Determinants of treatment-related paradoxical reactions during anti-tuberculosis therapy: a case control study

Abstract

BackgroundInflammatory response following initial improvement with anti-tuberculosis (TB) treatment has been termed a paradoxical reaction (PR). HIV co-infection is a recognised risk, yet little is known about other predictors of PR, although some biochemical markers have appeared predictive. We report our findings in an ethnically diverse population of HIV-infected and uninfected adults.MethodsProspective and retrospective clinical and laboratory data were collected on TB patients seen between January 1999–December 2008 at four UK centres selected to represent a wide ethnic and socio-economic mix of TB patients. Data on ethnicity and HIV status were obtained for all individuals. The associations between other potential risk factors and PR were assessed in a nested case-control study. All PR cases were matched two-to-one to controls by calendar time and centre.ResultsOf 1817 TB patients, 82 (4.5 %, 95 % CI 3.6–5.5 %) were identified as having a PR event. The frequency of PR was 14.4 % (18/125; 95 % CI 8.2–20.6 %) and 3.8 % (64/1692; 2.9–4.7) for HIV-positive and HIV-negative individuals respectively. There were no differences observed in PR frequency according to ethnicity, although the site was more likely to be pulmonary in those of black and white ethnicity, and lymph node disease in those of Asian ethnicity. In multivariate analysis of the case-control cohort, HIV-positive patients had five times the odds of developing PR (aOR = 5.05; 95 % CI 1.28–19.85, p = 0.028), whilst other immunosuppression e.g. diabetes, significantly reduced the odds of PR (aOR = 0.01; 0.00–0.27, p = 0.002). Patients with positive TB culture had higher odds of developing PR (aOR = 6.87; 1.31–36.04, p = 0.045) compared to those with a negative culture or those in whom no material was sent for culture. Peripheral lymph node disease increased the odds of a PR over 60-fold 4(9.60–431.25, p < 0.001).ConclusionHIV was strongly associated with PR. The increased potential for PR in people with culture positive TB suggests that host mycobacterial burden might be relevant. The increased risk with TB lymphadenitis may in part arise from the visibility of clinical signs at this site. Non-HIV immunosuppression may have a protective effect. This study highlights the difficulties in predicting PR using routinely available demographic details, clinical symptoms or biochemical markers.

Multifocal Tuberculosis with Prolonged Paradoxical Reaction

“…Those of Black ethnicity conversely exhibited more pulmonary involvement than people of South Asian and White ethnicity. HIV was strongly associated with the development of PR [8] . Table 1 shows a summary of previously published reports of PR.…”

“…Brown and colleagues reviewed records of 1817 patients treated for TB; 82 (4.5 %; 95% CI 3.6-5.5) patients experienced PR, the site of which varied by ethnic group [8] . Extra-pulmonary TB involving lymph node was found to be signifi cantly more common among South Asians than Blacks adjusted for other ethnicities.…”

Management of intracranial tuberculous mass lesions: how long should we treat for?

“…However, many of these patients are asymptomatic during these episodes and the frequency of detecting paradoxical tuberculoma development or enlargement increases substantially (from 29% to 65%) if surveillance brain imaging is performed during the first six months of TB treatment 35 . Paradoxical TB reactions are more common in HIV-infected patients, particularly in those who commence antiretroviral therapy (ART) after starting TB treatment, in which case it is referred to as paradoxical TB-immune reconstitution inflammatory syndrome (TB-IRIS) [48][49][50][51] . The influence of HIV on the frequency of paradoxical tuberculoma reactions (separate from the effect of ART) has rarely been reported.…”

Longitudinal analysis of serum cytokine profile among patients with tubercular multifocal serpiginoid choroiditis: a pilot study

“…In a study of 1817 patients with pulmonary/extrapulmonary TB, increased incidence of paradoxical worsening was associated with higher antigenic load, HIV positivity and peripheral lymphadenopathy. Thus, development of paradoxical worsening may be related to host immunity [6]. In the context of ocular TB, very few studies have shed light on the biochemical basis of the disease (but not on paradoxical worsening).…”