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CASE 11
A previously healthy 9-month-old infant presented in mid-February with a 2-day history of irritability, fever, and upper respiratory congestion. The mother reported that over the previous 24 hours the child had difficulty breathing with coughing and wheezing. The child’s medical history included a normal delivery after a 9-month gestation without complications. She was up to date on all immunizations. At age 6 weeks the child was placed in a day care center so that the mother could return to work. Several of the infants at the center had been ill recently with colds, and one infant required hospitalization because of severe breathing problems.
On examination the child appeared agitated and had a temperature of 38.6°C. She had both tachypnea (respiratory rate of 70 per minute) and tachycardia (pulse, 200 beats/min). The ears, eyes, and throat were normal except that the oral mucous membranes and tongue were dry. The nasal mucosa was boggy with clear discharge. The lungs revealed diffuse inspiratory and expiratory wheezes. Findings from the rest of the examination were normal.
A chest radiograph revealed hyperexpansion of the lungs but no infiltrates. Arterial blood gases revealed hypoxemia and respiratory alkalosis. The child was admitted to the hospital because of moderate respiratory distress. Supplemental oxygen and intravenous fluids were administered along with bronchodilators and systemic corticosteroids. A rapid molecular test performed on a nasopharyngeal swab provided the diagnosis.
1 1. This child presented with bronchiolitis, an acute viral lower respiratory tract illness generally occurring in the first 2 years of life. What viruses can cause this syndrome? What are the epidemiologic clues in this case that makes one of the viruses most likely?
2 2. Describe the epidemiology of the agent causing her infection.
3 3. What characteristics of this virus are important in determining how the virus spreads in the respiratory epithelium? How does the pathogenesis of the virus contribute to the wheezing that often accompanies this infection?
4 4. Describe the diagnostic strategies available for the detection of this agent. Why is it important to establish this diagnosis quickly?
5 5. What prevention strategies exist to avoid initial infection with this virus and to keep it from spreading within the hospital?
6 6. Is specific therapy available to treat this virus?
CASE 11 CASE DISCUSSION
1. The differential diagnosis for this patient’s bronchiolitis included respiratory viruses such as the parainfluenza viruses, adenovirus, influenza A and B viruses, coronavirus, rhinovirus, metapneumovirus, and respiratory syncytial virus (RSV). Mycoplasma pneumoniae or Bordetella pertussis also could have caused her illness. RSV causes ~70% of bronchiolitis cases in children <2 years of age, with more severe cases typically occurring in children <6 months of age and premature infants. In the day care setting, any of these agents could spread easily. However, the fact that another child had recently been hospitalized supports RSV or influenza as the most likely causes, as these viruses generally cause more severe disease. All of the potential viral causes circulate in the winter months, with RSV infections typically occurring between December and February. Increased RSV incidence often overlaps with both influenza and metapneumovirus, so those viruses cannot be excluded based on the time of the year the patient presented. To definitively diagnose this patient with RSV, a laboratory test must be performed, but this patient’s clinical presentation and epidemiologic setting points to RSV as the most likely etiology.
2. RSV is the most important viral etiology of childhood respiratory illness in the industrialized world in terms of morbidity and mortality, particularly in children <1 year old. The World Health Organization estimates that ~160,000 deaths occur worldwide annually due to RSV. Approximately two-thirds of infants have an RSV infection during the first year of life, with nearly all children infected by the end of the second year. Clinical manifestations of RSV infection range from mild upper respiratory tract illness to severe lower respiratory tract illness, including bronchiolitis, croup, and pneumonia. Lower airway disease occurs in 15 to 50% of young children, with approximately 1 to 3% requiring hospitalization. This represents about 125,000 hospitalizations annually in the United States due to RSV. Premature infants, infants with chronic lung disease, and infants with significant congenital heart disease have hospitalization rates four to five times higher than healthy infants. Although deaths from RSV are uncommon outside of developing countries, premature infants and those with preexisting pulmonary or cardiovascular disease are at greatest risk. Incomplete protective immunity following RSV infection leads to reinfections throughout life. Reinfections in older children and adults generally result in minimal respiratory tract symptoms. However, immunocompromised individuals, patients with chronic cardiopulmonary disease, and the elderly who reside in long-term care facilities are at greater risk for developing severe lower respiratory tract disease. RSV is second only to influenza as a cause of death due to viral respiratory infections in elderly individuals.
RSV is spread by large droplets and on fomites. In hospitals and day care centers, it can be spread to the susceptible child on the hands of caregivers who do not use good hand-washing practices. Epidemics of RSV occur each winter in temperate climates. In the United States, peak disease incidence is seen from mid-December to early February. Although there is only one serotype of RSV, it has two antigenically distinct subgroups, designated A and B. RSV-A and RSV-B cocirculate during epidemics, although one type tends to predominate. Both epidemiologic and in vitro data have suggested that RSV-A causes more severe disease. However, the antigenic heterogeneity that occurs within the subgroups makes this hypothesis difficult to confirm.
3. First, RSV must bind and enter the target cells, which are the apical ciliated epithelial cells of the airway lumen. The virus attaches to the cell membrane using electrostatic interactions and the viral G protein. Then the viral F protein, along with a cellular receptor, mediates fusion to the cell membrane and thereby viral entry. The fusion protein also causes neighboring cells to coalesce, resulting in multinucleated cells, or syncytia (where the virus gets its name). The end result of the infection is damage to the airway epithelium and loss of ciliated epithelial cells. Histopathologic evidence shows sloughed epithelial cells, fibrin, mucus, and inflammatory cells in the large airways. In vivo evidence of apoptosis and syncytia formation has also been noted. Only recently, with the use of the well-differentiated primary airway epithelial cell culture model, has RSV pathogenesis started to be understood. In this model, much of the RSV-infected epithelium
