Mitigation of Discordant Rifampicin-Susceptibility Results Obtained by Xpert Mycobacterium tuberculosis/Rifampicin and Mycobacterium Growth Indicator Tube.

BACKGROUND: Simultaneous use of genotypic and phenotypic diagnostic tools for detection of rifampicin (RIF) susceptibility may yield discrepant results. OBJECTIVE: To measure the discordance between the RIF-susceptibility results by Xpert MTB/RIF and Mycobacterium Growth Indicator Tube (MGIT), to evaluate if application of both tests to the same sample affects the discrepancy, and to evaluate treatment outcome in patients with the discordant strains. DESIGN: Sputa from patients with tuberculosis managed in the penitentiary system of Azerbaijan during 2011-2015 were examined for RIF susceptibility using Xpert MTB/RIF and MGIT. Strains with discrepant results were sequenced. RESULTS: Of 532 patients included, 6.2% had discordant RIF-susceptibility results. No significant association of the discordant RIF-susceptibility results with application of both tests on one sample versus sequential samples was found. L511P mutation accounted significantly (p = 0.006) for the discrepancy among those RIF resistant on Xpert MTB/RIF, but sensitive on MGIT. No significant association was identified between the outcomes of treatment with the first- or second-line drugs and the presence of any mutation. CONCLUSION: The Xpert MTB/RIF and MGIT testing may be used in sequential sputum samples without increase in the RIF-susceptibility discordance rate. L511P mutation significantly accounts for discordant RIF-susceptibility results, but its clinical relevance may be low.

HLA class II sequence variants influence tuberculosis risk in populations of European ancestry.

Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 × 10(-13)) and PTB (OR = 1.25, P = 5.8 × 10(-12)), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 × 10(-12))--both located between HLA-DQA1 and HLA-DRB1--and a missense variant encoding p.Ala210Thr in HLA-DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 × 10(-9), OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 × 10(-4)). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells.

[Multidrug resistant tuberculosis in Iceland--case series and review of the literature]. / Fjölónaemir berklar á Islandi--tilfellaröd og yfirlit.

BACKGROUND: Multidrug resistant tuberculosis (MDR-TB) is a growing health problem in the world. Treatment outcomes are poorer, duration longer and costs higher. We report three cases of MDR-TB diagnosed in Iceland in a six year period, 2003-8. CASE DESCRIPTIONS: The first case was a 23-year-old immigrant with a prior history of latent TB infection treated with isoniazid. He was admitted two years later with peritoneal MDR-TB. He was treated for 18 months and improved. The second case was a 23-year-old immigrant diagnosed with pulmonary MDR-TB after having dropped out of treatment in his country of origin. Clinical and microbiological response was achieved and two years of treatment were planned. The third case involved a 27-year-old asymptomatic woman diagnosed with MDR-TB on contact tracing, because of her brother's MDR-TB. 18 months of treatment were planned. CONCLUSIONS: Clustering of cases of MDR-TB in the last six years, accounting for almost 5% of all Icelandic TB cases in the period, suggests that an increase in incidence might be seen in Iceland in coming years. The infection poses a health risk to the patients and the general public as well as a financial burden on the health care system. Emphasis should be put on rapid diagnosis and correct treatment, together with appropriate immigration screening and contact tracing.

Barriers to reaching the targets for tuberculosis control: multidrug-resistant tuberculosis.

The development and expansion of WHOs DOTS strategy was successful, with 83% of the worlds population living in countries or parts of countries covered by this strategy by the end of 2004. Treatment success in the 2003 DOTS cohort of 1.7 million patients was 82% on average, close to the 85% target. Treatment success was below average in the African Region (72%), which can be partly attributed to occurrence of HIV co-infection, and in the European Region (75%), partly due to drug resistance. Drug resistance, specifically multidrug resistance and extensive drug resistance, is a serious threat to public health in all countries, especially in the Russian Federation, where the highest rates of multidrug resistance are presently accompanied by a rapid increase in HIV infection. Based on the experience of the first projects approved by the Green Light Committee, the treatment success of patients with multidrug-resistant tuberculosis (MDR-TB) is lower than that of drug-susceptible cases, but nevertheless reaches 70%. The collaborative effort of different organizations, professionals and communities is needed to address the development and spread of multidrug resistance and extensive drug resistance, which combined with the epidemic of HIV infection is one of the barriers to dealing effectively with TB. This effort should be directed towards facilitating the diagnosis and treatment of TB patients, in particular by improving access to drug susceptibility testing and strengthening treatment delivery by rigorous adherence to DOTS as outlined by the Stop TB Partnership.

Multidrug-resistant tuberculosis management in resource-limited settings.

Evidence of successful management of multidrug-resistant tuberculosis (MDRTB) is mainly generated from referral hospitals in high-income countries. We evaluate the management of MDRTB in 5 resource-limited countries: Estonia, Latvia, Peru, the Philippines, and the Russian Federation. All projects were approved by the Green Light Committee for access to quality-assured second-line drugs provided at reduced price for MDRTB management. Of 1047 MDRTB patients evaluated, 119 (11%) were new, and 928 (89%) had received treatment previously. More than 50% of previously treated patients had received both first- and second-line drugs, and 65% of all patients had infections that were resistant to both first- and second-line drugs. Treatment was successful in 70% of all patients, but success rate was higher among new (77%) than among previously treated patients (69%). In resource-limited settings, treatment of MDRTB provided through, or in collaboration with, national TB programs can yield results similar to those from wealthier settings.