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Title: Rotavirus transmission in the context of reduced vaccine effectiveness in low income countries
Author: Bennett, Aisleen May
ISNI:       0000 0004 7428 6013
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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Introduction. Rotavirus vaccine has been introduced into over 80 countries with substantial impact on rotavirus disease. However vaccine effectiveness is reduced in low-income countries. Patterns of rotavirus transmission could explain some of the observed reduced vaccine effectiveness, and vaccine-mediated reductions in rotavirus transmission may increase overall vaccine impact. A detailed understanding of rotavirus transmission in low income countries (LIC) is required to inform policy decisions to improve vaccine performance, however such data are currently lacking. Methods. Mixture models were used as a novel method to estimate population level incidence of rotavirus in young children from serology data and describe transmission patterns in India and Malawi. Surveillance data from Queen Elizabeth Central Hospital, Malawi, were used to describe the ongoing burden of rotavirus disease after vaccine introduction and investigate for vaccine indirect effects. To investigate whether rotavirus vaccine could reduce the infectiousness of a child with rotavirus disease a household transmission study was conducted in Blantyre, Malawi to describe rates of rotavirus transmission from a symptomatic index child to household contacts, investigate predictors of viral shedding density in the index child and identify risk factors for transmission. In a final study transmission of vaccine virus from vaccinated infants to unvaccinated contacts was evaluated to investigate for horizontal transmission of vaccine virus. Results. Mixture models described clear differences in patterns of rotavirus incidence in young children from India and Malawi. Analysis of surveillance data showed that rotavirus remains an important cause of hospitalised diarrhoeal disease in Blantyre despite high vaccine coverage, and identified some evidence of an indirect effect in unvaccinated infants. Household studies found a high rate of transmission of infection to household contacts (434/665, 65%) but a lower rate of transmission for disease (37/698, 5.3%). Disease severity in the index child was associated with an increased risk of transmission to household contacts, independent of viral shedding density. Rates of transmission of vaccine virus to household contacts were very low (2/151, 1.3%). Conclusions. These studies demonstrate that rotavirus remains a significant cause of admitted diarrhoeal disease in Blantyre, Malawi and describe some evidence of a vaccine indirect effect. Transmission rates of rotavirus infection to household contacts are associated with disease severity in the index child. As vaccine provides incremental protection against severe disease, vaccination therefore has potential to reduce the infectiousness of a vaccinated index child. Horizontal transmission of vaccine virus is infrequent and unlikely to make a substantial contribution to rotavirus vaccine indirect effects in this setting. In view of high vaccine coverage future studies should consider mathematical models to make inferences on the impact of vaccine and inform ongoing vaccine strategy.
Supervisor: Cunliffe, Nigel ; Bar-Zeev, Naor ; Everett, Dean Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral