13-valent pneumococcal conjugate vaccine in Africa
Authors: Robert Cohen, Corinne Levy
Journal: The Lancet Global Health (2017)

Pneumococcus is the leading cause of bacterial infections in human beings and is a major source of mortality and morbidity worldwide. The incidence of pneumococcal diseases in children varies among populations and countries, and differences have been attributed to several factors, including overcrowding, poverty, underlying conditions (such as HIV infection), and genetics. Accumulation of many of these factors in low-income and middle-income countries, particularly those in Africa, accounts for why a large amount of the global burden of pneumococcal diseases and most of the related deaths are in these countries.1Global Burden of Disease Study 2013 CollaboratorsGlobal, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet. 2015; 386: 743-800Summary Full Text Full Text PDF PubMed Scopus (4421) Google Scholar Therefore, use of a vaccine effective against pneumococcus for children in low-income and middle-income countries is crucial.1Global Burden of Disease Study 2013 CollaboratorsGlobal, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet. 2015; 386: 743-800Summary Full Text Full Text PDF PubMed Scopus (4421) Google Scholar, 2Madhi SA Nunes MC The potential impact of pneumococcal conjugate vaccine in Africa: considerations and early lessons learned from the South African experience.Hum Vaccin Immunother. 2016; 12: 314-325Crossref PubMed Scopus (23) Google Scholar, 3Mackenzie 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 South Africa was the first African country to implement the seven-valent pneumococcal conjugate vaccine (PCV7) in its routine infant immunisation programme (in 2009), with the novel schedule aligned to WHO's recommended Expanded Programme on Immunisation (EPI)—ie, a 2 + 1 schedule with doses at age 6, 14, and 40 weeks—with no catch-up programme for older children.2Madhi SA Nunes MC The potential impact of pneumococcal conjugate vaccine in Africa: considerations and early lessons learned from the South African experience.Hum Vaccin Immunother. 2016; 12: 314-325Crossref PubMed Scopus (23) Google Scholar The switch to the 13-valent vaccine (PCV13) in 2011 was associated with a catch-up programme for children younger than 30 months, and the coverage of three doses was estimated at 99% in 2012.2Madhi SA Nunes MC The potential impact of pneumococcal conjugate vaccine in Africa: considerations and early lessons learned from the South African experience.Hum Vaccin Immunother. 2016; 12: 314-325Crossref PubMed Scopus (23) Google Scholar After the switch from PCV7 to PCV13, the first published study from South Africa entailed national laboratory-based surveillance and showed a decline in overall cases of invasive pneumococcal disease, from 54·8 to 17·0 per 100 000 person-years for children younger than 2 years.4von 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 However, a part of this decrease had been attributed to improvements in the care of people with HIV infection.2Madhi SA Nunes MC The potential impact of pneumococcal conjugate vaccine in Africa: considerations and early lessons learned from the South African experience.Hum Vaccin Immunother. 2016; 12: 314-325Crossref PubMed Scopus (23) Google Scholar, 4von 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, 5Cohen C von Mollendorf C de Gouveia L et al.Effectiveness of 7-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in HIV-infected and -uninfected children in South Africa: a matched case-control study.Clin Infect Dis. 2014; 59: 808-818Crossref PubMed Scopus (37) Google Scholar In the same country, a matched case-control study from 2010 to 2012 showed effectiveness of PCV7 against invasive pneumococcal disease due to PCV7 serotypes in children without HIV infection (two or more doses of PCV7, 74% effectiveness, 95% CI 25 to 91) but not in those with HIV infection.5Cohen C von Mollendorf C de Gouveia L et al.Effectiveness of 7-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in HIV-infected and -uninfected children in South Africa: a matched case-control study.Clin Infect Dis. 2014; 59: 808-818Crossref PubMed Scopus (37) Google Scholar After implementation of PCV13, population-based active surveillance of invasive pneumococcal disease in The Gambia showed a reduction in the overall incidence of the disease of 55% (95% CI 30 to 71) in children younger than 2 years, owing to the striking decrease in disease caused by PCV13 serotypes (82%, 95% CI 64 to 91).3Mackenzie 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 The effectiveness of PCV7 and PCV13 in high-income countries has been well documented, with two case-control studies of PCV13 effectiveness done in the USA and the UK.6Moore MR Link-Gelles R Schaffner W et al.Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study.Lancet Respir Med. 2016; 4: 399-406Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 7Miller E Andrews NJ Waight PA Slack MP George RC Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine.Vaccine. 2011; 29: 9127-9131Crossref PubMed Scopus (172) Google Scholar However, the effectiveness reported in high-income countries is not automatically transposable to countries of low and middle income: the proportion of serotypes covered by pneumococcal conjugate vaccines could be different, as could the serotype replacement. Few studies have been done in low-income and middle-income countries, particularly in Africa. In The Lancet Global Health, Cheryl Cohen and colleagues present findings of a case-control study from South Africa of PCV13 effectiveness against invasive pneumococcal disease in children not infected with HIV and in those with HIV infection, from 2012 to 2014.8Cohen C von Mollendorf C de Gouveia L et al.for the South African IPD Case-Control Study GroupEffectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study.Lancet Glob Health. 2017; (published online Jan 27.)http://dx.doi.org/10.1016/S2214-109X(17)30043-8Summary Full Text Full Text PDF Scopus (37) Google Scholar Cohen and colleagues found the 2 + 1 schedule effective for preventing invasive pneumococcal disease caused by PCV13 serotypes in children without HIV infection (two or more doses of PCV13, 85% effectiveness, 95% CI 37 to 96).8Cohen C von Mollendorf C de Gouveia L et al.for the South African IPD Case-Control Study GroupEffectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study.Lancet Glob Health. 2017; (published online Jan 27.)http://dx.doi.org/10.1016/S2214-109X(17)30043-8Summary Full Text Full Text PDF Scopus (37) Google Scholar However, PCV13 was not effective for overall invasive pneumococcal disease in children not infected with HIV (52%, 95% CI −12 to 79) nor for PCV13-serotype invasive pneumococcal disease in children with HIV infection (91%, −35 to 100).8Cohen C von Mollendorf C de Gouveia L et al.for the South African IPD Case-Control Study GroupEffectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study.Lancet Glob Health. 2017; (published online Jan 27.)http://dx.doi.org/10.1016/S2214-109X(17)30043-8Summary Full Text Full Text PDF Scopus (37) Google Scholar The findings of Cohen and colleagues fit with those of current international studies of the effect of PCV13, confirming the great efficacy of PCV13 against pneumococcal disease caused by PCV13 serotypes.3Mackenzie 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, 4von 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, 6Moore MR Link-Gelles R Schaffner W et al.Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study.Lancet Respir Med. 2016; 4: 399-406Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 7Miller E Andrews NJ Waight PA Slack MP George RC Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine.Vaccine. 2011; 29: 9127-9131Crossref PubMed Scopus (172) Google Scholar One concern draws our attention: the difference in distribution of non-vaccine serotypes in children not infected with HIV versus those with HIV infection. In children not infected with HIV, the main non-vaccine serotypes were 15B/C, 12F, 35B, and 8, and in those with HIV infection, the primary non-vaccine serotype was 16F. Streptococcus pneumoniae has more than 95 serotypes; each can presumably cause pneumococcal disease, and nasopharyngeal colonisation is the precursor of invasive and mucosal pneumococcal diesase.9Varon 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 (63) Google Scholar, 10Cohen R Varon E Doit C et al.A 13-year survey of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 and PCV13 implementation.Vaccine. 2015; 33: 5118-5126Crossref PubMed Scopus (58) Google Scholar The effectiveness of pneumococcal conjugate vaccines against vaccine-type pneumococcal disease and carriage was shown with the same range of intensity in many countries, although, overall, pneumococcal carriage decreased only slightly and the replacement was almost complete.2Madhi SA Nunes MC The potential impact of pneumococcal conjugate vaccine in Africa: considerations and early lessons learned from the South African experience.Hum Vaccin Immunother. 2016; 12: 314-325Crossref PubMed Scopus (23) Google Scholar, 10Cohen R Varon E Doit C et al.A 13-year survey of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 and PCV13 implementation.Vaccine. 2015; 33: 5118-5126Crossref PubMed Scopus (58) Google Scholar By contrast, worldwide, implementation of pneumococcal conjugate vaccines has resulted in a reduction in overall incidence of pneumococcal disease. However, because serotypes do not have the same disease potential, the magnitude of the overall decline in invasive pneumococcal disease has differed depending on the country and population.3Mackenzie 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, 4von 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, 6Moore MR Link-Gelles R Schaffner W et al.Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study.Lancet Respir Med. 2016; 4: 399-406Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 7Miller E Andrews NJ Waight PA Slack MP George RC Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine.Vaccine. 2011; 29: 9127-9131Crossref PubMed Scopus (172) Google Scholar, 9Varon 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 (63) Google Scholar, 11Waight PA Andrews NJ Ladhani SN Sheppard CL Slack MPE Miller E Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study.Lancet Infect Dis. 2015; 15: 535-543Summary Full Text Full Text PDF PubMed Scopus (414) Google Scholar Many of the emerging non-vaccine serotypes in carriage after PCV13 implementation (11A, 15B/C, 15A, 21, 23B, and 35F) show low potential for causing invasive disease, but some—eg, 12F, 22F, 24F, 8, and 9N—have high disease potential.9Varon 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 (63) Google Scholar, 12Lindstrand A Galanis I Darenberg J et al.Unaltered pneumococcal carriage prevalence due to expansion of non-vaccine types of low invasive potential 8 years after vaccine introduction in Stockholm, Sweden.Vaccine. 2016; 34: 4565-4571Crossref PubMed Scopus (56) Google Scholar Moreover, in vulnerable populations (eg, immunocompromised people), serotypes with low disease potential could induce severe invasive pneumococcal disease.13Cohen R Varon E Bechet S Bonacorsi S Levy C Comparative impact of pneumococcal conjugate vaccines on pneumococcal meningitis according to underlying conditions.Vaccine. 2016; 34: 4850-4856Crossref PubMed Scopus (14) Google Scholar Changes in serotype distribution have resulted in changes in the profile and spectrum of pneumococcal disease (eg, in the proportion of meningitis, bacteraemic pneumonia, and bacteraemia without focus) and an increase in the proportion of patients with underlying conditions who are easily infected by non-vaccine serotypes.13Cohen R Varon E Bechet S Bonacorsi S Levy C Comparative impact of pneumococcal conjugate vaccines on pneumococcal meningitis according to underlying conditions.Vaccine. 2016; 34: 4850-4856Crossref PubMed Scopus (14) Google Scholar Not surprisingly, in the study by Cohen and colleagues, 26% of children with invasive pneumococcal disease who were not infected with HIV had an underlying condition.8Cohen C von Mollendorf C de Gouveia L et al.for the South African IPD Case-Control Study GroupEffectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study.Lancet Glob Health. 2017; (published online Jan 27.)http://dx.doi.org/10.1016/S2214-109X(17)30043-8Summary Full Text Full Text PDF Scopus (37) Google Scholar The study by Cohen and colleagues probably underestimates the effectiveness of PCV13 not only because case-control studies ignore the herd effect but also because of the use of small sample sizes, as the authors underline.8Cohen C von Mollendorf C de Gouveia L et al.for the South African IPD Case-Control Study GroupEffectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study.Lancet Glob Health. 2017; (published online Jan 27.)http://dx.doi.org/10.1016/S2214-109X(17)30043-8Summary Full Text Full Text PDF Scopus (37) Google Scholar The new data from South Africa and The Gambia show a high degree of effectiveness of pneumococcal conjugate vaccine, comparable with that seen in high-income countries, and should encourage countries that have not yet incorporated pneumococcal conjugate vaccines into their national immunisation programmes to do so. Assessing the effect of pneumococcal conjugate vaccines should be multifaceted (invasive pneumococcal disease, pneumonia, nasopharyngeal flora) and continual because of the permanent adaptation of pneumococcus to escape external pressures such as vaccination and antibiotics. RC and CL's institution (ACTIV) has received research grant support from Pfizer, GlaxoSmithKline, Sanofi Pasteur, MSD, and AstraZeneca. RC reports personal fees from Pfizer and GlaxoSmithKline. CL reports personal fees from Pfizer. Effectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control studyOur results indicate that PCV13 in a 2 + 1 schedule is effective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine effectiveness in children infected with HIV was high, it did not reach significance, possibly because of the small sample size. These findings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries. Full-Text PDF Open Access