The Effect of Intermittent Preventive Treatment for Malaria with Dihydroartemisinin-Piperaquine on Vaccine-Specific Responses Among Schoolchildren in Rural Uganda: Results of the POPVAC B Randomised, Controlled Trial

• DOI: 10.2139/ssrn.4667621
• Publication Date: 2023-12-21T14:51:17Z
• Authors: Ludoviko Zirimenya; Agnes Natukunda; Jacent Nassuuna; Gyaviira Nkurunungi; Christopher Zziwa; Caroline Ninsiima; Christine Kukundakwe; Christine Musoke...; Charity Katushabe; Loyce Kisakye Na...; Gloria Oduru; Grace Kabami; Joel Kabali; John Kayiwa; Joyce Kabagenyi; Govert J. van Dam; Paul Corstjens; Stephen Cose; Anne Wajja; Sarah Staedke; Pontiano Kaleebu; Alison Eliott; Emily Webb
• Keywords: Piperaquine

Background: Several important vaccines differ in immunogenicity and efficacy between populations. We hypothesized that malaria suppresses responses to unrelated this effect can be reversed, at least partially, by monthly intermittent preventive treatment (IPT) high-transmission settings. Methods: conducted an individually randomised, double-blind, placebo-controlled trial of the IPT with dihydroartemisinin-piperaquine (DP) on vaccine among schoolchildren (9-17 years) Jinja district, Uganda (registration ISRCTN62041885). Participants were recruited from two schools lacked exposure interest after five years age (except HPV). Computer-generated 1:1 randomisation was implemented REDCap. Three-day courses DP (dosage weight), or placebo administered monthly, including twice before first vaccination. received BCG [week zero], yellow fever, oral typhoid (Ty21a), HPV-prime 4], HPV-boost, tetanus/diphtheria 28]. Primary outcomes week 8 and, for tetanus/diphtheria, 52. Malaria parasite prevalence enrolment during follow up determined retrospectively PCR. Results: Between 25th May 14th July 2021, we enrolled 341 participants, 44% male, randomised 170 DP, 171 placebo; 145 (85%) 140 (82%) participants followed 52, respectively. At enrolment, 60% positive; reduced ≤6.2% all follow-up visits arm. There no versus primary outcomes: BCG-specific IFN-γ GMR 0.99 (95%CI 0.77-1.28); fever neutralising antibody 1.18 (0.91-1.54); IgG Ty21a 1.04 (0.82-1.32), HPV-16 0.98 (0.58-1.64), HPV-18 0.93 (0.59-1.46), tetanus 1.12 (0.84-1.48), diphtheria 0.97 (0.83-1.12). some evidence waning response. Interpretation: Intermittent safely effectively but did not improve peak responses. Possible longer-term effects response should further explored.Trial Registration: This is registered ISRCTN registry, ISRCTN62041885.Funding: The POPVAC programme work supported primarily Medical Research Council (MRC) United Kingdom (grant # MR/R02118X/1 MC_PC_21034). award jointly funded UK Foreign Commonwealth Development Office (FCDO) under MRC/FCDO Concordat agreement also part EDCTP2 European Union. SC JN Makerere University – Virus Institute Centre Excellence Infection Immunity Training (MUII-plus), DELTAS Africa Initiative DEL-15-004). independent funding scheme African Academy Sciences, Alliance Accelerating Science New Partnership Africa’s Planning Coordinating Agency Wellcome Trust Government. AN, LZ, ELW AME additional support National Health Care (NIHR; grant NIHR134531) using aid Government global health research; GN Union TMA2019PF-2707) 224263/Z/21/Z); through International Statistics Epidemiology Group (ISEG) MRC MR/R010161/1. MRC/UVRI LSHTM Unit; both I-SEG Unit are Innovation Foreign, Union.Declaration Interest: All authors declare competing interests.Ethical Approval: their parents guardians gave written, informed assent consent, espectively. Ethics approval granted (reference: GC/127/18/09/681), London School Hygiene Tropical Medicine 16033), Technology HS2487) Drug Authority CTC 0117/2020). Independent steering data safety monitoring committees oversaw trial.