MDR-TB: An emerging global threat
Rachel Jones discusses a recent WHO report on multidrug resistant TB
A new report recently issued by the WHO (1) reports a growing global trend in multidrug resistant tuberculosis (MDR-TB). This trend is focused in India and China which are responsible for up to half of all global cases. (1) MDR-TB is defined as tuberculosis resistant to isoniazid and rifampicin, two first line drug therapies for TB. With this in mind, there are fewer therapies that are effective for treating multidrug resistant tuberculosis and these are not as effective as first line treatments. MDR-TB therefore carries higher mortality and morbidity rates than conventional strains.
The British Medical Bulletin (2) attributes most cases of MDR-TB to either doctor error and/or patient non-compliance. Doctor error includes prescribing and diagnostic errors. MDR-TB prescription errors were explored in a paper by Jain (3) where 70% of patients were prescribed the incorrect medication dose. Diagnostic error often occurs due to lack of equipment. Without facilities for drug sensitivity studies many places are unable to diagnose MDR-TB. Patients therefore undergo conventional tuberculosis treatment which can increase resistance and leave patients infectious.
Resistance can be defined as either primary or acquired. Acquired resistance is more common. This generally happens to patients who have had previous exposure to TB and may have undergone prior TB treatment. These may also be called retreatment cases. Primary resistance is MDR-TB in a patient presenting without previous TB exposure.
The recent WHO report (1) shows global spread, with at least one country in every WHO region having a MDR-TB rate of greater than 3%. Areas of particular concern are India and China. Both countries have emerged as manufacturing hotspots with increased global travel and potential for transmission. In 2006, one of every ten new MDR-TB cases diagnosed with primary resistance originated in China. Overall the WHO estimates there are half a million new cases of MDR-TB each year. This represents 5% of all new TB cases. When compared on a percentage base, China and India appear to have only 5% prevalence rates. Yet together they are responsible for a quarter of a million MDR-TB cases.
The report also stresses that only six countries in the whole of Africa are able to report data due to a lack of equipment. This reiterates that the true extent of MDR-TB may well not be known. However, the report did have a glimmer of hope. Both the United States and Hong Kong have falling MDR-TB rates and tuberculosis notification. Hong Kong is a particular success story with MDR-TB rates falling faster than the fall in tuberculosis rates.
So what is the WHO doing about this emerging threat? In 1999 they introduced a DOTS-plus (directly observed therapy, short-course) program to combat MDR-TB. It is a management plan for areas with high prevalence of MDR-TB. It is meant as a supplement for areas running an effective DOTS program. The WHO DOTS approach is used to manage normally susceptible TB in a cheap and efficient way. DOTS encompasses five elements (6):
- Political commitment
- Case detection by sputum smear microscopy (examining a sample of sputum under a microscope and searching for TB bacteria)
- A regular and uninterrupted supply of drugs
- A standardized treatment regimen of at least 6 months with direct observation for at least the first two months of treatment
- Standardized recording and reporting systems
DOTS-plus uses second-line TB therapies following the five elements of DOTS. Resistance can be tested by susceptibility to rifampicin. Those who are resistant have a 95% chance of also being resistant to isoniazid. The drug treatment is dependent on sensitivity testing. Basic MDR-TB, according to the WHO suggestions, (7) is treated with a five drug, combination therapy that takes nearly two years to complete. By making therapy observed, compliance can be monitored. Only those who are present are given the drug therapy and observed taking it. While this cannot enforce that everyone attends, it does make follow-up and research figures more accurate.
DOTS-plus programs are not currently available globally and only present in certain countries. Some of these programs and their results have been released but are only on a very small scale. In the Tupasi paper (8) the DOTS-plus pilot program in Manila, Philippines, is reviewed. Here the results are based on only 85 cases. With such a small case base it is very hard to make absolute decision based on this information. However the general trend indicates that the Manila pilot program is successful with a 73.4% cure or likely cure rate.
There is another emerging global problem that was discovered in 2006 in the Tugela Ferry study in KwaZulu-Natal, South Africa. (4) Extensively drug resistant tuberculosis or XDR-TB, is tuberculosis resistant to first and second line treatment options. It is seen in immuno-compromised hosts, commonly HIV-positive patients, and carries up to a 100% mortality rate due to the lack of treatment options. The prevalence of XDR-TB is lower than MDR-TB but currently for the first time, it is being reported by the WHO. Although, data is limited due to there being few countries able to diagnose XDR-TB.
The figures published in the latest WHO report show that the threat of MDR-TB is increasing at a rapid pace and must be stopped. The report contains data from 33 new countries. Increased surveillance is a positive step in the right direction. The WHO has also helped arrange a global upgrade of diagnostic services which has helped fight MDR-TB, however this is still not enough. More funding and awareness are needed to stop MDR-TB from becoming the next big killer. The WHO (1) estimates at present that there is a shortfall of US$500 million in the control of MDR-TB and XDR-TB. These are worrying statistics especially if current figures are underestimated.
Rachel Jones
3rd year medical student
Bristol University
UK
rj5309@bristol.ac.uk
(1) Anti-tuberculosis drug resistance in the world, Fourth Global Report, The WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance 2002-2007
(2) Ormerod, Multidrug-resistant tuberculosis: epidemiology, prevention and treatment, British Medical Bulletin 2005;73 and 74
(3) N.K. Jain. Faulty prescription - an avoidable cause OF MDR - TB , Ind. Jour. Tuberc. 1998, 45, 141
(4) Heymann et al, The need for Global Action Against Multidrug-Resistant Tuberculosis, JAMA 1999; 281:2138-2140
(5) http://www.who.int/tb/dots/dotsplus/management_old/en
(6) http://www.who.int/tb/dots/whatisdots/en/index.html
(7) Guidelines for the management of drug resistant tuberculosis, WHO, 1997
(8) Tupasi et al, DOTS-Plus for multidrug-resistant tuberculosis in the Philippines: global assistance urgently needed, Tuberculosis, 2003
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