Herd protection induced by pneumococcal conjugate vaccine
Authors: Keith P Klugman
Journal: The Lancet Global Health (2014)

Why is herd protection from pneumococcal disease important? The pneumococcus is the leading cause of death in children worldwide,1O'Brien KL Wolfson LJ Watt JP et al.for the Hib and Pneumococcal Global Burden of Disease Study TeamBurden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates.Lancet. 2009; 374: 893-902Summary Full Text Full Text PDF PubMed Scopus (1869) Google Scholar and children who die are likely to be those who are unable to access lifesaving antibiotics and pneumococcal conjugate vaccine (PCV). However, if vaccination of other children in the community stops transmission of the serotypes in the vaccine, then protection is provided to those most at risk of mortality, even if they are not given the vaccine themselves. The immunisation of infants with PCV in developed countries extends protection beyond direct protection of the immunised infants, to include children too young to be immunised,2Poehling KA Talbot TR Griffin MR et al.Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine.JAMA. 2006; 295: 1668-1674Crossref PubMed Scopus (383) Google Scholar adults with substantial risk of pneumococcal disease such as those infected by HIV,3Cohen AL Harrison LH Farley MM et al.for the Active Bacterial Core Surveillance TeamPrevention of invasive pneumococcal disease among HIV-infected adults in the era of childhood pneumococcal immunization.AIDS. 2010; 24: 2253-2262Crossref PubMed Scopus (60) Google Scholar and older people.4Simonsen L Taylor RJ Young-Xu Y Haber M May L Klugman KP Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalization and mortality in all age groups in the United States.MBio. 2011; 2: e00309-e00310Crossref Scopus (191) Google Scholar Indeed, the cost-effectiveness of PCV is such that in developed countries, despite the high cost of the vaccine, herd protection means use of the vaccine is cost saving.5Rubin JL McGarry LJ Strutton DR et al.Public health and economic impact of the 13-valent pneumococcal conjugate vaccine (PCV13) in the United States.Vaccine. 2010; 28: 7634-7643Crossref PubMed Scopus (76) Google Scholar More than 90% of hospital admissions averted by the vaccine in developed countries occur in unimmunised adults,4Simonsen L Taylor RJ Young-Xu Y Haber M May L Klugman KP Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalization and mortality in all age groups in the United States.MBio. 2011; 2: e00309-e00310Crossref Scopus (191) Google Scholar who are indirectly protected by the cessation of transmission to them of the serotypes in the vaccine. Do these herd benefits exist in developing countries and how best can we study herd protection in settings that do not have microbiological confirmation of invasive pneumococcal disease, much less the serotyping of isolated strains, and also do not have electronic International Classification of Diseases to record pneumonia hospital admissions and deaths? The first part of the question—do herd benefits exist in developing countries—is being answered by a series of reports that consistently suggest that the rollout of PCV in Africa seems to be associated with reductions in transmission of vaccine-type pneumococci in the community. In a trial of 7-valent PCV (PCV7) in The Gambia,6Roca A Hill PC Townend J et al.Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in The Gambia: a cluster-randomized trial.PLoS Med. 2011; 8: e1001107Crossref PubMed Scopus (96) Google Scholar and after PCV7 rollout in a 6-week, 14-week, and 9-month schedule in rural South Africa,7Nzenze SA Shiri T Nunes MC et al.Temporal changes in pneumococcal colonization in a rural African community with high HIV prevalence following routine infant pneumococcal immunization.Pediatr Infect Dis J. 2013; 32: 1270-1278Crossref PubMed Scopus (44) Google Scholar reductions in carriage of vaccine types were found in unimmunised children and adults in the community. In The Lancet Global Health Laura Hammitt and colleagues8Hammitt LL Akech DO Morpeth SC et al.Population effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and non-typeable Haemophilus influenzae in Kilifi, Kenya: findings from cross-sectional carriage studies.Lancet Glob Health. 2014; (published online May 28.)http://dx.doi.org/10.1016/S2214-109X(14)70224-4Google Scholar extend these data to PCV10 and show that in the coastal demographic surveillance area around Kilifi, Kenya, where PCV10 was introduced in January, 2011, a reduction in nasopharyngeal carriage of vaccine serotypes occurred not only in immunised children, but also in unimmunised children and adults over the next 2 years. To speed up the prospect of herd protection from PCV10 in the area, children younger than 5 years were offered the vaccine.8Hammitt LL Akech DO Morpeth SC et al.Population effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and non-typeable Haemophilus influenzae in Kilifi, Kenya: findings from cross-sectional carriage studies.Lancet Glob Health. 2014; (published online May 28.)http://dx.doi.org/10.1016/S2214-109X(14)70224-4Google Scholar Carriage of vaccine types was reduced by 66% (95% CI 38–82) in unimmunised children and adults at least 5 years old. Was the catch-up immunisation of children 12–59 months old the key to the rapid appearance of herd protection in older age groups? A similar level of reduction in carriage (61%) among unvaccinated children 1–5 years old was noted in the same 2 years after PCV10 introduction in Kenya without catch-up, in an urban slum,9Kim L Conklin L Bigogo G et al.Pneumococcal carriage in Kenyan children before and after 10-valent pneumococcal conjugate vaccine (PCV10) introduction, 2009 and 2012.Pneumonia. 2014; 3 (abstr).: 35Google Scholar suggesting that perhaps the key vaccine-type pneumococcal transmitters are probably younger than 2 years. Detailed data were available in Kilifi not only on carriage of vaccine types of pneumococci, but also on receipt of vaccine by the individuals in the study, and the overall vaccine coverage in the community was also known. The data suggest that vaccine coverage of around two-thirds of children younger than 5 years was sufficient to induce herd protection. This number is similar to the estimate of coverage of children (65–75%) needed to induce herd protection to PCV13 in Boston (MA, USA).10Loughlin AM Hsu K Silverio AL Marchant CD Pelton SI Direct and indirect effects of PCV13 on nasopharyngeal carriage of PCV13 unique pneumococcal serotypes in Massachusetts' children.Pediatr Infect Dis J. 2014; 33: 504-510Crossref PubMed Scopus (82) Google Scholar More data are needed in many developing countries before we can be confident about the coverage needed to induce herd protection in those settings. We need to know the number of immunisations that need to be given and their timing; the extent to which urban settings differ from rural; the effect, if any, of HIV infection in adults (particularly mothers) and infants on transmission; how herd protection shows patterns of social mixing; the role of carriage in adults; the importance of pneumococcal density for transmission; the role of serotype and viral infections in transmission; and the differences, if any, between PCV10 and PCV13 in induction of herd protection. A modification of the approach in the Massachusetts study10Loughlin AM Hsu K Silverio AL Marchant CD Pelton SI Direct and indirect effects of PCV13 on nasopharyngeal carriage of PCV13 unique pneumococcal serotypes in Massachusetts' children.Pediatr Infect Dis J. 2014; 33: 504-510Crossref PubMed Scopus (82) Google Scholar suggests a reasonable way forward to measure herd protection from vaccine-type pneumonia in developing countries. In this study, children were recruited and swabs taken when they attended a paediatric practice for any reason as the vaccine was rolled out in the state. Records were kept on the vaccination status of each child who was swabbed. Similarly, children younger than 5 years who come to a clinic or hospital in a developing country with signs and symptoms of pneumonia could have a nasopharyngeal swab taken and their vaccination status recorded from the time the vaccine is rolled out in the country. This method would allow the detection of carriage of invasive serotypes such as 1, 4, 5, and 7F, which are rarely found in carriage among healthy children. It would also provide data to calculate both the point in time and the rate of vaccine coverage at which carriage of vaccine-type pneumococci in unimmunised children with pneumonia equals that in the immunised children, which is the very point at which herd protection is induced. I have been a consultant for Pfizer, GlaxoSmithKline, and Merck. Population effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and non-typeable Haemophilus influenzae in Kilifi, Kenya: findings from cross-sectional carriage studiesAfter programmatic use of PCV10 in Kilifi, carriage of vaccine serotypes was reduced by two-thirds both in children younger than 5 years and in older individuals. These findings suggest that PCV10 introduction in Africa will have substantial indirect effects on invasive pneumococcal disease. Full-Text PDF Open Access