title: 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.
authors.affiliation: Department of Community Health, Christian Medical College, Vellore, India.
authors.forename: Jacob
authors.initials: J
authors.lastname: John
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Carola J C
authors.initials: CJ
authors.lastname: Van Aart
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Grassly
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D010284:Paratyphoid Fever / Q000453:epidemiology*; D015995:Prevalence; D019371:Topography, Medical; D014435:Typhoid Fever / Q000453:epidemiology*; D055815:Young Adult