Epidemiology

Pneumonia—inflammation of the parenchyma of the lungs—is a substantial cause of morbidity and mortality in childhood throughout the world, rivaling diarrhea as a cause of death in developing countries (Fig. 392-1). With ≈158 million episodes of pneumonia per year, of which ≈154 million are occurring in developing countries, pneumonia is estimated to cause ≈3 million deaths, or an estimated 29% of all deaths, among children younger than 5 yr worldwide. The incidence of pneumonia is more than 10-fold higher (0.29 episodes versus 0.03 episodes), and the number of childhood-related deaths due to pneumonia ≈2000-fold higher, in developing than in developed countries (Table 392-1).

Figure 392-1 Pneumonia is the leading killer of children worldwide, as shown by this illustration of global distribution of cause-specific mortality among children <5 yr in 2004. Pneumonia causes 19% of all under-5 deaths. This illustration, however, does not include deaths due to pneumonia during the neonatal period. It is estimated that 26% of neonatal deaths, or 10% of under-5 deaths, are caused by severe infections. Large proportions of these infections are caused by pneumonia/sepsis. If these deaths were added to the overall estimate, pneumonia would account for up to 3 million, or as many as one third (29%), of under-5 deaths worldwide.

(Sources of data: Cause-specific mortality estimates from WHO. World Health Report 2005: Make Every Mother and Child Count. Geneva: World Health Organization, 2005; under-five mortality estimates from UNICEF. The state of the world’s children 2006. New York: United Nations Children’s Fund, 2005. From Wardlaw T, Salama P, Johansson EW: Pneumonia: the leading killer of children, Lancet 368:1048–1050, 2006.)

In the USA from 1939 to 1996, pneumonia mortality in children declined by 97%. It is hypothesized that this decline is attributable to the introduction of antibiotics, vaccines, and the expansion of medical insurance coverage for children. Haemophilus influenzae type b (Hib) (Chapter 186) was an important cause of bacterial pneumonia in young children but has become uncommon with the routine use of effective vaccines. The introduction of heptavalent pneumococcal conjugate vaccine and its impact on pneumococcal disease (Chapter 175) has reduced the overall incidence of pneumonia in infants and children in the USA by ≈30% in the 1st yr of life, ≈20% in the 2nd yr of life, and ≈10% in children >2 yr of age. In developing countries, the introduction of measles vaccine has greatly reduced the incidence of measles-related pneumonia deaths.

Etiology

Although most cases of pneumonia are caused by microorganisms, noninfectious causes include aspiration of food or gastric acid, foreign bodies, hydrocarbons, and lipoid substances, hypersensitivity reactions, and drug- or radiation-induced pneumonitis. The cause of pneumonia in an individual patient is often difficult to determine because direct culture of lung tissue is invasive and rarely performed. Cultures performed on specimens obtained from the upper respiratory tract or “sputum” often do not accurately reflect the cause of lower respiratory tract infection. With the use of state-of-the-art diagnostic testing, a bacterial or viral cause of pneumonia can be identified in 40-80% of children with community-acquired pneumonia. Streptococcus pneumoniae (pneumococcus) is the most common bacterial pathogen in children 3 wk to 4 yr of age, whereas Mycoplasma pneumoniae and Chlamydophila pneumoniae are the most frequent pathogens in children 5 yr and older. In addition to pneumococcus, other bacterial causes of pneumonia in previously healthy children in the USA include group A streptococcus (Streptococcus pyogenes) and Staphylococcus aureus (Chapter 174.1) (Table 392-2).

Table 392-2 CAUSES OF INFECTIOUS PNEUMONIA

* Atypical pneumonia syndrome; may have extrapulmonary manifestations, low-grade fever, patchy diffuse infiltrates, poor response to beta-lactam antibiotics, and negative sputum Gram stain.

From Kliegman RM, Greenbaum LA, Lye PS: Practical strategies in pediatric diagnosis & therapy, ed 2, 2004, Philadelphia, Elsevier, p 29.

S. pneumoniae, H. influenzae, and S. aureus are the major causes of hospitalization and death from bacterial pneumonia among children in developing countries, although in children with HIV infection, Mycobacterium tuberculosis (Chapter 207), atypical mycobacteria, Salmonella (Chapter 190), Escherichia coli (Chapter 192), and Pneumocystis jiroveci (Chapter 236) must be considered. The incidence of H. influenzae has been significantly reduced in areas where routine Hib immunization has been implemented.

Viral pathogens are a prominent cause of lower respiratory tract infections in infants and children <5 yr of age. Viruses are responsible for 45% of the episodes of pneumonia identified in hospitalized children in Dallas. Unlike bronchiolitis, for which the peak incidence is in the 1st yr of life, the highest frequency of viral pneumonia occurs between the ages of 2 and 3 yr, decreasing slowly thereafter. Of the respiratory viruses, influenza virus (Chapter 250), and respiratory syncytial virus (RSV) (Chapter 252) are the major pathogens, especially in children <3 yr of age. Other common viruses causing pneumonia include parainfluenza viruses, adenoviruses, rhinoviruses, and human metapneumovirus. The age of the patient may help identify possible pathogens (Table 392-3).

Table 392-3 ETIOLOGIC AGENTS GROUPED BY AGE OF THE PATIENT

From Kliegman RM, Marcdante KJ, Jenson HJ, et al: Nelson essentials of pediatrics, ed 5, Philadelphia, 2006, Elsevier, p 504.

* H. influenzae type b is uncommon with routine H. influenzae type b immunization.

Lower respiratory tract viral infections in the USA are much more common in the fall and winter, in relation to the seasonal epidemics of respiratory viral infection that occur each year. The typical pattern of these epidemics usually begins in the fall, when parainfluenza infections appear and most often manifest as croup. Later in winter, RSV, human metapneumovirus, and influenza viruses cause widespread infection, including upper respiratory tract infections, bronchiolitis, and pneumonia. RSV attacks infants and young children, whereas influenza virus causes disease and excess hospitalization for acute respiratory illness in all age groups. Knowledge of the prevailing viral epidemic may lead to a presumptive initial diagnosis.

Immunization status is relevant because children fully immunized against H. influenzae type b and S. pneumoniae are less likely to be infected with these pathogens. Children who are immunosuppressed or who have an underlying illness may be at risk for specific pathogens, such as Pseudomonas spp. in patients with cystic fibrosis.

Pathogenesis

The lower respiratory tract is normally kept sterile by physiologic defense mechanisms, including mucociliary clearance, the properties of normal secretions such as secretory immunoglobulin A (IgA), and clearing of the airway by coughing. Immunologic defense mechanisms of the lung that limit invasion by pathogenic organisms include macrophages that are present in alveoli and bronchioles, secretory IgA, and other immunoglobulins. Additional factors that promote pulmonary infection include trauma, anesthesia, and aspiration.

Viral pneumonia usually results from spread of infection along the airways, accompanied by direct injury of the respiratory epithelium, which results in airway obstruction from swelling, abnormal secretions, and cellular debris. The small caliber of airways in young infants makes such patients particularly susceptible to severe infection. Atelectasis, interstitial edema, and ventilation-perfusion mismatch causing significant hypoxemia often accompany airway obstruction. Viral infection of the respiratory tract can also predispose to secondary bacterial infection by disturbing normal host defense mechanisms, altering secretions, and modifying the bacterial flora.

Bacterial pneumonia