BackgroundThe efffectiveness of tuberculosis (TB) contact screening programmes using interferon γ release assays remains uncertain as prospective contact TB risk is not well characterised. Objectives To quantify 2-year TB risk and evaluate screening performance with single-step QuantiFERON TB Gold-In Tube (QFT) in adult contacts. To compare TB risk between QFT tested subgroups stratified by exposure type (smear positive pulmonary (SP) versus non-smear positive (NSP) TB) and age (younger (16-35 years) versus older (≥36 years)). Methods Screening involved QFT testing in older contacts of SP and all younger contacts, 8-12 weeks after index notification. Chemoprevention (3RH) was offered to QFT positive (+) younger adults. TB risk was determined in a prospective cohort study. Results 43 TB events occurred in 1769 adult contacts observed for median 717 days (2-year rate (95% CI) =2·5% (1.7 to 3.2)). Index-contact strain matching was demonstrable for 18 of 22 (82%) paired samples. No contacts (0/98) receiving 3RH developed TB. 215 of 817 appropriately tested adults (26.3%) were QFT+. 14 of 112 untreated QFT+ adults developed TB (2-year rate (95% CI)=13·4% (7.7 to 21.1)). The model required 35 contacts screened with QFT to identify one contact developing TB at 2 years. TB rates were comparable in QFT+ contacts of SP and NSP (rate ratio (RR)=0.98, p=0·962). For QFT+ older contacts, the disease rate was lower (8.9% (3.3 to 19
Introduction Diagnosis of tuberculosis (TB) ideally involves culture and sensitivity of the organism but in low income countries this is not practised routinely. The World Health Organisation estimates that substandard detection occurs in 40% of patients globally, with many diagnosed on clinical suspicion or response to medication. TB produces a strong antibody response suitable for simple, inexpensive and rapid serodiagnostic assays. Ongoing evaluation of a new point of care rapid serological test based on lateral flow immunochromatography (TB-ST Rapid Test, Lionex, Germany) has shown 100% specificity, with no false positive tests in normal controls and latently infected patients, but sensitivity of 36%, with false negatives in culture proven TB. Aim Using this test in a resource poor setting to investigate whether cases of active TB may be being missed by current diagnostic methods. Methods 498 patients in chest and HIV clinics in two rural Kenyan hospitals were investigated with the TB-ST Rapid Test and a scored questionnaire to determine symptoms and risk of TB. Results were compared with clinical diagnoses made, usually based on symptoms alone. Chest radiographs were performed in only 111 and sputum smears in 75.Results 127/498 patients were HIV positive. Of these, only 59(46%) had a clinical diagnosis of TB, whereas 87(68.5%) had significant TB symptoms and/or risk factors, and 82(64.6%) tested TB-ST positive (p<0.001). Therefore clinical diagnosis accounted for significantly fewer diagnoses of active TB than suggested by either symptom and risk score or TB-ST rapid results in the HIV+ population. Of the 375 HIVÀ patients, 73 (19.7%) had a clinical diagnosis of TB, 46 (12.3%) scored positive for TB on the questionnaire, and 149 (40.2%) were TB-ST+ (p<0.001). Abstract P165 Conclusions Many more patients had positive TB-ST and risk and symptom scores than were being diagnosed with active TB, suggesting that TB may not always be being diagnosed or treated. Sputum smears were in greater agreement with the TB-ST in HIVÀ but not HIV+ patients, in whom there were considerably fewer positive smears than TB-ST results.
plasma small RNA (0-150 nucleotides) concentration was significantly higher (p < 0.0001) in 31 individuals before therapy (median 332pg µL -1 plasma, range 93-1603pg µL -1 ) than at the end of therapy at week 24 (median 86pg µL -1 plasma, range 16-1098pg µL). Expression analysis of small RNA genes revealed that, in 5 tuberculosis-infected HIV-1 negative individuals, 36 of 90 genes (> 2-fold, p < 0.05) were upregulated before compared to post-therapy completion. 29a, 133a, small RNA concentration and SNORD61 were further tested and this analysis revealed that in 84% of individuals (n = 31) at least one of these biomarkers was upregulated > 2 fold in active tuberculosis. Co-infection with HIV-1 was not found to change the expression of these six tested biomarkers. S60 RISK FACTORS ASSOCIATED WITH MYCOBACTERIUM TUBERCULOSIS (MTB) INFECTION AND PROGRESSION TO ACTIVE TB DISEASE IN CHILD CONTACTSN Karnani, S Sridhar, D Connell, A Lalvani; Imperial College London, London, United Kingdom 10. 1136/thoraxjnl-2013-204457.67 Background Mathematical modelling has shown the most effective strategy to eliminate tuberculosis (TB) worldwide is to address the large burden of latent TB infection (LTBI). Identification of the risk factors which predispose individuals to acquire Mtb infection and those determining risk of progressing from infection to active disease will enable risk stratification for targeted TB interventions. Objective To identify host, socioeconomic and environmental risk factors for acquiring Mtb infection following exposure to TB and risk factors for progression from infection to active TB disease. Methods Risk factors associated with infection and progression were investigated in a primary analysis of a well-defined cohort of 965 Turkish household child contacts exposed to smear positive pulmonary TB patients. Risk factors for infection were assessed in study subjects with and without Mtb infection. Mtb infection was defined by interferon gamma-release assay (IGRA) results at two time points-baseline and 6 months-thus creating robust criteria to avoid misclassification of IGRA converters and IGRA reverters. Adjusted odd ratios were estimated using stepwise logistic regression including variables with p < 0.2 on univariate regression. ResultsIn the child cohort passive smoking was found to be an independent risk factor for Mtb infection (OR: 1.52, 95% CI: 1.09 -2.12). Higher household monthly income was an independent protective factor against Mtb infection (OR: 0.55, 95% CI: 0.38 -0.79). Increasing age was associated with a decreased risk of progressing from infection to disease (OR: 0.67, 95% CI: 0.51-0.87). Children exposed to more than 1 TB patient were 8 times more likely to progress to disease (OR: 8.66, 95% CI: 1.54-48.55). Conclusion Identification of an association between passive exposure to cigarette smoke and acquisition of Mtb infection in children adds new evidence for smoking cessation strategies to be incorporated into TB prevention programmes. To aid TB elimination we therefore advocate an...
31 year old man was referred with prolonged loss of vision after a typical migraine attack. His usual migraine attacks consisted of a left sided headache preceded by nausea and vomiting and a visual aura of coloured and flashing lights in both visual fields. Visual loss after his migraines could last up to one hour. The frequency of his headaches had markedly increased eight months before presentation and these were relieved with a combination of pizotifen and naratriptan. Three weeks before presentation, he suffered a typical migraine but noticed that the visual loss after the migraine persisted as a "hole" in the vision of the left eye. Two weeks later he developed a similar scotoma in the field of the right eye with distortion of vision in that eye such that straight lines appeared wavy. He had no other relevant past medical history. On examination, his visual acuity was restricted to perception of movement only in the left eye and 6/60 in the right eye. Fundoscopy revealed the presence of arteriolar-venous nipping, "flame
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