Extensively drug-resistant TB rapidly fatal in South Africa

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Tuberculosis (TB) that is resistant to practically every medication that can be used to treat it is alarmingly common in South Africa, and proved uniformly and rapidly fatal in one outbreak in rural South Africa, warned Dr Neel Gandhi, Assistant Professor of Medicine at Albert Einstein College of Medicine of Yeshiva University, at last week’s Sixteenth International AIDS Conference in Toronto, Canada.

Multi-drug resistant TB emerges in one of two ways: either a person develops drug resistance as a result of poor adherence to treatment, or they acquire a strain of TB that already has some resistance to drugs used in its treatment. Further drug treatment increases the level of resistance, leading to treatment failure and multi-drug resistance.

Multi-drug resistant TB can also be transmitted from person to person, and anyone who acquires it has a poorer prognosis than someone infected with drug-sensitive TB. Multi-drug resistant TB is especially likely to kill people with HIV, because neither drugs nor a depleted immune system can control it.

Glossary

extensively drug-resistant TB (XDR-TB)

A form of drug-resistant tuberculosis in which bacteria are resistant to isoniazid and rifampicin, the two most powerful anti-TB drugs, plus any fluoroquinolone and at least one injectable second-line drug. 

transmission cluster

By comparing the genetic sequence of the virus in different individuals, scientists can identify viruses that are closely related. A transmission cluster is a group of people who have similar strains of the virus, which suggests (but does not prove) HIV transmission between those individuals.

strain

A variant characterised by a specific genotype.

 

sputum

Material coughed up from the lungs, which can be examined to help with diagnosis and management of respiratory diseases.

isoniazid

An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

In some cases TB may become resistant to most of the drugs used to treat it. This form of TB is classified as extensively drug-resistant.

Little research has been done on extensively drug-resistant TB in Africa, and only 347 TB isolates have been detected worldwide that can be classified as XDR, according to the US Centers for Disease Control.

However, in one study in Tugela Ferry in the Msinga district of KwaZulu-Natal, researchers from the United States and South Africa detected 53 cases in just over a year, and found a high likelihood that most of these cases had been transmitted from person to person in the community, without any failure of prior TB treatment.

They set out to look at the prevalence of multi-drug resistant TB in the rural population of Kwazulu-Natal by conducting a cross-sectional study at a district hospital between January 2005 and March 2006. Despite the introduction of antiretroviral therapy in the district, which has reduced the death rate, 67% of remaining deaths in HIV-positive people are documented as due to multi-drug resistant TB, illustrating the scale of the problem posed by MDR TB in South Africa.

When they carried out cultures from 1,540 patients with suspected TB, they found 544 culture-positive TB cases, of which 221 had resistance to both isoniazid and rifampicin. This compares to 128 cases in the whole of the United States in 2004.

Even worse, they found that 53 isolates showed resistance not only to isoniazid and rifampicin but to all first and second line drugs used to treat TB.

Also, said Neel Gandhi, the vast majority of cases appeared to be recent infections and to be potentially infectious, since 79% were sputum-positive and 51% occurred in individuals who had received no prior treatment for TB, suggesting new infection with a drug-resistant strain.

Initially the researchers believed that they were looking at a hospital outbreak caused by poor infection control procedures, but 36% of the patients had no prior history of hospitalisation.

Thirty isolates were sequenced to examine potential transmission patterns, and 87% were found to be genetically highly similar, implying a recent transmission cluster, said Neel Gandhi.

All patients diagnosed with XDR TB except for one subsequently died, and those who died survived for a median of only 16 days after sputum collection at the hospital. All patients with a known HIV status at the time of death were HIV-positive.

"Some of these patients really weren't that sick," Dr Gandhi cautioned. "They weren't brought in near death."

The South African government has not yet indicated how it plans to deal with the problem of XDR-TB, although its health officials will meet with the World Health Organization soon in order to develop a plan, according to Gerald Friedland of Yale University, one of the co-authors of the study.

References

Gandhi NR et al. High prevalence and mortality from extensively-drug resistant (XDR) TB in TB/HIV coinfected patients in rural South Africa. Sixteenth International AIDS Conference, Toronto, abstract ThLB0210, 2006.