Pneumococcal Disease: The Whole Story in 10 Points

Streptococcus pneumoniae is the leading cause of life-threatening illness globally.

The gram-positive bacterium Streptococcus pneumoniae (S pneumoniae or simply pneumococcus) was identified in 1886.^1-3 It spreads via airborne droplets and is the leading cause of pneumonia and other life-threatening illnesses globally.^4-6 Approximately 4 million Americans contract pneumococcal infections every year.^7-9 The most serious infection, invasive pneumococcal disease (IPD), causes 400,000 to 500,000 hospitalizations annually and about 10% of patients die.^6,10-14 This scourge is vaccine preventable to a great extent. This article explains pneumococcal disease in 10 points.

1. Pneumococcal disease infects our most vulnerable disproportionately (online Table 1). Furthermore, small children and the elderly are at greater risk of death if they develop IPD.^5,6

Table 1: Populations at Risk for Pneumococcal Disease

Children:

· Younger than 2 years

· Who attend group child care

· Who have certain chronic or autoimmune illnesses

· With cochlear implants or cerebrospinal fluid (CSF) leaks

· Who are of American Indian, Alaska Native, and African American origin

Adults:

· Aged 65 years and older

· At any age who

· Have chronic heart, kidney liver, or lung disease; asthma; diabetes; or alcoholism

· Have autoimmune conditions

· Reside in long-term care facilities

· Have cochlear implants or cerebrospinal fluid (CSF) leaks

· Smoke

Source: Reference 15

2. Because of its changeable polysaccharide capsule, pneumococcus occurs as more than 90 known serotypes and 46 serogroups, all of which can cause otitis media (OM), sinusitis, and bronchitis. A few serotypes can enter blood, cerebrospinal, joint, pleural, or pericardial sites to cause IPD.¹⁰

3. Workers and war created pressure to find vaccines. The earliest interest in a pneumococcal vaccine occurred in South Africa in 1911. The country’s economy depended on gold mining. The labor force, much of which emigrated from distant rural areas, was prone to infections. Britain considered closing mines due to escalating morbidity and mortality from lobar pneumonia, prompting the mining industry to push for a vaccine.^16-18 While researchers did not find a vaccine, they delineated the disease-causing pneumococcal serotypes and clarified the typical immune response.^19,20

World War I’s flu pandemic created more pressure for a vaccine as soldiers and civilians—more than 70 million—died of flu complications. Pneumococcal pneumonia was also a problem during World War II. The barrier: pharmaceutical companies' financial challenges were high, and societal acceptance of vaccinations was low. When antibiotic resistance emerged in the 1970s, society became more receptive to the idea of a vaccine. The FDA approved a 14-valent vaccine in 1978.²¹

Even with the vaccine, the World Health Organization (WHO) tagged pneumococcal disease as a global problem. WHO assembled a multinational survey to determine which serotypes posed the greatest problem, then recommended moving to 23-valent vaccines. This simple proposal translated into an intimidating, costly challenge. Merck and Lederle independently introduced pneumococcal polysaccharide vaccines (PPV23) in 1983 that covered approximately 87% of pneumococcal diseases in the United States. The Advisory Committee on Immunization Practices (ACIP) immediately recommended vaccinating 2 high-risk groups: children older than 2 years who had certain underlying chronic medical conditions, and people older than 65 years.^7,22

4. The earliest vaccines weren’t for little kids! Nonconjugated PPVs activate B cells but elicit T-cell independent immune responses. Children younger than 2 years cannot mount these protective responses. Additionally, PPVs do not induce immune memory, are devoid of booster effect, and have almost no effect on nasopharyngeal carriage in patients of any age.²³ Researchers continued to search for vaccines for wide use in small children.

5. Today’s vaccines are effective in all age groups. The FDA licensed a 7-valent pneumococcal conjugate vaccine (PCV) in 2000. PCV7 could be used in infants and young children. Safe and highly effective (~97%) against IPD, PCV7 was also moderately effective against pneumonia, and somewhat effective in reducing OM episodes and office visits.^24-26 ACIP now recommends routine PCV7 use for children aged 2 to 59 months.^14,27

The PCV7 vaccine’s routine use decreased rates of IPD caused by PCV7-covered serotypes by more than 90% over the next few years. Within a year, IPD caused by PCV7-covered serotypes had been completely eliminated in children younger than 5 years in the United States. Overall and over several years, the vaccine reduced preventable infection by 94% in all ages.²⁸

Given the high burden of IPD caused by serotypes in PPV23 but not newer vaccines, patients who are immunocompromised or at elevated risk (online Table 2) still need the PPV23 vaccine. Additionally, clinical trials have not been conducted using the PCVs in these populations.

6. Pneumococcal disease is an intergenerational issue even though most children receive immunizations. Up to 50% of young children are colonized with S pneumoniae, and almost all children in day care are carriers. Before the PCV7 vaccine was available, statisticians identified an annual post-holiday spike of IPD in January among elderly people in January among elderly people—a spike attributed to family holiday gatherings.^32,33 Adults who live with a day care—attending child 6 years or younger are at an increased risk of pneumococcal infection. HIV-infected adults who have contact with children are at elevated risk for IPD.^32-35

Herd immunity is working. After children were routinely vaccinated with PCV7, the incidence of IPD caused by the 7 serotypes in the vaccine declined 92% in adults older than 65 years.^32-35

Table 2: Serotype Coverage at a Glance

Serotypes

PPV23

PCV7

PCV13

1

+

+

2

+

3

+

+

4

+

+

+

5

+

+

6A

+

6B

+

+

+

7F

+

+

8

+

9N

+

9V

+

+

+

10A

+

11A

+

12F

+

14

+

+

+

15B

+

17F

+

18C

+

+

+

19A

+

+

19F

+

+

+

20

+

22F

+

23F

+

+

+

33F

+

Source: References 22, 29, 30, and 31

7. The picture of pneumococcal disease changes under pressure from vaccination. After PCV7 became available, the incidence of diseases caused by non-PCV7 serotypes (especially 6A, 15, and 19A) increased in children and at-risk adult populations. These increases were small compared with the overall reduction in disease.^36-40 Regardless, PCV7’s coverage was imperfect.

In February 2010, the FDA approved a 13-valent pneumococcal conjugate vaccine (PCV13).³¹ In addition to the 7 serotypes included in PCV7, PCV13 has 6 more serotypes (1, 3, 5, 6A, 7F, and 9A). PCV13 is approved for prevention of IPD caused by the 13 serotypes in the vaccine among infants and young children. This product is labeled for OM prevention related to the 7 serotypes covered by PCV7 only. ACIP now recommends PCV13 for all children aged 2 months to 5 years and others at risk. In 2011, the FDA approved PCV13 for people 50 years and older to prevent pneumonia and IPD.³¹

8. Despite the availability of vaccines, IPD and influenza are the eighth-leading cause of death in the United States.⁴¹ Some experts blame serotype replacement, which has increased prevalence of serotypes already present in the population, or the appearance of new serotypes formerly unable to compete with more pathogenic serotypes to cause disease.⁴² Experts agree that serotype replacement, while disquieting, doesn’t outweigh vaccination’s benefits.⁴³

9. Vaccination uptake rates among adults need improvement. Healthy People 2020 identifies a target vaccination rate of 90% for people 65 years and older,⁴⁴ but only 30.5% of patients in high-risk groups have been vaccinated.45 Cost should not be a barrier, as Medicare covers this vaccine.

10. Influenza and pneumococcus coinfection is common during epidemics, causing about one-fourth of influenza-related deaths.⁴⁶ The incidence of all-cause pneumonia is 29% less and mortality is 35% less in elders vaccinated against both influenza and pneumococcal disease. This also reduces and shortens hospitalizations.⁴⁷ Let’s remind elders that they need both pneumococcal and influenza vaccinations.

Conclusion

Pharmacists in many states can vaccinate against pneumococcal disease. However, patients often refuse the vaccine for various reasons. A small number (>7%) belong to the anti-vaccine movement. Elders, feeling that they are approaching life’s end, simply abandon preventive care.⁴⁸ The most important thing we can do is offer the vaccine and explain its importance.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a certified pharmacist immunizer.

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