Incidence of typhoid fever higher in urban India than in rural areas

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1. In this prospective cohort study, the incidence of typhoid fever in children was higher in urban areas of India compared to rural areas.

2. There was no association between the incidence of typhoid fever and seasonality.

Evidence Rating Level: 2 (Good)

Study Rundown: Typhoid fever is responsible for significant mortality worldwide for children under the age of 15. Although vaccination has been widely recommended, available vaccines could not previously be used in children. However, Vi polysaccharide-based typhoid conjugate vaccines are now available and safe for children. In this prospective study in India, the incidence of acute febrile illness was highest among children from six months to four years old. About a quarter of children met the criteria for enteric fever. Cases of culture-confirmed typhoid were greatest in Vellore and least in Pune. There was no seasonality or association with wetter monsoon months to the incidence of typhoid. The risk of typhoid was associated with larger households, fewer assets, and those without access to a sanitary toilet. The incidence of typhoid was also greater for children without access to safe water compared to those with access to safe water. The incidence of typhoid was lower for children who were vaccinated. Common symptoms for culture-confirmed typhoid fever were cough, nausea or vomiting, abdominal pain, and headache. A limitation of this study is the variable sites across India that were studied, primarily as the sites were not randomized and may not be representative of the national incidence and characteristics of typhoid fever.

Click to read the study in NEJM

Relevant Reading: A cluster-randomized effectiveness trial of Vi Typhoid vaccine in India

In-Depth [prospective cohort]: Typhoid fever accounts for a significant portion of deaths each year. However, systematic surveillance has been limited. The National Surveillance System for Enteric Fever in India (NSSEFI) study conducted weekly surveillance for acute febrile illness and evaluated the incidence of typhoid and paratyphoid fever in four community areas and six sites combined with hospitals. Eligible children between six months and 13 years old at four sites were enrolled, three in urban and one rural center. Children were followed for 24 months or until their 15^th birthday. A total of 24,062 children were enrolled at four sites, with 89.2% completing 24 months of follow-up. The study recorded 76,027 cases of acute febrile illness across four cohorts, and the highest incidence was among children between the ages of six months to four years. The criteria for potential enteric fever were met in 20,911 cases (27.5%). Positive blood culture was performed in 86.6% of the potential cases. Antibiotics were administered in 67.7% of potential enteric fever cases. A total of 299 children had culture-confirmed cases of typhoid. The incidence of typhoid varied over time, but there was no association with seasonality or monsoon months (hazard ratio, 0.95; 95% Confidence Interval [CI], 0.69 to 1.32). The incidence of typhoid was lower for children who were vaccinated (hazard ratio, 0.60; 95%CI, 0.28 to 1.27). In summary, this study represented regional variation in typhoid fever infection in children in India.

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