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

Background. The World Health Organization (WHO) recommends case definitions for influenza surveillance that are also used in public health research, although 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 real-time reverse transcription-polymerase chain reaction (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 modeling. Results. Of 5444 eligible illness episodes among 3965 participants, 310 (6%) were positive for influenza. In a multivariable model, measured fever >= 38 degrees C (adjusted odds ratio [95% confidence interval], 4.6 [3.1-6.8]), myalgia (3.0 [2.2-4.0]), cough (2.7 [1.9-3.9]), and chills (1.6 [1.1-2.4]) were independently associated with influenza illness. A definition based on these 4 (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.