TB Treatment Under Threat As Standard Tests Miss Some Resistance Mutations

Drug-resistant tuberculosis (TB) could pose a growing challenge in the coming years, as researchers have identified mutations in TB-causing bacteria that may not be detected by standard drug-resistance tests.

A scientific review by researchers from IIT Guwahati and IIT Madras has highlighted limitations in current testing methods used to detect resistance to rifampicin, one of the key drugs used in TB treatment.

Standard Test Checks Only Part Of The Gene

According to the review, tests approved by the World Health Organization (WHO) currently examine a specific portion of the rpoB gene, known as the rifampicin resistance-determining region (RRDR).

The RRDR contains 81 base pairs of DNA. However, the researchers noted that mutations responsible for drug resistance can also occur outside this region.

If such mutations are not detected, doctors may continue treating patients with standard drugs even though the bacteria may be resistant to them.

Undetected Resistance Could Allow Spread

The researchers explained that this can create a serious public-health concern. If a patient's drug-resistant TB is not identified, ineffective treatment may continue while the resistant bacteria can potentially spread to family members and the wider community.

The review cited examples of mutations outside the RRDR from Northeast India, Eswatini, Myanmar, Peru and South Africa.

How Do The Mutations Cause Drug Resistance?

The researchers described two possible mechanisms.

In the first, the mutation changes the structure of the protein targeted by rifampicin. This can prevent the drug from binding effectively to the bacteria, reducing its ability to kill them.

In the second, certain mutations outside the RRDR can occur alongside conventional resistance mutations. These additional mutations may help the bacteria regain growth and fitness, potentially allowing drug-resistant strains to survive and spread more effectively.

30% Of Tested Drug-Resistant Cases In Eswatini Had Such Mutation

The review cited real-world examples of mutations outside the RRDR in patients.

In Eswatini, such an additional drug-resistant mutation was reportedly identified in 30% of the drug-resistant TB cases examined. The standard tests failed to detect these mutations, potentially allowing resistant bacteria to continue spreading and acquire further drug resistance.

The findings highlight the need for continued research into TB drug resistance and the limitations of relying solely on the currently targeted genetic region for detecting rifampicin resistance.