Pathogen chip for respiratory tract infections

Abstract

Determining the viral etiology of respiratory tract infections (RTI) has been limited for the most part to specific primer PCR-based methods due to their increased sensitivity and specificity compared to other methods, such as tissue culture. However, specific primer approaches have limited the ability to fully understand the diversity of infecting pathogens. A pathogen chip system (PathChip), developed at the Genome Institute of Singapore (GIS), using a random-tagged PCR coupled to a chip with over 170,000 probes, has the potential to recognize all known human viral pathogens. We tested 290 nasal wash specimens from Filipino children <2 years of age with respiratory tract infections using culture and 3 PCR methods-EraGen, Luminex, and the GIS PathChip. The PathChip had good diagnostic accuracy, ranging from 85.9% (95% confidence interval [CI], 81.3 to 89.7%) for rhinovirus/enteroviruses to 98.6% (95% CI, 96.5 to 99.6%) for PIV 2, compared to the other methods and additionally identified a number of viruses not detected by these methods.

Fig 1

Sample PathChip report. The 1st section contains a summary of the report. The 2nd section contains hybridization, labeling, and PCR controls. The 3rd section shows the heat maps of the detected pathogens and the closest matches to known strains found in the patient sample.

Fig 2

OC43 detection score plot. EraGen identified 40 specimens with coronavirus OC43 infection (samples indicated by red and blue). The PathChip identified 12 specimens with coronavirus OC43 (red). The other 30 specimens (blue) were not identified by either PathChip or Luminex. The background detection scores of coronavirus OC43 in other specimens are also shown in green. TruePos, true positive; FalseNeg, false negative.