Density of carriage - Can it predict pneumonia?

Abstract

The discovery of a diagnostic test for the etiology of pneumonia that is both sensitive and specific is an important goal in the diagnosis and treatment of the disease as well as the surveillance of vaccines such as pneumococcal vacine that may impact the burden of pneumonia. A nasopharyngeal swab is easily obtained but the disctinction between asymptomatic carriage and pneumonia has not been clear to date. There is evidence that upper respiratory viral infections increase the density of bacterial colonization including pneumococcal colonization in the nasopharynx (NP). It is possible that a higher density of pneumococci in the NP increases the likelihood of microaspiration and pneumonia as well as the risk of bacteremia. We explored therefore in adults whether the density of pneumococcal carriage in the NP differed between individuals with X-ray confirmed pneumonia and prospectively collected samples from age and HIV status matched asymptomatic controls. The density of pneumococci as measured by lytA real time PCR was 10 000 fold higher among pneumonia patients than controls. Subsequent studies have documented an association between NP density using this technique and pneumonia mortality. The density of pneumococcal carriage in adults may be a useful diagnostic test for pneumonia and a cutoff of greater than 8000 pneumococcal lytA products /ml of original sample increased the attributable fraction of X ray confirmed pneumonia to the pneumococcus from 27% to over 50%. This assay is readily applicable to a platform of diagnostic tests using NP swabs - its usefulness in making an etiological diagnosis of pediatric pneumonia remains to be clarified as the differential increased density of pneumococci in pneumonia versus carriage may be several logs less than in adults, as the background density of carriage is higher in children than in adults. These initial observations made in the context of an African population with a high burden of HIV need to be extended to other populations, but density of bacterial (and viral) pathogens in the nasopharynx may be a useful basis for futher exploration of novel quantitative diagnosic tests for the etiology of pneumonia.