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Trends of respiratory syncytial virus infections in children under 2 years of age in Puerto Rico.

Objective: The respiratory syncytial virus (RSV) is the most significant viral pathogen causing bronchiolitis and pneumonia in infants, today. In tropical climates the RSV infection may occur throughout the year. The purpose of this study was to asses RSV infections during the 2009-2010 RSV season in children under 2 years of age and to evaluate the trend of positive RSV tests in the period of 2007 to 2009.

Methods: A retrospective review of data collected from 6 hospitals in Puerto Rico was performed. Patients with confirmed RSV bronchiolitis were included in the study.

Results: A total of 4,678 patients were included. The mean age of the patients was 7 months. Data showed that RSV infection occurred throughout the studied months.

Conclusion: Data confirms a year-round presence of RSV in Puerto Rico. The RSV surveillance system needs to be reinforced to establish and understand the epidemiology of RSV and to review the current immunoprophylaxis guidelines. [P R Health Sri J 2015;34: 98-101]

Key words: Respiratory syncytial virus, Bronchiolitis, Hospitalizations, Puerto Rico

Objetivo: El Virus Respiratorio Sincitial (VRS) es el patogeno viral mas importante que causa bronchiolitis y pulmonia en infantes. En climas tropicales la infeccion por el VRS puede ocurrir durante todo el ano. El proposito de este estudio es revisar las infecciones por el VRS durante la temporada 2009-2010 en ninos menores de 2 anos de edad, y evaluar la tendencia de las pruebas positivas para el VRS en el periodo de 2007 a 2009. Metodos: Se realizo una revision retrospectiva de los datos de 6 hospitales en Puerto Rico. Se incluyeron en el estudio a los pacientes con bronchiolitis confirmada por el VRS. Resultados: Un total de 4,678 pacientes fueron incluidos en el estudio. La edad media de los pacientes fue de 7 meses. Los datos demostraron que la infeccion por el VRS ocurrio a traves de todos los meses estudiados. Conclusiones: Los datos confirman la presencia del VRS a traves de todo el ano en Puerto Rico. La vigilancia del VRS necesita ser reforzada para poder establecer y entender mejor su epidemiologia, y para reevaluar las guias de inmunoprofilaxis.

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The respiratory syncytial virus (RSV) is the most significant viral pathogen causing bronchiolitis and pneumonia in infants, today (1). There is a high risk of serious RSV illness in infants who were born prematurely or who have bronchopulmonary dysplasia (BPD), congenital heart disease (CHD), congenital abnormalities of the airway or neuromuscular disease, or certain immunodeficiencies. Up to 90% of infant hospitalizations in the United States are related to RSV, and most of them occur in infants under 6 months of age (1), and it is estimated to cause 40,000 to 125,000 hospitalizations each year in infants younger than 1 year old (l, 2, 3).

The mortality rate in children hospitalized with RSV infection is less than 1 %, with fewer than 500 deaths per year attributed to RSV (4). However, in high-risk infants, there is higher mortality and significant morbidity associated with RSV. An example of this is the 3 to 5% mortality rate reported in infants with chronic lung disease of infancy (i.e., bronchopulmonary dysplasia) or congenital heart disease or who are markedly premature when hospitalized for RSV (4).

Palivizumab, an antibody that is given by intramuscular injection, is licensed in the United States as an immunoprophylaxis and is recommended for infants and children who are at increased risk for severe RSV disease. The American Academy of Pediatrics (AAP) has developed guidelines for palivizumab administration using data from previous RSV seasons to suggest a period for administration. However, specific dates for palivizumab administration have not been clearly established (5).

Since 2004, eligible infants in Puerto Rico have been receiving up to 9 doses of palivizumab during the RSV season, which has been established to run from July through March of the following year. In 2009, the revised AAP guidelines recommending a decrease in the number of palivizumab doses in all geographical areas were published (5,6). After taking these new recommendations into account, the Puerto Rico Health Department decreased RSV prophylaxis with palivizumab to 3 doses or, in some patients, 5 doses, depending on eligibility criteria. No new consensus, surveillance system reports or epidemiologic data of RSV infections supporting these changes have been reported in Puerto Rico. The purpose of this study was to assess RSV infections during the 2009-2010 RSV season (July 09 to March 10) in children under 2 years of age in Puerto Rico and evaluate the trend of positive RSV tests in the period of 2007 to 2009, based on information from 6 hospitals from around the island, so as to provide data to review the current immunoprophylaxis guidelines.

Methods

A retrospective review of data collected from 6 Puerto Rico hospitals during the 2009-2010 season (from July 2009 to March 2010) was performed. Only patients who were under 2 years of age and had confirmed RSV bronchiolitis were included in the study. The 6 hospitals that participated provide service to patients around Puerto Rico who have medical insurance, either private or that offered by the government. The data from all the hospitals included the mean age of the subjects and the total number of patients with RSV bronchiolitis (confirmed by an RSV rapid test).

Retrospective data from 2007 through 2009 were available year round for 2 hospitals. We examined RSV trends represented by the cases drawn from the participating hospitals. Data analysis was performed by using frequency, mean, median, and range of collected data. Each institution approved the use of its data for this study. The study was approved by the University of Puerto Rico Medical Sciences Campus Institutional Review Board.

Results

At the 6 participating institutions, 4,678 patients with respiratory symptoms were evaluated. Table 1 shows the number of patients that were at each hospital. The mean age of the patients with RSV bronchiolitis was 7 months of age (range, 0 to 15 months). During the 2009-2010 RSV season, 77% of patients with a positive RSV test were hospitalized with bronchiolitis in the participating institutions.

Figure 1 shows the total number of positive RSV tests per month in the participating hospitals during the 2009-2010 RSV season and the number of patients hospitalized with RSV bronchiolitis. This information demonstrates that RSV infections occur throughout the season (from July to March of the following year).

Data from 3 years, covering from 2007 through 2009, from hospitals E and F (n = 3,778) show the occurrences of RSV infection throughout the year, with an increase in the number of occurrences being reported from September through December (Figures 2 and 3). In addition, the data show that there was an increase in positive RSV cases in both hospitals (that is, E and F) during the first 6 months of the 2009-2010 RSV season compared to what had occurred in previous seasons.

Discussion

RSV is the only respiratory virus that produces important outbreaks every year (7). Reinfection with this virus is common. It has been reported that by 2 years of age, 99% of all children will experience at least 1 infection, and 50% of them will experience at least 2 infections (7). Different geographical regions have different specific seasons, and the outbreak length (for each region) is also subject to variation. In the United States, typical outbreaks last an average of 5 months, although there are regions where year-round infections have been reported. In tropical climates, such as that of Puerto Rico, the pattern of RSV infection is less predictable, and outbreaks may occur throughout the year (8).

RSV activity is considered widespread, that is, at epidemic or outbreak level, when at least half of the participating laboratories report having detected RSV for at least 2 consecutive weeks or when more than 10% of all specimens test positive for the virus (9). Prior to 2004, because of the lack of an RSV surveillance system, health care workers in Puerto Rico used Florida data to determine when the local RSV season had started and, subsequently, when prophylaxis should be implemented; the season generally lasted from August to December of any given year and patients were prescribed Synagis (palivizumab). In 2004, after a consensus was reached by experts in Puerto Rico, and in the face of evidence confirming the year-round incidence of RSV infection, the Puerto Rico Health Department established the RSV season as covering from July through March of the subsequent year, thereby ensuring that eligible infants would be offered prophylaxis for 9 months (8).

In 2009, the American Academy of Pediatrics (AAP) guidelines for the use of palivizumab for the prevention of RSV infections were updated. Recent descriptions from the Centers for Disease Control and Prevention (CDC) regarding RSV seasonality in different geographic locations were used to recommend new initiation and termination periods for prophylaxis. For all locations, a maximal number of 5 doses was recommended (without regard to the month of prophylaxis initiation) for infants with significant congenital heart disease or chronic lung disease (CLD) or who had been born before 32 weeks, 0 days, of gestation. A maximal number of 3 doses was recommended for infants with a gestational age (GA) of 32 weeks, 0 days, to 34 weeks, 6 days, and without significant CHD or CLD (5).

These new recommendations have created concerns among physicians in the US and other countries. Recommendations for infants at a GA of 32 to 35 weeks were the most divergent. The Canadian guidelines recommended that localized policies be implemented in each (Canadian) province and territory, with each region considering its own particular risk factors and then implementing a specific and appropiate risk-scoring tool. Canadian authors stated that the use of 1 to 3 doses of palivizumab over the course of an entire RSV season is a strategy untested in randomized controlled trials and that such use is not supported by the pharmacokinetics and therapeutic efficacy of the drug, as evidenced in the earlier phases 1 and 2 of the IMpact trials (10, 11). In an analysis of infants under 1 year of age and who had been hospitalized for RSV infection in 9 hospitals around the US, it was found that a GA of 33 to 35 weeks was a significant risk factor for mechanical ventilation, a longer stay in the ICU (7.7 vs. 5.8 days for <32 weeks GA), and longer hospitalization (8.4 vs. 6.8 days for <32 weeks GA) (12).

Other aspects that need to be taken into consideration are the long-term effects of RSV infection. Investigators in Arizona demonstrated that children with RSV bronchiolitis early in life had a significantly higher risk of wheezing until they reached 6 years of age. The majority of these children did not require hospitalization and yet developed a subsequent post-bronchiolitis wheeze. Studies conducted in Sweden showed that children hospitalized because of RSV bronchiolitis had an increased risk of wheezing and asthma until reaching the age of 18. Study investigators concluded that interventions directed at preventing RSV bronchiolitis could provide long-term benefits by reducing recurrent wheezing episodes in childhood (13).

Data from our study confirm the year-round presence of RSV in Puerto Rico, with increased activity occurring from September through December. This pattern correlates with the one reported in the southeastern region of Florida, which pattern usually takes place of a period of 11 to 12 months (l, 14, 15). This study is limited by the retrospective nature of the analyzed data. The demographic characteristics of the patients in the study population and the clinical courses followed for those patients were not available for analysis. RSV infections seen in private offices or in other settings are not included in this study, and not all the institutions collect the same surveillance data or parameters. Furthermore, the data are presented as number of cases instead of as percent of positive tests, precluding the interpretation of epidemic levels throughout a given year. A prospective study would help us analyze age groups and preexisting risk factors associated with RSV infections in Puerto Rico. Nevertheless, the impact of these data reinforces the importance of the implementation of a prospective and accurate surveillance system in all the institutions that provide pediatric care in Puerto Rico, to understand and monitor the epidemiology of RSV infections. In addition, such a system would allow us to set priorities in the form of RSV immunoprophylaxis guidelines and so further guide public health policy and strategies.

Acknowledgments

The hospitals included in this study were the following: Hospital A: University of Puerto Rico Hospital Dr. Federico Trilla, in Carolina, Hospital B: Interamerican Hospital for Advanced Medicine, in Caguas, Hospital C: San Antonio Hospital in Mayaguez, Hospital D: Manati Medical Center Hospital in Manati, Hospital E: Sanjorge Children's Hospital in San Juan, Hospital F: University Pediatric Hospital in San Juan. We acknowledge the contributions of all the team members to improve the quality and safety of medical care for newborn infants, children, and their families, and for their participation in this research.

References

(1.) Light M, Bauman J, Mavunda K, Malinoski F, Eggleston M. Correlation Between Respiratory Syncytial Virus (RSV) Test Data and Hospitalization of Children for RSV Lower Respiratory Tract Illness in Florida. Pediatr Infect Dis J 2008;27:512-518.

(2.) Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009;360:588-598.

(3.) Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA 1999;282:1440-1446.

(4.) Krilov L, Steele R. Respiratory Syncytial Virus Infection. [Medscape Web site], September 22,2010. Available at: Url: http://emedicine.medscape. com/article/971488-overview#aw2aab6b2b4. Accessed May 8, 2011.

(5.) American Academy of Pediatrics. Respiratory syncytial virus. In: Pickering LK, Baker CJ, Long SS, Kimberlin D, eds. Red Book. 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2009:560-569.

(6.) Matias I, Garcia-Garcia I, Garcia-Fragoso L, Valcarcel M. Palivizumab Compliance by Infants in Puerto Rico During the 2009-2010 Respiratory Syncytial Virus Season. J Community Health 2014 Apr 23. [Epub ahead of print].

(7.) RSV educational slide library [compact disk digital audio] Gaithersburg, MD: MediMedia Educational Group. MedImmune Inc.; 2003.

(8.) Molinari M, Garcia I, Garcia L, Puig G, Pedraza L, Marin J, Valcarcel M. Respiratory Syncytial Virus-Related Bronchiolitis in Puerto Rico. P R Health SciJ 2005;24:137-140.

(9.) Centers for Disease Control and Prevention (CDC). Respiratory and Enteric Viruses Branch: respiratory syncytial virus. December 2004.

(10.) The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 1998;102:531-537.

(11.) Smart KA, Lanctot KL, Paes BA. Rebuttal: palivizumab for the prevention of respiratory syncytial virus infection. Can Fam Physician 2010;56:988-991.

(12.) Horn SD, Smout RJ. Effect of prematurity on respiratory syncytial virus hospital resource use and outcomes. J Pediatr 2003; 143(5 Suppl):S133-141.

(13.) Bont L, Ramilo O. The relationship between RSV bronchiolitis and recurrent wheeze: the chicken and the egg. Early Hum Dev 2011;87 Suppl 1: S51-54. Epub 2011 Feb 3.

(14.) Centers for Disease Control and Prevention (CDC). National Respiratory and Enteric Virus Surveillance System (NREVSS). Available at: Url: http://www.cdc.gov/surveillance/nrevss. Accessed May 8, 2011.

(15.) Centers for Disease Control and Prevention (CDC). Respiratory syncytial virus activity--United States, July 2008-December 2009. MMWR Morb Mortal Wkly Rep 2010;59:230-233.

Israel Matias, MD *; Ines Garcia, MD *; Lourdes Garcia-Fragoso, MD *; Gilberto Puig, MD ([dagger]); Lourdes Pedraza, MD ([dagger]); Luis Rodriguez, MD ([double dagger]); Alvaro Santaella, MD ([section]); Sylvia Arce, MD **; Marilyn Toledo, MD ([dagger]) ([dagger]); Edwin Soto, MD ([dagger]) ([dagger]); Marta Valcarcel, MD *

* Department of Pediatrics, Neonatology Section, University of Puerto Rico Medical Sciences Campus, San Juan, PR; ([dagger]) San Jorge Children's Hospital, San Juan, PR; ([double dagger]) University of Puerto Rico Hospital Dr. Federico Trilla, Carolina, PR; ([section]) Interamerican Hospital for Advanced Medicine, Caguas, PR; ** San Antonio Hospital, Mayagiiez, PR; ([dagger]) ([dagger]) Manati Medical Center Hospital, Manati, PR

The authors have no conflicts of Interest to disclose.

Address correspondence to: Israel Matias, MD, Department of Pediatrics, Neonatology Section, University of Puerto Rico Medical Sciences Campus, PO Box 365067, San Juan, PR 00936-5067. Email: israel.matias@upr.edu

Table 1. Subjects with respiratory symptoms reported by each hospital

Hospital   Subjects N
           (percent)

A          128 (2.7%)
B          210 (4.5%)
C          159 (3.4%)
D          279 (6.0%)
E          3,710 (79.3%)
F          192 (4.1%)
Total      4678

Figure 1. Positive RSV tests and hospitalized patients with RSV
bronchiolitis in the participating hospitals during the 2009-2010
season

Month      RSV Bronchiolitis   Positive RSV tests

09, July   22                  23
09, Aug    37                  40
09, Sept   154                 169
09, Oct    377                 495
09, Nov    271                 391
09, Dec    108                 161
10, Jan    53                  61
10, Feb    39                  41
10, Mar    23                  25
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Article Details
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Title Annotation:BRIEF REPORT
Author:Matias, Israel; Garcia, Ines; Garcia-Fragoso, Lourdes; Puig, Gilberto; Pedraza, Lourdes; Rodriguez,
Publication:Puerto Rico Health Sciences Journal
Article Type:Report
Date:Jun 1, 2015
Words:2809
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