Publication Date

2013-07-29

Availability

Embargoed

Embargo Period

2015-07-29

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Epidemiology (Medicine)

Date of Defense

2013-06-25

First Committee Member

David J. Lee

Second Committee Member

Kristopher L. Arheart

Third Committee Member

John C. Beier

Fourth Committee Member

Mary Jo Trepka

Abstract

Influenza pandemics occur at unpredictable intervals and can cause significant illness and death, as well as disruptions to society. With each new influenza pandemic there is a need to understand basic parameters of the virus and illness to facilitate the public health response. These parameters relate, among others, to the transmission dynamics of the new virus, such as secondary attack rate and serial interval; risk factors for infection, severe illness, and death; and efficacy of existing diagnostic, preventive, and therapeutic measures applied to the new pandemic virus. In 2009, a global influenza pandemic occurred, more than 40 years following the previous pandemic. As in past pandemics, the 2009 pandemic presented various applied research needs to inform the public health response. This dissertation represents applied public health research, conducted in Florida, and addressing 3 areas: 1) estimating secondary household transmission of the pandemic virus; 2) characterizing adverse maternal and neonatal outcomes among pregnant women infected with pandemic influenza; and 3) assessing the impact of timing of antiviral therapy on maternal and neonatal outcomes among pregnant women in Florida, and comparing these results to those previously reported in a national case series. Data used for this dissertation were collected under public health authority of the Florida Department of Health, in response to the pandemic. In the first instance, secondary household transmission was assessed following an outbreak of 2009 pandemic influenza A(H1N1) [pH1N1] at a residential summer camp for boys aged 10 to 16 years. In the second instance, a retrospective population based cohort was established of all live births occurring in Florida during the first 15 months of the pandemic. Illness with pH1N1 during pregnancy was ascertained through record linkage with the Florida state notifiable disease surveillance database. Data from the birth record, including pre-pregnancy body mass index, were analyzed to assess risk of adverse outcomes associated with pH1N1 illness. In the third instance, data from the same women with laboratory confirmed pH1N1 illness during pregnancy were used to assess the impact of the timing of antiviral treatment on maternal and neonatal outcomes, and results were compared with previously published findings from a national case series. For the household secondary transmission study, among approximately 212 study participants who attended camp, 49 had confirmed or probable influenza for a primary attack rate of 23%. Among 87 exposed household contacts who did not attend camp, only 3 instances of probable transmission were observed, for a household secondary attack rate of 3.5%. All secondary cases occurred in households where the ill camp attendee returned home one day after onset of illness, with an attack rate of 14.3% among household contacts in this category. For the study of maternal and neonatal outcomes, children born to women with pH1N1 illness during pregnancy were at increased risk for low birth weight [OR (95% CI): 1.78 (1.11-2.86)], premature birth [2.21 (1.47-3.33)], and infant death [4.46 (1.80-11.00)], after adjusting for other factors. Women with pH1N1 illness during pregnancy were at increased risk for severe outcomes including admission to an intensive care unit. Obesity was an observed risk factor, both for the more severe pH1N1 illness detected through surveillance and for severe maternal outcomes. Adverse maternal and neonatal outcomes were associated with delays in antiviral treatment for influenza. Results from the Florida case series were consistent with previous findings from the national case series. In the secondary transmission study, returning home after peak infectivity to others and advanced warning prior to reintegration of sick individuals into the household likely contributed to the overall low secondary attack rate observed. For the maternal and neonatal outcomes study, pregnant women continue to be a high-risk group for severe illness due to influenza and should continue to be targeted for appropriate prophylaxis and early treatment.

Keywords

influenza; pandemic; outcomes; secondary transmission

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