Streptococcus pneumoniae: still a major pathogen.

Streptococcus pneumoniae remains one of the major pathogens in children and adults worldwide. In addition to the 100 000 000 ear infections in children, it is estimated that it is responsible for more than 5 000 000 pneumonia cases and approximately 100 000 meningitis cases, the whole being associated with 10 000 000 bacteraemia cases every year. Mortality is still considerable, despite a wide battery of antibiotics. The ability of this bacterium to cause invasive disease is linked to multiple virulence factors, described in detail in the review by Mitchell and Mitchell. In addition to its capsule, an essential factor for virulence that allows the bacteria to escape opsonization–phagocytosis, many surface proteins enable it to colonize and adhere to the nasopharyngeal and respiratory tract epithelium. Among these, we must mention the choline-binding proteins and divalent metal ion-binding lipoproteins, some of which behave as adhesins, different exoglycosidases, such as the neuraminidase, which facilitates access to cell receptors, the autolysins, leading to lysis and releasing cell wall bacterial constituents, and different intracellular proteins, among which is pneumolysin. Combined with major inflammatory reactions, all of these factors, which impede the ciliary dynamic, facilitate access and adhesion of pneumococci to the pulmonary epithelium. Some of the virulence factors (pneumolysin, choline-binding proteins, etc.), by mechanisms still not well understood, will facilitate access to the circulation after breaching of the epithelium and enable the bacterium to reach other locations. All of these pathologies, which are particularly common at the extremes of life, can be explained, in part, by immaturity of the immune system before the age of 2 years and a decline in the immune response in the elderly. Not only humoral but also cellular immunity plays an important role in the fight against invasive infections, and well-defined deficiencies in innate or acquired immunity are factors conducive to their occurrence. If the 91 serotypes of pneumococci are distributed unevenly according to age and country, they contribute, despite the progress in vaccination, by their great numbers and their evolution in successive waves, to the maintenance of pneumococci in the population. In this context, the introduction of the conjugate vaccine, which includes a limited number of serotypes, has reduced not only the incidence of invasive infections, but also pneumococcal carriage in vaccinated children, resulting in herd immunity that decreases the frequency of pneumococcal disease in those age groups that are not receiving the vaccine; but the drawback is the rapid serotype replacement, requiring constant changes to its formulation. At present, the search for a universal pneumococcal vaccine covering all serotypes, using different associations of conserved proteins, remains in its infancy. In fact, we do not know what would be the result of complete eradication of S. pneumoniae from the human nasopharynx. Should we fear replacement by other pathogens, which could possibly be favoured by the loss of related species such as Streptococcus mitis? Should the ideal vaccine strategy not, rather, seek to protect only against certain clonal complexes that remain to be defined? All of this would be less of a problem in the absence of antibiotic resistance; however, as described in the review by Linares et al., constant antibiotic pressure and the ability of pneumococci, through transformation, to incorporate DNA of other pneumococci or closely related species, such as oral streptococci, are the major contributors to the acquisition and evolution of resistance traits. Thus, epidemiological surveillance of the serotype distribution and of antibiotic resistance remains the major strategy for the design of future vaccines and for the optimal adaptation of empirical therapy.