Novel relationship between tuberculosis immune reconstitution inflammatory syndrome and antitubercular drug resistance.
BACKGROUND
Tuberculosis (TB) immune reconstitution inflammatory syndrome (IRIS) is emerging as an important early complication of combination antiretroviral therapy in patients with TB in developing countries. The differential diagnosis of TB IRIS includes deterioration caused by other human immunodeficiency virus-related morbidities and drug-resistant TB.


METHODS
We prospectively evaluated consecutive patients with suspected TB IRIS from February 2005 through July 2006 at a community-based secondary hospital in Cape Town, South Africa, by means of clinical case definitions for TB IRIS. Specimens were sent for TB culture and susceptibility testing, and a rapid test (FASTplaque-Response) was performed to expedite determination of rifampin susceptibility.


RESULTS
One hundred patients with suspected TB IRIS were evaluated, 26 of whom were being retreated for TB. IRIS symptoms developed a median of 14 days (interquartile range, 7-25 days) after the initiation of combination antiretroviral therapy. In 7 patients, an alternative opportunistic disease was diagnosed. Rifampin-resistant TB was present in 13 patients, 9 of whom received a diagnosis after study entry (7 of 9 had multidrug-resistant TB). Undiagnosed rifampin-resistant TB was thus present in 10.1% of patients (95% confidence interval, 3.9%-16.4%) who presented with TB IRIS, once those with alternative diagnoses and TB with known rifampin resistance were excluded. In the remaining 80 patients, TB IRIS without rifampin resistance was the final diagnosis.


CONCLUSIONS
TB IRIS that is clinically indistinguishable from TB IRIS that occurs in the context of drug-susceptible disease may occur in patients with undiagnosed multidrug-resistant TB. Antitubercular drug resistance should be excluded in all cases of suspected TB IRIS, and corticosteroids should be used with caution for patients with presumed TB IRIS until the result of drug-susceptibility testing is known.
Meintjes
Graeme
G
Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. graemein@mweb.co.za
Rangaka
Molebogeng X
MX
Maartens
Gary
G
Rebe
Kevin
K
Morroni
Chelsea
C
Pepper
Dominique J
DJ
Wilkinson
Katalin A
KA
Wilkinson
Robert J
RJ
D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology*; D011446:Prospective Studies; D013019:South Africa; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
D000995:Antitubercular Agents