Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

You Li, Rachel M. Reeves, Xin Wang, Quique Bassat, W. Abdullah Brooks, Cheryl Cohen, David P. Moore, Marta Nunes, Barbara Rath, Harry Campbell, Harish Nair, Sozinho Acacio, Wladimir J. Alonso, Martin Antonio, Guadalupe Ayora Talavera, Darmaa Badarch, Vicky L. Baillie, Gisela Barrera-Badillo, Godfrey Bigogo, Shobha BroorDana Bruden, Philippe Buchy, Peter Byass, James Chipeta, Wilfrido Clara, Duc-Anh Dang, Carla Cecilia de Freitas Lazaro Emediato, Menno de Jong, Jose Alberto Diaz-Quinonez, Lien Anh Ha Do, Rodrigo A. Fasce, Luzhao Feng, Mark J. Ferson, Angela Gentile, Bradford D. Gessner, Doli Goswami, Sophie Goyet, Carlos G. Grijalva, Natasha Halasa, Orienka Hellferscee, Danielle Hessong, Nusrat Homaira, Jorge Jara, Kathleen Kahn, Najwa Khuri-Bulos, Karen L. Kotloff, Claudio F. Lanata, Olga Lopez, Maria Renee Lopez Bolanos, Marilla G. Lucero, Florencia Lucion, Socorro P. Lupisan, Shabir A. Madhi, John P. McCracken, Omphile Mekgoe, Cinta Moraleda, Jocelyn Moyes, Kim Mulholland, Patrick K. Munywoki, Fathima Naby, Thanh Hung Nguyen, Mark P. Nicol, D. James Nokes, Daniel E. Noyola, Daisuke Onozuka, Nandhini Palani, Yong Poovorawan, Mustafizur Rahman, Kaat Ramaekers, Candice Romero, Elizabeth P. Schlaudecker, Brunhilde Schweiger, Phil Seidenberg, Eric A. F. Simoes, Rosalyn Singleton, Sujatha Sistla, Katharine Sturm-Ramirez, Nungruthai Suntronwong, Agustinus Sutanto, Milagritos D. Tapia, Somsak Thamthitiwat, Ilada Thongpan, Gayani Tillekeratne, Yeny O. Tinoco, Florette K. Treurnicht, Claudia Turner, Paul Turner, Rogier van Doorn, Marc Van Ranst, Benoit Visseaux, Sunthareeya Waicharoen, Jianwei Wang, Lay-Myint Yoshida, Heather J. Zar, Ting Shi, Shanshan Zhang, Peter Openshaw, Jadwicha Wedzicha, Ann Falsey, Mark Miller, Philippe Beutels, Louis Bont, Andrew Pollard, Eva Molero, Federico Martinon-Torres, Terho Heikkinen, Adam Meijer, Thea Kolsen Fischer, Maarten van den Berge, Carlo Giaquinto, Rafael Mikolajczyk, Judy Hackett, Laura Dillon, Eskinder Tafesse, Bing Cai, Charles Knirsch, Antonio Gonzalez Lopez, Ilse Dieussaert, Nadia Dermateau, Amanda Leach, Sonia K. Stoszek, Scott Gallichan, Alexia Kieffer, Clarisse Demont, Angeline Denouel, Arnaud Cheret, Sandra Gavart, Jeroen Aerssens, Veronique Wyffels, Matthias Cleenewerck, Robert Fuentes, Brian Rosen

Research output: Contribution to journalArticleResearchpeer-review


Background Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (= 65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control.

Methods In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5 degrees by 5 degrees grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628.

Findings We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0.3 months [95% CI -0.3 to 0.9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3.8 months [3.6 to 4.0]) in temperate sites and longer duration (5.2 months [4.9 to 5.5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4.6 months [4.3 to 4.8]), as it was for metapneumovirus (4.8 months [4.4 to 5.1]). By comparison, parainfluenza virus had longer duration of epidemics (6.3 months [6.0 to 6.7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0.2 months [-0.6 to 0.1]; respiratory syncytial virus 0.1 months [-0.2 to 0.4]).

Interpretation This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.

Original languageEnglish
Pages (from-to)E1031-E1045
Number of pages15
JournalThe Lancet Global Health
Issue number8
Publication statusPublished - Aug 2019



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