Gitte Kronborg

Diagnostic value of soluble CD163 serum levels in patients suspected of meningitis: comparison with CRP and procalcitonin.

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<0.02 and p<0.06) compared to that of sCD163 (AUC =0.72). For the diagnosis of systemic bacterial infection, the AUC of sCD163 (0.83) did not differ significantly from those of CRP or PCT. All markers had AUCs <0.75 for differentiating between purulent meningitis and other conditions. In conclusion, CRP and PCT had high diagnostic value and were superior as markers of bacterial infection compared to sCD163. However, sCD163 may be helpful in rapid identification of patients with systemic bacterial infection. If used as an adjunct to lumbar puncture, PCT and CRP had very high diagnostic accuracy for distinguishing between bacterial and viral infection in patients with spinal fluid pleocytosis. However, none of the markers was useful as an independent tool for the clinical diagnosis of patients with purulent meningitis.

Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV‐1‐infected individuals receiving combination antiretroviral therapy

To investigate, using a longitudinal design, whether biomarkers of cardiovascular risk change after a switch to an abacavir (ABC)‐containing regimen in HIV‐1‐infected individuals already receiving combination antiretroviral therapy (ART).

Plasma Soluble CD163 Level Independently Predicts All-Cause Mortality in HIV-1-Infected Individuals

BACKGROUNDnCD163, 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).nnnMETHODSnPlasma 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.nnnRESULTSnAt baseline, 86% were receiving antiretroviral treatment, 73% had plasma a HIV RNA level of <50 copies/mL, and the median CD4(+) T-cell count was 503 cells/µL. During 10.5 years of follow-up, 167 (17.9%) died. Plasma sCD163 levels were higher in nonsurvivors than in survivors (4.92 mg/L [interquartile range {IQR}, 3.29-8.65 mg/L] vs 3.16 mg/L [IQR, 2.16-4.64 mg/L]; P = .0001). The cumulative incidence of death increased with increasing plasma sCD163 levels, corresponding to a 6% or 35% increased risk of death for each milligram per liter or quartile increase, respectively, in baseline plasma sCD163 level (adjusted HR, 1.06 [95% CI, 1.03-1.09] and 1.35 [95% CI, 1.13-1.63], respectively).nnnCONCLUSIONSnPlasma 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.

Incidence and Risk Factors for Invasive Pneumococcal Disease in HIV-Infected and Non-HIV-Infected Individuals Before and After the Introduction of Combination Antiretroviral Therapy: Persistent High Risk Among HIV-Infected Injecting Drug Users

BACKGROUNDnInvasive pneumococcal disease (IPD) is an important cause of morbidity among individuals infected with human immunodeficiency virus (HIV). We described incidence and risk factors for IPD in HIV-infected and uninfected individuals.nnnMETHODSnNationwide population-based cohort study of HIV-infected adults treated at all Danish HIV treatment centers during 1995-2012. Nineteen population-matched controls per HIV-infected individual were retrieved. The risk of IPD was assessed using Poisson regression.nnnRESULTSnThe incidence of IPD was 304.7 cases per 100 000 person-years of follow-up (PYFU) in HIV-infected and 12.8 per 100 000 PYFU in HIV-uninfected individuals. After adjusting for confounders, HIV infection (relative risk [RR], 24.4 [95% confidence interval [CI], 23.7-25.1]), male sex (RR, 1.20 [95% CI, 1.16-1.24]), increasing age (per year) (RR, 1.03 [95% CI, 1.03-1.04]), and calendar period (pre-cART RR, 2.80 [95% CI, 2.70-2.91] compared with late cART) were significantly associated with an increased risk of IPD. Among HIV-infected individuals, male sex (RR, 1.57 [95% CI, 1.49-1.66]), smoking (RR, 1.34 [95% CI, 1.26-1.42]), and injecting drug use (RR, 2.51 [95% CI, 2.26-2.67]) were associated with an increased risk of IPD. Detectable viral loads (RR, 1.88 [95% CI, 1.79-1.98]) and a relative fall in CD4 T-cell counts were also associated with an increased risk (≥500 to 350-500 CD4 T cells/µL: RR, 1.29 [95% CI, 1.21-1.37] and <100 cells/µL: RR, 7.4 [95% CI, 6.87-8.02]). The risk of IPD declined over time, although this was not the case for IDUs where the risk remained unchanged.nnnCONCLUSIONSnThe incidence of IPD in HIV-infected individuals remained significantly higher than the incidence observed in non-HIV-infected subjects, despite the widespread use of cART. IDUs have a persistently high risk of IPD. Injecting drug use, smoking, and the receipt of cART are suitable targets for preventive measures in the future.

Increased concentrations of the soluble mannose receptor in serum from patients with pneumococcal bacteraemia, and prediction of survival

Abstract Background: The soluble mannose receptor (sMR) is a new serum marker of macrophage activation. The aim of the present study was to investigate sMR as a prognostic marker in patients with invasive pneumococcal disease (IPD), and compare it to other inflammatory biomarkers. Methods: Samples from 128 patients with IPD were collected at the time of first positive blood culture and analysed using an in-house sMR assay. Clinical data were retrieved from patient files. The main outcome investigated was in-hospital mortality. Results: The median sMR concentration in the entire group of patients was 0.77 mg/L. There was a significant difference in sMR concentration between patients below (n = 92, sMR = 0.82 mg/L) or above (n = 36, sMR = 0.73 mg/L) the age of 75 (p < 0.001). In the entire group there was a significant difference in sMR concentrations between survivors (n = 107, sMR = 0.72 mg/L) and non-survivors (n = 21, sMR = 1.38 mg/L), but for patients 75 years or older this difference was not statistically significant. For prediction of survival sMR seemed most promising (area under the receiver operating characteristic curve (AUC) = 0.79) compared with sCD163 (AUC = 0.70) and CRP (AUC = 0.73). In patients 75 years or older the AUC was lower for all three markers (sMR = 0.56, sCD163 = 0.38, CRP = 0.66). Conclusions: The results of this study designate sMR as a potential new biomarker in infectious disease. Additionally, it emphasizes the importance of research into macrophage malfunction in elderly patients.

Death from the Nile crosses the Atlantic: the West Nile Fever story.

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.

Prediction of liver disease, AIDS and mortality based on discordant absolute and relative peripheral CD4 T lymphocytes in HIV/HCV co-infected individuals

Hepatitis C virus (HCV)-induced liver fibrosis and splenomegaly may lead to discordance between absolute numbers and percentages of lymphocytes and subpopulations because of sequestration. We investigated lymphocyte discordance in HIV/HCV-coinfected individuals and its relationship to progression to liver disease, AIDS, and all-cause mortality. This is an observational retrospective cohort study. Adjusted hazard ratios (aHRs) with 95% confidence intervals (95% CIs) associated with liver disease, AIDS, or mortality were computed by time-updated Cox proportional hazards regression. Of 380 HIV/HCV-coinfected adult individuals followed for a median of 8.2 years, 360 individuals had a median of 11 discordant measurements corresponding to 5,080 of 9,091 paired samples (56%). Discordance alone was not associated with any of the outcomes. By multivariable analysis, a doubling of absolute or percentage CD4 cells was associated with comparable lower risks of mortality (aHR: 0.60, 95% CI: 0.53-0.67, pu2009<u2009.0001 and aHR: 0.67, 95% CI: 0.56-0.79, pu2009<u2009.0001, respectively). Higher CD4/CD8 ratio was associated with a lower mortality risk (aHR: 0.39, 95% CI: 0.22-0.71 per doubling, pu2009=u2009.002). Only absolute CD4 cell measurements predicted AIDS. Development of liver disease was not predicted by total lymphocyte count or subpopulations. Despite a high prevalence of lymphocyte-subpopulation discordance with HIV/HCV coinfection, absolute CD4 cell count predicted mortality and AIDS, whereas CD4 percentage only predicted mortality. Neither CD4 T lymphocyte count nor CD4 percentage was associated with liver disease in this cohort. These findings may be necessary and useful in countries where antiretroviral treatment is not initiated for all HIV-infected individuals.