Detection of Multidrug Resistant Tuberculosis (MDR-TB) among Rifampicin-resistant TB patients using Line Probe Assay (LPA) in Kano, Nigeria

Abstract

The Emergence of drug-resistant Mycobacterium tuberculosis strains especially multidrug resistant-TB (MDR-TB) and indeed extensively drug resistant TB (XDR-TB) is considered a real threat to achieving TB control. Thus, the WHO identified the need for accelerated access to rapid testing for rifampicin resistance to improve case detection in all patients with suspected MDR and XDR-TB. This study aimed at detecting MDR status of rifampicin-resistant TB patients in north western part of Nigeria, as such information was found to be rare in this part of Nigeria. It was a descriptive cross-sectional study conducted at Aminu  Kano Teaching Hospital, North-West TB reference Laboratory and purposive sampling technique was used in selecting  patients for the study. Data generated was presented using descriptive statistics. Sputum samples were collected and  processed according to standard mycobacteriological procedures. The presence of M. tuberculosis complex (MTBC) was  confirmed using SD BIOLINE TB Ag MPT64 Rapid test. Genotypic assays were carried out on these samples by the  GenoType® MTBDRplus molecular line prove assay (LPA). The results of the study revealed that of the 88 sputum samples  collected from rifampicin resistant (confirmed by Genxpert from referring centres) TB patients, 74 (84.09%) were males and  14 (15.9%) were females. Most of them were aged 21-30 years and 31-40 years. Also, 86 of the sputum samples were  confirmed as MTBC. Genotypic assays revealed that 48/88 (54.5%) of the samples were identified as MDR-TB, 29 (32.9%) were rifampicin mono-resistant cases while only 1(1.36%) was resistant to isoniazid and 8 samples were found to be  susceptible to both isoniazid and rifampicin. The pattern of genetic mutations revealed that rifampicin resistance due to the missing rhoB WT gene and the presence of rhoB MUT gene was seen in 77/78 (98.7%) and 51/78 (61.4%) of the rifampicin-resistance samples respectively and isoniazid resistance due to katG missing WT gene and katG MUT gene region was seen in 35/78 (44.9%) of the samples. Among the MDR-TB cases rifampicin resistance was associated with rpoB WT gene and rpoB MUT gene in 100% and 62% of the isolates, and INH resistance was associated with katG WT gene and katG MUT gene in 70.8% and 72.9% of the isolates respectively. INH resistance in the MDR-TB cases was further associated with InhA WT and InhA MUT in 16.67% and 4.17% of the isolates respectively. The study concludes by identifying that the reported MDR-TB rate of 54.5% among rifampicin-resistant TB patients in the study was rather alarming and also identifies the need for expertize in the conduct and diagnosis of rifampicin-resistance status of TB patients using the GeneXpert techniques lack of which may be detrimental to the health of the patient.Thus, the study solicits for a much more committed TB control programmesincluding provision and training of manpower by the relevant agencies as a well as putting more efforts towards rapid and accurate diagnosis of TB patients, and proper treatment and management of the infected cases to minimize the spread and evolution of MDR-TB and indeed XDR-TB whose treatment is presented with more challenges.

Keywords: Rifampicin resistance, MDR-TB, LPA, North-Western zone, Nigeria.