Above photo provided by Professor Ron Dagan
What is pneumococcal pneumonia? Can pneumococcal conjugate vaccines help answer the question? By Ron Dagan
It is well accepted that acute lower respiratory tract infection (LRI) is the leading cause of death in children in developing countries, and the most common cause of hospital visits in young children in the developed world. However, no appropriate clinical definition exists as to what is pneumonia and how to distinguish it from other LRIs. Without such “gold standard” we were unable to predict the potential impact of pneumococcal conjugate vaccines (PCVs) before their implementation.
Furthermore, we know that LRIs are often caused by more than a single pathogen, either because one pathogen paves the way for another (e.g., influenza with bacterial secondary infections) or because two or more pathogens co-infect the lung simultaneously. The important involvement of Streptococcus pneumoniae (pneumococcus) in LRIs has always been recognized, but the actual extent of this involvement has not been clear, especially in those presenting with non-alveolar pneumonia (also termed lobar pneumonia or consolidated pneumonia). Since PCVs currently cover up to 13 pneumococcal serotypes, and one can only rarely isolate the organism in pneumonia, the extent to which the vaccines could reduce LRIs, even if pneumococcus had an important role, constituted a great enigma. This is why PCV experts have decided that prospective surveillance projects looking at the impact of PCVs on LRIs should be initiated and long-term follow-up implemented. This could allow us to look separately at various LRI outcomes (e.g., consolidated pneumonia, all-cause clinically diagnosed pneumonia [consolidated and non-consolidated], or even all-cause LRIs, including what is considered to be viral LRI). The impact of PCV on each of these outcomes can provide insights regarding the pneumococcal etiology or cost-benefit analyses, and also could shed light on the true role of PCVs in reducing LRIs, the number one killer of young children worldwide. Gaining insights on vaccine-preventable disease burden by observing the impact of vaccines, is termed the “vaccine probe” approach.
The first hint that PCVs could do much more than just reduce classical consolidated pneumococcal pneumonia came from South Africa, where during a clinical trial of an experimental PCV, they observed a substantial reduction in pneumonia in which viruses were detected, until then classified as “viral pneumonia.” The insight gained from that study was the importance of bacterial-viral co-infections. Currently, 20 years after the first implementation of a PCV - PCV7 in the USA in 2000 - we have enormously advanced our understanding of PCVs’ potential to reduce all-cause LRIs. Multiple studies have shown a reduction of consolidated pneumonia in young children, with an observed decline in 50% or higher, attesting to the important role of vaccine serotypes in this entity. The big enigma was whether a considerable reduction could also be observed in non-consolidated LRIs, indicating the important involvement of pneumococcal vaccine-serotypes.
The message deriving from the vaccine probe approach measuring the impact of PCVs on all-cause LRIs was very loud and clear: There was a decline of up to one-third (and sometimes even more) of any of the currently used diagnoses of LRIs (all-cause clinical pneumonia, all-cause LRI, viral-bacterial co-infections), in each region/country where PCVs were implemented and high vaccination coverage was achieved.
The impact of PCVs on all-cause LRIs is therefore many fold higher than expected. Two decades ago, we wondered “What is pneumococcal pneumonia?” Currently, using the vaccine probe approach, we can answer - the spectrum of pneumococcal pneumonia ranges from simple “viral” LRI all the way to consolidated pneumonia. Pneumococci, and in particular the serotypes included in the PCVs, are frequently involved in LRIs of all sorts, which then makes the entire spectrum of LRIs vaccine-preventable. The currently widely implemented PCVs have made the world a better place to be born into.
Author: Professor Ron Dagan is Distinguished Professor of Pediatrics and Infectious Diseases and Gunzburger Chair for Study of Infectious Diseases at the Faculty of Health Sciences of the Ben-Gurion University of the Negev in Beer-Sheva, Israel. His contribution to the field of infectious diseases prevention, in particular pneumococcal diseases, is globally recognized.