Respiratory Syncytial and Influenza Viruses in ...

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Respiratory Syncytial and Influenza Viruses in Colombia between 1997 and 2014 Franklin Alejandro Rico Mendoza1*, Fernando de la Hoz Restrepo1, Alexandra Porras Ramírez2, and José Moreno Montoya1 Researcher Group of Epidemiology and Evaluation in Public Health GREESP, National University of Colombia, Colombia 2 Department of Public Health, National University of Colombia, Colombia 1

*Corresponding author Franklin Alejandro Rico Mendoza, Researcher Group of Epidemiology and Evaluation in Public Health GREESP, National University of Colombia, Direction: Carrera 7 B # 123-90, Piso 3. Colombia, Tel: 571-6030-303, Ext: 5715; Submitted: 12 May 2017 Accepted: 02 June 2017 Published: 05 June 2017 Copyright © 2017 Rico Mendoza et al. OPEN ACCESS

Keywords • Respiratory tract infections; Influenza virus A; Influenza virus B; Respiratory syncytial virus infections

Abstract Objective: Characterize the phenomenon of influenza A/B and respiratory syncytial virus (RSV), and its association with mortality in Colombia from 1997 to 2014. Methodology: An ecological time-series study was done using the viral surveillance respiratory disease data of the surveillance in Colombia from 1997 to 2014. The association between the viral circulation and excess mortality by month was estimated. Death was defined by the ICD-10 code classification. An autoregressive function was used to identify the temporal pattern. A Poisson regression was calculated to determinate the association between the mortality rate and influenza. Results: The autoregressive model suggested the existence of seasonal patterns of influenza A and B, showing that influenza might occur every eleven months, and it could influence the following month and the next year. Respiratory syncytial virus circulation also occurs every nine months. The results suggested a link between excess of mortality from pneumonia with a circulation of respiratory syncytial virus and Influenza A. It was found that an excess in mortality occurred from the respiratory disease associated with H3N2 influenza circulation (RTI 1.20 95% CI 1.03-1.45. The syncytial respiratory virus was associated with an increase of 1% in pneumonia mortality in 2012 and 2014. Conclusion: The relationship between the mortality rate and the circulation of the virus provides knowledge essential to implementing prevention and control measures during the peaks. The present analysis is important for increasing the knowledge about influenza and syncytial respiratory virus in the region.

ABBREVIATIONS RSV: Respiratory Syncytial Virus; DANE: Departamento Administrativo de Estadísticas DANE; IRR: Incidence Rate Ratio

INTRODUCTION

Influenza pandemics occur in the human population due to the transmission of the virus from birds to humans or due to seasonal influenza. Even though pandemics are an uncommon event, they occur throughout human history. The last influenza pandemic, caused by H1N1 virus in 2009, showed the vulnerability of the whole world to influenza virus [1]. Influenza is an important cause of recurring respiratory disease in humans; this is due to the subtypes A and B, both types especially potentially harmful to susceptible young children and the elderly [1]. Human influenza exhibits a strong seasonal cycle in temperate regions, frequently occurring during winter months [1]. Consequently, annual seasonal epidemics are associated with the increase in the cases and hospitalizations [2,3]. However, in tropical and subtropical regions, it might be associated with the rainy seasons, characterized in semi-annual epidemics or an unspecific season [2,3].

Human respiratory syncytial virus (RSV) is a highly contagious respiratory pathogen and the leading cause of acute lower respiratory infection that notably includes bronchiolitis, pneumonia, and chronic obstructive pulmonary infections, and in some cases nosocomial infections [4]. RSV has been recognized as one of the most dangerous important virus that affects young children. Worldwide, it is considered as the cause of at least 33.8 million illness in children less than 5 years old [5]. Epidemiological studies have suggested that the influenza virus also presents a seasonal behavior with epidemic waves [6,7].

Since 1997, Colombia has a sentinel surveillance system for the circulation of respiratory virus. The information generated through the surveillance has contributed to the knowledge of the virus behavior in the country. However, the understanding about the seasonality, its association with other diseases and behavior remains incomplete. Also, there is limited data on the circulation. Therefore, in this study the aim was to characterize influenza type A, B and RSV in Colombia during 1997-2014, using a modeling method and extrapolating the mortality in Colombia. Demonstrating the existence of an association among mortality and mortality caused by pneumonia in viral circulations periods.

Cite this article: Rico Mendoza FA, de la Hoz Restrepo F, Ramírez AP, Montoya JM (2017) Respiratory Syncytial and Influenza Viruses in Colombia between 1997 and 2014. JSM Allergy Asthma 2(2): 1013.

Rico Mendoza et al. (2017) Email: 

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Data analysis

A serial correlation function was used to identify temporal patterns of influenza in monthly series. In order to verify the existence of seasonal patterns or trends in the phenomenon, a degree of association of the current series values was assessed against previous values. The calculations were made separately for the monthly circulation of influenza A, B, and respiratory syncytial virus. An autocorrelogram was done using Stata®. A Poisson regression was used to calculate the association between the mortality and the influenza presence during 1997 and 2014, estimating the incidence rate ratio (IRR) with confidence intervals of 95%.

RESULTS

During 1997 to 2014, a total of 9.435 respiratory samples from different regions of the country were analyzed. In this samples were detected the respiratory syncytial virus (17.2%, n=1.622), influenza A (6.6%, n=623) and influenza B (2.0%, JSM Allergy Asthma 2(2): 1013 (2017)

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From 1997 to 2014, information on the predominant influenza virus was obtained from the data of viral surveillance performed Colombia. Prevalence data were obtained from Virology Group, Instituto Nacional de Salud. In Colombia, since 1997, a monitoring of respiratory diseases in the country has been done, using the immunofluorescence technique with monoclonal antibodies on patient respiratory samples. The virus are subtyped and characterized by the isolation in cell cultures.

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Surveillance data

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Figure 1 Variable of the absolute number of cases for Influenza A (Flu A), 1997 to 2014.

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Influenza-associated with mortality in each season was estimated as the summation of the monthly values of excess deaths, defined as the difference between “the number of deaths observed “and” the number of expected deaths” during the months in which circulation was identified. The upper and lower limits of the 95% confidence interval of the expected deaths were used to calculate the lower and upper limits, respectively, of the estimated excess mortality rate.

The autoregressive model suggested the existence of seasonal patterns of influenza A. The current values of circulation of influenza occurred every eleven months, influencing the values of the following month, coinciding in the months that the phenomenon is observed in the following year (Figure 3). The autoregressive model suggested the existence of seasonal

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Excess of deaths

Autoregressive model analysis

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In the present study, the classification of mortality was considered by the ICD-10, the J10- J11 and J12 to J18 codes, and deaths by any cause of influenza and pneumonia, respectively were considered. In the respiratory tract, infections were considered the J00, J06, J20 and J99 codes. Mortality Colombian information from 1997 to 2014 was obtained from the Direction National de Statistics (DANE) (Departamento Administrativo de Estadísticas DANE, 2016) based on records of the vital system of Colombia.

VSR

Mortality definition

The series for Influenza A corresponded the hypothesis of randomness. According to the statistician of Dickey-Fuller, the existence of trend showed that the series of Influenza A had no tendency (Figure 1). For the respiratory syncytial virus, according to the statistic or test of Gusts, the result indicates that the series seems to correspond to a series of time since the hypothesis of randomness of the data was not accepted. In addition, the DickeyFuller statistic showed that the series had no trend (Figure 2).

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This is an ecological time-series study based on secondary sources data in Colombia. Seasonal circulation of influenza and the respiratory syncytial virus was associated with exposure, using the information of the months where positive human samples were found by the Virology Group, Instituto Nacional de Salud. The population studied was established by young children of less 1 month, 1 to 12 months, 24 to 48 months, 49 to 120 months and less than 9 years old.

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Study design

n=189). Influenza A was most frequently present in male children (52.8%), followed by Respiratory Syncytial Virus (32.6%) and influenza B (20.2%). A higher frequency of viral respiratory disease was observed in children less than 1 month old (42.7%), followed by children between 1 and 12 months old (40.5%), 12 to 48 months (8.2%), 49 to 120 months (4.3%) and < 9 years old (4.3%).

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MATERIALS AND METHODS

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Figure 2 Variable of the absolute number of cases for respiratory syncytial virus, 1997 to 2014.

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patterns of influenza B. The current values of circulation of influenza occurred every eleven months, influencing the values of the following month. The seasonality of the series analysis suggests a seasonal behavior to RSV of 12 months, with the potential to influence the following month and year. A seasonal pattern appeared every nine months for the next year (Figure 4). An increase in global mortality was observed, excluding the external causes of injury and mortality from respiratory diseases. The study found an upsurge of death resulting from respiratory diseases (excluding pneumonia) when the influenza A/H1N1 cases were present. Consequently, an increase of 1% in the mortality by this cause was significant (RTI 1.01 IC 95% 1.0011.020) (Table 1). In 2003, excess mortality was found for all the causes and it was related to the increase of influenza H3N2 cases, also to the months of circulation that were established for this year. An increase of 1% in the global mortality was associated to influenza H3N2, being significant (RTI = 1.003, IC 95%1.0021.004). In addition, circulation syncytial respiratory virus was associated with an increase of 1% in the pneumonia mortality in 2012 and 2014.

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Autocorrelations of flua -0.10 0.00 0.10 0.20

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In the 49 to 120 months’ age group, an excess of mortality from acute respiratory disease was equivalent to 1.22 95% CI 1.20 to 1.24, which occurred in the circulation of influenza. Also, in this group, an increase of 22% in the mortality caused

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Bartlett's formula for MA(q) 95% confidence bands

Figure 3 Influenza A autocorrelogram in Colombia, during 1997 to 2014. 0.60 Autocorrelations of vsr 0.00 0.20 0.40

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Bartlett's formula for MA(q) 95% confidence bands

Figure 4 Autocorrelogram for Respiratory Syncytial Virus in Colombia, during 1997 to 2014.

JSM Allergy Asthma 2(2): 1013 (2017)

In the general population, an increase of 2% in the mortality for 1999 was not observed, but in 2002, when circulation of Influenza A H3N2 was present, the excess mortality changed from 2% to 20% IC95 % (RTI = 1036-1405). In 2003 and 2004, influenza A (H3N2) season, excess mortality increased by 3% (RTI = 1.036, CI (1.027 to 1.046). In 2013 and 2014, an increase was significant (RTI 1.34 IC 95% 1.21-1.98) with the influenza A/ H1N1 and syncytial respiratory virus.

DISCUSSION

The relationship between influenza circulation and increased mortality has been amply demonstrated in both developed and developing countries [8-10]. However, there are few studies in the inter-tropical areas that show the relationship of the virus circulation with the mortality. In this study, the pattern of seasonality of the circulation of influenza A, B, and RSV in Colombia showed that outbreaks of influenza occurred seasonally in intervals of 10 months (among 48-50 weeks), where the peak was often found in the last half of the year. The highest peaks of influenza A occurred between September and November. Even though influenza A was detected in the first years examined (1999, 2000, 2004, 2005 and 2006), only in 2000, it was dominant, compared to the years after 2006. This suggests an association with periods with more torrential rains in Colombia, which usually occurs between October and November [11].

Variability in the occurrence of peaks of influenza in tropical countries has been reported in several studies. In India a 12year study showed a peak of isolates occurred between July and September with greater positivity in July, which coincided with the rainy season [8]. In Singapore, a regression model showed that influenza A (H3N2) was the predominant virus subtype, with a significant effect on mortality population [9]. Also, in Brazil, a strong seasonal component was found, although the peak of influenza activity in this country occurs differently for regions that make up the country, being from May to October in the southeast, and from November to May in the North [10].

A study conducted in Argentina showed that epidemics occurred in the winter of 1993, 1995, 1999 and the spring of 1997, and an excess of deaths associated with the circulation of a predominant strain of influenza virus type A was identified/H3N2 [12]. Being similar to the results in the present study, where an excess mortality was associated with circulation of influenza A in the year 1997 was evident, and in 1999 by influenza virus type A (H3N2).

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by respiratory disease was observed (IC 1.20 - 1.24). During 1997-2005, the excess mortality from pneumonia increased 20% in global population. The greatest impact of this excess was observed in children under four years. In addition, the excess mortality from pneumonia increased 15% in 2012 and 2014 in the age group 5 to 9 years (CI 95% 12.3-21.2).

In the winter season, the circulation of strains of influenza type A in 1992, and B in 1997 were associated with low mortality. These data are broadly consistent with those found in a study in Singapore, which was linked to the circulation of influenza and mortality from all causes, and it was found that the circulation of influenza was associated with increased mortality from these causes and the magnitude of the increase was between 1 and 13% [9]. Our study showed an excess in the number of deaths from pneumonia in children 1 to 4 years. Also, an increase in

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Table 1: The excess mortality rate by acute respiratory disease and circulation of influenza A, 1997-2014. Excess mortality Year

Months

Influenza in children less than 9 year 1997 July, August, September, October 2002 October, November, December May, June, July, August, September, 2014 October Influenza in children less than 1 month 1997

March, April, May

2014 May, June Influenza in children of 1 to 12 months 1997 March, April, May 2014 May, June Influenza in children of 12 to 48 months 1997 March, April, May 2012 May, June Influenza in children of 49 to 120 months 1997 Mach, April, May 2014 May, June RSV in children less than 9 year 1997

2002

May, June, October

September, October

Pneumonia RTI (IC95)

1.22 (1.11 1.30)

1.02 (1.04 1.07)

1.06 (1.04 1.07)

1.23 (1.17 1.29) 2.07 (1.42 3.03)

1.09 (1.08 1.11)

1.10 (1.08 1.111)

1.09 (1.01 1.21)

1.20 (1.13 1.98)

1.27 (1.19 1.36) 1.09 (1.03 1.22)

1.05 (1.04 1.06)

June, July, August

1.28 (1.14 2.35)

1997

June, July, August

2014

1.87 (1.07 2.14) 1.34 (1.10 2.54)

1.74 (1.24 2.31) 1.02 (1.01 1.87)

1.54 (1.21 2.16)

1.24 (1.18 1.30) 2.07 (1.42 3.02)

1.11 (1.09 1.12)

1.75 (1.25 2.36)

1.65 (1.14 2.17)

1.70 (1.12 2.13)

1.49 (1.10 1.89)

In the present study, the circulation of RSV occurred in the first half of the year, except the 2000 year that cycle in October and November, it is similar to the a study Mexico, where the circulation in the periods of rain and outbreaks (during the winter season 2001-2002) showed a significant increase in hospitalization of children for lower respiratory tract infection, which tripled the number of medical consultation in comparison with previous years, and it increased up to three times the percentage of positive RSV for bronchiolitis over 18% and affectations in the lower respiratory tract [14]. The proportion of infections caused by different influenza viral agents is significant, the detection range of non-influenza

1.73 (1.25 2.39)

1.20 (1.15 1.25) 1.73 (1.25 2.39)

1.24 (1.20 1.29) 1.73 (1.25 2.39)

1.25 (1.21 1.30) 1.02 (1.02 1.02)

2.3 (1.17 2.58)

1.13 (1.09 2.04)

mortality and morbidity during the flu season was observed. This was similar to the mortality associated with influenza and respiratory syncytial virus in the United States [13].


1.20 (1.15 1.25)

1.19 (1.13 1.24) 2.07 (1.42 3.03)

1.26 (1.18 1.35)

1.20 (1.15 1.25) 1.01 (1.00 1.03)

1.73 (1.25 2.39)

1.22 (1.14 1.30)

2.07 (1.42 3.03)

Influenza, pneumonia ARIs RTI (IC95)

1.73 (1.25 2.39) 1.06 (1.04 1.07)

1997

January, February, Mach

1.06 (1.04 1.07)

1.05 (1.04 1.07)

RSV in children of 1 to 12 months

July, august, september, october, november

1.06 (1.04 1.07)

1.19 (1.13 1.24)

1.01 (1.02 - 1.03)

1997

1.19 (1.13 1.125)

1.23 (1.15 1.31)

May, June, July, August, September

February, March, April, May, October, 2014 November RSV in children of 49 to 120 months

All causes* RTI (IC95)

2.08 (1.42 3.02)

2014

April, may, june, july, septembrer, 2014 october RSV in children of 12 to 48 months

ARIs RTI (IC95)

Global RTI (IC95)

1.32 (1.08 2.01) 1.29 (1.04 1.94)

respiratory virus spanning from 16.5 to 72.7% in studies conducted worldwide and depending on factors, such as the study design, study population, detection technique used, and period covered by the study [15-20]. In our case, the prevalence of the analyzed virus in Colombia was 35.8%. The most prevalent virus was rhinovirus, respiratory syncytial virus, and metapneumovirus. The only virus that was not detected was metapneumovirus. This result was consistent with other studies in which type 2 parainfluenza virus had the lowest detection frequency [16,19]. Our findings have public health implications for RSV in terms of health care system planning. Immunoprophylaxis with the monoclonal antibody, and palivizumab, have been found to be effective in reducing the severity of RSV-related disease, but require an understanding of the RSV epidemic timing for implementation. While there is no licensed vaccine for RSV, there are several candidates undergoing clinical trials

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[21]. Understanding the dynamics of RSV epidemics in different regions will be important for planning optimal vaccine allocation. This study presented some limitations. First, the definition of the influenza season, due to the number of samples were each week was relatively small, which could generate a misclassification in the definition of influenza seasons, and lead to misclassification bias, and no differential with a decreasing in the magnitude of the association between circulating influenza and mortality. Second, the possible misclassification of causes of death from pneumonia could reduce the magnitude of the association. Finally, considering the possibility that influenza seasons coincide with the circulation of other viruses such as RSV, and confounding negatively the association of influenza pneumonia mortality. All results were adjusted, but it showed no differences with the results obtained without adjustment. However, it was not possible to exclude the existence of a mixing effect among different viruses.

In conclusion, according to the results, the circulation of influenza A, B, and RSV can be found in greater magnitude in September to December. This study suggests that it is necessary to increase research on influenza in Colombia; also, it is mandatory to continue with the active surveillance for respiratory illness from sentinel surveillance. The national government must provide funds to implement strategies to prevent a pandemic, to maintain continued monitoring, and to ensure properly diagnoses. An important strength of our study is the use of available surveillance data for respiratory virus in a country that covers a wide range of latitudes and very diverse in terms of their geographical and climatic characteristics.

ACKNOWLEDGEMENTS

We thank the Universidad Nacional de Colombia GRESP for having made available the data analysis in the study. We also thank Lisa Johnson for the review of the manuscript.

REFERENCES

1. Trock SC, Burke SA, Cox NJ. Development of Framework for Assessing Influenza Virus Pandemic Risk. Emerg Infect Dis. 2015; 21: 13721378. 2. Carrat F, Valleron A, Statistics H. Influenza Epidemics in the United. 2004; 10. 3. Durand LO, Cheng PY, Palekar R, Clara W, Jara J, Cerpa M, et al. Timing of influenza epidemics and vaccines in the American tropics, 20022008, 2011-2014. Influenza Other Respir Viruses. 2016; 10: 170-175. 4. Gomez RS, Guisle-marsollier I, Bohmwald K, Bueno SM, Kalergis AM. Respiratory Syncytial Virus?: Pathology , therapeutic drugs and prophylaxis. Immunol Lett. 2016; 162: 237-247.

5. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and metaanalysis. Lancet. 2016; 375: 1545-1555.

6. Haynes AK, Manangan AP, Iwane MK, Sturm-Ramirez K, Homaira N, Brooks WA, et al. Respiratory syncytial virus circulation in seven countries with global disease detection regional centers. J Infect Dis. 2013; 208: 246-254.

7. Fleming DM, Pannell RS, Elliot AJ, Cross KW. Respiratory illness associated with influenza and respiratory syncytial virus infection. Arch Dis Child. 2005; 90: 741-746. 8. Rao BL, Banerjee K. Influenza surveillance in Pune, India, 1978-90. Bull World Health Organ. 1993; 71: 177-181.

9. Chow A1, Ma S, Ling AE, Chew SK. Influenza-associated deaths in tropical Singapore. Emerg Infect Dis. 2006; 12: 114-121.

10. Gurgel RQ, Bezerra PG, Duarte Mdo C, Moura A, Souza EL, Silva LS, et al. Relative frequency, Possible Risk Factors, Viral Codetection Rates, and Seasonality of Respiratory Syncytial Virus Among Children With Lower Respiratory Tract Infection in Northeastern Brazil. Medicine (Baltimore). 2016; 95: e3090. 11. IDEAM. Caracteristicas climatologicas de ciudades principales y municipios turisticos. 12. Kusznierz GF, Imaz MS, Zerbini EV, Savy V, Knez V, Sequeira MD. [Effect of influenza epidemics on mortality in Santa Fe, Argentina, during 1992-1999]. Rev Panam Salud Publica. 2002; 12: 26-36.

13. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003; 289: 179-186. 14. Muraira A, Villarreal E, Quiroga A, Ábrego V, Guadalupe A, Cárdenas del Castillo B. Frecuencia de niños hospitalizados por el virus sincitial respiratorio en tres periodos invernales. Revista Mexicana de Pediatría 2003; 70: 4. 15. Pancer KW, Gut W, Abramczuk E, Lipka B, Litwinska B. Non-influenza viruses in acute respiratory infections among young children. High prevalence of HMPV during the H1N1V. 2009 pandemic in Poland. Przegl Epidemiol. 2014; 68: 627-632. 16. Diaz J, Morales-Romero J, Pérez-Gil G, Bedolla-Barajas M, DelgadoFigueroa N, García-Román R, et al. Viral coinfection in acute respiratory infection in Mexican children treated by the emergency service: A cross-sectional study. Ital J Pediatr. 2015; 41: 33. 17. Landes MB, Neil RB, McCool SS, Mason BP, Woron AM, Garman RL, et al. The frequency and seasonality of influenza and other respiratory viruses in Tennessee: two influenza seasons of surveillance data, 2010-2012. Influenza Other Respir Viruses. 2013; 7: 1122-1127.

18. Wansaula Z, Olsen SJ, Casal MG, Golenko C, Erhart LM, Kammerer P, et al. Surveillance for severe acute respiratory infections in Southern Arizona, 2010-2014. Influenza Other Respir Viruses. 2016; 10: 161169. 19. Wong-Chew RM, Espinoza MA, Taboada B, Aponte FE, Arias-Ortiz MA, Monge-Martínez J, et al. Prevalence of respiratory virus in symptomatic children in private physician office settings in five communities of the state of Veracruz, Mexico. BMC Res Notes. 2015; 8: 261.

20. Zimmerman RK, Rinaldo CR, Nowalk MP, Gk B, Thompson MG, Moehling KK, et al. Influenza and other respiratory virus infections in outpatients with medically attended acute respiratory infection during the 2011-12 influenza season. Influenza Other Respir Viruses. 2014; 8: 397-405. 21. Broadbent L, Groves H, Shields MD, Power UF. Respiratory syncytial virus, an ongoing medical dilemma: an expert commentary on respiratory syncytial virus prophylactic and therapeutic pharmaceuticals currently in clinical trials. Influenza Other Respir Viruses. 2015; 9: 169-178.

Cite this article

Rico Mendoza FA, de la Hoz Restrepo F, Ramírez AP, Montoya JM (2017) Respiratory Syncytial and Influenza Viruses in Colombia between 1997 and 2014. JSM Allergy Asthma 2(2): 1013.


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