Epidemiology of influenza B virus by lineage

Abstract

Influenza A virus (IAV) and Influenza B virus (IBV) are the most common seasonal influenza viruses and have caused substantial disease burden worldwide. Since its discovery in the 1940s, IBV has gained relatively little research attention compared to IAV despite sharing similar clinical characteristics, presumably because IBV demonstrates exclusive transmission among human population and hence poses a low pandemic threat, whereas IAV is known to have caused several pandemics in the past century. In the 1970s, IBV split into two antigenically distinct lineages, termed B/Victoria and B/Yamagata. Co-circulating globally since the 2000/01 season, they were found to demonstrate potential differences and interaction, namely distinctive evolutionary pattern, irregular predominance, different age distribution of infection and cross-lineage reactivity of antibodies, all of which makes disease control of IBV more difficult, hence the need for further research on IBV lineages.

This thesis focuses on the epidemiology of IBV by lineage. A descriptive analysis was conducted on the epidemiological patterns of IBV in China based on national sentinel surveillance data. IBV was mainly active during the winter-spring period, while alternating predominance of IBV lineages across seasons was identified. A discrepancy in age distribution between lineages was also found where elder adults were more susceptible to infection of B/Yamagata lineage than B/Victoria lineage, which was consistent with the observations from other countries.

The epidemiology of IBV lineages was also assessed from a serological perspective based on data collected from a community-based cohort study in Hong Kong. A mathematical model was developed to describe the lineage-specific response in hemagglutination-inhibition (HAI) titer associated with IBV lineage infection confirmed by real-time reverse transcription polymerase chain reaction (PCR). Among half of the PCR-confirmed cases showing HAI response, it was found that the infection would induce a substantial boost in the homologous antibodies and a moderate boost in the heterologous antibodies, which suggests a possibility of cross-lineage reactivity. The association between lineage-specific pre-infection HAI titer against the risk of IBV infection was further assessed with a survival hazard model, revealing a moderate degree of cross-lineage protection associated with heterologous HAI titer against IBV infection among PCR-confirmed cases.

In order to investigate the epidemiological impact of cross-lineage protection on the transmission dynamics of IBV by lineage in Hong Kong, a deterministic compartmental model was constructed. Cross-lineage protection was parameterized as the proportional reduction in susceptibility to infection by the opposing lineage due to immunity acquired after infection by a certain lineage. B/Yamagata lineage was found to be more active than B/Victoria lineage in Hong Kong. The model estimated that the degree of cross-lineage protection was approximately 50%, which might have contributed to the irregular seasonality of IBV lineage epidemics in Hong Kong.

This thesis identifies age as an important factor to the epidemiology of IBV and provides some evidence of cross-lineage reactivity and partial cross-lineage protection. This may have implications on the optimization of vaccination strategy during seasons when there is a lineage mismatch between the vaccine strain and the predominant strain.