Co-infected HIV-TB patients with suspected TB immune reconstitution inflammatory syndrome (IRIS) should undergo TB drug-susceptibility testing before corticosteroid treatment is considered. Furthermore, better TB IRIS diagnostic procedures are urgently needed to differentiate TB IRIS from other opportunistic infections.
The recommendations, published in the January 23rd edition of the journal Clinical Infectious Diseases, follow a study of suspected TB IRIS patients in Cape Town, South Africa.
TB IRIS is a collection of symptoms that frequently emerge soon after antiretroviral therapy is started in co-infected individuals. It is believed to result from a rejuvenated immune system mounting a TB-specific inflammatory response. Risk factors for developing TB IRIS include low CD4 count, early initiation of anti-HIV treatment and the existence of TB outside the lung area.
HIV-TB co-infection is a large and growing problem in sub-Saharan Africa and, accordingly, treating TB IRIS effectively is an escalating concern.
Suspected cases of TB IRIS are sometimes treated with corticosteroids that are supposed to relieve symptoms by dampening the inflammatory immune response to TB infection (inflammatory responses are known to be a major cause of TB pathology).
A recently reported randomised study showed that a four-week course of treatment with the steroid prednisone significantly reduced the need for medical intervention in people diagnosed with TB IRIS.
However, severe complications can arise from corticosteroid treatment because TB IRIS diagnoses often fail to distinguish between drug-resistant and drug-susceptible TB infections.
In patients with a previous history of TB, IRIS is a response to lingering mycobacteria, and may lead to a paradoxical worsening of symptoms. TB IRIS may also represent an inflammatory reaction to previously undiagnosed TB.
In people with a drug-resistant TB infection, on the other hand, IRIS is a response to the presence of drug-resistant mycobacteria in the tissues and the blood.
Patients undergoing TB treatment, but infected with drug-resistant TB (or other opportunistic infections), are at risk of deteriorating dangerously when treated with immunosuppressant corticosteroids because first-line antibiotic treatment is pitted against resistant microbial organisms.
In order to gain a better understanding of the extent to which TB IRIS is misdiagnosed (or symptomatic of drug-resistant TB) the South African research team closely scrutinised 100 suspected TB IRIS sufferers over a 17-month period.
The patients participating in the study were in the process of receiving TB treatment at the time that anti-HIV therapy was initiated. Drug resistance to rifampicin was assessed with both a rapid FASTplaque-Response test and a standard (but protracted) drug-susceptibility test. TB IRIS symptoms, as interpreted by the standard case definition, developed a median of 14 days after anti-HIV treatment.
Seven patients suffered from an alternative opportunistic infection that had been mistaken for TB and, more worryingly, 13 were diagnosed with rifampicin -resistant infections. Of this subgroup, seven were later confirmed to have multi-drug-resistant TB.
Undiagnosed, rifampicin-resistant TB was accordingly present in 10.1% of the study population (95% confidence interval, 3.9% to 16.4%). To complicate matters, one patient was suspected of having developed multidrug resistance during the treatment programme whilst others were suspected of being co-infected with both drug-resistant and drug-susceptible TB.
The findings suggest that the current TB IRIS diagnostic approach is, in many cases, inadequate. The investigators accordingly advise a thorough investigation of alternative diagnoses before a TB IRIS verdict is reached. Furthermore, suspected TB IRIS sufferers should undergo extensive drug-susceptibility testing before and during treatment to evaluate whether TB infection is (or has recently become) resistant to treatment.
The findings support the view that corticosteroids should only be administered to patients in whom TB drug resistance (and multidrug-resistance) is absent.
The authors conclude that rapid, low-cost diagnostic procedures are urgently needed to aid health practitioners in South Africa assess TB drug resistance and, hence, design better treatment regimens for co-infected HIV-TB patients.
Meintjes G et al. Novel relationship between tuberculosis immune reconstitution inflammatory syndrome and antitubercular drug resistance. Clinical Infectious Diseases 48: 667-76, 2009.