John Kubale1, Guillermina Kuan2, Lionel Gresh3, Sergio Ojeda3, Amy Schiller1, Nery Sanchez3, Roger Lopez4, Eduardo Azziz-Baumgartner5, Steph Wraith1, Eva Harris6, Angel Balmaseda4, Jon Zelner1, Aubree Gordon1. 1. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA. 2. Sócrates Flores Vivas Health Center, Ministry of Health, Managua, Nicaragua. 3. Sustainable Sciences Institute, Managua, Nicaragua. 4. Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua. 5. Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 6. Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California, USA.
Abstract
BACKGROUND: Pneumonia is a leading cause of mortality worldwide. Influenza may result in primary pneumonia or be associated with secondary bacterial pneumonia. While the association with secondary pneumonia has been established ecologically, individual-level evidence remains sparse and the risk period for pneumonia following influenza poorly defined. METHODS: We conducted a matched case-control study and a prospective cohort study among Nicaraguan children aged 0-14 years from 2011 through 2018. Physicians diagnosed pneumonia cases based on Integrated Management for Childhood Illness guidelines. Cases were matched with up to 4 controls on age (months) and study week. We fit conditional logistic regression models to assess the association between influenza subtype and subsequent pneumonia development, and a Bayesian nonlinear survival model to estimate pneumonia hazard following influenza. RESULTS: Participants with influenza had greater risk of developing pneumonia in the 30 days following onset compared to those without influenza (matched odds ratio [mOR], 2.7 [95% confidence interval {CI}, 1.9-3.9]). Odds of developing pneumonia were highest for participants following A(H1N1)pdm09 illness (mOR, 3.7 [95% CI, 2.0-6.9]), followed by influenza B and A(H3N2). Participants' odds of pneumonia following influenza were not constant, showing distinct peaks 0-6 days (mOR, 8.3 [95% CI, 4.8-14.5] days) and 14-20 (mOR, 2.5 [95% CI, 1.1-5.5] days) after influenza infection. CONCLUSIONS: Influenza is a significant driver of both primary and secondary pneumonia among children. The presence of distinct periods of elevated pneumonia risk in the 30 days following influenza supports multiple etiological pathways.
BACKGROUND: Pneumonia is a leading cause of mortality worldwide. Influenza may result in primary pneumonia or be associated with secondary bacterial pneumonia. While the association with secondary pneumonia has been established ecologically, individual-level evidence remains sparse and the risk period for pneumonia following influenza poorly defined. METHODS: We conducted a matched case-control study and a prospective cohort study among Nicaraguan children aged 0-14 years from 2011 through 2018. Physicians diagnosed pneumonia cases based on Integrated Management for Childhood Illness guidelines. Cases were matched with up to 4 controls on age (months) and study week. We fit conditional logistic regression models to assess the association between influenza subtype and subsequent pneumonia development, and a Bayesian nonlinear survival model to estimate pneumonia hazard following influenza. RESULTS: Participants with influenza had greater risk of developing pneumonia in the 30 days following onset compared to those without influenza (matched odds ratio [mOR], 2.7 [95% confidence interval {CI}, 1.9-3.9]). Odds of developing pneumonia were highest for participants following A(H1N1)pdm09 illness (mOR, 3.7 [95% CI, 2.0-6.9]), followed by influenza B and A(H3N2). Participants' odds of pneumonia following influenza were not constant, showing distinct peaks 0-6 days (mOR, 8.3 [95% CI, 4.8-14.5] days) and 14-20 (mOR, 2.5 [95% CI, 1.1-5.5] days) after influenza infection. CONCLUSIONS: Influenza is a significant driver of both primary and secondary pneumonia among children. The presence of distinct periods of elevated pneumonia risk in the 30 days following influenza supports multiple etiological pathways.
Authors: Seema Jain; Wesley H Self; Richard G Wunderink; Sherene Fakhran; Robert Balk; Anna M Bramley; Carrie Reed; Carlos G Grijalva; Evan J Anderson; D Mark Courtney; James D Chappell; Chao Qi; Eric M Hart; Frank Carroll; Christopher Trabue; Helen K Donnelly; Derek J Williams; Yuwei Zhu; Sandra R Arnold; Krow Ampofo; Grant W Waterer; Min Levine; Stephen Lindstrom; Jonas M Winchell; Jacqueline M Katz; Dean Erdman; Eileen Schneider; Lauri A Hicks; Jonathan A McCullers; Andrew T Pavia; Kathryn M Edwards; Lyn Finelli Journal: N Engl J Med Date: 2015-07-14 Impact factor: 91.245
Authors: C Launes; J-J García-García; M Triviño; N Peris; R Pallarés; C Muñoz-Almagro Journal: Clin Microbiol Infect Date: 2014-08-13 Impact factor: 8.067
Authors: Christa L Fischer Walker; Igor Rudan; Li Liu; Harish Nair; Evropi Theodoratou; Zulfiqar A Bhutta; Katherine L O'Brien; Harry Campbell; Robert E Black Journal: Lancet Date: 2013-04-12 Impact factor: 79.321
Authors: Simon P Jochems; Fernando Marcon; Beatriz F Carniel; Mark Holloway; Elena Mitsi; Emma Smith; Jenna F Gritzfeld; Carla Solórzano; Jesús Reiné; Sherin Pojar; Elissavet Nikolaou; Esther L German; Angie Hyder-Wright; Helen Hill; Caz Hales; Wouter A A de Steenhuijsen Piters; Debby Bogaert; Hugh Adler; Seher Zaidi; Victoria Connor; Stephen B Gordon; Jamie Rylance; Helder I Nakaya; Daniela M Ferreira Journal: Nat Immunol Date: 2018-10-29 Impact factor: 25.606
Authors: Eduardo Azziz-Baumgartner; Alfredo Bruno; Michael Daugherty; Martha E Chico; Andrea Lopez; Carmen Sofia Arriola; Domenica de Mora; Alba María Ropero; William W Davis; Meredith McMorrow; Philip J Cooper Journal: Influenza Other Respir Viruses Date: 2021-08-25 Impact factor: 5.606