Performance-based technical support for drug-resistant TB responses: lessons from the Green Light Committee.

Drug-resistant tuberculosis (DR-TB) constitutes a global threat and a major contributor to deaths related to antimicrobial resistance. Despite progress in DR-TB detection and treatment over the last decade, huge gaps remain in treatment coverage, access to quality care and treatment outcome. Global Fund investments have been critical to scaling up the existing and new diagnostic tools, treatment coverage and people-centred service delivery. The United Nations General Assembly (UNGA) high-level meeting represents unprecedented opportunities to accelerate towards addressing DR-TB. Established in 2000 and funded by the Global Fund since 2009, the Green Light Committee (GLC) mechanism has evolved from project approval to providing demand-based technical assistance to countries to scale up response to DR-TB based on their need and priorities. Lessons learnt from the GLC mechanism over 10 years demonstrate that a result-based, systematic and accountable technical assistance model to support scale-up of DR-TB response is critically important. Meeting the UNGA declaration targets requires major scale-up of current efforts and new tools, and hence the need for predictable, consistent and sustained technical support to countries, including through the regional GLC mechanism. The application of the principles and processes of this model could be adapted and replicated to design a similar performance-based and quality-assured technical support mechanism.

Point of care diagnostics for tuberculosis.

The goals of the End TB strategy, which aims to achieve a 90% reduction in tuberculosis (TB) incidence and a 95% reduction in TB mortality by 2035, will not be achieved without new tools to fight TB. These include improved point of care (POC) diagnostic tests that are meant to be delivered at the most decentralised levels of care where the patients make the initial contact with the health system, as well as within the community. These tests should be able to be performed on an easily accessible sample and provide results in a timely manner, allowing a quick treatment turnaround time of a few minutes or hours (in a single clinical encounter), hence avoiding patient loss-to-follow-up. There have been exciting developments in recent years, including the WHO endorsement of Xpert MTB/RIF, Xpert MTB/RIF Ultra, loop-mediated isothermal amplification (TB-LAMP) and lateral flow lipoarabinomannan (LAM). However, these tests have limitations that must be overcome before they can be optimally applied at the POC. Furthermore, worrying short- to medium-term gaps exist in the POC diagnostic test development pipeline. Thus, not only is better implementation of existing tools and algorithms needed, but new research is required to develop new POC tests that allow the TB community to truly make an impact and find the "missed TB cases".

Geographical heterogeneity of multidrug-resistant tuberculosis in Georgia, January 2009 to June 2011.

In 2011, Georgia, in the Caucasus, reported that 11% of new and 32% of previously treated tuberculosis (TB) cases nationally had multidrug-resistant TB (MDR-TB). To help understand the mechanisms driving these high risks of drug-resistance and plan for targeted interventions, we identified geographical variability in the MDR-TB burden in Georgia and patient-level MDR-TB risk factors. We used routinely collected surveillance data on notified TB cases to estimate the MDR-TB incidence/100,000 people and the percentage of TB cases with MDR-TB for each of 65 districts and regression modelling to identify patient-level MDR-TB risk factors. 1,795 MDR-TB cases were reported (January 2009­June 2011); the nationwide notified MDR-TB incidence was 16.2/100,000 but far higher (837/100,000) in the penitentiary system. We found substantial geographical heterogeneity between districts in the average annual MDR-TB incidence/100,000 (range: 0.0­5.0 among new and 0.0­18.9 among previously treated TB cases) and the percentage of TB cases with MDR-TB (range: 0.0%­33.3% among new and 0.0%­75.0% among previously treated TB cases). Among treatment-naïve individuals, those in cities had greater MDR-TB risk than those in rural areas (increased odds: 43%; 95% confidence interval: 20%­72%). These results suggest that interventions for interrupting MDR-TB transmission are urgently needed in prisons and urban areas.

Outcomes of children treated for tuberculosis with second-line medications in Georgia, 2009-2011.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a major public threat in countries of the former Soviet Union, including Georgia. There are few studies of pediatric DR-TB cases, especially at a national level. OBJECTIVE: To report the characteristics and treatment outcomes of pediatric multidrug-resistant TB (MDR-TB) cases in Georgia. METHODS: We extracted data on all pediatric (age <16 years) MDR-TB cases notified in Georgia from 2009 to 2011. We assessed the baseline and treatment characteristics and treatment outcomes of this cohort. RESULTS: Between 2009 and 2011, there were 45 notified pediatric DR-TB cases in Georgia. Just over half had previously received anti-tuberculosis treatment and the median age was 7.7 years. Time from diagnosis to treatment was short (median 16 days), and the median length of treatment was 20.2 months. Of those not still on treatment, 77.1% (95%CI 61.0-87.9) had a successful outcome. CONCLUSIONS: One of the first reports of pediatric DR-TB treatment outcomes at a national level, this study demonstrates that successful outcomes can be achieved.

Outcomes among tuberculosis patients with isoniazid resistance in Georgia, 2007-2009.

BACKGROUND: The optimal management strategy for patients with isoniazid (INH) monoresistant forms of tuberculosis (TB) has been widely debated. The current daily 9-month regimen of rifampin, pyrazinamide and ethambutol was established based largely on trials in settings with low TB rates and low rates of drug resistance. OBJECTIVE: To explore the outcomes of patients with INH-monoresistant TB in the country of Georgia, a setting with both high TB rates and drug-resistant forms of the disease. METHODS: Retrospective record review of all patients diagnosed with smear-positive pulmonary TB resistant to either INH or INH+SM (streptomycin) in Georgia between 2007 and 2009. RESULTS: Of 8752 patients with pulmonary TB registered in Georgia, 909 were found to have INH or INH+SM resistance. Treatment outcomes were relatively poor in this group, with only 71% treatment success. Outcomes were significantly worse among patients with older age and a history of previous treatment. CONCLUSIONS: INH or INH+SM resistance in pulmonary TB patients in Georgia is common. The low rates of treatment success suggest the need for an improved treatment regimen for patients with resistance to these first-line drugs; this need is particularly pronounced among the subset of patients with a history of previous treatment.