Respiratory syncytial virus and sudden infant death.
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Humans↗
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Respiratory syncytial virus infection. Rapid diagnosis in children by use of indirect immunofluorescence.
Specimens of 387 nasopharyngeal suction smears obtained from 354 children hospitalized with acute respiratory infections during an eight-month period were examined for the presence of respiratory syncytial (RS) virus by the indirect immunofluorescence antibody technique (IFAT) and by conventional tissue culture infectivity techniques. Respiratory syncytial virus was identified in nasopharyngeal suction smear specimens from 123 of these specimens (32%) with the use of both techniques. Of the specimens positive on tissue culture 92% were also positive for RS virus by IFAT. However, eight specimens positive for RS virus by tissue culture were negative by IFAT, although three of the specimens were technically unsuitable. Six percent of the specimens negative for RS virus by tissue culture were positive for RS virus antigen when tested by IFAT. Using IFAT, identification of RS virus could be accomplished within four to six hours, whereas isolation by tissue culture took an average period of ten days. These data suggest that IFAT is a reliable means for the rapid diagnosis of RS virus infection in infants and children.
Adolescent↗
Secretory antibody response to respiratory syncytial virus infection.
The secretory antibody response to primary and secondary infection with respiratory syncytial virus (RSV) in Igg, IgM and 11S IgA immunoglobulin classes was determined using an indirect immunofluorescence antibody technique. Nasopharyngeal secretions were collected after naturally acquired primary or secondary infection with RSV. Immunoglobulin A responses to RSV were significantly greater in infants older than 6 months of age at the time of infection than in younger infants. Reinfection with RSV resulted in enhanced antibody production in all three immunoglobulin classes, and virus-specific antibody persisted for longer periods after secondary infection. Repeated immunizations with live RSV vaccine may be necessary for the development of immunity to severe illness.
Age Factors↗
Treatment of respiratory viral infection in an immunodeficient infant with ribavirin aerosol.
An infant with severe combined immunodeficiency syndrome (SCIDS) secondary to adenosine deaminase deficiency had pneumonitis and combined infection with respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3). Four separate courses of ribavirin were delivered by small-particle aerosol. The PIV3 disappeared during the first course, and RSV disappeared after the fourth course on the 58th hospital day. Neither virus returned during profound immunosuppression for bone marrow transplantation. Secretory antibody to both viruses was found and may have assisted in recovery. Strains of RSV from the 9th, 15th, 29th, and 55th hospital days showed similar sensitivities to ribavirin in vitro. Ribavirin can be a useful drug in the treatment of respiratory viral infections in patients with SCIDS.
Adenosine Deaminase↗
Fever in respiratory virus infections.
The case records of 258 children with adenovirus; influenza A or B virus; parainfluenza 1, 2, or 3 virus; or respiratory syncytial virus infections were studied retrospectively with special attention to the degree and duration of fever. A temperature of 39.0 degrees C or higher was most frequently recorded in adenovirus, influenza A, and influenza B virus infections (in 68%, 84%, and 65%, respectively). The mean highest degree of fever in respiratory virus infections (39.2 degrees C +/- 0.6 degrees C) during hospitalization did not differ from that in defined serious bacterial infections, ie, meningitis, epiglottitis, sepsis, and urinary tract infections (39.3 degrees C +/- 0.7 degrees C). The mean duration of fever varied from 2.5 days (parainfluenza 2) to 5.2 days (influenza B). Of all children with respiratory virus infections, 37% had fever lasting five days or longer. The data show that high and prolonged fever is frequently associated with respiratory virus infections in hospitalized children and that it does not differ significantly from fever in severe bacterial infections.
Adenovirus Infections, Human↗
Roentgenographic features of common pediatric viral respiratory tract infections.
Viral infections of the respiratory tract in infants and children are common. Little has been reported on roentgenographic findings associated with infection caused by common viruses other than with respiratory syncytial virus. We studied chest roentgenograms from 128 previously healthy infants and children who were infected with respiratory syncytial virus, parainfluenza virus, influenza virus, or adenovirus. Four common roentgenographic findings were detected: parahilar peribronchial infiltrates, hyperexpansion, segmental or lobar atelectasis, and hilar adenopathy. Diffuse interstitial infiltrates and significant pleural fluid accumulations rarely occurred in our series. We confirmed the popular but not well-documented belief that other common respiratory viruses can be associated with roentgenographic findings similar to those caused by respiratory syncytial virus. However, respiratory syncytial virus infection is associated with more abnormal chest roentgenograms than any of the other viruses regardless of the clinical syndrome. Hilar adenopathy was more common in adenovirus infection. Young infants had significantly more abnormal chest roentgenograms, with more hyperexpansion and parahilar peribronchial infiltration than older children. We also found a significant correlation between lobar atelectasis and severity of the illness. In infants and children with viral infection of the lower respiratory tract, roentgenographic information can be a useful adjunct to clinical viral diagnosis.
Adenoviridae Infections↗
Respiratory syncytial virus outbreak on American Samoa. Evaluation of risk factors.
Acute respiratory illness is one of the leading causes of childhood mortality in developing nations. We investigated an increase in hospitalizations of children less than 2 years old for severe lower respiratory tract illness (LRI) from October 1986 through December 1986 on the island of American Samoa. Hospitalization rates were highest in children less than 6 months of age (60 of 1000 compared with 22 of 1000 for those 6 to 11 months of age, and seven of 1000 for those 12 to 24 months of age). The outbreak was more severe than in previous years, with ten (19%) of 54 patients admitted to the intensive care unit (ICU) compared with three (7%) of 42 and one (3%) of 40 during the same months of 1985 and 1984. Two patients died. Most patients had clinical bronchiolitis; of 34 patients tested, serologic or nasal aspirate evidence of recent respiratory syncytial virus (RSV) infection was found in 18 (53%). A study of patients younger than 1 year of age demonstrated that patients hospitalized with LRI were more likely to have a household member who smoked cigarettes (18/20, 90%) than outpatient controls without recent respiratory illness (8/15, 53%). Maternal sera obtained between December 1985 and October 1986 showed no protective effect of either detectable IgG or neutralizing antibody to two major groups of RSV. Our study documents the involvement of RSV in an outbreak of severe LRI among infants in a tropical area and further suggests that exposure to cigarette smoke is a risk factor for LRI infants.
Disease Outbreaks↗
Impact of treatment guidelines on use of ribavirin.
During the 1987 through 1988 seasonal peak of respiratory syncytial virus (RSV), 177 courses of ribavirin were administered at St Christopher's Hospital for Children, a tertiary care medical center in Philadelphia, Pa. Charts were reviewed on 100 treated patients with proved or suspected RSV disease to determine adherence to American Academy of Pediatrics treatment guidelines. Ninety-four percent fulfilled criteria for the risk of significant morbidity: cardiac, pulmonary, or immunodeficiency conditions (38%); an age of 6 weeks or younger (35%); or severe illness (21%). Severe illness was defined as hypoxemia, hypercapnia, or marked tachypnea. Of those treated because of underlying conditions, 71% had RSV documented, as did 71% of patients aged 6 weeks or younger and 81% of patients with severe disease. A study of 80 consecutive patients who were hospitalized with illness compatible with RSV infection revealed that 56% of patients were treated with ribavirin. Adherence to guidelines led to ribavirin use in half of the hospitalized patients with suspected RSV infection. The majority of these patients received therapy because of underlying conditions or very young age.
Drug Prescriptions↗
The causes of hospital-treated acute lower respiratory tract infection in children.
OBJECTIVE: To determine the etiologic agents in children with acute lower respiratory infection. DESIGN: A survey of a series of patients. SETTING: General pediatric hospital serving an urban population with and without referrals in Helsinki, Finland. PARTICIPANTS: 135 Finnish children aged 2 months to 15 years (mean, 1.75 years), with clinically defined acute lower respiratory infection (with difficulty of breathing), or found to have fever and a pneumonic infiltrate on chest roentgenogram. SELECTION PROCEDURES: Consecutive sample on voluntary basis. INTERVENTIONS: None. MAIN RESULTS: Of 121 children with adequate samples, an etiologic diagnosis could be established in 84 (70%): 30 (25%) had bacterial, 30 (25%) viral, and 24 (20%) mixed infections. Antibody assays alone identified the agent in 91% of positive cases. CONCLUSIONS: Bacterial infections are common but generally underestimated in acute lower respiratory infection; serologic methods add significantly to their detection.
Acute Disease↗
Influenza in children. Relationship to other respiratory agents.
During the 1975-1976 respiratory disease season, influenza A/Victoria virus exceeded respiratory syncytial (RS) virus as a cause of lower respiratory tract disease (LRD) in children admitted to the hospital. This was a reversal of their usual roles in the etiology of LRD; however, the importance of influenza viruses in causing serious disease in children has been underestimated because of failure to appreciate the full spectrum of disease associated with influenza virus infections. In addition to those with LRD, several children were hospitalized with nonspecific febrile illnesses or CNS involvement. Furthermore, in the ambulatory care setting, influenza viruses were the most important cause of illness that necessitated children's being brought for medical care during a three-year period. During the peak of epidemics, influenza viruses appeared to interfere with the spread of other major respiratory viruses--particularly RS virus.
Adolescent↗
Enzyme immunoassay for respiratory syncytial virus: rapid detection in nasopharyngeal secretions and evaluation of isolates representing different RSV subgroups.
The presence of respiratory syncytial virus (RSV) was investigated by immunofluorescent antibody (IFA) technique and by an enzyme immunoassay (EIA) in 169 samples of nasopharyngeal secretions of infants and children with acute respiratory infections. Of 31 samples positive by EIA, 25 were positive by IFA. In 24 samples from a retrospective study, RSV positive by IFA and/or tissue culture isolation (TCI), 22 were also positive by EIA. The EIA was also evaluated with 111 RSV isolates in Hep2 cell cultures representing different RSV subgroups. All were positive by EIA.
Antigens, Viral↗
Evaluation of five temperature-sensitive mutants of respiratory syncytial virus in primates: I. Viral shedding, immunologic response, and associated illness.
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Animals↗
Evaluation of five temperature-sensitive mutants of respiratory syncytial virus in primates: II. Genetic analysis of virus recovered during infection.
Five temperature-sensitive (ts) mutants of respiratory syncytial (RS) virus (ts-1, ts-1 NG-1, ts-1 NG-16, ts-2, and ts-7), previously evaluated forinfectivity and virulence in chimpanzees and owl monkeys, were also assayed for in vivo genetic stability. None of the five mutants tested was completely stable genetically. Thus, virus which had lost some or all of the ts property was recovered from each infected chimpanzee. Significantly, each ts-1 NG-1 isolate retained some degree of temperature sensitivity and hence was not true wild-type virus. Clonal analysis of viruses shed by ts-1, ts-1 NG-1, ts-1 NG-16, or ts-7 infected chimpanzees indicated that in most instances only a minority of the virus shed was altered genetically. Of five chimpanzees infected with the ts-2 mutant, three shed only ts virus, and the remaining two chimpanzees shed only ts+ virus. Such ts+ virus proved to be avirulent when evaluated in chimpanzees or owl monkeys, indicating that loss of the ts property did not restore virulence. Based upon these findings, the ts-2 mutant appears to be a suitable candidate for clinical trials in man.
Animals↗
Detection by ELISA of IgA and IgM antibodies in secretion and IgM antibodies in serum in primary lower respiratory syncytial virus infection.
Twenty-six infants and children with primary lower RS virus infection, diagnosed by the detection of RS virus in nasopharyngeal secretion (NPS) by use of immunofluorescent antibody (FA) technique, were studied with respect to the presence of IgA and IgM antibodies. Samples of NPS and serum obtained during the first 3-4 months following the beginning of illness, were investigated. Employing a reverse ELISA technique, we found IgM antibodies in the acute, but not during the convalescent, phase of illness in NPS from 20 of the patients and in serum from 21 of the patients. The majority of the IgM antibody conversions observed occurred in NPS as well as in serum on days 5-8 following the illness. RS virus IgA antibodies, also detected by a reverse ELISA technique, were demonstrated in NPS in 22 of the patients, with antibody conversions being found in 19 of the patients on days 5-8 following the beginning of the illness. Two patients still had IgA antibodies in NPS approximately 3 months FSOI. By comparison, RS virus was detected in acute-phase NPS by double-antibody sandwich ELISA in 25 of the 26 patients investigated.
Enzyme-Linked Immunosorbent Assay↗
Detection by ELISA of IgG-subclass-specific antibodies in primary respiratory syncytial (RS) virus infections.
The IgG-subclass specific antibody response was investigated in primary RS-virus infections in infants and small children by using an ELISA with monoclonal antibodies against the four human IgG subclasses. When 78 serum samples obtained from 21 patients during the first 3-4 mo following the onset of illness were studied, only IgG-1 and IgG-3 antibodies could be detected. Both of these subclass specific antibodies appeared during the second week following the beginning of illness. Approximately 4 wk after the onset of illness, IgG-1 antibodies reached maximum levels, which persisted during the following months. Approximately 3 wk after the onset of illness, IgG-3 antibodies reached maximum levels, which decreased during the following months. Both IgG-1 and IgG-3 antibodies showed neutralizing capacity.
Acute Disease↗
Detection of RS-virus IgG-subclass-specific antibodies: variation according to age in infants and small children and diagnostic value in RS-virus-infected small infants.
The variation according to age of RS-virus IgG-subclass specific antibodies was investigated by ELISA in 140 acute phase sera from 140 infants and children 1-47 mo of age who were hospitalized with acute respiratory disease. Sixty-nine of these serum samples were obtained from patients with RS-virus infections. Mean OD values of IgG-1 antibodies decreased corresponding to the decrease in maternal antibodies. In patients with RS-virus infections, the mean IgG-1 OD values increased in children who were 3 yr old, but in patients without RS-virus infections this increase was observed in children at 1 yr of age. RS-virus IgG-3 antibodies were detected only in children 1-3 yrs of age, and only in 18% of samples from children without RS-virus infections. The concept of the transient nature of RS-virus IgG-3 antibodies as compared with RS-virus IgG-1 antibodies is supported by these results. RS-virus subclass specific antibodies were studied in paired serum samples from 12 infants 1-5 mo of age with acute lower RS-virus disease. IgG-1 antibodies developed in six infants, but only in one of six infants aged 1-3 mo. IgG-3 antibodies developed in nine infants, including four of six infants who were 1-3 mo old. These results suggest that in small infants with RS-virus infections the detection of IgG-3 antibodies is of higher diagnostic value than the detection of IgG-1 antibodies.
Acute Disease↗
Respiratory syncytial virus: a report of a 5-year study at a children's hospital.
A study over a 5-year period (1979-1983) of RSV infections in children in Sydney, Australia is reported. In common with findings made elsewhere in the world, annual epidemics of RSV infection commencing in autumn and lasting 4-6 months, with peak activity in mid-winter, were observed in 1979, 1980, and 1983. However, in 1981 and 1982 virus activity was first detected in midsummer, peaked in autumn, and was present throughout most months of the year. The alteration in virus activity in 1981 and 1982 was not associated with changes restricted to these 2 years in factors such as the age groups or sex ratio of patients affected or in the clinical categories predominantly affected. A study of climatic variables, however, indicated unusually low rainfall in 3 of 4 years encompassing this period. Study over a longer period is indicated to determine if these observed alterations in seasonal activity of RSV will be repeated in future years. Any possible relationship of such a change to rainfall could then also be better assessed.
Age Factors↗
Immunogenicity and pathogenicity of temperature-sensitive modified respiratory syncytial virus in adult volunteers.
Single temperature-sensitive (ts) mutants of a subgroup A strain of respiratory syncytial (RS) virus whose multiplication is restricted at 39 degrees C in MRC-6 cells and double ts mutants that are restricted at 38 degrees C, were obtained following mutagenesis using 5-fluorouracil and acridine-like compounds. Isolation and propagation of the parental RSS-2 strain of RS virus and its derived ts mutants were carried out entirely in MRC-5 human diploid cells. The immunogenicity and disease-producing ability of four of these mutants and the parental unmodified strain have been assessed by intranasal administration into groups of about 20 adult volunteers. The results of these trials indicate that the capacity of the parental RSS-2 strain to produce upper respiratory tract infection in adults was not diminished by limited propagation in MRC-5 cells. The mutants on the other hand were impaired in this respect to varying extents. The double mutant tslB in particular has characteristics that suggest that it may be suitable for further development as a live RS virus vaccine. It retained near normal immunogenicity and replicative ability in the upper respiratory tract, while exhibiting greatly reduced disease-producing potential.
Adult↗