Total RIF resistance indicative of MDR-TB in treatment-naive patients was 5.52%, far exceeding the World Health Organization predictions (0 to 4.3%). RIF resistance was found in 6/213 (2.8%) cases, INH resistance was found in 3/215 (1.4%) cases, and MDR-TB was found in 8/223 (3.6%) cases. We found significantly different amounts of DR-TB by location (18.18% in the south of the country versus 3.91% in the north central region [P < 0.01]). Furthermore, RIF resistance was genetically distinct, suggesting possible location-specific strains are responsible for the transmission of drug resistance (P < 0.04). Finally, GenoType MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. We found that total DR-TB in HIV-infection is high and that transmission of drug-resistant TB in HIV-infected patients in Nigeria is higher than predicted. Human immunodeficiency virus (HIV) greatly increases the risk for tuberculosis (TB), and the two epidemics continue to fuel one another (31). HIV-infected patients are significantly more likely to develop active TB diseases than non-HIV-infected people and are more likely to die from TB (13,27,28). In subSaharan Africa, 30% of HIV-infected patients who are diagnosed with TB die 12 months after the initiation of treatment (12,33). With an estimated national prevalence of HIV in Nigeria of 3.6% (7), the number of people living with HIV (3.3 million) represents the second largest burden of disease on the continent (32). Nigeria has the world's third largest TB burden, with the prevalence of 830,000 cases. The World Health Organization (WHO) estimates that 26% of patients with TB infection in Nigeria are HIV infected (37).Multidrug-resistant TB (MDR-TB), defined by resistance to isoniazid (INH) and rifampin (RIF), is a growing global health problem (5,19,22). While MDR-TB emerges as a consequence of poor adherence to anti-TB treatment (34,35), it can also be transmitted. MDR-TB results in significantly higher mortality rates in HIV-infected patients than drug-susceptible TB (18). The estimates based on modeling predict MDR-TB prevalence in Nigeria to range from 1.8% (0.0 to 4.3%) for new cases up to 7.7% (0.0 to 18.0%) for previously treated patients (36). Currently in Nigeria, streptomycin is the only treatment available for patients previously treated for TB or suspected of infection with MDR-TB. Furthermore, MDR-TB in HIV-infected individuals leads to higher mortality compared to mortality in non-HIV-infected patients or HIV-infected individuals with susceptible TB (18,24). These findings, combined with alarming evidence that MDR-TB can be transmitted, calls for close monitoring of the incidence of drug resistance, especially in HIV-infected populations (6).The conventional methods of drug resistance testing involve growth of Mycobacterium tuberculosis on liquid or solid culture medium (35). Culture methods are costly and time-consuming, thus limiting both utility for patient care and likelihood of timely treatment. Recently, several new commerci...

Multi-drug (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continues to be a global public health problem especially in high TB burden countries like Nigeria. Many of these cases are undetected and go on to infect high risk individuals. Clinical samples from positive rifampicin resistant Xpert®MTB/Rif assay were subjected to direct whole genome sequencing and bioinformatics analysis to identify the full antibiotics resistance and lineage profile. We report two (2) XDR TB samples also belonging to the East-Asian/Beijing family of lineage 2 Mycobacterium tuberculosis complex from clinical samples in Nigeria. Our findings further reveal the presence of mutations that confer resistance to first-line drugs (rifampicin, isoniazid, ethambutol and pyrazanimide), second-line injectables (capreomycin, streptomycin, kanamycin and/or amikacin) and at least one of the fluoroquinolones (ofloxacin, moxifloxacin, levofloxacin and/or ciprofloxacin) in both samples. The genomic sequence data from this study not only provide the first evidence of XDR TB in Nigeria and West Africa, but also emphasize the importance of WGS in accurately detecting MDR and XDR TB, to ensure adequate and proper management treatment regimens for affected individuals. This will greatly aid in preventing the spread of drug resistance TB in high burden countries.

Multi-drug (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continues to be a global public health problem especially in high TB burden countries like Nigeria. Many of these cases are undetected and go on to infect high risk individuals. Clinical samples from positive rifampicin resistant Xpert®MTB/Rif assay were subjected to direct whole genome sequencing and bioinformatics analysis to identify the full antibiotics resistance and lineage profile. We report two (2) XDR TB samples also belonging to the East-Asian/Beijing family of lineage 2 Mycobacterium tuberculosis complex (MTBC) from clinical samples in Nigeria. Our findings further reveal the presence of resistance genes to first-line drugs (rifampicin, isoniazid, ethambutol and pyrazanimide), second-line injectables (capreomycin, streptomycin, kanamycin and/or amikacin) and at least one of the fluoroquinolones (ofloxacin, moxifloxacin, levofloxacin and/or ciprofloxacin) in both samples. The genomic sequence data from this study not only provide the first evidence of XDR TB in Nigeria and West Africa, but also emphasize the importance of WGS in accurately detecting MDR and XDR TB, to ensure adequate and proper management treatment regimens for affected individuals. This will greatly aid in preventing the spread of drug resistance TB in high burden countries.

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