Last Updated : 8/1/2015
Ira Shah
Pneumococcal disease is caused by Streptococcus pneumoniae (pneumococcus). There are over 90 serotypes based on differences in the composition of the polysaccharide capsule that surrounds it. However, the majority of pneumococcal disease in infants is associated with a small number of these serotypes, which may vary by region. Globally, about 20 serotypes are associated with>80% of invasive pneumococcal disease worldwide. Invasive pneumococcal infections include pneumonia, meningitis and febrile bacteremia. It can also lead to otitis media, sinusitis and bronchitis.

Pneumococcal disease burden: At least 1 million children die of pneumococcal disease every year. In developing countries, infants under three months of age are at particularly high risk, especially for pneumococcal meningitis. In spite of the importance of pneumococcal disease, there is a scarcity of information on disease burden, particularly from developing countries. This is partly due to the inherent problem of obtaining an etiological diagnosis in cases of pneumonia. National estimates of pneumococcal attributable deaths among children under five years of age ranged from 1,41,000 in India to fewer than 10 deaths in 46 countries in the year 2000. As per World Health Organization, 19% of all pneumococcal deaths under five years of age occurred in India.In Europe and the United States, pneumococcal pneumonia is the most common community-acquired bacterial pneumonia. The risk of disease is highest among young children, older adults, smokers and persons with certain chronic illnesses.

It is estimated that in USA, annually pneumococcus leads to 3000 cases of meningitis, 50,000 cases of sepsis, 500,000 cases of pneumonia and 7 million cases of ear infection with 40,000 deaths. . Vaccination is the only available tool to prevent pneumococcal disease.

Pneumococcal transmission: Pneumococcus is an exclusively human pathogen, usually carried harmlessly and often asymptomatically in the nasopharynx, especially by children. Transmission occurs by direct contact with respiratory secretions or inhalation of respiratory aerosols from carriers or from individuals with pneumococcal disease.

Types of Pneumococcal vaccine
Justification for pneumococcal vaccine: Vaccination is the only available tool to prevent pneumococcal disease. The recent development of widespread microbial resistance to essential antibiotics underlines the urgent need for pneumococcal vaccines. Pneumococcal resistance to essential antimicrobials such as penicillins, cephalosporins and macrolides is a serious and rapidly increasing problem worldwide.

Pneumococcal vaccine: There are 2 types of pneumococcal vaccines polysaccharide unconjugated pneumococcal vaccine and conjugated pneumococcal vaccine. Immunity following pneumococcal disease is directed primarily against the capsular serotype involved.

Polysaccharide pneumococcal vaccine: It is based on the 23 most common serotypes, has an overall protective efficacy of about 60%-70%. Children under two years of age, and persons suffering from immunodeficiency do not consistently develop immunity following vaccination, thus reducing the protective value of the vaccine in some major target groups for pneumococcal disease. Due to reduced immunogenicity and unclear efficacy in children under two years of age, the current polysaccharide vaccine is not recommended for routine immunization of children in this age group.

Conjugated pneumococcal vaccine: The original seven valent conjugated pneumococcal vaccine (PCV7) was produced from the seven most prevalent strains of S. pneumoniae in the US. The bacterial capsule sugar was linked to CRM197, a non-toxic recombinant variant of diphtheria toxin. The original 7-valent formulation contains serotypes 4, 6B, 9V, 14, 18C,19F, and 23F. While the proportion of serotypes in children potentially covered by PCV-7 varies markedly from region to region and even from country to country; in most places, at least 50% of invasive isolates from children aged < 5 years are represented by PCV-7. It resulted in protection of 80% of the pneumococcal disease in infants in the US. In Western Europe, at least two-thirds of all isolates are covered by PCV-7.

Efficacy of PCV 7:The incidence of invasive pneumococcal disease due to vaccine serotypes has decreased substantially after the introduction of PCV-7 in the US in vaccinated and unvaccinated children. According to the Centers for Disease Control and Prevention's Active Bacterial Core surveillance system, from 1998-1999 through 2007, overall and PCV7-serotype-specific IPD rates decreased by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100 000 population), respectively. The largest reductions in IPD incidence have been observed in children aged less than 5 years, the target population of the vaccination program, with remarkable reductions in all and PCV7-serotype-specific IPD rates of 76 and 100%, respectively. In addition to the substantial reductions in the incidence of IPD among vaccinated children, the introduction of PCV7 in 2000 has also resulted in marked reductions in nasopharyngeal colonization with vaccine serotypes and subsequent reductions in IPD incidence among age groups that were not vaccinated. This indirect population protection benefited both infants who were too young to receive PCV7 and children or adults for whom PCV7 was not recommended. Declines in IPD have also been consistently documented in high-risk subjects, including those with HIV and children with sickle cell disease. However, significant increases in the incidences of disease due to serotypes 3, 15, 19A, 22F, and 33F were observed among children during this period; serotype 19A has become the predominant cause of invasive disease in US children.

Safety and immunogenicity of PCV 7: PCV-7 is well tolerated and has a good safety profile. It induces a T-cell dependent immune response characterized by immune memory as well as a booster antibody response on subsequent challenge with the pneumococcal polysaccharides included in the vaccine. It also stimulates mucosal immunity, resulting in reduced nasopharyngeal carriage. The herd immunity effect observed with this vaccine is most likely the result of reduced transmission of vaccine-type pneumococci in the community as a result of decreased carriage.

Conjugated Pneumococcal 13 valent Vaccine (PCV13): A recent report on global serotype distribution developed by Global Alliance for Vaccines and Immunisation (GAVI) concluded that serotype 1, 5, 14 are the most common serotypes in children aged less than 5 years in regions with the highest pneumococcal disease burden (Africa, Asia, and Latin American countries). The World Health Organization statement on pneumococcal conjugate vaccine noted that the inclusion of additional serotypes beyond the ones included in PCV7 will significantly help to reduce the global burden of pneumococcal disease. A second-generation 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended for universal immunization of children through age 5 years in 2010. This vaccine acts against serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. Prelicensure studies demonstrated PCV13 to be at least as immunogenic as PCV7 for common serotypes, and to induce comparable levels of antibodies for serotypes unique to PCV13. Each of the six new serotypes selected for PCV13 represents a specific target for prevention that is an important cause of 'epidemic' IPD on a global basis , or has emerged as a frequent cause of invasive disease in at least some of the countries where PCV7 has been introduced (19A, 7F, 3), or represents a cross-reactive serotype that has persisted as a potential cause of IPD (6A) or expanded its role in colonization in children but may not as yet have been demonstrated to be a frequent cause of IPD (6C).

Conjugated Pneumococcal 10 valent Vaccine (PCV10): In 2009 a 10-valent pneumococcal conjugate vaccine (PCV10) covering the 7 serotypes in PCV7 plus three extra serotypes 1, 5 and 7F was licensed for use in infants and children up to the age of 2 years for the prevention of invasive pneumococcal disease. PCV10 includes serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F

Dosing and Schedule
Infants and children who have not previously received PCV: Indian Academy of Pediatrics recommends 3 doses at 6, 10 and 14 weeks with a booster at 15 months. Infants receiving their first dose at age <11 months should receive 3 doses of PCV13 at intervals of approximately 4 weeks with a booster at 15 months. Children aged 12--23 months should receive 2 doses with an interval of at least 8 weeks between doses. Unvaccinated healthy children aged 24-59 months should receive a single dose of PCV.

Children incompletely vaccinated with PCV: infants less than 24 months should receive one or more doses based on the number of doses of PCV received to date and the age of the child.

Children who have received four doses of PCV7 or PCV9: a single dose of PCV10 or PCV13 is recommended for all children 14 through 59 months of age.

Children 6 through 18 years of age with high-risk conditions: a single dose of PCV may be administered for who are at increased risk for invasive pneumococcal disease because of sickle cell disease, HIV infection or other immunodeficiency state, regardless of whether they have previously received PCV7 or pneumococcal polysaccharide vaccine (PPSV) 23.


Contributor Information and Disclosures

Ira Shah
Consultant Pediatrician, B J Wadia Hospital for Children, Mumbai, India

First Created : 1/10/2006


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