Respiratory Syncytial Virus Case File

Respiratory Syncytial Virus Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 36

A 10-month-old female is brought to the pediatric emergency room in late December with a cough and fever. She started getting sick with a mild cough and runny nose approximately 3 days ago, but has progressively worsened. She is now coughing frequently and has vomited after coughing. She has no history of asthma or other respiratory illness. She was born after an uncomplicated, full-term pregnancy and has no significant medical history. She attends day care 3 days a week. On examination, her temperature is 38.3°C (100.9°F), pulse is 110 beats per minute, respiratory rate is 30 breaths per minute, and her oxygen saturation is low at 91 percent by pulse oximetry. Her head and neck examination shows her to have a right otitis media but is otherwise normal. Her cardiac exam is notable only for tachycardia. Her pulmonary examination shows her to be in moderate respiratory distress. She has prominent nasal flaring and subcostal retractions on inspiration. She has loud expiratory wheezes in all lung fields. The remainder of her examination is normal. A chest x-ray shows hyperaeration but no infiltrates.

◆ What is the likely infectious cause of her respiratory illness?

◆ Following resolution of this illness, her mother asks whether she is protected from getting this disease again. How do you respond?

ANSWERS TO CASE 36: RESPIRATORY SYNCYTIAL VIRUS

Summary: A 10-month-old female presents with bronchiolitis. A chest x-ray shows hyperaeration but no infiltrates.

◆ Likely infectious cause of her respiratory illness: Respiratory syncytial virus (RSV).

◆ Is she protected from getting this disease again: The immunity developed with an RSV infection is incomplete, and reinfections are common. However, the severity of disease with repeat infections appears to be reduced, especially in older children and adults.

CLINICAL CORRELATION

RSV is a ubiquitous and highly contagious viral infection and is the single most common cause of fatal respiratory tract infections in infants under 12 months of age. It accounts for approximately 25 percent of pediatric hospitalizations of this age group, resulting in severe respiratory illnesses such as bronchiolitis, pneumonia, and respiratory failure. It is also highly prevalent in childcare settings, with 70–95 percent of children attending day care being infected by 3–4 years of age. Less severe illness occurs in older children and adults and may present as a common cold.

APPROACH TO SUSPECTED RSV INFECTION

Objectives

1. Be able to describe the characteristics of the virus.
2. Be able to describe the strategies for prevention and treatment of the infection.

Definitions

Bronchiolitis: Inflammation of the bronchioles or thin-walled branches of the lungs.

Right otitis media: Inflammation of the right middle ear marked with pain, fever, dizziness, and abnormal hearing.

DISCUSSION

Characteristics of RSV That Impact Transmission

RSV belongs to the Pneumovirus genus of the family Paramyxoviridae. It is a common cause of upper and lower respiratory tract infections in all age groups, but tends to cause more severe, lower respiratory disease in infants and young children. RSV is an enveloped virus with a single-stranded, negativesense RNA genome. It is transmitted by the inhalation of aerosolized respiratory droplets. It can survive on nonporous surfaces, such as countertops, for 3–30 hours but is inactivated by many detergents and does not tolerate changes in temperature or pH well. RSV infections primarily remain localized in the respiratory tract. The virus infects target respiratory epithelial cells by fusion of its envelope with the host cytoplasmic membrane via the action of two viral envelope glycoproteins. However, unlike the related influenza and parainfluenza viruses, RSV envelope glycoproteins do not possess hemagglutinin or neuraminidase activities. RNA transcription, protein synthesis, replication, and assembly all occur in the cytoplasm and newly formed virions are released by budding from the host cell. RSV is also capable of promoting cellcell fusion, resulting in multinucleated giant cells known as syncytia, an ability for which it derives its name.

RSV is initially transmitted to the nasopharynx through contact with infected secretions and fomites, resulting in localized infections of respiratory epithelium. Although viremia is rare, progressive infections can extend to the middle and lower airways. Disease caused by RSV is primarily the result of the host immune system mediating damage to infected respiratory epithelial cells. In adults and older children, mild upper respiratory tract symptoms such as a runny nose or mild cough usually develop with clinical symptoms lasting for 1–2 weeks. In infants or younger children, more serious illness such as bronchiolitis can occur. This occurs when there is inflammation and plugging of the bronchi and bronchioles with mucous and necrotic tissue from immunemediated cellular damage. The smaller airways of infants and young children are especially susceptible and may result in cough, tachypnea, respiratory distress, wheezing, and hypoxia.

Mortality is high in infants with underlying disease or reduced immune function, and causes of death often include respiratory failure, cor pulmonale (right-sided heart failure), or bacterial superinfection. The immune response to RSV is not entirely understood, but both humoral and cell-mediated systems appear to play a role. The immunity developed with an infection does not appear to be complete. Repeat infections with RSV are common, but symptoms tend to be less severe with subsequent infections. Although outbreaks of RSV infection can occur in elderly patients resulting in severe illness, particularly in those residing in long-term care facilities.

Diagnosis

In addition to the presenting clinical symptoms, RSV can be diagnosed more definitively through viral genome or antigen detection. Direct identification of RSV antigens is performed via immunofluorescence analysis on exfoliated epithelial cells or with ELISA (enzyme-linked immunosorbent assay) testing on nasal secretions. Large amounts of viral particles are present in nasal washings, particularly from infected children, making it a good clinical specimen for viral genome detection via RT-PCR. When attempting to isolate the virus in culture, clinical samples should be inoculated immediately into cell cultures, because of the labile nature of RSV. The presence of RSV can be recognized by the formation of giant cells or syncytia formation in inoculated cultures in 1–2 weeks.

Treatment and Prevention

Treatment of RSV infections relies mainly on supportive care including oxygenation, ventilatory support, IV fluids, and nebulized cold steam. These modalities are used in an effort to remove or reduce mucus secretions in the airways and allow for adequate oxygen exchange. The antiviral agent ribavirin has been approved for use via aerosolization in high-risk infants exposed to RSV and in severe lower respiratory tract illnesses caused by RSV infection. Close observation of severe cases is critical. Currently there is no vaccine approved for RSV. However, passive immunization with anti-RSV

immunoglobulin is available for premature infants, using monoglonal antibodies, Synagis. Premature infants especially with bronchopulmonary dysplasia and congenital heart disease should be vaccinated.

Additionally, preventative measures are particularly important in hospital and specifically neonatal intensive care units, because RSV is highly contagious. Prevention of nosocomial spread requires strict enforcement of the following precautions: hand washing; isolation of RSV infected infants; and changing of gloves, gowns, and masks between patients.

COMPREHENSION QUESTIONS

[36.1] Which of the following paramyxoviruses lacks an envelope viral attachment protein with hemagglutinin activity?

A. Parainfluenza virus

B. Mumps virus

C. Measles virus

D. Respiratory syncytial virus

[36.2] An 8-month-old infant is brought to the emergency room with a suspected RSV infection. Which of the following clinical illnesses would you be most concerned about this child having as a result of infection with this virus?

A. Bronchiolitis

B. Encephalitis

C. Meningitis

D. Pancreatitis

E. Pharyngitis

[36.3] Which of the following statements most accurately describes the chemical and physiologic properties of RSV?

A. RSV is a nonenveloped virus with a single-stranded, negativesense RNA genome.

B. Newly formed RSV particles are released via host cell lysis.

C. RSV infects erythroid precursor cells via fusion of its viral envelope glycoproteins with the host cytoplasmic membrane.

D. Transcription of the RSV genome occurs in the nucleus of the host cell, while protein synthesis, replication, and assembly occur in the cytoplasm.

E. RSV is sensitive to detergents and is inactivated by changes in temperature and pH.

Answers

[36.1] D. Respiratory syncytial virus, differs from other paramyxoviruses in that it does not have a hemagglutinin protein in its viral envelope; answers A, B, and C all have viral envelope proteins with hemagglutinin activity.

[36.2] A. Bronchiolitis is a common clinical manifestation of RSV infection in infants, which results from inflammation and plugging of the bronchi and bronchioles with mucous and necrotic tissue; answers B, C, D, and E are incorrect as they are not symptoms specific to infection with RSV.

[36.3] E. RSV is an enveloped virus and is inactivated by many detergents as well as changes in temperature and pH.; answers A, B, C, and D are incorrect: (A) RSV is an enveloped virus with a single-stranded, negative-sense RNA genome; (B) RSV virions are released by budding from the host cell membrane, not by cell lysis; (C) RSV infects respiratory epithelial cells, not erythroid precursor cells, via fusion with the host membrane; (D) RSV is an RNA virus, and transcription, protein synthesis, replication, and assembly of new virions occurs in the cytoplasm of the host cell.

MICROBIOLOGY PEARLS ❖ RSV is highly contagious and is the primary cause of respiratory tract infections in infants under 1 year of age. ❖ Clinical manifestations: respiratory symptoms including rhinitis, pneumonia, and blockage of airways leading to respiratory distress. ❖ Vaccination for RSV is available for children at high-risk for the disease. ❖ Treatment with ribavirin in severe cases or in high-risk infants exposed to the virus.

REFERENCES

Brooks GF, Butel JS, Morse SA. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 23rd ed. New York: McGraw-Hill, 2004:558–60. 

Ryan JR, Ray CG. Sherris Medical Microbiology, 4th ed. New York: McGraw-Hill, 2004:503–6.

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