Isoniazid mono-resistant tuberculosis: Time to take it seriously.

BACKGROUND/AIMS: In drug resistant tuberculosis (DRTB) suspects, rifampicin resistance has always been prioritized, hence Cartridge Based Nucleic Acid Amplification Test (CBNAAT) is recommended under Revised National Tuberculosis Control Programme (RNTCP), India. However, since it doesn't detect isoniazid resistance, rifampicin sensitive patients with unknown isoniazid status may be erroneously treated as drug sensitive TB, leading to poor treatment outcomes and emergence of multidrug resistant (MDR) TB. Hence isoniazid mono-resistance should be specifically looked for and treated as per recommendations. The objective of the present study, almost the first of its kind in India, was to evaluate the burden of isoniazid mono-resistance amongst patients diagnosed with DRTB and to study the association of different patient and disease related factors with treatment outcomes under the treatment regimen specific for isoniazid mono-resistance, started from January 1, 2017 in our state, under RNTCP.

METHODS

It was a retrospective study which scrutinized medical records of 52 isoniazid mono-resistant TB patients started on treatment under RNTCP between January 1 to December 31, 2017. Necessary information on possible patient and disease related predicting factors like gender, age, type of mutation (katG/inhA), weight band (26-45 kg/46-70 kg), total serum protein/albumin levels, previous history of anti-tubercular treatment (ATT), history of smoking, HIV status, presence of diabetes mellitus (DM), presence of anemia, occurrence of adverse drug reactions (ADR) during treatment and duration of intensive phase (IP), was retrieved. These factors were analyzed for their possible association with treatment outcomes.

RESULTS

Out of 103 DRTB patients enrolled, 50.5% (52/103) patients were diagnosed with isoniazid mono-resistance. 50/103 were MDR-TB and 1/103 were extensively-drug resistant TB (XDR-TB). Further analysis of these 52 isoniazid mono-resistant patients revealed:35 (67.3%) were males and 17 (32.7%) females. 27 (51.9%) patients were <30 years, 25 (48.1%) being ≥30 years of age. All patients were negative for HIV. 34/52 (65.4%) patients were declared cured, 15/52 were lost to follow up (LTFU) and 3/52 died (1 male, 2 females). Excluding these 3 patients who died, cure rates were significantly better in females (14/15 = 93.3%), with only 1/15 LTFU, than males (20/34 = 58.8% cure, 14/34 = 41.2% LTFU), (p = 0.019). Patients who were <30 years of age had significantly better cure rates (21/25 = 84%) with lesser LTFU's (4/25 = 16%), than those ≥30years of age (13/24 = 54.2% cure, 11/24 = 45.8% LTFU), (p = 0.032). Review of previous history of ATT revealed that 33 patients had primary isoniazid mono-resistance, 4 patients had previous history of being LTFU, 9 had recurrent TB and 3 were labeled as failure. Cure rates were significantly better in primary isoniazid mono-resistant patients (26/33 = 78.8%), than those with previous history of being LTFU(0/4), (p = 0.04). Type of mutation, weight band, total serum protein/albumin, history of smoking, presence of DM, presence of anemia, occurrence of ADR and duration of IP did not affect treatment outcomes.

CONCLUSION

Isoniazid mono-resistance formed a major chunk of DRTB, with majority of the patients detected with primary mono-resistance. Strategically framed treatment regimens for isoniazid mono-resistance under RNTCP in India are effective in a wide range of population. Still, there are high chances of LTFU/default, which needs to be addressed on priority. Male gender, age ≥30 years and being LTFU in the past are associated with poorer cure rates, hence should be paid special attention.