Diagnosing tuberculosis (TB) and also getting to know with accuracy about resistance to one of the two most powerful anti-TB drugs (Rifampicin) is increasingly becoming a reality on the ground. The largest-ever roll-out of Gene Xpert MTB/RIF machines in countries most severely hit by drug-resistant TB was launched on 10th September 2013 at the National Tuberculosis Reference Laboratory in Yangon, Myanmar, with support from UNITAID, an organization whose 70% funding is raised by innovative financing mechanisms such as levying a small fee on airline tickets.
UNITAID has invested USD 25.9 million to purchase over 220 GeneXpert machines and 1.4 million test cartridges for 21 countries in Africa, Eastern Europe and Asia. Coordinated by the World Health Organization (WHO) and the Stop TB Partnership, this project – known as TBXpert – is estimated to save an additional 62,000 lives.
TURNAROUND TIME REDUCED FROM 2-3 MONTHS TO WITHIN 2 HOURS
TB and drug susceptibility testing - DST (test done to find to which anti-TB drugs TB bacterium might be sensitive or resistant to) reports take a long time to come unless done by rapid diagnostic techniques. Solid culture TB diagnostic method takes about 2-3 months, liquid culture TB diagnostic method takes about 2-3 weeks and Line Probe Assay (LPA) TB diagnostic method takes about 3-7 days to give back a report. Now with Gene Xpert MTB/RIF on the ground the patient can get the report within two hours. Unlike Gene Xpert MTB/RIF, solid and liquid cultures and LPA TB diagnostic test methods require highly equipped state-of-the-art bio safety level II and III laboratories to function. Gene Xpert MTB/RIF can operate with satisfactory efficiency in clinic setting. By rolling out GeneXpert machines in resource-poor and high burden TB (and Multidrug-Resistant TB or MDR-TB) countries we are surely overcoming a major hurdle of establishing cost-intensive laboratories.
Dr Fuad Mirzayev of the WHO Global Tuberculosis Programme said that 1400 Gene Xpert MTB/RIF machines have already been put to use in 88 countries. Three million cartridges have been used from December 2010 till end of last year. Largest-ever roll-out of Gene Xpert in 21 countries will increasingly make early and accurate diagnosis of TB and drug resistance a reality on the ground.
Gene Xpert MTB/RIF is also empowering clinics and DOTS centres on the frontlines with their expanded capacity to hand over the TB test report (and Rifampicin drug sensitivity report) within two hours to the patient, reducing the time for initiating proper treatment as required. "Diagnosing TB and rifampicin drug resistance earlier will not only help improve early access to care for people with TB or drug-resistant TB but also reduce TB transmission in the community," said Dr Tin Mi Mi Khaing, Regional TB Officer, Yangon Region in Myanmar.
SPUTUM SMEAR NEGATIVE SAMPLES CAN BE TESTED WITHIN TWO HOURS
“Gene Xpert MTB/RIF fills in a big niche”, remarked Dr Fuad Mirzayev. Samples from patients that are sputum smear positive are sent to laboratories with LPAs for testing, reports of which take 3-7 days to come. But sputum smear negative samples cannot be tested by LPA and had to be sent for culture testing (reports of which will take between 2-3 weeks to 2-3 months to come). Gene Xpert MTB/RIF has helped reduce the time for testing of sputum smear negative samples as well to within two hours. The best is yet to come, as point-of-care TB and drug susceptibility testing (DST) is top on the wish list for research and development of new TB diagnostics, which Dr Fuad believes will help boost TB control significantly.
SEEING IS BELIEVING: Gene Xpert MTB/RIF at DOTS centres
Citizen News Service – CNS visited a Model DOTS Centre of North Okkalapa Township, in Yangon, Myanmar where a Gene Xpert MTB/RIF machine has been installed with support from UNITAID on 27 August 2013. Dr Khin Zaw Latt, a microbiologist at this DOTS centre said that 17 samples have been tested by this machine since then out of which 7 came positive for TB and 2 also had Rifampicin resistance. Resistance to rifampicin is considered as a surrogate marker for resistance to isoniazid, another powerful anti-TB drug as mono-resistance to rifampicin is fairly uncommon. So a positive result for Rifampicin resistance by Gene Xpert MTB/RIF indicates that the patient has MDR-TB and should be put on the standard MDR-TB treatment.
POWER OUTAGE IS A CHALLENGE
Speaking to CNS about her experience of using a Gene Xpert MTB/RIF machine at a DOTS centre, Dr Khin Zaw Latt said that electricity supply is one of the challenges. If there is a power breakdown when Gene Xpert is testing samples then the cartridges will go waste. To overcome this challenge, Gene Xpert machine installed at this DOTS centre had a power backup from batteries and very soon a generator is expected to be installed to further ensure uninterrupted power supply. We also saw another Gene Xpert machine installed at the Mandalay General Hospital in Myanmar that had a power backup too.
Air-conditioning required where temperatures are over 35-40 degrees Celsius
Dr Fuad Mirzayev explained to CNS that Gene Xpert performs PCR (Polymerase Chain Reaction) that increases the temperature manifold but does not have an advanced cooling mechanism other than a fan. For DOTS centres or places where temperature is more than 35-40 degrees Celsius installing an air-conditioner will ensure normal functioning of Gene Xpert. Diagnosing TB and testing for drug resistance outside of resource intensive Bio-Safety Level (BSL) II or III laboratories is finally becoming a reality in increasing centres in high burden TB countries.
POTENTIAL TO IMPROVE PUBLIC HEALTH IN MYANMAR
Dr Min Than Nyunt, Director General, Department of Health, Myanmar said that bio-safety level III laboratories where solid and liquid culture and LPA testing is done for TB and DST were launched in Yangon and Mandalay in 2009 onwards. UNITAID had helped support building the infrastructure and training of technical staff to improve TB diagnostics and drug susceptibility testing in Myanmar.4.2% of new TB cases and about 10% of previously treated TB cases are found resistant to two most powerful anti-TB drugs in Myanmar thus needing treatment for MDR-TB. About 3,300 MDR-TB patients have benefited since then by receiving standard and quality assured diagnostics and treatment support since then. Cure rate of MDR-TB treatment in Myanmar is 70%.
There are 19 Gene Xpert machines functioning in Myanmar presently which includes: 4 machines provided with support from UNITAID; 3 machines provided with support from the International Union Against Tuberculosis and Lung Disease (The Union); 3 machines provided with support from Medicins Sans Frontieres (MSF) Holland; 6 machines provided with support from Global Fund to Fight AIDS, Tuberculosis and Malaria (The Global Fund), 1 machine provided with support from FHI 360; and 2 machines provided with support from Stop TB CIDA.
GETTING MORE VALUE FOR EVERY DOLLAR SPENT ON TB CONTROL
Dr Denis Broun, Executive Director, UNITAID, said that UNITAID's priority was to find market solutions to benefit everyone globally. UNITAID was part of the team that negotiated significantly reduced prices for TB diagnostics and supplies so that everyone can get more value for the investment they make in TB control. The cost of Gene Xpert machine and cartridges has come down after successful negotiations were held by US Agency for International Development (USAID), US President's Emergency Plan For AIDS Relief (PEPFAR), UNITAID and Bill and Melinda Gates Foundation with the manufacturer, Cepheid. The cost of cartridges of Gene Xpert came down by nearly 42% to USD 9.98 (from USD 17) and cost of Gene Xpert machine came down to USD 17,000 (with desktop) or USD 17,500 (with laptop).
TB financing has also increased in Myanmar over the past years. Dr Erwin Cameroon of WHO said that few years back TB was among the orphan diseases disproportionately affecting poor with very little financial and political commitments. However now the TB response has changed for good and budget for TB control in Myanmar has increased twenty fold.
Diagnosing people with TB and drug-resistant TB early and accurately is one of the top priorities. Providing standard and quality assured uninterrupted treatment as early as possible after accurate diagnosis is another challenge confronting countries heavily affected by TB. More investment and strengthening of procurement and logistical systems must happen without delay to ensure the gains made by early diagnosis are optimally able to improve treatment success and cure rates on the ground.