Evidence map›Paper›PMID 39424572›Full record

Trial reportThe Lancet. Global health2024

The effect of intermittent preventive treatment for malaria with dihydroartemisinin-piperaquine on vaccine-specific responses among schoolchildren in rural Uganda (POPVAC B): a double-blind, randomised controlled trial.

Ludoviko Zirimenya, Agnes Natukunda, Jacent Nassuuna, Gyaviira Nkurunungi, Christopher Zziwa, Caroline Ninsiima, Christine Kukundakwe, Christine M Nankabirwa, Charity Katushabe, Loyce K Namusobya and 14 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in The Lancet. Global health, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Ludoviko ZirimenyaImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
Agnes NatukundaImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda; International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Jacent NassuunaImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Gyaviira NkurunungiImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda; Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: gyaviira.nkurunungi@mrcuganda.org.
Christopher ZziwaImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Caroline NinsiimaImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Christine KukundakweImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Christine M NankabirwaImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Charity KatushabeImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Loyce K NamusobyaImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Gloria OduruImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Grace KabamiImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Joel KabaliImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
John KayiwaDepartment of Arbovirology, Uganda Virus Research Institute, Entebbe, Uganda.
Joyce KabagenyiImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Govert J van DamDepartment of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
Paul L A M CorstjensDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Stephen CoseImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
Anne WajjaImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers, Amsterdam, Netherlands.
Sarah G StaedkeDepartment of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
Pontiano KaleebuImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Alison M ElliottImmunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
Emily L WebbInternational Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
POPVAC trial team

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundSeveral important vaccines differ in immunogenicity and efficacy between populations. We hypothesised that malaria suppresses responses to unrelated vaccines and that this effect can be reversed-at least partially-by monthly malaria intermittent preventive treatment (IPT) in high-transmission settings.

methodsWe conducted an individually randomised, double-blind, placebo-controlled trial of the effect of malaria IPT with dihydroartemisinin-piperaquine on vaccine responses among schoolchildren aged 9-17 years in Jinja district, Uganda. Participants were recruited from two schools and did not have exposure to vaccines of interest after the age of 5 years, with the exception of human papillomavirus (HPV). Computer-generated 1:1 randomisation was implemented in REDCap. 3-day courses of dihydroartemisinin-piperaquine (dosage by weight) or placebo were administered monthly, including twice before the first vaccination. Trial participants were vaccinated with the live parenteral BCG vaccine (Serum Institute of India, Pune, India) at week 0; yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France); live oral typhoid vaccine (Ty21a; PaxVax, London, UK), and quadrivalent virus-like particle HPV vaccine (Merck, Rahway, NJ, USA) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated, and a tetanus-diphtheria booster was given after completion of the trial at week 52. Primary outcomes were vaccine responses at week 8 and, for tetanus-diphtheria, at week 52, and analysis was done in the intention-to-treat population. Malaria parasite prevalence at enrolment and during follow-up was determined retrospectively by PCR. The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN62041885) and is complete.

findingsBetween May 25 and July 14, 2021, we assessed 388 potential participants for eligibility. We enrolled and randomly allocated 341 participants to the two groups (170 [50%] to dihydroartemisinin-piperaquine and 171 [50%] to placebo); 192 (56%) were female and 149 (44%) participants were male. 145 (85%) participants in the dihydroartemisinin-piperaquine group and 140 participants (82%) in the placebo group were followed up until the week 52 endpoint. At enrolment, 109 (64%) of all participants in the dihydroartemisinin-piperaquine group and 99 (58%) of 170 participants in the placebo group had malaria; this reduced to 6% or lower at all follow-up visits in the dihydroartemisinin-piperaquine group. There was no effect of dihydroartemisinin-piperaquine versus placebo on primary outcomes: BCG-specific IFNγ ELISpot response had a geometric mean ratio (GMR) of 1·09 (95% CI 0·93-1·29), p=0·28; yellow fever neutralising antibody was 1·19 (0·91-1·54), p=0·20 for plaque reduction neutralising reference tests (PRNT

interpretationIPT for malaria with dihydroartemisinin-piperaquine did not improve peak vaccine responses, despite reducing malaria prevalence. Possible longer-term effects on response waning should be further explored.

fundingUK Medical Research Council. TRANSLATION: For the Luganda translation of the abstract see Supplementary Materials section.

Indexed as

AntimalarialsArtemisininsMalaria VaccinesQuinolinesAdolescentChildDouble-Blind MethodFemaleHumansMalariaMalePiperazinesRural PopulationUgandaAntimalarialsArtemisininsartenimolMalaria VaccinespiperaquinePiperazinesQuinolines

Identifiers

PMID39424572
PMCPMC11483247

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.