Need for new TB test highlighted on World TB Day

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p>International efforts to combat TB are falling short, despite optimistic statements by the World Health Organisation, because of an international failure to detect TB cases and provide prompt treatment, it emerged today at the Stop TB Partners Forum in New Delhi, India.

WHO set a target of diagnosing 70% of TB cases worldwide by 2005, but the Global Tuberculosis Control report issued yesterday shows that only 37% of cases are estimated to be diagnosed. Coupled with an 85% cure rate, a detection rate of 70% is predicted to lead to a 6-7% year on year decline in new TB cases.

In a recent paper in The Lancet Mario Raviglione and colleagues from WHO’s Stop TB Department argue that only with the arrival of HIV treatment and improved prevention measures will TB be contained in African countries with high HIV prevalence.

Glossary

latent TB

A form of TB that is not active. Persons with latent TB are infected with M. tuberculosis but do not have any symptoms and they cannot spread TB infection to others. Only specific tests will tell if anyone has latent TB. Treatment for latent TB is recommended in people living with HIV. 

immune response

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

assay

A test used to measure something.

standard of care

Treatment that experts agree is appropriate, accepted, and widely used for a given disease or condition. In a clinical trial, one group may receive the experimental intervention and another group may receive the standard of care.

multidrug-resistant tuberculosis (MDR-TB)

A specific form of drug-resistant TB, due to bacilli resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. MDR-TB usually occurs when treatment is interrupted, thus allowing organisms in which mutations for drug resistance have occurred to proliferate.

However, improved case detection will be essential in areas where HIV is causing a massive increase in TB cases, since it will be a key mechanism by which people can be drawn into TB and HIV treatment services.

Improving diagnosis

Medecins sans Frontieres (MSF) today criticised international commitment to TB control.

“Delivering adequate TB care would require a reliable diagnostic test for TB to begin with, but we don't have one,” said Dr Rowan Gillies, president of MSF International. “A growing number of TB patients worldwide also have HIV/AIDS, but the current diagnostic tool can only detect TB in 50% of HIV patients, even in a well-run TB programme.”

“TB kills two million people every year, but where is the sense of urgency that will secure resources and accelerate the process of developing new tools to fight it?” Dr Gillies asked.

In contrast, a diagnostic test for SARS was developed by the Genome Institute of Singapore just months after the outbreak of the disease last year.

Diagnosis

However, a new diagnostic test may be on the horizon if resources are made available for its development. Italian researchers reported this month that an overnight test can not only detect the presence of tuberculosis in a blood sample, but can also be used to monitor response to TB treatment.

The test, developed by teams at the University of Oxford and the Italian Institute for Infectious Diseases, is called an ELISPOT and reacts to the presence of the T-lymphocytes that are produced in response to tuberculosis infection. The lymphocytes are highly specific to mycobacterium tuberculosis and do not cross-react with other antigens, so the test is highly specific and is also highly sensitive to the presence of TB.

In an editorial in the March 1st edition of Clinical Infectious Diseases, Dr Ajit Lalvani of Oxford University’s Nuffield Department of Clinical Medicine suggests that a number of studies need urgent suppport to carry forward this promising diagnostic test.

A large study of people receiving TB treatment should be carried out in order to determine whether the immune response to cleared TB, characterised by memory T-cells, can be distinguished from the immune response to active TB, characterised by effector T-cells.

The assay may also be of importance in assessing the presence of latent TB infection and the impact of preventive therapy with isoniazid on latent TB infection.

The test could also be used to measure the effectiveness of new anti-TB agents undergoing trials, since Italian researchers showed that it was possible to plot the decay of active m.TB replication using the ELISPOT assay. New induction and maintenance regimens could be designed using this information. It would also prove highly informative in multidrug-resistant TB treatment, where m.TB decline is much slower and more unpredictable.

Treatment improvements

New agents are needed, says MSF, because patients must take the medicines for six to eight months. It is a recipe for high levels of default on treatment if the intensive adherence support provided to people with HIV is not available for TB patients throughout this period.

Community action

WHO’s Stop TB Department recommends that communities need to have much greater involvement in the delivery of care, especially in ensuring that treatment courses are completed by community members.

Communities can also act as important advocates for improvements in TB control. In their Lancet paper, WHO experts note that some important countries have not implemented DOTS, and most do not have full geographic coverage. In particular, non-governmental organisations tend to provide a lower standard of care.

Further information on this website

Stop TB Partnership

References

Carrara S et al. Use of a T cell based asssay for monitoring efficacy of antituberculosis therapy. Clinical Infectious Diseases 38: 757-9, 2004.

Elzinga G, Raviglione MC, Maher D. Scale up: meeting targets in global tuberculosis control. Lancet 363: 814-19, 2004.

Lalvani A. Counting antigen-specific T-cells: a new approach for monitoring response to tuberculosis treatment? Clinical Infectious Diseases 38: 757-9, 2004.