BackgroundNigeria has a high tuberculosis incidence, and genotyping studies of Mycobacterium tuberculosis Complex (MTC) in the country are necessary in order to improve our understanding of the epidemic.MethodsIsolates of MTC were isolated from cases of pulmonary tuberculosis in Jos, North Central region of Nigeria during 2006-2008. Drug susceptibility test (DST) was performed on 77 of 111 isolates by proportion method on Lowenstein Jensen (LJ) slope while genotyping of mycobacterial DNA was performed by spoligotyping. The SpolDB4 database and the model-based program 'spotclust' were used to assign isolates to families, subfamilies and variants.ResultsA total of 111 pulmonary isolates from consecutive tuberculosis patients in the city of Jos, Plateau State, Nigeria were spoligotyped. A total of 84 (76%) of the isolates belonged to the Latin American Mediterranean (LAM) family. Of these, 78 isolates were assigned to the LAM10 lineage. Among these, 66 exhibited identical spoligopatterns. Drug susceptibility profiles obtained were not consistently associated with any spoligopattern.ConclusionsThe dominance of few M. tuberculosis lineages suggests either a high rate of transmission, frequent import of closely related strains, or a highly conserved genotype. It remains to be confirmed whether the predominance of identical LAM10 represent an outbreak.Spoligotyping was useful to gain an overall understanding of the local TB epidemic. This study demonstrated that the incidence of TB in Jos, Nigeria may be caused by a few successful M. tuberculosis families, dominated by the LAM10 family.
BackgroundXpert MTB/Rif (Xpert) is described as a game changer in tuberculosis (TB) control. We evaluated the impact of Xpert on diagnosis, time to treatment, and treatment outcome among patients with HIV associated TB in Nigeria.MethodsAdults with HIV being evaluated for pulmonary TB (PTB) were consecutively enrolled into the study cohort. At baseline, expectorated sputa were examined using Xpert and smear microscopy for Mycobacterium tuberculosis (MTB) and acid fast bacilli, respectively. Patients diagnosed with TB were followed-up until 6 months post TB diagnosis. TB was defined as sputum positive by smear microscopy, Xpert detection of MTB (bacteriologically confirmed case), or clinician diagnosed TB with initiation of full TB treatment (clinical diagnosis). Time to treatment was time from first clinic presentation for TB evaluation to initiation of TB treatment. We examined the proportion PTB patients with a positive Xpert result and compared time to TB treatment and outcome of TB treatment in patients based on sputum test results.ResultsA total of 310 adults with HIV were enrolled. The median CD4 cell count was 242 (interquartile range (IQR) 120–425) cells/mm3 and 88.1% were receiving antiretroviral therapy (ART). PTB was diagnosed in 76 (24.5%) patients, with 71 (93.4%) being bacteriologically confirmed. Among patients with PTB, 56 (73.7%) were Xpert positive. Median time to treatment was 5 (IQR 2–8) days and 12 (IQR 5–35) days in patient with and without Xpert positive results, respectively; p = 0.005. Overall 73.1% had symptom free survival at 6 months post PTB treatment initiation with no significant differences observed based on TB test method. 10 (14.9%) died within 6 months of TB treatment initiation. In analysis adjusted for age, sex, and mode of diagnosis (Xpert positive or negative), only ART use independently predicted mortality (AOR 0.10; 95% CI 0.01–0.93).ConclusionThe use of Xpert for routine care reduced time to PTB treatment, but did not improve survival in patients with HIV treated for susceptible PTB.
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...
Background: To achieve early diagnosis and effective treatment of pulmonary tuberculosis, simple and sensitive methods that enhance the detection of Mycobacterium tuberculosis (M. tuberculosis) from clinical specimens are needed. This study compared the effectiveness and suitability of an insertion sequence (IS 6110) based polymerase chain reaction (PCR) assay with conventional methods for the detection of M. tuberculosis from clinical specimens in a resource-limited setting. Methods: Sputa from 101 HIV-positive patients and 40 clinical specimens (sputa, gastic wash out, ascitic fluid, pleural fluid and cerebrospinal fluid) collected from children (HIV status unknown), all suspected for pulmonary tuberculosis at the Jos University Teaching Hospital, Jos, (JUTH) Nigeria, were examined by Ziehl Neelsen (ZN) smear microscopy, Lowenstein Jensen's (LJ) egg-based culture, and PCR methods for the detection of M. tuberculosis Results: Mycobacteria was detected in 45/101 (44.6%) of the specimens from the HIV-positive patients and comprised of 6% ZN
The drug resistance profile of 100 Mycobacterium tuberculosis isolates from pulmonary tuberculosis (PTB) cases in Jos, Nigeria, was investigated between August 2006 and September 2007. Drug susceptibility testing for 50 new, 11 follow-up and 39 unclassified cases of PTB was performed on Löwenstein-Jensen medium by the proportion method, using isoniazid (0.2 microg/ml), rifampicin (40 microg/ml), ethambutol (2 microg/ml) and streptomycin (4 microg/ml). Susceptibility to all four drugs was found in 76, 62 and 55%, and multidrug resistance (combined resistance to isoniazid and rifampicin with or without resistance to any other drug) in 4, 31 and 18% of the new, unclassified and follow-up cases, respectively. Monoresistance was found in 15% of the cases. Nine of the 16 isolates (56%) showing multidrug resistance were resistant to all four drugs. These findings are critical and the risk to public health is high, particularly with an overall multidrug resistance of 16%. We suggest that TB management and control programs in Jos are revised to enhance patient's accessibility to treatment sites, promote patients' adherence to drugs, improve diagnostic practices, regularly assess drug resistance profiles, and undertake contact tracing for patients with multidrug-resistant TB.
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