Early and accurate diagnosis of tuberculosis (TB) in all populations, including people living with HIV (PLHIV) and children, is essential to reducing TB transmission, morbidity and mortality.


Smear microscopy and mycobacterial culture

Smear microscopy, which involves the examination of sputum under a microscope to identify mycobacteria, and mycobacterial culture, which involves observation for detection of mycobacterial growth during a six-week incubation period, are the most widely used TB diagnostic tests today. Microscopy, though inaccurate — missing over half of cases and not good at detecting TB in people living with HIV and in children – is relatively fast, while culture is accurate but slow. Drug susceptibility testing (DST) is often performed using solid or liquid culture and provides information on which TB drugs the bacterium is susceptible to, necessary for detecting multi- and extensively drug-resistant TB (M/XDR-TB) and for getting patients on appropriate and effective treatment regimens. Newer molecular assays have shortened the time to drug susceptibility testing results, yet a true point of care diagnostic remains elusive.

GeneXpert/Xpert MTB/RIF

Xpert MTB/RIF is a molecular diagnostic test that can detect TB and resistance to one of the key first-line TB drugs, rifampicin, in just two hours. Rifampicin resistance is commonly considered a surrogate marker of multi-drug resistant TB (MDR-TB). In addition to being faster than traditional smear microscopy, Xpert MTB/RIF can better detect TB in samples from people living with HIV and children. While Xpert MTB/RIF may give a faster and more sensitive result, it is more expensive and requires an uninterrupted supply of electricity.

Genotype MTBDR and INNO-LiPA Rif TB

Two other molecular tests that can detect TB and resistance to rifampicin are Genotype MTBDR, and INNO-LiPA Rif TB. INNO-LIPA Rif TB can also detect resistance to isoniazid, another key first-line TB drug. These tests are called “line probe assays” because they detect mutations in the TB bacterium’s DNA using a coloring agent that highlights gene mutations associated with drug resistance. In theory, both tests can detect TB and resistance in one day; however, unlike Xpert MTB/RIF, these technologies must be hosted at centralized laboratory facilities with adequate equipment and trained personnel and require laboratory turn around time, often delaying results for patients and initiation of appropriate treatment.


The MGIT (Mycobacteria Growth Indicator Tube) system uses liquid culture to test if TB bacteria will grow in the presence of various TB drugs. If TB grows, then the TB bacterium is resistant to the drug being tested. MGIT results take several days, but are available much quicker than conventional solid culture, where TB bacteria are grown on a solid surface in a laboratory (in a container called a petri dish) over a long period of time, usually more than 30 days. Similar to Genotype MTBDR and INNO-LiPA Rif TB, MGIT must be hosted in a laboratory facility with adequate equipment and trained personnel.


Other commonly used TB diagnostic tests include symptom screening, tuberculin skin test (TST), and chest X-ray. Clinical TB symptoms include cough, fever, night sweats, chest pain, weight loss, and blood in sputum. Symptom screening is more challenging in patients with TB outside of the lungs (extrapulmonary TB).

TSTs cannot distinguish between active and latent TB and can be falsely positive in people vaccinated with Bacille Calmette-Guérin (BCG). They require refrigeration and a TB protein derivative to be injected under the skin. Chest X-rays can be used to rule out or confirm active pulmonary TB in people with positive TST results.


Other TB tests that cannot differentiate between latent and active TB are interferon gamma release assays (IGRAs) such as QuantiFERON-TB Gold, manufactured by Qiagen, and Immucheck TB Platinum, manufactured by Immunoshop. IGRAs and other serological tests are blood based and measure a person’s immune response to TB bacteria. White blood cells in someone infected with TB will release interferon-gamma when mixed with protein derivatives of TB.

The pipeline for diagnostics, though full with new technology, offers little hope of a true point-of-care test in the next few years.