News Release

Do studies underestimate the prevalence of typhoid?

Peer-Reviewed Publication


Blood culture surveillance programs are critical for estimating the prevalence of typhoid and paratyphoid fevers, but cases can be missed when patients don't seek medical care, or seek medical care and don't have a blood culture test. Researchers writing in PLOS Neglected Tropical Diseases have now calculated inflation factors that can be used to adjust these incidence rates to account for under-detection.

Typhoid and paratyphoid fever are infections caused by the bacteria Salmonella enterica Typhi and S. Paratyphi. In countries with a high incidence rate of the diseases, vaccine programs are used to control typhoid fever. Surveillance programs to estimate these incidence rates, however, can miss cases, when patients don't receive blood cultures or in settings where patients self-treat with widely available antibiotics. Therefore, the true burden of disease is thought to be underestimated.

In the new work, Merryn Voysey of the University of Oxford, UK, and colleagues used data from an ongoing Typhoid Vaccine Acceleration Consortium (TyVAC) clinical trial of a typhoid vaccine in Nepal. Children aged 9 months through 16 years in the Lalitpur area of Kathmandu were eligible and local healthcare providers--including 18 community clinics and one tertiary care hospital--were instructed to collect blood samples to culture for patients who had a fever for at least two days or a current temperature of at least 38 degrees. There was also an active surveillance effort included in the trial.

During the first year of passive surveillance, data was collected on 2,393 fever presentations. Overall, 1615 (68%) of patients had blood cultures. Children were more likely to have blood taken for culture if they were older, had a longer fever, a higher temperature or clinicians suspected typhoid or a urinary tract infection. Models revealed that patients who had blood taken were 1.87 times more likely to be positive for Salmonella than those without blood cultures.

"Crude typhoid incidence estimates should be adjusted for both the proportion of cases that go undetected due to missing blood cultures as well as the lower likelihood of culture-positivity in the group with missing data," the researchers say.


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Citation: Voysey M, Pant D, Shakya M, Liu X, Colin-Jones R, et al. (2020) Under-detection of blood culture-positive enteric fever cases: The impact of missing data and methods for adjusting incidence estimates. PLOS Neglected Tropical Diseases 14(1): e0007805.

Funding: The authors thank the Bill & Melinda Gates Foundation (OPP1151153) for funding TyVAC, including the Nepal trial; the Wellcome Trust and the Bill & Melinda Gates Foundation for funding of The Strategic Typhoid Alliance across Africa and Asia, which supported the surveillance that underpins this trial; and the National Institute for Health Research Oxford Biomedical Research Centre.

The Typhoid Vaccine Acceleration Consortium (TyVAC), a partnership between the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, the Oxford Vaccine Group at the University of Oxford, and PATH, an international nonprofit, aims to accelerate the introduction of new typhoid conjugate vaccines (TCVs) as part of an integrated approach to reducing the burden of morbidity and mortality from typhoid in countries eligible for support from Gavi, the Vaccine Alliance.

MV is funded by a National Institute of Health Research (NIHR) Doctoral Research Fellowship (DRF-2015-08-048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: I have read the journal's policy and the authors of this manuscript have the following potential competing interests:

AJP is Chair of UK Dept. Health and Social Care's (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) & the European Medicine Agency (EMA) scientific advisory group on vaccines, and is a member of the WHO's Strategic Advisory Group of Experts. VEP is a member of the WHO Immunization and Vaccine-related Implementation Research Advisory Committee. The views expressed in this article do not necessarily represent the views of DHSC, JCVI or WHO.

MV is funded by a National Institute of Health Research (NIHR) Doctoral Research Fellowship (DRF-2015-08-048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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