Background: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most
common viruses associated with acute lower respiratory infections in young children (<5 years) and older people
(≥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Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data.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 threestage 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° by 5° 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. |