Respiratory Tract Infections: Aspects of Aetiology, Virulence, and Communicable Disease Control

University dissertation from Infectious Diseases Research Unit

Abstract: The paediatric nasopharyngeal flora is regarded as the largest reservoir for Streptococcus pneumoniae, and the carrier state is always antecedent to infection and a prerequisite for dispersion of these bacteria. Pneumococci are the predominant aetiology of bacterial respiratory tract infections and a major cause of morbidity and mortality, in the most severe cases due to invasive pneumococcal disease (IPD; mainly sepsis and meningitis).The development and spread of resistant pneumococci are facilitated in day care centres (DCCs), which constitute an optimal environment for these processes. In Sweden, penicillin non-susceptible pneumococci (PNSP) have remained relatively uncommon,an important aspect considering that penicillin is the drug of choice for respiratory tract infections. When a tendency towards increasing PNSP was noted in Skåne County in southern Sweden, a DCC intervention program including screening started when an attending child has been found to be PNSP carrier. To restrict dispersion, all carriers were suspended from DCCs until they were declared free from PNSP. Today, there is no scientific proof that such DCC interventions can effectively restrict PNSP dispersion on a community level. Our retrospective study of the DCC interventions showed that 5% of the children were PNSP carriers during an outbreak. Personnel were rarely carriers (0.4%) and, if so, for only a very short time. PNSP was found a long time after the intervention started in a few children cultured late due to absence from the DCC for other reasons, indicating a long-lasting risk for dispersion. Furthermore, PNSP carriage was observed in a substantial number of children at DCC departments other than the department attended by the index case, indicating that the index case is not always at the centre of an outbreak. There was also significant seasonal variation seen as lower carrier rates after major holidays, indicating that these rates decline when children are not at DCCs. Day care group size and young age proved to be risk factors for pneumococcal carriage. Our findings can support development of future guidelines for managing PNSP outbreaks in DCCs. Eradication therapy of children with prolonged PNSP carriage was effective, but none of the treated children harboured any highly resistant or multidrug-resistant strains. Our retrospective study of IPD demonstrated that pneumococcal serotypes differ regarding their capacity to cause septic shock and, together with age and co-morbidities, have an important impact on outcome. The primary endpoint in our investigation was septic shock, a state produced by the immune system and triggered by the invading microorganism. This parameter was chosen instead of the case fatality rate (CFR),which is usually studied as outcome but is biased because serotypes with a low CFR infect healthier and younger individuals and vice versa. Septic shock was significantly more common among patients infected with serotype 3 compared to those with serotype 14, a worrisome finding since the effect of the conjugate vaccine on this serotype seems to be uncertain. Ventilator-associated pneumonia (VAP) is a common infection and complication in intensive care units. We found that the bacterial aetiology in VAP differed depending on whether the patients were receiving antibiotics at the time of the VAP diagnosis. Pseudomonas aeruginosa was a surprisingly widespread cause of early-onset VAP, but most of the patients had been treated with antibiotics. There was a trend towards more resistant bacteria in late-onset VAP.