RSV is the most important cause of lower respiratory tract illness in infants and young children, usually outranking all other microbial pathogens as the cause of bronchiolitis and pneumonia in infants younger than 1 year. It is estimated to account for approximately 25% of pediatric hospitalizations caused by respiratory disease in the United States.

Pathogenesis and Pathology

 RSV replication occurs initially in epithelial cells of the nasopharynx. Virus may spread into the lower respiratory tract and cause bronchiolitis and pneumonia. Viral antigens can be detected in the upper respiratory tract and in shed epithelial cells. Viremia occurs rarely if at all.

The incubation period between exposure and onset of illness is 3–5 days. Viral shedding may persist for 1–3 weeks from infants and young children, but adults shed virus for only 1–2 days. High viral titers are present in respiratory tract secretions from young children. Inoculum size is an important determinant of successful infection in adults (and possibly in children as well).

An intact immune system seems to be important in resolving an infection because patients with impaired cell mediated immunity may become persistently infected with RSV and shed virus for months.

Although the airways of very young infants are narrow and more readily obstructed by inflammation and edema, only a subset of young babies develops severe RSV disease. It has been reported that susceptibility to bronchiolitis is genetically linked to polymorphisms in innate immunity genes.

Clinical Findings

The spectrum of respiratory illness caused by RSV in infants includes inapparent infection, the common cold, bronchiolitis, and pneumonia. Bronchiolitis is the distinct clinical syn drome associated with this virus. About one-third of primary RSV infections involve the lower respiratory tract severely enough to require medical attention. Almost 2% infected babies require hospitalization, resulting in an estimated 75,000–125,000 hospitalizations annually in the United States, with the peak occurrence at 2–3 months of age. It has been reported that higher viral loads in respiratory secretions is a predictor of longer hospitalizations.

Progression of symptoms may be very rapid, culminating in death. With the availability of modern pediatric intensive care, the mortality rate in normal infants is low (∼1% of hospitalized patients). But if an RSV infection is superimposed on preexisting disease, such as congenital heart disease, the mortality rate may be high.

Reinfection is common in both children and adults. Although reinfections tend to be symptomatic, the illness is usually limited to the upper respiratory tract, resembling a cold, in healthy individuals.

RSV infections account for about one-third of respiratory infections in bone marrow transplant patients. Pneumonia develops in about half of infected immunocompromised children and adults, especially if infection occurs in the early posttransplant period. Reported mortality rates range from 20% to 80%.

Infections in elderly adults may cause symptoms simi lar to influenza virus disease. Pneumonia may develop. Esti mates of RSV prevalence in long-term care facilities include infection rates of 5–10%, pneumonia in 10–20% of those infected, and mortality rates of 2–5%.

Children who have had RSV bronchiolitis and pneumonia as infants often exhibit recurrent episodes of wheezing illness for many years. However, no causal relationship has been shown between RSV infections and long-term abnormalities. It may be that certain individuals have underlying physiologic traits that predispose them both to severe RSV infections and to reactive airway disease.

RSV is an important cause of otitis media. It is estimated that 30–50% of wintertime episodes in infants may be caused by RSV infection.

Immunity

High levels of neutralizing antibody that is maternally trans mitted and present during the first several months of life are believed to be critical in protective immunity against lower respiratory tract illness. Severe respiratory syncytial disease begins to occur in infants at 2–4 months of age when maternal antibody levels are falling. However, primary infection and reinfection can occur in the presence of viral antibodies. Serum neutralizing antibody appears to be strongly correlated with immunity against disease of the lower respiratory tract but not of the upper respiratory tract.

RSV is not an effective inducer of interferon—in contrast to influenza and parainfluenza virus infections, in which interferon levels are high and correlate with disappearance of virus.

Both serum and secretory antibodies are made in response to RSV infection. Primary infection with one subgroup induces cross-reactive antibodies to virus of the other subgroup. Younger infants have lower IgG and IgA secretory antibody responses to RSV than do older infants. Cellular immunity is important in recovery from infection.

An association has been noted between virus-specific IgE antibody and severity of disease. Viral secretory IgE anti bodies have been correlated with occurrence of bronchiolitis.

It is apparent that immunity is only partially effective and is often overcome under natural conditions; reinfections are common, but the severity of ensuing disease is lessened.

Laboratory Diagnosis

Methods described for diagnosis of parainfluenza viruses are applicable to RSV. Detection of RSV is strong evidence that the virus is involved in a current illness because it is rarely found in healthy people. Detection of viral RNA or viral anti gen in respiratory secretions is the test of choice.

Large amounts of virus are present in nasopharyngeal swabs and washes from young children (10³–10⁸ plaque-forming units/mL), but much less is present in specimens from adults (< 100 plaque-forming units/mL). Nucleic acid testing is the preferred method and is especially useful for adult specimens in which only small amounts of virus are often present. Such assays also are useful for subtyping RSV isolates and for the analysis of genetic variation in outbreaks. Antigen detection is much less sensitive than nucleic acid detection.

RSV can be isolated from nasal secretions. The virus is extremely labile and samples should be inoculated into cell cultures immediately; freezing of clinical specimens may result in complete loss of infectivity. Human heteroploid cell lines HeLa and HEp-2 are the most sensitive for viral isolation. The presence of RSV can usually be recognized by development of giant cells and syncytia in inoculated cultures. It may take as long as 10 days for cytopathic effects to appear. More rapid isolation of RSV can be achieved by inoculation of shell vials containing tissue cultures growing on coverslips. Cells can be tested 24–48 hours later by immunofluorescence or RT-PCR. RSV differs from other paramyxoviruses in that it does not have a hemagglutinin; therefore, diagnostic methods cannot use hemagglutination or hemadsorption assays.

Serum antibodies can be assayed in a variety of ways. Although measurements of serum antibody are important for epidemiologic studies, they typically are not used in clinical decision making.

Epidemiology

RSV is distributed worldwide and is recognized as the major pediatric respiratory tract pathogen. About 70% of infants are infected by age 1 and almost all by age 2 years. Serious bronchiolitis or pneumonia is most apt to occur in infants between the ages of 6 weeks and 6 months, with peak incidence at 2 months. The virus can be isolated from most infants younger than age 6 months with bronchiolitis, but it is almost never isolated from healthy infants. Subgroup A infections appear to cause more severe illness than subgroup B infections. RSV is the most common cause of viral pneumonia in children younger than age 5 years but may also cause pneumonia in elderly adults or in immunocompromised persons. RSV infection of older infants and children typically results in milder respiratory tract infection than in those younger than age 6 months.

RSV is spread by large droplets and direct contact. Although the virus is very labile, it can survive on environ mental surfaces for up to 6 hours. The main portal of entry into the host is through the nose and eyes.

Reinfection occurs frequently (despite the presence of specific antibodies), but resulting symptoms are those of a mild upper respiratory infection (a cold). In families with an identified case of RSV infection, virus spread to siblings and adults is common.

RSV spreads extensively in children every year during the winter season. Although the virus persists throughout the summer months, outbreaks tend to peak in January or February in the Northern Hemisphere. In tropical areas, RSV epidemics may coincide with rainy seasons.

RSV causes nosocomial infections in nurseries and on pediatric hospital wards. Transmission can occur via hospital staff members.

RSV can also cause symptomatic disease in healthy young adults in crowded conditions (eg, military recruits in basic training). In a study in 2000, RSV was identified in 11% of recruits with respiratory symptoms. This compared with identification of adenoviruses (48%), influenza viruses (11%), and parainfluenza virus 3 (3%) in the symptomatic recruits.

Treatment and Prevention

 Treatment of serious RSV infections depends primarily on supportive care (eg, removal of secretions and administration of oxygen). The antiviral drug ribavirin is approved for treatment of lower respiratory tract disease caused by RSV, especially in infants at high risk for severe disease. The drug is administered in an aerosol for 3–6 days. Oral ribavirin is not useful.

Immune globulin with high-titer antibodies against RSV is of marginal benefit. Humanized antiviral monoclonal anti bodies are available.

Much research effort has been expended in an attempt to develop an RSV vaccine. In the late 1960s, an experimental formalin-inactivated RSV vaccine was tested. Recipients developed high titers of nonneutralizing serum antibodies, but when immunized children encountered a subsequent infection with wild-type RSV, they had significantly more severe lower respiratory tract illness than did children from the control group. It has been suggested that the formalin treatment destroyed protective epitopes on the virus or that because of lack of stimulation of Toll-like receptors, the vac cine induced only low-avidity antibodies that were not protective. No vaccine is available today.

RSV poses special problems for vaccine development. The target group, newborns, would have to be immunized soon after birth to afford protection at the time of greatest risk of serious RSV infection, and eliciting a protective immune response at this early age is difficult in the presence of maternal antibody. A strategy being tested is maternal immunization with a vaccine. The aim is to ensure transfer of protective levels of virus-specific neutralizing antibody to infants that would persist for 3–5 months, the period of greatest vulnerability of newborns to severe RSV disease.

Control measures necessary when nosocomial outbreaks occur are the same as described above for parainfluenza viruses (contact isolation, handwashing, and restriction of visitors).

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم حفظ النظام ينهي استعداداته الخاصة بحفل تخرج طالبات الجامعات العاشر

العتبة العباسية المقدسة تنشر أكاليل الزهور ومظاهر الفرح بمناسبة ذكرى ولادة أمير المؤمنين (عليه السلام)

مجمع الشيخ الكليني يواصل تحضيراته لاستقبال المشاركات في حفل تخرج طالبات الجامعات العاشر

وصول المشاركات في فعاليات مهرجان روح النبوة الثقافي النسوي العالمي الثامن إلى كربلاء

المزيد

الآخبار الصحية

ماذا يحدث لجسمك عند تناول الوجبات السريعة يوميا؟

لصحة عظام المرأة.. الشاي أفضل أم القهوة؟

لبناء العضلات وإنقاص الوزن.. ما أفضل توقيت لتناول البيض؟

أطعمة صحية تساعد على التعافي من "الإنفلونزا الخارقة"

المزيد

الآخبار التكنلوجية

دراسة تكشف قدرة الحيتان على سماع الأصوات منخفضة وعالية التردد من مسافة بعيدة

تجربة جديدة: الأسفلت المدعوم بالطحالب يقاوم الحفر ويقلل الانبعاثات الكربونية

تسريبات تكشف ملامح أول هاتف قابل للطي من "أبل"

رصد نوع نادر من القطط في تايلاند للمرة الأولى منذ عقود

المزيد

مواضيع ذات صلة

Mumps Virus Infections

Human Metapneumovirus Infections

Parainfluenza Virus Infections

SARS-CoV-2 Variants

Polyomaviruses

Picornaviruses

Parvoviruses

Paramyxoviruses

Properties of Paramyxoviruses

Influenza Virus Replication

Antigenic Drift and Antigenic Shift

Structure and Function of Neuraminidase