Respiratory Syncytial Virus Infection

Background:Respiratory syncytial virus (RSV) infection, which manifests primarily as bronchiolitis and/or viral pneumonia, is the leading cause of lower respiratory tract (LRT) infection in infants and young children.

Pathophysiology:

RSV infection is limited to the respiratory tract. Initial infection in young infants or children frequently involves the LRT and most often manifests as the clinical entity of bronchiolitis. Spread of the virus down the respiratory tract occurs by cell-to-cell transfer of the virus along intracytoplasmic bridges (syncytia) from the URT to the LRT.

The illness may begin with URT symptoms and progress rapidly over 1-2 days to the development of diffuse small airway disease characterized by cough, coryza, wheezing and rales, low-grade fever (<101°F), and decreased oral intake.

Mortality/Morbidity:Even in children hospitalized with RSV infection, the mortality rate is less than 1%. However, in select groups of high-risk patients, appreciable mortality and increased morbidity still may occur from this infection.

· Infants with chronic lung disease of infancy (ie, bronchopulmonary dysplasia), congenital heart disease, or marked prematurity when hospitalized for this disease still may have a 3-5% mortality rate. Additionally, such infants and patients with immunodeficient states have been shown to spend, on average, twice as long in the hospital as other patients with RSV infection (7-8 d vs 3-4 d in normal full-term infants).

Age:Severe RSV disease is primarily a disease of young infants and children, with a peak occurrence at age 2-8 months.

Clinical:

History:Patients with respiratory syncytial virus may present with the following symptoms:

· Fever (typically low-grade)

· Cough

· Tachypnea

· Cyanosis

· Retractions

· Wheezing

· Rales

Physical:Physical examination of the infant with RSV LRT reveals evidence of diffuse small airway disease. Up to 40% of children have an associated otitis media, which may be viral and/or bacterial. Additionally, assessment of the infant's hydration status (eg, skin turgor, capillary refill, mucous membranes) is an important part of the physical examination of the infant with bronchiolitis.

Causes:

· In the community setting, a number of factors have been associated with increased risk of acquiring RSV disease, including the following:

· Childcare attendance

· Older siblings in preschool or school

· Exposure to environmental pollutants (eg, cigarette smoke)

· Multiple birth sets (especially triplets or greater)

· Minimal breastfeeding

· In assessing an infant with RSV infection, several factors have been correlated with more severe disease and the need for hospitalization.

· Prematurity, especially birth at less than 35 weeks' gestation

· Age younger than 3 months at time of infection

· Chronic lung disease

· Congenital heart disease

· Toxic appearance at time of presentation

· Respiratory rate more than 70 per minute in room air

· Atelectasis and/or pneumonitis on chest x-ray

· Oxygen less than 95% on room air

Lab Studies:

· Nonspecific laboratory studies may include CBC count, serum electrolytes, urinalysis, and oxygen saturation measurement.

· Specific diagnostic tests for confirmation of RSV infection are readily available. These tests can be performed on samples of secretions obtained by washing, suctioning, or swabbing the nasopharynx.

· The antigen revealing methods offer the potential for diagnosis within hours and may be obtained reliably in the absence of a sophisticated virology laboratory.

Imaging Studies:

· Chest radiography is frequently obtained in children with severe RSV infection. Chest radiographs typically reveal hyperinflated lung fields with a diffuse increase in interstitial markings. In 20-25% of cases, focal areas of atelectasis and/or pulmonary infiltrate are also noted. Generally, these findings are neither specific to RSV infection nor predictive of the course or outcome, except for the observation that infants who have the additional findings of atelectasis and/or pneumonia may have a more severe course with their illness.

Treatment:
Medical Care:

· Supportive care is the mainstay of therapy for RSV infection. If the child can take in fluids by mouth and tolerate room air, outpatient management, with close physician contact as needed, is reasonable, especially in the absence of significant underlying risk factors.

· For children who require hospitalization for RSV infection, supportive therapy is still the mainstay of care. Supportive care may include administration of supplemental oxygen (guided by respiratory rates, oxygen saturation, and arterial blood gases, as indicated), mechanical ventilation, and fluid replacement, as necessary. Additionally, bronchodilator therapy with beta-agonists frequently is used, although data on their benefit in this condition are conflicting.

Drug Category:

Antiviral agents -- Antiviral therapy for severe RSV disease is indicated in high-risk patients. Treatment must be initiated promptly at the onset of the infection to inhibit the replicating virus effectively.

Drug Name	Ribavirin (Virazole) -- Analog of the nucleic acid guanosine. Ribavirin inhibits viral replication.
Adult Dose	Reconstitute 6 g in 300 mL of distilled water to a concentration of 20 mg/mL Administer as aerosol for 12-20 h/d for 3-7 d based on clinical response Alternatively, 6 g in 100 mL of distilled water aerosol in 2-h pulses tid has been suggested as equally effective in small studies
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; pregnancy; women who may become pregnant during drug course

Drug Category:

Bronchodilators -- These act to decrease muscle tone in the small and large airways in the lungs, thereby increasing ventilation. Beta2-adrenergic and alpha-adrenergic agents frequently are used (via inhalation) in an attempt to treat the bronchospasm observed in bronchiolitis.

Drug Name	Albuterol (Salbutamol, Proventil, Ventolin) -- As a selective beta2-agonist, this agent produces bronchial smooth muscle relaxation. Efficacy in older children with reactive airway disease is well established, but the benefits in acute bronchiolitis are less well established. Available in inhalation and PO preparations.
Pediatric Dose	Acute bronchiolitis: 0.01-0.05 mL/kg inhaled (via nebulization of 5 mg/mL of solution) q4-6h Outpatient: 2-4 mg/dose PO (syrup) tid/qid sometimes is used in young children
Contraindications	Documented hypersensitivity
Precautions	Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders

Drug Name	Racemic epinephrine (microNefrin, Nephron, S-2) -- This drug is 1-1.125% of epinephrine base solution given by aerosol. Recent studies suggest it may be superior to beta2-agonists in RSV LRTI.
Adult Dose	Not applicable in adults
Pediatric Dose	Bronchiolitis: 0.1 mL/kg/dose (diluted with 0.9% NaCl to final volume of 3 mL) inhaled via nebulizer q3-4h
Contraindications	Documented hypersensitivity; cardiac arrhythmias; angle-closure glaucoma
Precautions	Monitor for tachycardia and hypertension

Drug Category:

Antiviral immunoglobulins -- Specific immunoglobulin products with anti-RSV activity have been developed for the prophylaxis of high-risk patients against RSV infection.

Drug Name	Palivizumab (Synagis) -- A humanized monoclonal antibody directed against the F (fusion) protein of RSV. Administered monthly through the RSV season, it has been demonstrated to decrease the chances of RSV hospitalization in premature babies who are at increased risk for severe RSV-related illness.
Pediatric Dose	15 mg/kg/dose IM every mo through RSV season
Contraindications	Documented hypersensitivity
Precautions	Thrombocytopenia or coagulation disorder, as with any IM injection

Deterrence/Prevention:

· attention to hand washing and cleaning of environmental surfaces likely are important in preventing RSV transmission. In the hospital setting, isolation of patients infected with RSV as a group and wearing of mask and gown during close contact with infected children are important in controlling nosocomial spread. Transmission of RSV on pediatric units has been shown to be a significant problem.

· Despite good environmental hygiene, RSV infection is likely to occur with significant frequency.

· Immunoglobulin products with high anti-RSV antibody titers have proved beneficial when given monthly for prophylaxis in select groups of high-risk infants.

o RSV-IGIV (RespiGam; MED Immune; Gaithersburg, MD) is a pooled polyclonal human immunoglobulin product prepared from donors with high titers of RSV antibodies. When administered to high-risk infants with prematurity and/or chronic lung disease, a significant decrease in RSV-related hospitalization was noted.

o Palivizumab (Synagis) is approved for prophylaxis of children at high risk for severe RSV disease.

· The AAP Committee on Infectious Diseases guidelines for candidates for palivizumab (Synagis) prophylaxis are as follows:

o Infants younger than 24 months who have hemodynamically significant congenital heart disease (cyanotic or acyanotic lesions) or chronic lung disease and are off oxygen and/or pulmonary medications for less than 6 months at the start of RSV season

o Premature infants born at less than 28 weeks' gestational age who are younger than 1 year chronological age at the start of RSV season

o Premature infants born at 29-32 weeks' gestational age who are younger than 6 months chronological age at the start of RSV season

Adenoviruses

Background:A nonenveloped double-stranded DNA virus, adenovirus was first isolated in the 1950s in adenoid tissue–derived cell cultures, hence the name.

An extremely hardy virus, adenovirus is ubiquitous in human and animal populations, survives long periods outside a host, and is endemic throughout the year.

The virus is capable of infecting multiple organ systems; however, most infections do not cause symptoms. Adenovirus is often cultured from the pharynx and stool of asymptomatic children, and most adults have measurable titers of antiadenovirus antibodies, implying prior infection.

Mortality/Morbidity:

· Severe morbidity and mortality are rare in an immunocompetent host. Uncommon complications include meningoencephalitis and pneumonitis.

· Severe infection is associated with host immune deficiency, as in the setting of transplantation or inherited and acquired immunodeficiency states.

Age:

· Adenovirus infection typically affects children from infancy to school age, but children of any age may be affected. Young adults in any setting of close quarters and stress may be affected, as in military trainees.

History: