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1.
Clin Dermatol ; 32(2): 282-5, 2014.
Article in English | MEDLINE | ID: mdl-24559564

ABSTRACT

In 2011, the estimated number of people living with HIV in Europe and Central Asia was 2.3 million. This is more than twice the 2001 figure. At the same time, approximately 50% of the infected people may not know their HIV status. The Europe/Central Asia region is one of only two regions in which HIV infections continue to increase. The estimated prevalence rate in the west and center of the region, however, has remained stable at 0.2%. The HIV epidemics in Eastern Europe and Central Asia are typically driven by unsafe drug injection and by onward transmission to the sexual partners of people who inject drugs. In the western part of the region, the epidemic remains concentrated among men who have sex with men and migrants from countries with generalized epidemics. Means of preventing and fighting HIV should, first and foremost, be directed to those parts of the population that are most exposed to the risk of the infection. Proceeding from the data presented, recommendations are given for ways of decreasing HIV prevalence in the region, such as promoting dialogue and awareness among multistakeholders, including policy makers, donors, and population groups most exposed to the infection.


Subject(s)
HIV Infections/epidemiology , HIV Infections/transmission , Africa South of the Sahara/ethnology , Europe/epidemiology , HIV Infections/diagnosis , HIV Infections/ethnology , Homosexuality, Male/statistics & numerical data , Humans , Male , Prevalence , Substance Abuse, Intravenous/epidemiology , Transients and Migrants/statistics & numerical data
2.
Lancet Neurol ; 12(12): 1159-69, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24183309

ABSTRACT

BACKGROUND: Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials. METHODS: In this case-control study, samples were collected prospectively from patients with mutation-proven AGS. The expression of six interferon-stimulated genes (ISGs) was measured by quantitative PCR, and the median fold change, when compared with the median of healthy controls, was used to create an interferon score for each patient. Scores higher than the mean of controls plus two SD (>2·466) were designated as positive. Additionally, we collated historical data for interferon activity, measured with a viral cytopathic assay, in CSF and serum from mutation-positive patients with AGS. We also undertook neutralisation assays of interferon activity in serum, and looked for the presence of autoantibodies against a panel of interferon proteins. FINDINGS: 74 (90%) of 82 patients had a positive interferon score (median 12·90, IQR 6·14-20·41) compared with two (7%) of 29 controls (median 0·93, IQR 0·57-1·30). Of the eight patients with a negative interferon score, seven had mutations in RNASEH2B (seven [27%] of all 26 patients with mutations in this gene). Repeat sampling in 16 patients was consistent for the presence or absence of an interferon signature on 39 of 41 occasions. Interferon activity (tested in 147 patients) was negatively correlated with age (CSF, r=-0·604; serum, r=-0·289), and was higher in CSF than in serum in 104 of 136 paired samples. Neutralisation assays suggested that measurable antiviral activity was related to interferon α production. We did not record significantly increased concentrations of autoantibodies to interferon subtypes in patients with AGS, or an association between the presence of autoantibodies and interferon score or serum interferon activity. INTERPRETATION: AGS is consistently associated with an interferon signature, which is apparently sustained over time and can thus be used to differentiate patients with AGS from controls. If future studies show that interferon status is a reactive biomarker, the measurement of an interferon score might prove useful in the assessment of treatment efficacy in clinical trials. FUNDING: European Union's Seventh Framework Programme; European Research Council.


Subject(s)
Adenosine Deaminase/genetics , Autoimmune Diseases of the Nervous System/metabolism , Exodeoxyribonucleases/genetics , Gene Expression Regulation , Interferon Type I/physiology , Monomeric GTP-Binding Proteins/genetics , Nervous System Malformations/metabolism , Phosphoproteins/genetics , Ribonuclease H/genetics , Adolescent , Adult , Autoantibodies/blood , Autoimmune Diseases of the Nervous System/genetics , Biomarkers , Case-Control Studies , Child , Child, Preschool , Female , Genetic Heterogeneity , Genotype , Humans , Infant , Interferon Type I/blood , Interferon Type I/cerebrospinal fluid , Interferon Type I/immunology , Male , Mutation , Nervous System Malformations/genetics , Neutralization Tests , Prospective Studies , RNA, Messenger/biosynthesis , RNA-Binding Proteins , SAM Domain and HD Domain-Containing Protein 1 , Up-Regulation , Young Adult
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