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Background Typhoid fever causes substantial global mortality, with almost half occurring in India. New typhoid vaccines are highly effective and recommended by the World Health Organization for high-burden settings. There is a need to determine whether and which typhoid vaccine strategies should be implemented in India. Methods We assessed typhoid vaccination using a dynamic compartmental model, parameterized by and calibrated to disease and costing data from a recent multisite surveillance study in India. We modeled routine and 1-time campaign strategies that target different ages and settings. The primary outcome was cost-effectiveness, measured by incremental cost-effectiveness ratios (ICERs) benchmarked against India’s gross national income per capita (US$2130). Results Both routine and campaign vaccination strategies were cost-saving compared to the status quo, due to averted costs of illness. The preferred strategy was a nationwide community-based catchup campaign targeting children aged 1–15 years alongside routine vaccination, with an ICER of $929 per disability-adjusted life-year averted. Over the first 10 years of implementation, vaccination could avert 21–39 million cases and save $1.6–$2.2 billion. These findings were broadly consistent across willingness-to-pay thresholds, epidemiologic settings, and model input distributions. Conclusions Despite high initial costs, routine and campaign typhoid vaccination in India could substantially reduce mortality and was highly cost-effective.

Background Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden. Methods Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting. Results In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8–152.4) in tier 2 and US$405.7 (95% CI, 366.9–444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure. Conclusions The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed.

Background The case-fatality ratio (CFR) for enteric fever is essential for estimating disease burden and calibrating measures that balance the likely health gains from interventions against social and economic costs. Methods We aimed to estimate the CFR for enteric fever using multiple data sources within the National Surveillance System for Enteric Fever in India. This surveillance (2017–2020) was established as a multitiered surveillance system including community cohorts (tier 1), facility-based (tier 2), and tertiary care surveillance (tier 3) for estimating the burden of enteric fever in India. The CFR was calculated after accounting for healthcare-seeking behavior for enteric fever and deaths occurring outside the hospital. Results A total of 1236 hospitalized patients with blood culture–confirmed enteric fever were enrolled, of which 9 fatal cases were identified, for an estimated hospitalized CFR of 0.73% (95% confidence interval [CI], .33%–1.38%). After adjusting for severity, healthcare-seeking behavior, and deaths occurring out-of-hospital, the CFR was estimated to be 0.16% (95% CI, .07%–.29%) for all enteric fevers. Conclusions Our estimates of the CFR are relatively lower than previously estimated, accounting for care-seeking behavior and deaths outside the hospital.

Introduction World Health Organization has prequalified the use of typhoid conjugate vaccine (TCV) in children over six months of age in typhoid endemic countries. We assessed the cost-effectiveness of introducing TCV separately for urban and rural areas of India. Methods A decision analytic model was developed, using a societal perspective, to compare long-term costs and outcomes (3% discount rate) in a new-born cohort of 100,000 children immunized with or without TCV. Three vaccination scenarios were modelled, assuming the protective efficacy of TCV to last for 5, 10 and 15 years following immunization. Incidence of typhoid infection estimated under ‘National Surveillance System for Enteric Fever’ (NSSEFI)’ was used. The prices of vaccine and cost of service delivery were included for vaccination arm. Both health system cost and out-of-pocket expenditures for treatment of typhoid illness and its complications was included. Results TCV introduction in urban areas would result in prevention of 17% to 36% typhoid cases and deaths. With exclusion of indirect costs, the incremental cost per QALY gained was ₹ 151,346 (54,730–307,975), ₹ 61,710 (−5250 to 163,283) and ₹ 45,188 (−17,069 to 141,093) for scenario 1, 2 and 3 respectively. While, with inclusion of indirect costs, all 3 scenarios were cost saving. Further, in rural areas, TCV is estimated to reduce the typhoid cases and deaths by 19% to 36%, with ICER (incremental cost per QALY gained) ranging from ₹ 2340 (1316–4370) to ₹ 3574 (2057 – 6691) thousand (inclusive of indirect costs) among the 3 vaccination scenarios. Conclusion From a societal perspective, introduction of TCV is a cost saving strategy in urban India. Further, due to low incidence of typhoid infection, introduction of TCV is not cost-effective in rural settings of India.

Background Typhoid fever remains a major public health problem in India. Recently, the Surveillance for Enteric Fever in India program completed a multisite surveillance study. However, data on subnational variation in typhoid fever are needed to guide the introduction of the new typhoid conjugate vaccine in India. Methods We applied a geospatial statistical model to estimate typhoid fever incidence across India, using data from 4 cohort studies and 6 hybrid surveillance sites from October 2017 to March 2020. We collected geocoded data from the Demographic and Health Survey in India as predictors of typhoid fever incidence. We used a log linear regression model to predict a primary outcome of typhoid incidence. Results We estimated a national incidence of typhoid fever in India of 360 cases (95% confidence interval [CI], 297–494) per 100 000 person-years, with an annual estimate of 4.5 million cases (95% CI, 3.7–6.1 million) and 8930 deaths (95% CI, 7360–12 260), assuming a 0.2% case-fatality rate. We found substantial geographic variation of typhoid incidence across the country, with higher incidence in southwestern states and urban centers in the north. Conclusions There is a large burden of typhoid fever in India with substantial heterogeneity across the country, with higher burden in urban centers.

Background Lack of reliable data in India drove the “Surveillance of Enteric Fever in India” (SEFI) concept. Hybrid surveillance, combining facility-based surveillance for the crude incidence, and a community-based healthcare utilization survey (HCUS) to calculate the factor needed to arrive at the adjusted incidence, was used in 6 sites. The HCUS aimed to determine the percentage of utilization of study facilities by the catchment population for hospitalizations due to febrile illness. Methods Population proportional to size sampling and systematic random sampling, in 2 stages, were used to survey 5000 households per site. Healthcare utilization was assessed. Results Febrile illness accounted for 20% of admissions among 137 990 individuals from 30 308 households. Only 9.6%–38.3% of those admitted with febrile illness sought care in the study hospitals. The rate of rural utilization of the private sector for hospitalization was 67.6%. The rate of hospitalization for febrile illness, per 1000 population, ranged from 2.6 in Manali to 9.6 in Anantapur; for 25.8% of the deaths associated with febrile illness, no facility was used before death. Conclusions One in 5 hospitalizations were associated with fever. Rural utilization of the private sector for hospitalization due to febrile illness was more than that of the public sector. Healthcare utilization patterns for hospital admissions due to febrile illness varied across sites. A meticulously performed HCUS is pivotal for accurate incidence estimation in a hybrid surveillance. Clinical Trials Registration ISRCTN72938224.

Background Primary data on causes and costs of hospitalization are necessary for costing and cost-effectiveness analysis. Data on incidence and causes of hospitalization and consequent expenses among Indian children are limited. Methods A cohort of 6000 children aged 0.5–15 years residing in urban Vellore was followed for 3 years, under the Vellore Typhoid Study, 2016–2017, and later under the Surveillance for Enteric Fever project, 2017–2019. Data on hospitalization events and associated antibiotic use, and direct medical costs for fever-related hospitalization of study children were obtained from caregivers through weekly follow-up by study field workers. Results The incidence of hospitalization was 33 per 1000 child-years of observation. Children aged 0.5–5 years had the highest incidence of hospitalization. The top 5 infectious causes for hospitalization were acute undifferentiated fevers, respiratory tract infections, acute gastroenteritis, enteric fever, and dengue. The overall median cost of hospitalization for fever was 4243 (interquartile range, 2502–7215) Indian rupees (INR). An episode of dengue had a median cost of 5627 INR, followed by acute undifferentiated fevers and enteric fever with median costs of 3860 and 3507 INR, respectively. Conclusions Hospitalization for fever is common in young children and impacts household finances in low-income Indian households.

BackgroundEnteric fever is a significant health challenge in low and middle-income countries. “Surveillance of Enteric Fever in India” (SEFI) network was set up to obtain reliable incidence data. Six sites utilised a hybrid surveillance model, a combination of facility-based surveillance and community-based healthcare utilisation survey (HCUS). HCUS was performed to determine the percentage of the catchment population utilising the study facilities for febrile episodes, and is described here.MethodsA two-stage sampling process was utilised for the HCUS to select 5000 households per site. Demographic data and healthcare-seeking behaviour were assessed.ResultsFebrile hospitalisation rate ranged from 2.5/1000 in Kullu to 9.6/1000 in Anantapur. The percentage of febrile admissions that sought care in the study hospital from the catchment area is 17% in Anantapur, 38% in Karimganj, 38% in Chandigarh, 10% in Nandurbar, 36% in Kullu and 24% in East Champaran respectively.ConclusionsThe variability in healthcare utilisation for fever admissions in the study hospitals underscores the importance of periodic healthcare utilisation surveys in hybrid surveillance. It is essential to adjust for those cases which have slipped out of the facility surveillance radar for obtaining an accurate estimate of the disease burden.

To report rotavirus-associated AGE (AGE) profile of admitted children among vaccine-introduced areas in Bhubaneswar, Odisha. This study was conducted between 2016 and 2019 at the Capital Hospital, Jagannath hospital and Hi-Tech Medical College and Hospital. All AGE patients below five years old, hospitalized in the study facilities were enrolled. A stool sample was collected and transported to the central laboratory (Christian Medical College, Vellore) for rotavirus antigen detection and genotyping. Clinical and demographic information was collected using a predesigned case report format (CRF). Out of the 1213 stool samples, 447 (36.9%) were identified to have rotavirus with 350 (78.3%) of them belonging to 6 mo to 2 y age group. Rotavirus gastroenteritis exhibited a single peak from November to February. A total of 414 (92.6%) of rotavirus gastroenteritis children had severe or very severe dehydration with odds of rotavirus diarrhea leading to severe dehydration being 1.5 (95% CI, 1–2.4) compared to moderate dehydration. The common genotype combination was G3P[8] (46%) followed by G1P[8] (19%), G2P[4] (5%), and G9P[4] (3%). Rotavirus gastroenteritis peaked between December to February while the most common genotype combination among the rotavirus GE was G3P[8] and G1P[8]. The present study provides the clinical profile of admitted children in the hospitals with diarrhea and the circulating strains of rotavirus which will help in documenting the epidemiology and the performance of vaccine against the disease in the state.

This study is aimed to determine the reliability of the Box and Block (BB) Test for manual dexterity of upper extremity function in patients with rheumatoid arthritis (RA) and to compare the results with age- and sex-matched healthy controls, and also with available normative data.The reliability of BB Test was assessed within and between testers using the intraclass correlation coefficient (ICC) in patients with RA attending rheumatology clinics of Christian Medical College Hospital, India. The dexterity scores of patients were then compared with age- and sex-matched controls and the Mathiowetz's population-based normative data by Student's independent t-test.The interrater and intrarater reliability of the BB Test in patients with RA (n = 60) ranged from 0.92 to 0.97 and 0.91 to 0.95, respectively. The dexterity scores in patients with RA were lower as compared to the control group (dominant hand 54.87 vs. 68.18, P 0.001; contralateral hand 52.65 vs. 65.6, P 0.001) and population-based normative score (dominant hand 54.87 vs. 80.02, P 0.001; contralateral hand 52.65 vs. 77.23; P 0.001). The control group scores were also lower than the normative data. Higher age of patient, longer disease duration and higher disease activity reflected by Disease Activity Score of 28 joints (DAS-28) also correlated well with lower dexterity score.The BB Test is a reliable tool for assessing upper extremity function in patients with RA and the dexterity scores are lower for RA patients. The scores had correlation with age, disease duration and disease activity.