Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the 'POPulation differences in VACcine responses' (POPVAC) programme. Issue 2 (16th February 2021)

• Record Type: Journal Article
• Authors: Nkurunungi, Gyaviira; Zirimenya, Ludoviko; Nassuuna, Jacent; Natukunda, Agnes; Kabuubi, Prossy N; Niwagaba, Emmanuel; Oduru, Gloria; Kabami, Grace; Amongin, Rebecca; Mutebe, Alex; Namutebi, Milly; Zziwa, Christopher; Amongi, Susan; Ninsiima, Caroline; Onen, Caroline; Akello, Florence; Sewankambo, Moses; Kiwanuka, Samuel; Kizindo, Robert; Kaweesa, James; 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-2020-040426
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response. Methods and analysis: We have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni -endemic Ugandan islands. Vaccines to be studied comprise BCG on day 'zero'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset. 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. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses. Ethics and dissemination: Ethics approval has been obtained from relevant ethics committes of Uganda and UK. 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: ISRCTN60517191 .