Filling evidence gaps on the impact of pneumococcal vaccines
Authors: Daniel M Weinberger
Journal: The Lancet Infectious Diseases (2017)

Pneumococcal conjugate vaccines (PCVs) are now widely used for children around the world. Because of the high cost of the vaccine, donor organisations, such as GAVI, The Vaccine Alliance, have developed innovative financing schemes to encourage their introduction in low-income countries. Given these efforts, it is essential to quantify the effect of the vaccines on disease rates. In The Lancet Infectious Diseases, Grant Mackenzie and colleagues1Mackenzie GA Hill PC Sahito SM et al.Effect of the introduction of pneumococcal conjugate vaccination on pneumonia in The Gambia: population-based surveillance and case-control studies.Lancet Infect Dis. 2017; (published online June 7)http://dx.doi.org/10.1016/S1473-3099(17)30321-3Summary Full Text Full Text PDF PubMed Scopus (64) Google Scholar use data from a population-based surveillance study in The Gambia to show the important impact of PCV7/13 against pneumonia. This study fills a crucial gap in our understanding of the effects of PCVs in low-income settings. The effects of PCVs on invasive pneumococcal disease and pneumonia have been well documented, with data from randomised controlled trials and observational studies showing a consistent benefit across different epidemiological settings.2Loo JD Conklin L Fleming-Dutra KE et al.Systematic review of the indirect effect of pneumococcal conjugate vaccine dosing schedules on pneumococcal disease and colonization.Pediatr Infect Dis J. 2014; 33: S161-S171Crossref PubMed Scopus (76) Google Scholar, 3Loo JD Conklin L Fleming-Dutra KE et al.Systematic review of the effect of pneumococcal conjugate vaccine dosing schedules on prevention of pneumonia.Pediatr Infect Dis J. 2014; 33: S140-S151Crossref PubMed Scopus (77) Google Scholar, 4Feikin DR Kagucia EW Loo JD et al.Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites.PLoS Med. 2013; 10: e1001517Crossref PubMed Scopus (345) Google Scholar However, relatively few data are available on the population-level impact of routine PCV use in Africa, where the burden of disease is among the highest in the world. Although several studies have reported a benefit from the vaccine for invasive pneumococcal disease,5Von Gottberg A De Gouveia L Tempia S et al.Effects of vaccination on invasive pneumococcal disease in South Africa.N Engl J Med. 2014; 371: 1889-1899Crossref PubMed Scopus (258) Google Scholar, 6Mackenzie GA Hill PC Jeffries DJ et al.Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study.Lancet Infect Dis. 2016; 16: 703-711Summary Full Text Full Text PDF PubMed Scopus (120) Google Scholar most of the burden of disease caused by pneumococcus is thought to be attributable to pneumonia.7O'Brien KL Wolfson LJ Watt JP et al.Burden 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 (1843) Google Scholar Therefore, evaluations of the effect of PCVs against pneumonia in Africa are crucial for understanding the overall impact of the vaccine. The study by MacKenzie and colleagues has several notable strengths. The data on pneumonia are drawn from a well characterised population-based surveillance system, allowing for accurate estimates of incidence rates over time. Moreover, detailed clinical characteristics of the cases were known, allowing for evaluations of impact against several different definitions of pneumonia that vary in severity and specificity for pneumococcus. The study is also unusual in that the investigators did both an analysis of changes in diseases rates and a case-control analysis in the same population. Together, these analyses provide complementary pieces of evidence, with the analysis of disease rates providing an estimate of the population-level effect of the vaccine (direct and indirect effects) and the case-control analysis providing an estimate of direct effectiveness. The conclusions of the study are also strengthened by the inclusion of pre-specified sensitivity analyses, well justified control conditions, and detailed data on referral and testing patterns over time. There are also notable caveats to the interpretation of the results from this study. While the vaccine had an impressive effect on laboratory-confirmed pneumococcal pneumonia, radiologically-confirmed pneumonia, and hypoxic pneumonia, the relative declines in the more common clinical pneumonia were modest (0–15% decline, depending on the definition). This result is expected because clinical pneumonia is the least specific definition.8Madhi SA Klugman KP World Health Organisation definition of “radiologically-confirmed pneumonia” may under-estimate the true public health value of conjugate pneumococcal vaccines.Vaccine. 2007; 25: 2413-2419Crossref PubMed Scopus (56) Google Scholar However, this finding highlights the large remaining burden of pneumonia caused by other pathogens that needs to be addressed with other interventions. Additionally, the analysis was limited by methodological challenges. The short pre-vaccine baseline period (<2 years) made it impossible for the investigators to do a formal time series analysis, which could be used to detect and adjust for underlying secular trends in pneumonia rates—the simple pre-vaccine vs post-vaccine comparison might improperly attribute unrelated declines to the vaccine.9Bruhn CA Schuck-Paim C Kürüm E Taylor RJ Simonsen L Weinberger DM Improving assessments of population-level vaccine impact.Epidemiology. 2017; 28: 233-236Crossref PubMed Scopus (8) Google Scholar Finally, the results were sensitive to the use of a crude adjustment for changing referral patterns, which could potentially bias the results. Nonetheless, these data are among the best available evidence for the effects of PCVs on pneumonia in low-income settings. These findings are likely to be impactful as WHO begins to review the evidence for the effects of PCVs against different outcomes, the effects of different PCV dosing schedules, and the indirect (herd) effects of different vaccines.10WHOSAGE Working Group on Pneumococcal Conjugate Vaccines. 2016http://www.who.int/immunization/policy/sage/sage_wg_pcv_dec2016/en/Google Scholar Additional analyses of the trajectories of decline in different age groups in this population could help to resolve questions about the ability of a 3 + 0 dosing schedule (ie, three doses and no booster) to disrupt transmission and induce indirect protection in unvaccinated individuals. MacKenzie and colleagues' study presents an important set of estimates of the impact of PCVs against pneumonia in a low-income setting with a high burden of disease. This study can serve as a benchmark against which studies of PCV impact repeated in other countries in the region can be compared. I have previously received an investigator-initiated research grant from Pfizer and consulting fees from Pfizer, Merck, GSK, and Affinivax, but have no active relationships with these entities. Impact of the introduction of pneumococcal conjugate vaccination on pneumonia in The Gambia: population-based surveillance and case-control studiesThe introduction of PCV in The Gambia was associated with a moderate impact on the incidence of radiological pneumonia, a small reduction in cases of hospitalised pneumonia, and substantial reductions of pneumococcal and hypoxic pneumonia in young children. Low-income countries that introduce PCV13 with reasonable coverage can expect modest reductions in hospitalised cases of pneumonia and a marked impact on the incidence of severe childhood pneumonia. Full-Text PDF Open Access