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

Background Current tuberculosis management algorithm in Nigeria recommends commencement of multi-drug resistant tuberculosis (MDR-TB) treatment on rifampicin resistance detection, following XpertMTB/Rif (Genexpert) test and subsequent re-direction of therapy after phenotypic drug susceptibility testing. With the current dearth of phenotypic drug susceptibility testing facilities in Nigeria, for quick and precise identification of drug resistant tuberculosis, 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. Method 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), Flouroquinolone (Ofloxacin-1.0 µg), Capreomycin (2.5 µg/ml), Amikacin (2 µg/ml) and Kanamycin (5.0 µg/ml). Result 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). Conclusion With the current MDR-TB treatment algorithm and lack of programmatic support for drug susceptibility testing, a significant number of patients with rifampicin mono-resistance are treated as MDR-TB for prolonged periods. More programmatic support and scale up of simpler susceptibility techniques are required.