Recommendations for useFor EPI The burden of pneumococcal disease is the greatest among the underprivileged children in India. The conjugate pneumococcal vaccines are thus of public health importance and ideally should be available to all children. However the high cost of PCV vaccines and the limited coverage of the currently available vaccine are impediments. GAVI has offered to supply PCV at a cost of 0.150.3 USD/dose to India for inclusion in the national immunization schedule and commits to extending this support till the year 2015. Also, broader serotype vaccines will be available in future. IAPCOI feels that Government of India should avail of this opportunity and apply for GAVI support, establish a pneumococcal disease surveillance system and set into motion a process for inclusion of PCV in EPI once broader serotype vaccines are available. High Risk Children Children at high risk of pneumococcal disease are listed in Table 1. The IAP COI recommends offering both PCV and PPV 23 to all high-risk children who can afford the vaccine in schedules discussed below. The PCV vaccines provide robust immune response and immune memory while PPV 23 provides expanded serotype coverage. If PCV is not affordable, at least PPV 23 should be given to high-risk children above 2 years of age. Healthy Children Pneumococcus is a cause of significant morbidity and mortality in children (especially those less than 2 years) and merits prevention. However as of current data, PCV7 covers only 55% of pneumococcal serotypes prevalent in India. Therefore IAPCOI recommends offering the currently available conjugate pneumococcal vaccine (PCV 7) after one to one discussion with parents in healthy children aged less than 2 years (Category 3) in schedule discussed below. The risk of invasive pneumococcal disease is significantly lower in healthy children above the age of 2 years and thus benefit achieved with vaccination of these children is likely to be low. Vaccination with single dose of PCV vaccine may be considered in children aged 2-5 years if demanded by parents. Since induction of immune system memory, reduction in carriage, efficacy against serotypes causing most invasive disease, and effectiveness against noninvasive syndromes (e.g., non bacteremic pneumonia and AOM) are superior with PCV, PCV is preferred to PPV 23 in this setting. There is no data to support pneumococcal vaccination in healthy children aged 5 years and above and is not recommended. Dose and Schedule Healthy children (PCV vaccine)
High risk children (PCV and PPV 23) (Table 1)
Only one repeat dose of PPV 23 is recommended only for children who have sickle cell disease, hyposplenia, asplenia, congenital/acquired immunodeficiency, those on immunosuppressive therapy, renal failure and nephrotic syndrome. The repeat dose of PPV 23 may be given after 3-5 years if the child is less than 10 years of age and after 5 years if child is aged more than 10 years. |
S. pneumoniae is responsible for 15-50% of all episodes of community acquired pneumonia, 30-50% of all cases of acute otitis media and a significant proportion of bacterial meningitis and bacteremia. It is estimated that 50% of the 2 million deaths due to pneumonia globally every year are attributable to S pneumoniae. Ninety serotypes of S. pneumoniae have been described of which a handful are responsible for most cases of invasive pneumococcal disease (IPD). Serotypes 14, 6, 19, 18, 9, 23, 7 are responsible for 85% of invasive pneumococcal disease in the developed world. Children under the age of 2 years are at greatest risk for invasive pneumococcal disease.
Data on prevalence of pneumococcal disease is scanty in India but it has been estimated that S. pneumoniae causes 6.6-22 million episodes of pneumonia and 200,000 deaths yearly from pneumonia in India. Results of the IBIS study in patients with invasive pneumococcal disease (IPD) indicate that serotypes 6, 1, 19, 14, 4, 5, 45, 12, 7, 23 are the most prevalent with serotypes 1 and 5 accounting for 30% of invasive pneumococcal disease. It is also known that serotypes causing pneumonia and otitis media differ from that causing invasive pneumococcal disease and usually reflect those serotypes present in the nasopharyngeal carriage.
Table 1: Children at high risk for pneumococcal disease
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Two vaccines are available; the unconjugated pneumococcal polysaccharide vaccine and the conjugate vaccines.
The unconjugated polysaccharide vaccine is a 23 valent vaccine (PPV 23) containing the following serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F. It is a T-cell independent vaccine that is poorly immunogenic below the age of 2 years, has low immune memory, does not reduce nasopharyngeal carriage and does not provide herd immunity.
It has at best 70% efficacy against prevention of invasive pneumococcal disease in the high-risk population but offers no protection against non-bacteremic pneumonia/otitis media. It is stored at 2 to 8° C and the dose is 0.5 ml subcutaneous/intramuscularly. It is a safe vaccine with occasional local side effects. Not more than two life time doses are recommended as repeated doses may cause immunologic hyporesponsiveness.
Conjugate pneumococcal vaccines (PCV) were developed primarily to address the problem of low immunogenicity of the polysaccharide vaccine in children below the age of 2 who are at high risk for pneumococcal disease. Conjugation of the pneumococcal polysaccharide of varying number of serotypes has been done with CRM 197 protein, protein D of non capsulated Hib, DT and TT and finally Men OMP. The only licensed PCV till date is CRM 197 PnC-7v (henceforth referred to as PCV 7) containing polysaccharide antigen of serotypes 4, 6B, 9V, 14, 18C, 19F and 23 linked to CRM 197.
The landmark randomized controlled NCKP trial in the US in around 40,000 children with three primary doses at 2, 4, 6 months and 1 booster at 12-15 months demonstrated 95% protection against IPD due to vaccine serotypes, 89% protection against any serotype, 4% protection against clinically diagnosed pneumonia, 30% protection against radiological pneumonia, 6% protection against acute otitis media and 20% protection against placement of tympanostomy tubes over a 5 year follow up.
No serious adverse effects were noted; 15-20% of the vaccinees had local side effects. The PCV 7 vaccine has been licensed for universal immunization in the US and 19 more countries of the developed world since the year 2000. The benefits seen in trials were replicated in program settings in USA, Canada and Australia among many other countries with dramatic declines noted in IPD, pneumonia admissions, AOM outpatient visits, prescription of antimicrobials for AOM, placement of tympanostomy tubes and antimicrobial resistance.
Apart from the direct benefits, a significant decline in pneumococcal disease in unvaccinated contacts including young infants, adults and the elderly was noticed due to herd effect resulting from reduced nasopharyngeal carriage. Though increase in disease due to non vaccine serotypes particularly 19A has been small till date compared to a vast decrease in overall burden of disease; continued surveillance to monitor serotype replacement is warranted.
Trials with an experimental 9 valent vaccine (CRM 197 as carrier) which incorporates serotypes 1 and 5 in South Africa showed a 20% decline in radiologically positive pneumonia in HIV non infected children and 13% decline in HIV infected. A trial in Gambia with 3 primary doses of the same 9 valent vaccine showed reduction in the incidence of invasive disease due to all serotypes by 50%, radiologically diagnosed pneumonia by 37%, clinical pneumonia by 7%, hospital admissions by 15% and all cause childhood mortality by 16%. The non significant protection against clinical pneumonia noted in trials is probably due to poor specificity of the case definition that allowed inclusion of several children with reactive airway disease and viral pneumonia.
A trial in the Czech Republic with an 11 valent vaccine (conjugated with protein D of Hib, additional serotypes of 1, 3, 5 and 7)) has shown 30% protection against AOM. The US and South African but not the Gambian trials have noted an increased incidence of reactive airway disease in vaccine recipients as compared to controls but causal association is not clear. Trials are currently underway with a 10 valent (protein D carrier and additional serotypes 1, 5, 7) and 13 valent vaccines (CRM 19 as carrier and additional serotypes 1, 3, 5, 6A, 7F and 19A). Studies with alternative schedules and fewer doses are also underway.
An expert
committee of the WHO has proposed 0.35 ėg/ml as the
serologic correlate for protection against IPD.