Postgraduate Medicine: Volume 121: No.6

Susan J. Rehm, MD; Monica M. Farley, MD; Thomas M. File Jr., MD, MSc; William J. Hall, MD; Robert Hopkins, MD; Orin S. Levine, PhD; Kristin L. Nichol, MD, MPH; Pekka Nuorti, MD, DSc; Richard K. Zimmerman, MD, MPH; and William Schaffner, MD

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Abstract: Pneumococcal disease, which includes pneumococcal pneumonia, meningitis, and bacteremia, is associated with substantial morbidity, mortality, and health care costs in adults. Advanced age, chronic lung or cardiovascular disease, immunosuppressive conditions, and smoking increase the risk for infection. Despite the availability of an effective pneumococcal polysaccharide vaccine (PPSV23), vaccination rates among adults remain suboptimal. This is of immediate concern given the current H1N1 pandemic, since secondary bacterial infection with Streptococcus pneumoniae is common and can contribute to morbidity and mortality. The Centers for Disease Control and Prevention has recently called for increased efforts to vaccinate recommended persons against pneumococcal disease. Long-term trends including the growth of the elderly population and an increase in the number of patients with chronic conditions also underscore the importance of improving pneumococcal vaccination rates. It is important for health care providers, public health officials, and policy makers to recognize the serious health impact of pneumococcal disease in adults and to ensure increased coverage; at present, this is the best way to protect against invasive pneumococcal infection and its consequences.

Keywords: pneumococcal disease; PPSV23; H1N1 influenza; community-acquired pneumonia; invasive pneumococcal disease

Pneumococcal disease, caused by the common bacteria Streptococcus pneumoniae, is associated with considerable morbidity and mortality as well as sizeable health care costs in the United States. The most serious clinical manifestations of pneumococcal disease are pneumonia and invasive pneumococcal disease (IPD), which includes meningitis and bacteremia. In the United States, routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) in children since 2000 has led to waning disease incidence in this population, as well as reductions in IPD cases among adults as a result of “herd immunity.”^1-4 The widespread use of PCV7 in children has altered the epidemiology of pneumococcal infections, bringing the toll of adult pneumococcal disease into sharper relief. Adults presently bear the major burden of serious IPD in this country; about 85% of all IPD cases now occur in persons aged ≥ 18 years.^5,6 All adults aged ≥ 65 years are at increased risk of developing pneumococcal disease, as are persons of any age with immunosuppressive conditions (eg, cancer, HIV/AIDS, diabetes, alcoholism, chronic diseases of the heart, lung, liver, and kidney, and those who smoke cigarettes).^7,8

The impact of disease in adults can be reduced with increased use of the pneumococcal polysaccharide vaccine (PPSV23), which has been available since 1983. Despite comprehensive recommendations from the Centers for Disease Control and Prevention (CDC) (Table 1) adults aged ≥ 65 years and eligible high-risk persons in the United States are not vaccinated optimally against pneumococcal disease (Figure 1).^9,10 The suboptimal rate of pneumococcal vaccination in US adults is a matter of immediate concern given the novel influenza A (2009 H1N1) outbreak. Pneumococcal pneumonia is a serious infectious complication of influenza.⁷

During previous influenza pandemics, secondary bacterial pneumonia was a significant cause of illness and death and Streptococcus pneumoniae was the most common etiology.¹¹ According to interim guidelines issued by the CDC, all persons with existing indications for PPSV23 should be vaccinated following current recommendations, as this may be useful in preventing secondary infections and reducing illness and death.¹¹

The low vaccination rate is also a major long-term concern given several concurrent trends. The number of people with chronic conditions and HIV/AIDS is growing. The elderly population will also increase dramatically between 2010 and 2030, as the baby boom generation reaches age 65 years.¹² The number of people aged ≥ 65 years will more than double by 2050, from 39 to 89 million.¹³ Moreover, many elderly persons have comorbidities that further increase their risk of contracting pneumococcal disease.^14-16 In non-elderly, immunocompetent adults, cigarette smoking is the strongest independent risk factor for IPD.^8,17 In 2007, an estimated 19.8% of US adults (43.4 million) were smokers.¹⁸ In addition, notable antibiotic resistance has been reported with pneumococcal disease,⁷ strengthening the case for renewed efforts against this vaccine-preventable infection. Thus, it is important for health care providers, public health officials, and policy makers to recognize the serious health impact of pneumococcal disease in adults and to ensure adequate immunization, as this represents the best way to protect against pneumococcal illness and its consequences.

Pneumococcal disease is transmitted from person to person through close contact via respiratory droplets. The symptoms and severity of the disease vary depending on the clinical syndrome. Streptococcus pneumoniae is the predominant pathogen in community-acquired pneumonia (CAP).¹⁹ It has been estimated that 915 900 cases of CAP occur in adults aged ≥ 65 years each year in the United States.^17,20 Symptoms develop suddenly and include fever, shaking chills, cough, shortness of breath, and chest pain.

Invasive pneumococcal disease, which includes pneumococcal meningitis and pneumococcal bacteremia, occurs less frequently than pneumococcal pneumonia, but has a higher case-fatality rate. In 2008, there were approximately 43 000 cases of invasive disease and 4400 deaths; the majority of cases and almost all deaths were in adults.⁶ Pneumococcal meningitis is highly lethal, with a case-fatality rate of about 16% to 37% in adults, despite appropriate therapy.^4,21,22 The symptoms of pneumococcal meningitis include stiff neck, fever, disorientation, and sensitivity to light. The symptoms of bacteremia may resemble those of pneumonia and meningitis, along with joint pain. Even with advances in treatment, the case-fatality rate for pneumococcal bacteremia ranges from 15% to 20% among adults.⁷ Bacteremia occurs in about 25% to 30% of patients with pneumococcal pneumonia.

Pneumococcal disease leads to substantial health care utilization and expenditures.^23,24 Although studies have shown decreasing rates of hospitalizations for IPD in the elderly since the introduction of routine childhood vaccination with PCV7 in 2000, thousands of older adults still require hospitalization for CAP as well as invasive disease each year.^3,15,21,25 The national cost for hospitalized CAP in the elderly population is estimated to be $6.4 billion annually.²⁵ Moreover, concurrent cardiac events are common in patients who are hospitalized for pneumococcal pneumonia,²⁶ and survivors of pneumococcal meningitis frequently develop long-term sequelae, leading to additional costs. These consequences may include hearing loss, seizures, blindness, and paralysis.

There are at least 91 distinct pneumococcal serotypes, of which approximately 20 are responsible for > 70% of invasive disease worldwide.⁷ Surveillance studies indicate that pneumococcal resistance to commonly used antibiotics such as penicillins, cephalosporins, and macrolides has become a global problem,^7,19 although resistance rates vary with time and geographical region. Resistance to antibiotics is reported among pneumococci in the United States;^5,6 however, resistance appears to have decreased since the introduction of PCV7.²⁷ Antibiotic resistance threatens the effectiveness of treatment, with implications for morbidity, mortality, and health care costs, and underscores the importance of effective immunization and appropriate use of antibiotics.

Widespread use of PCV7 as part of the childhood immunization schedule has reduced the incidence of PCV7-type IPD in all age groups; nonetheless, substantial opportunities remain for the prevention of IPD among adults. The PPSV23 vaccine has been consistently effective against IPD in adults and individuals with various comorbidities who are not severely immunosuppressed.⁷ The CDC provides comprehensive, detailed recommendations for those who should be vaccinated with PPSV23 (Table 1). Despite these recommendations, no group is vaccinated optimally (Figure 1). The pneumococcal vaccination rate in adults aged ≥ 65 years is 60%, a figure well below the national goal of 90% coverage.^10,28 Working-age adults (19–64 years) with underlying medical conditions have very low coverage (25%) as do certain ethnic groups (15.8% for high-risk Hispanic or Latino, 19–64 years).¹⁰ Approximately 70 million persons in the United States have an indication for PPSV23 but have not been vaccinated.²⁹ According to one study, among adults with IPD who had a vaccine indication, fewer than half were vaccinated and one or more missed opportunities for vaccination (in an outpatient or hospital setting) were documented.³⁰

Polysaccharide and conjugate pneumococcal vaccines have had a positive direct and indirect impact on the incidence of invasive disease in adults, but challenges remain in reducing the overall pneumococcal disease burden. The reduction in IPD rates among adults following widespread pediatric immunization with a 7-valent conjugate vaccine has occurred primarily in healthy adults without predisposing illnesses.² Available data suggest differences in PPSV23 vaccine effectiveness across population groups. While PPSV23 is effective in preventing IPD among healthy adults and those with underlying illnesses who are not severely immunosuppressed,⁷ it affords less robust protection in those who are immunocompromised or very old. Vaccination in these populations is still recommended, as it can reduce the severity of disease, helping to limit complications. There are also conflicting data about the vaccine’s effectiveness against all-cause pneumonia. Moreover, PPSV23 has not been shown to reduce bacterial carriage and transmission, and the duration of protection and the effectiveness of revaccination with PPSV23 are unclear.^7,31

Opportunities for additional gains may come in the form of pneumococcal vaccines currently under development. New 10- and 13-valent pneumococcal conjugate vaccine formulations have been developed and are under licensure review and protein-based vaccines are in various stages of development. Some potential benefits of new vaccines include high serotype coverage, extended duration of coverage with boosting, better immunogenicity among immunocompromised individuals, greater effectiveness against pneumonia, as well as reduction of carriage with resultant diminution of transmission.

Now and in the future, the identification and immunization of all eligible persons is a key component of disease prevention. Health care providers are in a unique position to raise awareness of pneumococcal disease and ensure that vaccination is a high priority. In particular, the use of computerized patient reminder systems, standing orders, and the simultaneous administration of influenza and pneumococcal vaccines may help reduce missed opportunities in outpatient settings.^30,32 In addition, hospitalizations may be used as opportunities to check immunization status and to administer the vaccine.³⁰ Adult vaccination rates are a measure of the quality of medical care. The current influenza pandemic highlights the urgency of enhanced prevention efforts for serious pneumococcal disease. It is therefore imperative that health care providers and organizations act aggressively to improve vaccine uptake among eligible adults.

The authors of this statement comprise the National Foundation for Infectious Diseases’ (NFID) Pneumococcal Disease Advisory Board. The Board and its efforts are supported through an unrestricted educational grant to NFID from Wyeth Pharmaceuticals. Editorial support for this statement was provided by Alembic Health Communications. Authors are collectively responsible for the content of this statement.
The NFID is a nonprofit, tax-exempt (501 c3) organization, founded in 1973, dedicated to educating the public and health care professionals about the causes, treatment, and prevention of infectious diseases.

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