The Burden of Typhoid and Paratyphoid in India: Systematic Review and Meta-analysis

Abstract

Background: Typhoid is an important public health challenge for India, especially with the spread of antimicrobial resistance. The decision about whether to introduce a public vaccination programme needs to be based on an understanding of disease burden and the age-groups and geographic areas at risk.

Methods: We searched Medline and Web of Science databases for studies reporting the incidence or prevalence of typhoid and paratyphoid fever confirmed by culture and/or serology, conducted in India and published between 1950 and 2015. We used binomial and Poisson mixed-effects meta-regression models to estimate prevalence and incidence from hospital and community studies, and to identify risk-factors.

Results: We identified 791 titles and abstracts, and included 37 studies of typhoid and 18 studies of paratyphoid in the systematic review and meta-analysis. The estimated prevalence of laboratory-confirmed typhoid and paratyphoid among individuals with fever across all hospital studies was 9.7% (95% CI: 5.7-16.0%) and 0.9% (0.5-1.7%) respectively. There was significant heterogeneity among studies (p-values<0.001). Typhoid was more likely to be detected among clinically suspected cases or during outbreaks and showed a significant decline in prevalence over time (odds ratio for each yearly increase in study date was 0.96 (0.92-0.99) in the multivariate meta-regression model). Paratyphoid did not show any trend over time and there was no clear association with risk-factors. Incidence of typhoid and paratyphoid was reported in 3 and 2 community cohort studies respectively (in Kolkata and Delhi, or Kolkata alone). Pooled estimates of incidence were 377 (178-801) and 105 (74-148) per 100,000 person years respectively, with significant heterogeneity between locations for typhoid (p<0.001). Children 2-4 years old had the highest incidence.

Conclusions: Typhoid remains a significant burden in India, particularly among young children, despite apparent declines in prevalence. Infant immunisation with newly-licensed conjugate vaccines could address this challenge.

Fig 1. Flow diagram showing the number of articles identified in the systematic review on typhoid and paratyphoid in India.

Fig 2. Prevalence of laboratory confirmed typhoid among patients with fever or suspected typhoid fever ordered by study year.

Error bars indicate 95% confidence intervals, which are also given in square brackets for each study. Diamonds show the pooled estimates by patient group and overall together with 95% confidence intervals based on the fit of the random effects (RE) binomial (meta-) regression model. *indicates studies carried out during an outbreak of typhoid fever. ^indicates studies that used serology (alone or in addition to culture) to test for typhoid fever.

Fig 3. Prevalence of laboratory confirmed paratyphoid among patients with fever or suspected typhoid fever ordered by study year.

Details as for Fig 2.

Fig 4. Incidence of typhoid fever based on community cohort studies.

A) Incidence by study and pooled estimates (diamonds) are shown based on the fit of the random effect (RE) Poisson (meta-) regression model. The error bars and horizontal extent of the diamonds correspond with the 95% confidence intervals, which are also given in square brackets. B) Incidence by age-group for each study. Note differences in the definitions of the age-categories. We used the number of people enumerated at baseline to estimate the number of individuals at risk for the Kolkata 2004 estimate, since person-years of observation was not reported in this study [29].