group (risk ratio [RR] 0·50, two-sided α=0·05), which required 898 participants (449 per group), allowing for 20% loss to follow-up.”
“Balanced randomisation was done using computer-generated permuted block randomisation stratified by site and HIV status”
“All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment.”
“The study was designed to achieve 80% power to detect a 50% reduction in the cumulative incidence of Plasmodium infection from 12% in the co-trimoxazole plus placebo group to 6% in the co-trimoxazole plus dihydroartemisinin–piperaquine group (risk ratio [RR] 0·50, two-sided α=0·05), which required 898 participants (449 per group), allowing for 20% loss to follow-up.”
All participants are women, and the study is in pregnant women, so sex is reported. Age, weight, gestational age, HIV status, etc. are given. Demographics such as residence, education, socioeconomic status are provided.
“Maternal age (years) | 29·2 (5·6) | 29·2 (5·7)”
“Newly diagnosed HIV infection | 75/448 (17%) | 77/456 (17%) | | Known HIV infection | 373/448 (83%) | 379/456 (83%)”
IRB approval from KEMRI, College of Medicine Malawi, and Liverpool School of Tropical Medicine is stated. Written informed consent was obtained. However, the paper does not mention adherence to a specific regulatory framework such as ICH-GCP or the Declaration of Helsinki.
“Ethics committees of the Kenya Medical Research Institute (KEMRI), the College of Medicine in Malawi, and the Liverpool School of Tropical Medicine approved the study.”
“All participants provided written informed consent.”
“Ethics committees of the Kenya Medical Research Institute (KEMRI), the College of Medicine in Malawi, and the Liverpool School of Tropical Medicine approved the study.”
“All participants provided written informed consent.”
Reagents: D-Artepp (Fosun Pharma) and Sulfran-DS (Universal Corporation) are described with strengths and doses. Software: Stata version 17 is named. Other resource categories are not applicable.
“Daily co-trimoxazole consisted of one double-strength tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim (Sulfran-DS, Universal Corporation, Nairobi, Kenya).”
“Each monthly dihydroartemisinin–piperaquine course consisted of a fixed dose of three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine (D-Artepp, Fosun Pharma, Shanghai, China) given daily for 3 days until delivery.”
“Statistical analyses were done with Stata version 17.”
“Each monthly dihydroartemisinin–piperaquine course consisted of a fixed dose of three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine (D-Artepp, Fosun Pharma, Shanghai, China)”
“Daily co-trimoxazole consisted of one double-strength tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim (Sulfran-DS, Universal Corporation, Nairobi, Kenya).”
“Statistical analyses were done with Stata version 17.”
Log-binomial regression, modified Poisson regression, linear regression, Poisson regression, and mixed models for repeated measures are named, with 95% CIs and p-values reported. Stata 17 is identified, and per-group n with SDs or proportions are tabulated. The paper uses p<0.0001 thresholds in places, but also provides many exact p-values and this is consistent with standard clinical reporting for very small p-values. Spot-checks of proportions (e.g., 29/446 = 6.5% rounded to 7%; 70/452 = 15.5% rounded to 15%) were plausible.
“risk ratio 0·45, 95% CI 0·30–0·67; p=0·0001”
“Data are mean (SD) or n/N (%), unless otherwise specified.”
“Statistical analyses were done with Stata version 17.”
The data availability statement names a concrete repository (WWARN) and a timeframe. Since the data are individual patient data, repository deposit and accession numbers are not applicable. No custom code was shared, which is typical for such trials.
“Individual participant data will be available from the Worldwide Antimalarial Resistance Network (WWARN) repository approximately 3 months after publication.”
“Individual participant data will be available from the Worldwide Antimalarial Resistance Network (WWARN) repository approximately 3 months after publication.”
Methods are complete. Trial registration number provided. All pre-specified outcomes are reported. Limitations are discussed. Conclusions are proportional. Funding and COI are declared. Reporting guideline (CONSORT) is not explicitly referenced, but the paper follows CONSORT structure.
“This trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov) , NCT04158713 (https://clinicaltrials.gov/ct2/show/NCT04158713) .”
“Another limitation is that only the first-day course of monthly dihydroartemisinin–piperaquine was directly observed, and subsequent doses were taken home.”
“We declare no competing interests.”
“Declaration of interests We declare no competing interests.”
Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
None foundReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Checked — nothing surfaced.
Checked 33 references by DOI: 1 verified — 32 no DOI (shown, not verified).
- NO DOIThe burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-saharan AfricaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISafety and efficacy of co-trimoxazole for treatment and prevention of Plasmodium falciparum malaria: a systematic reviewNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPrevention of malaria in pregnancyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICotrimoxazole prophylaxis versus mefloquine intermittent preventive treatment to prevent malaria in HIV-infected pregnant women: two randomized controlled trialsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIntermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITolerability of mefloquine intermittent preventive treatment for malaria in HIV-infected pregnant women in BeninNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIReduced nevirapine concentrations among HIV-positive women receiving mefloquine for intermittent preventive treatment for malaria control during pregnancyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIntermittent preventive treatment with dihydroartemisinin-piperaquine for the prevention of malaria among HIV-infected pregnant womenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAntiretroviral therapy with efavirenz accentuates pregnancy-associated reduction of dihydroartemisinin-piperaquine exposure during malaria chemopreventionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPredicting optimal dihydroartemisinin-piperaquine regimens to prevent malaria during pregnancy for human immunodeficiency virus-infected women receiving efavirenzNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIntermittent preventive treatment for malaria in pregnancy: optimization of target concentrations of dihydroartemisinin-piperaquineNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImpact of dolutegravir-based antiretroviral therapy on piperaquine exposure following dihydroartemisinin-piperaquine intermittent preventive treatment of malaria in pregnant women living with HIVNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIInterpreting trial results following use of different intention-to-treat approaches for preventing attrition bias: a meta-epidemiological study protocolNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffect of dihydroartemisinin/piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIVNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDrug interactions between dolutegravir and artemether-lumefantrine or artesunateamodiaquineNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMefloquine for preventing malaria in pregnant womenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIPTp with dihydroartemisinin-piperaquine versus sulphadoxine-pyrimethamine in Africa: an individual participant data meta-analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIntermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin–piperaquine versus intermittent preventive treatment with sulfadoxine–pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDihydroartemisinin-piperaquine for the prevention of malaria in pregnancyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMonthly sulfadoxine–pyrimethamine versus dihydroartemisinin–piperaquine for intermittent preventive treatment of malaria in pregnancy: a double-blind, randomised, controlled, superiority trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffectiveness of intermittent preventive treatment with dihydroartemisinin-piperaqunine against malaria in pregnancy in Tanzania: a randomized controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffect of monthly intermittent preventive treatment with dihydroartemisinin–piperaquine with and without azithromycin versus monthly sulfadoxine–pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEfficacy and safety of IPTp-DP versus IPTp-SP in Malawi (STOPMIP-MW)No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEpidemiology and burden of malaria in pregnancyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMalaria in pregnancy: from placental infection to its abnormal development and damageNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe anti-inflammatory effects of cotrimoxazole prophylaxis for people living with human immunodeficiency virus in sub-Saharan AfricaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe positive effect of malaria IPTp-SP on birthweight is mediated by gestational weight gain but modifiable by maternal carriage of enteric pathogensNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIOverall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine on birthweight: a mediation analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPiperaquine-induced QTc prolongation decreases with repeated monthly dihydroartemisinin-piperaquine dosing in pregnant Ugandan womenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEfficacy and safety of intermittent preventive treatment and intermittent screening and treatment versus single screening and treatment with dihydroartemisinin–piperaquine for the control of malaria in pregnancy in Indonesia: a cluster-randomised, open-label, superiority trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWHO Guidelines for malariaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISpatiotemporal spread of Plasmodium falciparum mutations for resistance to sulfadoxine-pyrimethamine across Africa, 1990–2020No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
1 data/code link checked; 1 live.
- datahttps://clinicaltrials.gov/ct2/show/NCT04158713LIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
3 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 3 minor suggestions below.
3 copyedit issues flagged: mostly typo, clarity, consistency.
- MINORtypoTable 3 footnote“co-trimoxazole plus dihydroartemisinin-piperaquine group, n=4l6”→ co-trimoxazole plus dihydroartemisinin–piperaquine group, n=416Lowercase 'l' used in place of the numeral '1' in the sample size footnote.
- MINORclarityMethods: Study design and participants“The protocol is available in the .”→ The protocol is available in the Supplementary Appendix.Incomplete sentence; the supplementary reference is missing.
- MINORconsistencyThroughout“cotrimoxazole”→ co-trimoxazoleBoth 'cotrimoxazole' and 'co-trimoxazole' appear; use the hyphenated form consistently.
In this post-publication audit, the paper is robust overall. The missing regulatory compliance statement and CONSORT reference are minor reporting gaps that do not undermine the study's findings but would warrant a correction to improve transparency. The statistical checks are consistent, and no data integrity concerns were detected. An informed reader should weigh the implicit justification for the single-sex population and the absence of explicit assumption checks for regression models.
- 1.HIGHethicsAdd a statement of compliance with the Declaration of Helsinki and/or ICH-GCP to the Methods (ethics) section, referencing the named approvals. This could be done via a correction.The absence of an explicit regulatory compliance statement is a standard reporting gap that journals or readers may expect to be addressed.
- 2.HIGHreportingReference the CONSORT 2010 checklist in the Methods and include the completed checklist as supplementary material. A correction would suffice.CONSORT is the standard reporting guideline for RCTs; its omission reduces transparency and may be flagged by reviewers or readers.
- 3.MEDIUMreportingComplete the sentence in Methods: 'The protocol is available in the .' by specifying the Supplementary Appendix or providing a permanent link.The incomplete sentence is a copyedit error that could confuse readers seeking the protocol.
- 4.MEDIUMcopyeditCorrect the typo in Table 3 footnote: change 'n=4l6' to 'n=416'.The lowercase 'l' instead of the numeral '1' is a typographical error that could mislead readers.
- 5.MEDIUMcopyeditStandardise the spelling of 'co-trimoxazole' (hyphenated) throughout the manuscript, replacing instances of 'cotrimoxazole'.Inconsistent hyphenation is a minor but noticeable copyedit issue.
- 6.MEDIUMreportingAdd one sentence in the Methods or Discussion explicitly justifying the single-sex (pregnant women) study population, even if the justification is implicit.Explicit justification of sex composition is a standard reporting criterion and addresses a reviewer concern.
- 7.MEDIUMdata codeSpecify the WWARN data-access mechanism (e.g., application with a data-use agreement) and the expected deposit date or identifier in the Data Availability Statement.Providing more detail on the data access process enhances reproducibility and reader confidence.
- 8.LOWstatisticsConsider replacing threshold p-values (e.g., 'p<0.0001') with exact values (e.g., p=0.00004) or state that values are truncated by Stata's output.Exact p-values are preferred for transparency, though threshold reporting is common in clinical trials.
- 9.LOWstatisticsInclude a brief note on verification of statistical assumptions (e.g., normality, dispersion) for the regression models used, or cite that the methods are robust to violations.Assumption checks are not currently reported; adding them would strengthen the statistical analysis reporting.
- 10.LOWdata codeConsider depositing the analysis code (e.g., Stata do-files) in a public repository (e.g., GitHub, Zenodo) to enhance reproducibility.Code sharing, while not mandatory, would allow full verification of the analyses.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.