About MDR-TB

Multidrug Resistant Tuberculosis (MDR-TB)

Presently, Tuberculosis (TB) is the second greatest contributor among infectious diseases to adult mortality, being responsible for approximately two million deaths a year worldwide. Therefore, World Health Organization (WHO) has implemented a tuberculosis control strategy called DOTS. It gives strict guidelines on how this disease should be treated. In countries where DOTS has been implemented the cure rate for drug susceptible cases (susceptible tuberculosis) has increased up to approximately 85%.
There is another reason besides improving the survival rate and curbing the spread of the tuberculosis why the WHO has introduced the DOTS program. If tuberculosis is treated inappropriately (the administration of drugs is stopped prematurely or is not done properly) the patient may not only remain sick, but the bacteria that causes the illness may develop resistance to drugs ordinarily used to treat tuberculosis. In the most severe form, this resistance to drugs is called Multi-drug Resistant Tuberculosis (MDR-TB). It is extremely dangerous, and if not treated, lethal. It is difficult to treat, as the drugs used are often toxic and can cause side effects. The treatment time is approximately 2 years and the cost is far greater than that of drug susceptible tuberculosis. The people infected with this disease spread it readily to others. Therefore, it is of utmost importance to stop the development of and spreading of MDR-TB. The estimates are that MDR-TB is found mostly in former Soviet Union countries and in Central Asia. There, cases of MDR-TB reach 10% of all tuberculosis cases. Among cases never treated, the proportions of primary multi-drug resistant cases were very high in the Baltic states (9-12%) and Central Asia states (10 -14%) (EuroTB, report on 2000).
WHO has introduced another set of guidelines that regulate treatment of MDR-TB. This program is called DOTS-Plus. Implementation of DOTS-Plus program requires specific knowledge and skills; therefore, the doctors, nurses and other people involved in it need additional training

MDR-TB is a regional problem in the Baltic and the former Soviet Union; the factors that have led to its development and spread as well as the patient populations affected are highly similar throughout the region.
Latvia has one of the highest rates of drug resistance in the world; in 1997, 8.9% of new patients had MDR-TB; this compares with 1.6% in the USA and less than 1% in most African countries. Rates of MDR-TB in the civilian population in Russian oblast where drug resistance has been measured are similar to those in Latvia; levels in Estonia are even higher, with 15% of new patients having MDR-TB.
TB program of Latvia is in the vanguard in the region. Its basic TB program was initiated in 1995, in advance of the rest of the former Soviet Union and follows the WHO DOTS strategy. Coverage was nearly 95%, and the cure rate of 72% in 1999 although not as high as desired by the national program, is approaching acceptable values according to the WHO standards. Furthermore, Latvia was the only country in the region performing large-scale treatment of MDR-TB patients according to WHO recommendations, with 200-250 patients yearly on treatment with drugs funded by the Latvian Government.
WHO recommends that MDR-TB treatment cannot be initiated until strong basic TB program is in place to prevent the development of additional cases of MDR-TB and ensure that patients who are treated for MDR-TB do not develop resistance to the few remaining drugs that are used in its treatment. The management of MDR-TB is complex and WHO recommends that it be treated only in specialized centers with high trained clinical staff and a quality laboratory.
Several of the countries (in the case of Russia, several oblasts) are now implementing the WHO recommended TB strategy for basic TB treatment known DOTS. Countries in the region that have started DOTS will achieve adequate coverage and acceptable cure rates. At this point, they will need to begin MDR-TB treatment and there will be a substantial need for expertise in treating MDR-TB.

DOTS

The internationally-recommended TB control strategy is DOTS. DOTS combines five elements: political commitment, microscopy services, drug supplies, surveillance and monitoring systems, and use of highly efficacious regimes with direct observation of treatment.
Once patients with infectious TB (bacilli visible in a sputum smear) have been identified using microscopy services, health and community workers and trained volunteers observe and record patients swallowing the full course of the correct dosage of anti-TB medicines (treatment lasts six to eight months). The most common anti-TB drugs are isoniazid, rifampicin, pyrazinamide, streptomycin and ethambutol.
Sputum smear testing is repeated after two months, to check progress, and again at the end of treatment. A recording and reporting system documents patients' progress throughout, and the final outcome of treatment.

DOTS
is THE MOST EFFECTIVE STRATEGY
available for controlling the TB epidemic today

• DOTS produces cure rates of up to 95 percent even in the poorest countries.
• DOTS prevents new infections by curing infectious patients.
• DOTS prevents the development of multidrug-resistant tuberculosis (MDR-TB) by ensuring the full course of treatment is followed.
• A six-month supply of drugs for DOTS costs US $11 per patient in some parts of the world. The World Bank has ranked the DOTS strategy as one of the "most cost-effective of all health interventions."

Since DOTS was introduced on a global scale in 1995, over 10 million infectious patients have been successfully treated under DOTS programmes. In half of China, cure rates among new cases are 96 percent. In Peru, widespread use of DOTS for more than ten years has led to the successful treatment of 91 percent of cases, and a reduction in incidence of new cases.

THE FIVE ELEMENTS OF THE DOTS STRATEGY
DOTS has FIVE key components:

• Government commitment to sustained TB control activities.
• Case detection by sputum smear microscopy among symptomatic patients self-reporting to health services.
• Standardized treatment regimen of six to eight months for at least all sputum smear- positive cases, with directly observed therapy (DOT) for at least the initial two months.
• A regular, uninterrupted supply of all essential anti-TB drugs.
• A standardized recording and reporting system that allows assessment of treatment results for each patient and of the TB control programme performance overall.

Political commitment

Government commitment to sustained TB control is ESSENTIAL for the mobilization of resources and the sustainability of TB programmes.

Case detection and diagnosis

Sputum smear microscopy is the MOST COST-EFFECTIVE method of screening pulmonary TB suspects referring to health services. It identifies sputum smear-positive, highly infectious TB cases.
TB is diagnosed using patient history, clinical examination and diagnostic tests. A sputum sample is submitted to the laboratory and the results of the microscopic exam are entered into the laboratory register. The goal is for all suspects to have a sputum smear microscopy exam and for all patients diagnosed with TB to be registered and treated.

Standardized short-course chemotherapy with direct observation of drug intake

Short-course chemotherapy refers to a TREATMENT REGIMEN THAT LASTS SIX TO EIGHT MONTHS AND USES A COMBINATION OF POWERFUL ANTI-TB DRUGS.
Directly observed therapy (DOT) is ESSENTIAL AT LEAST DURING THE INTENSIVE PHASE OF TREATMENT (the first two months) to ensure that the drugs are taken in the right combinations and for the appropriate duration.
With direct observation of treatment, the patient doesn't bear the sole responsibility of adhering to treatment. Health care workers, public health officials, governments, and communities must all share the responsibility and provide a range of support services patients need to continue and finish treatment. One of the aims of EFFECTIVE TB CONTROL is to organize TB services which are integral part of health systems so that the patient has flexibility in where he or she receives treatment, for example in the home or at the workplace. Treatment observers can be anyone who is willing, trained, responsible, acceptable to the patient and accountable to the TB control services.

Drug supply

Where DOTS is implemented, an accurate recording and reporting system provides the information needed to plan and MAINTAIN ADEQUATE DRUG STOCKS.

Recording and reporting

The recording and reporting system is used to SYSTEMATICALLY EVALUATE PATIENT PROGRESS AND TREATMENT OUTCOME. The system consists of: a laboratory register that contains a log of all patients who have had a smear test done; patient treatment cards that detail the regular intake of medication and follow-up sputum examinations; the TB register, which lists patients starting treatment and monitors their individual and collective progress towards cure; and reporting forms from districts to the national level, which allow assessment of control efforts.

DOTS-Plus

• Secure political commitment for treatment of TB, including MDR-TB
• Acquire long-term investment of staff and resources
• Coordinate efforts between and within the community, local government, and international agencies.
• Create a project manual detailing all the aspects of the pilot project and outlining every participating institution’s roles and responsibilities.
• Form a specialized unit for managing MDR-TB patients.
• Guarantee the availability of specific laboratory services [including reliable drug-susceptibility testing (DST)].
• Design an appropriate treatment strategy that utilizes second-line anti-TB drugs.
• Establish a reliable supply of high-quality second-line anti-TB drugs.
• Institute parameters to promote patient adherence to treatment.
• Implement an information system to allow proper management of data, monitoring of performance, and evaluation of the intervention.

Main requirements of DOTS-Plus

In order to successfully combat the threat of MDR-TB, WHO has conceived a set of guidelines called DOTS-Plus. Above you can see the main requirements of DOTS-Plus strategy. It will be shortly explained why each of them is necessary.
Political commitment is of utmost importance in treatment of tuberculosis in general, and MDR-TB specifically. For DOTS-Plus it is necessary to obtain the support of the local authorities, because first of all, financing is necessary in order to set up this project. Secondly, government should regulate the distribution of tuberculosis drugs. Patients should not be allowed to buy them in drugstores, because if self-administered, it can be done inappropriately, thus creating more resistant strains of Mycobacteria tuberculosis.
Coordination of all parties involved in the DOTS-Plus project is necessary. At the community level, former patients can be recruited to help current patients. Social workers must be taught how to deal with MDR-TB patients. The DOTS-Plus project should be integrated with an existing DOTS project and with the National Tuberculosis Program. On the international level, there must be collaborative projects.
Laboratory aspects include culture identification of Mycobacterium tuberculosis and providing drug susceptibility tests to first and second line drugs. Ensure high quality of work.
Treatment Strategy. The doctors should use treatment strategy where by ascertain that the patients actually take the drugs given to them. For two years the patients must either receive drugs in a hospital or at a local medical center. The doctors should know what kind of side effects to expect and how to deal with them.
Information Systems and Data Management. A well functioning DOTS-Plus program has to have efficient information systems in order to allow the tracking of treatment of each individual and usage of data in the research of the disease.
The DOTS-Plus strategy is a new one and is only in the pilot stage. Treatment of MDR-TB is rather different from ordinary tuberculosis; therefore, all people involved should be trained in order to successfully implement DOTS-Plus program.