To determine hepatitis C incidence and the demographic and behavioural predictors in seronegative drug injecting prisoners. Prisoners in New South Wales, Australia who: were aged 18 years and over; reported IDU; had been continuously imprisoned; had a documented negative HCV antibody test result in prison in the last 12 months; provided written informed consent. Subjects were interviewed about their demographic characteristics and detailed risk factors for transmission prior to, and since, imprisonment. A blood sample was collected to screen for HCV antibodies by ELISA and RNA by PCR. Of 253 inmates recruited, 120 were continuously imprisoned and included in this analysis. Sixteen acquired HCV infection indicating an incidence of 34.2 per 100 person years (CI: 19.6-55.6). Risk factors for transmission included prior imprisonment, methadone treatment and greater than 10 years of education. Although the frequency of injecting was reduced in prison, 33.6% continued to inject drugs, most commonly methamphetamine, and 90% of these reported sharing injecting equipment. Prison inmates were at high risk of HCV infection, despite some reduction in high-risk behaviours and access to prevention services. To prevent HCV transmission in prisons, better prevention strategies are required.

BackgroundHepatitis C virus (HCV) infection is common in prisoner populations, particularly those with a history of injecting drug use (IDU). Previous studies of HCV incidence have been based on small case numbers and have not distinguished risk events in prison from those in the community.MethodsHCV incidence was examined in a longitudinal cohort of 488 Australian prisoners with a history of IDU and documented to be seronegative within 12 months prior to enrolment. Inmates were tested for anti-HCV antibodies and viremia, and interviewed about demographic and behavioral risk factors for transmission.ResultsThe cohort was predominantly male (65%) with high rates of prior imprisonment (72%) and tattooing (73%), as well as longstanding IDU (mean 8.5 years). Ninety-four incident HCV cases were identified (incidence 31.6 per 100 person years). Independent associations were observed between incident infection and prior imprisonment (p = 0.02) and tattooing (p = 0.03), and surprisingly also with methadone maintenance treatment (MMT) (p < 0.001).ConclusionsHigh rates of new HCV infection were found in this prisoner cohort reflecting their substantive risk behavior profile, despite having remained uninfected for many years. The association with MMT is challenging and highlights the need for better understanding of prison-specific HCV transmission risks, as well as the uptake and effectiveness of prevention programs.

Multiple sclerosis (MS) is an enigmatic disease of the central nervous system resulting in sclerotic plaques with the pathological hallmarks of demyelination and axonal damage, which can be directly or indirectly orchestrated by cells from the peripheral circulation. The majority of patients with MS follow a relapsing-remitting course in the early stages of the disease (RRMS) but most ultimately enter a secondary progressive phase (SPMS). About 10% of patients follow a primary progressive course from the onset (PPMS). We measured gene expression in whole blood of people with and without chronic progressive MS (CPMS), PPMS and SPMS, to discover genes which may be differentially expressed in peripheral blood in active disease, and so identify pathologically significant genes and pathways; and we investigated genetic differences in the promoters of dysregulated genes encoded in genomic regions associated with MS. If SPMS and PPMS were independently compared to the controls, there was little overlap in the set of most dysregulated genes. Ribosomal protein genes, whose expression is usually associated with cell proliferation and activation, were dramatically over-represented in the set of most down-regulated genes in PPMS compared to SPMS (P < 10(-4), chi(2)). The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. One interleukin 7 receptor (IL7R) promoter single nucleotide polymorphism (SNP), -504 C, was undertransmitted in PPMS trios (P = 0.05, TDT), and carriers of this allele were under-represented in PPMS cases from two independent patient cohorts (combined P = 0.006, FE). The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P < 0.01, t test). These data support the hypothesis that PPMS has significant pathogenetic differences from SPMS, and that IL7R may be a useful therapeutic target in PPMS.

We have investigated the interleukin-7 receptor (IL-7R) a-chain gene as a positional and functional candidate gene for susceptibility to multiple sclerosis (MS), in view of its chromosomal location on 5p14-p12, a region that has shown suggestive linkage in MS genome screens, and its role in T-and B-cell proliferation and reactivity. Amplification and DNA sequencing of the IL-7Ra gene in pooled and individual samples identified 13 single nucleotide polymorphisms (SNPs), 11 of which are novel, including three in the promoter region, three in exons encoding amino-acid changes (ACC(Thr)66ATC(Ile), ATC(Ile)244ACC(Thr), ATC(Ile)336GTC(Val)), four in introns and one in the 3 0 untranslated region. Four IL-7R haplotypes were identified for nine SNPs, showing linkage disequilibrium across the gene, and allowing haplotype frequency determination from just three of the nine SNPs. Genotyping of the À504 polymorphism in 101 MS and 90 controls showed a suggestive (P ¼ 0.1) association of the T allele with MS; however, this was not supported by transmission disequilibrium testing in 186 MS trio families (P ¼ 0.8). There were trends towards an increase of the GTG+ haplotype (odds ratio ¼ 1.45), and underrepresentation of the TTA+ haplotype (OR ¼ 0.65) in DRB1*1501-positive MS cases, suggesting that larger sample sizes and comparison in more defined MS patient groups may support an association with the IL-7R gene. These polymorphisms would also be useful for studying genetic associations with other immunologic diseases.