PEDIATRICS Vol. 109 No. 2 February 2002, pp. 210-216
Risk Factors for Severe Respiratory Syncytial Virus Infection Among Alaska Native Children
* Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska
Alaska Native Tribal Health Consortium, Anchorage, Alaska
Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland
|| Infectious Diseases Epidemiology Research Unit, University of Pittsburgh Graduate School of Public Health and School of Medicine, Pittsburgh, Pennsylvania
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONTHE CHANGING FACE OF...REFERENCES |
|---|
Objective. The incidence of hospitalization for respiratory syncytial virus (RSV) infection among Alaska Native children is much higher than among non-Native populations in the United States. We conducted this study to better understand factors associated with hospitalization attributable to RSV infection in this high-risk population.
Design. Case-control study, including collection of cord blood for RSV-neutralizing antibody measurement.
Setting. Remote region of southwest Alaska served by 1 regional hospital and 2 referral hospitals.
Subjects. Case-patients identified through surveillance for RSV infection and matched control subjects without acute respiratory infection hospitalization.
Results. Breastfeeding was associated with a lower risk of RSV hospitalization (odds ratio: 0.34), whereas underlying medical conditions (primarily prematurity) were associated with increased risk (odds ratio: 6.25). Environmental factors associated with a higher risk of hospitalization included household crowding (4 or more children in the household and crowding index 
2). The level of maternal RSV-neutralizing antibody was not associated with the risk of hospitalization.
Conclusions. In this region with extremely high risk of RSV hospitalization, several measures, such as encouraging breastfeeding and reducing household crowding, could reduce the risk of hospitalization attributable to RSV.
Key Words: respiratory syncytial virus • Alaska Natives • breastfeeding
Abbreviations: RSV, respiratory syncytial virus • ARI, acute respiratory infection • YK, Yukon Kuskokwim • YKDRH, YK Delta Regional Hospital • JHU, Johns Hopkins University • OR, odds ratio • BPD, bronchopulmonary dysplasia • LRI, lower respiratory infection
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONTHE CHANGING FACE OF...REFERENCES |
|---|
Respiratory syncytial virus (RSV) infection is responsible for up to 126 300 hospital admissions1 and as many as 510 deaths among children in the United States each year.2 Acute respiratory infections (ARIs) are a major cause of morbidity in Alaska Natives, especially in the Yukon Kuskokwim (YK) Delta of southwest Alaska where ARIs account for two thirds of all hospitalizations in children <3 years of age.3
Using active laboratory surveillance of all children from the YK Delta admitted to hospitals with ARIs in 1993–1996, we have reported the highest annual RSV hospitalization rates in the world (156 per 1000 infants <1 year of age).4 This statistic is many-fold higher than rates of 1 to 20 per 1000 reported in populations in other developed countries.5–7 Surveillance also showed a young peak age of hospitalization (0–2 months of age), a large proportion of RSV cases associated with pneumonia (45%), and high readmission rates within a year of the first RSV hospitalization (34%). We conducted a case-control study among YK Delta children hospitalized during 1993–1996 with confirmed RSV infections to determine factors that increased or decreased the risk of RSV hospitalization.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONTHE CHANGING FACE OF...REFERENCES |
|---|
The study population, surveillance, and laboratory methods have been described elsewhere.4 Briefly, the YK Delta region of southwestern Alaska has an area of 195 000 square kilometers and is approximately the size of South Dakota. The 1995 population of almost 20 000 is made up primarily of Yupik Eskimos (85%) who live in 52 villages ranging in population from 50 to 1000 persons and in the regional hub of Bethel (1995 population = 5195). The villages are typically connected to one another only by air, water, and snow machine trails (during winter months), and the entire region is not connected to the remainder of the state by any roads. The lifestyle of the people living in these villages is primarily subsistence with a heavy reliance on local fishing and hunting. Commercial fishing is the main export industry of the area.
Hospital services for the entire region are provided through the YK Delta Regional Hospital (YKDRH) located in Bethel. Patients may be transferred to hospitals in Anchorage, either for more intensive care or if the YKDRH lacks bed space. Acute care and routine preventive and follow-up care are provided in the villages by community health aides who work with standing orders and maintain radio contact with hospital physicians.8
Approximately 600 births occur each year in the YK Delta region. During the study period, nurses saved the cord blood of every infant whose parents gave informed consent. A registry of high-risk infants with chronic medical conditions (cardiac, pulmonary, metabolic, or immunologic disease, neurologic impairment, or prematurity with gestational age 
36 weeks) in the YK Delta region was maintained beginning January 1, 1992. For this analysis, a high-risk infant was defined as a child born in the YK Delta with 1 of the disorders mentioned. This study was approved by the YK Health Board, the YK Health Corporation Human Studies Committee, the institutional review board of Providence Health System in Alaska, the Alaska Area Native Health Service Research and Publications Committee, and the Indian Health Service Research Study Section.
Case Definition
We defined a case of disease as an ARI occurring in a child <3 years of age from the YK Delta and requiring admission to the YKDRH or an Anchorage hospital between October 1, 1993, and September 30, 1996. From children whose parents agreed to participate, a nasopharyngeal aspirate was obtained for viral isolation and RSV antigen detection. Each nasopharyngeal aspirate was tested for RSV by rapid antigen enzyme immunoassay test pack (Abbott, Oak Park, IL) or by direct fluorescent antibody (Bartels, Issaquah, WA). The rest of each sample was snap frozen and transported to a virology laboratory (at Johns Hopkins University [JHU]) where it was cultured for RSV as previously described.4 Virus isolates were identified by an indirect immunofluorescence assay (Bartels). RSV culture-negative specimens were retested by rapid enzyme immunoassay test (Abbott Testpak). Cord serum specimens were tested for RSV-neutralizing antibody by complement-enhanced plaque-reduction neutralization assay as previously described.9
Case-patients were eligible for inclusion in the case-control study if they had a positive RSV nasopharyngeal culture or antigen test during ARI hospitalization. Patients were classified as definite if their culture specimen or 2 antigen tests by different assays (enzyme immunoassay and fluorescent antibody) were positive; probable if the same antigen test was repeatedly positive; and possible if 1 antigen test was positive for RSV. During a given study year, October 1 to September 30, a child was considered eligible for the case-control study based only on his or her first RSV hospitalization during that year.
Data from the ARI admission of each case-patient were obtained by review of the medical record. The severity of the case-patient’s illness was classified by using a published severity index.10 This score ranges from 0 through 7 points, with a point each for oxygen saturation <87%, pH <7.35, PCO2 >45 mm Hg, apnea during hospital stay, and hospital stay greater than 5 days and 2 points for use of mechanical ventilation.
Control Selection
Control subjects were selected from a master list of YK Delta children, constructed from births at YKDRH or Anchorage hospitals and updated with children born in the villages. To be considered for inclusion, control subjects could not have had an ARI hospitalization during the year of the case-patient’s hospitalization. Control matching, with the goal of matching 2 control subjects to each case-patient, was done using a caliper method, and we attempted to match based on the case-patient’s date of birth and village/region of residence. Villages within the YK Delta were grouped by proximity and travel patterns into 10 subregions. A list of possible control subjects was generated for each case-patient, moving outward in time in both directions from the case-patient’s date of birth, but within the case-patient’s village, for up to 30 days difference in birth date. If 2 or more eligible control subjects could not be identified within the village, infants from within the same subregion were added beginning again at the case-patient’s birth date and moving outward in both directions. After this list was created, the charts of potential control subjects were reviewed. To help reduce misclassification, infants who were hospitalized for a respiratory infection during the study year before the case-patient’s date of illness were deleted from the list and were not eligible to be control subjects. After development of the list of potential control subjects, project nurses traveled to villages and offered the parents of case-patients and potential control subjects the opportunity to participate in the case-control study. Researchers interviewed those who consented using a standardized questionnaire and reviewed their village and hospital medical records. The questionnaire included questions about breastfeeding, food prechewing (a common cultural practice), household size and composition, smoking within the household, methods of heating and cooking, use of day care, parental education levels, and potential economic indicators. All questions referred to the status of the infant and household at the age of the respective case-patient at admission. The consent obtained also included permission to test cord blood (if obtained) for RSV-neutralizing antibody. Interviews with mothers from the most remote villages were conducted by phone.
Statistical Analysis and Data Definitions
Case-patients and control subjects were compared by using conditional logistic regression to preserve the case-control matching. Matched bivariate analysis was done with a single predictor variable and multivariate analysis with multiple predictor variables. Conditional multivariate regression models were developed by using a forward stepwise approach. Any risk factor that was statistically significant (P < .05) in any of the bivariate subgroup analyses was considered for entry into the multivariate model. Separate models were developed for each of the following subgroups of case-patients and the corresponding control subjects: entire group, case-patients <6 months of age at admission, and case-patients 6 months of age at admission. All P values reported are 2-sided. No adjustments were made for multiple comparisons. The household crowding index was calculated as the total persons in the household divided by the number of rooms (excluding bathrooms, hallways, closets, etc). Stata, Release 5 (Stata Corporation, College Station, TX) was used for statistical calculations.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONTHE CHANGING FACE OF...REFERENCES |
|---|
Study Population
There were 431 hospitalizations for RSV infection in YK Delta children <3 years of age from October 1, 1993, through September 30, 1996. Sixty-one (14.2%) of these were readmissions of children previously hospitalized with an RSV infection during the same RSV study year and hence were excluded from participating in the case-control study. Of the 370 eligible children with hospital admissions, 204 (55.1%) were recruited into the study along with 1 or more matched controls. Of the 166 eligible case-patients who were not recruited, 13 (3.5% of total eligible) had parents who were approached and refused to participate. The other nonparticipants were not contacted because adequately matched control subjects could not be identified or because travel logistics resulted in a long delay before recruitment could begin. Four case-patients were known to have moved from the study area.
The case-patients who were included in the study were similar to other case-patients in terms of gender, disease severity, and age at illness but were more likely to have a definite rather than a possible or probable RSV infection (Table 1). The proportion of eligible case-patients who were included in the case-control study decreased over the course of the study from 71.7% (27/38) in the first year, to 60.0% (126/210) in the second year, and 41.8% (51/122) in the third year (
2 = 14.2; P < .001).
|
The case-patients who were included in the study ranged in age from <1 month to 34 months of age (median: 5.9 months). Eighty-eight (43.1%) of the 204 case-patients had a disease severity score of 0, 78/204 (38.2%) had a disease severity of 1, 38 (18.6%) had a disease severity of
2. The case-patients came from 36 of the 52 communities in the YK Delta, including Bethel, where 19 case-patients lived. The case-patients included 6 (2.9%) who were mechanically ventilated, 9 (4.4%) who had apnea during their hospital stay, 28 (13.7%) with PCO2 >45 mm Hg, 31 (15.2%) with oxygen saturation <87%, 23 (11.3%) with pH <7.35, and 104 (51.0%) who were hospitalized for >5 days.
Case-Control Matching
The 204 case-patients were matched with a total of 338 control subjects. Seventy-four (36.3%) case-patients were matched to 1 control subject, 126 (61.8%) to 2 control subjects, and 4 (2.0%) to 3 control subjects. Matching for birth date and village was generally achieved, with 74% of control subjects born within 30 days of the case-patient, and 96% within 60 days. All control subjects were from the same subregion as the case-patient, and 171 (50.6%) control subjects were from the same village as the case-patient. In addition case-patients and control subjects were very similar in terms of the location (home, clinic, telephone) and timing of the interview (median days from the case-patient’s admission: case-patients 109 days, control subjects 108 days).
Bivariate Analysis
Table 2 gives observed proportions or other summary measures of case-patients and control subjects for a number of the characteristics examined, along with the results of matched bivariate analysis. Risk of RSV hospitalization was greater for high-risk infants and those with 7 or more additional persons in the household, 2 or more children under 2 years of age in the household, 4 or more children <12 years of age in the household, a household crowding index of 2 or more, other persons sleeping in the same bed with the child, or a smoker in the household. Risk was significantly decreased with all breastfeeding measures and with having a mother with >12 years of formal education.
|
The case-patient’s or control subject’s having been breastfed at some point before the admission age was a protective factor overall and in all subgroups. Among case-patients <6 months of age at illness, 38% (41/108) were being breastfed at the time of admission, compared with 55% (94/171) of their matched control subjects. Among older case-patients, 14% (13/96) were breastfed, compared with 28% (47/167) of matched control subjects. The presence of any breastfeeding and prolonged duration (>6 months) were more common in control subjects than in older case-patients. Eating prechewed food emerged as a protective factor for children <6 months of age.
High-risk status because of an underlying medical condition was clearly a risk factor. Sixteen percent of the case-patients, compared with only 2.4% of control subjects, had some underlying medical condition (Table 3). The most common underlying medical condition in both case-patients and control subjects was prematurity, the diagnosis of 28/40 (70.0%) high-risk infants. Case-patients born prematurely ranged from 31 to 36 weeks’ gestational age with a median of 35 weeks. Prematurely born control subjects ranged from 34 to 36 weeks with a median of 35.5 weeks (P = .190).
|
The effect of RSV-neutralizing antibody in cord sera was assessed in the subgroup of case-patients <6 months of age at their hospitalization and among their control subjects for whom cord serum specimens were available (Table 4). Levels of RSV-neutralizing antibody, either as a linear term on a logarithmic scale or dichotomized to a titer <1:250 or
1:250, did not differ between case-patients and control subjects.
|
Multivariate Conditional Logistic Regression
Sixteen of the 31 possible factors were entered into a multivariate model. For the complete data set, the logistic model identified includes high risk (odds ratio [OR]: 6.63; P < .001), having ever been breastfed more than half of feedings (OR: 0.38; P = .001), having been breastfed within 8 weeks of the case-patient’s age at admission (OR: 0.44; P = .004), having 4 or more children <12 years of age in the household (OR 2.13; P = .011), and having a household crowding index of 2 or greater (OR: 1.72; P = .024; Table 5).
|
Among case-patients <6 months of age at admission, the model obtained by forward selection includes high risk (OR: 4.34; P = .016), having been breastfed more than half of feedings (OR: 0.33; P = .001), having 4 or more children <12 years of age in the household (OR: 3.28; P = .007), and living in a household with a crowding index of 2 or more (OR: 2.41; P = .007). Among older case-patients (
6 months of age), the simplest model includes high risk (OR: 20.5; P < .001), ever having been breastfed (OR: 0.25; P = .001), having been breastfed within 8 weeks of the case-patient’s admission age (OR: 0.27; P = .004), and sharing a bed (OR: 2.20; P = .036). |
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONTHE CHANGING FACE OF...REFERENCES |
|---|
In this case-control study, we attempted to delineate factors that increased or decreased risk of RSV hospitalization in a population of Alaska Native children who experience extremely high rates of hospitalization for RSV infection. Nonhigh-risk children hospitalized with RSV at YKDRH have similar overall disease severity to children hospitalized at JHU Hospital,4 suggesting that hospitalization for mild disease does not account for the high rates of hospitalization. Similarly, high rates of hospitalization for RSV infection in Canadian Inuit children (oral communication, Bruce D. Martin, University of Manitoba, November 2000) suggest that environmental factors, such as household crowding, poorly ventilated homes, extremely cold weather conditions, and limited indoor plumbing, all contribute to high rates of disease and rapid spread within communities.
Other studies have demonstrated that factors associated with severe RSV disease include young age; underlying medical problems (prematurity, lung disease, congenital heart disease, other major congenital anomalies, compromised immune function); low levels of RSV-neutralizing antibody; and environmental conditions such as crowding, low socioeconomic status, lack of breastfeeding, and passive smoke exposure.11–21 In our final multivariate analysis, we found that underlying medical conditions and crowding were associated with higher risk of RSV hospitalization, whereas breastfeeding was protective.
In our study, underlying medical conditions, primarily prematurity, were associated with an approximately sixfold increased risk of hospitalization for RSV infection compared with controls. Increased risk for RSV hospitalization was seen in all infants born 36 weeks’ gestation whether or not they had required mechanical ventilation or oxygen therapy as newborns. Cunningham et al12 found that, although premature infants with bronchopulmonary dysplasia (BPD) had a greater incidence of rehospitalization than those without BPD, even premature infants without BPD had a 10-fold increase in rehospitalization over matched full-term infants.
Several studies have demonstrated a decreased risk of severe RSV infection in infants with high levels of RSV-neutralizing antibodies.11,15–17 We were unable to show any significant difference in overall hospitalization rates based on levels of RSV-neutralizing antibody in cord blood. Cellular immune responses also play a critical role in both recovery from and modulation of RSV disease.22 In addition, in this population with extremely high rates of RSV disease transmission, the initial inoculum of virus may be so great as to overcome the protective effects of neutralizing antibody.
Studies evaluating respiratory illnesses in relation to breastfeeding have found conflicting results. Some studies23 did not find evidence of protection from mild illness, whereas other studies18 found decreased severity but not decreased incidence of respiratory disease in breastfed infants. Wright24 and Beaudry25 demonstrated a protective effect of breastfeeding against wheezing lower respiratory infection (LRI) only during the first 4 to 6 months of life, whereas others found more generalized decreased risk of LRI or hospitalization with RSV infection in breastfeeding infants.18,19,26
In our study, all measures of breastfeeding in both children <6 months and 6 months of age were associated with a lower rate of hospitalization with RSV infection. Among children 6 months of age, having ever been breastfed and being breastfed within 8 weeks of the hospitalization are independently significant, even when examined simultaneously. Breastfeeding rates are high in this population. Eighty-one percent of control subjects in our study were breastfed at some point. From this study, we cannot ascertain the mechanism of protection by breastfeeding and cannot exclude the possibility that breastfeeding protects infants for social rather than biological reasons (eg, prolonged contact with the mother and lessened contact with other individuals). Nevertheless, regardless of the reasons for protection, the strong association between breastfeeding and lack of severe RSV infection suggests that increasing the proportion of mothers who breastfeed their infants could result in substantial disease reduction.
Household crowding has been associated with increased risk of RSV hospitalization.25–27 In our study, the presence of 4 or more children <12 years of age in the household and a crowding index of 2 or more were associated with increased RSV hospitalization risk. Unlike Anderson et al,20 we did not show an association between number of people sleeping in the same room as the child and increased risk of RSV hospitalization; however, our study showed an association between increased numbers sleeping in the same bed as the infant and risk of RSV hospitalization. Day care attendance was not associated with increased risk; however, few members of this population use formal day care.
Maternal smoking during pregnancy has been shown to cause diminished lower airway function in infants.28 Most studies of smoking related to LRIs in the first year of life have found an association with maternal smoking,27,29 or household smoke exposure.27,30 Presence of a household smoker was associated with higher risk of RSV hospitalization in the matched bivariate analysis, but was not significantly associated with RSV hospitalization in a multiple logistic regression. Frequent visiting between households in a village may have decreased our ability to demonstrate an effect of household smokers on RSV hospitalization.
Unlike Robin et al,31 we were unable to demonstrate an increased risk of LRI hospitalization in children living in households that cooked with wood-burning stoves. The type of cooking fuel is likely to be more similar within a village than between villages; therefore, the fact that children in our study were age-matched within villages may have limited our ability to measure the potential impact of stove type on the risk of RSV hospitalization.
The failure to enroll a substantial proportion of potentially eligible cases could have biased the results of our study. However, the comparison of these cases with those that were enrolled suggests that they were relatively similar in terms of severity of illness and village environment. The ORs reported above may overestimate the relative risk because the RSV hospitalizations are common in this population. The exclusion of children with hospital admissions attributable to non-RSV ARIs would tend to accentuate the differences we observed. However, the purpose of this study was to identify factors that differentiated children with RSV hospitalization from children who did not require hospitalization attributable to ARI, not to compare children with severe RSV infection with children with other forms of severe ARI.
|
CONCLUSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONTHE CHANGING FACE OF...REFERENCES |
|---|
We have identified preventable factors that may contribute to the extremely high risk of RSV hospitalization among Alaska Native children. Underlying medical condition, primarily prematurity, is associated with a higher risk of hospitalization, and premature infants have been targeted for prophylaxis with RSV monoclonal antibody.32 Breastfeeding is associated with a decreased risk of RSV infection resulting in hospitalization. Maternal education efforts could raise breastfeeding rates even above their already high levels leading to an additional reduction in hospitalizations related to RSV infections. Household crowding also increases risk for severe RSV infection. Although household crowding is not easily remedied, disease transmission can be decreased through educational programs aimed at increasing the practice of handwashing before caring for infants and lessening exposure of small infants to large groups of people.
|
THE CHANGING FACE OF PEDIATRIC HIV-1 INFECTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONTHE CHANGING FACE OF...REFERENCES |
|---|
"The availability of potent combination therapies has altered the clinical course of HIV-1 infection in children. In the United States today, fewer than 200 children acquire HIV-1 infection each year, and these infections are in large part the result of the failure of HIV-1-infected pregnant women to obtain prenatal care or adhere to prescribed regimes. Current diagnostic methods permit the identification of the majority of vertically infected infants by 1 month of age, and the current guidelines recommend the initiation of combination antiretroviral therapy as soon as the diagnosis is confirmed...more than 90% of the estimated 1700 new pediatric infections that occur each day around the world occur in developing countries. Advances in the developed world have been difficult to replicate in resource-poor settings."
Sullivan JL, Luzuriaga K. N Engl J Med. 2001;345:1568–1569
Noted by JFL, MD
|
ACKNOWLEDGMENTS |
|---|
This study was funded by grants from the Indian Health Service and Wyeth-Lederle Vaccines and Pediatrics and in-kind donation of RSV test pack kits from Abbott Laboratories.
We thank Dr Jay Butler for his thoughtful editing. We are indebted to the families of the YK Delta region and the YK Health Corporation for their participation in and support of this project.
Alaska RSV Study Group: Patricia Martinez, Donna Brown, Carol Lilly, Elizabeth Hughes, and Doris Bonilla, Yukon-Kuskokwim Health Corp, Bethel, Alaska; Gilbert Varney, Marilyn Getty, Susan Seidel, Helen Peters, Rhonda Baisden, and Mary Anne Fitzgerald, Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, Alaska; Nina Davidson and James Berner, Alaska Area Native Health Service, Anchorage, Alaska; Dion Roberts, Jack Jacobs, and Sharon Hulman, Providence Alaska Medical Center, Anchorage, Alaska; Shahina Amin, Division of Disease Control, Department of International Health, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland.
|
FOOTNOTES |
|---|
Received for publication Feb 7, 2001; Accepted Sep 4, 2001.
Reprint requests to (R.J.S.) Arctic Investigations Program, Centers for Disease Control and Prevention, 4055 Tudor Centre Dr, Anchorage, AK 99508. E-mail: rsingleton{at}cdc.gov
The opinions expressed in this article are those of the authors and do not necessarily reflect the views of the Indian Health Service.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONTHE CHANGING FACE OF...REFERENCES |
|---|
- 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[Medline]
- Shay DK, Holman RC, Roosevelt GE, Clarke MJ, Anderson LJ. Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979–1997. J Infect Dis.2001; 183 :16 –22[Medline]
- Singleton RJ, Peterson KM, Berner JE, et al. Hospitalizations for respiratory syncytial virus infection in Alaska Native children. Pediatr Infect Dis J.1995; 14 :26 –30[Medline]
- Karron RA, Singleton RJ, Bulkow L, et al. Severe respiratory syncytial virus disease in Alaska Native children. J Infect Dis.1999; 180 :41 –49[Medline]
- Martin AJ, Gardner PS, McQuillin J. Epidemiology of respiratory viral infection among paediatric inpatients over a six-year period in northeast England. Lancet.1978; 2 :1035 –1038[Medline]
- Institute of Medicine. Diseases of importance in the United States. In: Committee on Issues and Priorities for New Vaccine Development, ed. New Vaccine Development: Establishing Priorities. Washington, DC: National Academy Press;1985 :397 –409
- Dagan R, Landau D, Haikin H, Tal A. Hospitalization of Jewish and Bedouin infants in southern Israel for bronchiolitis caused by respiratory syncytial virus. Pediatr Infect Dis J.1993; 12 :381 –386[Medline]
- Berner BJ. Provision of health care in a frontier setting: an Alaskan perspective. J Am Acad Nurse Pract.1992; 4 :89 –94[Medline]
- Connors M, Collins PL, Firestone CY, et al. Cotton rats previously immunized with a chimeric RSV FG glycoprotein develop enhanced pulmonary pathology when infected with RSV, a phenomenon not encountered following immunization with vaccinia–RSV recombinants or RSV. Vaccine.1992; 10 :475 –484[Medline]
- McConnochie KM, Hall CG, Walsh EE, Roghmann KJ. Variation in severity of respiratory syncytial virus infections with subtype. J Pediatr.1990; 117 :52 –62[Medline]
- Glezen WP, Paredes A, Allison JE, Taber LH, Frank AL. Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level. J Pediatr.1981; 98 :708 –715[Medline]
- Cunningham CK, McMillan JA, Gross SJ. Rehospitalization for respiratory illness in infants of less than 32 weeks’ gestation. Pediatrics.1991; 88 :527 –532[Abstract]
- Groothuis JR, Gutierrez KM, Lauer BA. Respiratory syncytial virus infection in children with bronchopulmonary dysplasia. Pediatrics.1988; 82 :199 –203[Abstract]
- MacDonald NE, Hall CB, Suffin SC, et al. Respiratory syncytial viral infection in infants with congenital heart disease. N Engl J Med.1982; 307 :397 –400[Abstract]
- Lamprecht CL, Krause HE, Mufson MA. Role of maternal antibody in pneumonia and bronchiolitis due to respiratory syncytial virus. J Infect Dis.1976; 134 :211 –217[Medline]
- Ogilvie MM, Vathenen AS, Radford M, Codd J, Kay S. Maternal antibody and respiratory syncytial virus infection in infancy. J Med Virol.1981; 7 :263 –271[Medline]
- Bruhn FW, Yeager AS. Respiratory syncytial virus in early infancy: circulating antibody and the severity of infection. Am J Dis Child.1977; 131 :145 –148[Medline]
- Frank AL, Taber LH, Glezen WP, Kasel GL, Wells CR, Paredes A. Breastfeeding and respiratory virus infection. Pediatrics.1982; 70 :239 –245[Abstract]
- Downham MAPS, Scott R, Sims DG, et al. Breast-feeding protects against respiratory syncytial virus infection. BMJ.1976; 2 :274 –276[Medline]
- Pullan CR, Toms GL, Martin AJ, et al. Breast-feeding and respiratory syncytial virus infection. BMJ.1980; 281 :1034 –1036[Medline]
- Anderson LJ, Parker RA, Strikas RA, et al. Day care center attendance and hospitalization for lower respiratory tract illness. Pediatrics.1988; 88 :300 –308
- Prober CG, Sullender WM. Advances in prevention of respiratory syncytial virus infections. J Pediatr.1999; 135 :546 –558[Medline]
- Fergusson DM, Horwood LJ, Shannon FT, et al. Infant health and breast-feeding during the first 16 weeks of life. Aust Paediatr J.1978; 14 :254 –258[Medline]
- Wright AL, Holberg CJ, Taussig LM, Martinez FD. Relationship of infant feeding to recurrent wheezing at age 6 years. Arch Pediatr Adolesc Med.1995; 149 :758 –763[Medline]
- Beaudry M, Dufour R, Marcoux S. Relation between infant feeding and infections during the first six months of life. J Pediatr.1995; 126 :292 –197
- Holberg CJ, Wright AL, Martinez FD, Ray CG, Taussig LM, Lebowitz MD. Risk factors for respiratory syncytial virus-associated lower respiratory illnesses in the first year of life. Am J Epidemiol.1991; 133 :1135 –1151[Abstract]
- McConnochie KM, Roghmann KJ. Parental smoking, presence of older siblings, and family history of asthma increase risk of bronchioliti. Am J Dis Child.1986; 140 :806 –811[Medline]
- Hanrahan JP, Tager IB, Segal MR, et al. The effect of maternal smoking during pregnancy on early infant lung function. Am Rev Respir Dis.1992; 145 :1129 –1135[Medline]
- Wright AL, Holberg C, Martinez FD, Taussig LM. Relationship of parental smoking to wheezing and non-wheezing lower respiratory tract illnesses in infancy. J Pediatr.1991; 118 :207 –213[Medline]
- Duff AL, Pomeranz ES, Gelber LE. Risk factors for acute wheezing in infants and children: viruses, passive smoke, and IgE antibodies to inhalant allergens. Pediatrics.1993; 92 :535 –539[Abstract]
- Robin LF, Lees PS, Winget M, et al. Wood burning stoves and lower respiratory illnesses in Navajo children. Pediatr Infect Dis J.1996; 15 :859 –865[Medline]
- Meissner HC, Welliver RC, Chartrand SA, et al. Immunoprophylaxis with palivizumab, a humanized respiratory syncytial virus monoclonal antibody, for prevention of respiratory syncytial virus infection in high risk infants: a consensus opinion. Pediatr Infect Dis J.1999; 18 :223 –231[Medline]
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  R. J. Singleton, E. A. Wirsing, D. L. Haberling, K. Y. Christensen, C. D. Paddock, J. A. Hilinski, B. J. Stoll, and R. C. Holman Risk Factors for Lower Respiratory Tract Infection Death Among Infants in the United States, 1999-2004 Pediatrics, October 1, 2009; 124(4): e768 - e776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Gaur, K. L. Dominguez, M. L. Kalish, D. Rivera-Hernandez, M. Donohoe, J. T. Brooks, and C. D. Mitchell Practice of Feeding Premasticated Food to Infants: A Potential Risk Factor for HIV Transmission Pediatrics, August 1, 2009; 124(2): 658 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Singleton, S. Holve, A. Groom, B. J. McMahon, M. Santosham, G. Brenneman, and K. L. O'Brien Impact of Immunizations on the Disease Burden of American Indian and Alaska Native Children Arch Pediatr Adolesc Med, May 1, 2009; 163(5): 446 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. G. Nichols, A. J. Peck Campbell, and M. Boeckh Respiratory Viruses Other than Influenza Virus: Impact and Therapeutic Advances Clin. Microbiol. Rev., April 1, 2008; 21(2): 274 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kovesi MD, N. L. Gilbert MSc, C. Stocco MSc, D. Fugler PEng, R. E. Dales MD MSc, M. Guay MSc, and J. D. Miller PhD Indoor air quality and the risk of lower respiratory tract infections in young Canadian Inuit children Can. Med. Assoc. J., July 17, 2007; 177(2): 155 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A.F. Simoes Maternal Smoking, Asthma, and Bronchiolitis: Clear-Cut Association or Equivocal Evidence? Pediatrics, June 1, 2007; 119(6): 1210 - 1212. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Somech, G. Tal, E. Gilad, A. Mandelberg, A. Tal, and I. Dalal Epidemiologic, Socioeconomic, and Clinical Factors Associated with Severity of Respiratory Syncytial Virus Infection in Previously Healthy Infants Clinical Pediatrics, September 1, 2006; 45(7): 621 - 627. [Abstract] [PDF]
|
|
|
|
|
|
J. M. Paricio Talayero, M. Lizan-Garcia, A. O. Puime, M. J. B. Muncharaz, B. B. Soto, M. Sanchez-Palomares, L. S. Serrano, and L. L. Rivera Full Breastfeeding and Hospitalization as a Result of Infections in the First Year of Life Pediatrics, July 1, 2006; 118(1): e92 - e99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Choudhuri, L. G. Ogden, A. J. Ruttenber, D. S.K. Thomas, J. K. Todd, and E. A.F. Simoes Effect of Altitude on Hospitalizations for Respiratory Syncytial Virus Infection Pediatrics, February 1, 2006; 117(2): 349 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Broughton, R Bhat, A Roberts, M Zuckerman, G Rafferty, and A Greenough Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants Arch. Dis. Child., January 1, 2006; 91(1): 26 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Broughton, A Roberts, G Fox, E Pollina, M Zuckerman, S Chaudhry, and A Greenough Prospective study of healthcare utilisation and respiratory morbidity due to RSV infection in prematurely born infants Thorax, December 1, 2005; 60(12): 1039 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Holman, A. T. Curns, J. E. Cheek, J. S. Bresee, R. J. Singleton, K. Carver, and L. J. Anderson Respiratory Syncytial Virus Hospitalizations Among American Indian and Alaska Native Infants and the General United States Infant Population Pediatrics, October 1, 2004; 114(4): e437 - e444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Singleton, G. J. Redding, T. C. Lewis, P. Martinez, L. Bulkow, B. Morray, H. Peters, J. Gove, C. Jones, D. Stamey, et al. Sequelae of Severe Respiratory Syncytial Virus Infection in Infancy and Early Childhood Among Alaska Native Children Pediatrics, August 1, 2003; 112(2): 285 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. R. G. Bachrach, E. Schwarz, and L. R. Bachrach Breastfeeding and the Risk of Hospitalization for Respiratory Disease in Infancy: A Meta-analysis Arch Pediatr Adolesc Med, March 1, 2003; 157(3): 237 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Holman, A. T. Curns, J. E. Cheek, R. J. Singleton, L. J. Anderson, and R. W. Pinner Infectious Disease Hospitalizations Among American Indian and Alaska Native Infants Pediatrics, February 1, 2003; 111(2): e176 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Munoz, W. P. Glezen, R. Singleton, L. R. Bulkow, R. A. Karron, and L. H. Harrison Why No Effect of Maternal Respiratory Syncytial Virus-Neutralizing Antibody? Pediatrics, January 1, 2003; 111(1): 218 - 220. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
