Extensive drug-resistant tuberculosis and health care workers

Article 1: Epidemiology and diagnosis

This is the first of a series of four papers on drug-resistant tuberculosis, dealing specifically with extensively drug-resistant tuberculosis (XDR-TB) and how health-care providers (HCPs) can protect themselves against infection.

The publication of this series also coincides with the annual World Tuberculosis Day on 23 March 2010. Annually the world celebrates this day in commemoration of the day in 1882 when Robert Koch identified Mycobacterium tuberculosis as the cause of tuberculosis (Migliori, 2007).

Health-care providers (HCPs) in South Africa are at the forefront of the tuberculosis epidemic and have to cope with ever increasing numbers of patients in overcrowded public health facilities, while appropriate measures to prevent the air-borne transmission of the disease are mostly absent.

The tuberculosis situation in South Africa is grave, and has worsened over the past years (WHO, 2009). The situation is exacerbated by the convergence of HIV and tuberculosis, with more than 50% of tuberculosis patients being coinfected (Weyer et al, 2007). Tuberculosis control efforts are further compounded by an epidemic of drug-resistant tuberculosis strains within the overall drug-susceptible epidemic, contributing to low cure rates and high mortality.

Defining XDR-TB
XDR-TB is a form of drug-resistant tuberculosis which is even more resistant to drug treatment than multi-drug (MDR-TB) tuberculosis. XDR-TB is caused by M. Tb organisms which acquired resistance to some drugs used for treatment. MDR-TB is caused by resistance to isoniazid and rifampicin, the two most potent drugs available for treating fully susceptible disease, also known as first-line drugs. When a MDR-TB strain acquires resistance to two other drugs such as aminoglycosides and fluoroquinolones (second-line drugs), the organism becomes extensively drug-resistant. Treatment options for XDR-TB are seriously limited, due to the resistance against the strongest first- and second-line drugs.  
A person can develop XDR-TB in two ways: (i) if the organism that infected the person already has some resistance to drugs, or (ii) when a patient’s own tuberculosis develops resistance through inappropriate treatment.

Diagnosis
It is important to be diagnosed as early as possible, although it depends on the patient’s access to health-care services and awareness of the signs and symptoms of tuberculosis. The signs and symptoms of tuberculosis of the lung (pulmonary tuberculosis), whether from susceptible or resistant forms, are the same and confirmation of drug-resistance requires a series of laboratory tests.
If the patient has pulmonary tuberculosis, the infecting organisms can be detected in sputum within a day or two. However, this microscopic test cannot differentiate between drug-susceptible or –resistant forms.

To determine drug-susceptibility, the bacteria in the sputum need to be cultivated and tested in a suitable laboratory which may take 6-16 weeks. In people infected with HIV, pulmonary tuberculosis does not develop to the same extent and fewer organisms are expelled via the sputum. In these patients the initial investigation by microscopy may not show the organisms.  The sputum needs to be cultivated before tuberculosis organism can be detected, resulting in a longer time-to-diagnosis.

Who is at risk of contracting XDR-TB?
Tuberculosis can only be acquired through inhalation of air containing suspended M. Tb-organisms, with probably no difference between the speed of transmission of drug-resistant versus drug-sensitive disease. People who are ill with pulmonary tuberculosis spread the disease by coughing and talking which expels the bacteria into the air. The organisms stay suspended in non-circulating air for a long time, and a person close enough to inhale them may become infected.

The spread of tuberculosis organisms depends on factors such as the number and concentration of infectious people in any one place together with the presence of people at higher risk of being infected. The risk of becoming infected depends on exposure, and increases directly with the length of time which a previously uninfected person spends with an infected person in a close confined space with poor air movement.

A third of the world’s population is latently infected with tuberculosis organisms and only once the organisms become active, do people develop disease. In latently infected people the bacteria become active as a result of anything that can reduce the person’s immunity such as HIV, advancing age, or certain medical conditions.

The risk of spreading tuberculosis will be reduced and eventually eliminated if infectious patients are diagnosed early, receive proper treatment, and if proper infection control interventions are implemented in confined spaces like overcrowded houses, hospitals, clinics and prisons. 

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.

Weyer, K. Brand, J. Lancaster, J. Levin, J. van der Walt, M.(2007) Determinants of multidrug-resistant tuberculosis in South Africa: results from a national survey. South African Medical Journal, Koornhof Festschrift supplement to the SAMJ, Vol. 97, Nr 11.

WHO (2009) WHO Review TB Control Program.

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).