Burden of Typhoid and Paratyphoid Fever in India

Abstract

Background: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection.

Methods: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community.

Results: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age.

Conclusions: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.).

Figure 1. Location of study sites in India.

Cohort and hospital-based (‘hybrid’) surveillance sites are shown.

Figure 2. Flow diagram indicating the numbers of children enrolled at each site, completion of 24 months follow-up and number of child years of observation.

Reasons for loss to follow-up are shown on the right.

Figure 3. Adjusted incidence of typhoid fever in children aged 6 months to 14 years from urban and rural cohorts and hospital-based surveillance.

Cohort incidence estimates (red points) without adjustments. Hospital-based incidence estimates (blue points) are adjusted for health care seeking in the corresponding age-group, missed blood collection due to non-consent, the proportion of typhoid cases that require hospitalization and blood culture sensitivity. Error bars show 95% uncertainty intervals based on the Poisson distribution or Monte Carlo simulation respectively.