Challenges and controversies in defining totally drug-resistant tuberculosis.

In March 2012, in response to reports of tuberculosis (TB) resistant to all anti-TB drugs, the World Health Organization convened an expert consultation that identified issues to be resolved before defining a new category of highly drug-resistant TB. Proposed definitions are ambiguous, and extensive drug resistance is encompassed by the already defined extensively drug-resistant (XDR) TB. There is no evidence that proposed totally resistant TB differs from strains encompassed by XDR TB. Susceptibility tests for several drugs are poorly reproducible. Few laboratories can test all drugs, and there is no consensus list of all anti-TB drugs. Many drugs are used off-label for highly drug resistant TB, and new drugs formulated to combat resistant strains would render the proposed category obsolete. Labeling TB strains as totally drug resistant might lead providers to think infected patients are untreatable. These challenges must be addressed before defining a new category for highly drug-resistant TB.

Selected risk factors associated with pulmonary tuberculosis among Saharia tribe of Madhya Pradesh, central India.

Tuberculosis (TB) is a major public health problem among the Saharia, a marginalized tribal group in Madhya Pradesh state, central India. However, there is no information on the risk factors associated with the development of TB disease in this community. A cross-sectional TB prevalence survey was conducted among the Saharia residing in Sheopur district of Madhya Pradesh. Information on tobacco smoking and alcohol consumption was collected from all the individuals. Persons aged ≥45 years, males, smokers and alcohol consumers had higher risks of developing TB disease. There is an urgent need to develop and implement culturally appropriate awareness raising activities to target smoking and alcohol consumption to support the efforts to control TB in this community.

Safety and availability of clofazimine in the treatment of multidrug and extensively drug-resistant tuberculosis: analysis of published guidance and meta-analysis of cohort studies.

OBJECTIVES: Given the spread of multidrug-resistant tuberculosis (MDR-TB), new therapies are urgently needed, including the repurposing of existing drugs. We aimed to assess key considerations for the clinical and programmatic use of clofazimine (Cfz), a riminophenazine with antimycobacterial activity currently used to treat leprosy. DESIGN: Fixed and random effects meta-analysis of cohort studies and systematic review. SETTING: Electronic and manual searches were combined. INCLUSION CRITERIA: Observational studies on treatment of multidrug-resistant and extremely drug-resistant tuberculosis with Cfz or a Cfz-containing regimen, and published guidance and documents relating to cost and availability were eligible. RESULTS: 5 observational studies enrolled 861 patients, of which 602 received Cfz. The pooled proportion of adverse drug reactions requiring discontinuation of Cfz treatment was 0.1% (95% CI (0.0 to 0.6%)), and the median frequency of all adverse events was 5.1%. Cfz showed in vitro efficacy against Mycobacterium tuberculosis, and Cfz-containing regimens may have had a useful role in the treatment of patients with drug-resistant strains and who had limited alternative treatment options. However, Cfz uptake remains insufficient to meet global needs; there is only one internationally quality-assured manufacturer, which produces a limited quantity of the drug prioritised for treatment of leprosy, the only indication for which the drug is registered. CONCLUSIONS: While the data were limited, Cfz was associated with a risk for adverse drug reactions comparable to that of first-line TB treatment, which could be reasonably managed under programmatic conditions. However, low market availability and high cost are important barriers to access to Cfz for patients with MDR-TB.