Comparative epidemiology of respiratory syncytial virus (RSV) and influenza viruses

Abstract

Respiratory syncytial virus (RSV) and influenza virus infections cause substantial disease burden worldwide. This thesis aimed to i) enhance understanding of the epidemiology of RSV and influenza virus; ii) review the protection against influenza virus infection at an hemagglutination inhibition (HAI) titer of 40. I used generalized additive model (GAM) to estimate influenza-associated mortality based on the individual death data in Yancheng during 2011-2015. An annual average of 4.59 (95% confidence interval: 3.94, 7.41) excess respiratory deaths per 100,000 persons were estimated to be associated with influenza, which corresponded to 4.6% of all respiratory deaths during the study period. Influenza A(H3N2) had the greatest impact on mortality, which accounted for more than 50% of influenza-associated respiratory deaths during the study period. The majority of influenza- associated mortality was estimated to occur in older adults. I estimated the impact of RSV on mortality and hospitalization rates by cause and by age in Hong Kong during1998-2015 using GAM. I estimated that annual averages of 0.20 (95% CI: 0.05, 0.36) and 31 (95% CI: 22, 40) excess respiratory deaths per 100,000 persons per year were associated with RSV in persons <65y and older adults ≥65y, respectively. Most RSV-associated respiratory deaths occurred in older adults. Annual rates of RSV-associated respiratory hospitalizations were highest in infants <1y and older adults ≥65y, being 2500 (95% CI: 2300, 2700) and 330 (95% CI: 230, 430) per 100,000 person-years respectively, and these two age groups contributed 22% and 53% of all RSV-associated respiratory hospitalizations respectively. There was an indication from a comparison of hospitalization and mortality rates that RSV infection could cause much more severe diseases than influenza virus infection among older adults. I used three different approaches to provide an overview of RSV seasonality in Hong Kong during 1998-2017 based on the surveillance data. Temperature and relative humidity were found to be positively related to RSV detection rates. I established a compartmental Susceptible-Exposed- Infectious-Recovered-Susceptible model with seasonal forcing to model RSV epidemics. The estimated R0 fell in the range 1.08-1.64, and meteorological factors were found to play a role in RSV transmission. The average transmission parameter was sensitive to the variation of latent period and infectious period, but much more stable to variation in the assumed duration of immunity.

I performed a systematic review and meta-analysis to explore the association between HAI titer level and protection against influenza virus infection. 23 studies were included, an HAI titer of 40 was associated with protection against influenza virus infection, and the protection ranged from 19% to 87% with high heterogeneity (I2=83%). In the subset of studies where infection was identified using a virological test (i.e. PCR or virus culture), an HAI titer of 40 was associated with 43% (95% CI: 36-50%) protection with low heterogeneity (I2=3%). A particular HAI titer may correspond to different levels of protection due to heterogeneous immune responses elicited from recent or past vaccination or infection, which could be related to different antibody qualities, or to additional protection through other mechanisms, e.g. cell-mediated immunity.