DNA sequencing accelerates infection diagnosis

A new diagnostic technique provides fast and accurate identification of causal pathogen in patients with serious infectious diseases, offering the possibility of accelerated diagnosis and treatment.

For patients with serious infectious diseases, rapid identification of the causative pathogen is crucial to enable early administration of the correct treatment. However, the techniques currently used for pathogen identification have significant drawbacks. Growing pathogen cultures takes days or even weeks, and though polymerase chain reaction (PCR) tests can quickly identify pathogens, a different test is needed for each, meaning a specific pathogen must be suspected or multiple tests are needed.

A team led by Charles Chiu of the University of California San Francisco, USA, set out to address these problems by developing a more efficient test based on metagenomic next-generation sequencing (mNGS). Their approach involves analysis of all genetic material in a patient’s body fluid sample to identify pathogens present.

“The pathogens causing infectious syndromes are often indistinguishable on the basis of the clinical presentation, and the current diagnostic paradigm is slow, laborious and costly,” Chiu explains. “Metagenomic sequencing allows detection of the full spectrum of viruses, bacteria, fungi and parasites that cause infections in a single test.”

In the study, 182 samples of various fluids were collected from 160 individuals with serious infectious diseases. Most were hospitalized, and 39% required intensive care. The samples were analysed with mNGS to detect and identify any pathogens present. The pathogen responsible for the infection was known in 170 of the 182 samples, enabling the accuracy of the new test to be determined. The other 12 samples were from patients with probable infections for which standard tests had not identified the causative pathogen.

The mNGS test identified the correct pathogen in more than 75% of the bacterial and 91% of fungal infections and had a low rate of false-positives. The test also identified the pathogens in 7 of the 12 samples for which culture and PCR tests had been negative. Furthermore, the results could be obtained in as little as 6 hours. These findings demonstrate that an mNGS test could be used to accelerate diagnoses in hospitals.

“More timely and rapid diagnosis has the potential to improve outcomes by providing actionable information to guide management and treatment of infectious diseases,” says Chiu. “We are now performing formal clinical validation of the assay in a clinically licensed laboratory and clinical trials to evaluate the utility of the body fluids assay in clinical practice.”

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