Respiratory syncytial virus (RSV) is the most frequent cause of pneumonias in children with lower respiratory tract involvement (~50% cases) and is a particular problem in infants and young toddlers. RSV usually occurs in epidemics during the winter and early spring months, and infects virtually all children during the first 3 years of life. RSV is spread by direct or close contact with contaminated secretions or large infectious droplets in the air. Clinical features in RSV bronchiolitis include copious nasal discharge, cough, irritability, fever, and anorexia. Symptoms may progress over 3-7 days with worsening cough, dyspnea, and respiratory distress. Patients may develop significant tachypnea, nasal flaring, and sternal retractions. Wheezing is often a prominent feature that is accompanied by a prolonged expiratory phase. Underlying conditions that increase the risk of severe disease from RSV include children with congenital heart disease, immune deficiencies, or pulmonary disorders such as bronchopulmonary dysplasia (BPD).
RSV antigens in clinical specimens such as nasopharyngeal swabs are best detected using any of several rapid diagnostic tests that utilize immunofluorescent and enzyme immunoassay techniques. As with other viral causes of lower respiratory tract infection, treatment for RSV bronchiolitis includes adequate hydration, fever control, palliative measures, and supplemental oxygen in children who show hypoxemia. More aggressive therapeutic approaches have been proposed for RSV bronchiolitis, but lack evidence at present of their benefit in altering disease course, notably bronchodilators (albuterol, epinephrine), corticosteroids, and the antiviral agent ribavirin. Clinicians have found that a patient's response to bronchodilators may change as the illness progresses, particularly in atopic children (eg, those with eczema) or in those with a strong family history of allergic disease. Prophylaxis against RSV infection in those infants at highest risk of severe disease is available in the form of a humanized monoclonal antibody that is directed against an RSV surface protein. Thus, palivizumab is approved for children <24 months of age who have BPD or a history of prematurity (<32 weeks' gestation). It is administered once monthly as an intramuscular injection during the high risk months of RSV disease (in North America, those being November through March).
In addition to RSV, other viruses and atypical organisms are capable of causing lower respiratory tract infections such as bronchiolitis or pneumonia. Parainfluenza viruses are second in frequency to RSV and cause ~25% of viral lower respiratory disease in this population, with type 3 the most likely to cause severe pneumonia. Parainfluenza infections can occur at any time of the year. Types 1 and 2 cause about one-third of all parainfluenza disease and are generally endemic in late summer and fall; type 3 tends to peak in the late spring and accounts for two-thirds of all parainfluenza cases. The parainfluenza viruses more typically cause upper respiratory tract disease, accounting for over half of the cases of laryngotracheitis (croup).
Adenoviruses cause 5%-7% of viral respiratory disease in children, often with a variety of syndromes that also affect the eyes, heart, bladder, and gastrointestinal tract. Adenoviral types 3, 4, 7, and 21 are associated with respiratory illnesses in children. Types 3, 7, and 21 have been identified in patients with severe adenoviral pneumonias and are linked to case fatality rates as high as 5%-10%. Residual adenovirus-caused morbidities can occur, notably bronchiectasis, unilateral hyperlucent lung syndrome, bronchiolitis obliterans, or rarely, pulmonary fibrosis. Among the many viral etiologies of lower respiratory tract infections in children, adenoviral infections most often have features that are more usually identified with bacterial infections, such as lobar consolidations, pleural effusions, and high fevers.
Infections with influenza virus type A or type B cause another 5% of childhood respiratory illnesses. These are often accompanied by a variety of systemic symptoms including fever, headache, anorexia, malaise, myalgia, sore throat, vomiting, and abdominal pain. Respiratory complications from influenza may be limited to upper respiratory tract symptoms (croup, rhinitis), or the patient may present with pneumonia or a bronchiolitis-like illness. More so than in other viral infections, influenza infection is associated with an increased risk of secondary bacterial infections, particularly pneumonias due to S. aureus or S. pneumoniae. In this setting, the patient may improve clinically from the initial influenza illness but then have renewed fever, chills, cough, and respiratory distress, reflecting the bacterial superinfection. Treatment for routine influenza infections is supportive. In cases where more severe disease is a concern, antiviral agents can be administered provided this therapy is begun within 48 hours of the onset of symptoms.
CLINICAL CORRELATION 40.2
Influenza viral infections occur in epidemics with a high attack rate lasting a relatively brief period of time. Influenza pandemics have led to millions of deaths worldwide in the past. The most dramatic example of this occurred in 1918, when an estimated 20 million people worldwide died. Outbreaks of influenza in the United States typically peak in the winter months with the highest attack rates in children. Influenza types A and B are the primary causes of epidemic disease worldwide and are further subdivided by distinct serotypes. Antigenic shift of these serotypes mandates changes in the composition of the annual influenza vaccine. The seasonal influenza vaccine is recommended for patients at high risk for severe complications from influenza (those with pulmonary or cardiac disorders) and in all children less than 5 years of age. Household contacts and caregivers of children with chronic disease should be vaccinated as well.
Metapneumovirus is a recently described pathogen (2001) which causes ~5% of lower respiratory tract disease, primarily in infants, but is reported in all age groups. Outbreaks occur in late winter and early spring in temperate climates and often coincide with the RSV season. Transmission probably occurs by direct contact with infected individuals, and nosocomial outbreaks have been described. Epidemiological studies point to metapneumovirus being the second leading cause of bronchiolitis in infants, after RSV. It causes pneumonia and croup in all age groups and is thought to be a major trigger of asthma exacerbations in children and adults. Clinical manifestations of metapneumovirus infection are similar to RSV disease with cough, wheeze, and respiratory distress being prominent features. More severe disease occurs in patients with congenital or acquired immune deficiencies, and likely those with underlying cardiopulmonary disorders and premature birth. Treatment for metapneumovirus, as with most viral lower respiratory tract infections, is supportive.
Mycoplasma pneumoniae is included with the discussion of viral pathogens since it is a frequent cause of "atypical" pneumonia, accounting for 5%-10% of respiratory tract infections in the pediatric population. Mycoplasmata are the smallest free-living microorganisms, lacking a cell wall. Pneumonia caused by M. pneumoniae is the prototype of the primary atypical pneumonia syndrome, although a variety of pathogens may be associated with this syndrome, including many described above. M. pneumoniae is the most common infectious agent causing pneumonia in older children and adolescents. It is a highly transmissible organism, with human to human spread by symptomatic individuals being a common cause of propagation within a family, school, military, or prison setting.
Initial symptoms in children with Mycoplasma pneumonia include malaise and fever. Cough may be an early symptom but typically arises or worsens later. Within a few days of the onset of illness a nonproductive cough develops with diffuse crackles often found on lung exam. Cough may become productive later in the illness and last up to four or more weeks. About 10% of children develop a maculopapular rash in the course of the illness. Radiographically, the typical pattern is bilateral diffuse infiltrates that may be particularly pronounced in the lower lobes. Definitive diagnosis of Mycoplasma disease relies on acute and convalescent sera utilizing complement fixation or immunofluorescent assays. A fourfold or greater increase in titer or the presence of specific IgM antibodies confirms recent infection. By the second week of illness, cold agglutinin titers of 1:32 or greater are present in half of patients with pneumonia. However, this test lacks specificity. Treatment with tetracyclines, or with macrolides such as erythromycin or newer derivatives (clarithromycin, azithromycin) are effective in shortening the clinical manifestations of the disease.
S. pneumoniae (formerly Pneumococcus pneumoniae) is frequently detected in the upper respiratory tract of children. There it can cause disease including sinusitis or otitis media, or more invasively pneumonia, meningitis, or bacteremic sepsis. It is a common cause of community-acquired pneumonia in children, responsible for more than 50% of patients requiring hospital admission. The near-universal use of the heptavalent pneumococcal conjugate vaccine in the United States has had a substantial impact on the epidemiology of invasive pneumococcal disease. The incidence of invasive disease has dropped among vaccinated children, and upper respiratory tract colonization with this organism has fallen, but there has been a notable shift in pneumococcal serotypes causing disease in those not covered by the vaccine. As noted, the introduction of a conjugate vaccine protecting against 13 serotypes may have a broader impact on the incidence of pneumococcal disease (see Clinical Correlation 40.1). High-risk groups for invasive disease include Native American and African-American children, children with sickle cell disease, children with acquired or congenital splenic disorders, and children with HIV infection or other immune deficiencies.
Clinical manifestations of pneumococcal disease are protean, with most children presenting with spiking fevers, cough, an elevated leukocyte count, and lobar or segmental consolidation on chest radiographs. Notably, up to one-fourth of children may have no signs or symptoms attributable to respiratory tract disease and instead present with fever, abdominal pain, or diarrhea. Further, many different radiographic patterns have been described in pneumococcal pneumonia, above and beyond the typical lobar abnormalities (Fig. 40.2). Complications arising from pneumococcal pneumonia are not uncommon in hospitalized children and include parapneumonic effusions, empyema, abscess formation, and necrotizing pneumonia. Although antibiotic-resistant isolates are not predictive of these morbidities, patients with complicated pneumonias tend to be older, are more likely to be Caucasian, and more likely to present with chest pain. Provided that empiric antibiotic choices are correct, most patients will improve within 2-4 days. Ongoing fever, chills, chest or abdominal pain, or the lack of an improvement in the overall clinical picture should raise concerns for one of the above complications.
Pleural effusions accompanying pneumococcal chest infections are the result of a complicated pathophysiologic process (Chap. 29). Parenchymal lung injury causes an inflammatory response of the pleural surfaces and a subsequent increase in regional capillary permeability. This pleural inflammation also reduces the dynamic process of pleural fluid reabsorption by the parietal pleura. When this is combined with the change in capillary permeability, considerable amounts of fluid can accumulate. Initially, pleural effusions are sterile, free flowing, and contain fluid with few leukocytes. This exudative phase (or stage 1) may last for 3-5 days before giving way to the fibrinopurulent phase where an increase in leukocytes and a positive Gram stain indicative of infected fluid are observed (Chap. 19). With the development of pus in the pleural space, fibrin deposition between the visceral and parietal pleura ensues. The infected fluid accordingly becomes loculated, fibrin and cellular debris accumulate and more fluid becomes apparent as lymphatic channels become obstructed. The organizing stage (stage 3) is characterized by infiltration of fibroblasts, thickening of the pleural membranes and "trapped" lobes (Chap. 26).
In the initial stages of a pleural effusion, fluid removal is amenable to simple needle thoracentesis or via chest tube placement. This approach may be both diagnostic and therapeutic (Chap. 19). In the later stages, these approaches may not be successful as the loculated, purulent fluid may be difficult to drain. Video-assisted thoracoscopic surgery (VATS) to evacuate pleural fluid and perform decortications with debridement of thickened pleural membranes is a surgical option. On the other hand, some clinicians favor an approach of chest tube placement in conjunction with a fibrinolytic agent such as tissue plasminogen activator instilled into the chest tube (Chap. 27). Less frequently, continuing medical therapy with IV antibiotics alone to manage pneumonias with large effusions is an option. Though S. pneumoniae is the most common cause of pneumonias with effusions, other organisms such as Group A Streptococcus, S. aureus, H. influenzae, Pseudomonas aeruginosa, and Mycoplasma spp. can also cause complicated parapneumonic effusions.
The development of a pulmonary abscess is another complication of bacterial pneumonias, including those caused by S. pneumoniae. A lung abscess is a thick-walled cavity containing pus, leukocytes, and cellular debris. In some circumstances, it is the result of an aspiration event, especially in children with neurodevelopmental deficits. The clinical presentation of a pulmonary abscess mirrors that of children with typical bacterial pneumonias, with fever and cough being the prominent features. The course of illness may be subacute with a slower evolution of signs and symptoms. The chest radiograph shows a typical appearance of a fluid-filled cavity with an air-fluid level (Fig. 40.4). Chest ultrasound or CT scan may be an adjunct to diagnosis and guide possible drainage procedures. Most clinicians recommend IV antibiotics for up to 2 weeks with an additional 2-4 weeks of oral therapy. Newer information suggests that draining abscess fluid or placing a pigtail catheter in the cavity in conjunction with IV antibiotic therapy may shorten the hospital stay.
A PA x-ray of a previously healthy 7-year-old girl with cough, fever, and chest pain. A cavity with an air-fluid level is present in the left lung, indicative of a pulmonary abscess. A culture from a needle aspiration of this cavity was positive for S. pneumoniae.
Other Bacterial Pathogens
H. influenzae type B was a frequent cause of significant bacterial disease among children in the past. Invasive diseases caused by H. influenzae type B include sepsis, meningitis, epiglottitis, cellulitis, and pneumonia. An effective vaccine to prevent disease caused by this organism became available in the late 1980s and resulted in a dramatic decrease in the incidence of these illnesses. Although H. influenzae type B is no longer a significant cause of bacterial pneumonia in affluent countries, the worldwide morbidity and mortality from this organism remains an important problem. Nearly 90% of children who develop infections with this pathogen are <5 years of age, and the majority of these are <2 years old. Pneumonias due to H. influenzae cannot be differentiated by clinical criteria from pneumonias caused by other bacteria. Radiographic findings vary, with pleural effusion a common finding. Because of the risk of systemic complications (bacteremia, meningitis) in children <12 months of age in whom H. influenzae is considered a likely pathogen, IV antibiotics should be administered. Older children who are at lower risk of developing these complications may be treated with oral therapy.
While not very common, the community-acquired pneumonia caused by Group A Streptococcus (S. pyogenes) is often associated with a particularly protracted and difficult course in some children. Group A Streptococcus causes a variety of infections involving the upper respiratory tract and skin, but when it involves the lower respiratory tract, a diffuse infection with interstitial pneumonia may occur. In its severe form, necrosis of the airway mucosa and lung parenchyma takes place accompanied by hemorrhage, exudates, edema, and pleural involvement (Chap. 34). Previous infection with influenza virus, measles, or Varicella may place the patient at particular risk of developing severe complications of Group A Streptococcal disease.
In most cases of community-acquired pneumonia caused by Staphylococcus aureus, infection is either by direct inoculation of the organism into the respiratory tree or, less commonly, following bacteremic illness. Exceptions are those patients with indwelling catheters or a recent history of intravenous drug use, where the bacteremic route more commonly causes pneumonia (Chap. 28). Since most clinical protocols for treatment of community-acquired pneumonias do not include therapy directed against S. aureus, the clinical picture may be one of ongoing fever, cough, chills, and supplemental oxygen requirement. A subacute or acute deterioration in clinical status may be observed if this organism is not suspected. Radiographically, unilateral lung involvement is typical with confluent bronchopneumonia and alveolar infiltrates (Chap. 15). As the illness evolves, these areas may coalesce and cavitate, leading to the formation of pneumatoceles. In a large proportion of patients whose pneumonia is caused by S. aureus, complicated parapneumonic effusions and empyema develop. More severely in some patients, a pyopneumothorax may occur characterized by both pus and air in the pleural space. With the increasing prevalence of methicillin-resistant S. aureus (MRSA) in the United States and elsewhere, antibiotic therapy may need to be adjusted to account for this organism, depending on local microbiologic surveillance data.