Timing of respiratory syncytial virus and influenza epidemic activity in five regions of Argentina, 2007‐2016

Background Within‐country differences in the timing of RSV and influenza epidemics have not been assessed in Argentina, the eighth largest country in the world by area. Objective We aimed to compare seasonality for RSV and influenza both nationally and in each of the five regions to inform Argentina’s prevention and treatment guidelines. Method The Argentine National Laboratories and Health Institutes Administration collected respiratory specimens from clinical practices, outbreak investigations, and respiratory virus surveillance in 2007‐2016; these were tested using immunofluorescence or RT‐PCR techniques. We calculated weekly percent positive (PP) and defined season onset as >2 consecutive weeks when PP exceeded the annual mean for the respective year and region. Median season measures (onset, offset and peak) and the established mean method were calculated for each virus. Results An annual median 59 396 specimens were tested for RSV and 60 931 for influenza; 21–29% tested positive for RSV and 2–7% for influenza. National RSV activity began in April; region‐specific start weeks varied by 7 weeks. Duration of RSV activity did not vary widely by region (16–18 weeks in duration). National influenza activity started in June; region‐specific start weeks varied by 3 weeks. Duration of influenza epidemic activity varied more by region than that of RSV (7–13 weeks in duration). Conclusion In Argentina, RSV and influenza activity overlapped during the winter months. RSV season tended to begin prior to the influenza season, and showed more variation in start week by region. Influenza seasons tended to vary more in duration than RSV seasons.


| INTRODUC TI ON
Respiratory syncytial virus (RSV) and influenza viruses cause substantial disease and economic burden. 1,2 Surveillance systems in temperate countries demonstrate that RSV and influenza activity are seasonal and typically peak during colder months. [3][4][5][6] In large countries like China and India, regional differences in respiratory virus activity can be substantial. 7,8 These differences can be large enough that public health officials recommend administering different influenza vaccine formulations at different times of the year within the same country to mitigate seasonal activity. 9,10 Regional differences in seasonal activity might also affect when persons at high risk of influenza-related complications are empirically treated with antivirals 11 and when RSV immunoprophylaxis is administered. 12 Optimizing the timing of these interventions may increase national coverage and cost-effectiveness. [6][7][8]13,14 It is therefore useful to establish the timing of RSV and influenza seasons to inform providers when they should anticipate administering virus-specific interventions.
Argentina's prevention and treatment guidelines for RSV and influenza are provided at the national level. Starting in 2015, Argentina's Pediatric Society recommended the use of palivizumab, a monoclonal antibody, as a cost-effective method to prevent severe RSV illness among Argentinian children at high risk of hospitalizations due to RSV infection. 15 Specifically, the Society recommended that clinicians administer five doses of palivizumab (15 mg/kg) every 30 days during April-September for children aged ≤2 years with prematurity, congenital heart disease, or bronchopulmonary dysplasia. 16 Rodriguez et al 17 found that treating ~5 high-risk patients with palivizumab averted one RSV-associated hospitalization.
In addition, the Argentina Ministry of Health (MOH) recommends influenza vaccination for all persons aged >6 months and especially for those at high risk of influenza illness complications like pregnant women and very young children. 18 Influenza vaccination starts as early as March in Buenos Aires, Argentina's capital and largest city, and continues throughout the influenza season. Influenza vaccines have been shown to provide moderate protection against influenza-associated hospitalizations in young children and older adults. 19 In Argentina, vaccine coverage among young children has reached 80% 20 and about half of adults report getting vaccinated against influenza. 21 The MOH also recommends the use of empiric oseltamivir among persons at high risk of influenza illness complications and among hospitalized persons suspected of having influenza throughout the season. 22 In this study, we characterize RSV and influenza seasonality in five regions of Argentina: northwest, northeast, central, cuyo (central west), and south. Neighboring provinces share similar geoclimatic settings and work together as regions for administrative purposes. Awareness of the regional and annual timing of these seasons might help policymakers and clinicians better time annual subnational RSV and influenza prevention and control efforts.

| Data source
The design and methods for the Argentine World Health Organization's (WHO) National Influenza Center (NIC) has been described previously. 23   To describe annual virus activity at the national and regional levels, the following parameters were first determined for each calendar year for each virus: the mean percent positive for the year, and the season start, peak, and end. We defined the season start for a given calendar year as the week when the proportion of specimens testing positive for a specific virus was greater than the annual mean percent positive for two or more consecutive weeks over a 1-year period. The season ended when the proportion of positive specimens for a specific virus fell below the annual mean for two or more consecutive weeks. The peak was defined as the week with the maximum weekly proportion of positive specimens that occurred between the start and end of the season. Having defined the virus annual activity for each year, we applied a median method to calculate summary virus activity for the 10-year period by taking the median (and interquartile range) of the annual activity start, peak, and end week values over the 10 years. These calculations were performed at the national level and for each region.

| Descriptive data analyses
Because separate published "mean methods" have been previously described and validated to assess multiannual influenza circulation, 5 an additional mean method was applied to specimens

| Ethical considerations
The deidentified data used in this study were collected via routine clinical and public health functions; their analysis was part of a program evaluation and not considered human subjects research.   (Table 2).

| RE SULTS
Among RSV-tested specimens, RSV positivity was highest among

| D ISCUSS I ON
Our analysis of Argentinian surveillance data from 2007 to 2016 indicates that RSV and influenza cocirculated during the winter months, as has been observed in other temperate climates. 26 However, RSV seasons tended to precede influenza seasons at the national and regional levels during a 10-year period, and for most of the individual study years assessed. In addition, the timing of RSV The cocirculation of RSV and influenza also has important implications for public health officials modeling the etiologic burden of disease in Argentina; because these viruses cocirculate, models must include robust age-specific virologic data to meaningfully attribute clinical syndromes like pneumonia to RSV and/or influenza infection. 32,33 Certain limitations of these analyses should be considered.

ACK N OWLED G EM ENTS
We would like to thank Daniella Figueroa-Downing and Francisco Palomeque-Rodriquez for their contributions to this study.

D I SCL A I M ER
The findings and conclusions in this report are those of the authors and do not necessarily represent the view of the CDC.