Use of Pneumococcal Vaccines for Influenza Pandemic Preparedness
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Influenza predisposes individuals to bacterial community-acquired pneumonia. During previous pandemics, secondary bacterial pneumonia has been an important cause of morbidity and mortality1-3 with 7-20 percent of persons with influenza infection during 1918-1919 developing secondary bacterial pneumonia, depending on the population and the phase of the pandemic4-6. Attack rates of secondary bacterial pneumonia during the less severe 20th century pandemics are less well-documented but are thought to be lower, perhaps five percent. Among those who acquired secondary bacterial pneumonia during pandemics, 20-36 percent died7. In virtually all published series, Streptococcus pneumoniae has been the most common etiology of secondary bacterial pneumonia, accounting for 25-75 percent of cases3,6,8-15. Severe pneumococcal pneumonia associated with inter-pandemic influenza has also been described16. The biological basis for the influenza-pneumococcus association is likely related to the neuraminidase activity of individual influenza A virus subtypes17.
A key difference between previous influenza pandemics and the next one is the widespread availability in the United States of two pneumococcal vaccines. An important question is whether these vaccines could be used to prevent secondary pneumococcal pneumonia.
A growing body of literature suggests that the 7-valent pneumococcal conjugate vaccine (PCV7) can prevent both invasive and non-invasive pneumococcal pneumonia caused by serotypes included in the vaccine. In clinical trials, 7- and 9-valent pneumococcal conjugate vaccines have been shown to be 20-37 percent effective against radiographically-confirmed pneumonia among young children18-21. In studies using active, population-based surveillance to evaluate the impact of PCV7 in the U.S., rates of all invasive pneumococcal disease (IPD) among children aged less than five years have declined by 75 percent while rates caused by PCV7-serotypes have declined by 98 percent22; approximately 20 percent of all IPD cases in this age group present with pneumonia. Routine use of PCV7 in the U.S. infant immunization program has also been shown to reduce all-cause pneumonia hospitalizations among children less than two years of age by 39 percent23. A South African trial of a 9-valent pneumococcal conjugate vaccine (PCV9) closely related to the 7-valent product showed that PCV9 could prevent secondary pneumococcal pneumonia among children. Children who had received PCV9 experienced 55% fewer hospitalizations for laboratory-confirmed influenza infection than children who had received placebo, suggesting that the vaccine was directly preventing pneumococcal pneumonia as a complication of influenza infection24.
Although direct vaccination of adults with pneumococcal conjugate vaccine has not been studied extensively, considerable evidence suggests a large public health impact of pediatric immunization on IPD among adults. Between 1998 and 2005, rates of IPD caused by PCV7 serotypes among adults declined by 75-85 percent, depending on the age group. In contrast to children where a minority of IPD manifests as pneumonia, approximately 75 percent of IPD cases among adults present as pneumonia, almost always requiring hospitalization25. These indirect effects of PCV7 vaccination of children apparently are not limited to IPD; in one study, routine use of PCV7 in children led to a 26 percent reduction in all-cause pneumonia hospitalizations among adults aged 18-39 years23. Reductions occurred in other age groups but were not statistically significant.
While evidence for the ability of pneumococcal conjugate vaccines to prevent invasive and non-invasive pneumococcal pneumonia is mounting, evidence for effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) is limited to pneumococcal bacteremia, where published studies estimate the effectiveness to be 44%-81%26,27. The duration of protection of PPV23 may be greater than five years among persons aged less than 65 years but is probably less than five years among people aged greater than 65 years28. Importantly, evidence of effectiveness of PPV23 against pneumonia without bacteremia is lacking despite multiple studies that have looked for such an effect29.
CDC’s Advisory Committee on Immunization Practices (ACIP) recommends a single dose of pneumococcal polysaccharide vaccine for all people 65 years and older and for persons 2 to 64 years of age with certain high-risk conditions (Table 1)30. A single revaccination at least five years after initial vaccination is recommended for people 65 years and older who were first vaccinated before age 65 years.
For children, four doses of PCV7 are recommended by the ACIP, one each at two, four, six, and 12 to 15 months of age, with catch-up schedules for children who start the series late or who miss doses (Table 1)31.
The ACIP is currently reviewing existing recommendations for routine use of pneumococcal conjugate and polysaccharide vaccines. At this time, there are no plans to change existing recommendations for PCV7 or PPV23 use specifically in preparation for a possible influenza pandemic. Instead, emphasis should be placed on increasing vaccination coverage among those for whom the vaccines are already recommended. Administering pneumococcal vaccines during a pandemic may be complicated by personnel shortages due to illness and vaccine shortages due to excessive demand. Therefore, ensuring that all persons with pneumococcal vaccine indications have been vaccinated before a pandemic occurs may be the best way to prevent pneumococcal disease during a pandemic (Table 2)30,31.
To reduce the burden of secondary bacterial pneumonia during the next influenza pandemic, CDC urges healthcare providers and state immunization programs to improve pneumococcal vaccination delivery systems for patients under their care so that national vaccine coverage increases. The ideal time to accelerate vaccination efforts is during the inter-pandemic and pandemic alert phases (phases 1 through 3), when the threat of a pandemic is not imminent. At this time, CDC does not recommend changes to existing recommendations for use or stockpiling of pneumococcal vaccines in anticipation of a pandemic.
Table 1. U.S. recommendations for use of pneumococcal vaccines30,31.
| | Pneumococcal polysaccharide vaccine | Pneumococcal conjugate vaccine |
|---|
Universal vaccination | Persons 65 years and older | Children <2 years of age |
| | | |
Medical Indications | Persons 2-64 years with | Children 24-59 months with |
|---|
| | - chronic cardiovascular disease (congestive heart failure and cardiomyopathies)
- chronic pulmonary disease including chronic obstructive pulmonary disease and emphysema but excluding asthma
- diabetes mellitus
- alcoholism
- chronic liver disease, including cirrhosis
- cerebrospinal fluid leaks
- functional or anatomic asplenia including sickle cell disease and splenectomy
- living situations in special environments or social situations including Alaska Natives and certain American Indian populations
- immuno-compromised conditions including HIV infection, leukemia, lymphoma, Hodgkin’s disease, multiple myeloma, generalized malignancy, chronic renal failure, nephrotic syndrome; or those receiving immunosuppressive chemotherapy (including corticosteroids); and those who have received an organ or bone marrow transplant
| - chronic cardiac disease, particularly cyanotic congenital heart disease and cardiac failure
- chronic pulmonary disease, excluding asthma unless on high dose corticosteroid therapy
- diabetes mellitus
- cerebrospinal fluid leaks
- sickle cell disease and other hemoglobinopathies
- congenital or acquired asplenia or splenic dysfunction
- renal failure and nephrotic syndrome
- immunocompromising conditions, including HIV; congenital B- (humoral) or T-lymphocyte immunodeficiencies; complement (c1, c2, c3, and c4) deficiencies; phagocytic disorders, excluding chronic granulomatous disease
- diseases associated with immuno-suppressive therapy or radiation therapy, including malignant neoplasms, leukemias, lymphomas, Hodgkin’s disease, or solid organ transplantation
|
Consider use of vaccine in: | | All children 24-59 months with priority given to children aged 24-35 months, children of Alaska Native or American Indian descent, children of African-American descent, and children who attend day care centers |
Table 2. Population-based interventions to improve vaccination coverage, ranked as high priority in the Guide to Community Preventive Services32.
Increasing community demand for vaccination services:
Client recall/reminder
Multi-component interventions with education
Vaccination requirements for childcare and school attendance
Community-wide education only
Clinic-based education only
Client or family incentives
Client-held medical records
Enhancing access to vaccination services:
Reducing out-of-pocket costs
Expanding access in healthcare settings through multi-component interventions
Expanding access only in healthcare settings
Expanding access in Women, Infants, & Children (WIC) programs
Introducing home visits
Enhancing school programs
Enhancing childcare center programs
Provider-based interventions:
Provider reminder/recall
Assessment and feedback for providers
Standing orders for adults
Standing orders for children
Provider education only
References
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2. Robertson L, Caley JP, Moore J. Importance of Staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A. Lancet 1958;2(7040):233-6.
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17. McCullers JA. Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev 2006;19(3):571-82.
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19. Cutts FT, Zaman SM, Enwere G, et al. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet 2005;365(9465):1139-46.
20. Hansen J, Black S, Shinefield H, et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: updated analysis using World Health Organization standardized interpretation of chest radiographs. Pediatr Infect Dis J 2006;25(9):779-81.
21. Klugman KP. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection.[see comment]. International Journal of Infectious Diseases 2003;7 Suppl 1:S27-31.
22. Moore M, Pilishvili T, Thomas A, et al. Geographic Trends in Invasive Pneumococcal Disease caused by Nonvaccine Serotypes. Infectious Diseases Society of America 44th Annual Meeting 2006, Toronto, Canada.
23. Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet 2007;369(9568):1179-86.
24. Madhi SA, Klugman KP. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med 2004;10(8):811-3.
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