Anne-Mette Lebech

Fever of unknown origin: prospective comparison of diagnostic value of 18F-FDG PET and 111In-granulocyte scintigraphy

The diagnostic work-up in patients with fever of unknown origin (FUO) is often challenging and frequently includes nuclear medicine procedures. Whereas a role for leucocyte or granulocyte scintigraphy in FUO is generally accepted, a possible role of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in these patients remains to be established. To study this, we compared prospectively, on a head-to-head basis, the diagnostic value of FDG-PET and indium-111 granulocyte scintigraphy in patients with FUO. Nineteen patients with FUO underwent both FDG-PET and 111In-granulocyte scintigraphy within 1 week. FDG-PET scans and granulocyte scintigrams were reviewed by different doctors who were blinded to the result of the other investigation. The diagnostic values of FDG-PET and granulocyte scintigraphy were evaluated with regard to identification of a focal infectious/inflammatory or malignant cause of FUO. The sensitivity of granulocyte scintigraphy and FDG-PET were 71% [95% confidence interval (CI): 37–85%] and 50% (CI: 16–84%), respectively. The specificity of granulocyte scintigraphy was 92% (71–100%), which was significantly higher than that of FDG-PET, at 46% (34–62%). Positive and negative predictive values for granulocyte scintigraphy were both 85%. Positive and negative predictive values for FDG-PET were 30% and 67%, respectively. 111In-granulocyte scintigraphy has a superior diagnostic performance compared to FDG-PET for detection of a localised infectious/inflammatory or neoplastic cause of FUO. The poorer performance of FDG-PET is in particular attributable to a high percentage of false positive scans, leading to low specificity.

Borrelia burgdorferi-specific intrathecal antibody production in neuroborreliosis: a follow-up study.

We used a capture ELISA with biotinylated Borrelia burgdorferi flagella as antigen to analyze the kinetics of intrathecal antibody production against B burgdorferi in 27 patients with neuroborreliosis. All patients had lymphocytic pleocytosis, 13/27 had intrathecal specific IgM production, and 26/27 had intrathecal IgG synthesis against B burgdorferi before therapy. All patients improved after antibiotic treatment. At follow-up, 11 months to 8 years later (median, 1 frac12;years), 20 patients had had a complete clinical recovery, and seven suffered from sequelae. One patient without sequelae had persistent specific intrathecal IgM synthesis. Ten of 20 patients without sequelae and five of seven patients with sequelae had persistent intrathecal IgG production against B burgdorferi. None of the 16 patients with persistent specific intrathecal antibody synthesis had pleocytosis at follow-up. Therefore, intrathecal immunoglobulin production against B burgdorferi, especially IgG, may persist for years after treatment of neuroborreliosis without clinical signs of active disease.

Taxonomic classification of 29 Borrelia burgdorferi strains isolated from patients with Lyme borreliosis: a comparison of five different phenotypic and genotypic typing schemes

Twenty-nine European and North American Borrelia burgdorferi strains isolated from patients with Lyme borreliosis, were investigated by restriction fragment length polymorphism (RFLP) of two phylogenetically highly conserved chromosomal genes encoding flagellin (fla) and the p60 common antigen (CA), as well as of the plasmid-borne outer surface protein A (ospA) gene. RFLP of the ospA, fla and CA gene revealed five, two and four distinct subspecies-specific patterns, respectively. RFLP classification of the B. burgdorferi strains was compared with four different classification schemes proposed by others: (i) molecular mass profile of OspA and OspB (Adam et al. [1]); (ii) OspA serotyping (Wilske et al. [34]); (iii) genomic fingerprinting on the central region of the B. burgdorferi fla gene (Picken [24]) and (iv) 16S rRNA signature nucleotide analysis (Marconi and Garon [19]). Results obtained with the different methods correlated highly. All strains classified as B. burgdorferi sensu stricto and B. afzelii could be unequivocally identified as one distinct group by all five typing methods. B. garinii isolates, however, were more heterogeneous and according to RFLP of the CA and ospA gene fell into either two or three subgroups. The agreement of the different approaches supports the recent concept that B. burgdorferi sensu lato strains should be delineated to three genomic groups and that B. burgdorferi sensu lato is clonal. All 12 US strains were B. burgdorferi sensu stricto, whereas the 17 European isolates belonged to any of three genospecies. Among European B. burgdorferi isolates there was an association between B. burgdorferi genospecies and the clinical manifestation of Lyme borreliosis. B. afzelii strains were found to predominate in 11 skin isolates (75%), whereas all 6 cerebrospinal fluid isolates from patients with neuroborreliosis were B. garinii. These findings support the concept of a straindependent organotropism of B. burgdorferi.

Hepatitis C virus infection and risk of coronary artery disease: a systematic review of the literature

Several chronic infections have been associated with cardiovascular diseases, including Chlamydia pneumoniae, human immunodeficiency virus and viral hepatitis. This review evaluates the literature on the association between chronic hepatitis C virus (HCV) infection and the risk of coronary artery disease (CAD).

Changes in lung function of HIV-infected patients: a 4·5-year follow-up study

To investigate the development of lung function in HIV‐infected patients.

Autonomic dysfunction in HIV patients on antiretroviral therapy: studies of heart rate variability

Background:  The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Introduction of highly active antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis and decreased morbidity. At present it is not known whether introduction of ART also has decreased autonomic dysfunction.

Immunoserologic Evidence of Human Granulocytic Ehrlichiosis in Danish Patients with Lyme Neuroborreliosis

Human Granulocytic Ehrlichiosis (HGE) is a recently described human illness in the US which manifests as fever, myalgia and headache combined with pancytopenia and elevated concentrations of hepatic transaminases. Genetic analyses indicate that the agent of HGE appears to be an Ehrlichia species that is closely related to E. equi and E. phagocytophila. Ixodes dammini and I. scapularis were identified as potential vectors of HGE. Ixodes ticks are also the vector of Borrelia burgdorferi, the agent of Lyme borreliosis. The presence of antibodies against Ehrlichia in 132 sera from Danish patients with definite Lyme neuroborreliosis were examined in order to provide immunoserologic evidence of this infection in Denmark. Patients with Lyme neuroborreliosis were chosen as a test cohort, as these patients had been infested by a tick sufficient for transmission of B. burgdorferi. All had cerebrospinal fluid lymphocytic pleocytosis. As controls, serum samples from 50 healthy Danish blood donors were included. Of the 132 patients with Lyme neuroborreliosis, 5 (3.8%) reacted with the E. equi antigen substrate at titres 1:128. None of the blood donors were found seropositive for E. equi. At least 2 of the patients found seropositive for HGE constituted probable cases of HGE with E. equi antibody titres of at least 80 combined with fever, headache and myalgias. However, in no cases were we able to detect the presence of the HGE agent in the serum by PCR. We conclude that human exposure to granulocytic Ehrlichiae species may also occur in Europe, although further studies will be necessary to document active infection with these potential pathogens.

Carotid intima-media thickness in HIV patients treated with antiretroviral therapy.

Introduction:  Increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) may be due to HIV infection, direct effect of ART or dyslipidaemia induced by ART. Our aim was to study the relative importance of HIV, ART and dyslipidaemia on atherosclerosis, assessed by the comparison of carotid artery intima–media thickness (IMT) in non‐smoking HIV patients with high or low serum cholesterol levels as well as in healthy volunteers.

Long-term serological follow-up of patients treated for chronic cutaneous borreliosis or culture-positive erythema migrans

The kinetics of antibodies to Borrelia burgdorferi following successful treatment of early and late cutaneous borreliosis were analysed in consecutive serum samples by an enzyme-linked immunosorbent assay (ELISA) technique. Twenty-three patients with culture positive erythema migrans were followed for 23+/-14 months: 41% stayed seronegative, 35% showed an isolated immunoglobulin M (IgM) response, 8% an isolated IgG response and 16% a combined IgM and IgG responses. In general, antibody levels peaked within the first 3 months of symptom onset, whereafter a gradual decline was observed within 1 year. Twenty-two patients with chronic cutaneous borreliosis were followed for 23+/-11 months and all patients stayed IgG positive. Nearly three-quarters showed a clear decline in IgG levels over the years, while the rest did not. After 9+/-1 years 88% of 16 patients examined were still IgG positive. In conclusion, treatment of erythema migrans should be initiated on clinical appearance as a substantial number of patients stayed seronegative. Treatment success may in part be monitored serologically for both seropositive erythema migrans and chronic cutaneous borreliosis as most patients show declining titres after successful treatment. However, continuously high titres do not necessarily indicate treatment failure.

Silent Ischemic Heart Disease and Pericardial Fat Volume in HIV-Infected Patients: A Case-Control Myocardial Perfusion Scintigraphy Study

Objectives to determine the prevalence of asymptomatic ischemic heart disease (IHD) in HIV patients by myocardial perfusion scintigraphy (MPS) and to determine the value of coronary artery calcium score (CACS), carotid intima-media thickness (cIMT) and pericardial fat volume as screening tools for detection of IHD in subjects with HIV. Background Patients with HIV seem prone to early development of IHD. Methods 105 consecutive HIV patients (mean age 47.4 years; mean duration of HIV 12.3 years; mean CD4+ cell count 636×106/L; all receiving antiretroviral therapy) and 105 controls matched for age, gender and smoking status, without history of IHD were recruited. MPS, CACS, cIMT, pericardial fat volume, and cardiovascular risk scores were measured. Results HIV patients demonstrated higher prevalence of perfusion defects than controls (18% vs. 0%; p<0.001) despite similar risk scores. Of HIV patients with perfusion defects, 42% had a CACS = 0. CACS and cIMT were similar in HIV patients and controls. HIV patients on average had 35% increased pericardial fat volume and increased concentration of biomarkers of atherosclerosis in the blood. HIV patients with myocardial perfusion defects had increased pericardial fat volume compared with HIV patients without perfusion defects (314±43 vs. 189±12 mL; p<0.001). Conclusions HIV patients had an increased prevalence of silent IHD compared to controls as demonstrated by MPS. The finding was strongly associated with pericardial fat volume, whereas cardiovascular risk scores, cIMT and CACS seem less useful as screening tools for detection of myocardial perfusion defects in HIV patients.