Severe Respiratory Syncytial Virus Illness Research Articles

Nirsevimab Effectiveness Against Medically Attended Respiratory Syncytial Virus Illness and Hospitalization Among Alaska Native Children - Yukon-Kuskokwim Delta Region, Alaska, October 2023-June 2024.

Respiratory syncytial virus (RSV) is a leading cause of hospitalization among young children. Historically, American Indian and Alaska Native (AI/AN) children have experienced high rates of RSV-associated hospitalization. In August 2023, a preventive monoclonal antibody (nirsevimab) was recommended for all infants aged <8 months (born during or entering their first RSV season) and for children aged 8-19 months (entering their second RSV season) who have increased risk for severe RSV illness, including all AI/AN children. This evaluation in Alaska's Yukon-Kuskokwim Delta region estimated nirsevimab effectiveness among AI/AN children in their first or second RSV seasons during 2023-2024. Among 472 children with medically attended acute respiratory illness (ARI), 48% overall had received nirsevimab ≥7 days earlier (median=91 days before the ARI-related visit). For children in their first RSV season (292), nirsevimab effectiveness was 76% (95% CI = 42%-90%) against medically attended RSV illness and 89% (95% CI = 32%-98%) against RSV hospitalization. For children in their second RSV season (180), effectiveness against medically attended RSV illness was 88% (95% CI=48%-97%). Nirsevimab is effective for preventing severe RSV illness among infants entering their first RSV season and children entering their second season with increased risk for severe RSV, including all AI/AN children.

The cost of care for children hospitalized with respiratory syncytial virus (RSV) associated lower respiratory infection in Kenya

BackgroundRespiratory syncytial virus (RSV) is one of the main causes of hospitalization for lower respiratory tract infection in children under five years of age globally. Maternal vaccines and monoclonal antibodies for RSV prevention among infants are approved for use in high income countries. However, data are limited on the economic burden of RSV disease from low- and middle-income countries (LMIC) to inform decision making on prioritization and introduction of such interventions. This study aimed to estimate household and health system costs associated with childhood RSV in Kenya.MethodsA structured questionnaire was administered to caregivers of children aged < 5 years admitted to referral hospitals in Kilifi (coastal Kenya) and Siaya (western Kenya) with symptoms of acute lower respiratory tract infection (LRTI) during the 2019–2021 RSV seasons. These children had been enrolled in ongoing in-patient surveillance for respiratory viruses. Household expenditures on direct and indirect medical costs were collected 10 days prior to, during, and two weeks post hospitalization. Aggregated health system costs were acquired from the hospital administration and were included to calculate the cost per episode of hospitalized RSV illness.ResultsWe enrolled a total of 241 and 184 participants from Kilifi and Siaya hospitals, respectively. Out of these, 79 (32.9%) in Kilifi and 21(11.4%) in Siaya, tested positive for RSV infection. The total (health system and household) mean costs per episode of severe RSV illness was USD 329 (95% confidence interval (95% CI): 251–408 ) in Kilifi and USD 527 (95% CI: 405– 649) in Siaya. Household costs were USD 67 (95% CI: 54–80) and USD 172 (95% CI: 131– 214) in Kilifi and Siaya, respectively. Mean direct medical costs to the household during hospitalization were USD 11 (95% CI: 10–12) and USD 67 (95% CI: 51–83) among Kilifi and Siaya participants, respectively. Observed costs were lower in Kilifi due to differences in healthcare administration.ConclusionsRSV-associated disease among young children leads to a substantial economic burden to both families and the health system in Kenya. This burden may differ between Counties in Kenya and similar multi-site studies are advised to support cost-effectiveness analyses.

RSV Vaccination Intention Among People Who Are or Plan to Become Pregnant.

Respiratory syncytial virus (RSV) is a common pediatric infection, with young infants being at the highest risk of hospitalization and long-term sequela. New preventive agents have been recommended to prevent severe RSV illness in infants, including a vaccine administered during pregnancy. The current rates of recommended vaccination in pregnancy are suboptimal. Our objective was to characterize interest in RSV vaccination during pregnancy among people across the United States who were pregnant or planning to become pregnant. In March 2023, we conducted a national cross-sectional online survey of individuals 18 to 45 years old who were currently pregnant or trying to become pregnant on their perceptions of RSV-related illness and intentions to get vaccinated against RSV. We performed logistic regression analyses to determine the odds and predicted proportions of the likelihood of RSV vaccination during pregnancy, controlling for sociodemographic factors. Of 1619 completed surveys, 1528 were analyzed. 54% of respondents indicated that they were "very likely" to get vaccinated against RSV during pregnancy. The perception of RSV as a serious illness was the strongest predictor of vaccination likelihood. In the full regression model, predicted proportions of "very likely" to vaccinate against RSV followed a similar pattern (63% if RSV infection was perceived as serious and likely, 55% if serious and unlikely, 35% if not serious; P < .001). Raising awareness of RSV infection as likely and potentially serious for infants may be an influential component of targeted communications that promote RSV vaccine uptake during pregnancy.

Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Respiratory syncytial virus. Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

Summary of the National Advisory Committee on Immunization (NACI) statement update on the recommended use of palivizumab to reduce complications of respiratory syncytial virus infection in infants.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children worldwide. Underlying health conditions, especially premature birth, chronic lung disease and congenital heart disease, predispose to severe RSV illness. The only means of prophylaxis against RSV disease is passive prophylaxis with the monoclonal antibody, palivizumab (PVZ) (SynagisTM). The National Advisory Committee on Immunization (NACI) published a statement for PVZ use in 2003. The purpose of this article is to update previous NACI recommendations for the use of PVZ, taking into consideration recent data on RSV burden of illness, effectiveness of PVZ in infants at risk of more severe RSV disease and economic implications of PVZ use. The NACI Working Group and external experts performed systematic literature reviews on three topics to support updated NACI guidance: 1) RSV burden of disease; 2) PVZ effectiveness; and 3) cost effectiveness of PVZ prophylaxis. Full details and results are presented in the statement and supporting documents. Respiratory syncytial virus hospitalization (RSVH) rates are highest in children younger than one year of age and especially in the first two months of life. In various populations of infants at risk of severe RSV infection, PVZ prophylaxis is associated with reductions of 38%-86% in the risk of RSVH. Only rare cases of anaphylaxis have been reported after decades of use. Palivizumab is expensive and only cost-saving in rare scenarios. Updated NACI recommendations on use of PVZ for the prevention of complications of RSV in infants are now available.

Modelling the household-level impact of a maternal respiratory syncytial virus (RSV) vaccine in a high-income setting

BackgroundRespiratory syncytial virus (RSV) infects almost all children by the age of 2 years, with the risk of hospitalisation highest in the first 6 months of life. Development and licensure of a vaccine to prevent severe RSV illness in infants is a public health priority. A recent phase 3 clinical trial estimated the efficacy of maternal vaccination at 39% over the first 90 days of life. Households play a key role in RSV transmission; however, few estimates of population-level RSV vaccine impact account for household structure.MethodsWe simulated RSV transmission within a stochastic, individual-based model framework, using an existing demographic model, structured by age and household and parameterised with Australian data, as an exemplar of a high-income country. We modelled vaccination by immunising pregnant women and explicitly linked the immune status of each mother-infant pair. We quantified the impact on children for a range of vaccine properties and uptake levels.ResultsWe found that a maternal immunisation strategy would have the most substantial impact in infants younger than 3 months, reducing RSV infection incidence in this age group by 16.6% at 70% vaccination coverage. In children aged 3–6 months, RSV infection was reduced by 5.3%. Over the first 6 months of life, the incidence rate for infants born to unvaccinated mothers was 1.26 times that of infants born to vaccinated mothers. The impact in older age groups was more modest, with evidence of infections being delayed to the second year of life.ConclusionsOur findings show that while individual benefit from maternal RSV vaccination could be substantial, population-level reductions may be more modest. Vaccination impact was sensitive to the extent that vaccination prevented infection, highlighting the need for more vaccine trial data.

Respiratory Syncytial Virus (RSV) Neutralizing Antibodies at Birth Predict Protection from RSV Illness in Infants in the First 3 Months of Life.

BackgroundRespiratory syncytial virus (RSV) is a leading cause of viral pneumonia and bronchiolitis during the first 6 months of life. Placentally transferred antibodies can prevent severe RSV illness, and maternal immunization may reduce illness in young infants. Identification of protective antibody levels facilitates the advancement of vaccine candidates and maternal immunization.MethodsWe conducted a nested case-control study with 587 Malian mother–infant pairs, followed from birth to age 6 months. RSV cases were infants who developed influenza-like illness (ILI) or pneumonia and were RSV-positive by polymerase chain reaction. Cases were matched to healthy controls and RSV-negative ILI controls. RSV-A and RSV-B neutralizing antibodies were measured in maternal, cord blood, and infant sera at age 3 and 6 months.ResultsMaternal antibodies were efficiently transferred to infants. Maternal and infant RSV titers were strongly correlated. Infant antibody titers against RSV-A were 3 times higher than those against RSV-B. At birth, infants who remained healthy had significantly higher RSV-A and RSV-B titers compared with infants who subsequently contracted RSV. RSV-A inhibitory concentration (IC)80 titer >239 or RSV-B titer >60 at birth was significantly associated with being a healthy control compared with an RSV case within the first 3 months of life. RSV-A IC80 titers in cord blood were associated with decreased episodes of pneumonia.ConclusionsMaternally acquired RSV antibodies were associated with protection of infants against community-detected cases of RSV-ILI and pneumonia. RSV titers in cord blood can predict whether an infant will be infected with RSV or remain uninfected.

Informing randomized clinical trials of respiratory syncytial virus vaccination during pregnancy to prevent recurrent childhood wheezing: A sample size analysis

BackgroundEarly RSV illness is associated with wheeze-associated disorders in childhood. Candidate respiratory syncytial virus (RSV) vaccines may prevent acute RSV illness in infants. We investigated the feasibility of maternal RSV vaccine trials to demonstrate reductions in recurrent childhood wheezing in general paediatric populations. MethodsWe calculated vaccine trial effect sizes that depended on vaccine efficacy, allocation ratio, rate of early severe RSV illness, risk of recurrent wheezing at age 3, and increased risk of RSV infection on recurrent wheezing. Model inputs came from systematic reviews and meta-analyses. For each combination of inputs, we estimated the sample size required to detect the effect of vaccination on recurrent wheezing. ResultsThere were 81 scenarios with 1:1 allocation ratio. Risk ratios between vaccination and recurrent wheezing ranged from 0.9 to 1.0 for 70% of the scenarios. Among the 57 more plausible scenarios, the lowest sample size required to detect significant reductions in recurrent wheezing was 6196 mother-infant pairs per trial arm; however, 75% and 47% of plausible scenarios required >31,060 and >100,000 mother-infant pairs per trial arm, respectively. Studies with asthma endpoints at age 5 will likely need to be larger. DiscussionClinical efficacy trials of candidate maternal RSV vaccines undertaken for licensure are unlikely to demonstrate an effect on recurrent wheezing illness due to the large sample sizes likely needed to demonstrate a significant effect. Further efforts are needed to plan for alternative study designs to estimate the impact of maternal RSV vaccine programs on recurrent childhood wheezing in general populations.

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 Tract Infection and Risk of Hospitalization in Children with Congenital Heart Defects During Season and Off-Season: A Swedish National Study.

Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006–2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD.

Children with Down Syndrome Are High-Risk for Severe Respiratory Syncytial Virus Disease

To assess Down syndrome as an independent risk factor for respiratory syncytial virus (RSV) hospitalization in children younger than 3 years of age and to evaluate illness severity. A retrospective cohort study of children enrolled in the military health system database was conducted. The effect of Down syndrome on RSV hospitalization was assessed by Cox proportional hazards model, while we controlled for risk factors. Disease severity was assessed by length of hospital stay, need for respiratory support, and age at hospitalization. The study included 633 200 children and 3 209 378 person-years. Children with Down syndrome had a hospitalization rate of 9.6% vs 2.8% in children without Down syndrome. Down syndrome had a greater adjusted hazard ratio (HR) for RSV hospitalization than most risk factors, 3.46 (95% CI 2.75-4.37). A sensitivity analysis demonstrated HR 3.21 (95% CI 2.51-4.10) for patients with Down syndrome ages 0-23 months and HR 5.07 (95% CI 2.21-11.59) ages 24-36 months. The median (IQR) length of stay of children with and without Down syndrome was 4 days (2-7) and 2 days (1-4) (P < .001). Patients with Down syndrome had a greater risk of requiring respiratory support (relative risk 5.5; 95% CI, 2.5-12.3). The median (IQR) ages at admission for children with and without Down syndrome were 9.8 months (5.5-17.7) and 3.5 months (1.7-8.7) (P < .001). Down syndrome is independently associated with an increased risk for RSV hospitalization. Children with Down syndrome are older at time of RSV hospitalization and have more severe RSV illness than children without Down syndrome. This increased risk for hospitalization continues beyond 24 months.

Antibody response and avidity of respiratory syncytial virus‐specific total IgG, IgG1, and IgG3 in young children

Respiratory syncytial virus (RSV) is a major cause of acute respiratory disease in infants and young children. Considering that several aspects of the humoral immune response to RSV infection remain unclear, this study aimed to investigate the occurrence, levels, and avidity of total IgG, IgG1, and IgG3 antibodies against RSV in serum samples from children ≤5 years old. In addition, a possible association between antibody avidity and severity of illness was examined. The occurrence and levels of RSV-specific IgG depended on age, with infants <3 months old displaying high levels of antibodies, which were probably acquired from the mother. Children ≥24 months old also showed frequent occurrence and high levels of IgG, which was produced actively during infection. In addition, the avidity assay showed that the avidity of RSV-specific total IgG and IgG1 was lower in infants <3 months old who had acute respiratory disease than in age-matched controls. The avidity of RSV-specific IgG detected in children ≥24 months old with lower respiratory infection was lower than that in children with upper respiratory infection. These results indicate that the presence of high avidity RSV-specific IgG antibodies may lead to better protection against RSV infection in children <3 months old, who may have a lower probability of developing disease of increased severity. In addition, children ≥24 months old with RSV-specific IgG antibodies of low avidity tended to develop more severe RSV illness. These findings may be helpful in establishing vaccination schedules when a vaccine becomes available.

The Role of Immunoprophylaxis in the Reduction of Disease Attributable to Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is an RNA virus that infects human respiratory epithelial cells and causes annual outbreaks of respiratory tract disease among infants and young children, as well as recurrent infections throughout life. Annual outbreaks of RSV disease are attributable to first-time infection in susceptible infants, reinfection in children and adults with waning or incomplete immunity, and infection by viral genotypes with sufficient antigenic variation to avoid innate and acquired immunity. In industrialized countries, few infectious diseases have a greater effect on the health of young children than does lower respiratory tract disease caused by RSV. By 2 years of age, almost all children will experience an RSV infection, and ∼50% will be infected twice.1 Results from the New Vaccine Surveillance Network (a prospective, population-based surveillance program sponsored by the Centers for Disease Control and Prevention [CDC]) define the burden of RSV disease in children younger than 5 years of age.2 An estimated 2 million children require medical care because of RSV infection, and ∼57500 children younger than 5 years are hospitalized annually. The major burden of RSV disease occurs among previously healthy infants and children whose susceptibility to severe RSV illness cannot be predicted by risk factors. Protection against RSV infection is mediated by serum antibody, secretory antibody, cytotoxic T lymphocytes, and innate immune responses. A vaccine offers the greatest promise for control of RSV disease, but vaccine development has been slowed by concerns about safety (enhancement of naturally occurring disease), the limited ability of infants to mount an immune response to RSV glycoprotein antigens, and the presence of maternal neutralizing antibody, which may attenuate an active immune response. Passive immunization with either a hyperimmune globulin or a monoclonal antibody preparation has been demonstrated in randomized, placebo-controlled trials to reduce the risk of hospitalization caused by … Address correspondence to H. Cody Meissner, MD, Tufts Medical Center, 750 Washington St, Boston, MA 02111. E-mail: cmeissner{at}tuftsmedicalcenter.org

Factors impacting compliance with palivizumab prophylaxis

To the Editors: Palivizumab prophylaxis has proved effective in the prevention of serious respiratory syncytial virus (RSV) illness in high risk preterm infants. 1–3 Palivizumab is a humanized IgG antibody with a half-life of 17 to 20 days; therefore for optimal prevention it is crucial that palivizumab injections be administered every 30 days to maintain protective serum concentrations of anti-RSV antibody throughout the RSV season. A palivizumab outpatient prophylaxis program was initiated in 2000 in our tertiary level neonatal intensive care unit at the Anna Meyer Children’s Hospital of Florence, Italy. During the subsequent three respiratory seasons (November through April of 2000 to 2001, 2001 to 2002, 2002 to 2003), 156 high risk infants were prophylaxed according to the inclusion criteria for prophylaxis recommended by the American Academy of Pediatrics 4 and the Italian Neonatology Society. 5 We have retrospectively identified factors impacting compliance with the prophylaxis program. Compliance was defined as the receiving of all recommended palivizumab doses and was determined by comparing the actual number of injections given with the projected number an infant would receive. For each child we reviewed medical records and recorded demographic data. Several families (n = 16) were foreign-born and did not speak Italian. The overall compliance rate with all recommended doses of palivizumab throughout the three respiratory seasons was 86%. No demographic or neonatal characteristics seemed to impact compliance except for younger age at the beginning of the prophylaxis. Families with younger children were more compliant than those with older children (P < 0.05). We speculate that the family’s perception of their child’s health gradually changes with their growth and that the larger children were perceived as being healthier and therefore not requiring prophylaxis. Further evaluation is needed. We found that the strongest predictor for poor compliance was being foreign-born and nonnative speakers (P < 0.01). The overall compliance rate in foreign parents was 56%. The factors resulting in poor compliance in non-native speakers may include cultural differences and biases, ignorance or misunderstanding of clinical instructions, misperception of RSV illness severity and inadequate time spent on educating and informing these families. 6 In our opinion the most important characteristic was the difference in language and, related to this, our difficulties to communicate effectively. The use during the first 2 years of nonmedical translators was of little help in improving compliance with palivizumab, and we speculate that lack of medical training can lead to inadequate education and clarification of RSV risk and the importance of prophylaxis. For the third RSV prophylaxis season a letter was also included that explained the risks of RSV infection and the benefits of palivizumab prophylaxis for nonnative families. The addition of letters for nonnative families and their physicians improved compliance from 80% to 88%. This suggests a positive effect of written information and reinforcement by family health care providers. In Italy 4.2% of the population are immigrants; this is 1.0% less than the average in other European countries. 7 These families, often poor and living in crowded conditions, may bring additional risk factors for severe RSV illness. In Italy medication and health care for children is funded by the Public Health System, and this fact did not pose a barrier to compliance in this study. Italian law allows parents to have free days from work to care for their children’s health. As a result poor compliance was not thought to be job-related. Because the effectiveness of palivizumab in preventing severe RSV illness is highly dependent on compliance with the monthly injection regimen during the RSV season, we suggest that more innovative and effective approaches should be developed to overcome the barriers of an effective and compliant prophylaxis regimen. Maria Serenella Pignotti, M.D. Giuseppe Indolfi, M.D. Gianpaolo Donzelli, M.D., Ph.D. Acknowledgments. Our grateful thanks to the following for their contribution in preparing this paper: J. R. Groothuis, Global Medical Director Immunoscience Development, Abbott Laboratories; R. Merolla, Medical Manager, Abbott Laboratories; and G. M. Barbarotto, Senior Associate, Medical Communications, Abbott Laboratories.

Clinical perspectives on the association between respiratory syncytial virus and reactive airway disease.

Asthma is a leading cause of morbidity and mortality among children worldwide, as is respiratory syncytial virus (RSV). This report reviews controlled retrospective and prospective studies conducted to investigate whether there is an association between RSV bronchiolitis in infancy and subsequent development of reactive airway disease or allergic sensitization. Findings indicate that such a link to bronchial obstructive symptoms does exist and is strongest for children who experienced severe RSV illness that requires hospitalization. However, it is not yet clear what roles genetic predisposition and environmental or other risk factors may play in the interaction between RSV bronchiolitis and reactive airway disease or allergic sensitization. Randomized, prospective studies utilizing an intervention against RSV, such as a passive immunoprophylactic agent, may determine whether preventing RSV bronchiolitis reduces the incidence of asthma.

Severe Respiratory Syncytial Virus Disease in Alaska Native Children

Hospitalization rates for respiratory syncytial virus (RSV) infection range from 1 to 20/1000 infants. To determine the rate and severity of RSV infections requiring hospitalization for infants in the Yukon-Kuskokwim (YK) Delta of Alaska, a 3-year prospective surveillance study was conducted. The annual rate of RSV hospitalization for YK Delta infants <1 year of age was 53-249/1000. RSV infection was the most frequent cause of infant hospitalization. RSV disease severity did not differ among non-high-risk infants in the YK Delta and at Johns Hopkins Hospital (JHH). On average, 1/125 infants born in the YK Delta required mechanical ventilation for RSV infection. During the peak season, approximately $1034/child <3 years of age was spent on RSV hospitalization in the YK Delta. In YK Delta infants </=6 months old, RSV microneutralizing antibody titers <1200 were associated with severe disease (odds ratio=6.2, P=.03). In the YK Delta and at JHH, newborns may be at greater risk for severe RSV illness than previously thought.

RESPIRATORY SYNCYTIAL VIRUS IMMUNOGLOBULIN AS PROPHYLAXIS AGAINST RESPIRATORY SYNCYTIAL VIRUS IN CHILDREN WITH CONGENITAL HEART DISEASE. • 662

Respiratory Syncytial Virus (RSV) lower respiratory tract infection produces significant morbidity and mortality in young children with congenital heart disease (CHD). Respiratory Syncytial Virus Immunoglobulin (RSVIG) is effective in preventing severe RSV illness in high-risk preterm infants. A 3 year prospective multicenter blinded study was undertaken to determine safety and efficacy of RSVIG as RSV prophylaxis in CHD. Children <48 months were randomized to an infusion group (I) receiving 750 mg/kg RSVIG monthly over the RSV season, or to a control group (C) receiving no RSVIG. Weekly phone surveillance, monthly visits and evaluation of RSV respiratory illness was performed by blinded personnel. Study children included 202 (I) and 214 (C). P=NS for (I) vs (C) for the following variables: mean age [9.3 mo. (I), 10.7 mo. (C)]; gender; crowding; smoke exposure and cardiac severity score but more children with cyanotic CHD were randomized to receive RSVIG [78/202 (I) vs 47/214 (C), p=0.001]. Reduction in RSV hospitalization, ICU admission and mechanical ventilation rates were not statistically significant when the entire group was analyzed. However, in infants <6 months of age at study entry, RSVIG reduced hospitalization by 57% (p=0.01). In acyanotic CHD RSVIG recipients, a trend towards reduced hospital rates and days was also observed[18% (I) vs 10% (C), p=0.06]. Surgically-related severe events (SSE) were more frequent in cyanotic CHD [22/78 (I) vs 4/47 (C), p=0.01] as were surgically-related fatalities [5 (I) vs 0 (C)]. We conclude that RSVIG is safe and should be effective in decreasing serious RSV illness in children <6 months of age with acyanotic CHD. While the increased SSE and surgically-related fatalities appeared to be unrelated to RSVIG administration, children with cyanotic CHD should not be given RSVIG until the cause for this finding has been determined.

Treatment and prevention options for respiratory syncytial virus infections

Although the therapeutic antiviral agents ribavirin and amantadine ameliorate illness caused by influenza A and respiratory syncytial virus (RSV) in children, these agents are used infrequently because they are not cost-effective. Research currently is directed toward defining the high-risk groups for which these antiviral drugs should be used. Treatment of severe respiratory infection with specific immune globulin, either alone or in combination with antiviral drugs, is another therapeutic approach. Prevention of viral respiratory diseases is preferable because some lung damage occurs before the beginning of treatment, and damage resulting from the immune response may continue even after the virus is inhibited. As natural history and animal studies suggest, passive immunization can be achieved for neonates through active immunization of the mother during pregnancy. However, this approach is limited by the half-life of the transferred antibodies and the lack of antibody in premature infants. Standard immune globulin does not contain sufficient RSV neutralizing antibody titer to fully protect against severe RSV illness. Passive immunization with RSV immune globulin in infants and children has been shown to prevent or attenuate RSV in high-risk groups. Active immunization against some respiratory viruses has been achieved by administration of inactive virus (or their subunits), recombinant viral antigens, and live attenuated virus. Large trials are under way to determine the safety and immunogenicity of these vaccines for children in whom young age and serious underlying illness are significant barriers to primary immune response. The current research environment is suitable for the development of an immunization strategy to prevent many of the significant respiratory infections in children. (J PEDIATR 1994;124:S22-S7)

Role of antibody and the use of respiratory syncytial virus immunoglobulin in the prevention of respiratory syncytial virus disease in preterm infants with and without bronchopulmonary dysplasia.

Respiratory syncytial virus (RSV) is the only viral respiratory pathogen that produces an annual epidemic of respiratory illness. Infants with cardiac disease or infants born prematurely with or without bronchopulmonary dysplasia are at increased risk of severe RSV disease. A recently developed RSV immunoglobulin (RSVIG) was studied to determine safety and efficacy in prevention of severe RSV disease in such children who are high risk for severe RSV illness. Results from this prospective, blinded trial involving 249 children (102 with broncho-pulmonary dysplasia, 87 with congenital heart disease and 60 who were born prematurely) indicate that high dose RSVIG reduced the incidence and severity of RSV lower respiratory tract infection. It is a safe and effective means of RSV prophylaxis in selected high risk children.

Role of antibody and use of respiratory syncytial virus (RSV) immune globulin to prevent severe RSV disease in high-risk children

Infants with cardiac disease or infants born prematurely with or without bronchopulmonary dysplasia are at increased risk of severe respiratory syncytial virus (RSV) disease. A recently developed RSV immune globulin (RSVIG) was studied in a 3-year multicenter trial to determine safety and efficacy in the prevention of severe RSV disease in children who are at high risk of severe RSV illness. Two hundred forty-nine children were studied; 102 had bronchopulmonary dysplasia, 87 had congenital heart disease, and 60 were born prematurely. RSVIG was given on a monthly basis to 81 children at a high dose of 750 mg/kg (15 ml/ kg) and to 79 children at a low dose of 150 mg/kg (3 ml/kg). The 89 children in the control group did not receive RSVIG. There were 64 episodes of RSV infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. High-dose recipients had significantly fewer RSV lower respiratory tract infections, hospitalizations, hospital days, intensive care unit days, and less use of ribavirin compared with control subjects. Only 19 adverse events were reported during the 580 infusions administered (3%). No death was attributed to RSV disease or RSVIG therapy. Treated children did not acquire exaggerated RSV illness in a subsequent year. Thus high-dose RSVIG reduced the incidence and severity of RSV lower respiratory tract infection. It is a safe and effective means of RSV prophylaxis in selected high-risk children. (J PEDIATR 1994;124:S28-S32)