PMID- 27600661 OWN - NLM STAT- MEDLINE DCOM- 20170705 LR - 20220331 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 16 IP - 1 DP - 2016 Sep 6 TI - Determinants of treatment-related paradoxical reactions during anti-tuberculosis therapy: a case control study. PG - 479 LID - 10.1186/s12879-016-1816-4 [doi] LID - 479 AB - BACKGROUND: Inflammatory 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. METHODS: Prospective 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. RESULTS: Of 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). CONCLUSION: HIV 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. FAU - Brown, Colin Stewart AU - Brown CS AD - Hospital for Tropical Diseases, University College London Hospitals Foundation Trust, 235 Euston Road, London, NW1 2BU, UK. AD - UCL Division of Infection and Immunity, University College London, Rowland Hill Street, London, NW3 2PF, UK. FAU - Smith, Colette Joanne AU - Smith CJ AD - Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK. FAU - Breen, Ronan Angus MacCormick AU - Breen RA AD - Guy's and St Thomas' Hospital NHS Trust, Westminster Bridge Road, London, SE1 7EH, UK. FAU - Ormerod, Lawrence Peter AU - Ormerod LP AD - Royal Blackburn Hospital, Blackburn, Lancs, BB2 3LR, UK. FAU - Mittal, Rahul AU - Mittal R AD - Royal Blackburn Hospital, Blackburn, Lancs, BB2 3LR, UK. FAU - Fisk, Marie AU - Fisk M AD - Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UK. FAU - Milburn, Heather June AU - Milburn HJ AD - Guy's and St Thomas' Hospital NHS Trust, Westminster Bridge Road, London, SE1 7EH, UK. FAU - Price, Nicholas Martin AU - Price NM AD - Guy's and St Thomas' Hospital NHS Trust, Westminster Bridge Road, London, SE1 7EH, UK. FAU - Bothamley, Graham Henry AU - Bothamley GH AD - Homerton University Hospital, Homerton Row, London, E9 6SR, UK. FAU - Lipman, Marc Caeroos Isaac AU - Lipman MC AUID- ORCID: 0000-0001-7501-4448 AD - Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UK. marclipman@nhs.net. AD - UCL Respiratory, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK. marclipman@nhs.net. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20160906 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (Antitubercular Agents) SB - IM MH - Adult MH - Antitubercular Agents/adverse effects/*therapeutic use MH - Case-Control Studies MH - Cohort Studies MH - Coinfection/epidemiology MH - Ethnicity MH - Female MH - *HIV Infections/drug therapy MH - Humans MH - Male MH - Multivariate Analysis MH - Prospective Studies MH - Retrospective Studies MH - Risk Factors MH - Tuberculosis, Pulmonary/complications/*drug therapy/epidemiology MH - United Kingdom/epidemiology PMC - PMC5013570 OTO - NOTNLM OT - Determinants OT - Ethnicity OT - HIV OT - IRIS OT - Paradoxical reactions OT - Predictors OT - Treatment OT - Tuberculosis EDAT- 2016/09/08 06:00 MHDA- 2017/07/06 06:00 PMCR- 2016/09/06 CRDT- 2016/09/08 06:00 PHST- 2016/04/27 00:00 [received] PHST- 2016/09/03 00:00 [accepted] PHST- 2016/09/08 06:00 [entrez] PHST- 2016/09/08 06:00 [pubmed] PHST- 2017/07/06 06:00 [medline] PHST- 2016/09/06 00:00 [pmc-release] AID - 10.1186/s12879-016-1816-4 [pii] AID - 1816 [pii] AID - 10.1186/s12879-016-1816-4 [doi] PST - epublish SO - BMC Infect Dis. 2016 Sep 6;16(1):479. doi: 10.1186/s12879-016-1816-4.