Long-term surveillance of the effect of PCV13: the future challenge in Africa
Authors: Corinne Levy, Robert Cohen
Journal: The Lancet Infectious Diseases (2016)

Pneumococcal infections are a leading cause of morbidity and mortality in children. In Africa, the greatest burden of pneumococcal disease and most associated deaths occur in children younger than 5 years.1O'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 (1851) Google Scholar In 2008, this continent still accounted for more than half of the 541 000 deaths caused by pneumococcal disease in this age group.2World Health OrganizationEstimated Hib and pneumococcal deaths for children under 5 years of age, 2008 (updated December, 2013).http://www.who.int/immunization/monitoring_surveillance/burden/estimates/Pneumo_hib/en/Google Scholar The effectiveness of the seven-valent pneumococcal conjugate vaccine (PCV7) has been shown in many countries—the incidence of invasive pneumococcal disease has fallen in all age groups, especially in children younger than 2 years.3Centers for Disease Control and PreventionDirect and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease—United States, 1998–2003.MMWR Morb Mortal Wkly Rep. 2005; 54: 893-897PubMed Google Scholar However, in some countries, this decrease was mitigated by an increased incidence of invasive pneumococcal disease caused by non-vaccine serotypes, most belonging to the extended-spectrum PCV.4Miller E Andrews NJ Waight PA Slack MP George RC Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study.Lancet Infect Dis. 2011; 11: 760-768Summary Full Text Full Text PDF PubMed Scopus (521) Google Scholar Soon after the switch from PCV7 to PCV13, many countries such as the USA, France, the UK, and Israel reported the expected pronounced decrease in invasive pneumococcal disease.5Ben-Shimol S Greenberg D Givon-Lavi N et al.Early impact of sequential introduction of 7-valent and 13-valent pneumococcal conjugate vaccine on IPD in Israeli children <5 years: an active prospective nationwide surveillance.Vaccine. 2014; 32: 3452-3459Crossref PubMed Scopus (108) Google Scholar, 6Lepoutre A Varon E Georges S et al.Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001–2012.Vaccine. 2015; 33: 359-366Crossref PubMed Scopus (108) Google Scholar, 7Moore CE Paul J Foster D et al.Reduction of invasive pneumococcal disease 3 years after the introduction of the 13-valent conjugate vaccine in the Oxfordshire region of England.J Infect Dis. 2014; 210: 1001-1011Crossref PubMed Scopus (76) Google Scholar, 8Simonsen L Taylor RJ Schuck-Paim C Lustig R Haber M Klugman KP Effect of 13-valent pneumococcal conjugate vaccine on admissions to hospital 2 years after its introduction in the USA: a time series analysis.Lancet Respir Med. 2014; 2: 387-394Summary Full Text Full Text PDF PubMed Scopus (156) Google Scholar The high effectiveness of the PCV10 vaccine has also been shown in Finland for invasive pneumococcal disease and clinically suspected invasive pneumococcal disease.9Palmu AA Jokinen J Nieminen H et al.Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal disease: a cluster-randomised trial.Lancet Respir Med. 2014; 2: 717-727Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar These results led to PCVs being classified among the more potent available vaccines: in the USA, 55 000 deaths from pneumococcus-related diseases in children were prevented by PCVs between 2001 and 2013.10Whitney CG Zhou F Singleton J Schuchat A Centers for Disease Control and PreventionBenefits from immunization during the vaccines for children program era—United States, 1994–2013.MMWR Morb Mortal Wkly Rep. 2014; 63: 352-355PubMed Google Scholar However, in developed countries, which benefit from favourable living conditions and well organised health-care systems, the early (and sustained) assessment of PCV performance is helped by active and well established surveillance of invasive pneumococcal disease. The burden of invasive pneumococcal disease remains highest in low-income countries. Some had introduced PCVs through the GAVI Alliance with a small self-financed contribution. However, little published evidence is available about the effect of PCVs on invasive pneumococcal disease in this context, because of the challenges in surveillance. In The Lancet Infectious Diseases, Grant Mackenzie and colleagues report the results of a well designed population-based active and standardised surveillance study for invasive pneumococcal disease in The Gambia before and after PCV implementation (PCV7 in 2009 and PCV13 in 2011).11Mackenzie 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; (published online Feb 17.)http://dx.doi.org/10.1016/S1473-3099(16)00054-2PubMed Google Scholar Apart from the reported expected findings, of significance is the admirable effort by the authors to do such a study by rigorously standardising the clinical and laboratory aspects of the surveillance. The project involved several teams, with conceptualisation beginning about 10 years ago. The authors investigated 14 650 patients and identified 320 cases of invasive pneumococcal disease, to do a robust assessment of the effect of PCV13. Despite suboptimal PCV13 coverage, in children 2–23 months of age, the incidence of invasive pneumococcal disease fell by 55% (95% CI 30–71) and that of PCV13 serotype prevalence fell by 82% (95% CI 64–91). In older children (2–4 years of age), the incidence of invasive pneumococcal disease fell by 56% (95% CI 25–75) owing to a 68% (95% CI 39–83) reduction in the prevalence of PCV13 serotypes, which suggests that a combination of direct and herd protection effects were in force. All these results support the substantial benefit of PCVs introduced in African countries. However, two concerns draw our attention: first, the report of a slight increase in invasive pneumococcal disease incidence in all age groups (except adults) in 2014, and second, a significant increase in prevalence of non-PCV13 serotypes, especially in children aged 2–59 months, in whom the incidence of invasive pneumococcal disease almost doubled. This potentially worrying result should be balanced by the fact that the serotypes that emerged are unlikely to be as invasive as those included in the PCVs.12Varon E Cohen R Bechet S Doit C Levy C Invasive disease potential of pneumococci before and after the 13-valent pneumococcal conjugate vaccine implementation in children.Vaccine. 2015; 33: 6178-6185Crossref PubMed Scopus (65) Google Scholar In the post-PCV13 era, the main non-PCV13 serotypes that the authors reported in children 2–59 months old were serotypes 12F, 10A, 15A, 35B, and 16F.11Mackenzie 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; (published online Feb 17.)http://dx.doi.org/10.1016/S1473-3099(16)00054-2PubMed Google Scholar A recent study showed that of the non-PCV13 serotypes, only two—24F and 12F—had high disease potential in the PCV13 era.12Varon E Cohen R Bechet S Doit C Levy C Invasive disease potential of pneumococci before and after the 13-valent pneumococcal conjugate vaccine implementation in children.Vaccine. 2015; 33: 6178-6185Crossref PubMed Scopus (65) Google Scholar In Mackenzie and colleagues' study in The Gambia, serotype 24F was rare (only two cases were reported) in the PCV13 era, so serotype 12F remained the only one with high disease-causing potential.11Mackenzie 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; (published online Feb 17.)http://dx.doi.org/10.1016/S1473-3099(16)00054-2PubMed Google Scholar Besides the reduced incidence of invasive pneumococcal disease in developed countries, the spectrum and profile of invasive pneumococcal disease has changed following the changed serotype distribution, and the proportion of patients with underlying illnesses has increased.13Levy C Varon E Bechet S Cohen R Effect of the 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children.Clin Infect Dis. 2016; 62: 131-132Crossref PubMed Scopus (12) Google Scholar We have shown that patients with meningitis are infected more frequently with non-PCV13 serotypes than other serotypes, whereas serotypes implicated in pneumococcal pneumonia are usually PCV13 serotypes, especially 1, 7F, 19A, and 3.13Levy C Varon E Bechet S Cohen R Effect of the 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children.Clin Infect Dis. 2016; 62: 131-132Crossref PubMed Scopus (12) Google Scholar These results agree with those reported by Kaplan and colleagues,14Kaplan SL Barson WJ Lin PL et al.Early trends for invasive pneumococcal infections in children after the introduction of the 13-valent pneumococcal conjugate vaccine.Pediatr Infect Dis J. 2013; 32: 203-207Crossref PubMed Scopus (222) Google Scholar showing greater reduction in cases of pneumococcal bacteraemia, pneumonia, and mastoiditis than those of meningitis after PCV13 introduction in eight children's hospitals in the USA. Similarly, the data reported by Mackenzie and colleagues11Mackenzie 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; (published online Feb 17.)http://dx.doi.org/10.1016/S1473-3099(16)00054-2PubMed Google Scholar show that patients with meningitis were infected more frequently with non-PCV13 serotypes than PCV13 serotypes (44·7% vs 26·3%), whereas for pneumonia, the rates were reversed (21·7% vs 56·1%).11Mackenzie 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; (published online Feb 17.)http://dx.doi.org/10.1016/S1473-3099(16)00054-2PubMed Google Scholar This serotype distribution clearly explains the notable decrease in pneumonia cases and the slight fall in meningitis cases. With a more prolonged period after PCV13 introduction, the expected decrease in pneumonia cases will be substantial. This study has important implications for the introduction of PCVs in all African countries, where the rates of invasive pneumococcal disease remain around ten-fold higher than those in developed countries. However, maintenance of invasive pneumococcal disease surveillance is essential to clarify the role of PCVs in changing the serotype incidence, in view of the possible increase in invasive pneumococcal disease cases related to non-vaccine serotypes. The authors' institution (ACTIV) has received research grant support from Pfizer, GlaxoSmithKline, and Sanofi Pasteur MSD. CL has received personal fees from Pfizer and Novartis outside the submitted work. RC has received personal fees from Pfizer, GSK, Sanofi, and Novartis outside the submitted work. Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance studyThe Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2–59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2–4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease. Full-Text PDF Open Access