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.).

Safety monitoring of ROTAVAC vaccine and etiological investigation of intussusception in India: study protocol.

BACKGROUND: ROTAVAC, an indigenous rotavirus vaccine, was introduced in the universal immunization program of India in four states in 2016 and expanded to five more states in 2017. The clinical trial on efficacy of ROTAVAC did not detect an increased risk of intussusception, but the trial was not large enough to detect a small risk. This protocol paper describes the establishment and implementation of a surveillance system to monitor the safety of rotavirus vaccine and investigate the potential infectious etiologies of intussusception. METHODS: This is a multi-centric hospital-based active surveillance being conducted at 28 hospitals in nine states of India. Data gathered from surveillance will be used to assess the risk of intussusception after ROTAVAC administration and to determine the infectious etiologies of intussusception. For safety assessment of ROTAVAC vaccine, children aged less than two years with intussusception admitted at the sentinel hospitals are enrolled into surveillance, a case report form completed, and a copy of the vaccination card obtained. The risk of intussusception following rotavirus vaccination will be assessed using a self-controlled case-series design. The investigation for potential infectious etiologies of intussusception is through a matched case-control design. Children enrolled for the safety assessment serve as cases and for each case, an age, gender and location matched control is enrolled within 30 days of case enrollment. Stool specimens are obtained from cases and controls. All forms and specimens are sent to the referral laboratory for data entry, analysis, multiplexed molecular testing, and storage. DISCUSSION: Anticipated public health benefits of this surveillance include the generation of information useful to national government on safety of vaccine and to make future decisions on vaccine use through risk-benefit analysis. Investigating infectious agents may help to determine the potential infectious etiologies of intussusception.

Developing and demonstrating an atomistic and holistic model of anthropometric failure among children under five years of age using the National Family Health Survey (NFHS)-5 data from India.

Introduction: Composite Index of Anthropometric Failure (CIAF) and its further modifications have not incorporated all the combinations of malnutrition. We propose a new model incorporating all the forms of malnutrition among children under five years of age. However, the current models might misclassify a growing child as malnourished. Our objective is to develop a comprehensive scoring system using the three anthropometric Z-scores [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) Z-scores] and demonstrate the proposed CIAF model using the National Family Health Survey-5 (NFHS-5) data from India. Methods: A new scoring system was developed using the WAZ, HAZ, and WHZ scores to determine the child's nutritional status. We also proposed a new CIAF model by including all possible categories of malnutrition and practically demonstrated it using the NFHS-5 dataset after applying the new scoring system. Under-five children with heights, weights, and ages available were included in the analysis. The groups of malnutrition are presented as weighted proportions before and after applying the new score to the proposed model. Results: Our final analysis included individual-level data of 198,802 children under five years of age (weighted N = 195,197). After applying the new scoring system to the proposed model, the prevalence of stunting has reduced to 11.8% (95% CI 11.66-11.94) from 13.2% (95% CI 13.09-13.39) and wasting prevalence has reduced to 4.9% (95% CI 4.85-5.04) from 6.4% (95% CI 6.29-6.51). The most common forms of anthropometric failures among Indian children by using the newly developed CIAF model are: "Stunting and underweight" (30,127; 15.4%), Stunting only (23,035; 11.8%), and "wasting and underweight" (14,698; 7.5%). We found a new category called "Stunting, underweight, and overweight" (stunting = HAZ < -2SD, underweight = WAZ < -2SD, overweight = WHZ > +2SD). It constituted 0.1% (220 children) of the total sample. Conclusion: When the new scoring system is applied to the proposed CIAF model, it captures all forms and combinations of malnutrition among under-five children without overlap and prevents misclassifying a growing child as malnourished. The newly identified category shows that stunting (HAZ < -2SD), overweight (WHZ > +2SD) and underweight (WAZ < -2SD) can co-exist in the same child.