Abstract
Rotavirus vaccine effectiveness is reduced among children in low-income countries. Indirect (transmission-mediated) effects of rotavirus vaccine might contribute to the total population effect of vaccination. We aimed to examine risk factors for transmission of rotavirus to household contacts in Blantyre, Malawi, and estimated the effectiveness of rotavirus vaccine in preventing transmission of infection to household contacts. In this prospective household cohort study, we recruited children born after Sept 17, 2012, and aged at least 6 weeks (vaccine-eligible children) with acute rotavirus gastroenteritis and their household contacts, in four government health facilities in Blantyre, Malawi. Clinical data, a bulk stool sample, and 1-2 mL of serum were collected from case children at presentation. Clinical data and stool samples were also prospectively collected from household contacts over 14 days from presentation. A single stool sample was collected from control households containing asymptomatic children who were frequency age-matched to case children. Samples were tested for rotavirus using semi-quantitative real-time PCR and for anti-rotavirus IgA using a semi-quantitative sandwich ELISA. Risk factors for household transmission of rotavirus infection and clinical disease, including disease severity and faecal shedding density, were identified using mixed effects logistic regression. Vaccine effectiveness against transmission was estimated as 1 minus the ratio of secondary attack rates in vaccinated and counterfactual unvaccinated populations, using vaccine effectiveness estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual secondary attack rate without vaccination. Between Feb 16, 2015, and Nov 11, 2016, we recruited 196 case households (705 members) and 55 control households (153 members). Household secondary attack rate for rotavirus infection was high (434 [65%] of 665 individuals) and secondary attack rate for clinical disease was much lower (37 [5%] of 698). Asymptomatic infection in control households was common (40 [28%] of 144). Increasing disease severity in an index child (as measured by Vesikari score) was associated with increased risk of transmission of infection (odds ratio 1·17 [95% CI 1·06-1·30) and disease (1·28 [1·08-1·52]) to household contacts. Estimated vaccine effectiveness against transmission was 39% (95% CI 16-57). Rotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This finding should be considered in clinical and health economic assessments of vaccine effectiveness. Wellcome Trust, US National Institutes of Health, and US National Institute of Allergy and Infectious Diseases.
Highlights
Rotavirus vaccine has been introduced into over 90 countries worldwide, including 45 low-income and middle-income countries.1 rotavirus vaccine effectiveness is reduced in low-income countries, where disease burden is highest, compared with high-income countries.2 despite high vaccine coverage, rotavirus remains the commonest cause of hospital admissions due to diarrhoeal disease in some low-income countries.3 Because direct vaccine effectiveness is reduced in low-income and middle-income countries, additional transmission-mediated effects of the vaccine have the potential to make important contributions to population-level vaccine effects
Rotavirus vaccination mimics immunity induced by natural rotavirus infections, which confer incremental protection against severe rotavirus disease to a degree that varies by location
Rotavirus disease severity has been shown to correlate with density of faecal rotavirus shedding in studies in India and Malawi,8 and evidence suggests that severity of symptoms is related to the risk of transmission
Summary
Rotavirus vaccine has been introduced into over 90 countries worldwide, including 45 low-income and middle-income countries. rotavirus vaccine effectiveness is reduced in low-income countries, where disease burden is highest, compared with high-income countries. despite high vaccine coverage, rotavirus remains the commonest cause of hospital admissions due to diarrhoeal disease in some low-income countries. Because direct vaccine effectiveness is reduced in low-income and middle-income countries, additional transmission-mediated (indirect) effects of the vaccine have the potential to make important contributions to population-level vaccine effects. Rotavirus vaccine has been introduced into over 90 countries worldwide, including 45 low-income and middle-income countries.. Rotavirus vaccine effectiveness is reduced in low-income countries, where disease burden is highest, compared with high-income countries.. Despite high vaccine coverage, rotavirus remains the commonest cause of hospital admissions due to diarrhoeal disease in some low-income countries.. Because direct vaccine effectiveness is reduced in low-income and middle-income countries, additional transmission-mediated (indirect) effects of the vaccine have the potential to make important contributions to population-level vaccine effects. The magnitude of indirect effects that are attributable to rotavirus vaccine and the mechanisms which underpin them are poorly understood.. Rotavirus vaccination mimics immunity induced by natural rotavirus infections, which confer incremental protection against severe rotavirus disease to a degree that varies by location.. Vaccination, not providing complete protection against disease, might Rotavirus vaccination mimics immunity induced by natural rotavirus infections, which confer incremental protection against severe rotavirus disease to a degree that varies by location. Rotavirus disease severity has been shown to correlate with density of faecal rotavirus shedding in studies in India and Malawi, and evidence suggests that severity of symptoms is related to the risk of transmission. vaccination, not providing complete protection against disease, might
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