Burden of Typhoid and Paratyphoid Fever in India.

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.).

Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Prediction of hookworm prevalence in southern India using environmental parameters derived from Landsat 8 remotely sensed data.

Soil-transmitted helminth infections propagate poverty and slow economic growth in low-income countries. As with many other neglected tropical diseases, environmental conditions are important determinants of soil-transmitted helminth transmission. Hence, remotely sensed data are commonly utilised in spatial risk models intended to inform control strategies. In the present study, we build upon the existing modelling approaches by utilising fine spatial resolution Landsat 8 remotely sensed data in combination with topographic variables to predict hookworm prevalence in a hilly tribal area in southern India. Hookworm prevalence data collected from two field surveys were used in a random forest model to investigate the predictive capacity of 15 environmental variables derived from two remotely sensed images acquired during dry and rainy seasons. A variable buffer radius (100-1000 m) was applied to the point-prevalence locations in order to integrate environmental conditions around the village centroids into the modelling approach and understand where transmission is more likely. Elevation and slope were the most important variables in the models, with lower elevation and higher slope correlating with higher transmission risk. A modified normalised difference water index was among other recurring important variables, likely responsible for some seasonal differences in model performance. The 300 m buffer distance produced the best model performance in this setting, with another spike at 700 m, and a marked drop-off in R2 values at 1000 m. In addition to assessing a large number of environmental correlates with hookworm transmission, the study contributes to the development of standardised methods of spatial linkage of continuous environmental data with point-based disease prevalence measures for the purpose of spatially explicit risk profiling.

Study design and baseline results of an open-label cluster randomized community-intervention trial to assess the effectiveness of a modified mass deworming program in reducing hookworm infection in a tribal population in southern India.

INTRODUCTION: Hookworm infection is a leading cause of iron deficiency anemia and malnutrition in resource-poor settings. Periodic mass deworming with anthelminthic drugs remains the cornerstone of hookworm control efforts worldwide. Reinfection following treatment occurs, reflecting the human host's inability to acquire immunity following exposure to an untreated reservoir of infection. This cluster randomized trial will evaluate the effectiveness of a modified, population-based, mass deworming strategy in reducing hookworm infection in an endemic southern Indian population. METHODS: Forty five tribal villages were randomized into three groups: one received annual treatment; the second received two rounds of treatment at 1-month intervals; and the third received four rounds of treatment - two rounds 1 month apart at the beginning, followed by another two after 6 months. Stool samples collected through cross-sectional parasitological surveys pre- and post-intervention, and at 3-monthly intervals for a period of 1 year were tested for presence of hookworm ova. Long-term effectiveness of treatment will be assessed through another survey conducted 2 years after the last treatment cycle. RESULTS: From a population of 11,857 individuals, 8681 (73.2%) were found to be eligible and consented to participate, out-migration being the primary reason for non-participation. Baseline stool samples were obtained from 2082 participants, with 18.5% having hookworm infection, although majority were low intensity infections (<2000 eggs per gram of feces). DISCUSSION: This study will help identify the optimal mass deworming strategy that can achieve the greatest impact in the shortest period of time, particularly in settings where long-term program sustainability is a challenge.