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OBJECTIVE: To examine if monocyte and macrophage activity may be on the mechanistic pathway to non-AIDS comorbidity by investigating the associations between plasma-soluble CD163 (sCD163) and incident non-AIDS comorbidities in well treated HIV-infected individuals.DESIGN: Prospective single-center cohort study.METHODS: Plasma sCD163 was quantified by ELISA technique at study entry in 2004/2005, and non-AIDS comorbidity was identified by International Classification of Disease Tenth revision diagnosis codes and registry linkage in 2014/2015. Associations between sCD163 and incident comorbidity was examined using multivariable Cox proportional hazards models adjusted for pertinent covariates.RESULTS: In HIV-1-infected individuals (n = 799), the highest quartile of plasma sCD163 was associated with incident chronic lung disease [adjusted hazard ratio (aHR), 3.2; 95% confidence interval (CI): 1.34; 7.46] and incident chronic kidney disease (aHR, 10.94; 95% CI: 2.32; 51.35), when compared with lowest quartiles. Further, (every 1 mg) increase in plasma sCD163 was positively correlated with incident liver disease (aHR, 1.12; 95% CI: 1.05; 1.19). The sCD163 level was not associated with incident cancer, cardiovascular disease or diabetes mellitus.CONCLUSION: sCD163 was independently associated with incident chronic kidney disease, chronic lung disease and liver disease in treated HIV-1-infected individuals, suggesting that monocyte/macrophage activation may be involved in the pathogenesis of non-AIDS comorbidity and a potential target for therapeutic intervention.

BACKGROUND: CD163, a monocyte- and macrophage-specific scavenger receptor, is shed as soluble CD163 (sCD163) during the proinflammatory response. Here, we assessed the association between plasma sCD163 levels and progression to AIDS and all-cause mortality among individuals infected with human immunodeficiency virus type 1 (HIV).METHODS: Plasma sCD163 levels were measured in 933 HIV-infected individuals. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with mortality were computed by Cox proportional hazards regression.RESULTS: At baseline, 86% were receiving antiretroviral treatment, 73% had plasma a HIV RNA level of CONCLUSIONS: Plasma sCD163 was an independent marker of all-cause mortality in a cohort of HIV-infected individuals, suggesting that monocyte/macrophage activation may play a role in HIV pathogenesis and be a target of intervention.

Objectives Risk of subsequent diagnosis of HIV in persons diagnosed with newly acquired syphilis, and syphilis in HIV-infected persons, are of interest as these infections are markers of unsafe sex. Methods From a nationwide register, all Danish men aged >16 years diagnosed with syphilis in the period 2000–2010 (n=1217) were identified, and subsequently data on HIV status was extracted from the Danish HIV Cohort Study. We used Kaplan–Meier analysis to estimate the 5-year risk of HIV and second syphilis infection, and Cox regression to determine incidence rate ratios (IRR). Results The 5-year risk of HIV diagnosis was 9.8% (95% CI 7.0% to 12.6%). Those with a second diagnosis of syphilis had a higher risk of being diagnosed with HIV (IRR=3.1, 95% CI 1.2 to 8.0). The 5-year risk for a second diagnosis of syphilis was 14.8% (95% CI 12.1% to 17.4%) and HIV-infected persons had a higher risk of a second syphilis diagnosis (IRR=4.0, 95% CI 2.8 to 5.9). Sixty-five percent of the persons were men having sex with men (MSM). Thirty-four percent of the HIV-infected persons had viral load >1000 copies/ml at time of syphilis diagnosis. Conclusions The substantial risks of syphilis and HIV infection in men diagnosed with one of these sexually transmitted diseases indicate a high frequency of unsafe sex in the Danish MSM population. As one-third of the HIV-infected persons diagnosed with syphilis had high viral loads, our data support initiation of antiretroviral therapy in all HIV-infected MSM to reduce HIV transmission.

The aim of this nationwide study is to determine the strain type diversity among patients diagnosed with syphilis by PCR during a 4-year period in Denmark. Epidemiological data, including HIV status, for all patients were obtained from the Danish national syphilis registration system. Molecular strain typing was based on characterization of 3 variable treponemal genes, arp, tpr and tp0548. A total of 278 specimens from 269 patients were included. Among the fully typeable specimens (n = 197), 22 strain types were identified, with 1 type, 14d/g, accounting for 54%. The majority (93%) of the patients reported acquiring syphilis in Denmark. Among patients with concurrent HIV, 9 full strain types were identified and no difference in strain type was found by HIV status (p = 0.197). In conclusion, the majority of patients were infected in Denmark and the HIV-infected syphilis patients were diagnosed with a wide spectrum of different strain types of Treponema pallidum.

The recent identification of a novel clinical entity, the severe acute respiratory syndrome (SARS), the rapid subsequent spread and case fatality rates of 14–15% have prompted a massive international collaborative investigation facilitated by a network of laboratories established by the World Health Organization (WHO). As SARS has the potential of becoming the first pandemic of the new millennium, a global warning by the WHO was issued on 12 March 2003. The disease, which is believed to have its origin in the Chinese Guangdong province, spread from Hong Kong via international airports to its current worldwide distribution. The concerted efforts of a globally united scientific community have led to the independent isolation and identification of a novel coronavirus from SARS patients by several groups. The extraordinarily rapid isolation of a causative agent of this newly emerged infectious disease constitutes an unprecedented scientific achievement. The main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of SARS. On the basis of the recently published viral genome and structural features common to the members of the coronavirus family, a model for host cell–virus interaction and possible targets for antiviral drugs are presented. The epidemiological consequences of introducing a novel pathogen in a previously unexposed population and the origin and evolution of a new and more pathogenic strain of coronavirus are discussed.

A syndrome involving acute urinary retention in combination with sacral radiculitis and cerebrospinal fluid pleocytosis was first described by the American neurosurgeon Charles Elsberg in 1931. In many instances the aetiology is herpes simplex virus type 2 (HSV-2) reactivation from sensory neurons. In this case report we present a 34-year-old pregnant woman with previous undiagnosed sensory lumbosacral symptoms. She was hospitalized with HSV-2 meningitis and lumbosacral radiculitis but no genital rash. A week after the onset of symptoms she developed acute urinary retention, thus indicating Elsberg syndrome.

HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Δ32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter −2459 A/G transition that has been discovered recently, have also been shown to influence HIV progression. Since genetic linkages make these polymorphisms interdependent variables, the aim of the present study was to isolate and evaluate the effect on HIV disease progression for each of these mutations independently. Genotypes were determined in 119 individuals enrolled in the Copenhagen AIDS Cohort. When including the concurrent effects of the CCR5 Δ32 and CCR2 64I mutations, homozygous carriers of the CCR5 promoter −2459A allele had a significantly faster progression towards death than heterozygous A/G individuals (P = 0.03), whereas this adverse effect was not significant when comparing A/A and G/G individuals. However, independent analysis revealed a significant adverse effect of the CCR5 promoter −2459A allele. Homozygous carriers of the −2459A allele that lack the protective effects of the CCR5 Δ32 and CCR2 64I mutations were found to have a median survival of 6.0 years, whereas carriers of the −2459G allele had a median survival of 9.4 years (P

Syphilis is still a serious disease with diagnostic difficulties. In the present clinical case a patient had a routine serology screen for syphilis and HIV at a venerology clinic. He had previously presented with anogenital tumors, but the diagnosis was uncertain. A polymerase chain reaction (PCR) analysis was performed in addition to serology, and the diagnosis of syphilis in the secondary stage was confirmed. This case demonstrates how PCR technology can assist in the diagnosis of syphilis at early stages and underlines the importance of syphilis screening in homosexual men presenting with anogenital complaints.

Chancroid is a sexually transmitted disease characterized by painful ulcers with a soft margin, necrotic base and purulent exudate. Previously, only sporadic, imported cases have been reported in Denmark. The bacterium is difficult to culture and novel polymerase chain reaction (PCR)-based methods for direct demonstration of bacterial DNA have facilitated rapid verification of the clinical diagnosis. We report two cases which demonstrate import and subsequent local transmission in Denmark. In both cases, the clinical diagnosis was rapidly verified by a combined PCR testing for multiple causes of venereal ulcers.

BACKGROUND:The monocyte/macrophage system plays important roles in host defense, regulation of immune responses, tissue repair, neovascularization, and inflammation. These diverse roles are performed by specific subpopulations of macrophages that are differently activated by surrounding stimuli, simplified by the M1-M2 dichotomy of classically activated (M1), pro-inflammatory cells and alternatively activated (M2), anti-inflammatory cells. Macrophages, however, display a large degree of flexibility and are able to switch between activation states (1).The hemoglobin scavenger receptor CD163 is expressed exclusively on monocytes and macrophages, and its expression is strongly induced by anti-inflammatory stimuli like IL10 and glucocorticoid, making CD163 an ideal M2 macrophage marker (2). Furthermore a soluble variant of CD163 (sCD163) is shed from the cell surface to plasma by protease mediated cleavage of the receptor. The shedding of sCD163 is dependent on a pro-inflammatory signal such as toll-like receptor (TLR) activation by LPS (3).These unique properties led us to investigate whether an index of combined soluble- and monocyte membrane CD163 could be used as a surrogate marker for macrophage activation. MATERIALS AND METHODS:Blood sample were obtained from 53 patients with malignant hematological disease and 74 healthy individuals. The cellular (mCD163) and soluble (sCD163) CD163 expression were measured by flow cytometry and ELISA respectively. In addition, blood mRNA expression of inflammatory markers (IL-1β, IL-6, IL-8, IL-10, and TNF-α) was determined by RT-qPCR. Normalized values of sCD163 and mCD163 were calculated by dividing each value by the median value of the healthy population. The MAcS-index was then calculated as the ratio between normalized sCD163 and normalized mCD163. A MAcS-index > 1 indicates relative increase in sCD163 as compared to mCD163, suggested to reflect a predominant M1 activation. RESULTS AND DISCUSSION: The MAcS-index of healthy individuals clustered around 1 (2.5-97.5 percentile: 0.28-3.11), whereas the MAcS-index of the patients varied from 0.06 to 5139, with 4% below the 2.5 % limit of healthy individuals, and 60% above the 97.5 upper limit of healthy individuals. The MAcS-index in infected patients (with assumed M1 activation) was clearly elevated. The index was significantly higher in patients with clinical signs of infection (median: 9.01; range: 1.41-3490) and patients in antibiotic therapy (median: 9.74; range: 0.91-5139) compared to non-infected patients (median: 2.53; range: 0.058-551.5, p treatment (median: 9.4; range: 0.57-3490), ppatients with MAcS-index within reference range. Patients with malignant myeloma (median: 0.89; range: 0.63-1.51) had significantly lower MAcS-index than patients with AML (median: 20.71; range: 0.57-2214) (pa differentiation towards an anti-inflammatory state. CONCLUSION:We present a CD163-derived macrophage activation switch (MAcS)-index, which seems able to differentiate between (predominantly) pro-inflammatory and anti-inflammatory macrophage activation. The index needs further validation, however, may be very useful for monitoring diseases with macrophage involvement and response to therapeutic interventions. REFERENCES:1. Porcheray F, Viaud S, Rimaniol AC, Léone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G. Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol. 2005 Dec;142(3):481-9.2. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004 Dec;25(12):677-86.3. Weaver LK, Hintz-Goldstein KA, Pioli PA, Wardwell K, Qureshi N, Vogel SN, Guyre PM. Pivotal advance: activation of cell surface Toll-like receptors causes shedding of the hemoglobin scavenger receptor CD163. J Leukoc Biol. 2006 Jul;80(1):26-35.

The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected of meningitis on admission to a 27-bed infectious disease department at a Danish university hospital. Biomarker serum levels on admission were measured. Sensitivity and specificity were evaluated at pre-specified cut-off values and overall diagnostic accuracies were compared using receiver-operating characteristic AUCs (areas under curves). Patients were classified by 2 sets of diagnostic criteria into: A) purulent meningitis, serous meningitis or non-meningitis, and B) systemic bacterial infection, local bacterial infection or non-bacterial disease. An elevated serum level of sCD163 was the most specific marker for distinguishing bacterial infection from non-bacterial disease (specificity 0.91; sensitivity 0.47). However, the overall diagnostic accuracy of CRP (AUC =0.91) and PCT (AUC =0.87) were superior (p Udgivelsesdato: 2007-null

Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0–6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 µg/mL). The difference in survival was significant during TB treatment (log rank, p < 0.02) and after long-term follow-up (log rank, p < 0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04–1.36) per µg of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06–16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan–Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan–Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per µg of sCD163 was 1.27 (95% CI, 1.14–1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44–5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28–14.58) and 2.48 (95% CI, 1.09–5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.

The present paper reviews the American epidemic of West Nile Fever (WNF), which is the largest recorded outbreak ever. The epidemiological consequences of introducing a novel and immunologically unknown pathogen in a previously unexposed population and the possible evolution of a more pathogenic viral strain are discussed. In view of recent reports of imported cases in Denmark the issue of possible disease spread to Scandinavia is likewise addressed. However, the main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of the disease.

In the light of the current American epidemic, and since West Nile fever (WNF) has never previously been reported in Denmark, we describe two cases imported from Israel and Canada, respectively. WNF was diagnosed in a 46-year-old Danish tourist returning from Israel and a visiting 73-year-old Canadian citizen with Danish ancestry. The former manifested itself clinically as a mild flu-like illness, the latter as serious infection of the central nervous system. Thus, in addition to representing a rare case of West Nile encephalitis, it also constitutes one of the first reported cases of human infection of Canadian origin.

The CCR5 Delta32, CCR2 64I, SDF1 3'A, and CCR5 promoter 59029 polymorphisms have been suggested to influence HIV-1 disease progression. Furthermore, the CCR5 Delta32 and the CCR2 64I polymorphisms have been associated with various other diseases. The purpose of the present study was to develop a multiplex assay for the simultaneous determination of these four polymorphisms. Results obtained with the multiplex assay were compared to results obtained by conventional RFLP-PCR and no differences were observed. The multiplex assay offers a quick tool for the determination of the CCR5 Delta32, CCR2 64I, SDF1 3'A, and CCR5 promoter 59029 A/G polymorphisms.

Within the last three years, major progress in the understanding of acquired immune deficiency syndrome pathogenesis has been achieved. The discovery that human immunodeficiency virus (HIV), in addition to the CD4 receptor, requires the presence of a coreceptor in order to infect cells has led to a series of breakthroughs in HIV research and knowledge. These include an increased understanding of viral entry, a connection of viral phenotype to specific coreceptor use, and an unequivocal linkage of a single human gene to host susceptibility. All in all these achievements provide a number of promising new strategies for combating HIV.