Performance of Symptom-Based Case Definitions to Identify Influenza Virus Infection Among Pregnant Women in Middle-Income Countries: Findings From the Pregnancy and Influenza Multinational Epidemiologic (PRIME) Study

Abstract

Background The World Health Organization (WHO) recommends case definitions for influenza surveillance that are also used in public health research, though their performance has not been assessed in many risk groups, including pregnant women in whom influenza may manifest differently. We evaluated the performance of symptom-based definitions to detect influenza in a cohort of pregnant women in India, Peru, and Thailand. Methods In 2017 and 2018, we contacted 11,277 pregnant women twice weekly during the influenza season to identify illnesses with new or worsened cough, runny nose, sore throat, difficulty breathing or myalgia, and collected data on other symptoms and nasal swabs for influenza rRT-PCR testing. We calculated sensitivity, specificity, positive predictive value and negative predictive value of each symptom-predictor, WHO respiratory illness case definitions and a de novo definition derived from results of multivariable modelling. Results Of 5,444 eligible illness episodes among 3,965 participants, 310 (6%) were positive for influenza. In a multivariable model, measured fever ≥38° Celsius (adjusted odds ratio = 4.6, 95% confidence interval [CI] = 3.1, 6.8), myalgia (3.0, 95% CI: 2.2, 4.0), cough (2.7, 95% CI: 1.9, 3.9), and chills (1.6, 95% CI: 1.1, 2.4) were independently associated with influenza illness. A definition based on these four (measured fever, cough, chills or myalgia), was 95% sensitive and 27% specific. The WHO influenza-like illness (ILI) definition was 16% sensitive and 98% specific. Conclusions The current WHO ILI case definition was highly specific but had low sensitivity. The intended use of case definitions should be considered when evaluating the tradeoff between sensitivity and specificity.

Incidence of influenza and other respiratory viruses among pregnant women: A multi‐country, multiyear cohort

“… c Estimates assume that untested women with ARI in the Panama and El Salvador cohorts would have been as likely to test positive for specific respiratory viruses as persons aged 15–49 years identified through each country's national surveillance system. For influenza, specifically, we adjusted the proportion of influenza detections among afebrile versus febrile adults with ARI (i.e., 0.24) 14 because untested women were typically afebrile, while those tested were febrile. To partially account for uncertainty in these estimates, we also incorporated the variance in the proportion of persons testing positive each week into the respiratory virus‐specific rates and the variance in the proportion of afebrile persons testing positive versus those who were febrile.…”