Tackling childhood pneumonia in Africa: a dream that becomes reality
Authors: Corinne Levy, Robert Cohen
Journal: The Lancet Global Health (2019)

The close relationship between pneumococcus and pneumonia is a very old story. In 1882, Friedlander reported pneumococci in tissue from humans with pneumonia and, in 1884, recovered pneumococci from the blood of patients with pneumonia for the first time. However, regardless of the microbiological method used (culture, antigen detection, or molecular tools), only a small proportion of pneumonia cases can be attributed to pneumococcus, and pneumococcal bacteraemic pneumonia represents only a small portion of pneumonia cases. There is a disparity between the low proportion of pneumonia cases attributed to pneumococcus (7·2%, 95% CI 5·1–9·5), even if more accurate diagnostic methods are used, and the large worldwide reported effect of pneumococcal conjugate vaccines (PCVs) on pneumonia.1Cohen R Cohen JF Chalumeau M Levy C Impact of pneumococcal conjugate vaccines for children in high- and non-high-income countries.Expert Rev Vaccines. 2017; 16: 625-640Crossref PubMed Scopus (47) Google Scholar, 2O'Brien KL Pneumococcal findings in the pneumonia etiology research for child health (PERCH) study. International Symposium on Pneumococci and Pneumococcal Diseases.https://www.jhsph.edu/ivac/wp-content/uploads/2018/05/ISPPD_2018_PERCH_Spn_FINAL.pdfDate: April, 2018Date accessed: January 17, 2019Google Scholar This contrast highlights the need to specifically assess the effect of PCV implementation on pneumonia, particularly in low-income countries.1Cohen R Cohen JF Chalumeau M Levy C Impact of pneumococcal conjugate vaccines for children in high- and non-high-income countries.Expert Rev Vaccines. 2017; 16: 625-640Crossref PubMed Scopus (47) Google Scholar In Africa, morbidity and mortality due to pneumonia (commonly non-bacteraemic pneumonia) represent a heavy burden for public health and are one of the leading causes of childhood death.3Global 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 (4424) Google Scholar With a difference in serotype distribution between bacteraemic pneumonia versus other invasive pneumococcal disease, we believe that surveillance of the effect of PCVs should be multifaceted and include pneumonia surveillance, which is a crucial—but different—marker of vaccine impact than invasive pneumococcal disease.1Cohen R Cohen JF Chalumeau M Levy C Impact of pneumococcal conjugate vaccines for children in high- and non-high-income countries.Expert Rev Vaccines. 2017; 16: 625-640Crossref PubMed Scopus (47) Google Scholar, 4Ben-Shimol S Greenberg D Hazan G et al.Differential impact of pneumococcal conjugate vaccines on bacteremic pneumonia versus other invasive pneumococcal disease.Pediatr Infect Dis J. 2015; 34: 409-416Crossref PubMed Scopus (17) Google Scholar In 2009, Gavi, The Vaccine Alliance created the pneumococcal Advance Market Commitment to tackle the burden of pneumococcal diseases in low-income countries by encouraging the implementation of PCVs.5Gavi, The Vaccine Alliance2015 Pneumococcal AMC. Annual Report.https://www.gavi.org/library/gavi-documents/amc/2015-pneumococcal-amc-annual-report/Date: 2015Date accessed: January 17, 2019Google Scholar Low-income countries face a double challenge: reaching high vaccination coverage and developing a sustained surveillance system to assess the effect of PCVs. This scenario requires considerable effort, and several African countries have at least one ongoing study assessing the effectiveness and impact of PCVs. Thanks to the willingness of local health authorities and to Gavi, today we benefit from a real picture of the effect of PCVs in Africa.1Cohen R Cohen JF Chalumeau M Levy C Impact of pneumococcal conjugate vaccines for children in high- and non-high-income countries.Expert Rev Vaccines. 2017; 16: 625-640Crossref PubMed Scopus (47) Google Scholar, 6Silaba M Ooko M Bottomley C et al.The impact of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis.Lancet Glob Health. 2019; 7: e337-e346Scopus (30) Google Scholar In The Lancet Global Health, Micah Silaba and colleagues6Silaba M Ooko M Bottomley C et al.The impact of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis.Lancet Glob Health. 2019; 7: e337-e346Scopus (30) Google Scholar provide insights into the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia in children in Kenya. The authors used an interrupted time-series analysis, accounting for seasonal and temporal trends. PCV10 was introduced in Kenya in January, 2011, with a three-dose catch-up campaign for infants. Children aged 1–4 years had a two-dose catch-up campaign at Kilifi County Hospital. This Article contains at least two interesting findings that we would like to highlight and discuss. First, as expected, the authors found that, over the 13-year study period (2002–15), admissions to hospital for clinically-defined pneumonia fell by 27% and incidence of radiologically-confirmed pneumonia fell by 48%, after PCV10 was implemented. These results suggest that vaccine-serotype pneumococci accounted for proportionately more cases of radiologically confirmed pneumonia than did clinically-defined pneumonia. Second, unexpectedly, the effect of the vaccine was greater for severe pneumonia than for very severe pneumonia, also suggesting a higher proportion of cases attributable to pneumococcal infection among the severe group than the very severe group. We would like to raise two other hypotheses. First, the serotypes not included in PCV10 could also have been involved in very severe cases. For example, one study7Lai CY Huang LM Lee PY Lu CY Shao PL Chang LY Comparison of invasive pneumococcal disease caused by serotype 19A and non-19A pneumococci in children: more empyema in serotype 19A invasive pneumococcal disease.J Microbiol Immunol Infect. 2014; 47: 23-27Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar showed that empyema and necrotising pneumonia occurred more frequently in invasive pneumococcal disease due to serotype 19A than it did in invasive pneumococcal disease not caused by 19A.7Lai CY Huang LM Lee PY Lu CY Shao PL Chang LY Comparison of invasive pneumococcal disease caused by serotype 19A and non-19A pneumococci in children: more empyema in serotype 19A invasive pneumococcal disease.J Microbiol Immunol Infect. 2014; 47: 23-27Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar Second, viruses or other bacterial species that are able to produce toxins, such as Group A Streptococcus or Staphylococcus aureus, could also be involved in very severe cases.8Loffler B Niemann S Ehrhardt C et al.Pathogenesis of staphylococcus aureus necrotizing pneumonia: the role of PVL and an influenza coinfection.Expert Rev Anti Infect Ther. 2013; 11: 1041-1051Crossref PubMed Scopus (50) Google Scholar, 9Bellulo S Sommet J Levy C et al.When should clinicians suspect group A streptococcus empyema in children? A multicentre case-control study in French tertiary care centres.Arch Dis Child. 2016; 101: 731-735Crossref PubMed Scopus (7) Google Scholar The main limitation of this Article is the association between the decreasing incidence of diarrhoea (control condition) and PCV10 introduction. Selecting the best control condition is challenging because it should be unaffected by the intervention being studied. Obviously, the decrease in diarrhoea-related admissions cannot be due to the effect of PCV10. However, other interventions were probably used simultaneously with PCV10. For example, a campaign of community-led total sanitation to eliminate open defecation, improved nutrition, better access to care, general improvements in maternal education, decreased prevalence of malaria, improved care of HIV-positive people, or implementation of rotavirus vaccine.6Silaba M Ooko M Bottomley C et al.The impact of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis.Lancet Glob Health. 2019; 7: e337-e346Scopus (30) Google Scholar The authors tried to circumvent these biases and chose to assume that these improvements were linear throughout the study. Despite this choice, some of the decrease in the hospital burden of pneumonia should probably be attributed to these improvements in care of children. Long-term surveillance of both invasive pneumococcal disease and pneumonia should continue because several years after PCV implementation, serotype distribution, and replacement continue to evolve. In several countries, the emergence of non-vaccine serotypes in invasive pneumococcal disease—such as serotype 24F in France and Germany and serotypes 8, 12F, and 9N in the UK—have raised concerns.10Weinberger R von Kries R van der Linden M Rieck T Siedler A Falkenhorst G Invasive pneumococcal disease in children under 16years of age: Incomplete rebound in incidence after the maximum effect of PCV13 in 2012/13 in Germany.Vaccine. 2018; 36: 572-577Crossref PubMed Scopus (36) Google Scholar, 11Ouldali N Levy C Varon E et al.Incidence of paediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey.Lancet Infect Dis. 2018; 18: 983-991Summary Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 12Ladhani SN Collins S Djennad A et al.Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study.Lancet Infect Dis. 2018; 18: 441-451Summary Full Text Full Text PDF PubMed Scopus (306) Google Scholar The rapid development of more extended-spectrum PCVs or non-capsular pneumococcal vaccine candidates, or both, seems again to be necessary to decrease invasive pneumococcal disease. Reassuringly, non-vaccine serotype replacement in invasive pneumococcal disease has not been found for pneumonia yet.13Ouldali N Levy C Minodier P et al.Long-term impact of PCV13 implementation on community-acquired pneumonia in children: a time-series analysis of an 8-year prospective multicenter study.JAMA Pediatrics. 2019; (in press).PubMed Google Scholar Our institution, ACTIV, has received research grant support from Pfizer, GlaxoSmithKline, Merck, and Sanofi Pasteur MSD. CL reports personal fees from Pfizer, outside the submitted work. RC reports personal fees from Pfizer, GlaxoSmithKline, Merck, Sanofi, and Astra Zeneca, outside the submitted work. Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysisOver 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10. Full-Text PDF Open Access