According to the World Health Organization (WHO), Viet Nam ranks 12th among 22 high burden tuberculosis (TB) countries, and 14th among 27 high burden multidrug-resistant TB (MDR-TB) countries in the world. “2.7% of new TB cases, and 19% of previously treated cases have MDR-TB in Viet Nam” said Dr Hoang Thanh Thuy of Viet Nam’s national TB Programme (NTP). She was speaking with Citizen News Service – CNS at the 4th Union Asia Pacific Region Conference on Lung Health in Hanoi, Viet Nam. Viet Nam has 3,700 MDR-TB cases annually. Although evidence is weak due to lack of data but people living with HIV (PLHIV) are more likely to get drug-resistant TB, said Dr Thuy basing her observation on higher MDR-TB rates in places where TB-HIV co-infection was reported more in Viet Nam.
Establishing a programme to fight drug-resistant TB is no easy challenge for any country. Drug-resistant TB requires a much stronger and very-well equipped laboratory diagnostic system for correct and early diagnosis and drug susceptibility testing, robust drug supply to ensure uninterrupted therapy for a very long duration (two years or more), and very sensitive counselling and care support system in place to support patients of drug-resistant TB in all possible ways to successful completion of treatment. We also need much more resources to support strengthening of Programmatic Management of Drug-resistant TB (PMDT) in a country among other key measures.One of the fundamental pillars surely is strengthening basic TB care and control to reduce number of new cases of drug-resistant TB.
PMDT in VIETNAM
Viet Nam began establishing PMDT in 2007 after it received approval from Green Light Committee (GLC). GLC serves as a technical advisory body to the Stop TB Partnership and WHO and helps countries that wish to benefit from quality-assured, Second Line anti-TB Drugs (SLDs) at reduced prices. By 2009, first pilot PMDT site was up and running in Ho Chi Minh City of Viet Nam and by 2011, Viet Nam had expanded PMDT to 20 sites which included: 6 MDR-TB treatment sites and 14 sites in satellite provinces. By 2012, 4 satellite provincial sites were upgraded into treatment sites, and 15 more satellite provincial sites were trained adding up to 10 treatment sites and over all 35 PMDT sites in the country. By end of February 2013, 1580 patients of MDR-TB were enrolled and 1379 patients are currently on MDR-TB treatment. Viet Nam NTP aims to enroll 4000 patients in PMDT by 2015.
Dr Thuy said that PMDT in Viet Nam is based upon five principles: 1) sustained political commitment with long-term and sustained investment and leadership; 2) rational case finding strategy, with accurate and timely diagnosis by qualified drug susceptibility testing (DST); 3) proper case management by using standard SLDs with close supervision; 4) uninterrupted supply of SLDs; and 5) standardized recording and reporting systems.
Where should one look for presumptive cases of drug-resistant TB? Dr Thuy said that Viet Nam NTP considers the following people for presumptive MDR-TB: people with TB re-treatment history (relapse or treatment failure cases with history of more than a month’s anti-TB re-treatment), non-converters (people with TB who do not convert from sputum smear positive to sputum smear negative), people co-infected with TB and HIV co-infection and contacts of MDR-TB patients.
Although basic microscopy, solid and liquid culture testing for TB, and drug susceptibility testing (DST) if done properly on quality sputum samples, are reliable, yet new tools such as Line Probe Assay (LPA), Gene Xpert MTB/RIF, have been the game changer in terms of early diagnosis. There are limitations with new tools too, mostly associated with costs and logistics, but their specificity and sensitivity for TB and drug resistance are quite good and reliable.
STRENGTHENING LABORATORY CAPACITY
Viet Nam was successful in mobilizing support from a range of International agencies to support expansion of sites equipped with modern diagnostic tools such as Gene Xpert MTB/RIF. Dr Thuy informed CNS that presently there are 21 culture laboratories in Viet Nam, 27 Gene Xpert laboratories, and 2 DST laboratories (including one DST laboratory in National Lung Hospital).
Out of 27 Gene Xpert MTB/RIF machines currently in use in Viet Nam, 17 were funded by TB CARE I, 5 by TB REACH, 2 by Canadian International Development Agency (CIDA), 1 by Oxford University Clinical Research Unit (OUCRU), 1 by PANTHER, 1 by Foundation for Innovative New Diagnostics (FIND). Viet Nam is currently planning and making efforts to mobilize more resources from The Global Fund to Fight AIDS, Tuberculosis and Malaria (The Global Fund) to establish 26 additional Gene Xpert MTB/RIF machines, and another 9 Gene Xpert MTB/RIF machines from a possible support from UNITAID.
Xpert MTB/RIF is an automated, cartridge-based nucleic amplification assay for the simultaneous detection of TB and rifampicin resistance directly from sputum in under two hours. The technology is based on the GeneXpert platform and was developed as a partnership between FIND, Cepheid Inc. and the University of Medicine and Dentistry of New Jersey, with support from the US National Institutes of Health (NIH).
The WHO had recommended use of Xpert MTB/RIF in December 2010 for diagnosis of TB and initial diagnosis of presumptive cases of drug-resistant TB. Viet Nam puts most presumptive cases of MDR-TB who test positive for rifampicin resistance on MDR-TB treatment without waiting for confirmatory DST and culture results (which may take 2-3 months to come in). Only the following cases of presumptive MDR-TB are not put on standard MDR-TB treatment despite positive diagnosis of rifampicin resistance from Xpert MTB/RIF: children who are newly diagnosed with TB; people co-infected with TB and HIV; those who have been previously been treated with anti-TB SLDs; among others. Some countries such as Indonesia do not begin MDR-TB treatment despite Xpert MTB/RIF diagnosis of rifampicin resistance and prefer to rather confirm the diagnosis with follow-up DST and culture before MDR-TB treatment begins.
Viet Nam has two treatment regimens for MDR-TB, one regimen for new cases of MDR-TB and second regimen for previously treated cases. The difference between the two regimens is that Kanamycin is replaced with Capreomycin; and Cycloserine (Cs) and p-aminosalicylic acid (PAS) both are given for re-treatment cases (and either of them for new cases).
As per PMDT guidelines in Viet Nam, MDR-TB treatment begins with an inpatient treatment phase for about 15 days and discharged when patient is stable and meets other PMDT requirements. Coordination among treatment sites, satellite provinces, districts and communes in the case transfer and treatment monitoring, 100% direct observation, periodic reexamination at the treatment sites, financial support for patients (to meet their travelling and food expenses), financial support for medical staff and health volunteers, financial support for adverse reactions, are other necessary components to strengthen PMDT.
2009 to 2013: 1 to 35 PMDT sites across Viet Nam
PMDT in Viet Nam has expanded coverage from 1 site in 2009 to 35 sites across the country which includes expansion from 1 PMDT treatment centre in 2009 to 10 in 2013.
Proportion of patients who are diagnosed with MDR-TB and those who are enrolled in PMDT and put on treatment has also improved dramatically. In 2010, 252 patients were diagnosed out of which only 38% (97 patients) were enrolled in PMDT. By 2011, 83% of those diagnosed were enrolled in PMDT (578 out of 697 patients), and by 2012, 92% of those diagnosed were enrolled in PMDT (713 out of 774 patients).
Number of re-treatment cases who get screened for MDR-TB also went up as PMDT expanded in Viet Nam. From only 10% re-treatment cases getting screened for MDR-TB in 2009-2010, the number went up to 46% by 2012. Viet Nam has set a target for 2015 to screen 77% re-treatment cases for MDR-TB in 35 provinces and 55% of re-treatment cases for MDR-TB in the entire country.
The PMDT training provided to all 35 sites in the country includes: general PMDT management, clinical management, and a parallel online computer based reporting and recording system (in addition to paper reporting and recording system) called ‘e-TB manager’ software, etc).
Viet Nam has achieved a sputum conversion rate of 75% after 6 months of treatment. The treatment success rate in Viet Nam’s PMDT is 73% (WHO has set a MDR-TB treatment success target of 75% by 2015).
The fight against drug-resistant TB is not easy indeed. Challenges continue to compound the problem. Establishing and maintaining sustained supply chain management system for diagnostic tests and SLDs, developing and updating standards of procedure (SOPs), improving sputum transportation processes, upgrading the information management system from paper to omputerized e-TB manager, regulating private sector where TB drugs are available in open market, calibration of new diagnostic tools, are among some of the key challenges Dr Thuy identifies.
She envisions that Viet Nam’s PMDT will be able to scale up treatment for 916 new MDR-TB patients by end of 2013, 1313 new MDR-TB patients by end of 2014, and 1773 new MDR-TB patients by end of 2015. This might bring total number of patients who might get enrolled in PMDT by 2015 (since 2009 onwards) in Viet Nam to 5490.
GETTING BACK TO BASICS
Some of the very effective ways to reduce number of new cases of drug-resistant TB is to do basic TB care and control as best as possible, uphold high infection control in healthcare settings and communities, and early diagnose and successfully cure people with drug-resistant TB.
DOTS, community based TB care and control initiatives, and other innovative ways to improve basic TB care and control are going to influence how successful PMDT can be in any country globally. Infection control, addressing structural drivers that up the risk of TB or developing drug resistance, high quality adherence counselling, boosting research and development for better and more effective new diagnostics, drugs and vaccines, are among other measures that are likely to impact success of PMDT too. With biggest conference on lung health in Asia Pacific region being held in Hanoi, let us hope Viet Nam gets stronger political and financial mandate to contain TB, including drug-resistant TB.