Article Text
Abstract
Introduction Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12–27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics.
The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies.
Methods/design Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers.
Ethics and dissemination This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences.
Trial registration number ISRCTN 12131979.
Ethics references Oxford (Oxford Tropical Research Ethics Committee 39-15).
Bangladesh (icddr,b Institutional Review Board PR-15119).
Malawi (National Health Sciences Research Committee 15/5/1599).
Nepal (Nepal Health Research Council 306/2015).
- enteric fever
- vaccination programme
- infection transmission
- salmonella typhi
- salmonella paratyphi a
- serosurveillance
- seroepidemiology
- healthcare utilisation
- resource-limited setting
- diagnosis
- febrile illness
- africa
- asia
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
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Footnotes
Contributors SB, BB, JDC, GD, CD, MAG, RSH, VEP, FQ, KZ, SD, KH and AJP contributed to the conception and design of the study. ST drafted the protocol of the study. This manuscript was drafted by TD and JM. SB, BB, JDC, GD, SD, CD, MAG, KH, RSH, VEP, FQ, ST, KZ, MAK, FK, MS, DT and AJP read and critically revised the protocol and this manuscript prior to submission.
Funding Funding for the STRATAA study has been provided by a Wellcome Trust Strategic Award (no. 106158/Z/14/Z) and the Bill and Melinda Gates Foundation (no. 617 OPP1141321). The Malawi-Liverpool-Wellcome Programme and the Oxford University Clinical Research Unit in Vietnam are supported by the Wellcome Trust with Major Overseas Programme core awards.
Disclaimer Neither funding body had any role in designing the study, writing this manuscript or the decision to submit.
Competing interests AJP chairs the UK Department of Health’s (DH) Joint Committee on Vaccination an Immunisation (JCVI) and the European Medicines Agency (EMA) Scientific Advisory Group on Vaccines and is a member of WHO’s SAGE. The views expressed in this manuscript do not necessarily reflect those of JCVI, DH, EMA or WHO. AJP has previously conducted clinical trials on behalf of the University of Oxford funded by vaccine manufacturers but has no personal financial interests.
Ethics approval Oxford Tropical Research Ethics Committee, icddr, b Institutional Review Board, Nepal Health Research Council, Malawi National Health Sciences Research Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Collaborators Abhilasha Karkey, Sabina Dongol, Amit Aryjal (Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal); Nirod Chandra Saha (International Center for Diarrhoeal Diseases Research, Dhaka, Bangladesh); Tikhala Makhaza Jere, Chisomo Msefula, Tonney Nyirenda (University of Liverpool, UK, and the Malawi Liverpool Wellcome Trust Clinical Research Programme, Malawi); Tan Trinh Van (The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam); Stephen Reece (Wellcome Trust Sanger Institute, Cambridge, UK); Merryn Voysey, Christoph J. Blohmke, Yama Farooq, Jennifer Hill (Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK); Neil J. Saad (Yale School of Public Health, Yale University, New Haven, Connecticut, USA).