Influenza Susceptibility and Transmission

Abstract

Influenza causes substantial burden in terms of illness, lost productivity, hospi- talization, and death worldwide, with the highest burden in lower income countries. Vaccines are one of the best protective measures we have against influenza, but cur- rent seasonal influenza vaccines offer suboptimal protection, and are strain-specific necessitating yearly vaccine updates and offering no protection against potential pan- demic strains. Identifying risk factors for influenza susceptibility and disease severity is important to be able to effectively target prevention and treatments to lower the burden and reduce transmission, particularly in low-resourced settings. This dissertation looks at immune factors that could improve next generation vaccines in chapter II and obesity as a risk factor for influenza outcomes in chapters III and IV. The work presented here uses data from studies of household influenza transmission in Managua, Nicaragua. I used Accelerated Failure Time (AFT) models (chapters II and III) and logistic regression (chapter IV) to investigate these questions. In chapter II, we found that pre-existing neuaraminidase (NA) antibodies were associated with decreased viral shedding duration. This suggests that increasing NA immune response could improve future influenza vaccines by decreasing influenza dis- ease duration and thus also decreasing transmission. Chapters III and IV identified obesity as a risk factor for increased influenza A viral shedding duration, which can increase transmission, and increased susceptibility to influenza A(H1N1)pdm, respec- tively. Identifying obesity as a risk factor for increased influenza susceptibility and transmission may help target future preventive and therapeutic measures.