Pneumococcal Disease: Infections Caused by Streptococcus pneumoniae

Geographic Distribution and Burden of Disease

The World Health Organization (WHO) estimates that pneumococcal infections accounted for approximately 5% of all-cause child mortality in children younger than 5 years of age in 2008. Countries implementing routine use of pneumococcal conjugate vaccines in infancy have seen a marked reduction in the incidence of serious diseases due to pneumococcal serotypes in the vaccines. Still, pneumonia is the single largest infectious cause of death in children worldwide. The WHO estimated that pneumonia accounted for 15% of all deaths of children younger than 5 years old, S. pneumoniae being the most common cause of bacterial pneumonia in children. Among adults living in Europe and the United States, S. pneumoniae is the most common cause of community-acquired bacterial pneumonia.

Distribution of serotypes varies temporally and geographically. Outbreaks of pneumococcal disease caused by the same serotypes have been reported in institutional settings; however, epidemics in the general population are rare in developed countries.

In temperate regions, invasive pneumococcal disease (IPD), defined as an infection of a normally sterile body site, is more common during winter. Close proximity indoors and spread of viral respiratory pathogens facilitate transmissibility and invasiveness.

In low-income countries, data about the burden of pneumococcal disease are limited. Using information from hospital-based studies and vaccine efficacy trials and inferring from disease patterns among native populations, the estimated burden of disease is high. Rates of IPD among young children have been reduced substantially in countries in which the conjugate vaccines are in widespread use. After introduction of conjugate vaccines in the United States, annual rates of IPD in children young decreased from 100 cases per 100,000 people in 1998 to 9 cases per 100,000 in 2015, and IPD caused by the 13 conjugate vaccine serotypes decreased from 91 cases per 100,000 people in 1998 to 2 cases per 100,000 people in 2015.

S. pneumoniae is a common pathogen in middle ear aspirates from children with acute otitis media (AOM). AOM is also the leading reason for prescribing antibiotics during childhood, and this use contributes substantially to increased antimicrobial resistance.

Microbiology and Pathogenesis

S. pneumoniae is a strictly human pathogen consisting of gram-positive, encapsulated, lancet-shaped bacteria occurring in pairs (called diplococci ) and chains ( Fig. 5.1 ). At least 90 serotypes have been identified based on differences in the polysaccharide capsule, as observed with the quellung reaction, in which serotype-specific antibodies bind to the bacterial capsule causing the bacteria to appear opaque and enlarged on microscopy (see Fig. 5.1 ).

The polysaccharide capsule is considered the primary virulence factor of S. pneumoniae. Nonencapsulated strains are less likely to cause severe disease. The capsule contributes to pathogenesis by protecting the organism from phagocytosis. Antibody binding to the capsule can facilitate phagocytosis and bacterial killing by phagocytic cells. Some pneumococcal proteins, including hyaluronate lyase, pneumolysin, neuraminidase, major autolysin, choline-binding protein A, and pneumococcal surface protein A (PspA) have functions that also contribute to pathogenicity. These virulence proteins have also been considered for development as vaccine antigen candidates.

Risk Factors

Children younger than age 2 years carry the highest burden of S. pneumoniae disease worldwide. Other groups at increased risk of invasive disease include the elderly, people with impaired immunity (e.g., humoral immunodeficiency, complement deficiency, human immunodeficiency virus [HIV] infection, and anatomic or functional asplenia [e.g., sickle cell disease]), cigarette smokers, those with cochlear implants and cerebrospinal fluid (CSF) leaks, and individuals with chronic diseases such as diabetes and heart, kidney, and lung disorders. IPD occurs at higher rates among certain ethnic groups; for example, prior to widespread use of conjugate pneumococcal vaccines, Native Americans and Eskimos had rates of IPD that were several-fold higher than in the general population in the United States.

Clinical Presentation

S. pneumoniae organisms are transmitted person to person via contact with infected respiratory droplets. Asymptomatic nasopharyngeal (NP) carriage is common in children 6 months to 5 years of age, and they are a source of transmission among close contacts by projecting droplets (>5 μm) across a short distance (1 m).