Infectivity of respiratory syncytial virus by various routes of inoculation.

To understand the transmission of respiratory syncytial virus, we examined the frequency of infection in volunteers after inoculation by different routes with varying doses of virus. Thirty-two adult volunteers received serial dilutions of a safety-tested live strain of respiratory syncytial virus instilled into nose, eye, or mouth. The highest inoculum, 5.2 log10 50% tissue culture infective dose (TCID50), was administered to four groups of four subjects each, by nose to one group, by eye to one group, and by mouth to two groups. Subsequently, 1:100 and 1:1,000 dilutions of this inoculum were administered by nose and eye. At the highest inoculum, infection occurred in three of four subjects inoculated by nose and in three of four subjects inoculated by eye. Infection occurred in one of eight subjects inoculated by mouth, but this subject most likely was infected by secondary spread. With an inoculum of 3.2 log10 TCID50, the proportion of subjects infected by either route diminished to 25%. When the inoculum was further reduced to 2.2 log10 TCID50, no infections occurred by either route. Infections after the highest inoculum were characterized by earlier and greater shedding. These findings suggest that respiratory syncytial virus may infect by eye or nose and that both of these routes appear equally sensitive. In comparison, the mouth appears to be an insensitive route of inoculation. This is of potential import in infection control procedures and in the development of vaccines or other prophylactic measures.

Possible transmission by fomites of respiratory syncytial virus.

To test whether nosocomial spread of respiratory syncytial virus (RSV) could occur through contact with environmental surfaces contaminated by RSV-infected nasal secretions, survival in the environment of RSV isolated from media, pooled adult secretions, and secretions from hospitalized infants was examined. RSV in freshly obtained infant secretions was recovered from countertops for up to 6 hr, from rubber gloves for up to 1 1/2 hr, from cloth gowns and paper tissue for 30--45 min, and from skin for up to 20 min. RSV in media and pooled secretions survived for slightly longer periods. Further experiments demonstrated that infectious virus could be transferred to hands touching these contaminated surfaces and could be recovered from these hands for up to 25 min. These studies suggest that survival of RSV in the environment of infected infant secretions is sufficient to allow transfer of infectious virus to the hands of hospital personnel. Thus, self-inoculation by contact with contaminated infant secretions may be a potential mode of nosocomial transmission of RSV.

Viral shedding patterns of children with influenza B infection.

During an epidemic of influenza B, 43 ambulatory children were prospectively followed to determine the quantitative shedding patterns of influenza B viral infection, because these have not been previously described. The spectrum of illness included 74% with a typical influenzalike illness, 7% with an afebrile infection of the upper respiratory tract, and 19% with croup. Mild myositis occurred in 21%. For the first three days of illness, greater than or equal to 93% of the children shed virus, and 74% shed on day 4. The average peak quantity of virus shed in the nasal wash was 4.0 log10 50% tissue culture infective doses/ml(range, 1.5-6.0), which gradually declined over four days to 2.4 log10 50% tissue culture infective doses/ml. The quantities of virus shed correlated significantly with severity of illness and fever score, but not with sex, type of illness, or occurrence of myositis. These results suggest that the degree of clinical illness may be directly related to the cytotoxic effects of the virus and to the transmissibility of the disease.

Neonatal respiratory syncytial virus infection.

Respiratory syncytial virus infections are thought to be uncommon in the first month of life. During a community outbreak, we prospectively studied such infection in our neonatal units. Of 82 neonates studied, 66 were hospitalized for six days or longer, and 23 (35 per cent) acquired this virus. Four infants died, two unexpectedly. Infected infants had a significantly shorter gestation and birth weight. Illness was often atypical, with nonspecific signs, especially in infants under three weeks of age, who had significantly less lower-respiratory-tract involvement and lower quantities of virus in their nasal washes. The titer of virus shed correlated with the infants' postnatal, but not gestational, age. Infection was also acquired by 34 per cent of the staff, who appeared to be important in the spread of the virus. These findings suggest that respiratory syncytial virus may readily infect neonates, but the disease may be atypical and may be overlooked.

Control of nosocomial respiratory syncytial viral infections.

We evaluated methods to control the spread of respiratory syncytial virus (RSV) on our infants' ward during a community outbreak of RSV infection. Methods included isolation and cohorting of infected infants, strict handwashing, use of gowns, and the cohorting of staff to the ill infants. Of 123 infants studied, 36 were admitted with RSV infections. Of the remaining 87 contact infants, eight (19%) acquired nosocomial RSV disease. Three of the eight developed pneumonia and one died. Of the 43 staff members, 24 (56%) became infected and 82% were symptomatic. Four acquired repeated infections within weeks of the initial infection. Studies a year previously had revealed that 45% of contact infants and 42% of the staff had acquired nosocomial RSV infections. Thus, the employed procedures appeared to have decreased the transmission of RSV to infants but not to the staff. Staff may continue to be infected by large droplets from close contact with ill infants or by self-inoculation of contaminated secretions.

Interferon production in children with respiratory syncytial, influenza, and parainfluenza virus infections.

To better understand the recovery process of infants with lower respiratory tract disease due to respiratory syncytial virus, the production of interferon by 129 children (ages 10 days to 24 months) with RSV infection was compared to that of 20 children with influenza (ages 1 to 36 months), and 37 children with parainfluenza virus infection (ages 4 to 66 months). Interferon assays of 285 nasal washes from children with RSV revealed that interferon production occurred in only 5 (4%) of the children. Significantly more children infected with infleunza virus, 55% (P less than 0.001), and parainfluenza virus, 30% (P less than 0.001), produced interferon. In addition, the quantity of interferon produced by children with RSV (geometric mean titer = 2) was significantly less than that of children with influenza (GMT = 26.8, P less than 0.001) and parainfluenza virus (GMT = 23.5, P less than 0.001). In the children infected with RSV, in constrast to those with influenza, interferon detection was not associated with diminished shedding of virus.

Parainfluenza viral infections in children: correlation of shedding with clinical manifestations.

Children presenting with acute respiratory disease to a private group practice in the fall of 1975 were studied to: (1) evaluate the efficacy in a pediatric office of a simple technics of obtaining nasal washes for the diagnosis of parainfluenza virus infections and (2) to determine the quantities of virus shed in relation to clinical characteristics. The nasal wash technic proved feasible for an office or clinic. Parainfluenza virus type 1 was recovered from 26 (74%) of 35 children with croup and from 40 (56%) of the total 72 children presenting with any form of respiratory illness. Virus was recovered significantly more often from children with croup and from those of younger age. The mean quantity of virus in 26 nasal washes was 2.97 log10 TCID50/ml. The shedding of greater quantities was correlated with younger age and the more frequent occurrence of laryngitis, pharyngitis, and fever.

Respiratory syncytial virus infections in infants: quantitation and duration of shedding.

Infants hospitalized with respiratory syncytial virus infection were studied to delineate the quantitative shedding patterns and duration of shedding of RSV. Nasal wash specimens collected daily from 19 infants contained a mean maximal titer of 4.34 log10 50% tissue culture infective doses per milliliter. On admission, the mean titer was 4.14 log10 TCID50, with no consistent decline until after Day 6. The mean duration of shedding for 23 patients until they were virus negative was 6.7 days with a range of 1 to 21 days. Quantities of RSV shed were significantly greater in infants less than one month of age and in infants with evidence of pulmonary consolidation on chest roentgenogram. Shedding extended for a significantly longer time in infants with lower respiratory tract disease than in those with clinical manifestations limited to the upper respiratory tract.

Respiratory syncytial virus infections within families.

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.

Quantitative shedding patterns of respiratory syncytial virus in infants.

Quantitative shedding patterns of respiratory syncytial virus in 40 infants hospitalized with acute disease of the lower respiratory tract were determined for elucidation of the pathophysiology of infection with the virus. Nasal wash specimens were collected on admission and daily thereafter and were tested for the presence and quantities of respiratory syncytial virus. The following pattern of shedding was observed. (1) The virus was shed for prolonged periods. For the first seven days of hospitalization, 92%-100% of the infants tested continued to shed virus. At discharge 87% were still shedding the virus. (2) Respiratory syncytial virus was present in high titer in the nasal secretions obtained at the time of admission. The mean titer in these samples was 5.0 log10 TCID50. (3) The titer of respiratory syncytial virus did not fall during the first few days of hospitalization, despite clinical improvement of the infants. Neither peak nor admission titers of virus could be correlated with age or with the severity of disease. However, the mean admission titer in patients with bronchiolitis appeared to be significantly higher than that in those with pneumonia.

Nosocomial respiratory syncytial virus infections.

We studied the frequency and severity of respiratory syncytial virus infections acquired nosocomially on an infants' ward during a community outbreak. Every three or four days all infants and staff were examined, and specimens were obtained for viral isolation. During two months, 14 of 44 contact infants acquired the virus. All were ill, and four had pneumonia. Infected infants had a significantly longer mean hospital stay (21.5 days) than uninfected ones (9.2 days, P less than 0.001). Risk of nosocomial infection could not be related to age or to underlying disease, but was linked to length of hospitalization: 45 per cent of infants hospitalized for one week or more became infected, and the percentage increased with length of stay. Ten of 24 staff members also acquired the virus and appeared to play a major role as virus carriers. Nosocomial respiratory syncytial virus infection poses a major risk for hospitalized infants and adds to hospital costs.

Interactions between the vegetative states of phages lambda and T1.

Bacteria containing phage lambda in the vegetative state were produced either by induction of lambda lysogens or by infection of sensitive cells with lambda. These cells were superinfected with T1, and assayed for the production of lambda, T1, or both. Although most of the cells produced only lambda or T1, approximately 10% of the infectious centers were dual yielders. Examination of the progeny phage produced by the population of mixedly-infected cells showed that there was little, if any, phenotypic mixing, as determined by adsorption phenotype. T1am mutants in a variety of T1 genes were tested for their ability to exclude lambda, but none were defective in this ability. One gene of T1, gene 4, can be complemented by lambda.