Extensive drug-resistant tuberculosis and health care workers

Article 2: Treatment and Prevention

Drug-resistant tuberculosis (DR-TB) differs from normal or susceptible tuberculosis (TB) by having acquired resistance against drugs used for chemotherapy. The seriousness of this resistance depends on the specific drug, for instance resistance to both of the strongest first-line regimen (FLRs), i.e. rifampicin and isoniazid, is cause for concern and is known as multi-drug-resistant TB (MDR-TB). Similarly, once organisms have acquired resistance to drugs in the fluoroquinolone group and at least one of the injectable drugs kanamycin or amikacin, which form part of the second-line regimen (SLR) the disease is termed extensively drug-resistant tuberculosis (XDR-TB). For XDR-TB treatment, options are even more limited, resulting in high mortality rates. This has led to concern and the general impression that drug-resistant tuberculosis is an untreatable condition. This article, the second of the 4-series paper on drug-resistant TB, discusses treatment and prevention.

Treatment of M(X)DR-TB
Multi-drug-resistant tuberculosis and extensively drug-resistant tuberculosis can be successfully treated. However, it depends on the epidemiological setting, extent of drug-resistance, severity of the disease and whether the immune system has been compromised. Effective treatment of M(X)DR-TB requires use of drugs from all six groups of the SLR and special training of clinicians in drug-resistant tuberculosis (Department of Health, 2009). Treatment for MDR-TB takes up to 24 months and consists of an initial phase of four drugs and one injectable agent. The need for the daily injection is also the reason for prolonged hospitalisation of M(X)DR-TB cases. Daily injections continue for the first six months of treatment or until the organisms are undetected by sputum culture, known as culture conversion. After stopping the injectable drugs, treatment with three of the drugs need to be given for at least 18 months. Treatment for XDR-TB takes 36 months, again including an injectable phase of 6 – 9 months, depending on the duration up to culture conversion. In the case of XDR-TB, the most potent second-line drugs have become ineffective, and where possible, the regimen should contain drugs from all six classes.

Prevention of drug-resistant tuberculosis
Susceptible TB will not automatically develop into drug-resistant disease. It remains critical for a patient to continue taking all treatment exactly as prescribed. No doses should be missed and treatment should be taken throughout the treatment period. If side-effects become a problem, patients should inform their health care provider.

The TB vaccine, known as the BCG vaccine, prevents severe forms of TB in children, but are less effective in preventing pulmonary TB in adults, irrespective of the level of drug-resistance in the strain.

Health care providers (HCPs) are at especially high risk of contracting drug-resistant disease, as they are the most likely to come into contact with infectious TB patients. The risk of developing TB after exposure increases if the HCP is also HIV positive. To protect HCPs appropriately, strict infection control measures must be implemented and adhered to in health care facilities. HCPs are also encouraged to be aware of their HIV status to avoid risk of exposure.

The link between M(X)DR-TB and HIV/AIDS
Tuberculosis is the most common infection in people living with HIV/AIDS because many people are already infected with TB organisms. As soon as their immune system becomes compromised by HIV the dormant bacteria becomes active and the TB infection develops into active TB disease. In places where XDR-TB is most common, people living with HIV are at greater risk of becoming infected with TB due to their weakened immune system. If there are many HIV-positive people in a geographical setting, then there will be a strong link between XDR-TB and HIV (Gandhi et al, 2006). This is the reason why it is generally accepted that there is a direct association with XDR-TB and HIV. In general, most people with HIV-TB are not infected with the drug-resistant forms of the TB disease. Fortunately, in most places with high HIV rates, M(X)DR-TB is not widespread. South Africa and other sub-Saharan countries have high burdens of both diseases, and therefore in these settings, HIV infected cases need to be screened for drug-resistant disease, while among M(X)DR-TB cases, testing for HIV should be mandatory.

References
Migliori, GB. Loddenkemper, Blasi, RF. Raviglione, MC. (2007) 125 years after Robert Koch's discovery of the tubercle bacillus: the new XDR-TB threat. Is "science" enough to tackle the epidemic? European Respiratory Journal Vol 29 pp 423-427.
Department of Health. 2009. Management of Drug-resistant tuberculosis. Draft policy guidelines.
Gandhi, NR. Moll, A. Sturm, AW. Pawinski, R. Govender, T. Lallo, U. Zeller,K. Andrews, J. Friedland, G. (2006) Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 368 pp 1575-1580.

This article is also available in Afrikaans, Xhosa, Zulu, Sotho and Tsonga. Contact Joey Lancester at joey.lancester@mrc.ac.za or (012) 339-8561.

This article was developed and published in collaboration with the Tuberculosis Epidemiology and Intervention Research Unit and the Web and Media Technologies Platform of the South African Medical Research Council.

This series of publications has been made possible through a grant from the United States Department of Health and Human Services (HHS).