Original Article
Respiratory Syncytial Virus Infections within Families
N Engl J Med 1976; 294:414-419February 19, 1976DOI: 10.1056/NEJM197602192940803
- Abstract
- Abstract
To examine intrafamily spread of respiratory syncytial virus infections and their associated illnesses, 36 families with 188 members were studied during an outbreak of such infections. Nurses visited every three to four days to obtain specimens for viral isolation and interview household members. The virus infected 44.4 per cent of families, and 21.9 per cent of all members. All age groups had appreciable attack rates (with a range of 16.8 per cent in adults to 29.4 per cent in infants). In infected families, 45.9 per cent of members became infected, including 10 of 16 infants. Secondary attack rate for all ages was 27 per cent, and that for infants 45.4 per cent. An infant's older sibling appeared most likely to introduce the virus into the family. Associated acute respiratory illnesses occurred in 94.9 per cent of cases, and appeared more severe than those not associated with respiratory syncytial virus.
When the virus was introduced into a family the high attack rate produced an illness of age-related severity. (N Engl J Med 294:414–419, 1976)
Media in This Article
Figure 1
Number and Percentage of Family Members Positive for Respiratory Syncytial Virus (RSV) According to Date of Onset of Shedding.Figure 2
Distribution According to Date of Number and Percentage of Hospitalized Patients with Infection Due to Respiratory Syncytial Virus Admitted from within the City and from outside the City.Article Activity
- Article
Respiratory syncytial virus is recognized as the most important viral respiratory pathogen of infants.1 2 3 4 In spite of several previous surveys, many questions relating to the interfamily and intrafamily epidemiology of infection from this cause remain and are the focus of this study. A basic understanding of the transmission of the virus in families is important in any attempt to protect the infant in whom such an infection may be life-threatening. Questions that remain concern the way in which the virus is introduced into the family, and the spectrum of illness and attack rates within the family members of all ages.
Previous epidemiologic studies have been either serologic surveys, or studies of the cause of acute illness.5 6 7 8 9 10 11 12 13 14 15 16 Serologic surveys have the disadvantages of a recognized variability in antibody response to respiratory syncytial virus infection and difficulty in correlating symptoms with timing of infection.8 , 10 , 14 , 17 , 18 Studies of acutely ill persons obviously miss asymptomatic or very mild illness, which could be important in the spread of infections, since reinfection in older children and adults has been described as usually asymptomatic or causing mild illness.3 , 7 , 9 , 19 We therefore designed the present prospective study to obviate these problems by home visits every three to four days to determine symptoms and collect specimens for viral isolation from all members of a group of families during a community outbreak of infection with respiratory syncytial virus.
Methods
Subjects
Participation of families was obtained by their private pediatricians at the Genesee Health Service, a group practice. Families were selected during the two months before the study on the basis of including two or more children, one of whom was less than a year of age. Initially, the study was explained to the families by their private pediatricians at the time of office visits. Upon their consent to participate, a letter explaining the nature and the procedures of the study was sent to each family. Subsequently, study team members telephoned and then visited each family to explain the project and answer any further questions.
Study Design
The study was initiated as soon as respiratory syncytial virus was known to be in the community, and confirmed by viral isolation. Each family was visited every three to four days during the two months of the study by a team of two nurses. At that time the nurse recorded the symptoms of illness in all family members on a standardized form. In addition, nose and throat specimens were obtained for viral isolation on everyone present in the household. Blood samples were not taken. For comparison, epidemiologic information was obtained on children admitted to the hospital with lower-respiratory-tract infection due to the virus. This information was derived through an ongoing surveillance system for respiratory disease in our hospital and community.20
Background information on the families was obtained at the end of the survey when the nurses had established good rapport with the family members. This information included the number of rooms in the home (excluding closets and bathroom), education and employment of family members, smoking histories, childhood contacts and past medical history.
At the end of the study, the private physicians' records on the infants (less than one year of age) were reviewed. Data on the number and types of illnesses in these infants that required a physician's care were compared to the information obtained through the nurses' interviews.
Collection of Specimens
The nurses carried to each home cell cultures of a HFp-2 cell line especially sensitive to respiratory syncytial virus containing fresh medium (from Flow Laboratories, Rockville, Maryland). From each member of the family nose and throat swabs were obtained, and placed together into a tube containing 2 ml of veal infusion broth, 0.05 per cent bovine albumin and antibiotics. After the swabs were mixed with the veal infusion broth, 0.5 ml of this mixture was inoculated onto one cell culture. These cultures and the remaining specimen in ice were then transported back to the laboratory for further processing.
Viral Isolation
On return to the laboratory the remaining specimen in aliquots was rapidly frozen in alcohol and dry ice and stored at — 70°C. The returned cultures were incubated at 33°C for about one hour. They were then washed with minimum essential medium containing antibiotics and refed with the same medium containing 2 per cent fetal-calf serum, glutamine, penicillin, kanamycin, and 7.5 per cent sodium bicarbonate added to pH 7.6 to 7.8. Cultures were then reincubated at 33°C on a rotating drum, and observed daily for two weeks for the characteristic cytopathogenic effect of respiratory syncytial virus. Cultures that became positive or suspect were passed onto new cell cultures to confirm the presence or absence of cytopathogenic effect. In addition, cultures that became difficult to read (from toxicity, age or contamination) were passed, and aliquots of the original frozen specimen were reinoculated onto new cell cultures. All isolates were identified as respiratory syncytial virus complement-fixation testing using specific antiserums.21
Cell lines other than HEp-2 were only occasionally used, when the private physician requested that the recovery of other viral agents be attempted from the specimen of a family member who was ill. Bacterial cultures were obtained by the private physician.
Results
Families
Thirty-six families with 188 members participated in the study. A total of 1991 specimens were collected from 178 family members over a two-month period. Specimens were never collected from 10 family members, all adult males except for one 11-year-old boy. Of those tested, the average number of specimens per person was 10.7, and the median 13. All but five of these families were from the city, the majority being from the inner city. Fifty-two per cent were receiving Medicaid. Of the 178 family members tested, 123 were children under the age of 17 years (59 males and 64 females), with a median age of two years. Most of the adults were females — 40 of the 55. Thirty-six were mothers, 13 fathers, and three grandmothers. The average number of children per family was 3.5.
Epidemic Curve of Cases
Respiratory syncytial virus was first isolated in the third week in December from a hospitalized infant from the city. The first home visits started on December 30, 1974, and continued until March 1, 1975. The virus was isolated from 39 members of 16 families. Figure 1Figure 1
Number and Percentage of Family Members Positive for Respiratory Syncytial Virus (RSV) According to Date of Onset of Shedding. shows the date of the first positive culture from each infected member. The greatest number of cases occurred during the first few weeks of the study, with few isolates obtained after the end of January, as indicated by the declining percentage of cases that first became positive for respiratory syncytial virus as the study progressed (Fig. 1). In comparison, in most hospitalized cases of infection, patients were admitted throughout January and February, as shown in Figure 2Figure 2Distribution According to Date of Number and Percentage of Hospitalized Patients with Infection Due to Respiratory Syncytial Virus Admitted from within the City and from outside the City.. The greatest proportion of these hospitalized infants came from the inner city during December and January, with a rising percentage of infants from outside the city admitted in later January and February.Families with Infection
The attack rate according to age is shown in Table 1Table 1
Attack Rate of Respiratory Syncytial Virus (RSV) in Families According to Age.. Infants less than one year of age at the onset of the study had the highest crude infection rate (29.4 per cent), but all ages had appreciable infection rates (overall, 21.9 per cent). Within positive families 45.9 per cent of members became infected, including 10 of the 16 infants. The distribution of infected and uninfected infants according to month of age is shown in Table 2Table 2
Distribution of Infected and Uninfected Infants and Co-primary Cases According to Month of Age.. The attack rate according to sex was approximately the same in all age groups, except in infancy, in which males predominated. Eight of 11 males under 12 months were infected as compared with two of 11 female infants (Fisher exact test, P=0.11).Single primary cases occurred in 10 families and coprimary cases in an additional six families. Eight of the 10 single primary cases were in children, but none in an infant. Within co-primary pairs, five of the six included an infant (Table 2), and the sixth included a 19-month-old child. However, four of these six were positive for respiratory syncytial virus on the first day of the study. The secondary attack rate among members of infected families was 27 per cent, with the highest rate in infants (Table 1). Of the 16 positive families, half had three members infected, four had two members infected, three had one member infected, and one had four members infected. The average number of days between cases within a family was 5.6 days, with a range of three to 19 days.
Duration of Shedding
A total of 60 cultures yielded respiratory syncytial virus. The duration of documented shedding was between one and 36 days, with a mean of 3.4 days. (Since the time between cultures was three to four days, the actual mean would be greater than 3.4 and less than 7.4 days.) The mean duration of shedding was 3.9 days for children less than 16 years of age and 1.6 days for those over 16. Children less than two years of age had shedding for significantly longer periods with a mean of 9 days (t = 2.55, P < 0.01). However, it is likely that this mean is actually greater than nine days for the following reasons: six of the 12 children under two years of age were documented to shed respiratory syncytial virus for six, eight, 14, 19, 19 and 36 days. The virus was recovered from the other six on only one culture day, which was the initial day of culturing in five of these six cases. Since these children may well have been shedding virus before the first home visit, the actual mean duration of shedding of these younger children is unknown, but likely to be greater than nine days.
Illness
Symptoms of the acute illness were taken as those present on the day that the culture first became positive for respiratory syncytial virus and one culture day before or after this day. All but two, who were school-aged children, of the positive members had acute respiratory symptoms. Table 3Table 3
Frequency of Signs and Symptoms in 37 Illnesses Associated with Respiratory Syncytial Virus (RSV) and in 82 Illnesses Not Associated with RSV. shows the signs and symptoms associated with infection in these 37 members in whom clinical illness developed. Only one of them had nasal congestion alone; the rest had two or more such symptoms. Nasal congestion and cough were the most common signs. Fever (temperature > 38°C) occurred more commonly in children under two years of age (42 per cent) and earache in those under five years (24 per cent). Two infants had lower-respiratory-tract disease diagnosed at the time of emergency-room visits. Otherwise, the type of illness or frequency of symptoms differed little according to age. Symptoms occurring later in respiratory-syncytial-virus-associated illnesses are also shown in Table 3. The late illness was defined as symptoms occurring on the first dayafter the acute phase until the patient became asymptomatic. During this illness period, nasal congestion, cough and earache were most frequent. Illness lasted for an average of 8.9 days, with a range of one to 32 days.Illness in Virus-Negative Families
In the virus-negative families 110 episodes of respiratory illness occurred. In contrast to illnesses associated with respiratory syncytial virus, 28 of these illnesses consisted of nasal congestion alone. Excluding these cases, 82 virus-negative illnesses were examined for acute and late symptoms and compared to virus-associated illnesses (Table 3). For virus-negative illnesses, the acute symptoms were defined as those occurring on the day of onset plus the next culture day. Late symptoms were defined as those occurring thereafter, until the first asymptomatic day. Acute symptoms did not significantly differ between positive and negative cases (Table 3), although both fever and conjunctivitis occurred twice as frequently in virus-positive illnesses. However, persistence of symptoms was significantly longer in virus-associated illness as shown in Table 3. Sixty-eight per cent of subjects with respiratory syncytial virus continued to be symptomatic one culture day beyond the acute period, as compared to 26 per cent of those without the virus. Nasal congestion, cough and earache were significantly more common in the late period of illnesses (Table 3).
Illness in Infants According to Private Physicians' Records
For comparison we reviewed the private physicians' records for the 34 infants. Of the 10 virus–infected infants, six had visited their physician for illness associated with their infection. In two of the six the diagnosis of lower-respiratory-tract disease was made — information that was not obtained through the home interviews. In addition, five of the six had otitis media. In comparison, of the 24 infants who were not infected with respiratory syncytial virus, eight had illness visits at some time during the two-month study period. Otitis media was diagnosed in three, and pneumonia in one.
Characteristics of Positive and Negative Families
Households in which cases of respiratory syncytial virus occurred did not differ appreciably from households without cases of respiratory syncytial virus infection in age distribution of family members or size (5.8 vs. 5.5 members), crowding (1.1 vs. 1.2 rooms per person) or maximum years of education attained by a family member (12.9 vs. 13.5 years). Smoking histories obtained from adults showed that 14 of 26 smoked in families with cases of respiratory syncytial virus infection as compared to 11 of 29 in families without infected cases. Virus–infected families smoked an average of 1.8 half-packages daily, as compared to 1.4 half-packages among persons in families without such cases. Of the 24 infants who were negative for respiratory syncytial virus, nine (37.5 per cent) had a smoking mother. In comparison, six of 10 virus-positive infants had a smoking mother. Of the 20 children over one year of age who were positive, six had a smoking parent (31 per cent), as compared to 30 of 64 (47 per cent) negative for respiratory syncytial virus.
Discussion
The epidemic curve of cases in these families (Fig. 1), although peaking earlier than the curve derived from patients admitted to the hospital, closely parallels the proportion of infants admitted to the hospital from the city (Fig. 2). This finding suggests that during this outbreak of infection, respiratory syncytial yirus spread first or more rapidly through the inner city, later spreading to the suburbs and neighboring areas. Whether this is generally the pattern of spread in urban areas cannot be determined from this one study.
The crude attack rate obtained through this study may be falsely low. Some family members may already have been infected before the initiation of the study. In addition, some infected persons may have had negative cultures through technical difficulty in handling of the relatively labile virus, even though the specimens were inoculated in the home immediately after collection. Nevertheless, 45 per cent of these families were shown to be infected with respiratory syncytial virus, with an attack rate surprisingly high at all ages, and highest in infants under one year of age. Studies that have examined the incidence of infection due to respiratory syncytial virus in various respiratory syndromes have stressed and carefully documented the young age of those primarily affected.1 2 3 4 , 15 , 16 An appreciable attack rate in older age groups was suggested by Berglund's serologic study of family members of children hospitalized with infection with respiratory syncytial virus, and documented by the Seattle virus-watch study.10 , 22 In the Tecumseh study of respiratory diseases, the highest rate of serologically detected infection due to respiratory syncytial virus occurred among children live to nine years old, and similarly, in the Seattle study, in those two to nine years old.13 , 22 Serologic studies, however, may also underestimate the incidence of RSV infection since a proportion of infected subjects may not demonstrate an appreciable rise in complement-fixing antibodies.8 , 14 , 17 Our findings suggest that beyond the first year or two of life, age is not a primary factor in determining the attack rate.
Although infants appeared to have the highest attack rate, they were probably not the ones who introduced respiratory syncytial virus into the family. None of the single index cases were in an infant under one year of age, although two thirds of these infants who were exposed became infected. In contrast, 80 per cent of single index cases were in children two to 16 years of age. Most co-primary cases were positive for the virus on the first day of the study, suggesting that they were actually secondary cases. Thus, we believe that older siblings, all of whom had daily contact with many other children, introduced the virus into the family.
Acute respiratory illness was associated with the isolation of respiratory syncytial virus in all but two subjects. This is a higher occurrence of symptomatic infection for those over two years of age, which are presumably reinfections, than has generally been reported.17 , 19 , 22 23 24 In adult volunteers experimentally challenged with the virus, and in natural reinfections, less than 50 per cent of infections were associated with upper-respiratory-tract illness. 17 , 19 , 22 Our study also suggests both more prolonged and severe respiratory illness associated with respiratory syncytial virus than with upper-respiratory-tract syndromes not associated with respiratory syncytial virus. This hypothesis is in general agreement with the Tecumseh study, in which 13 respiratory-syncytial-virus-associated upper-respiratory-tract illnesses had a higher frequency of activity restriction than rhinovirus illnesses.12
Approximately half the infants have been estimated to contract respiratory syncytial virus during the first epidemic in their community, and in 40 per cent of those infected a febrile pneumonitis will develop.3 , 4 , 14 , 15 Similarly, Reilly and his co-workers examined children, mostly outpatients, with respiratory illness associated with infection due to respiratory syncytial virus and found that 46 per cent had involvement of the lower respiratory tract.7 The lower frequency of pneumonitis in this study is attributable in part to our study design, which did not select patients on the basis of illness. Furthermore, signs of lower-respiratory-tract involvement would not be recorded by our illness interviews unless reported by parents who had taken their child to a physician. Indeed, the private physicians' records revealed two cases of pneumonia not reported by parents. Thus, a total of four of the 10 infected infants could actually be documented to have lower-respiratory-tract involvement. Otitis media also appeared to have been under-reported for this age group. Of the 10 infected infants only two were reported by interviewing to have had ear infections, whereas the private physicians' records showed that five of six infants examined had otitis media.
Recent studies have suggested that children of smoking parents have a markedly increased risk of acquiring lower-respiratory-tract disease, especially during the first year of life.25 , 26 In this study a greater percentage of children infected with respiratory syncytial virus than those without the virus had a smoking parent. But the influence of smoking on acquisition of infection cannot adequately be assessed from this study since the numbers are small and most infections affected the upper rather than the lower respiratory tract.
Children under two years of age shed the virus for a significantly longer period than older persons. Young infants hospitalized with lower-respiratory-tract disease due to respiratory syncytial virus tend to shed the virus in high titer and for prolonged periods.27 The present study suggests that young children, especially those experiencing their first infection due to this virus with milder upper-respiratory-tract illness, can also have prolonged shedding. However, these less ill children had a shorter mean period of shedding than the hospitalized infants with lower-respiratory-tract disease, suggesting that duration of shedding may be related to severity of disease. This prolonged shedding by infants may also explain in part the high attack rate within these families.
Protection of infants from infection due to respiratory syncytial virus may ideally be accomplished by immunization during the first weeks of life. However, if this procedure proves not to be feasible, a second speculative approach might involve control of infection in the infant's older siblings, since they are most likely to introduce the virus into the family.
Supported in part by a contract (No. N01A1 22503) with the Infectious Disease Branch, National Institute of Allergy and Infectious Diseases.
Source Information
From the departments of Pediatrics and Medicine, University of Rochester School of Medicine and Dentistry, and the Genesee Health Service (address reprint requests to Dr. Hall at the Department of Pediatrics and Medicine, Box 695, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642).
- References
References
1
Chanock
Web of Science | Medline2
Loda
CrossRef | Web of Science | Medline3
Kim
Web of Science | Medline4
Parrott
CrossRef | Medline5
Chanock
Web of Science | Medline6
Hamparian
Web of Science | Medline7
Reilly
Full Text | Web of Science | Medline8
Suto
Web of Science | Medline9
Hamre
Web of Science | Medline10
Berglund
CrossRef | Web of Science | Medline11
Beem
Web of Science | Medline12
Monto
Web of Science | Medline13
Monto
Web of Science | Medline14
Parrott
Web of Science | Medline15
Brandt
Web of Science | Medline16
Mufson
Web of Science | Medline17
Johnson
CrossRef | Web of Science | Medline18
Hamre
CrossRef | Web of Science | Medline19
Johnson
Full Text | Web of Science | Medline20
Hall CB, Douglas RG Jr: Respiratory syncytial virus and influenza: practical community surveillance. Am J Dis Child (in press)
21
Beem M, Hamre D: Respiratory syncytial virus, Diagnostic Procedures for Viral and Rickettsial Infections. Fourth edition. Edited by EH Lennette, NJ Schmidt. New York, American Public Health Association, 1969, pp 498–499
22
Cooney
Web of Science | Medline23
Kravetz
Web of Science | Medline24
Berglund 25
Harlap
CrossRef | Web of Science | Medline26
Colley
CrossRef | Web of Science | Medline27
Hall
CrossRef | Web of Science | Medline
- Citing Articles (75)
Citing Articles
1
Andrea T. Borchers, Christopher Chang, M. Eric Gershwin, Laurel J. Gershwin. (2013) Respiratory Syncytial Virus—A Comprehensive Review. Clinical Reviews in Allergy & Immunology
2
J. Erik Johnson, Lisa K. McNeil, Shakuntala Megati, Susan E. Witko, Vidia S. Roopchand, Jennifer H. Obregon, Deanne M. Illenberger, Cheryl S. Kotash, Rebecca M. Nowak, Emily Braunstein, Irene Yurgelonis, Kathrin U. Jansen, Narender K. Kalyan, Maninder K. Sidhu. (2013) Non-propagating, recombinant vesicular stomatitis virus vectors encoding respiratory syncytial virus proteins generate potent humoral and cellular immunity against RSV and are protective in mice. Immunology Letters 150:1-2, 134-144
3
E. O. Ohuma, E. A. Okiro, R. Ochola, C. J. Sande, P. A. Cane, G. F. Medley, C. Bottomley, D. J. Nokes. (2012) The Natural History of Respiratory Syncytial Virus in a Birth Cohort: The Influence of Age and Previous Infection on Reinfection and Disease. American Journal of Epidemiology 176:9, 794-802
4
Chandini Raina MacIntyre, Iman Ridda, Holly Seale, Zhanhai Gao, Vigneswary Mala Ratnamohan, Linda Donovan, Frank Zeng, Dominic E. Dwyer. (2012) Respiratory viruses transmission from children to adults within a household. Vaccine 30:19, 3009-3014
5
Ann D Colosia, Anthony Masaquel, Caroline Hall, Amy M Barrett, Parthiv J Mahadevia, Ram Yogev. (2012) Residential crowding and severe respiratory syncytial virus disease among infants and young children: A systematic literature review. BMC Infectious Diseases 12:1, 95
6
Barney S. Graham. (2011) Biological challenges and technological opportunities for respiratory syncytial virus vaccine development. Immunological Reviews 239:1, 149-166
7
Xiu Ru Guan, Li Xin Jiang, Xue Hua Ma, Lan Feng Wang, Hude Quan, Hong Yuan Li. (2010) Respiratory Syncytial Virus Infection and Risk of Acute Myocardial Infarction. The American Journal of the Medical Sciences 340:5, 356-359
8
Rosemary C. She, Edward W. Taggart, Roland Ruegner, Weston C. Hymas, Jeffrey M. Bender, Peter Weir, Cathy A. Petti. (2010) IDENTIFYING RESPIRATORY VIRUSES IN NASAL MUCUS FROM CHILDREN. The Pediatric Infectious Disease Journal 29:10, 970-972
9
Rosemary C. She, Christopher R. Polage, Lauren B. Caram, Edward W. Taggart, Weston C. Hymas, Christopher W. Woods, Kenneth Schmader, Cathy A. Petti. (2010) Performance of diagnostic tests to detect respiratory viruses in older adults. Diagnostic Microbiology and Infectious Disease 67:3, 246-250
10
F. Eun-Hyung Lee, John Treanor. Viral Infections. In: Murray and Nadel's Textbook of Respiratory Medicine. Elsevier, 2010:661-698.
11
HALL CAROLINE BREESE. Respiratory Syncytial Virus. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Elsevier, 2010:2207-2221.
12
EDWARD E. WALSH. Acute Bronchitis. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Elsevier, 2010:873-876.
13
Emelda A. Okiro, Mwanajuma Ngama, Ann Bett, Patricia A. Cane, Graham F. Medley, D. James Nokes. (2008) Factors associated with increased risk of progression to respiratory syncytial virus-associated pneumonia in young Kenyan children*. Tropical Medicine & International Health 13:7, 914-926
14
N. S. Crowcroft, M. Zambon, T. G. Harrison, Q. Mok, P. Heath, E. Miller. (2008) Respiratory syncytial virus infection in infants admitted to paediatric intensive care units in London, and in their families. European Journal of Pediatrics 167:4, 395-399
15
Mark L. Everard. Respiratory Syncytial Virus–Associated Lower Respiratory Tract Disease. In: Pediatric Respiratory Medicine. Elsevier, 2008:491-499.
16
F. Freymuth. (2007) Virus respiratorio sincitial, metapneumovirus y virus parainfluenza humanos: características, multiplicación y epidemiología. EMC - Pediatría 42:4, 1-8
17
F. Freymuth. (2007) Virus respiratoire syncytial, métapneumovirus et virus para-influenza humains : propriétés des virus, multiplication, épidémiologie. EMC - Pédiatrie - Maladies infectieuses 2:1, 1-8
18
Wenzel , Richard P. , Fowler , Alpha A. III , . (2006) Acute Bronchitis. New England Journal of Medicine 355:20, 2125-2130
Free Full Text19
Matti Waris, Lisa J. White. (2006) Seasonality of Respiratory Syncytial Virus Infection. Clinical Infectious Diseases 43:4, 541-541
20
Mary Ellen B. Wohl. Bronchiolitis. In: Kendig's Disorders of the Respiratory Tract in Children. Elsevier, 2006:423-432.
21
Surendran Mahalingam, Jurgen Schwarze, Ali Zaid, Michael Nissen, Theo Sloots, Sharyn Tauro, James Storer, Rene Alvarez, Ralph A. Tripp. (2006) Perspective on the host response to human metapneumovirus infection: what can we learn from respiratory syncytial virus infections?. Microbes and Infection 8:1, 285-293
22
Patricia Cane. Molecular Epidemiology and Evolution of RSV. Elsevier, 2006:89-114.
23
F. Freymuth. (2006) Virus respiratoire syncytial, métapneumovirus et virus para-influenza humains. I. Propriétés des virus, multiplication, épidémiologie. EMC - Maladies infectieuses 3:2, 1-12
24
François Freymuth. (2006) Virus respiratoire syncytial. EMC - Biologie Médicale 1:1, 1-7
25
M. K. O'Shea, M. A. K. Ryan, A. W. Hawksworth, B. J. Alsip, G. C. Gray. (2005) Symptomatic Respiratory Syncytial Virus Infection in Previously Healthy Young Adults Living in a Crowded Military Environment. Clinical Infectious Diseases 41:3, 311-317
26
C. B. Hall. (2005) The Conundrum of Colds in the Corps. Clinical Infectious Diseases 41:3, 318-319
27
Falsey , Ann R. , Hennessey , Patricia A. , Formica , Maria A. , Cox , Christopher , Walsh , Edward E. , . (2005) Respiratory Syncytial Virus Infection in Elderly and High-Risk Adults. New England Journal of Medicine 352:17, 1749-1759
Free Full Text28
Jayesh M. Bhatt, Mark L. Everard. (2004) Do environmental pollutants influence the onset of respiratory syncytial virus epidemics or disease severity?. Paediatric Respiratory Reviews 5:4, 333-338
29
M Florencia Delgado, Fernando P Polack. (2004) Involvement of antibody, complement and cellular immunity in the pathogenesis of enhanced respiratory syncytial virus disease. Expert Review of Vaccines 3:6, 693-700
30
K Thorburn, S Kerr, N Taylor, H.K.F van Saene. (2004) RSV outbreak in a paediatric intensive care unit. Journal of Hospital Infection 57:3, 194-201
31
Fernando J. Martinez. (2004) Acute bronchitis: State of the art diagnosis and therapy. Comprehensive Therapy 30:1, 55-69
32
F Freymuth. (2004) Virus syncytial respiratoire et virus para-influenza humains : épidémiologie. EMC - Pédiatrie 1:1, 2-11
33
FERNANDO P. POLACK, RUTH A. KARRON. (2004) The future of respiratory syncytial virus vaccine development. The Pediatric Infectious Disease Journal 23:Supplement, S65-S73
34
Pearay L. Ogra. (2004) Respiratory syncytial virus: The virus, the disease and the immune response. Paediatric Respiratory Reviews 5, S119-S126
35
Iain Stephenson, Karl Nicholson. Respiratory Virus Infections in Adults and the Elderly. In: Respiratory Infections in Allergy and Asthma. CRC Press, 2003.
36
Nicole Le Saux, Isabelle Gaboury, Noni MacDonald. (2003) Maternal respiratory syncytial virus antibody titers: season and children matter. The Pediatric Infectious Disease Journal 22:6, 563-564
37
H. Bartz, O. Turkel, S. Hoffjan, T. Rothoeft, A. Gonschorek, U. Schauer. (2003) Respiratory syncytial virus decreases the capacity of myeloid dendritic cells to induce interferon-gamma in naive T cells. Immunology 109:1, 49-57
38
LOUIS BONT, JORIEN VERSTEEGH, WENDY T.N. SWELSEN, COBI J. HEIJNEN, ANNEMIEKE KAVELAARS, FRANK BRUS, JOS M.TH. DRAAISMA, MARTHA PEKELHARING-BERGHUIS, RONNIE A.A.M. van DIEMEN-STEENVOORDE, AND, JAN L.L. KIMPEN. (2002) Natural Reinfection with Respiratory Syncytial Virus Does Not Boost Virus-Specific T-Cell Immunity. Pediatric Research 52:3, 363-367
39
C.L. Collins, A.J. Pollard. (2002) Respiratory Syncytial Virus Infections in Children and Adults. Journal of Infection 45:1, 10-17
40
Nikolaos G. Papadopoulos, Maria Moustaki, Mariza Tsolia, Apostolos Bossios, Eleni Astra, Anargiroula Prezerakou, Dimitrios Gourgiotis, Dimitrios Kafetzis. (2002) Association of Rhinovirus Infection with Increased Disease Severity in Acute Bronchiolitis. American Journal of Respiratory and Critical Care Medicine 165:9, 1285-1289
41
Jean-François Valarcher, Hervé Bourhy, Agnès Lavenu, Nathalie Bourges-Abella, Maurice Roth, Olivier Andreoletti, Patrick Ave, François Schelcher. (2001) Persistent Infection of B Lymphocytes by Bovine Respiratory Syncytial Virus. Virology 291:1, 55-67
42
J. Barker, D. Stevens, S.F. Bloomfield. (2001) Spread and prevention of some common viral infections in community facilities and domestic homes. Journal of Applied Microbiology 91:1, 7-21
43
Hall , Caroline Breese , . (2001) Respiratory Syncytial Virus and Parainfluenza Virus. New England Journal of Medicine 344:25, 1917-1928
Full Text44
Patricia A. Cane. (2001) Molecular epidemiology of respiratory syncytial virus. Reviews in Medical Virology 11:2, 103-116
45
Gordana Mlinarić-Galinović, Dijana Varda-Brkić. (2000) Nosocomial respiratory syncytial virus infections in children’s wards. Diagnostic Microbiology and Infectious Disease 37:4, 237-246
46
Nicholas A Meanwell, Mark Krystal. (2000) Respiratory syncytial virus: recent progress towards the discovery of effective prophylactic and therapeutic agents. Drug Discovery Today 5:6, 241-252
47
Steven D. Wilson, Kathryn Roberts, Karen Hammond, Jon G. Ayres, Patricia A. Cane. (2000) Estimation of incidence of respiratory syncytial virus infection in schoolchildren using salivary antibodies. Journal of Medical Virology 61:1, 81-84
48
Bradford D. Gessner. (2000) The cost-effectiveness of a hypothetical respiratory syncytial virus vaccine in the elderly. Vaccine 18:15, 1485-1494
49
John Treanor, Ann Falsey. (1999) Respiratory viral infections in the elderly. Antiviral Research 44:2, 79-102
50
Maria Zambon. (1999) Active and passive immunisation against respiratory syncytial virus. Reviews in Medical Virology 9:4, 227-236
51
Svetomir N. Markovic, Arun Adlakha, Thomas F. Smith, Randall C. Walker. (1998) Respiratory Syncytial Virus Pneumonitis-Induced Diffuse Alveolar Damage in an Autologous Bone Marrow Transplant Recipient. Mayo Clinic Proceedings 73:2, 153-156
52
G. Mlinaric-Galinovic, A. R. Falsey, E. E. Walsh. (1996) Respiratory syncytial virus infection in the elderly. European Journal of Clinical Microbiology & Infectious Diseases 15:10, 777-781
53
A. J. A. M. Ven, R. Crevel, G. P. Bootsma, P. P. Koopmans, C. M. A. Swanink, J. M. D. Galama. (1996) Respiratory syncytial virus pneumonia in an AIDS patient. Infection 24:5, 375-377
54
J. M. Stuart, K. Cartwright, N. J. Andrews. (1996) Respiratory syncytial virus infection and meningococcal disease. Epidemiology and Infection 117:01, 107
55
Robert B. Miller, Blanche M. Chavers. (1996) Respiratory syncytial virus infections in pediatric renal transplant recipients. Pediatric Nephrology 10:2, 213-215
56
STANLEY A. PLOTKIN, MARK A. FLETCHER. (1996) Combination vaccines and immunization visits. The Pediatric Infectious Disease Journal 15:2, 103-105
57
O. Ruuskanen. (1995) Respiratory syncytial virus—is it preventable?. Journal of Hospital Infection 30, 494-497
58
Merja Möttönen, Matti Uhari, Marjatta Lanning, Hanna Tuokko. (1995) Prospective controlled survey of viral infections in children with acute lymphoblastic leukemia during chemotherapy. Cancer 75:7, 1712-1717
59
F FREYMUTH, G EUGENE, J BROUARD, A VABRET, J PETITJEAN, F BONNIN. (1995) Le virus respiratoire syncytial: importance en pathologie, méthodes diagnostiques, traitement et prévention. Annales de l'Institut Pasteur/Actualités 6:1, 23-29
60
Olli Ruuskanen, Pearay L. Ogra. (1993) Respiratory syncytial virus. Current Problems in Pediatrics 23:2, 50-79
61
M. L. Everard, A. D. Milner. (1992) The respiratory syncitial virus and its role in acute bronchiolitis. European Journal of Pediatrics 151:9, 638-651
62
Susanne Becker, Joleen Soukup, James R. Yankaskas. (1992) Respiratory Syncytial Virus Infection of Human Primary Nasal and Bronchial Epithelial Cell Cultures and Bronchoalveolar Macrophages. American Journal of Respiratory Cell and Molecular Biology 6:4, 369-374
63
John C. Baker. (1991) Human and bovine respiratory syncytial virus: Immunopathologic mechanisms. Veterinary Quarterly 13:1, 47-59
64
T. Nicolai, A. Pohl. (1990) Acute viral bronchiolitis in infancy: Epidemiology and management. Lung 168:S1, 396-405
65
Kenneth M. McConnochie, Caroline B. Hall, Edward E. Walsh, Klaus J. Roghmann. (1990) Variation in severity of respiratory syncytial virus infections with subtype. The Journal of Pediatrics 117:1, 52-62
66
G. Agius, G. Dindinaud, R. J. Biggar, R. Peyre, V. Vaillant, S. Ranger, J. Y. Poupet, M. F. Cisse, M. Castets. (1990) An epidemic of respiratory syncytial virus in elderly people: Clinical and serological findings. Journal of Medical Virology 30:2, 117-127
67
Gary P. Wormser, Miguel Nunez, David Horn. (1987) Non-Sexually transmitted infectious diseases of the oral, nasal, and vaginal mucosae. Clinics in Dermatology 5:2, 112-122
68
N. Nandapalan, C. E. Taylor, J. Greenwell, M. Scott, R. Scott, E. N. Hey, G. L. Toms. (1986) Seasonal Variations in Maternal Serum and Mammary Immunity to RS Virus. Journal of Medical Virology 20:1, 79-87
69
Hall , Caroline Breese , Powell , Keith R. , MacDonald , Noni E. , Gala , Christine L. , Menegus , Marilyn E. , Suffin , Stephen C. , Cohen , Harvey J. , . (1986) Respiratory Syncytial Viral Infection in Children with Compromised Immune Function. New England Journal of Medicine 315:2, 77-81
Full Text70
ELIZABETH K. TURNER, JOHN C. HIERHOLZER, GREGORY A. TANNOCK. (1986) Respiratory syncytial virus: A review of the virus, its epidemiology, immune response and laboratory diagnosis. Journal of Paediatrics and Child Health 22:2, 77-82
71
E. J. Stott, Geraldine Taylor. (1985) Respiratory syncytial virus. Archives of Virology 84-84:1-2, 1-52
72
Caroline Bresse Hall. (1981) Nosocomial viral respiratory infections: Perennial weeds on pediatric wards. The American Journal of Medicine 70:3, 670-676
73
G. L. Toms, P. S. Gardner, C. R. Pullan, M. Scott, C. Taylor. (1980) Secretion of respiratory syncytial virus inhibitors and antibody in human milk throughout lactation. Journal of Medical Virology 5:4, 351-360
74
Henderson , Frederick W. , Collier , Albert M. , Clyde , Wallace A. Jr. , Denny , Floyd W. , . (1979) Respiratory-Syncytial-Virus Infections, Reinfections and Immunity. New England Journal of Medicine 300:10, 530-534
Full Text75
(1976) Viral Cross-infections in Children's Wards. The Lancet 307:7974, 1391-1393
