Diagnosis of Respiratory Syncytial Virus Infections
F. Diagnosis
RSV infection may be diagnosed by cell culture techniques or by the identification of viral antigen through rapid diagnosis techniques. Rapid diagnosis is important for the initiation of proper infection control procedures and for possible antiviral chemotherapy. The diagnosis may be backed up by serological tests but these require a long time for the result to become available.
1. Rapid Diagnosis :-
(a) Immunofluorescence - both direct and indirect IF utilizing either polyclonal or monoclonal antibodies are available which possess a high degree of sensitivity and specificity. The general sensitivity of IF is 80 - 90% and for monoclonal antibody 95 - 100%. IF techniques are fast and easy to perform but the interpretation of results is subjective and the specimen must contain adequate nasopharyngeal cells.
(b) ELISA - several ELISA kits are available for the detection of RSV antigens on a solid phase. ELISA techniques offer the advantages of objective interpretation, speed, and the possibility of screening a large number of specimens. Disadvantages include a generally poorer sensitivity and a "grey zone" of equivocal results, which requires confirmation by a time-consuming blocking ELISA procedure.
2. Cell culture :- RSV has a high liability and any specimens should be transported to the laboratory promptly and inoculated into cell cultures. Nasopharyngeal aspirates, nasal washes or tracheal secretions are generally the best specimens for isolation. Specimens should not be subjected to major temperature changes such as freezing and thawing. Human heteroploid cells, such as HEP-2 and HeLa generally provide the best tissue culture for the isolation of RSV. RSV produces a characteristic CPE consisting of syncytia formation and appears in 4 to 5 days.
3. Serology :- serological diagnosis can be made by detecting antibody rises in acute and convalescent sera. It is unlikely to be of help in the management of the patient because of the length of time required. Furthermore, the serological response in young infants may be poor and not detectable by some antibody assays. Seroconversion does not occur for at least 2 weeks and may require 4 - 6 weeks. CFTs are less sensitive than neutralization and ELISA assays.
Syncytial formation caused by RSV in cell culture. (Courtesy of Linda Stannard, University of Cape Town, SA)
G. Management
Most infants with RSV infection recover with no difficulty. In infants with lower respiratory disease, the quality of the supportive care is most important. Virtually all infants with RSV lower respiratory tract disease are hypoxaemic and oxygen should be given to hospitalized infants. An antiviral agent, ribavirin, has been approved for specific treatment of RSV infection. Ribavirin is a synthetic nucleoside that appears to interfere with the expression of mRNA. It appears to have broad-spectrum antiviral activity against both DNA and RNA viruses in vitro and in vivo. For hospitalized infants with RSV lower respiratory disease, ribavirin can be administered by small-particle aerosol into an oxygen tent, oxygen hood or via a ventilator. The drug may be administered this way for 12 or more hours per day for 3 to 5 days. Controlled studies carried out in the UK and US showed that ribavirin aerosol have a beneficial effect on the clinical course of RSV infection in terms of the rate of clinical improvement and on the measured levels of oxygen saturation. Furthermore, ribavirin aerosol is not associated with any significant toxicity. Viral resistance to ribavirin has not occurred.
Administration of the drug requires hospitalization and is
expensive and therefore should be aimed at infants at most risk
for severe lower respiratory tract RSV disease. The American
Academy of Pediatrics has recommended that the children who
should be considered for ribavirin therapy are those with
underlying diseases, such as cardiac, pulmonary,
immunocompromising and neurological diseases. Premature and
infants with multiple congenital abnormalities should also be
considered. Infants who develop severe RSV infection, and those
who contract RSV in the neonatal period, should be considered for
ribavirin therapy.
H. Prevention
The obvious choice for the prevention of serious RSV infection would be the development of a vaccine. However, a vaccine against RSV poses particular problems, (1) it would have to induce an immunity which is more durable than that seen after natural infection, and (2) it would have to be given at a very young age, when maternal antibodies may be present. The first vaccine produced was an inactivated vaccine which produced high levels of serum antibody but resulted in a more severe course of disease following infection by the wild virus. Several live attenuated vaccines have been tried but these were found to be too reactive, unstable or overly attenuated. A double temperature-sensitive mutant strain of RSV is being evaluated at the moment. Research is also being carried out on the F and G envelope glycoproteins as possible candidates for subunit vaccines.
Other means of protection for limited periods may be possible e.g. immunization of the mother before the birth of the infant or chemoprophylaxis of high-risk infants may be feasible. Prevention of the nosocomial spread of RSV infection is of prime importance, as many hospitalized infants have underlying conditions which make them susceptible to severe RSV infection. Of the infection control measures employed, hand washing is the most important. The routine use of gowns and masks has not been shown to be of additional benefit. The use of gowns may be advisable during periods of close contact in which the infant's secretions are apt to contaminate the clothing. Since RSV primarily infects via the eyes and nose, masks are of limited value. Eye-nose goggles have been reported to be of benefit.
Other possible infection control procedures include the isolation or cohorting of infected infants and assigning nursing personnel to care for either infected infants or uninfected infants, but not both simultaneously. During epidemic periods, the numbers of patient contacts and visitors should be limited. Elective admission of infants with high-risk conditions should be avoided during epidemic periods. Recognition and cleaning of objects contaminated with infant secretions should be carried out as soon as possible.
RSV Hyperimmunoglobulin
RespiGam has been approved by the FDA for the prevention of respiratory syncytial virus (RSV) disease in children under 24 months with a chronic lung disease called bronchopulmonary dysplasia or a history of premature birth. RespiGam is made from plasma taken from large numbers of normal, healthy individuals and contains a high concentration of protective antibodies against RSV. These antibodies do not prevent RSV infections but help protect children against the most serious consequences of RSV. RespiGam is given intravenously in five monthly doses, with the first dose given in November before the start of the RSV season. RSV outbreaks occur in the U.S. during the late fall, winter, and early spring. Data supporting the licensing of RespiGam was obtained in several clinical trials including one known as the Prevent trial. This randomized, placebo-controlled double-blind study included 510 patients with BPD less than two years old or children under six months old with a history of premature birth (less than 35 weeks gestation). RespiGam reduced the number of hospitalizations by 41% and time in the hospital by 53% in the Prevent trial. In addition, children required fewer days of supplemental oxygen during their hospital stays.
