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
| Autor: | Caroline Onen, Agnes Natukunda, Prossy Kabuubi, Alison M. Elliott, Jacent Nassuuna, Emily L. Webb, Sarah G. Staedke, Ludoviko Zirimenya, Gyaviira Nkurunungi, Stephen Cose, Rebecca Amongin, Fred Kiwudhu, Samuel Kiwanuka, Popvac trial team, Denis Nsubuga, Susan Amongi, Florence Akello, Gloria Oduru, Moses Sewankambo, Robert Kizindo, Esther Nakazibwe, Alex Mutebe |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
education.field_of_study business.industry 030231 tropical medicine Population Human Papilloma Virus Vaccine General Medicine Booster dose medicine.disease Vaccine efficacy 03 medical and health sciences 0302 clinical medicine Dihydroartemisinin/piperaquine Internal medicine Piperaquine parasitic diseases medicine 030212 general & internal medicine education business BCG vaccine Malaria |
| Zdroj: | BMJ Open. 11:e040427 |
| ISSN: | 2044-6055 |
| DOI: | 10.1136/bmjopen-2020-040427 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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