Pneumococcus, Pneumococcal Disease, and Prevention

1

Introduction

First isolated in 1880 by Pasteur in the saliva of a patient with rabies, Streptococcus pneumoniae (also known as the pneumococcus) has been branded as the “captain of the men of death” by William Osler, for the nefarious role this organism plays in causing the demise of so many people particularly among the elderly. While certainly evocative, this description does not fully capture the intricate interaction between the pneumococcus bacteria and its human host, one characterized by repeated and persistent nasopharyngeal colonization events that start at the earliest age and can be documented throughout life. In the context of this relatively friendly coexistence, the pathology caused by this bacterium, which ranges from relatively benign (though thoroughly unpleasant) mucosal infections like otitis media and sinusitis to serious and potentially fatal conditions such as pneumonia, bacteremia, and meningitis, are relatively rare events in the host–pathogen relationship. Along with the great apes, humans are the main natural host for the pneumococcus; when other mammals develop pneumococcal disease, they are usually animals in captivity and acquire the organism through their handlers. The bacterium’s relatively limited host range creates the potential for effective control by vaccination and it is precisely through the ability of newer vaccines to prevent or reduce the likelihood of nasopharyngeal colonization that the greatest impact on prevention of pneumococcal disease has been achieved.

In this chapter, we review the organism, pathogenesis, and epidemiology of pneumococcal disease, as well as recent and potential future advances in immunization strategies.

2

The organism and associated pathology

S. pneumoniae is a Gram-positive, lancet-shaped coccus, which is often but not always seen microscopically in pairs. The organism is characterized by its polysaccharide capsule, which defines the serotype although some strains are unencapsulated ( Fig. 12.1 ). Identification of the capsule can be done serologically, using specific antisera (Quellung reaction) although more recently, molecular genetic approaches have been developed and are becoming widely used so that the standard term “serotype” should perhaps now be replaced with “capsular type.” Based on a combination of strategies, more than 94 serotypes have been identified (and more may be identified in the future). There are two systems used to classify the different capsular serotypes: the Danish system classifies similar, potentially (but not necessarily) cross-reacting serotypes into serogroups (eg, serotypes 6A, B, and C within serogroup 6), whereas the US system numbers serotypes in the order in which they were discovered (the Swedish 6A is 6 in the US system, whereas 6B is assigned the number 26). Because the Danish system is the one most commonly used worldwide, this chapter will follow that nomenclature.

Pneumococcus causes a variety of diseases in humans, with a predilection for infants, young children, the elderly, and the immunocompromised. The most common pneumococcal disease is acute otitis media (AOM, middle ear infections), with pneumococcus isolated from 28 to 55% of middle ear aspirates. The economic importance of otitis media, and pneumococcal otitis media in particular, cannot be overstated, as this disease is the most common reason for pediatric office visits in the United States, with more than 20 million visits annually. Before their first birthday, 60% of children in the United States have had at least one episode of otitis media albeit only a fraction of these are caused by pneumococcus. Sinusitis is also a frequent medical presentation of pneumococcal disease, although precise estimates of incidence are difficult to obtain, due to the general inability to obtain microbiologic confirmation. For very much the same reasons, while it is generally accepted that pneumococcal pneumonia is the next most common pneumococcal disease, precise estimates of incidence in different age groups are lacking. The classic presentation of an adult patient with pneumococcal pneumonia includes high fever, a single episode of rigor, and cough (which may be productive of purulent, rusty sputum). Other symptoms include chest pain, rapid breathing, and weakness. The picture of lobar or segmental opacification on the chest radiograph is classically associated with pneumococcal pneumonia although it is widely accepted that other less well-defined abnormalities often also occur. Pneumococcal pneumonia may be associated with bacteremia (presence of bacteria in the blood) in 5–15% of cases. The overall case-fatality rate in the United States and Europe is between 5 and 7%, and even higher in the elderly. Morbid complications of pneumococcal pneumonia are not uncommon and include infection of the pleural space (empyema), the heart (endocarditis), the sac surrounding the heart (pericarditis), and very rarely lung abscess formation. There is an increased risk of cardiac events up to one year after hospitalization for pneumococcal pneumonia, which is not explained by preexisting comorbidities, suggesting that infection with this organism may elicit cardiac complications as well.

The most serious forms of the pneumococcal disease include septicemia without pneumonia and infection of the lining of the brain (meningitis). Both of these diseases are relatively rare compared to other forms of pneumococcal infections, but have a much higher case-fatality rate. For example, bacteremia in the absence of pneumonia in adults has an overall fatality rate of 20% (60% in the elderly); similarly, meningitis in adults also has about a 20% fatality rate. While the mortality rate of pneumococcal meningitis in children is lower (around 8%), this disease is often associated with significant morbidity, such as developmental delay, deafness, and seizure disorders.

It is important to note that, while pneumococcal disease afflicts individuals in every geographic location, the majority of the burden of disease occurs in the developing world, where respiratory infections are the leading cause of death in children under 5 years of age. It has been estimated that in 2000 pneumococcus caused between 1 and 4 million cases of pneumonia in the developing countries of Africa alone, and more than 800,000 deaths in developing countries worldwide.

3

Epidemiology of pneumococcal disease

Pneumococcus is an organism whose clinical manifestations, age distribution of disease, serotype distribution, and mode of person-to-person community transmission have been studied and documented for more than 60 years across heterogeneous epidemiologic settings. This evidence base forms the foundation on which pneumococcal control and prevention strategies, vaccines in particular, have been developed.

3.2

Disease Descriptive Epidemiology

Pneumococcal disease is an uncommon but important result of upper respiratory tract acquisition of the pneumococcus and presents clinically as any one of various syndromes; pneumococcal disease events are categorized as either noninvasive or invasive, distinguished by whether the body site of infection is a normally sterile site ( Fig. 12.2 ). Invasive pneumococcal disease (IPD) is defined as the isolation of pneumococcus from a normally sterile body fluid such as blood, cerebrospinal fluid, pleural or joint fluid, among others. Pneumococcal pneumonia is of particular importance because it constitutes the greatest disease burden of all serious pneumococcal infections and because it is detected and characterized as an invasive infection only when the pneumococcus is isolated from the blood, a lung tap, or pleural fluid. Pneumococcal pneumonia events that are not associated with detection of the organism from a normally sterile body fluid, but instead detected through analysis of sputum, are not characterized as IPD events, even though the lower portions of the lung are generally characterized as a sterile body site.

The age distribution of pneumococcal disease follows a U-shaped curve with the highest burden of disease found in young infants, then in young children, and an increase found again in the elderly. Mortality due to the pneumococcus is highest among the elderly, followed by young infants and it is a significant contributor to overall deaths in children under 5 years old (U5). In 2008, it was estimated that there were 541,000 deaths due to the pneumococcus (uncertainty range 376,000–594,000 deaths) in children U5 worldwide, representing about 9% of all deaths in children U5 after the neonatal period.