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. Issue 2 (16th February 2021)

• Record Type: Journal Article
• Authors: Natukunda, Agnes; Nkurunungi, Gyaviira; Zirimenya, Ludoviko; Nassuuna, Jacent; Oduru, Gloria; Amongin, Rebecca; Kabuubi, Prossy N; Mutebe, Alex; Onen, Caroline; Amongi, Susan; Nakazibwe, Esther; Akello, Florence; Kiwanuka, Samuel; Kiwudhu, Fred; Sewankambo, Moses; Nsubuga, Denis; Kizindo, Robert; Staedke, Sarah G; Cose, Stephen; Webb, Emily; Elliott, Alison M
• Other Names: author non-byline.; Elliott Alison author non-byline.; Zirimenya Ludoviko author non-byline.; Nkurunungi Gyaviira author non-byline.; Cose Stephen author non-byline.; Amongin Rebecca author non-byline.; Nassanga Beatrice author non-byline.; Nassuuna Jacent author non-byline.; Nambuya Irene author non-byline.; Kabuubi Prossy author non-byline.; Niwagaba Emmanuel author non-byline.; Oduru Gloria author non-byline.; Kabami Grace author non-byline.; Webb Emily author non-byline.; Natukunda Agnes author non-byline.; Akurut Helen author non-byline.; Mutebe Alex author non-byline.; Wajja Anne author non-byline.; Namutebi Milly author non-byline.; Zziwa Christopher author non-byline.; Serubanja Joel author non-byline.; Onen Caroline author non-byline.; Nakazibwe Esther author non-byline.; Tumusiime Josephine author non-byline.; Ninsiima Caroline author non-byline.; Amongi Susan author non-byline.; Akello Florence author non-byline.; Akello Mirriam author non-byline.; Kizindo Robert author non-byline.; Sewankambo Moses author non-byline.; Nsubuga Denis author non-byline.; Kiwanuka Samuel author non-byline.; Kiwudhu Fred author non-byline.; Abiriga David author non-byline.; Kizza Moses author non-byline.; Nansukusa Samsi author non-byline.; Kaleebu Pontiano author non-byline.; Smits Hermelijn author non-byline.; Yazdanbakhsh Maria author non-byline.; Dam Govert van author non-byline.; Corstjens Paul author non-byline.; Staedke Sarah author non-byline.; Luzze Henry author non-byline.; Kaweesa James author non-byline.; Tukahebwa Edridah author non-byline.; Tumushabe Elly author non-byline.; Muwanga Moses author non-byline.;
• Is Part Of: BMJ open. Volume 11:Issue 2(2021)
• Publication Date: 2021-02-16
• Subjects: infection control -- parasitology -- public health -- immunology -- epidemiology -- paediatric infectious disease & immunisation; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2020-040427
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: Drivers 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 analysis: We 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 dissemination: Ethics 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 number: Current Controlled Trials identifier: ISRCTN62041885 .