Unmasking rifampicin mono-resistance in tuberculosis patients in Cross River State, Nigeria

Rifampicin resistance has been assumed to be synonymous with multi-drug resistant tuberculosis (MDR-TB), but this approach could be exposing tuberculosis (TB) patients with rifampicin mono-resistance to unduly long and toxic treatment regimens. The current tuberculosis management algorithm in Nigeria recommends commencement of MDR-TB treatment on rifampicin resistance detection, based on GeneXpert results and subsequent phenotypic testing. With the current dearth of phenotypic drug susceptibility testing facilities in Nigeria, several rifampicin mono-resistant tuberculosis patients may be inappropriately placed on toxic second-line drugs used for MDR-TB treatment for prolonged periods before susceptibility results are available. XpertMTB/Rif were performed on a total of 3,580 patient samples from 10 sites across Cross River State, Nigeria, as a prospective cross-sectional study. Rifampicin-resistant specimens were reprocessed and cultured on Lowenstein-Jensen medium. Indirect susceptibility testing following the microscopic observation drug susceptibility technique was performed using Rifampicin (1 µg/ml), Isoniazid (0.4 µg/ml), Fluoroquinolone (Ofloxacin-1.0 µg), Capreomycin (2.5 µg/ml), Amikacin (2 µg/ml) and Kanamycin (5.0 µg/ml). Mycobacterium tuberculosis was detected in 21.3% (763) of the 3,580 presumptive tuberculosis cases recruited, of which 4.6% (35/763) were resistant to rifampicin. Culture yielded isolates from 89.6% (31/35) of these rifampicin resistant cases while susceptibility testing using first and second line antimicrobials, revealed 32.2% (10/31) and 64.5% (20/31) rifampicin mono-resistant and MDR-TB, respectively. When categorized into treatment groups, 25.7% (27/105) and 1.2% (8/658) of patients with rifampicin resistance belonged to retreatment and naïve patient groups respectively. There was no correlation between rifampicin mono-resistant and MDR-TB with gender (χ2 = 0.793, P = 0.308) or HIV status (χ2 = 0.416, P = 0.398). Patients who presented with first-line treatment failure were most likely to have MDR-TB (χ2 = 9.121, P = 0.028). Our finding that 32.2% of cases were rifampicin mono-resistant, underscores the critical need for phenotypic drug susceptibility testing. The MODS can fill in the gap created when there is a dearth of the more conventional (and costly) DST platforms in a resource-limited setting like Nigeria. More programmatic support and scale up of simpler susceptibility techniques are required in Nigeria and similar contexts.