New research from Africa Health Research Institute (AHRI) scientists underlines the need for more effective screening and treatment for tuberculosis (TB) patients who are resistant to the drug isoniazid.

In a paper published in the International Journal of Tuberculosis and Lung Disease in June 2017, AHRI researchers and colleagues from the eThekwini Municipality, Vanderbilt University and UKZN show that patients who are resistant only to the drug isoniazid are more likely to fail their treatment, develop multi-drug resistant TB (MDR-TB) and die than those with drug-susceptible TB.


Isoniazid and rifampicin are part of the four drug combination used to treat drug susceptible TB. If patients are resistant to only isoniazid it is not clear how they should be treated. Previous studies into isoniazid resistance give contradictory results, and guidelines to date have proposed continuing with first-line drugs for patients with resistance only to isoniazid. It is in this context that, in the largest study of its kind in a high-burden setting, scientists from AHRI’s Pym Laboratory set out to compare the clinical outcomes of patients who are resistant to isoniazid to those with drug-susceptible TB.


The researchers looked at the records of 18 058 TB patients who were tested for drug-susceptibility and treated at the Prince Cyril Zulu Communicable Diseases Centre in Durban from January 2000 to December 2012. Of the 16 868 TB cases included in the study, 16 786 (99.5%) had an outcome reported.

The scientists found that isoniazid resistance cases were more likely to experience treatment failure than drug-susceptible cases (4.1% vs. 0.6%). Similarly, isoniazid resistant TB patients were more likely to die (3.2% vs. 1.8%). Among 507 patients with isoniazid resistance, 14 (3%) developed MDR-TB, compared to 1% with drug-susceptible TB.


The study shows that new protocols for treating patients with isoniazid-resistant TB are needed. In South Africa, the rapid molecular test in use (GeneXpert) only determines if TB is resistant to rifampin – meaning that isoniazid resistance is going undetected. A previous study from AHRI has shown that the origins of MDR and extensively drug resistant TB (XDR-TB) were isoniazid-resistant strains – so failing to diagnose isoniazid resistance is not only hurting patients but also driving the emergence of MDR/XDR-TB.

“We really need to start taking isoniazid resistance more seriously and introduce a rapid diagnostic for both rifampicin and isoniazid resistance. We also need a more coherent approach to treating patients with isoniazid resistance,” says Dr Alex Pym, one of the lead authors on the paper.

(Photograph: Patients wait at Hlabisa Hospital in northern KZN. Ben Gilbert – Wellcome)