Pneumococcal pneumonia prevention among adults: is the herd effect of pneumococcal conjugate vaccination in children as good a way as the active immunization of the elderly?

Abstract

The indirect protection of adults as a result of pneumococcal conjugate vaccination of infants has been discussed from different epidemiological points of view. In some countries, including Italy, even after pediatric vaccination, vaccine serotypes are still responsible for most pneumonia and invasive diseases in the elderly. Although the Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) produced encouraging results, it has not showed the efficacy of the 13-valent conjugate vaccine in preventing pneumococcal community-acquired pneumonia regardless of the number of episodes and serotype. Addressing these points by monitoring the direct impact of adult vaccination in real life distinguished from the effects of herd immunity will assist public health decision-making on the most effective adult pneumococcal vaccination strategies.

Keywords: :

• CAPITA
• PCV13 efficacy
• Pneumococcal adult vaccination
• Pneumococcal disease
• Pneumococcal herd immunity

Pneumococcal infection is a leading cause of morbidity and mortality among adults worldwide1. Routine administration of the 7-valent conjugate vaccine (PCV7) since 2000 and of the second-generation conjugate vaccines (PCV10 and PCV13) since 2010 has reduced pneumococcal disease burden in both vaccinated and unvaccinated children, and indirectly among adults in many countries, owing to herd immunity2–6. The indirect protection of adults as a result of pediatric pneumococcal vaccination has been widely discussed and different epidemiological interpretations have been raised. Some authors have suggested that herd immunity can be as good a way of preventing pneumococcal disease in people aged 65 or older as vaccinating the over-65s with pneumococcal vaccines7^,8. Others argued that as carriage of PCV13 additional serotypes and the disease they cause become progressively less common, the direct benefit of vaccinating older people is likely to decline within a few years9^,10. Some other authors suggested that estimating this indirect benefit provides an important benchmark in monitoring the effect of the recommendations for PCV13 in adults ≥65 years of age in countries that have adopted direct vaccination2^,11.

Another scenario has been poorly debated so far. In Italy, even after pediatric vaccination with PCVs, vaccine serotypes are still responsible for most pneumonia and invasive diseases in the elderly population. PCV7 was introduced in the national childhood immunization schedule in 2006 and was replaced with PCV13 between 2010 and 201112–14. In 2011, PCV13 coverage reached nearly 90% on a national basis. Despite the considerable variability in coverage rates between regions, ranging from 44.7% to 98.5%15, universal routine vaccination had a substantial impact on the most severe cases of S. pneumoniae diseases and nasopharyngeal carriage in children aged under 5 years old16. With regard to adults, the Italian immunization program has recommended the administration of the 23-valent pneumococcal vaccine, concurrently with flu vaccine, in the elderly and in defined at risk subjects, reaching very low vaccination coverage17. The hospitalization rates for pneumococcal pneumonia and the incidence rates of invasive disease in the elderly population have remained stable or increased over the past decade, suggesting that the indirect benefit of routine infant vaccination did not occur in this age group17. Not yet published preliminary analyses by Martinelli et al. seem to indicate that in Italy more than 65% of pneumococcal pneumonia cases in older adults were caused by the serotypes targeted by PCV1318. Moreover, data from the National Surveillance of Invasive Bacterial Diseases showed that, despite an uncertain reduction in the proportion of PCV13 serotypes in the period 2010–2012, these were still responsible for about 56% of cases among over-65s17.

In 2014, the Italian scientific societies of Hygiene Preventive Medicine and Public Health, Pediatrics, General Medical Physicians and Respiratory Medicine issued recommendations on pneumococcal vaccination in adults19^,20. Up to 2014, based on regional recommendations, PCV13 has been offered to subjects ≥65 years of age according to a cohort model (immunization of one or more age cohorts) in eight regions and to those with at-risk conditions in seven regions21. Results from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) were expected to support the introduction of PCV13 in adults on a national basis.

The CAPITA study in The Netherlands demonstrated 45.6% (95% CI = 21.8%–62.5%) efficacy of PCV13 against a first episode of vaccine-type pneumococcal pneumonia, 45.0% (95% CI = 14.2%–65.3%) efficacy against a first episode of vaccine-type non-bacteremic and non-invasive pneumococcal pneumonia, and 75.0% (95% CI = 41.4%–90.8%) efficacy against a first episode of vaccine-type invasive disease among adults aged ≥65 years22. Moreover, the vaccine efficacy in preventing ‘all episodes of confirmed vaccine-type community-acquired pneumonia’ was shown, leading to the ACIP recommendations for all elderly persons11.

Surprisingly, the authors have not published data from the trial regarding the efficacy against ‘all episodes of confirmed pneumococcal community-acquired pneumonia’ regardless of the number of episodes and serotype. From a clinical and public health perspective, it is pivotal for countries introducing PCV13 use in adults to know whether the vaccine prevents cases caused not only by vaccine serotypes, but also by any pneumococcal strain, making routine vaccination cost-effective for health care systems. Unpublished preliminary data in Italy (Martinelli et al.) would seem to suggest an overall PCV13 effectiveness against both vaccine- and non-vaccine-type community-acquired pneumonia in adults, either among vaccinated subjects or among those unvaccinated, or in the subgroup of patients with comorbidities18. These early findings support the importance of implementing the new recommendations for routine use of PCV13 (and PPSV23 in series) in adults aged 65 years and over10^,23 in countries where pneumococcal disease persists in this age group.

Recently conducted analysis from CDC and other studies suggest that PCV13 indirect effect from the pediatric immunization program may take time to develop and establish among adults or may not continue to occur in those settings where it has already been observed. Since herd effect alone may not be sufficient to impact the burden of adult pneumococcal disease, particularly pneumonia, PCV13 use deserves the opportunity to demonstrate its potential impact through rapid uptake and improved vaccine coverage among adults in the short term24^,25.

When countries that have introduced or are introducing PCV13 among adults review their recommendations11, the results of studies monitoring the effect of vaccination in real life will be crucial for distinguishing the effects of herd immunity from the direct impact of adult vaccination. The few recent large studies published exploring the impact of both PCV13 and PPSV23 on community acquired pneumonia in the elderly showed some limitations related to their applicability to different scenarios, since they were performed in high-risk subgroups or in homogeneous population with a low incidence of pneumococcal disease (such as the CAPITA study)22^,26–29. Continuous surveillance of serotypes that still influence the burden of pneumococcal diseases and clinical efficacy data in adults are essential for decision-making on the most appropriate adult pneumococcal vaccination policies24.

Transparency

Declaration of funding

This editorial was not funded.

Declaration of financial/other relationships

R.P. has disclosed that she has received sponsorship from GSK and Sanofi Pasteur MSD; has received grants from Pfizer, Novartis and GSK; and was an advisor to Pfizer and Sanofi Pasteur MSD. F.F. has disclosed that he has received grants from Pfizer and Novartis. D.M. has disclosed that he has received grants from Pfizer, Novartis and GSK.

The CMRO peer reviewer on this manuscript has no relevant financial or other relationships to disclose.

Acknowledgments

The authors have no editorial or manuscript support to disclose.