Before the introduction of pneumococcal conjugate vaccines (PCVs), an estimated 14.5 million episodes of pneumococcal diseases (including pneumonia, meningitis and sepsis occurred each year, just in children <5 years with ˜500,000 deaths (O’Brien et al., Lancet 2009;374:893-902) The true cases of severe infections in all incidences >5 years of age amounted to 20 times these figures, given that children <5 years old constitute the minority of the population, and considering the rates of pneumococcal diseases in all other ages. Streptococcus pneumoniae (the pneumococcus) resides in the nasopharyngeal space of perfectly healthy children worldwide, and thus can be considered part of the normal flora, at least in early childhood. This species can be classified by its polysaccharide capsule constituent to >90 serotypes, which, although having much in common, can be differentiated by their epidemiology, biology and often clinical involvement. Why does a component of the normal flora become a pathogen, has until now not been fully elucidated, but our knowledge is rapidly increasing in regard to its pathogenesis. The recent advance in the development of antipneumococcal vaccines has not only resulted in an incredible reduction in disease caused by pneumococci, but also enormously contributed to our understanding of biology, epidemiology, pathogenesis and clinical manifestations of the pneumococcus, when carefully observing he consequences of immunization (the “vaccine probe” approach).
The initial approach of prevention through immunizing with a selection of unconjugated pneumococcal polysaccharides failed in many aspects, especially in infants and young children, and in the compromised hosts of all ages. Thus, for those with the highest need for protection, the polysaccharide vaccines were the least helpful. In the last two decades or so, the second generation of vaccines, the PCVs were developed, initially mainly against invasive pneumococcal diseases (IPD) in infants and young children. Only a limited number of serotypes could be involved, but they seemed to cover most of IPD in this age group. Twenty years later, with uncountable studies and after hundreds of millions of administered doses, we can now look back and proudly declare a huge advance in both disease prevention and gained insights on pneumococcal biology and diseases.
As with almost all advances in science in general, and medicine in particular, progress is always associated with insight of complexity: Each piece of new information clarifies one point but raises may new questions. Pneumococcus is not an exception. It might even be one of the most flamboyant examples of how advance can initiate so many new issues. On the one hand, we have learned the complexity of pneumococcal biology, interaction with other microorganisms and the host, mechanisms of pathogenesis, antibiotic resistance and clinical manifestations. On the other hand, we have learned how vaccines can prevent not only IPD but many other, often more frequent or even more dangerous outcomes such as mucosal disease (i.e. pneumonia, otitis media) and antibiotic resistance. Furthermore, we have learned the importance of reduction of pneumococcal carriage by vaccination, with the consequent indirect protection (the so-called “herd protection”), and the potential prevention of disease caused by other organisms (such as viruses or other bacteria) with whom the pneumococcus is an essential collaborator.
Some aspects clarified during PCV developments were not completely expected. We have learned about the importance of the pneumococcal-specific nasopharyngeal pneumococcal niche through the observation of serotype replacement after reduction of carriage of vaccine serotype; we have learned that not all new vaccines have identical effects and we had to struggle with issues such as the cost of the vaccines, interaction with other vaccines or production difficulties and vaccine supply shortage. Not the least of the problems was the need to make progress in disease prevention in the poor and not always accessible regions of the world, where perhaps the need for pneumococcal vaccines is the greatest, widely opening a huge ethical and logistics Pandora box.
Finally, the new insights gained in the last 2 decades and the advanced technology brought up the question of whether the PCVs that constitute the second generation vaccines are the last step in development of pneumococcal prevention approach. How to improve the current vaccines by either increasing their spectrum or targeting them to the new antigens, are some of the points we struggle with now. Should we all aim at the elimination of all pneumococci, given their being part of the flora in healthy children?
The current issue includes 16 articles written by world experts, all related to pneumococcal vaccines. Most aspects mentioned above are elaborated in these articles. However, no one can expect all aspects to be covered. Nevertheless, the reader can “get a taste” of the diversity of these important topics. Some of the articles in the current issue point to the success of the current pneumococcal vaccines, others raise questions and point to problems while still others wonder about the future.
Specifically, 7 articles deal with post PCV implementation impact: Ben-Shimol et al. discuss carriage in children post PCV7/PCV13 implementation in Israel; Cohen et al., discuss the multifaceted impact of PCV implementation in France; Andrade et al. discuss the impact of PCV10 implementation on IPD in all ages in Brazil; 2 studies by Principi et al. discuss impact of PCV7 on carriage among some high-risk school children >5 years of age in Italy; Ceyhan et al. discuss post PCV7/13 distribution of IPD serotypes in Turkey; Madhi et al. discuss post vaccination direct and indirect protection in HIV-positive and HIV-negative individuals in south Africa. Four additional articles deal with diseases in adults in relation to PCV administration: Memish et al. discuss the potential use of PCVs during mass gathering; Daniel M. Musher raises the question of whether PCVs should be routinely administered to adults in the presence of widespread PCV vaccination in children; Namkoong et al. discuss theory and strategy of PCVs in the elderly; and Azzari et al. discuss the relationship between adult IPD diseases and childhood post-PCV implementation carriage by serotype.
Two additional papers deal with issues regarding immunology and bacteriology of S. pneumoniae in relation to vaccination: Regev-Yochay et al. discuss the introduction of S. pneumoniae with Staphylococcal carriage at the nasopharyngeal level; Hausdorff et al. discuss PCV post-implementation serotypes and replacement; Finn et al. discuss population density profiles of nasopharyngeal carriage of 5 bacterial species and insights gained in relation to transmission. Two additional articles deal with the potential next (third) generation of pneumococcal vaccines: Malley et al. discuss the rationale for more pneumococcal vaccines; and Odutola et al. describe the results of Phase II study on protein-based vaccine in Gambian children. To complete the list, Wu et al. present the results of a cost-effectiveness calculation of PCV10 vs. PCV13 introduction to Hong-Kong and Malaysia; and Rodgers et al. discuss implementation of PCVs in the developing world.
This compilation of 16 articles is just a relatively modest contribution compared to the entire spectrum of pneumococcal diseases and vaccines, but it provides evidence to the huge step forward PCVs brought to our world.