Publications by authors named "Åse Bengård Andersen"

39 Publications

Brain Abscesses in a Patient with Disseminated Non-Small Cellular Lung Cancer: MRI Findings.

Diagnostics (Basel) 2021 Jun 18;11(6). Epub 2021 Jun 18.

Heart Centre, Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.

Brain abscesses caused by (LM) are very rare and carry a high mortality risk. We present a patient with disseminated non-small cellular lung cancer (NSCLC) and multiple unusual LM brain abscesses. These abscesses have multiple elongated peripherally enhancing lesions in a characteristic formation that is "worm or tramtrack-like" following the white matter fiber tracts.
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http://dx.doi.org/10.3390/diagnostics11061115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235038PMC
June 2021

Classification of patients referred under suspicion of tick-borne diseases, Copenhagen, Denmark.

Ticks Tick Borne Dis 2021 01 9;12(1):101591. Epub 2020 Oct 9.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

To provide better care for patients suspected of having a tick-transmitted infection, the Clinic for Tick-borne Diseases at Rigshospitalet, Copenhagen, Denmark was established. The aim of this prospective cohort study was to evaluate diagnostic outcome and to characterize demographics and clinical presentations of patients referred between the 1st of September 2017 to 31st of August 2019. A diagnosis of Lyme borreliosis was based on medical history, symptoms, serology and cerebrospinal fluid analysis. The patients were classified as definite Lyme borreliosis, possible Lyme borreliosis or post-treatment Lyme disease syndrome. Antibiotic treatment of Lyme borreliosis manifestations was initiated in accordance with the national guidelines. Patients not fulfilling the criteria of Lyme borreliosis were further investigated and discussed with an interdisciplinary team consisting of specialists from relevant specialties, according to individual clinical presentation and symptoms. Clinical information and demographics were registered and managed in a database. A total of 215 patients were included in the study period. Median age was 51 years (range 17-83 years), and 56 % were female. Definite Lyme borreliosis was diagnosed in 45 patients, of which 20 patients had erythema migrans, 14 patients had definite Lyme neuroborreliosis, six had acrodermatitis chronica atrophicans, four had multiple erythema migrans and one had Lyme carditis. Furthermore, 12 patients were classified as possible Lyme borreliosis and 12 patients as post-treatment Lyme disease syndrome. A total of 146 patients (68 %) did not fulfil the diagnostic criteria of Lyme borreliosis. Half of these patients (73 patients, 34 %) were diagnosed with an alternative diagnosis including inflammatory diseases, cancer diseases and two patients with a tick-associated disease other than Lyme borreliosis. A total of 73 patients (34 %) were discharged without sign of somatic disease. Lyme borreliosis patients had a shorter duration of symptoms prior to the first hospital encounter compared to patients discharged without a specific diagnosis (p<0.001). When comparing symptoms at presentation, patients discharged without a specific diagnosis suffered more often from general fatigue and cognitive dysfunction. In conclusion, 66 % of all referred patients were given a specific diagnosis after ended outpatient course. A total of 32 % was diagnosed with either definite Lyme borreliosis, possible Lyme borreliosis or post-treatment Lyme disease syndrome; 34 % was diagnosed with a non-tick-associated diagnosis. Our findings underscore the complexity in diagnosing Lyme borreliosis and the importance of ruling out other diseases through careful examination.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101591DOI Listing
January 2021

[First Danish case of Mycobacteriumchimaerainfection from cardiac surgery with contaminated heater-cooler unit].

Ugeskr Laeger 2020 06;182(26)

Infection with Mycobacterium chimaera has globally been linked to cardiac surgery using cardiopulmonary bypass devices with contaminated heater-cooler units (HCU). This is a case report of M. chimaera infection linked to HCU in Denmark in which we show, how difficult the diagnosis can be. A 67-year-old man had an aortic graft and valvular replacement using HCU. Post-operatively he developed progressing symptoms of intermittent fever, malaise and endocarditis with septic embolic events, and despite extensive diagnostic work-up, he remained undiagnosed for 16 months following surgery.
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June 2020

Lyme neuroborreliosis in adults: A nationwide prospective cohort study.

Ticks Tick Borne Dis 2020 07 24;11(4):101411. Epub 2020 Feb 24.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address:

The goal of this paper is to characterize the clinical presentation, serological results, current antibiotic treatment practice, including compliance with current European guidelines, and outcome in adults with Lyme neuroborreliosis (LNB) diagnosed at departments of infectious diseases in Denmark. Using a nationwide prospective cohort of patients with central nervous system infections, we identified all adults (≥ 18 years of age) treated for LNB at departments of infectious diseases in Denmark from 2015 through 2017. The database contains information on baseline demographics, history of tick bite, erythema migrans, clinical presentation, laboratory results of blood samples, and cerebrospinal (CSF) biochemistry (e.g. specific Borrelia burgdorferi sensu lato (s.l.) antibodies in serum, B. burgdorferi s.l. intrathecal antibody index) as well as antibiotic therapy. Outcome was assessed by the Glasgow Outcome Scale (GOS) and the presence of residual symptoms at follow-up one month after discharge. We included 194 LNB patients with a median age of 59 years (range 18-85 years, interquartile range [IQR] 47-69 years). The female-to-male ratio was 0.8. A total of 177 of 191 (93 %) of patients had early (second stage) LNB. A history of tick bite or erythema migrans was registered in 75 (39 %) and 49 (25 %) patients, respectively. The median duration of neurological symptoms before first hospital contact was 21 days (range 0-600 days, IQR 10-42 days). Predominant symptoms consisted of radicular pain in 135 of 194 (70 %), cranial nerve paresis in 88 of 194 (45 %), headache in 71 of 185 (38 %), and extremity paresis in 33 of 194 (17 %) patients. Serum-B. burgdorferi s.l. IgM and/or IgG antibodies were detectable in 166 of 181 (92 %) patients at the time of first CSF investigation. Median duration of antibiotic treatment was 14 days (range 10-35 days, IQR 14-21 days) and 59 (39 %) of the patients received intravenous ceftriaxone and/or benzylpenicillin G throughout treatment. At the 1-month follow-up, GOS was unfavorable (< 5) in 54 of 193 (28 %) patients. An unfavorable GOS score was more often registered in patients with ≥ 45 days of symptom duration (20 of 45 (44 %) vs. 34 of 145 (23 %); P = 0.006). In conclusion, a European cohort of adult patients with LNB diagnosed between 2015-2017 presented with classic symptoms and CSF findings. However, a substantial diagnostic delay was still observed. In disagreement with current guidelines, a substantial part of LNB patients were treated with antibiotics longer than 14 days and/or intravenously as route of administration.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101411DOI Listing
July 2020

Infection and the role in cancer development.

APMIS 2020 02 18;128(2):71. Epub 2020 Mar 18.

Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

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http://dx.doi.org/10.1111/apm.13030DOI Listing
February 2020

Recurrent tuberculosis in patients infected with the predominant Mycobacterium tuberculosis outbreak strain in Denmark. New insights gained through whole genome sequencing.

Infect Genet Evol 2020 06 7;80:104169. Epub 2020 Jan 7.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; Research Unit for Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Denmark.

Objectives: Recurrent tuberculosis (TB) is defined by more than one TB episode per patient and is caused by reinfection with a new M. tuberculosis (Mtb) strain or relapse with the previous strain. In Denmark, a major TB outbreak caused by one specific Mtb genotype "DKC2" is ongoing. Of the 892 patients infected with DKC2 between 1992 and 2014, 32 had recurrent TB with 67 TB episodes in total.

Methods: The 32 cases were evaluated in terms of number of single-nucleotide polymorphism (SNP) differences and time between episodes derived from whole-genome sequencing data.

Results: For four TB cases, the subsequent episodes could be confirmed as relapse and for one case as reinfection. Eight cases with SNP differences <6, theoretically indicating relapse, could be classified as likely reinfections based on phylogenetic analysis in combination with geographical data. Subsequent TB episodes for the remaining 19 cases could not be classified as relapse or reinfection even though they all had a SNP difference of <6 SNPs.

Conclusions: In newer studies, investigating recurrent TB with the use of WGS, the number of SNPs has been used to distinguish between relapse and reinfection. The algorithm proposed for this is not valid in the Danish TB outbreak setting as our findings challenge the interpretation of few SNP differences as representing relapse. However, when including phylogenetic analysis and geographical data in the analysis, classification of 13 of the 32 cases were possible.
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http://dx.doi.org/10.1016/j.meegid.2020.104169DOI Listing
June 2020

[Testing for latent tuberculosis infection needs to be improved in Denmark].

Ugeskr Laeger 2019 Nov;181(48)

Tuberculosis (TB) remains a public health emergency worldwide. WHO recommends low-incidence countries to increase awareness of latent tuberculosis infection (LTBI) as part of a national preventive strategy. This review focuses on the burden of TB in Denmark, which might be reduced, if more focus was paid on diagnosing LTBI in relevant patients, and treatment to prevent future active TB cases was initiated. LTBI testing should be considered in persons at risk of TB disease, who will benefit from LTBI treatment, e.g. recently infected persons or persons having undergone organ transplantation or having comorbidity such as HIV, dialyses, and immunosuppression.
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November 2019

[Breast tuberculosis is a rare cause of breast abscess].

Ugeskr Laeger 2018 Sep;180(38)

Isolated secondary breast tuberculosis (TB) is an uncommon entity. This is a case report of a 27-year-old female who presented with a tumour in the breast. After four months with tedious examinations a positive polymerase chain reaction for TB was finally found, and the patient recovered after ten months of TB therapy and drainage of the abscess. One year later, a recurrence was seen after the patient had been breast feeding. Therapy was repeated, and more extensive surgery was performed with surgical excision of the abscess cavity, the fibrous tract to the pleura and resection of a pleural section. The patient achieved a full recovery afterwards.
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September 2018

A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations.

Sci Rep 2018 08 8;8(1):11869. Epub 2018 Aug 8.

Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark.

Denmark, a tuberculosis low burden country, still experiences significant active Mycobacterium tuberculosis (Mtb) transmission, especially with one specific genotype named Cluster 2/1112-15 (C2), the most prevalent lineage in Scandinavia. In addition to environmental factors, antibiotic resistance, and human genetics, there is increasing evidence that Mtb strain variation plays a role for the outcome of infection and disease. In this study, we explore the reasons for the success of the C2 genotype by analysing strain specific polymorphisms identified through whole genome sequencing of all C2 isolates identified in Denmark between 1992 and 2014 (n = 952), and the demographic distribution of C2. Of 234 non-synonymous (NS) monomorphic SNPs found in C2 in comparison with Mtb reference strain H37Rv, 23 were in genes previously reported to be involved in Mtb virulence. Of these 23 SNPs, three were specific for C2 including a NS mutation in a gene associated with hyper-virulence. We show that the genotype is readily transmitted to different ethnicities and is also found outside Denmark. Our data suggest that strain specific virulence factor variations are important for the success of the C2 genotype. These factors, likely in combination with poor TB control, seem to be the main drivers of C2 success.
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http://dx.doi.org/10.1038/s41598-018-30363-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082827PMC
August 2018

Cerebrospinal fluid pleocytosis level as a diagnostic predictor? A cross-sectional study.

BMC Clin Pathol 2017 24;17:15. Epub 2017 Aug 24.

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.

Background: Lumbar puncture with quantification of leukocytes and differential count of cellular subsets in the cerebrospinal fluid is a standard procedure in cases of suspected neuroinfectious conditions. However, a number of non-infectious causes may result in a low leukocyte number (0-1000 cells/ml). We wanted to assess the diagnostic diversity of unselected adult patients with pleocytosis in the cerebrospinal fluid.

Methods: The study is based on data from cerebrospinal fluid (CSF) analyses of all adult patients (15 years or older) admitted to a large university hospital in Denmark during a two-year period (2008-2009). Data from the local patient administrative system supplied with data from patient charts were combined with laboratory data.

Results: A total of 5390 cerebrospinal fluid samples from 3290 patients were included. Pleocytosis >5 leucocytes/μl was found in samples from 262 patients of which 106 (40.5%) were caused by infection of the central nervous system (CNS), 20 (7.6%) by infection outside CNS, 79 (30.2%) due to non-infectious neurological diseases, 23 (8.8%) by malignancy, and 34 (13.0%) caused by other conditions. Significantly higher mean CSF leukocytes was found in patients suffering from CNS infection (mean 1135 cells/μl, -value <0.0001).

Conclusions: CNS infection, non-infectious neurological disease, malignancy, and infection outside CNS can cause pleocytosis of the cerebrospinal fluid. Leukocyte counts above 100/μl is mainly caused by CNS infection, whereas the number of differential diagnoses is higher if the CSF leukocyte counts is below 50/μl. These conditions are most commonly caused by non-infectious neurological diseases including seizures.
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http://dx.doi.org/10.1186/s12907-017-0053-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571639PMC
August 2017

Genomic Epidemiology of a Major Mycobacterium tuberculosis Outbreak: Retrospective Cohort Study in a Low-Incidence Setting Using Sparse Time-Series Sampling.

J Infect Dis 2017 08;216(3):366-374

International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen.

Since 1992, Denmark has documented the largest outbreak of tuberculosis in Scandinavia ascribed to a single genotype, termed C2/1112-15. As of spring 2017, the International Reference Laboratory of Mycobacteriology in Copenhagen has collected and identified isolates from more than a thousand cases belonging to this outbreak via routine mycobacterial interspersed repetitive units-variable number of tandem repeats typing. Here, we present a retrospective analysis of the C2/1112-15 dataset, based on whole-genome data from a sparse time series consisting of 5 randomly selected isolates from 23 years of sampling. Even if these data are derived from only 12% of the collected isolates, we have been able to extract important key information, such as mutation rate and conserved single-nucleotide polymorphisms to identify discrete transmission chains, as well as the possible historical origins of the outbreak.
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http://dx.doi.org/10.1093/infdis/jix298DOI Listing
August 2017

[The current global tuberculosis state].

Ugeskr Laeger 2017 May;179(20)

Despite an increase in the total number of tuberculosis (TB) patients globally, positive trends in reduction of prevalence and mortality are observed. However, high numbers of drug-resistant cases are threatening this trend. Multidrug-resistant and extensively resistant cases constitute an increasing challenge in many parts of the world also within the European region - especially in former Sovjet Republic nations. Point-of-care test systems potentially replacing microscopy and urine antigen detection systems are currently launched in many TB-high endemic countries improving TB detection rates. However, the effect on key indicators like mortality is still waiting to break through.
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May 2017

Substantial molecular evolution and mutation rates in prolonged latent Mycobacterium tuberculosis infection in humans.

Int J Med Microbiol 2016 Nov 28;306(7):580-585. Epub 2016 May 28.

Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark. Electronic address:

The genome of Mycobacterium tuberculosis (Mtb) of latently infected individuals may hold the key to understanding the processes that lead to reactivation and progression to clinical disease. We report here analysis of pairs of Mtb isolates from putative prolonged latent TB cases. We identified two confirmed cases, and used whole genome sequencing to investigate the mutational processes that occur over decades in latent Mtb. We found an estimated mutation rate between 0.2 and 0.3 over 33 years, suggesting that latent Mtb accumulates mutations at rates similar to observations from cases of active disease.
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http://dx.doi.org/10.1016/j.ijmm.2016.05.017DOI Listing
November 2016

[Seemingly identical – but yet so different].

Ugeskr Laeger 2016 07;178(28)

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July 2016

Human pegivirus detected in a patient with severe encephalitis using a metagenomic pan-virus array.

J Clin Virol 2016 Apr 29;77:5-8. Epub 2016 Jan 29.

Virus Research and Development, Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark; Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Denmark.

We have used a metagenomic microarray to detect genomic RNA from human pegivirus in serum and cerebrospinal fluid from a patient suffering from severe encephalitis. No other pathogen was detected. HPgV in cerebrospinal fluid during encephalitis has never been reported before and its prevalence in cerebrospinal fluid needs further investigation.
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http://dx.doi.org/10.1016/j.jcv.2016.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106502PMC
April 2016

[Indicator-based HIV testing].

Ugeskr Laeger 2015 Sep;177(37):V03150266

The mortality of HIV-infected patients in Denmark approaches that of the background population. Still, half of the HIV-infected patients are diagnosed late, resulting in poorer response to therapy, larger cost and greater transmission rate. A pan-European initiative, "HIV in Europe" has published a guideline on indicator-based HIV testing in order to improve early HIV diagnosis. The Danish Society of Infectious Diseases wishes to highlight the importance of indicator-based HIV testing, in order to improve the possibility of early diagnosis and therapy of HIV-infection.
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September 2015

Height as a prognostic marker for survival during antituberculous therapy.

Infect Dis (Lond) 2015 Jul 26;47(7):515-6. Epub 2015 Feb 26.

From the Department of Nutrition, Exercise and Sports, University of Copenhagen , Frederiksberg , Denmark.

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http://dx.doi.org/10.3109/00365548.2015.1006676DOI Listing
July 2015

[Follow-up after non-typhoidal Salmonella bacteraemia is important due to risk of endovascular infection].

Ugeskr Laeger 2015 Jan;177(2A):90-1

Klinisk Mikrobiologisk Afdeling, Odense Universitetshospital, J.B. Winsløws Vej 21, 2., 5000 Odense C.

An 81-year-old male with atherosclerosis had an episode of bacteraemia with Salmonella dublin six weeks prior to admission to hospital. He presented with confusion, fever and abdominal pain. Blood cultures revealed S. dublin, and an 18F-fluor deoxyglucose positron emission tomography/computed tomography showed aortitis. Ceftriaxon and ciprofloxacin was administered. The patient was not a candidate for surgery and two weeks later he died from multiple organ failure. Follow-up visits with blood cultures after the first bacteraemia episode might have allowed for earlier diagnosis of the relapse.
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January 2015

[Progressive multifocal leukoencephalopathy in a patient with multiple myeloma].

Ugeskr Laeger 2014 Dec;176(49)

Dagmarsgade 10, 3. th., 2200 København N.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease in the central nervous system. It is caused by reactivation of John Cunningham-virus and has a grave prognosis. PML occurs most frequently in HIV-patients, but can also be seen in patients with iatrogenic immunodeficiency. Here, we present a patient with multiple myeloma and cardiac amyloidosis who developed PML after receiving treatment with several chemotherapeutics. This case report underlines the importance of bearing PML in mind when immunocompromised patients develop diffuse neurological symptoms.
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December 2014

Long-term mortality in patients with pulmonary and extrapulmonary tuberculosis: a Danish nationwide cohort study.

Clin Epidemiol 2014 13;6:405-21. Epub 2014 Nov 13.

Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Background: Long-term mortality and causes of death in patients with pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) are poorly documented. In this study, long-term mortality and causes of death in PTB and EPTB patients were compared with the background population and it was investigated whether mortality was associated with family-related risk factors.

Methods: A NATIONWIDE COHORT STUDY WAS CONDUCTED INCLUDING: all adult Danes notified with PTB or EPTB from 1977 to 2008 and alive 1 year after diagnosis; a randomly selected comparison cohort matched on birth date and sex; adult siblings of PTB patients; and population controls. Data were extracted from national registries. All-cause and cause-specific mortality rate ratios were calculated for patients and siblings and compared with their respective control cohorts. A total of 8,291 patients (6,402 PTB and 1,889 EPTB), 24,873 population controls, 1,990 siblings of PTB patients and 11,679 siblings of PTB population controls were included.

Results: Overall, the mortality rate ratio was 1.86 (95% confidence interval [CI] 1.77-1.96) for PTB patients and 1.24 (95% CI 1.12-1.37) for EPTB patients. Both patient cohorts had significantly increased risk of death due to infectious diseases and diabetes. Further, the PTB patients had increased mortality due to cancers (mainly respiratory and gastrointestinal tract), liver and respiratory system diseases, and alcohol and drug abuse. The PTB patients had increased mortality compared with their siblings (mortality rate ratio 3.55; 95% CI 2.57-4.91) as did the siblings of the PTB patients compared with the siblings of population controls (mortality rate ratio 2.16; 95% CI 1.62-2.87).

Conclusion: We conclude that adult PTB patients have an almost two-fold increased long-term mortality whereas EPTB patients have a slightly increased long-term mortality compared with the background population. The increased long-term mortality in PTB patients stems from diseases associated with alcohol, tobacco, and drug abuse as well as immune suppression, and family-related factors.
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http://dx.doi.org/10.2147/CLEP.S65331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235508PMC
November 2014

Evaluation of an immunoassay for determination of plasma efavirenz concentrations in resource-limited settings.

J Int AIDS Soc 2014 5;17:18979. Epub 2014 Jun 5.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.

Introduction: Therapeutic drug monitoring (TDM) may improve antiretroviral efficacy through adjustment of individual drug administration. This could result in reduced toxicity, prevent drug resistance, and aid management of drug-drug interactions. However, most measurement methods are too costly to be implemented in resource-limited settings. This study evaluated a commercially available immunoassay for measurement of plasma efavirenz.

Methods: The immunoassay-based method was applied to measure efavirenz using a readily available Humastar 80 chemistry analyzer. We compared plasma efavirenz concentrations measured by the immunoassay with liquid chromatography tandem mass spectrometry (LC-MS/MS) (reference method) in 315 plasma samples collected from HIV patients on treatment. Concentrations were categorized as suboptimal<1 µg/ml, normal 1-4 µg/ml or high>4 µg/ml. Agreement between results of the methods was assessed via Bland-Altman plot and κ statistic values.

Results: The median Interquartile range (IQR) efavirenz concentration was 2.8 (1.9; 4.5) µg/ml measured by the LC-MS/MS method and 2.5 (1.8; 3.9) µg/ml by the immunoassay and the results were well correlated (ρ=0.94). The limits of agreement assessed by Bland-Altman plots were -2.54; 1.70 µg/ml. Although immunoassay underestimated high concentrations, it had good agreement for classification into low, normal or high concentrations (K=0.74).

Conclusions: The immunoassay is a feasible alternative to determine efavirenz in areas with limited resources. The assay provides a reasonable approximation of efavirenz concentration in the majority of samples with a tendency to underestimate high concentrations. Agreement between tests evaluated in this study was clinically satisfactory for identification of low, normal and high efavirenz concentrations.
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http://dx.doi.org/10.7448/IAS.17.1.18979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049128PMC
September 2014

[Infections in the elderly].

Ugeskr Laeger 2013 Nov;175(47):2849

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November 2013

Diabetes is associated with lower tuberculosis antigen-specific interferon gamma release in Tanzanian tuberculosis patients and non-tuberculosis controls.

Scand J Infect Dis 2014 May 12;46(5):384-91. Epub 2014 Mar 12.

Department of Nutrition, Exercise and Sports, University of Copenhagen , Denmark.

Background: Diabetes is increasingly common in TB endemic regions and plays a role as a possible risk factor for increased progression from latent TB infection (LTBI) to active TB disease. Although the pathophysiological mechanisms are not fully understood, the immune system is weakened in diabetes patients and therefore the validity of interferon gamma release assays (IGRA) may be compromised. The aim of the present study was to assess the association between diabetes and Mycobacterium tuberculosis (Mtb) antigen-specific interferon gamma (IFN-γ) release in a TB endemic area among culture-confirmed TB patients and non-TB controls.

Methods: Culture-confirmed pulmonary TB patients (n = 187) and healthy non-TB neighbourhood controls (n = 190) from Mwanza, Tanzania were tested for the presence of circulating T cells recognizing Mtb antigens using an IGRA. The diabetes status of all participants was assessed using a standard oral glucose tolerance test. The impact of diabetes on the performance of the IGRA was estimated using robust linear and logistic regression.

Results: Compared to normal glucose tolerance, diabetes was associated with reduced levels of Mtb-specific IFN-γ. Increasing levels of fasting blood glucose (B - 0.3, 95% confidence interval - 0.6 to - 0.03, p = 0.033) was negatively associated with IFN-γ. Although TB patients had higher specific and lower unspecific mitogen IFN-γ responses compared to non-TB controls, the association between diabetes and IFN-γ did not depend on TB status.

Conclusion: Diabetes is associated with lower levels of Mtb antigen-specific IFN-γ, and the validity of IFN- γ tests for LTBI may be questionable in individuals with diabetes.
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http://dx.doi.org/10.3109/00365548.2014.885657DOI Listing
May 2014

[Continued problems with tuberculosis among Danes and Greenlanders in Denmark and the need for reinforced control--a systematic review].

Ugeskr Laeger 2012 Oct;174(44):2696-701

National Afdeling for TB og Mykobakterier, Statens Serum Institut, Artillerivej 5, Copenhagen.

Active transmission of Mycobacterium tuberculosis (Mt) continues at surprisingly high rates in Denmark. The transmission is particularly observed in specific high risk segments of the population with social problems such as homelessness, alcohol, and/or drug abuse. The patients are infected with the "Danish Cluster 2" Mt outbreak strain, and the transmission is attributed to delayed diagnosis. This situation demands increased focus on early tuberculosis diagnosis, control of transmission, and improved actions calls for prioritising the prevention and control of tuberculosis politically and economically.
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October 2012

The role of diabetes co-morbidity for tuberculosis treatment outcomes: a prospective cohort study from Mwanza, Tanzania.

BMC Infect Dis 2012 Jul 27;12:165. Epub 2012 Jul 27.

Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark.

Background: Due to the association between diabetes and pulmonary tuberculosis (TB), diabetes may threaten the control of TB. In a prospective cohort study nested in a nutrition trial, we investigated the role of diabetes on changes in anthropometry, grip strength, and clinical parameters over a five months follow-up period.

Methods: Among pulmonary TB patients with known diabetes status, we assessed anthropometry and clinical parameters (e.g. haemoglobin) at baseline and after two and five months of TB treatment. A linear mixed-effects model (repeated measurements) was used to investigate the role of diabetes during recovery.

Results: Of 1205 TB patients, the mean (standard deviation) age was 36.6 (13.0) years, 40.9% were females, 48.9% were HIV co-infected, and 16.3% had diabetes. TB patients with diabetes co-morbidity experienced a lower weight gain at two (1.3 kg, CI95% 0.5; 2.0, p = 0.001) and five months (1.0 kg, CI95% 0.3; 1.7, p = 0.007). Similarly, the increase in the level of haemoglobin was lower among TB patients with diabetes co-morbidity after two (Δ 0.6 g/dL, CI95% 0.3; 0.9 p < 0.001) and five months (Δ 0.5 g/dL, CI95% 0.2; 0.9 p = 0.004) of TB treatment, respectively.

Conclusion: TB patients initiating TB treatment with diabetes co-morbidity experience delayed recovery of body mass and haemoglobin, which are important for the functional recovery from disease.
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http://dx.doi.org/10.1186/1471-2334-12-165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462148PMC
July 2012

Cutaneous necrotic ulceration due to BCG re-vaccination.

Hum Vaccin Immunother 2012 Apr 28;8(4):423-4. Epub 2012 Feb 28.

Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.

The case report describes a severe local reaction with large cutaneous necrotic ulcer following bacillus Calmette-Guérin (BCG) re-vaccination. This is a very rare adverse event, and only a few reports have been described in the literature.
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http://dx.doi.org/10.4161/hv.19067DOI Listing
April 2012

Quantiferon test for tuberculosis screening in sarcoidosis patients.

Scand J Infect Dis 2011 Sep 27;43(9):728-35. Epub 2011 May 27.

Department of Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen.

Background: Tumour necrosis factor-alpha (TNF-α) inhibitors have been introduced in the treatment of refractory sarcoidosis. These biologics may reactivate latent tuberculosis infection (LTBI). Despite its known limitations, the tuberculin skin test (TST) is currently used for the diagnosis of LTBI in Danish sarcoidosis patients. We report the results of a screening using the interferon-gamma release assay (IGRA) QuantiFERON TB Gold (QFN) for the diagnosis of LTBI. We aimed to assess whether the QFN is reliable for diagnosing LTBI among sarcoidosis patients and if results are influenced by disease activity or immunosuppressive treatment.

Methods: A prospective study was performed from 2005 to 2007 among sarcoidosis patients who were candidates for TNF-α inhibitor treatment. Information on immunosuppressive treatment was obtained from the medical records. Disease activity was assessed by biochemistry, chest roentgenograms and pulmonary function tests. The predictive value of QFN results was evaluated by follow-up in the Danish National Tuberculosis Registry.

Results: A total of 44 sarcoidosis patients (22 men) with a median age of 39 y (range 25-59 y) were enrolled; 93% had a negative QFN test result and 7% had an indeterminate result. Forty-three percent had disease activity and 57% (n = 25) received immunosuppressive treatment. There was no significant difference in QFN interferon-γ response between subjects with or without disease activity (p > 0.4) and between treated vs non-treated patients (p > 0.5). At follow-up using the Danish tuberculosis registry, there was no occurrence of tuberculosis among study participants.

Conclusions: The predictive value of the QFN seems good among Danish sarcoidosis patients and the results appear to be unaffected by sarcoidosis disease activity and immunosuppressive treatment.
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http://dx.doi.org/10.3109/00365548.2011.582141DOI Listing
September 2011

[Treatment and diagnostics of tuberculosis: moving slowly forward].

Ugeskr Laeger 2011 Mar;173(12):897-9

Infektionsmedicinsk Afdeling Q, Odense Universitetshospital, 5000 Odense C, Denmark.

Development of new drugs for the treatment of drug sensitive and drug resistant tuberculosis is badly needed. Substantial progress has been made in the field and presently six new drug components are in clinical phase I and II trials. Drugs approved for other indications e.g. newer fluoroquinolones and oxazolidinones are also being assessed in human phase II and III trials. Efforts are made to develop easy-to-handle diagnostic tools that will allow early detection of potential MDR or XDR cases. The Xpert RIF/MTB is a prototype of such an invention. At long last the field is moving slowly forward.
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March 2011

Polyacrylamide gel treatment of antiretroviral therapy-induced facial lipoatrophy in HIV patients.

Aesthetic Plast Surg 2011 Oct 27;35(5):709-16. Epub 2011 Feb 27.

Clinic of Infectious Disease and Center of Clinical Research, Hvidovre Hospital, Hvidovre, Denmark.

Background: Today, highly active antiretroviral therapy is lifesaving for most HIV-infected patients, but the treatment can result in facial lipoatrophy, which changes the face so radically that patients may develop severe psychological and social problems. Since 2001 polyacrylamide gel (PAAG) has been used successfully in HIV patients abroad. This article describes the results of a Danish study.

Methods: Forty HIV patients recruited from two major referral hospitals in the capitol area of Copenhagen, Denmark, each received a series of PAAG gel injections (small deposits in several sessions) with a 14-day interval. Patient satisfaction, injector's evaluation, evaluation by an external specialist in plastic surgery, and long-term aesthetic effect and complications were registered with follow-up until 2 years.

Results: All patients were very satisfied or satisfied with the result. The injector found the result very satisfying in 33 cases and a slight irregularity in 7. The external specialist found improvement in all cases with a one-grade reduction of the lipoatrophy in 11 cases, a two-grade reduction in 20, and a three-grade reduction in 3 cases. No filler-associated complications were recorded.

Conclusion: This study has shown that PAAG can normalize contours in patients suffering from facial lipoatrophy within 3-6 sessions, with a mean amount of gel per session of 1.8 ml and a mean total amount of 8.8 ml. The results are in accordance with those of other large studies, confirming a high degree of biocompatibility and safety.
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http://dx.doi.org/10.1007/s00266-011-9671-6DOI Listing
October 2011
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