General Features

• Worldwide Ditribution
• Outbreaks: in temperate climates, outbreaks occur in late fall, winter, or spring
  • Epidemics are associated with increased pediatric hospitalizations and death in infants and young children (due to lower respiratory tract illness)

Childhood Cases

• Infection in Early Life: nearly 50% of children are infected with RSV within the first year and almost all are infected within the first 3 years
• Risk Factors for Severe RSV Infection in Infants
  • Crowding
  • Day Care Center Attendance
  • History of Allergic Disease
  • Lack of Breast Feeding
  • Low Socioeconomic Status
  • Maternal Smoking

Adult Cases

• Burden of Disease: RSV infection may result in a greater disease burden in elderly than in infants
  • In patients >65 y/o in the US, RSV accounts for 170k hospitalizations per year and 10k deaths per year
• Risk Factors for RSV Infection in Adults
  • Advanced Age
  • Bone Marrow/Stem Cell Transplant (see Bone Marrow Transplant): most commonly reported adult group
  • Institutionalization
  • Leukemia (see Acute Myeloid Leukemia and Acute Lymphocytic Leukemia) : especially in cases with severe chemotherapy-induced myelosuppression
  • Other Immunocompromised States

Viral Transmission

• Large Particle Aerosol Transmission via Close Personal Contact
• Hand Contamination by Infected Secretions with Self-Inoculation of Eyes/Nose

Infection Attack Rates/Reinfection

• Pediatric Wards: RSV is a major nosocomial pathogen
  • Attack rates are 20-50% in hospital staff and patients during epidemics
• Daycare Centers: attack rates may approach 100% during outbreaks
• Family Setting : with RSV introduction by another child, rate of transmission to infants is 50% and rate of transmission to adult contacts is 33%
• Reinfection: reinfection is common in children and adults (even with the same strain), suggesting that immunity is only partial
  • Reinfection may occur within weeks after the primary infection (and as early as 8 weeks in adults with secondary infections)

Viral Replication/Spread and Immune Response

• Viral Replication and Spread: recplication begins in upper respiratory tract with gradual (4-5 day) progression to then involve the lower respiratory tract
• Viral Shedding: 1-3 wks (in children)
• Serum and Mucosal Antibody Responses: both occur, but offer only partial protection
  • Antibody response is less in younger infants
  • Increased circulating and mucosal antibody levels occur with each successive (re)infection and are associated with milder illness
  • Higher levels of serum neutralizing antibody are associated with lower risk of severe illness in infants/children
• Cell-Mediated Immunity: important for viral clearance
  • Bone marrow transplant patients (with decreased cell-mediated immunity) are at high risk for severe RSV-related lower respiratory tract infection
  • AIDS patients (with decreased cell-mediated immunity), viral sheeding may continue for up to 6 mo even after a mild RSV infection
• Severity of RSV Disease: modulated by genetic polymorphisms in TLR4, surfactant, and cytokine/chemokine genes

General Comments

• Clinical Manifestations are Age-Dependent/Immune Status-Dependent: most severe RSV infections occur in infants <6 mo old
• Primary RSV Infection: almost all primary RSV infections are symptomatic
• Rate of Hospitalization in Infants/Young Adults:
  • 1-2% of RSV infections result in hospitalization
  • 10% of hospitalized infants require ventilatory support

Acute Viral Rhinosinusitis (“Common Cold”)/Pharyngitis (see Acute Rhinosinusitis)

• Epidemiology: as a group, parainfluenza virus/influenza virus/respiratory syncytial virus/adenovirus account for approximately 10-15% of “common cold” cases

Acute Bronchitis (see Acute Bronchitis)

Clinical

• Cough (see Cough)

Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS)

• Epidemiology: may occur

Acute Otitis Media (see Acute Otitis Media)

• Epidemiology: common in infants/young children

Bronchiolitis (see Bronchiolitis)

Epidemiology

• Peak Age Group: typically occurs in children <2 y/o (rare in adults)
  • Risk of Hospitalization and Severe Bronchiolitis: high in infants with congenital heart disease, immunodeficiency, prematurity, or chronic lung disease
  • Risk of Severe Bronchiolitis: high in infants with family history of asthma and second-hand smoke exposure
• Viral Etiology: most cases with a defined viral etiology are due to respiratory syncytial virus (RSV accounts for 45-90% of bronchiolitis cases in infants/young children)

Physiology

• Acute Inflammatory Disorder of Small Airways
  • Air Trapping/Hyperinflation
  • Atelectasis

Diagnosis

• Arterial Blood Gas (ABG)
  • Hypoxemia: may persist for weeks after recovery
• CBC: absence of leukocytosis (and normal differential)
• CXR: hyperinflation (with air trapping), flattened diaphragms, peribronchial thickening, atelectasis, bronchopneumonia (consolidation)
• Pulmonary Function Tests (PFT’s): increased airway resistance and peripheral airway obstruction (and hypoxemia) may be seen years later in children who have experienced repeated episodes of RSV bronchiolitis

Clinical

• General Comments
  • Prodrome: several days of upper respiratory tract symptoms
• Absence of Fever
• Atelectasis (see Atelectasis, [[Atelectasis]])
• Hyperinflation
• Hyperresonant Chest Exam
• Inspiratory Crackles on Chest Exam
• Inspiratory/Expiratory Wheezing (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
• Intercostal/Suprasternal Retractions
• Nasal Flaring
• Tachypnea (see Tachypnea, [[Tachypnea]])

Treatment

• Treatment of Hypoxemia
• Infection Control/Contact Precautions: crucial to prevent nosocomial spread (especially in immunocompromised populations)
• Antibiotics: only indicated if secondary bacterial infection is present
• Bronchodilators (see Albuterol, [[Albuterol]])
  • Meta-Analysis of Bronchodilator Use in Bronchiolitis (2014) [MEDLINE]: bronchodilators (albuterol, salbutamol) do not improve hypoxemia, decrease rate of hospital admission after outpatient treatment, decrease the duration of hospitalization, or decrease the time to resolution of illness at home
  • However, study was limited by small sample sizes, lack of standardized study design, and lack of validated outcomes across the studies
• Nebulized Racemic Epinephrine (see Epinephrine, [[Epinephrine]])
  • Infants: not efficacious [MEDLINE]
• Corticosteroids (see Corticosteroids, [[Corticosteroids]])
  • Infants: not recommended
  • Adults: useful to specifically treat exacerbation of bronchospasm (asthma, COPD) triggered by RSV infection
• Ribavirin (see Ribavirin, [[Ribavirin]]): ribavirin is highly active against RSV in vitro
  • Immunocompromised Adults with Stem Cell Transplant: aerosolized ribavirin decreases mortality rate in RSV pneumonia in this population [MEDLINE] [MEDLINE]
  • Immunocompromised Adults with Stem Cell Transplant: oral and intravenous ribavirin have been shown to be efficacious in small trials [MEDLINE] [MEDLINE]
  • Immunocompromised Adults with Lung/Solid Organ Transplant: the efficacy of ribavirin in these patients is unknown [MEDLINE] [MEDLINE]
• Palivizumab (Synagis) (see Palivizumab, [[Palivizumab]]): RSV-specific humanized monoclonal antibody
  • No clinical benefit in the therapy of RSV infection
  • Licensed for the prevention of serious RSV lower respiratory tract disease in children at high risk of RSV infection (prematurity, bronchopulmonary dysplasia, congenital heart disease)
• Combination Ribavirin + Intravenous Immunoglobulin (IVIG) (see Ribavirin, [[Ribavirin]] and Intravenous Immunoglobulin, [[Intravenous Immunoglobulin]]): may be indicated in severely ill patients with RSV
• Combination Palivizumab (Synagis) + Intravenous Immunoglobulin (IVIG) (see Palivizumab, [[Palivizumab]] and Intravenous Immunoglobulin, [[Intravenous Immunoglobulin]]): has not been studied
• RSV-Specific Immunoglobulin (RSVIG): no longer available
• Combination Ribavirin + Corticosteroids (see Ribavirin, [[Ribavirin]] and Corticosteroids, [[Corticosteroids]]): has been used in small series of lung transplant patients with RSV [MEDLINE]

Prognosis

• Mild Cases: resolve within several days
• Mortality Rates
  • Previously Healthy Infants: 0.5-1.5%
  • Infants with Immunodeficiency/Cancer Chemotherapy/Pulmonary or Heart Disease/Pulmonary Hypertension: 15-40%

Croup (see Croup)

Definitions

• Acute Infectious Croup (Acute Laryngotracheobronchitis): contagious disease in otherwise health children
  • Often associated with respiratory illness in the family
• Acute Spasmodic Croup: most common in young children who are prone to recurrent attacks
  • Possibly precipitated by a viral respiratory infection, allergic factors, or other factors
  • Fever is usually absent
  • Symptoms usually resolve within several hours

Epidemiology

• Peak Age: <6 y/o

Diagnosis

• CXR: glottic/subglottic edema -> may aid in differentiation from acute epiglottitis (although radiographs are of limited accuracy)

Clinical

• General Comments
  • Symptoms are preceded by several days of an upper respiratory illness
  • Symptoms are often worse at night
  • A fluctuating course is typical
• Brassy or Barking Cough (see Cough)
• Dyspnea (see Dyspnea)
• Hoarseness (see Hoarseness)
• Inspiratory Stridor (see Stridor)

Treatment

• Supportive Care
  • Humidified oxygen, mist therapy
  • Since most children have symptoms which decrease in intensity over several days, they can be managed at home: however, monitoring for upper airway obstruction is crucial
• Nebulized Racemic Epinephrine (see Epinephrine): used for symptomatic relief of upper airway obstruction
  • Mechanism: alpha adrenergic effect is believed to cause mucosal vasoconstriction, resulting in decreased subglottic edema
  • Latency: min
  • Duration of Action: <2 hrs
  • Has not been demonstrated to improve oxygenation
• Corticosteroids (see Corticosteroids): single-dose corticosteroids does not have significant adverse effects and is probably indicated for a child who has severe enough croup to be evaluated in a clinic or emergency room
  • Increase rate of symptomatic improvement
  • Decrease hospital length of stay
  • Decrease the rate of intubation
• Anti-Viral Agents: have not been evaluated in croup

Exacerbation of Underlying Obstructive Lung Disease

• Asthma (see Asthma)
• COPD (see Chronic Obstructive Pulmonary Disease): RSV infection accounts for 5-10% of COPD exacerbations

Increased Risk of Future Asthma (see Asthma)

• Wheezing from RSV Infection from Birth-3 y/o: increases odds ratio to 2.6 of developing asthma by age 6 (the odds ratio increased to 10.0 in presence of both RSV and rhinovirus-related wheezing illnesses from birth-3 y/o) [MEDLINE]
  • It is unclear if childhood RSV infection increases the risk of adult asthma

Increased Risk of Pneumococcal Pneumonia (Possible) (see Streptococcus Pneumoniae)

• Study Citing Association Between RSV Infection and Pneumococcal Pneumonia in Infants (2014) [MEDLINE]: interestingly, the study also cited a decrease in RSV-coded hospitalizations after introduction of the seven-valent pneumococcal conjugate vaccine

Influenza-Like Illness

Clinical

• General Comments: rapid onset of constitutional symptoms
  • Upper/lower respiratory tract symptoms occur concurrently or after the constitutional symptoms
• Asthenia (see Asthenia): common in second week of illness
• Clear Nasal Discharge without Obstruction: common
• Dry (Often Persistent) Cough (see Cough): predominates later in the first week of illness
• Excess Ocular Tearing: common early in the illness
• Fatigue (see Fatigue): common in second week of illness
• Fever/Chills (see Fever): common early in the illness
  • May peak to 39-40 degrees C
  • Lasts for 1-5 days
• Headache (see Headache): common early in the illness
• Mild Conjunctivitis (see Conjunctivitis): common
• Mild, Tender Cervical Lymphadenopathy (see Lymphadenopathy): common
• Myalgias (see Myalgias,): common early in the illness
• Pain with Eye Movement: common early in the illness
• Pharyngeal Injection/Pharyngitis (see Pharyngitis): common
• Photophobia (see Photophobia): common early in the illness
• Wheezing: more prominent feature in RSV than in influenza

Treatment

• Anti-Pyretics: avoid aspirin in pediatric cases (due to risk of Reye’s syndrome)
• Anti-Tussives
• Bed Rest
• Hydration
• Infection Control/Contact Precautions: crucial to prevent nosocomial spread (especially in immunocompromised populations)

Pleural Effusion (see Pleural Effusion-Exudate)

• Epidemiology: may occur in some cases

Pneumonia (see Pneumonia, [[Pneumonia]])

Epidemiology

• Childhood Cases: RSV accounts for 40% of pneumonia cases in infants/young children
  • Most severe RSV infections occur in infants <6 mo old
  • CDC EPIC Study of Children Hospitalized for Community-Acquired Pneumonia (2015) [MEDLINE]
    • Annual Incidence of Community-Acquired Pneumonia Requiring Hospitalization: 15.7 cases per 10k children <18 y/o
    • A pathogen was identified in 81% of cases
    • RSV was the most common pathogen (being detected in 28% of pneumonia cases)
    • The greatest burden of RSV was found in children <2 y/o
• Adult Cases: RSV pneumonia may occur in healthy adults

Diagnosis

• Sputum Gram Stain/Culture + Sensitivity
• Bronchoscopy
  • Bronchoalveolar Lavage: viral culture is positive/ELISA or IF viral antigen tests are positive
  • Transbronchial Biopsy: syncytial cells or viral cytoplasmic inclusions/immunohistochemical stains with monoclonal antibodies
• CXR/Chest CT Patterns: air trapping, multilobular alveolar infiltrates, poorly-defined nodularity

Clinical

• Acute Respiratory Failure (see Respiratory Failure)
  • Mechanical ventilation is required in 10% of elderly institutionalized patients who are hospitalized with RSV infection
  • Mechanical ventilation is required in 50% of myelosuppressed leukemics with RSV infection
  • Mechanical ventilation is required in 20% of lung transplant patients with RSV infection
• Cough (see Cough)
• Dyspnea (see Dyspnea)

Treatment

• Treatment of Hypoxemia
• Infection Control/Contact Precautions: crucial to prevent nosocomial spread (especially in immunocompromised populations)
• Ribavirin (see Ribavirin): ribavirin is highly active against RSV in vitro
  • Immunocompromised Adults with Stem Cell Transplant: aerosolized ribavirin decreases mortality rate in RSV pneumonia in this population [MEDLINE] [MEDLINE]
  • Immunocompromised Adults with Stem Cell Transplant: oral and intravenous ribavirin have been shown to be efficacious in small trials [MEDLINE] [MEDLINE]
  • Immunocompromised Adults with Lung/Solid Organ Transplant: the efficacy of ribavirin in these patients is unknown [MEDLINE] [MEDLINE]
• Palivizumab (Synagis) (see Palivizumab): RSV-specific humanized monoclonal antibody
  • No clinical benefit in the therapy of RSV infection
  • Licensed for the prevention of serious RSV lower respiratory tract disease in children at high risk of RSV infection (prematurity, bronchopulmonary dysplasia, congenital heart disease)
• Combination Ribavirin + Intravenous Immunoglobulin (IVIG) (see Ribavirin and Intravenous Immunoglobulin): may be indicated in severely ill patients with RSV
• Combination Palivizumab (Synagis) + Intravenous Immunoglobulin (IVIG) (see Palivizumab and Intravenous Immunoglobulin): has not been studied
• RSV-Specific Immunoglobulin (RSVIG): no longer available
• Combination Ribavirin + Corticosteroids (see Ribavirin and Corticosteroids): has been used in small series of lung transplant patients with RSV [MEDLINE]