The objective was to compare the quantitative T-cell responses measured by the commercial interferon-gamma (IFNgamma) release assays (IGRAs) in active and latent tuberculosis (TB) states. T-cell responses of culture-proven TB cases were compared with those of contacts with positive IGRA results and tuberculin skin tests >or= 15 mm. T-SPOT.TB results in 270 active TB cases and 183 community contacts showed the median spot-forming cells (SFCs) above negative control/2.5 x 10(5) peripheral blood mononuclear cells to be 27 (-1 to 203) vs 10 (-2 to 174) in response to ESAT-6 (p < 0.001); and 37 (0 to 293) vs 13 (0 to 225) to CFP-10 (p < 0.001). The median IFNgamma levels (antigen minus nil control) as measured by QuantiFERON-TB Gold In-tube in 270 cases and 142 contacts in congregate settings was 2.3 IU/ml (-0.58 to 31.44) vs 1.7 IU/ml (0.35 to 26.51, p = 0.98). Quantitative T-cell responses as measured by the T-SPOT.TB may indicate mycobacterial burden and disease activity, but cannot be used to discriminate active from latent TB.

ObjectivesThe aim of the study was to elucidate primary drug resistance and transmission of HIV-1 in acute and recent drug-naïve seroconverters in Singapore. MethodsAcute and recent HIV-1 seroconverters were enrolled in the study. The HIV-1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV-1 transmission clusters were inferred from phylogenetic clustering analysis. ResultsOf the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV-1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B 0 (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty-one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1. 65-23.95]. MSM (OR 5.63,, high viral load (OR 4.28, 95% CI 1.37-13.36) and young age (OR 0.92, 95% CI 0.85-0.99) were independently associated with clustered individuals. ConclusionsIn Singapore, HIV-1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV-1 transmission.Keywords: HIV-1, molecular epidemiology, phylogenetics, primary resistance, seroconverter Accepted 20 January 2009 Introduction Primary or transmitted drug resistance in HIV-1 has been a significant clinical and public health concern with the widespread use of antiretroviral therapy (ART) world-wide, particularly in the developed world [1]. A number of recent studies conducted in the USA and Western European countries have shown that the prevalence rates of HIV-1 primary resistance range from approximately 8 to 16% in recently infected, drug-naïve individuals [2][3][4][5][6]. Although HIV-1 primary resistance is less prevalent in Asian countries, a recent report from Thailand has demonstrated a comparable prevalence rate (12.4%) to those reported in developed countries, presumably reflecting increased access to ART in Thailand [7].In Singapore, antiretrovirals have been available since the early 1990s and ART has been readily accessible from the year 2000 [8]. However, a previous study conducted in our centre showed that none of the 35 variants of CRF01_AE (which is the predominant subtype in both Thailand and Singapore) obtained from newly diagnosed, drug-naïve patients was drug-resistant [9]. As certain drug resistance mutations of HIV-1 can persist in transmitted viruses for only about 2 years [10,11] and the durations of HIV-1 infection for the subjects in the previous Singapore study [9] are unknown, it was necessary to further validate this finding and to obtain a more recent picture of primary resis...

The high rate of positive baseline TST results in our BCG-vaccinated healthcare workers renders the TST unsuitable as a surveillance tool in this tuberculosis risk group. Use of an IGRA has enabled the detection and treatment of latent tuberculosis in this group. Our T-SPOT.TB conversion rate highlights the need for greater tuberculosis awareness and improved infection control practices in our healthcare institutions.

SUMMARYWe report a marked increase in the rate of notifications of tuberculosis in young adults in the London Borough of Lambeth. Analysis of notifications made to the Proper Officer over a 10-year period showed that the age specific notification rate in the cohort aged 20-44 years increased from 30/100000 in 1983 to 51/100000 in 1992. Analysis of St. Thomas' Hospital laboratory records of patients seen between 1984 and 1991 from whom Mycobacterium tuberculosis was isolated showed an increase in the number of patients of African origin from five in the first half of the study period (1984-7) to 25 in the second half (1988-91): 21 of these 25 had immigrated into England within 4 years of their illness. This finding is being further investigated in a prospective study of ethnicity, travel history and date of immigration of Lambeth residents notified with tuberculosis.