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BMJ Open. 2017 Jul 2;7(6):e016283. doi: 10.1136/bmjopen-2017-016283.

The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys.

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The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Department of Paediatrics, Oxford Vaccine Group,University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK.
International Centre for Diarrhoeal Diseases Research, Dhaka, Bangladesh.
Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
The Wellcome Trust Sanger Institute, Cambridgeshire, UK.
UCLA Fielding School of Public Health, Los Angeles, USA.
Mahidol-Oxford Tropical Medicine Research Unit,Mahidol University, Bangkok, Thailand.
The Peter Doherty Institute for Infection and Immunity,The University of Melbourne, Melbourne, Australia.
Institute of Infection and Global Health,University of Liverpool, Liverpool, UK.
Division of Infection and Immunity, University College London, London, UK.
Centre for Systems Genomics,University of Melbourne, Victoria, Australia.
Department of Biochemistry and Molecular Biology, University of Melbourne, Victoria, Australia.
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, USA.



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.


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.


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.


ISRCTN 12131979.


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).


africa; asia; diagnosis; enteric fever; febrile illness; healthcare utilisation; infection transmission; resource-limited setting; salmonella paratyphi a; salmonella typhi; seroepidemiology; serosurveillance; vaccination programme

[Indexed for MEDLINE]
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Conflict of interest statement

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.

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