RSV-associated Hospitalization Research Articles

Incidence and seasonality of respiratory syncytial virus hospitalisations in young children in Denmark, 2010 to 2015.

For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual RSV-associated admissions in children < 5 years-old for the period of 2010–2015. We identified ca 2,500 RSV-associated hospitalisations annually amounting to total direct medical-costs of ca EUR 4.1 million per year. The incidence of RSV-associated hospitalisations peaked in infants 1–2 months of age followed by infants 2–3 months of age, and infants < 1 month of age, respectively. Infant boys were at higher risk of severe RSV infection as compared to infant girls: male-to-female ratio peaked with 1.4 at four months of age and gradually levelled out with increasing age to 1.0 at 4 years of age. Five RSV-associated deaths were identified. Our findings demonstrate that in a western country as Denmark, RSV constitutes a considerable burden on childhood health. Furthermore, the best approach to reduce the high incidence of RSV-associated hospitalisations in young infants < 3 months of age may be maternal vaccination due to general challenges in achieving sufficient and protective immune responses in young infants.

The Impact of Pneumococcal Vaccination on Bacterial and Viral Pneumonia in Western Australian Children: Record Linkage Cohort Study of 469589 Births, 1996-2012.

Pneumococcal conjugate vaccine (PCV) was included in Australia's National Immunisation Program for all children from 2005. We assessed the impact of PCV on all-cause and pathogen-specific pneumonia hospitalizations in Western Australian (WA) children aged ≤16 years. All hospitalizations with pneumonia-related International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification diagnosis codes occurring in WA-born children (1996-2012) were linked to pathology records. Age-specific incidence rate ratios and temporal trends for all-cause and pathogen-specific pneumonia hospitalizations were calculated before and after PCV introduction. Among 469589 births, there were 15175 pneumonia-related hospitalizations. Hospitalization rates were 6.7 (95% confidence interval, 6.4-6.9) times higher in Aboriginal than in non-Aboriginal children. Following PCV introduction, all-cause pneumonia hospitalizations showed significant declines across all age groups. A pathogen was identified in 2785 of 6693 (41.6%) pneumonia hospitalizations that linked to a pathology record. Respiratory syncytial virus (RSV) was most frequently identified, with RSV-associated pneumonia hospitalization rates of 89.6/100000 child-years in Aboriginal and 26.6/100000 child-years in non-Aboriginal children. The most common bacterial pathogen was Streptococcus pneumoniae in Aboriginal children (32.9/100000 child-years) and Mycoplasma pneumoniae in non-Aboriginal children (8.4/100000 child-years). Viral pneumonia rates declined in all children following PCV introduction, with the greatest declines seen in non-Aboriginal children; declines in bacterial pneumonia were observed in non-Aboriginal children. Based on our ecological analyses, PCV seems to have had an impact on hospitalizations for pneumonia, suggesting that the pneumococcus is likely to play a role in both bacterial and viral pneumonia. Respiratory viruses remain an important pathogen in childhood pneumonia. Vaccines targeting respiratory viruses are needed to combat the residual burden of childhood pneumonia.

Respiratory syncytial virus hospitalization in middle-aged and older adults

BackgroundThe importance of Respiratory Syncytial Virus (RSV) is increasingly recognized in hospitalized adults, but mainly in those ≥ 65 years. ObjectivesWe sought to describe the epidemiology and clinical severity of RSV compared to influenza in hospitalized adults ≥18 years. Study designAdults hospitalized with acute respiratory illnesses (ARI) of ≤10days duration were prospectively enrolled from two Michigan hospitals during two influenza seasons. Collected specimens were tested for RSV and influenza by real-time, reverse transcription polymerase chain reaction (RT-PCR). Viral load and subtype were determined for RSV-positive specimens. We evaluated factors associated with RSV and outcomes of infection using multivariable logistic regression. RSV-positive patients were separately compared to two reference groups: RSV-negative and influenza-negative, and influenza-positive patients. ResultsRSV was detected in 84 (7%) of 1259 hospitalized individuals (55 RSV-B, 29 RSV-A). The highest prevalence was found in 50–64year olds (40/460; 8.7%); 98% of RSV cases in this age group had at least one chronic comorbidity. RSV detection was associated with obesity (OR: 1.71 95% CI: 0.99-3.06, p=0.03). Individuals with RSV were admitted to the hospital later in their illness and had a higher median Charlson comborbidity index (3 vs 2 p<0.001) compared to those with influenza. Clinical severity of RSV-associated hospitalizations was similar to influenza-associated hospitalizations. DiscussionIn this study we observed the highest frequency of RSV-associated hospitalizations among adult 50–64 years old; many of whom had chronic comorbidities. Our results suggest the potential benefit of including these individuals in future RSV vaccination strategies.

Costs of hospitalization with respiratory syncytial virus illness among children aged

BackgroundRespiratory syncytial virus (RSV) is the leading cause of acute respiratory illness in young children and results in significant economic burden. There is no vaccine to prevent RSV illness but a number of vaccines are in development. We conducted this study to estimate the costs of severe RSV illness requiring hospitalization among children <5 years and associated financial impact on households in Bangladesh. Data of this study could be useful for RSV vaccine development and also the value of various preventive strategies, including use of an RSV vaccine in children if one becomes available.MethodsFrom May through October 2010, children aged <5 years with laboratory–confirmed RSV were identified from a sentinel influenza program database at four tertiary hospitals. Research assistants visited case–patients’ homes after hospital discharge and administered a structured questionnaire to record direct medical costs (physician consultation fee, costs for hospital bed, medicines and diagnostic tests); non–medical costs (costs for food, lodging and transportation); indirect costs (caregivers’ productivity loss), and coping strategies used by families to pay for treatment. We used WHO–Choice estimates for routine health care service costs. We added direct, indirect and health care service costs to calculate cost–per–episode of severe RSV illness. We used Monte Carlo simulation to estimate annual economic burden for severe RSV illness.FindingsWe interviewed caregivers of 39 persons hospitalized for RSV illness. The median direct cost for hospitalization was US$ 62 (interquartile range [IQR] = 43–101), indirect cost was US$ 19 (IQR = 11–29) and total cost was US$ 94 (IQR = 67–127). The median out–of–pocket cost was 24% of monthly household income of affected families (US$ 143), and >50% families borrowed money to meet treatment cost. We estimated that the median direct cost of RSV–associated hospitalization in children aged <5 years in Bangladesh was US$ 10 million (IQR: US$ 7–16 million), the median indirect cost was US$ 3.0 million (IQR: 2–5 million) in 2010.ConclusionRSV–associated hospitalization among children aged <5 years represents a substantial economic burden in Bangladesh. Affected families frequently incurred considerable out of pocket and indirect costs for treatment that resulted in financial hardship.

Respiratory syncytial virus-neutralizing serum antibody titers in infants following palivizumab prophylaxis with an abbreviated dosing regimen.

BackgroundMonthly injections of palivizumab during the respiratory syncytial virus (RSV) season in at-risk infants reduces RSV-associated hospitalizations. However, the additive effect of naturally acquired immunity remains unclear. The objective of this study was to assess total neutralizing serum antibodies (NAb) against RSV in at-risk infants who had received an abbreviated course of palivizumab prophylaxis.MethodsSerum samples were collected from infants enrolled in the RSV Immunoprophylaxis Program in British Columbia, Canada over 2 consecutive RSV seasons (2013 to 2015). Infants in this program had received an abbreviated course of palivizumab in accordance with the provincial guidelines. Data were compared to adults and infants less than 12 months of age who did not receive palivizumab. Anti-RSV NAb titers were measured using an RSV microneutralization assay.FindingsInfants who received palivizumab had anti-RSV NAb titers at the end of the RSV season that persisted beyond what is expected from the pharmacokinetics of palivizumab alone. Moreover, 54% of the control infants who did not receive palivizumab and all tested adults had protective anti-RSV NAb titers.ConclusionsBased on our observations, we hypothesize that naturally acquired NAb provide additive protection, which may significantly reduce the need for additional doses of palivizumab in infants at risk of severe RSV infections.

Using probabilistically linked data to investigate the burden of Respiratory Syncytial Virus (RSV) in children &lt;5 years of age on secondary care in England

ABSTRACTObjectivesThis study aims to describe the burden of respiratory syncytial virus (RSV) in children &lt;5 years of age on secondary care in England using linked laboratory surveillance and hospital admissions databases. We will compare our results with previous estimates of the burden of RSV in secondary care based on statistical modelling techniques.&#x0D; ApproachNational laboratory surveillance data was probabilistically linked to the Hospital Episode Statistics (HES) database for children aged &lt;5 years in England from 01/08/2010 to 31/07/2012. Linkage was based on NHS and hospital number, date of birth, sex and post code. Only records where the laboratory test was within one week of hospital admission were included. Using the linked data, we estimated the probability of a respiratory hospital admission being related to RSV based on patient characteristics, calendar week and diagnostic coding. We used these probabilities to estimate the national incidence of RSV-associated hospital admissions. Admission rates were calculated by age group (&lt;1 year, 1-4 years) using Office for National Statistics (ONS) mid-year population estimates.&#x0D; ResultsThere was an average of 11,289 RSV-positive laboratory records per year during the study period. Preliminary results indicate that 75% of RSV-positive laboratory records linked to a hospital admission. 92% of linked hospital admissions occurred between November and March each year. 76% of the linked hospital admissions were in children aged &lt;1 year. There were significant differences in coding of RSV-associated hospital admissions by age, and over two-thirds of RSV-associated hospital admissions did not have a primary diagnosis indicating RSV as the cause of disease. We will present results on the number of linked hospital admissions, unlinked hospital admissions potentially caused by RSV and the total estimated number of RSV-associated hospital admissions, stratified by age, calendar week and primary diagnosis.&#x0D; ConclusionThis study is the first to link laboratory and hospital data for RSV in England, and therefore the first to describe laboratory-confirmed RSV-associated hospital admissions on a national scale. Our approach to estimate the national incidence of admissions based on developing probability weights from a smaller, linked sample has applications not just for RSV but for other seasonal infections. In addition, with a World Health Organization (WHO) consultation last year estimating that an RSV vaccine will be available commercially within 5-10 years, the results of this study can be used in mathematical models of potential vaccine strategy, contributing to the identification of optimal target groups for a potential licensed vaccine.

One-year observational study of palivizumab prophylaxis on infants at risk for respiratory syncytial virus infection in Latin America

ObjectiveThis study aims to describe real world palivizumab use and effectiveness in high-risk Latin American infants and young children. MethodProspective, multicenter observational study with infants at risk for severe RSV infection who received palivizumab according to routine clinical practice. Subjects were followed for one year with monthly visits after the first dose of palivizumab. An infant was considered adherent if receiving all the expected injections or five or fewer injections within appropriate inter-dose intervals. Annual incidence rates and risk factors of lower respiratory tract infection (LRTI) hospitalization were determined through Poisson regression models (α=0.05). ResultsThe study enrolled 458 children from seven countries in Latin America, from February 2011 to September 2012. The majority (98%) were born <36 weeks gestation. Overall, patients received 83.7% of their expected injections and 86.7% completed one year of follow-up. Of the 61 LRTI hospitalizations, 12 episodes were due to RSV infection. The RSV-associated hospitalization rate was 2.9 per 100 patient-years. Bronchopulmonary dysplasia was identified as an independent risk factor for LRTI hospitalization. A total of 1165 adverse events were recorded during one year of follow-up. One hundred and two patients (22.3%) had a total of 135 serious adverse events, but no events were considered to be related to palivizumab. ConclusionsThe rate of RSV hospitalization in high-risk infants in Latin America was low and aligned with those observed in randomized control trials and observational studies. Palivizumab prophylaxis appeared effective and had a good safety profile in this population.

Respiratory syncytial virus associated hospitalizations in preterm infants of 29 to 32\xa0weeks gestational age using a risk score tool for palivizumab prophylaxis

To evaluate the efficacy of palivizumab in infants of 29 to 32 weeks of gestational age (GA) based on a risk score tool developed for Austria. Retrospective single-center cohort study including all preterm infants of 29 (+0) to 32 (+6) weeks of GA born between 2004 and 2012 at a tertiary care university hospital. Data on RSV-related hospitalizations over the first 2 years of life were analyzed and compared between those having received palivizumab and those without. The study population was comprised of 789 of 816 screened infants, of whom 262 (33%) had received palivizumab and 527 (67%) had not. Nine of 107 rehospitalizations (8.4%) in the palivizumab group compared to 32 of 156 rehospitalizations (20.5%) in the group without prophylaxis were tested RSV-positive (p = 0.004; OR 0.356 [CI 90% 0.184–0.689]). Proven and calculated RSV hospitalization rate was 3.1% (8/262) in the palivizumab group and 5.9% (31/527) in the group without (p = 0.042; OR 0.504 [CI 90% 0.259–0.981]). Increasing number of risk factors (up to three) increased the RSV hospitalization rate in infants with (6.1%) and without (9.0%) prophylaxis. RSV-associated hospitalizations did not differ between groups with regard to length of stay, severity of infection, age at hospitalization, demand of supplemental oxygen, need for mechanical ventilation, and admission rate to the ICU. A risk score tool developed for infants of 29 to 32 weeks of gestational age led to a reduction of RSV-associated hospitalizations without influencing the severity of disease.

Predictors of RSV LRTI Hospitalization in Infants Born at 33 to 35 Weeks Gestational Age: A Large Multinational Study (PONI).

BackgroundPreterm infants are at high risk of developing respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI). This observational epidemiologic study evaluated RSV disease burden and risk factors for RSV-associated LRTI hospitalization in preterm infants 33 weeks+0 days to 35 weeks+6 days gestational age not receiving RSV prophylaxis.MethodsPreterm infants ≤6 months of age during RSV season (1 October 2013–30 April 2014) were followed at 72 sites across 23 countries from September 2013–July 2014 (study period). RSV testing was performed according to local clinical practice. Factors related to RSV-associated hospitalization for LRTI were identified using multivariable logistic regression with backward selection.ResultsOf the 2390 evaluable infants, 204 and 127 were hospitalized for LRTI during the study period and RSV season, respectively. Among these subjects, 64/204 and 46/127, respectively, were hospitalized for confirmed RSV LRTI. Study period and RSV season normalized RSV hospitalization rates (per 100 infant years) were 4.1 and 6.1, respectively. Factors associated with an increased risk of RSV-related LRTI hospitalization in multivariable analyses were smoking of family members (P<0.0001), non-hemodynamically significant congenital heart disease diagnosis (P = 0.0077), maternal age of ≤25 years at delivery (P = 0.0009), low maternal educational level (P = 0.0426), household presence of children aged 4 to 5 years (P = 0.0038), age on 1 October ≤3 months (P = 0.0422), and presence of paternal atopy (P<0.0001).ConclusionsDuring the 2013–2014 RSV season across 23 countries, for preterm infants 33–35 weeks gestation ≤6 months old on 1 October not receiving RSV prophylaxis, confirmed RSV LRTI hospitalization incidence was 4.1 per 100 infant years during the study period and 6.1 per 100 infant years during the RSV season. This study enhances the findings of single-country studies of common risk factors for severe RSV infection in preterm infants and suggests that combinations of 4–6 risk factors may be used to accurately predict risk of RSV hospitalization. These findings may be useful in the identification of infants most at risk of severe RSV infection.

Risk of Respiratory Syncytial Virus Infection in Cyanotic Congenital Heart Disease in a Subtropical Area

To compare the risk of respiratory syncytial virus (RSV)-associated hospitalization and analyze the epidemiology of RSV infection in patients with cyanotic and acyanotic congenital heart disease (CHD), we analyzed the nationwide health insurance database from 2005-2010. This study included 1050 patients with cyanotic CHD and 7077 patients with acyanotic CHD. Patients with acyanotic CHD were further classified into hemodynamically significant (hs)-acyanotic and non-hs-acyanotic groups according to whether they underwent surgery or took at least 2 anticongestive medications. RSV-associated hospitalization was higher in the cyanotic group than in hs-acyanotic and non-hs-acyanotic groups both before 1 year of age (4.8% vs 2.1% vs 1.5%, P < .001) and between 1 and 2 years of age (0.9% vs 0.56% vs 0.14%, P = .003). The hospitalization duration, intensive care, ventilator support prevalence, hospitalization cost, and mortality rate were significantly higher in the cyanotic group than in the other 2 groups. Logistic regression revealed that cyanotic CHD was the most significant risk factor for the ventilator support and RSV-associated mortality. In both patients with cyanotic and acyanotic CHD, RSV-associated hospitalization rate was higher in patients aged younger than 1 year and in spring and autumn in Taiwan, a subtropical country. The results show that patients with cyanotic CHD have a higher risk of severe RSV infection than do those with acyanotic CHD. RSV prophylaxis is more important and may reduce costs more for patients with cyanotic CHD.

Evaluation of case definitions for estimation of respiratory syncytial virus associated hospitalizations among children in a rural community of northern India.

BackgroundThe burden estimation studies for respiratory syncytial virus (RSV) have been based on varied case definitions, including case–definitions designed for influenza surveillance systems. We used all medical admissions among children aged 0–59 months to study the effect of case definitions on estimation of RSV–associated hospitalizations rates.MethodsThe hospital–based daily surveillance enrolled children aged 0–59 months admitted with acute medical conditions from July 2009–December 2012, from a well–defined rural population in Ballabgarh in northern India. All study participants were examined and nasal and throat swabs taken for testing by real–time polymerase chain reaction (RT–PCR) for RSV and influenza virus. Clinical data were used to retrospectively evaluate World Health Organization (WHO) case definitions (2011) commonly used for surveillance of respiratory pathogens, ie, acute respiratory illness (WHO–ARI), severe ARI (SARI) and influenza–like illness (ILI), for determination of RSV–associated hospitalization. RSV–associated hospitalization rates adjusted for admissions at non–study hospitals were calculated.FindingsOut of 505 children enrolled, 82 (16.2%) tested positive for RSV. Annual incidence rates of RSV–associated hospitalization per 1000 children were highest among infants aged 0–5 months (15.2; 95% confidence interval (CI) 8.3–26.8), followed by ages 6–23 months (5.3, 95% CI 3.2–8.7) and lowest among children 24–59 months (0.5, 95% CI 0.1–1.5). The RSV positive children were more likely to have signs of respiratory distress like wheeze, chest in–drawing, tachypnea, and crepitation compared to RSV–negative based on bivariate comparisons. Other less commonly seen signs of respiratory distress, ie, nasal flaring, grunting, accessory muscle usage were also significantly associated with being RSV positive. Compared to the estimated RSV hospitalization rate based on all medical hospitalizations, the WHO–ARI case definition captured 86% of the total incidence, while case definitions requiring fever like ILI and SARI underestimated the incidence by 50–80%.ConclusionsOur study suggests that RSV is a substantial cause of hospitalization among children aged <24months especially those aged <6 months. The WHO–ARI case definition appeared to be the most suitable screening definition for RSV surveillance because of its high sensitivity.

Adherence to Palivizumab for Respiratory Syncytial Virus Prevention in the Canadian Registry of Palivizumab.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants. Palivizumab, a means of passive prophylaxis, relies on patient adherence to ensure therapeutic effectiveness. The objective of this study is to evaluate the association between adherence and the incidence of RSV-associated outcomes and to identify demographic factors that may impact adherence. Infants were recruited into the Canadian registry of palivizumab (CARESS) with parental consent. Monthly interviews collected information on palivizumab administration and RSV-associated outcomes. An infant was considered adherent if they received all of their expected injections or ≥5 injections within the appropriate interdose intervals. Nineteen thousand two hundred thirty-five infants received a total of 83,447 injections from October 2005 to May 2014. Adherence was more likely in infants with higher maternal education and in those with siblings. Adherence was less likely in infants of aboriginal descent, with mothers who smoke and older infants. Adherence was significantly associated [odds ratio (95% confidence interval), P value] with a lower incidence of RSV infection [0.74 (0.60-0.93), 0.01] but not with RSV-associated hospitalization. However, in those hospitalized for RSV, adherence was significantly associated with the incidence of intubation and duration of hospitalization, intensive care stay and respiratory support. Adherence may have implications in children with less severe RSV infections and those who are already hospitalized for a RSV infection. Our study also identifies subpopulations that are more likely to be nonadherent to palivizumab therapy. Future studies should aim to validate the relationship among adherence, palivizumab levels and RSV-associated outcomes.

Clinical Endpoints for Respiratory Syncytial Virus Prophylaxis Trials in Infants and Children in High-income and Middle-income Countries.

Respiratory syncytial virus (RSV) continues to cause significant clinical and economic burden around the world. Historically, RSV-associated hospitalization was used as a primary endpoint for RSV prophylaxis trials in infants. However, because of the changing epidemiology and healthcare system landscape, this endpoint has become a critical bottleneck on the pathway to licensure for new therapeutics. A panel of 7 RSV experts was convened (Chicago, IL, May 22, 2014) to evaluate the challenges of defining RSV prevention endpoints for clinical trials and to develop endpoints that are clinically meaningful while minimizing subjectivity and bias to achieve sufficient consistency of response for regulatory approval. Particular consideration was given to the ability to collect data systematically and consistently in countries with different healthcare practices and systems, while capturing the greatest proportion of disease impact. The group consensus was that a clinically meaningful primary endpoint could include medically attended RSV illness in settings beyond RSV-associated hospitalizations alone, in particular, a composite reduction in hospitalization, emergency room or urgent care center visits because of an RSV respiratory infection. Relevant secondary endpoints included reductions in RSV lower respiratory tract infection, RSV-related intensive care unit rates, subsequent recurrent wheezing or asthma and direct and indirect costs.

Natural history and epidemiology of respiratory syncytial virus infection in the Middle East: Hospital surveillance for children under age two in Jordan

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children worldwide. In the Middle East and Arab countries, the burden of RSV-associated hospitalizations is not well characterized. We sought to determine the burden and clinical/epidemiological characteristics of RSV hospitalization in young children in Amman, Jordan. We investigated risk factors for severity including vitamin D levels. MethodsWe conducted viral surveillance with clinical and demographic data in children <2 years admitted with respiratory symptoms and/or fever at the Al-Bashir Government Hospital from March16, 2010 to March 31, 2013. Nasal/throat swabs were obtained and placed into lysis buffer, and frozen at −80°C until testing by real-time RT-PCR for 11 respiratory viruses. Heel stick blood or sera samples for 25-hydroxyvitamin D [25(OH)D] levels were obtained and sent to a central laboratory for mass spectrometry. ResultsOf the 3168 children, >80% testing positive for one virus, with RSV the most common virus detected (44%). The RSV-associated hospitalization rate was highest in children <6 months with an annual range of 21.1–25.9 per 1000, compared to 6.0–8.0 in 6–11-month-olds and 1.6–2.5 in 12–23-month-olds. RSV-positive children compared with RSV-negative were more likely to be previously healthy without underlying medical conditions, less likely to be born prematurely, had a higher frequency of supplemental oxygen use, and had lower median vitamin D levels. Risk factors for oxygen use in RSV-positive children included underlying medical conditions, lack of breastfeeding, younger age, and higher viral load. ConclusionRSV is a major cause of illness in hospitalized Jordanian children and is associated with increased severity compared to other respiratory viruses. Children with RSV in the Middle East would benefit from future RSV vaccines and antiviral therapy.

Hospitalizations associated with influenza and respiratory syncytial virus among patients attending a network of private hospitals in South Africa, 2007-2012.

BackgroundInfluenza and respiratory syncytial virus (RSV) infection are common causes of lower respiratory tract illness. Data on their burden in low and middle-income settings and from Africa are scarce. We aimed to estimate age-specific rates of hospitalization attributable to influenza and RSV among patients attending private hospitals in South Africa during 2007–2012.MethodsWe estimated annual age-specific rates of influenza- and RSV-associated hospitalization (that is respiratory hospitalizations likely due to influenza or RSV infection) by applying regression models to monthly administrative hospitalization data from a national private hospital group, using influenza and RSV surveillance data as covariates.ResultsEstimated mean hospitalization rates associated with seasonal influenza were 75 (95% confidence interval (CI), 41–108) and 3 (95% CI, 2–5) per 100,000 person-years for all-respiratory and all-circulatory causes, respectively. Children <1 year and adults ≥75 years were the most affected, with influenza-associated all-respiratory hospitalization rates estimated at 255 (95% CI, 143–358) and 380 (95% CI, 227–506) per 100,000 person-years, respectively. Excess all-circulatory hospitalizations associated with seasonal influenza were only observed in adults ≥65 years. Annual hospitalization rates associated with RSV averaged an estimate of 223 (95% CI, 128–317) per 100,000 person-years for all-respiratory causes. Among children <1 year, RSV-associated all-respiratory hospitalization rate of 7,601 (95% CI, 4,312-10,817) per 100,000 person-years was estimated.ConclusionsInfluenza and RSV substantially contributed to hospitalizations over the study period.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0694-x) contains supplementary material, which is available to authorized users.

Prolonged seasonality of respiratory syncytial virus infection among preterm infants in a subtropical climate.

ObjectiveThere is limited epidemiological data on the seasonality of respiratory syncytial virus (RSV) infection in subtropical climates, such as in Taiwan. This study aimed to assess RSV seasonality among children ≤24 months of age in Taiwan. We also assessed factors (gestational age [GA], chronologic age [CA], and bronchopulmonary dysplasia [BPD]) associated with RSV-associated hospitalization in preterm infants to confirm the appropriateness of the novel Taiwanese RSV prophylactic policy.Study DesignFrom January 2000 to August 2010, 3572 children aged ≤24-months were admitted to Taipei Mackay Memorial Hospital due to RSV infection. The monthly RSV-associated hospitalization rate among children aged ≤24 months was retrospectively reviewed. Among these children, 378 were born preterm. The associations between GA, CA, and BPD and the incidence of RSV-associated hospitalization in the preterm infants were assessed.ResultsIn children aged ≤24 months, the monthly distribution of RSV-associated hospitalization rates revealed a prolonged RSV season with a duration of 10 months. Infants with GAs ≤32 weeks and those who had BPD had the highest rates of RSV hospitalization (P<0.001). Preterm infants were most vulnerable to RSV infection within CA 9 months.ConclusionsGiven that Taiwan has a prolonged (10-month) RSV season, the American Academy of Pediatrics' recommendations for RSV prophylaxis are not directly applicable. The current Taiwanese guidelines for RSV prophylaxis, which specify palivizumab injection (a total six doses until CA 8–9 months) for preterm infants (those born before 286/7 weeks GA or before 356/7 weeks GA with BPD), are appropriate. This prophylaxis strategy may be applicable to other countries/regions with subtropical climates.

The burden of influenza and RSV among inpatients and outpatients in rural western Kenya, 2009-2012.

BackgroundIn Kenya, detailed data on the age-specific burden of influenza and RSV are essential to inform use of limited vaccination and treatment resources.MethodsWe analyzed surveillance data from August 2009 to July 2012 for hospitalized severe acute respiratory illness (SARI) and outpatient influenza-like illness (ILI) at two health facilities in western Kenya to estimate the burden of influenza and respiratory syncytial virus (RSV). Incidence rates were estimated by dividing the number of cases with laboratory-confirmed virus infections by the mid-year population. Rates were adjusted for healthcare-seeking behavior, and to account for patients who met the SARI/ILI case definitions but were not tested.ResultsThe average annual incidence of influenza-associated SARI hospitalization per 1,000 persons was 2.7 (95% CI 1.8–3.9) among children <5 years and 0.3 (95% CI 0.2–0.4) among persons ≥5 years; for RSV-associated SARI hospitalization, it was 5.2 (95% CI 4.0–6.8) among children <5 years and 0.1 (95% CI 0.0–0.2) among persons ≥5 years. The incidence of influenza-associated medically-attended ILI per 1,000 was 24.0 (95% CI 16.6–34.7) among children <5 years and 3.8 (95% CI 2.6–5.7) among persons ≥5 years. The incidence of RSV-associated medically-attended ILI was 24.6 (95% CI 17.0–35.4) among children <5 years and 0.8 (95% CI 0.3–1.9) among persons ≥5 years.ConclusionsInfluenza and RSV both exact an important burden in children. This highlights the possible value of influenza vaccines, and future RSV vaccines, for Kenyan children.

Malnutrition

Longitudinal information examining the effect of poor infant growth on respiratory syncytial virus (RSV) severity is limited. Children hospitalized with RSV lower respiratory infection represent those at the severe end of the disease spectrum. We followed up a cohort of 12,191 infants enrolled in a previous pneumococcal vaccine trial in Bohol, Philippines. Exposure measures were weight for age z-score at the first vaccination visit (median age 1.8 months) as well as the growth (the difference in weight for age z-score) between the first and third vaccination visits. The outcome was hospitalization with RSV lower respiratory infection. Children with a weight for age z-score ≤ -2 at their first vaccination visit had the highest rate of hospitalization with RSV lower respiratory infection, but this association was only evident in children whose mothers had >10 years of education (hazard ratio: 3.38; 95% confidence interval: 1.63-6.98). Children who had lower than median growth between their first and third vaccinations had a higher rate of RSV-associated hospitalization than those with growth above the median (hazard ratio: 1.34; 95% confidence interval: 1.02-1.76). Poor infant growth increases the risk for severe RSV infection leading to hospitalization.

Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective.

Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups.

Incidence and Clinical Features of Respiratory Syncytial Virus Infections in a Population-Based Surveillance Site in the Nile Delta Region

Most reports about respiratory syncytial virus (RSV) in developing countries rely on sentinel surveillance, from which population incidence is difficult to infer. We used the proportion of RSV infections from population-based surveillance with data from a healthcare utilization survey to produce estimates of RSV incidence in Damanhour district, Egypt. We conducted population-based surveillance in 3 hospitals (2009-2012) and 3 outpatient clinics (2011-2012) in Damanhour district. Nasopharyngeal and oropharyngeal specimens from hospitalized patients with acute respiratory illness and outpatients with influenza-like illness were tested by real-time reverse transcriptase polymerase chain reaction for RSV. We also conducted a healthcare utilization survey in 2011-2012 to determine the proportion of individuals who sought care for respiratory illness. Among 5342 hospitalized patients and 771 outpatients, 12% and 5% tested positive for RSV, respectively. The incidence of RSV-associated hospitalization and outpatient visits was estimated at 24 and 608 (per 100 000 person-years), respectively. Children aged <1 year experienced the highest incidence of RSV-associated hospitalizations (1745/100 000 person-years). This study demonstrates the utility of combining a healthcare utilization survey and population-based surveillance data to estimate disease incidence. Estimating incidence and outcomes of RSV disease is critical to establish the burden of RSV in Egypt.