Estimating the incidence of enteric fever in children in India: a multi-site, active fever surveillance of pediatric cohorts

Abstract

BackgroundSalmonella Typhi is responsible for about 20 million episodes of illness and over 140,000 deaths annually globally. South Asia has the highest documented burden of typhoid and is home to the multi-drug resistant H58 strain that makes treatment more challenging. The WHO recommends the use of Typhoid Conjugate Vaccines in typhoid endemic countries. Decisions on the preferred immunization strategy should be based on an analysis of disease burden, availability, affordability, and operational feasibility. Typhoid vaccines have so far remained unimplemented as public health measures because of a perceived decline in typhoid burden in recent years. The apparent decline, based on hospital reports, may be a result of rampant antimicrobial use in the community and therefore estimation of disease incidence at the community is necessary to better measure disease incidence and transmission.MethodsAge-specific incidence of typhoid fever in children between 6 months and 15 years will be estimated in four community based cohorts in varied settings across India using standardized protocols for active fever surveillance in the community. Data will be collected on secured cloud infrastructure using a combination of android and web-based real-time data collection tools. Blood cultures will be done for children with fever lasting 3 or more consecutive days using automated blood culture systems. Those with blood-culture confirmed typhoid fever will be followed up till 90 days to estimate costs and clinical outcomes of the illness episodes. Environmental factors, access to safe water, sanitation, hygiene, food hygiene, demography, population density and socioeconomic status will be assessed periodically to characterise risk factors and permit extrapolation of burden to similar risk settings.DiscussionWith the availability of licensed typhoid conjugated vaccines in India, it is important to consider whether the burden of disease is present and sufficient to require the use of vaccine in addition to other interventions. Active case finding in the community permits the detection of cases that would be missed in facility-based surveillance systems. Understanding the age distribution, burden, cost-of-illness and transmission of disease is essential to plan interventions and predict their potential impact.Trial registrationThe surveillance has been prospectively registered in the Clinical Trial Registry of India (CTRI/2017/09/009719) on 12 September 2017.

Spontaneous emergence of azithromycin resistance in independent lineages of Salmonella Typhi in Northern India

“…The ongoing Surveillance for Enteric Fever in India (SEFI) study is generating geographically representative, age-specific incidence data, as well as additional information regarding cost of illness, range of clinical severity, and antimicrobial resistance (AMR) patterns associated with S . Typhi in India 3 . These data will undoubtedly provide a more comprehensive understanding of typhoid fever incidence rates across the Indian sub-continent, and ultimately, in supporting decision-making concerning typhoid conjugate vaccine (TCV) introduction in India 4 .…”

The Surveillance for Enteric Fever in Asia Project (SEAP), Severe Typhoid Fever Surveillance in Africa (SETA), Surveillance of Enteric Fever in India (SEFI), and Strategic Typhoid Alliance Across Africa and Asia (STRATAA) Population-based Enteric Fever Studies: A Review of Methodological Similarities and Differences

“…Any fever of 3 or more consecutive days is considered a suspected case, and the child is referred to a study facility on the fourth day of fever, where a blood culture is performed if the child has had fever in the past 12 hours. Risk factors and other demographic data are also collected from participating households to permit extrapolation of incidence estimates to other similar risk settings [ 17 ].…”

Assessing the Feasibility of Typhoid Elimination

“…Since 2000, data on typhoid incidence have become more plentiful, thanks in part to multicenter studies like the Diseases of the Most Impoverished program [ 24 ] and the Typhoid Fever Surveillance in Africa Program (TSAP) [ 25 ]. With currently ongoing multicenter studies (eg, the Surveillance for Enteric Fever in Asia Project [SEAP] [ 26 ], Severe Typhoid in Africa [SETA] program [ 27 ], the Strategic Typhoid Alliance Across Africa and Asia [STRATAA] study [ 28 ], and Surveillance of Enteric Fever in India [SEFI] [ 29 ]), we expect data availability to continue to improve. Still, although data on typhoid incidence have improved, data abundance for typhoid trails behind other causes considered targets for elimination/eradication efforts, and most countries lack systematic typhoid surveillance systems.…”

“…Given the challenges associated with establishing surveillance systems in low-resource settings, and the cost, expertise, and equipment associated with blood culture, large-scale national surveillance systems are likely infeasible in most typhoid-endemic countries, which will necessitate alternative approaches. SEFI was initiated in 2017 and will use a hybrid system to integrate data collected from active fever surveillance cohorts with hospital and laboratory data to provide timely estimates of typhoid incidence and trends in India [ 29 ]. This program may offer a model for typhoid surveillance that could be applied in other endemic countries, and sites from previous studies of typhoid incidence (eg, SEAP, SETA, and TSAP) should be considered as sentinel surveillance sites so as to leverage the existing capacity and expertise.…”