| Extensively Drug-Resistant Tuberculosis (XDR-TB) |
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The emergence of extensively drug-resistant tuberculosis (XDR-TB), a virulent and virtually untreatable form of TB, is causing alarm in South Africa, particularly given the threat of spread of XDR-TB to vulnerable groups in our society and the extraordinarily high mortality reported for XDR-TB patients co-infected with HIV.
Basic facts about tuberculosis (http://www.who.int/tb/publications/2006/tb_factsheet_2006_1_en.pdf)
- TB is an airborne disease caused by a bacterium called Mycobacterium tuberculosis.
- One in three persons globally is estimated to be infected with dormant TB bacilli, but the vast majority of infected persons remain healthy, without TB signs and symptoms, and are not infectious, ie., they cannot transmit TB to other persons.
- Only when the TB bacteria become active do people become ill with TB. Bacteria most often become active as a result of immune suppression, ie., when the body’s immune system is no longer able to keep the TB infection in check.
- Conditions that result in compromised immunity include HIV infection, stress-related conditions, advancing age, alcohol and/or substance abuse, and certain medical conditions such as cancer and diabetes.
- 1 in 10 people infected with TB bacilli will become sick with active TB in their lifetime; people with HIV are at a much greater risk.
- TB is a disease of poverty, especially affecting the most vulnerable groups of society, i.e., those which are the poorest and malnourished. Most often, young adults in their productive years are affected.
- Virtually all TB deaths occur in the developing world, with TB killing 5000 people every day.
- Nearly 2 million deaths globally are caused by TB.
- TB is often contagious and spreads through the air; if not treated, a person with active TB infects on average 10 to 15 people every year.
- TB is curable and treatment is free of charge. TB treatment takes at least six months to be effective and require multiple antibiotics.
South Africa, HIV/AIDS and TB – what’s the connection?
HIV/AIDS is the single biggest risk factor for TB infection and active disease.1 One in four young adults in South Africa is infected with HIV,2 and of these, up to two thirds may also be infected with TB. Conversely, between 60% and 80% of new TB cases in South Africa also have HIV infection. HIV fuels TB because persons with HIV have weakened immune systems and are therefore more susceptible to opportunistic infections like TB. They also have a much higher risk of TB infection rapidly turning into active TB disease - A person infected with TB but without HIV infection usually has only a 5-10% risk of developing active TB throughout his or her lifetime. However, if a person is also HIV-infected, the risk of developing active TB after TB infection increases dramatically to 5-10% per year. |
Multidrug-resistant tuberculosis (MDR-TB)
TB can usually be treated very effectively with a 6-month course of four first-line anti-TB drugs. These are the first choice for treatment, as first-line TB drugs are safe, inexpensive and effective. However, if patients are incorrectly treated or do not complete their full course of treatment, drug-resistant strains of Mycobacterium tuberculosis can arise. Multidrug-resistant TB (MDR-TB) is defined as TB resistant to the two most potent first-line anti-TB drugs, ie. isoniazid and rifampicin. Once MDR-TB emerges, first-line anti-TB drugs do no longer work and doctors then have to resort to second-line anti-TB drugs.
Treatment of MDR-TB with second-line anti-TB drugs is lengthy (up to 24 months) and 100 times more expensive, and patients experience more severe and unpleasant side-effects than with the first-line drugs. Only a few second-line anti-TB drugs are available. Therefore, it is vital that MDR-TB treatment is used correctly and not interrupted, because if additional resistance develops, XDR-TB will be the result.
| MDR-TB is defined as TB caused by strains that are resistant to at least isoniazid and rifampicin, the two most powerful first-line anti-TB drugs |
MDR-TB can spread to vulnerable individuals in the same way as drug-susceptible TB, and infected persons have the same risks of developing active disease in the presence of HIV as those with drug-susceptible TB.
Extensively drug-resistant tuberculosis (XDR-TB)
XDR-TB can develop when the second-line drugs are misused or mismanaged and therefore also become ineffective. Because XDR-TB strains have developed resistance to most of the first- and second-line drugs available to treat TB, it is potentially untreatable. XDR-TB was first reported in early 2006 in KwaZulu Natal.3 In a group of 53 patients identified with XDR-TB, all but one died within an average of 25 days from the point when drug-resistant TB was first suspected. Forty-four of the 53 patients were tested for HIV and all were found to be positive.
In October 2006, a group of international experts lead by the World Health Organization (WHO) re-defined XDR-TB as follows:
| Mycobacterium tuberculosis isolates defined as multidrug-resistant, with additional resistance to a fluoroquinolone and one or more of the following injectable drugs: kanamycin, amikacin, capreomycin. |
Fluoroquinolones, kanamycin, amikacin and capreomycin are second-line drugs used against TB when the first-line drugs no longer work
The extent of the XDR-TB problem
Cases of XDR-TB have been found throughout the world. The extent of the XDR-TB situation in Southern Africa as a whole is unknown, as South Africa is the only country in the region with the technical laboratory capacity to diagnose XDR-TB strains. A survey of TB strains stored in laboratories of the SA National Health Laboratory Service (NHLS) since the beginning of 2005 indicated that XDR-TB was present in all nine provinces. The true epidemiological picture in South Africa is, however, not yet clear, as systematic surveys have not yet been carried out in any province.
Strategies to deal with XDR-TB
A seven-point emergency plan to deal with XDR-TB was drawn up an Expert Consultation meeting in Johannesburg on 7-8 September, 2006. The meeting was jointly organised by the Medical Research Council (MRC), WHO and the US Centers for Disease Control and Prevention (CDC) and was hosted by MRC. Subsequent technical meetings between the National Department of Health, WHO, MRC and other local stakeholders have identified key issues for South Africa and the Southern African region.
Another historical meeting was held in Geneva on the 17th of October 2006 where the WHO Global Task Force on XDR-TB was established. At this meeting, the WHO Global Task Force on XDR-TB outlined a series of measures that countries must put in place to effectively combat XDR-TB. The Task Force was assigned to mobilise teams that can respond to requests for technical assistance from countries and that can be deployed at short notice to XDR-TB risk areas.
The Task Force also made specific recommendations on drug resistant TB surveillance and laboratory capacity strengthening measures, implementing infection control measures to protect patients, health care workers and visitors (particularly those who are HIV infected), access to second line anti-TB and antiretroviral drugs for patients, communication and information-sharing strategies related to XDR-TB prevention, control and treatment, (including antiretroviral therapy), and accelerated research and development of new TB drugs, vaccines and diagnostics tests. A full version of the report from this meeting is available at http://www.who.int/tb/xdr/news_mar07.pdf.
It is essential that TB patients are treated according to international standards of care so that the emergence of MDR-TB and XDR-TB is prevented by ensuring that TB patients are cured the first time around.
Patients at risk for MDR-TB and XDR-TB should be diagnosed and treated as quickly as possible.
Preventing the spread of MDR-TB and XDR-TB through appropriate infection control interventions is another priority.
Detention of patients with XDR-TB: an ethical and legal dilemma
Calls have been made for the enforced detention of patients with XDR-TB. http://medicine.plosjournals.org/perlserv/?request=get-document&doi=
10.1371/journal.pmed.0040050. Public health legislation in South Africa does to a certain extent allow for this; however, a careful balance needs to be struck between community rights and human rights of the individual patients, taking constitutional rights such as dignity, equality and freedom into account.
The MRC has recently published a position statement on enforced detention of patients with XDR-TB, illustrating the dilemmas surrounding this highly controversial issue http://www.mrc.ac.za/pressreleases/2007/1pres2007.htm.
A joint responsibility
Dr Mario Raviglione, Director of the WHO Stop TB Department, recently said that the fight against TB and XDR-TB was now the responsibility of a wide range of individuals and organisations. Most importantly, TB control programmes need to function effectively, and patients with TB need access to proper drugs and should adhere to treatment regimens, according to WHO. It also is crucial to administer second-line TB drugs under very tightly controlled conditions so that they retain their potency.
The responsibility therefore jointly lies with individual patients as well as health authorities to ensure that TB drugs are taken correctly and responsibly to prevent XDR-TB.
References
- http://www.who.int/tb/publications/2006/tb_factsheet_2006_1_en.pdf
- Dorrington R E, Johnson L F, Bradshaw D and Daniel T. The Demographic Impact of HIV/AIDS in South Africa. National and Provincial Indicators for 2006. Cape Town: Centre for Actuarial Research, South African Medical Research Council and Actuarial Society of South Africa.
- Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, Zeller K, Andrews J, Friedland G. Extensively drug-resistant tuberculosis as a cause of death in patients infected with tuberculosis and HIV in rural South Africa. Lancet 2006 Nov 4; 368: 1575-80
Author: Mary Mattheyse, AfroAIDSinfo
Scientific editing: Dr Karin Weyer, TB Epidemiology and Intervention Research Unit |
