Contribution of vaccines to our understanding of pneumococcal disease

Abstract

Pneumonia is the leading cause of mortality in children in developing countries and is also the leading infectious cause of death in adults. The most important cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus pneumoniae, also known as the pneumococcus. It has thus become the leading vaccine-preventable cause of death and is a successful and diverse human pathogen. The development of conjugate pneumococcal vaccines has made possible the prevention of pneumococcal disease in infants, but has also elucidated aspects of pneumococcal biology in a number of ways. Use of the vaccine as a probe has increased our understanding of the burden of pneumococcal disease in children globally. Vaccination has also elucidated the clinical spectrum of vaccine-preventable pneumococcal infections; the identification of a biological niche for multiple pneumococcal serotypes in carriage and the differential invasiveness of pneumococcal serotypes; the impact of pneumococcal transmission among children on disease burden in adults; the role of carriage as a precursor to pneumonia; the plasticity of a naturally transformable pathogen to respond to selective pressure through capsular switching and the accumulation of antibioticresistance determinants; and the role of pneumococcal infections in hospitalization and mortality associated with respiratory viral infections, including both seasonal and pandemic influenza. Finally, there has been a recent demonstration that pneumococcal pneumonia in children may be an important cause of hospitalization for those with underlying tuberculosis.

Variation in Streptococcus pneumoniae susceptibility to human antimicrobial peptides may mediate intraspecific competition

“…Despite significant advances in our understanding of the mechanisms of pneumococcal pathogenesis and epidemiology, together with widely successful antibiotic treatment and vaccination programmes, this species remains responsible for high rates of morbidity and mortality worldwide [1,2]. A crucial first step in invasive disease for S. pneumoniae is host colonization.…”

“…Several lines of evidence suggest that S. pneumoniae strains may compete to establish carriage within hosts. Multiple serotypes co-circulate within host populations [1]; epidemiological modelling suggests that serotypes vary in their ability to displace, and to prevent displacement by, competing serotypes [3,7,10,13,14]. Instances of co-colonization by multiple S. pneumoniae strains have been observed during carriage in humans [15].…”

“…Differential responses between serotypes to the selection pressure of the innate immune response can be mediated by mucus clearance [19], neutrophils extracellular traps [20] and non-opsonic phagocytosis [12]. The capsule seems to have a prominent role in evading the host immune system, and it is thus probable that success of colonization is partly dependent on serotype [1,3,5,6,10,11]. The capsule prevents clearance from the adaptive immune system by inhibiting complement-mediated opsonophagocytosis [21].…”

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

“…In 2010, two new PCV formulations were released that conferred protection against an additional three (PCV-10) or six (PCV-13) serotypes emerging in the population as a result of serotype replacement or more commonly caused disease in low-and middle-income countries. Yet the large number of pneumococcal serotypes (currently 96) and the poor immunological responses against most nonvaccine serotypes inherently limit the utility of these vaccines in broadly protecting against disease (11). There is a critical need, therefore, to identify novel strategies and immunogens to expand coverage and to improve vaccine efficacy, especially in older and younger populations who are at highest risk.…”

Streptococcus pneumoniaepharyngeal colonization in school-age children and adolescents with cancer

“…We do not have a clear explanation for this finding. It is well-known that influenza vaccination has a role in prevention of pneumococcal infection 22,23 and in our study performed in patients with cystic fibrosis, 24 the majority of whom were vaccinated against influenza, influenza vaccination coverage was similar between carriers and non-carriers.…”