Diagnosis, prognosis and prevention of severe pneumococcal disease

Abstract: Streptococcus pneumoniae also known as pneumococcus is a major contributor to the disease burden in the world. Infections caused by this bacterium include a wide spectrum of different disease types, from non-severe upper respiratory tract infections to invasive disease forms like bacteremic pneumococcal pneumonia or meningitis, conditions attributed with a high rate of severe disease and mortality. An important feature of this bacterium is that it only causes disease under certain circumstances, and the most common outcome upon contact with this bacterium is transient nasopharyngeal colonization rather than disease from it. Some patient groups such as young children and older people are however at a substantially increased risk of severe disease from the pneumococcus. The aim of this thesis is to increase the understanding of factors of importance to severe pneumococcal disease. The first paper addresses the difficulties in obtaining an etiological diagnosis in pneumonias, which potentially would delay an optimal care and treatment of these patients. We were able to demonstrate that our RQ-PCR method targeting specific gene sequences within the bacteria S. pneumoniae, H. influenzae and M. catarrhalis, increased the diagnostic yield from sputum samples significantly and also that this method seemed especially valuable in finding the causative bacterium when the patient had received antibiotics prior to specimen sampling. The second paper addresses the issue of how to identify patients that are at special risk for a severe outcome from pneumococcal pneumonia. We investigated this by analysing the ability of three different severity score systems, initially developed for the assessment of severity in all cause community acquired pneumonia, to predict mortality and need of ICU admission in bacteraemic pneumococcal pneumonia. We concluded that these severity scores worked fairly well also in this subgroup of patients, but also identified the CURB-65 as the best score system since it was the most practical to use. The third paper addresses whether specific pneumococcal properties are able to influence the severity and outcome of invasive pneumococcal disease (IPD). We investigated the relationship between clonal affiliation / serotypes of pneumococci and patient characteristics and outcome of IPD. We concluded that some clones and serotypes seem more prone to cause severe disease among older patients burdened by comorbidities, and are thus behaving like opportunistic pathogens, while other clones and serotype tended to cause milder disease among younger and previously healthy individuals, thus behaving as primary pathogens. The fourth paper addresses the issue of preventing invasive pneumococcal disease. We investigated the effects of the large scale vaccination campaign with the 23-valent pneumococcal polysaccharide vaccine directed towards all elderly persons in Stockholm County between 1997 and 2001. We studied the effects on incidence and serotype distribution of IPD, and concluded that a substantial decrease in vaccine-type IPD was seen among the vaccinated population, but not among other age groups, and also that no serotype replacement occurred during the 5 year study period