Effect of intermittent preventive treatment for malaria with dihydroartemisinin-piperaquine on immune responses to vaccines among rural Ugandan adolescents: randomised controlled trial protocol B for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

Abstract

IntroductionDrivers of lower vaccine efficacy and impaired vaccine-specific immune responses in low-income versus high-income countries, and in rural compared with urban settings, are not fully elucidated. Repeated exposure to and immunomodulation by parasite infections may be important. We focus on Plasmodium falciparum malaria, aiming to determine whether there are reversible effects of malaria infection on vaccine responses.Methods and analysisWe have designed a randomised, double-blind, placebo-controlled, parallel group trial of intermittent preventive malaria treatment versus placebo, to determine effects on vaccine response outcomes among school-going adolescents (9 to 17 years) from malaria-endemic rural areas of Jinja district (Uganda). Vaccines to be studied comprise BCG vaccine on day ‘zero’; yellow fever, oral typhoid and human papilloma virus vaccines at week 4; and tetanus/diphtheria booster vaccine at week 28. Participants in the intermittent preventive malaria treatment arm will receive dihydroartemisinin/piperaquine (DP) dosed by weight, 1 month apart, prior to the first immunisation, followed by monthly treatment thereafter. We expect to enrol 640 adolescents. Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. In secondary analyses, we will determine effects of monthly DP treatment (versus placebo) on correlates of protective immunity, on vaccine response waning, on whether there are differential effects on priming versus boosting immunisations, and on malaria infection prevalence. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of the intervention on vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberCurrent Controlled Trials identifier: ISRCTN62041885.

NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard): Concept and Launch event report

“…Data and samples from ongoing and completed trials will be used to explore mechanisms and identify biomarkers of adverse biological status with respect to vaccine responses. In Uganda, three POPVAC trials are investigating the effects of rural versus urban location, and Schistosoma mansoni and malaria exposure and treatment, on responses to live parenteral (BCG, Yellow Fever), live oral (Typhoid [Ty21a]), Human Papilloma Virus (HPV) and toxoid (tetanus/diphtheria) vaccines; and the effect of BCG revaccination on response to other vaccines [27][28][29][30] . Results are expected in 2023, and samples will be available for investigation.…”

Protozoan co-infections and parasite influence on the efficacy of vaccines against bacterial and viral pathogens

“…Malaria is a highly prevalent disease in settings where poor responses to unrelated vaccines has been reported to occur (Natukunda, 2020). Several studies have shown that Plasmodium infection might impair vaccine induced protective immunity against other pathogens (Dietz et al, 1997;Cunnington and Riley, 2010).…”