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Overreaction of immune system to tuberculosis can be predicted

27 June 2012
Overreaction of immune system to tuberculosis can be predicted

In humans that are co-infected with HIV and tuberculosis, sometimes the immune system recovers too well after initiation of a treatment, attacking the patient as well. Until now there was no test to predict who would encounter the complication, and who wouldn’t. Anali Conesa Botella, researcher at the Antwerp Institute of Tropical Medicine, discovered such a test.

Between 10 and 40% of people suffering from a serious immune deficiency caused by HIV, plus an infection with tuberculosis, deteriorate instead of improve when they start a treatment against HIV. Apparently, their suppressed immune system recovers all too well and overcompensates. The phenomenon is known as TB-IRIS (tuberculosis-associated immune reconstitution inflammatory syndrome).

Luckily, only about 3% of patients die from it, but one in three requires hospitalization. Some lose their confidence in the health care providers and abandon treatment, leading to an increased risk of resistance, and of death.

Unfortunately, there is no useful laboratory test to determine or predict TB-IRIS. At the most one could say that a low count of CD4 lymphocytes – an advanced HIV infection – and a short interval between the start of the treatments against HIV and tuberculosis lead to a higher chance of TB-IRIS.

Conesa Botella tested 90 patients in Uganda, prior to their HIV-treatment, for urinary lipoarabinomannan (LAM), a well-known marker for TB infection. The LAM-test indeed showed prognostic value: the higher the LAM-concentration, the higher the chance of TB-IRIS. Which seems logical: the more the immune system is disrupted (the lower the CD4 count), the more opportunity for the tuberculosis bacillus (the higher the LAM), the farther the immune system has to come back and the higher the chance it goes over the top.

Moreover, it looks as if the effectiveness of a TB-treatment can be followed up through the LAM-concentrations in the urine.

She also looked at vitamin D in HIV-TB patients in Belgium, Uganda and South-Africa, because prior research had shown that people with a vitamin D deficiency are more likely to develop TB. Especially in the non-tropical areas, where people catch less sunlight, they often suffer from a vitamin D deficiency (70% of HIV patients in Belgium, and 96% of patients with HIV and TB in South-Africa). But the level of vitamin D had no prognostic value for TB-IRIS.

So far most studies on prediction of TB-IRIS have been executed in industrialized countries on samples collected in Africa. Now we have a ‘LAM lateral flow’ test, a promising point of care test that can transfer the research to the stricken countries. But the quest for other and possibly better markers for the risk of TB-IRIS should be continued.