Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia, bacteraemia, meningitis, otitis media and sinusitis. It is an encapsulated organism and the capsular polysaccharide is its most important virulence factor. Ninety one serotypes have been identified based on antigenic differences in their capsular polysaccharides, 15 of which cause the majority of diseases. Type-specific antibody to this capsular polysaccharide is protective.
There are 2 different types of pneumococcal vaccines – pneumococcal conjugate vaccine (PCV) and pneumococcal polysaccharide vaccine (PPV).
- While there are 2 conjugate vaccines available in Malaysia, PCV 10 and PCV 13, only the latter is approved for adult use.
- PCV 13 contains polysaccharide capsular antigens for 13 serotypes. The antigens are individually conjugated to diphtheria CRM197 conjugate protein, with aluminium phosphate used as an adjuvant.
- PCV 10 contains polysaccharide capsular antigens for 10 serotypes. The antigens are individually conjugated to tetanus and diphtheria toxoid protein, with aluminium phosphate used as an adjuvant
2. Pneumococcal polysaccharide vaccine (PPV)
- PPV23 contains pneumococcal capsular polysaccharides of 23 serotypes.PPV23 contains pneumococcal capsular polysaccharides of 23 serotypes.
Vaccine serotype coverage and effect of childhood immunisation program
Based on a review of 7 studies, which included 484 isolates causing IPD in Malaysia among all age groups, vaccine coverage for PCV 13 is estimated to be 75%. The estimated coverage for PPV23 is also similar (73%)
PCV reduces nasopharyngeal colonisation, thereby decreasing the spread of infection. Asymptomatic carriage is estimated to be 20-60% in children in contrast to 5-10% in adults. In countries with childhood vaccination coverage of >50%, the rate of invasive pneumococcal disease (IPD) in adults has decreased by 28% and rates of IPD due to strains covered by PCV13 has decreased by 40%. However, this has been accompanied by a 20% increase in IPD due to non-PCV13 strains in the elderly. Malaysia has introduced PCV in the national immunisation program at the end of 2020. So in the coming years, there will be a serotype shift in adults with relative increase in infections due to non-vaccine serotypes.
Vaccines Available in Malaysia
Polysaccharide vaccine (PPV)
- Pneumovax 23®
Merck Sharp & Dohme (M) Sdn Bhd/Merck Sharp & Dohme, US
Conjugate vaccine (PCV)
- Prevenar 13® (PCV13)
Pfizer (M) Sdn Bhd/Pfizer, Ireland
GlaxoSmithKline Pharmaceutical Sdn Bhd/GlaxoSmithKline, Belgium
Sequential dose of Pneumococcal vaccines
In PPV23-naïve individuals, PCV13 should be given first if both vaccines are to be given. In PPV23-naive adults, PCV13 improves the antibody response to subsequent PPV23 vaccination. Interval between vaccine administrations also may be critical to obtaining an optimal immunological effect. Longer intervals (ie, ≥ 1 year) may lead to improved immune responses against serotypes in both vaccines.
Coadministration with Other Vaccines
Pneumococcal vaccines can be administered concomitantly with influenza vaccines but at separate sites. Co-administration of Menactra® (Quadrivalent (ACWY) conjugate vaccine) with PCV13 should be avoided. This is because Menactra may interfere with the immune response against some pneumococcal serotypes. Menveo or Nimenrix can be co-administered with PCV13. If needed to be coadministered, administer Menactra 4 weeks after PCV13.
Contraindications and Adverse Events
- Contraindications to pneumococcal vaccines include anaphylaxis following a previous dose of any pneumococcal vaccine and persons with moderate or severe acute illness at the time of vaccination. However, minor illnesses such as upper respiratory infections are not a contraindication to vaccination.
- Data on the use of conjugate vaccine (PCV) during pregnancy and lactation is not available. For high-risk patients, it is recommended to administer PCV, either before a planned pregnancy or after delivery and cessation of breastfeeding.
- The safety of polysaccharide vaccine (PPV) for pregnant women has not been studied; however no adverse events have been reported among newborns whose mothers were inadvertently vaccinated during pregnancy. Similar to PCV, it is recommended to give PPV before a planned pregnancy or soon after delivery in high-risk individuals. PPV may be given to breastfeeding women.
- Local reactions include pain, redness and induration which usually last less than 48 hours. Systemic reactions such as fever, rash, myalgia and headache are uncommon. Severe reactions such as serum sickness and anaphylaxis are extremely rare.
- To date, the most frequently reported adverse events for pneumococcal vaccines received by the National Pharmaceutical Regulatory Agency (NPRA) include local site reactions such as injection site pain and swelling, fever, muscle pain and skin rash.
Evidence for Effectiveness
A meta-analysis found strong evidence of PPV efficacy against invasive pneumococcal disease in adults. There was efficacy against all-cause pneumonia in low-income but not high-income countries. However, PPV was not associated with substantial reductions in all-cause mortality. Vaccine efficacy against primary outcomes, seemed poorer in adults with chronic illness.
Six randomised controlled studies evaluated immunogenicity and safety of PCV13 in adults and showed that the conjugated vaccine elicited a greater immune response to the majority of the 13 serotypes compared to the PPV23.
Results of the CAPiTA trial conducted in Netherlands among 85,000 adults aged ≥65 years demonstrated 45.6% (95% CI = 21.8%-62.5%) efficacy of PCV13 against vaccine-type pneumococcal pneumonia, 45.0% (CI = 14.2%–65.3%) efficacy against vaccine-type nonbacteraemic pneumococcal pneumonia, and 75.0% (CI = 41.4%–90.8%) efficacy against vaccine-type IPD among adults aged ≥65 years.
- Bonten, M.J.,et al (2015). Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med;372(12):1114-25.
- Jauneikaite, E., Jefferies, J.M., Hibberd, M.L., Clarke, S.C. (2012). Prevalence of Streptococcus pneumoniae serotypes causing invasive and non-invasive disease in South East Asia: a review. Vaccine. 30(24):3503-14
- The Malaysian National Centre of Adverse Drug Reactions Database [Accessed: October 10, 2019]
- Marra, F., Vadlamudi, N.K. (2019). Efficacy and Safety of the Pneumococcal Conjugate-13 Valent Vaccine in Adults. Aging Dis. 1;10(2):404-418
- Moberley, S., Holden, J., Tatham, D.P., Andrews, R.M. (2013). Vaccines for preventing pneumococcal infection in adults. Cochrane Database Sys Rev.1:Cd000422
- National Pharmaceutical Regulatory Agency (NPRA) Ministry of Health Malaysia. Senarai Produk Vaksin Berdaftar Dengan Pihak Berkuasa Kawalan Dadah. Received on September 5, 2019
- Schmoele-Thoma, B., van Cleeff, M., Greenberg, R.N., Gurtman, A., Jones, T.R., Sundaraiyer, V., Gruber, W.C., Scott, D.A. (2019). Persistence of antibodies 1 year after sequential administration of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine in adults. Hum Vaccin Immunother.15(3):575-583
- Vadlamudi, N.K. et al (2019). Impact of the 13-valent pneumococcal conjugate vaccine among adults: A systematic review and meta-analysis. Clin Infect Dis; 69:34