Extensively drug-resistant tuberculosis

Extensively drug-resistant tuberculosis (XDR-TB) is a form of TB caused by bacteria that is resistant to the most effective anti-TB drugs. It has emerged from the mismanagement of multidrug-resistant TB (MDR-TB) and once created, can spread from one person to another.

One in three people in the world is infected with TB bacteria. [World Health Organization (2007). “Fact Sheet No. 104: Tuberculosis” [http://www.who.int/mediacentre/factsheets/fs104/en/index.html] ] Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the person’s immunity, such as HIV, advancing age, or some medical conditions. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs. If these drugs are misused or mismanaged, multidrug-resistant TB (MDR-TB) can develop. MDR-TB takes longer to treat with second-line drugs, which are more expensive and have more side-effects. XDR-TB can develop when these second-line drugs are also misused or mismanaged and therefore also become ineffective.

XDR-TB raises concerns of a future TB epidemic with restricted treatment options, and jeopardizes the major gains made in TB control and progress on reducing TB deaths among people living with HIV/AIDS. It is therefore vital that TB control is managed properly and new tools developed to prevent, treat and diagnose the disease.

The true scale of XDR-TB is unknown as many countries lack the necessary equipment and capacity to accurately diagnose it. It is estimated however that there are around 40,000 cases per year. As of June 2008, 49 countries have confirmed cases of XDR-TB. [World Health Organization (2008). “Countries with XDR-TB confirmed cases as of June 2008” [http://www.who.int/tb/challenges/xdr/xdr_map_june08.pdf] ]

Definition of XDR-TB

XDR-TB is defined as TB that has developed resistance to at least rifampicin and isoniazid (resistance to these first line anti-TB drugs defines Multi-drug-resistant tuberculosis, or MDR-TB), as well as to any member of the quinolone family and at least one of the following second-line anti-TB injectable drugs: kanamycin, capreomycin, or amikacin. [World Health Organisation (2006). Press release: "WHO Global Task Force outlines measures to combat XDR-TB worldwide" [http://www.who.int/mediacentre/news/notes/2006/np29/en/index.html] ] This definition of XDR-TB was agreed by the WHO Global Task Force on XDR-TB in October 2006. An earlier definition of XDR-TB is MDR-TB that is also resistant to three or more of the six classes of second-line drugs. [Center for Disease Control (2006). "Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs — Worldwide, 2000–2004". "MMWR Weekly" 55 (11): 301–305. ] This definition should no longer be used, but is referred to in many older publications.

Transmission

Like other forms of TB, XDR-TB is spread through the air. When a person with infectious TB coughs, sneezes, talks or spits, they propel TB germs, known as bacilli, into the air. A person needs only to inhale a small number of these to be infected. People infected with TB bacilli will not necessarily become sick with the disease. The immune system "walls off" the TB bacilli which, protected by a thick waxy coat, can lie dormant for years.

The spread of TB bacteria depends on factors such as the number and concentration of infectious people in any one place together with the presence of people with a higher risk of being infected (such as those with HIV/AIDS). The risk of becoming infected increases the longer the time that a previously uninfected person spends in the same room as the infectious case. The risk of spread increases where there is a high concentration of TB bacteria, such as can occur in closed environments like overcrowded houses, hospitals or prisons. The risk will be further increased if ventilation is poor. The risk of spread will be reduced and eventually eliminated if infectious patients receive proper treatment.

Diagnosis

Successful diagnosis of XDR-TB depends on the patient’s access to quality health-care services. If TB bacteria are found in the sputum, the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible and drug-resistant TB. To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Final diagnosis in this way for TB, and especially for XDR-TB, may take from 6 to 16 weeks. [World Health Organization (2006). “Frequently asked questions – XDR-TB” [http://www.who.int/tb/challenges/xdr/faqs/en/index.html] ] To the time needed for diagnosis, new tools for rapid TB diagnosis are urgently needed.

Treatment

The principles of treatment for MDR-TB and for XDR-TB are the same. Treatment requires extensive chemotherapy for up to two years. Second-line drugs are more toxic that the standard anti-TB regimen and can cause a range of serious side-effects including hepatitis, depression and hallucinations. Patients are often hospitalised for long periods, in isolation. In addition, second-line drugs are extremely expensive compared with the cost of drugs for standard TB treatment.

XDR-TB is associated with a much higher mortality rate than MDR-TB, because of a reduced number of effective treatment options. [Center for Disease Control (2006). "Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs — Worldwide, 2000–2004". "MMWR Weekly" 55 (11): 301–305. ] Despite early fears that this strain of TB was untreatable, recent studies have shown that XDR-TB can be treated through the use of aggressive regimens. A study in the Tomsk oblast of Russia, reported that 14 out of 29 (48.3%) patients with XDR-TB successfully completed treatment. [Keshavjee S, "et al". (2008). “Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study” "The Lancet" Early Online Publication DOI:10.1016/S0140-6736(08)61204-0]

Successful outcomes depend on a number of factors including the extent of the drug resistance, the severity of the disease and whether the patient’s immune system is compromised. It also depends on access to laboratories that can provide early and accurate diagnosis so that effective treatment is provided as soon as possible. Effective treatment requires that all six classes of second-line drugs are available to clinicians who have special expertise in treating such cases.

Prevention

Countries can prevent XDR-TB by ensuring that the work of their national TB control programmes, and all practitioners working with people with TB, is carried out according to the International Standards for TB Care. These emphasize providing proper diagnosis and treatment to all TB patients, including those with drug-resistant TB; assuring regular, timely supplies of all anti-TB drugs; proper management of anti-TB drugs and providing support to patients to maximize adherence to prescribed regimens; caring for XDR-TB cases in a centre with proper ventilation, and minimizing contact with other patients, particularly those with HIV, especially in the early stages before treatment has had a chance to reduce the infectiousness.

TB vaccine

The BCG vaccine prevents severe forms of TB in children, such as TB meningitis. It would be expected that BCG would have the same effect in preventing severe forms of TB in children, even if they were exposed to XDR-TB, but it may be less effective in preventing pulmonary TB in adults, the commonest and most infectious form of TB. [Aeras Global Vaccine Foundation. “Need for New TB Vaccines”. Retrieved 2008-09-12. [http://www.aeras.org/about-tb/need.php] ] The effect of BCG against XDR-TB would therefore likely be very limited. New vaccines are urgently needed, and WHO and members of the Stop TB Partnership are actively working on new vaccines.

XDR-TB and HIV/AIDS

TB is one of the most common infections in people living with HIV/AIDS. In places where XDR-TB is most common, people living with HIV are at greater risk of becoming infected with XDR-TB, compared with people without HIV, because of their weakened immunity. If there are a lot of HIV-infected people in these places, then there will be a strong link between XDR-TB and HIV. Fortunately, in most of the places with high rates of HIV, XDR-TB is not yet widespread. For this reason, the majority of people with HIV who develop TB will have drug-susceptible or ordinary TB, and can be treated with standard first-line anti-TB drugs. For those with HIV infection, treatment with antiretroviral drugs will likely reduce the risk of becoming infected with XDR-TB, just as it does with ordinary TB.

ymptoms

Symptoms of XDR-TB are no different from ordinary or drug-susceptible TB: a cough with thick, cloudy mucus (or sputum), sometimes with blood, for more than 2 weeks; fever, chills, and night sweats; fatigue and muscle weakness; weight loss; and in some cases shortness of breath and chest pain. A person with these symptoms does not necessarily have XDR-TB, but they should see doctor for a check-up. TB patients whose symptoms do not improve after a few weeks of treatment with TB and you are taking treatment should inform their clinician or nurse. [World Health Organization (2006). “Frequently asked questions – XDR-TB” [http://www.who.int/tb/challenges/xdr/faqs/en/index.html] ]

outh African epidemic

XDR-TB was first widely publicised following the report of an outbreak in South Africa in 2006. 53 patients in a rural hospital in KwaZulu-Natal were found to have XDR-TB of whom 52 died. [Gandhi NR, Moll A, Sturm AW, "et al". (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". "The Lancet" 368: 1575–80. doi:10.1016/S0140-6736(06)69573-1. [http://linkinghub.elsevier.com/retrieve/pii/S0140673606695731] ] The median survival from sputum specimen collection to death was only 16 days and that the majority of patients had never previously received treatment for tuberculosis suggesting that they had been newly infected by XDR-TB strains, and that resistance did not develop during treatment. [Gandhi NR, Moll A, Sturm AW, "et al". (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". "The Lancet" 368: 1575–80. doi:10.1016/S0140-6736(06)69573-1. [http://linkinghub.elsevier.com/retrieve/pii/S0140673606695731] ] This was the first epidemic for which the acronym XDR-TB was used, and although TB strains that fulfill the current definition have been identified retrospectively, [Shah NS, Wright A, Drobniewski F, "et al". (2005). "Extreme drug resistance in tuberculosis (XDR-TB): global survey of supranational reference laboratories for _Mycobacterium tuberculosis_ with resistance to second-line drugs". "Int J Tuberc Lung Dis" 9(Suppl 1): S77. ] [Centers for Diseases Control (2006). "Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs-worldwide, 2000-2004". "Morb Mort Wkly Rep" 55: 301–5.] this was the largest group of linked cases ever found. Since the initial report in September 2006, cases have now been reported in most provinces in South Africa. As of 16 March 2007, there were 314 cases reported, with 215 deaths. [Angela Quintal. "314 XDR-TB cases reported in SA". Cape Times. Retrieved on 2007-04-04.] It is clear that the spread of this strain of TB is closely associated with a high prevalence of HIV and poor infection control; in other countries where XDR-TB strains have arisen, drug resistance has arisen from mismanagement of cases or poor patient compliance with drug treatment instead of being transmitted from person to person. [Migliori GB, Ortmann J, Girardi E, "et al". (2007). "Extensively drug-resistant tuberculosis, Italy and Germany" 13 (5).] It is now clear that the problem has been around for much longer than health department officials have suggested, and is far more extensive. [Sidley P. (2006). "South Africa acts to curb spread of lethal strain of TB". "Brit Med J" 333: 825. doi:10.1136/bmj.333.7573.825-a. PMID 17053232. ]

ee also

* Tuberculosis
*Tuberculosis treatment
*Endobronchial valve
* Drug resistance
* Antibiotic resistance
* Andrew Speaker
* Multi-drug-resistant tuberculosis
*Drug resistant diseases
** MRSA
** Vancomycin-resistant enterococcus (VRE)

References

External links

* [http://www.who.int/tb/en/ World Health Organization Stop TB Department]
* [http://www.stoptb.org Stop TB Partnership]
* [http://www.stoptb.org/globalplan/ The Global Plan to Stop TB]
* [http://www.action.org Advocacy to Control TB Internationally - ACTION]
* [http://www.who.int/tb/publications/2006/istc/en/index.html International Standards of TB Care]
* [http://www.wilsoncenter.org/index.cfm?topic_id=116811&fuseaction=topics.event_summary&event_id=239772 Video: Drug-Resistant TB in Russia] July 24, 2007, Woodrow Wilson Center event featuring Salmaan Keshavjee and Murray Feshbach
* [http://xdrtb.org/ XDRTB.org: Spread the Story. Stop the Disease.] (photo documentary of XDR-TB by James Nachtwey)