Publications by authors named "Christoph Hauser"

55 Publications

Socioeconomic Status and Parental Lifestyle Are Associated With Vascular Phenotype in Children.

Front Public Health 2021 26;9:610268. Epub 2021 Mar 26.

Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland.

Socioeconomic barriers and lifestyle conditions affect development of cardiovascular disease in adults, but little is known about the association of parental lifestyle and education with childhood health. We aimed to investigate the association of socioeconomic status (SES), migration background, parental physical activity (PA) and smoking status with micro-and macrovascular health in children. In 2016/2017, 833 school children (aged 7.2 ± 0.4 years) in Basel (Switzerland) were screened for retinal arteriolar-to-venular ratio (AVR), pulse wave velocity (PWV), SES, migration background and parental PA as well as smoking status. High parental PA levels were associated with a favorable higher AVR ( = 0.020) and lower PWV ( = 0.035), but not independent of parental smoking status. Children with parents who smoked had a higher PWV [4.39 (4.35-4.42) m/s] compared to children with non-smoking parents [4.32 (4.29-4.34) m/s, = 0.001]. Children of parents with a low household income had a higher PWV [4.36 (4.32-4.41) m/s] compared to children of parents with a high household income [4.30 (4.26-4.34) m/s, = 0.033]. Low parental educational level was associated with a lower AVR [0.86 (0.85-0.88)] compared to children with highly educated parents [AVR:0.88 (0.87-0.88), = 0.007; PWV: 4.33 (4.30-4.35) m/s, = 0.041]. Children with a European background showed a higher AVR [0.88 (0.87-0.88)] compared to non-European children [AVR: (0.86 (0.85-0.87), = 0.034]. Parental PA is associated with better macro- and microvascular childhood health. However, the positive association is lost when parental smoking is considered in the analysis. Socioeconomic factors seem to associate with subclinical vascular alterations in children. Primary prevention programs should focus on including parental lifestyle interventions and educational programs to reduce the burden of lifestyle-associated barriers in order to improve cardiovascular health during lifespan. ClinicalTrials.gov Exercise and Arterial Modulation in Youth, https://clinicaltrials.gov/ct2/show/NCT02853747, NCT02853747.
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http://dx.doi.org/10.3389/fpubh.2021.610268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032988PMC
March 2021

Association of blood pressure, obesity and physical activity with arterial stiffness in children: a systematic review and meta-analysis.

Pediatr Res 2021 Apr 6. Epub 2021 Apr 6.

Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland.

Central pulse wave velocity (cPWV) is a biomarker for cardiovascular (CV) risk and a predictor for CV events in adulthood. Alterations of arterial stiffness have also been associated with CV risk in childhood. The study aimed to systematically review and meta-analyze the association of blood pressure (BP), body mass index (BMI), and cardiorespiratory fitness (CRF) with cPWV in children. Literature search was through the databases PubMed, Web of Science, Embase and the Cochrane Register of Controlled Trials. Twenty-two articles were included in the systematic review and eight articles in the meta-analysis. Higher systolic and diastolic BP were associated with higher cPWV (pooled estimated effect size (ES) 0.02 (95% CI: 0.012-0.027; P < 0.001), and ES 0.02 (95% CI: 0.011-0.029; P < 0.001); respectively). Higher BMI correlated with higher cPWV (ES 0.025 (95% CI: 0.013-0.038; P < 0.001)). CRF was inversely associated with cPWV (ES -0.033 (95% CI: -0.055 to -0.011; P = 0.002)). In children, higher BP and BMI are already related to increased cPWV, and enhanced CRF may be a preventive strategy to counteract development of CV disease later in life. IMPACT: This meta-analysis suggests that elevated blood pressure and body mass index in childhood correlate with increased central pulse wave velocity. Children with higher cardiorespiratory fitness appear to have favorably lower arterial stiffening. Elevated blood pressure and altered arterial stiffness originate early in life and childhood risk stratification as well as timely initiation of exercise treatment may help counteract development of manifest cardiovascular disease later in life.
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http://dx.doi.org/10.1038/s41390-020-01278-5DOI Listing
April 2021

Alcohol consumption and neurocognitive deficits in people with well-treated HIV in Switzerland.

PLoS One 2021 2;16(3):e0246579. Epub 2021 Mar 2.

Infectious Diseases Service, Lausanne University Hospital, Lausanne, Switzerland.

Background: Hazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively.

Results: Most participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P <0.05) and continuous (mean z-score difference -0.2 to -0.4, P ≤0.01) outcomes. A significant U-shaped distribution of AUDIT-C score was also observed for motor skills and overall neurocognitive function.

Conclusions: In this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246579PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924787PMC
March 2021

The association between depressive symptoms and neurocognitive impairment in people with well-treated HIV in Switzerland.

Int J STD AIDS 2021 Feb 25:956462420987434. Epub 2021 Feb 25.

Infectious Diseases Service, 30635Lausanne University Hospital, Lausanne, Switzerland.

Background: Depression may contribute to neurocognitive impairment (NCI) in people with HIV (PWH). Attributing NCI to depression rather than to HIV is complicated as depression may be both a causal factor and an effect of NCI. This study aimed to determine the association between depressive symptoms and NCI among PWH with well-controlled infection.

Methods: The Neurocognitive Assessment in the Metabolic and Ageing Cohort study is an ongoing, prospective, longitudinal study of PWH aged ≥45 years old nested within the Swiss HIV Cohort Study. Neurocognitive Assessment in the Metabolic and Ageing Cohort study participants underwent neurocognitive assessment and grading of depressive symptoms using the Centre for Epidemiological Studies Depression Scale. Neurocognitive impairment categories were defined using Frascati criteria. Participants with NCI related to neurological or psychiatric confounders other than depression were excluded. The cross-sectional association between the Centre for Epidemiological Studies Depression score and neurocognitive impairment was examined taking Centre for Epidemiological Studies Depression score as a continuous variable and then as a binary variable using two score thresholds, 16 and 27.

Results: Excluding 79 participants with confounding factors, 902 participants were studied: 81% were men; 96% had plasma viral loads <50 copies/ml; 35% had neurocognitive impairment; 28% had Centre for Epidemiological Studies Depression scores ≥16. Higher Centre for Epidemiological Studies Depression scores were associated with female sex ( = 0.0003), non-Caucasian origin ( = 0.011) and current/past intravenous drug use ( = 0.002). Whilst neurocognitive impairment was associated with higher Centre for Epidemiological Studies Depression scores, the Centre for Epidemiological Studies Depression score was a poor predictor of having neurocognitive impairment (area under the ROC curve 0.604). Applying a Centre for Epidemiological Studies Depression score threshold of 16 predicted the presence of neurocognitive impairment with a sensitivity of 38.3% (specificity 77.2%), increasing the threshold to 27 lowered sensitivity to 15.4% (specificity 93.6%).

Conclusion: In this large cohort of PWH in Switzerland, we did not observe a Centre for Epidemiological Studies Depression score threshold that was sensitive in predicting neurocognitive impairment. As neurocognitive impairment was however associated with higher Centre for Epidemiological Studies Depression scores, the data support the screening for and treatment of depression among PWH diagnosed with neurocognitive impairment.
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http://dx.doi.org/10.1177/0956462420987434DOI Listing
February 2021

Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis.

Nat Commun 2021 02 22;12(1):1219. Epub 2021 Feb 22.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland.

Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis.
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http://dx.doi.org/10.1038/s41467-021-21485-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900236PMC
February 2021

Changes in physical activity behavior and development of cardiovascular risk in children.

Scand J Med Sci Sports 2021 Feb 1. Epub 2021 Feb 1.

Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland.

The study aimed to investigate the association of changes in physical activity, screen time, and cardiorespiratory fitness (CRF) with development of body mass index (BMI), blood pressure (BP), and retinal microvascular health in children over four years. In 2014, 391 children aged 6-8 years were screened, and thereof 262 children were reexamined after four years following standardized protocols. Retinal arteriolar (CRAE) and venular diameters were measured by a retinal vessel analyzer. CRF was objectively assessed by a 20 m shuttle run, physical activity, and screen time by use of a questionnaire. Children who achieved higher CRF levels reduced their BMI (β [95% CI] -0.35 [-0.46 to -0.25] kg/m per stage, P ≤ .001) and thereby developed wider CRAE (β [95% CI] 0.25 [0.24 to 0.48] µm per stage, P = .03) at follow-up. Moreover, children with elevated or high systolic BP at baseline, but lower levels of screen time during the observation period, had wider CRAE at follow-up (β [95% CI] -0.37 [-0.66 to -0.08] µm per 10 min/d, P = .013). Change in CRF was not directly associated with better microvascular health at follow-up. However, an increase of CRF over four years was associated with a reduced BMI and consequently wider retinal arterioles at follow-up. In children with elevated or high systolic BP, a reduction of screen time significantly improved retinal microvascular health as a primary prevention strategy to promote childhood health and combat development of manifest CV disease later in life.
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http://dx.doi.org/10.1111/sms.13931DOI Listing
February 2021

Blood Pressure Increase and Microvascular Dysfunction Accelerate Arterial Stiffening in Children: Modulation by Physical Activity.

Front Physiol 2020 17;11:613003. Epub 2020 Dec 17.

Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland.

Background: Atherosclerotic remodeling starts early in life and can accelerate in the presence of cardiovascular risk (CV) factors. Regular physical activity (PA) can mitigate development of large and small artery disease during lifespan. We aimed to investigate the association of changes in body mass index (BMI), blood pressure (BP), PA behavior and retinal microvascular diameters with large artery pulse wave velocity (PWV) in prepubertal children over 4 years.

Methods: The school-based prospective cohort study included 262 children initially aged 6-8 years, assessing the above CV risk factors and retinal vessels by standardized procedures at baseline (2014) and follow-up (2018). PWV was assessed by an oscillometric device at follow-up.

Results: Children with increased systolic BP over 4 years showed higher PWV at follow-up (β [95% CI] 0.006 [0.002 to 0.011] mmHg per unit, = 0.002). In contrast, increased vigorous PA corresponded to a lower PWV at follow-up (β [95% CI] -0.009 [-0.018 to <0-0.001] 10 min/day per unit, = 0.047). Progression of retinal arteriolar narrowing and venular widening were linked to a higher PWV after 4 years (β [95% CI] -0.014 [-0.023 to -0.004] 0.01 changes per unit, = 0.003).

Conclusion: Increase in systolic BP and progression of microvascular dysfunction were associated with higher PWV after 4 years. Children with increasing levels of vigorous PA were found to have lower PWV at follow-up. Habitual vigorous PA has the potential to decelerate the process of early vascular aging in children and may thus help counteract CV disease development later in life.

Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT03085498.
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http://dx.doi.org/10.3389/fphys.2020.613003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773656PMC
December 2020

The Swiss STAR trial - an evaluation of target groups for sexually transmitted infection screening in the sub-sample of men.

Swiss Med Wkly 2020 Dec 31;150:w20392. Epub 2020 Dec 31.

Division of Infectious Diseases and Infection Control, Cantonal Hospital St. Gallen, Switzerland.

Objectives: In Switzerland, universal health insurance does not cover any routine testing for sexually transmitted infections (STIs), not even in individuals at high risk, and extra-genital swabbing is not standard of care. We determined the prevalence and incidence of human immunodeficiency virus (HIV), viral hepatitis and non-viral STIs in a multicentre prospective observational cohort of multi-partner men who have sex with men (MSM) and other men.

Materials And Methods: Between January 2016 and June 2017, we offered free STI testing to all men with multiple  sexual partners (three or more in the previous 12 months), with follow-up examinations every 6 months. We used multiplex polymerase chain-reaction testing (for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium) on pooled swabs (pharynx, urethra/vagina, anus), and antibody tests for HIV and Treponema pallidum at every visit, and for hepatitis B/C at baseline.

Results: We screened 779 multi-partner MSM and 92 other men. Previously undiagnosed HIV was found in 0.5% vs 0.0%, respectively and T. pallidum antibodies in 15.3% vs 1.1%. STIs requiring antibiotic treatment comprised: active syphilis 1.7% vs 0.0%; N. gonorrhoeae 10.3% vs 0.0%; C. trachomatis 8.7% vs 1.1%. One in four MSM versus 1 in 100 other multi-partner men had any of these three STIs at baseline. 10.4% vs 1.3% had a history of hepatitis B, 31.9% vs 47.3% had no immunity (HBs-AB <10 IU/l). Ten MSM had HCV antibodies (1.4%), with 8 out of the 10 being MSM with HIV; HCV seroprevalence was 0.3% among HIV-negative MSM. In MSM, incidence of the three bacterial STIs was 25.5 per year over 333 person years of follow-up, HIV incidence was 0.3%. Non-condom-use (in the last 3 months) for anal/vaginal sex was not associated with STIs. Independent risk factors were sex with men (adjusted odds ratio [aOR] 16.4) and the number of sexual partners (aOR 2.3 for >20).

Conclusion: Among MSM, but not among other multi-partner men, STIs, mostly asymptomatic, are common. Given the high risk of onward transmission, low-cost or free routine screening of multi-partner MSM is a public health priority.
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http://dx.doi.org/10.4414/smw.2020.20392DOI Listing
December 2020

The Swiss STAR trial - an evaluation of target groups for sexually transmitted infection screening in the sub-sample of women.

Swiss Med Wkly 2020 Dec 31;150:w20393. Epub 2020 Dec 31.

Division of Infectious Diseases and Infection Control, Cantonal Hospital St. Gallen, Switzerland / Communicable Diseases Division, Swiss Federal Office of Public Health, Bern, Switzerland.

Objectives: In Switzerland, universal health insurance does not cover any routine testing for sexually transmitted infections (STIs), not even in individuals at high risk, and extra-genital swabbing is not standard of care. We compared STI prevalence in a multicentre prospective observational cohort of multi-partner women with/without sex work and evaluated associated risk factors.

Materials And Methods: Between January 2016 and June 2017, we offered free STI testing to women with multiple  sexual partners (three or more in the previous 12 months), with follow-up examinations every 6 months. We used multiplex polymerase chain-reaction testing (for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium) for pooled swabs (pharynx, urethra/vagina, anus), and antibody tests for human immunodeficiency virus (HIV) and Treponema pallidum at every visit, and for hepatitis B and C at baseline.

Results: We screened 490 female sex workers (FSWs), including 17 trans women, and 92 other multi-partner women. More than half reported a steady partner. Previously undiagnosed HIV was found in 0.2% vs 0.0%, respectively, and T. pallidum antibodies in 5.9% vs 0.0%. STIs requiring antibiotic treatment comprised: active syphilis 1.2% vs 0.0%; N. gonorrhoeae 4.9% vs 0.0%; C. trachomatis 6.3% vs 5.4%, T. vaginalis 10.4% vs 0.0%; M. genitalium 6.7% vs 6.5%. One in four FSWs vs one in nine other women had one or more of these STIs at baseline. 15.8% vs 3.8% had a history of hepatitis B, 45.5% vs 22.8% had no immunity (HBs-AB <10 IU/l). Two FSWs had hepatitis C virus antibodies (0.4%) without concurrent HIV infection. Non-condom-use (last three months) for anal/vaginal sex was not associated with STIs. Independent risk factors were group sex (adjusted odds ratio [aOR] 2.1, 95% confidence interval [CI] 1.1–4.0), age less than 25 (aOR 3.7, 95% CI 1.6–8.9), and being active in sex work for less than 1 year (aOR 2.7, 95% CI 1.3–5.3).

Conclusion: HIV and HCV do not appear to pose a major public health problem among FSWs in Switzerland, whereas vaccination against HBV should be promoted. FSWs showed high rates of STIs requiring treatment to reduce transmission to clients and/or steady partners. FSWs should be offered low-cost or free STI screening as a public health priority.
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http://dx.doi.org/10.4414/smw.2020.20393DOI Listing
December 2020

Physical activity and exercise improve retinal microvascular health as a biomarker of cardiovascular risk: A systematic review.

Atherosclerosis 2020 12 23;315:33-42. Epub 2020 Sep 23.

Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland. Electronic address:

Background And Aims: Physical activity (PA) and fitness are important modulators of vascular ageing and may therefore help expand individual health span. We aimed to systematically review the association of PA and fitness, as well as the effects of exercise interventions on the new microvascular biomarkers retinal arteriolar (CRAE) and venular (CRVE) diameters and the retinal flicker light-induced dilatation (FID) in children and adults.

Methods: PubMed, Ovid, The Cochrane, EMBASE and Web of Science were searched. 805 studies were found, and 25 full-text articles analysed. Twenty-one articles were included in this systematic review.

Results: Higher PA levels were associated with narrower CRVE in children and adults. Physical inactivity was associated with wider CRVE in both age groups. Combined aerobic and motor skill training in school settings lead to wider CRAE in children. Aerobic exercise interventions in adults with or without CV risk factors induced wider CRAE and narrower CRVE. Studies on the effect of exercise on FID are scarce. In a twelve-week randomized controlled trial, high-intensity interval training significantly improved FID in older patients with CV risk factors.

Conclusions: Higher PA and fitness levels were associated with improved retinal microvascular health in children and adults. Short-term exercise interventions in healthy children and adults, as well as CV risk patients, improved retinal microvascular structure and function. Exercise has the potential to counteract microvascular remodelling and development of small vessel disease during lifespan. Retinal vessel analysis can differentiate the beneficial effects of exercise on target microvascular organ damage.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.09.017DOI Listing
December 2020

Accuracy of serological testing for SARS-CoV-2 antibodies: First results of a large mixed-method evaluation study.

Allergy 2021 03 13;76(3):853-865. Epub 2020 Nov 13.

University Institute of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland.

Background: Serological immunoassays that can identify protective immunity against SARS-CoV-2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed-design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS-CoV-2 proteins and assessed the neutralizing activity of antibodies in patient sera.

Methods: Consecutive patients admitted with confirmed SARS-CoV-2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in-house enzyme-linked immunosorbent assay utilizing recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was developed and compared to three commercially available enzyme-linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1), and a lateral flow immunoassay (LFI) based on full-length spike protein. Neutralization assays with live SARS-CoV-2 were performed.

Results: One thousand four hundred and seventy-seven individuals were included comprising 112 SARS-CoV-2 positives (defined as a positive real-time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS-CoV-2 positive individuals, 96.3% showed full neutralization of live SARS-CoV-2 at serum dilutions ≥ 1:16, while none of the 6 SARS-CoV-2-negative sera revealed neutralizing activity.

Conclusions: ELISAs targeting RBD and S1 protein of SARS-CoV-2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS-CoV-2.
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http://dx.doi.org/10.1111/all.14608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537154PMC
March 2021

Investigating selected adhesion molecules as urinary biomarkers for diagnosing endometriosis.

Reprod Biomed Online 2020 Apr 25;40(4):555-558. Epub 2020 Jan 25.

Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria.

Research Question: Are selected cell adhesion molecules useful as urinary biomarkers for diagnosing endometriosis?

Design: Prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent laparoscopic surgery for benign gynaecological pathologies. A total of 149 patients not receiving hormonal treatment for at least 3 months prior to recruitment were included and preoperative urine protein levels of soluble vascular adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), E-selectin and P-selectin were measured using a magnetic bead-based multiplex assay, normalized to creatinine levels of each sample. Levels were correlated with endometriosis status, menstrual cycle phase, body mass index, cigarette smoking and severity and entity of the lesions.

Results: Urine levels of sVCAM-1, sICAM-1, E-selectin and P-selectin did not differ between women with (n = 84) and without (n = 65) endometriosis and among subgroups. Accordingly, receiver operating characteristic analysis to examine the value of using sVCAM-1, sICAM-1, E-selectin and P-selectin levels and sVCAM/sICAM ratio to diagnose endometriosis were not significant. Whether the serum sVCAM-1 levels correlated with the urine levels of the protein in the same women was also investigated, which revealed no significant correlations for sVCAM or sICAM.

Conclusion: Although a previous study had suggested that serum sVCAM is a promising biomarker for diagnosing endometriosis, no significant differences were found in urine levels of sVCAM-1, sICAM-1, E-selectin and P-selectin between women with and without endometriosis. Other markers should be studied in an effort to establish a truly non-invasive urinary test for diagnosing endometriosis.
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http://dx.doi.org/10.1016/j.rbmo.2020.01.014DOI Listing
April 2020

Calvarial osteomyelitis in secondary syphilis: evaluation by MRI and CT, including cinematic rendering.

Heliyon 2020 Jan 9;6(1):e03090. Epub 2020 Jan 9.

University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Switzerland.

This is a case of a 22-year-old, HIV-negative, male patient with asymptomatic syphilitic osteomyelitis of the skull in the context of secondary syphilis. The diagnosis was made based on serology as well as CT and MRI scans. CT volumetric data was post-processed with cinematic rendering, which is a novel algorithm that allows for a photorealistic visualization of the lesions. Imaging and follow-up scans after treatment confirmed the diagnosis without the need to perform invasive procedures such as a biopsy.
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http://dx.doi.org/10.1016/j.heliyon.2019.e03090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953708PMC
January 2020

Antibodies against HPV16E6 oncoprotein in the Swiss HIV cohort study: Kinetics and anal cancer risk prediction.

Int J Cancer 2020 08 4;147(3):757-765. Epub 2019 Dec 4.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zurich, Switzerland.

Our aim was to describe HPV16E6 antibody kinetics prior to anal cancer in people living with HIV/AIDS (PLWHA) and evaluate the possible contribution of HPV16E6 serology to anal cancer risk prediction. For 91 persons diagnosed with anal cancer in the Swiss HIV Cohort Study (1989-2017), serial serum/plasma samples were tested for HPV16E6 antibodies using multiplex serology, supplemented with samples from 1,356 participants without anal cancer. Anal cancer incidence was estimated for PLWHA from 40 years-old in the cART era, stratified by HPV16E6 serostatus. HPV16E6 seroprevalence was 23.3% in samples <2 years prior to anal cancer diagnosis and decreased with increasing time prior to cancer: 16.7% at 2-4 years, 4.4% at 5-9, and 7.0% at ≥10 years. Of 25 individuals with anal cancer who were HPV16E6-seropositive at any time during follow-up, the majority (n = 18) remained seropositive in all samples after seroconversion, whereas for seven cases, seropositivity was transitory. Among individuals with anal cancer, HPV16E6 seroprevalence was marginally higher in women vs. men who have sex with men (adjusted OR = 4.3, 95% CI: 1.1, 17.2) and in older participants (adjusted OR = 6.2, 95% CI: 1.1, 34.8 for cases diagnosed at ≥55 vs. <45 years). Anal cancer incidence was 402/100,000 person-years in HPV16E6-positive vs. 82/100,000 in HPV16E6-negative PLWHA (incidence rate ratio = 4.9, 95% CI: 1.3, 13.1). In conclusion, HPV16E6 serology, despite its low sensitivity, allows characterization of a group of individuals with very high anal cancer incidence and may have a place in secondary prevention in groups at high risk for anal cancer such as PLWHA.
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http://dx.doi.org/10.1002/ijc.32784DOI Listing
August 2020

Self-reported Neurocognitive Impairment in People Living With Human Immunodeficiency Virus (HIV): Characterizing Clusters of Patients With Similar Changes in Self-reported Neurocognitive Impairment, 2013-2017, in the Swiss HIV Cohort Study.

Clin Infect Dis 2020 Jul;71(3):637-644

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.

Background: Self-reported neurocognitive impairment (SRNI) in people living with human immunodeficiency virus type 1 (HIV-1) infection is frequent. We use longitudinal information on SRNI in the Swiss HIV Cohort Study (SHCS) to identify and characterize groups of patients with persisting SRNI over time.

Methods: We included all SHCS patients who were assessed for SRNI during at least 5 visits spanning at least 2.5 years in 2013-2017. We first compared patients with SRNI to those without SRNI over the whole study period. Second, we used a hierarchical cluster algorithm to identify groups of patients with similar changes of SRNI over time. In both analyses, we studied clinical and demographic factors potentially influencing SRNI.

Results: In total, 79 683 questionnaires of 11 029 patients contained information about SRNI, and 8545 of 11 029 (77.5%) patients had longitudinal information. The overall percentage of patients with SRNI decreased from 19.6% in 2013 to 10.7% in 2017. Compared to patients in the cluster with low-level SRNI over time, patients in the cluster with high-level persisting SRNI more often had a prior opportunistic infection of the central nervous system (CNS) (odds ratio [OR], 3.7; P < .001), imperfect adherence to antiretroviral therapy (ART) (OR, 2.8; P < .001), and depression (OR, 1.9; P < .001).

Conclusions: Although overall SRNI is decreasing in the SHCS, there is a group of patients with persisting SRNI over time. Past opportunistic infections of the CNS, imperfect adherence to ART, and depression were associated most with persisting SRNI. Patients with these characteristics should be preferentially tested for neurocognitive impairment.Although overall self-reported neurocognitive impairment (SRNI) is decreasing in the Swiss HIV Cohort Study, there is a group of patients with persisting SRNI over time, characterized by more past opportunistic infections of the central nervous system, imperfect adherence to antiretroviral therapy, and depression.
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http://dx.doi.org/10.1093/cid/ciz868DOI Listing
July 2020

Cross-Sectional and Cumulative Longitudinal Central Nervous System Penetration Effectiveness Scores Are Not Associated With Neurocognitive Impairment in a Well Treated Aging Human Immunodeficiency Virus-Positive Population in Switzerland.

Open Forum Infect Dis 2019 Jul 8;6(7):ofz277. Epub 2019 Jul 8.

Infectious Diseases Service, Lausanne University Hospital, Switzerland.

Background: Neurocognitive impairment (NCI) in people with human immunodeficiency virus (PWH) remains a concern despite potent antiretroviral therapy (ART). Higher central nervous system (CNS) penetration effectiveness (CPE) scores have been associated with better CNS human immunodeficiency virus (HIV) replication control, but the association between CPE and NCI remains controversial.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a subgroup of the Swiss HIV Cohort Study (SHCS) that invited patients aged ≥45 years enrolled in the SHCS and followed-up at NAMACO-affiliated centers in Switzerland to participate between May 2013 and November 2016. In total, 981 patients were enrolled, all of whom underwent standardized neurocognitive assessment. Neurocognitive impairment, if present, was characterized using Frascati criteria. The CPE scores of NAMACO study participants with undetectable plasma HIV-ribonucleic acid at enrollment (909 patients) were analyzed. Cross-sectional CPE scores (at neurocognitive assessment) were examined as potential predictors of NCI in multivariate logistic regression models. The analysis was then repeated taking CPE as a cumulative score (summarizing CPE scores from ART initiation to the time of neurocognitive assessment).

Results: Most patients were male (80%) and Caucasian (92%). Neurocognitive impairment was present in 40%: 27% with HIV-associated NCI (mostly asymptomatic neurocognitive impairment), and 13% with NCI related to other factors. None of the CPE scores, neither cross-sectional nor cumulative, was statistically significantly associated with NCI.

Conclusions: In this large cohort of aviremic PWH, we observed no association between NCI, whether HIV-associated or related to other factors, and CPE score, whether cross-sectional or cumulative.
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http://dx.doi.org/10.1093/ofid/ofz277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612860PMC
July 2019

Using Malaise traps for collecting Lepidoptera (Insecta), with notes on the preparation of Macrolepidoptera from ethanol.

Biodivers Data J 2019 20(7):e32192. Epub 2019 Feb 20.

Vietnam National Museum of Nature, VAST, Hanoi, Vietnam Vietnam National Museum of Nature, VAST Hanoi Vietnam.

The present paper deals with the potential of employing Malaise traps for collecting butterflies and moths for morphological analysis and presents a protocol for preparing Macrolepidoptera from Malaise trap samples that were preserved in ethanol. About 80 specimens of Lepidoptera, including Nymphalidae, Geometridae, Hesperiidae, Erebidae, Noctuidae, Pyralidae and Tortricidae, were mounted, following the protocol. All specimens with robust wings and contrasting wing patterns were well suited for the study of external morphology, regardless of the family. The specimens used in this study were collected in highland forest areas of central Vietnam with a little known entomofauna, as part of the German-Vietnamese biodiversity project 'VIETBIO'. The study offers new methodological approaches in an attempt to make the most of the material that was obtained using Malaise traps.
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http://dx.doi.org/10.3897/BDJ.7.e32192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426827PMC
February 2019

Enhanced expression of TACE contributes to elevated levels of sVCAM-1 in endometriosis.

Mol Hum Reprod 2019 02;25(2):76-87

Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.

Study Question: Are increased sVCAM-1 and sICAM-1 levels associated with tumor necrosis factor-alpha-converting enzyme (TACE) activity in endometriosis?

Summary Answer: Here we provide the first functional evidence that induced TACE activity in human endometriotic epithelial cells is at least in part responsible for the enhanced release of sVCAM-1 from these cells.

What Is Known Already: We and others have shown that serum-soluble (s)VCAM-1 levels are significantly higher in women with endometriosis, compared to disease-free controls. Experimental evidence exists suggesting a role of sICAM-1 and sVCAM-1 in the pathogenesis of endometriosis. TACE was identified as the protease responsible for phorbol 12-myristate 13-acetate (PMA)-induced VCAM-1 release in murine endothelial cells. Additionally, it has recently been shown that TACE is upregulated in the endometrial luminal epithelium of the mid-secretory phase in infertile women.

Study Design, Size, Duration: This study was conducted at the Tertiary Endometriosis Referral Center of the Medical University of Vienna. Samples from a total number of 97 women were collected between July 2013 and September 2014.

Participants/materials, Setting, Methods: After complete surgical exploration of the abdominopelvic cavity, 49 women with histologically proven endometriosis and 48 endometriosis-free control women were enrolled. Each participating woman contributed only one sample of eutopic endometrium and normal peritoneum, and some of the women with endometriosis contributed samples of diverse types of endometriotic lesions (in total 52 ectopic samples). Among the 49 women with endometriosis, 36 matched samples of endometriotic lesions and corresponding eutopic endometrium were collected. In order to detect sVCAM-1 and TACE protein by ELISA, peritoneal fluid (PF) samples were collected from 44 cases and 32 controls during surgery. Expression of TACE mRNA was analyzed by qRT-PCR in 111 endometrium tissue samples (28 eutopic control samples, 33 eutopic samples from women with endometriosis, 50 ectopic samples from lesions) and 37 healthy peritoneum samples. Immunohistochemistry was performed in 123 tissue samples (39 eutopic control samples, 42 eutopic samples from women with endometriosis, 42 ectopic samples from lesions) and the relation between tissue TACE protein levels and sVCAM-1 secretion was examined. PMA-induced sVCAM-1 release, and TACE- and VCAM-1-transcripts or proteins were measured in an immortalized endometriotic epithelial cell line (11Z) pre-incubated either with TACE inhibitors or following TACE siRNA knockdown.

Main Results And The Role Of Chance: Here, we demonstrate that TACE protein is overexpressed in epithelium of tissue samples of both eutopic endometrium and ectopic lesions of women with endometriosis compared to disease-free controls (P < 0.001 both) and that the overexpression of the protein in the lesions is due to activation of TACE gene transcription (P < 0.001). Moreover, epithelial TACE protein was significantly higher in ectopic samples than in corresponding eutopic tissue of women with the disease (P < 0.001). High endometrial tissue TACE protein expression correlated with higher serum sVCAM-1 levels (P < 0.05) but not with sICAM-1 levels. Inhibition of TACE either by TACE inhibitors or by TACE siRNA knockdown resulted in decreased PMA-induced shedding of sVCAM-1 in vitro (P < 0.005 or P < 0.01, respectively), but the TACE inhibitors did not affect transcription of TACE or VCAM-1. Additionally, we observed an upregulation of TACE in proliferative endometrial epithelium of infertile (P < 0.005), compared to fertile women. TACE was increased in infertile women with endometriosis (P = 0.051) but not in infertile women without endometriosis.

Limitations, Reasons For Caution: Albeit well characterized, our control population included women with other gynecologic diseases, which may have impacted the levels of sVCAM-1 and tissue TACE expression levels, e.g. benign ovarian cysts or uterine fibroids. Thus, the results of our analysis have to be interpreted carefully and in the context of the current experimental settings.

Wider Implications Of The Findings: The dysregulation of TACE substrate shedding represents a promising yet relatively unexplored area of endometriosis progression and could serve as a basis for the development of new treatments of the disease.

Study Funding And Competing Interest(s): This work was supported by the Ingrid Flick Foundation. The authors have no competing interests to declare.
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http://dx.doi.org/10.1093/molehr/gay042DOI Listing
February 2019

The next generation of site-based long-term ecological monitoring: Linking essential biodiversity variables and ecosystem integrity.

Sci Total Environ 2018 Feb 6;613-614:1376-1384. Epub 2017 Oct 6.

Helmholtz Centre for Environmental Research UFZ, Department of Conservation Biology, Permoserstraße 15, D-04318 Leipzig, Germany; ECOLAB, Université de Toulouse, CNRS, INPT, UPS, Toulouse, France.

Global change effects on biodiversity and human wellbeing call for improved long-term environmental data as a basis for science, policy and decision making, including increased interoperability, multifunctionality, and harmonization. Based on the example of two global initiatives, the International Long-Term Ecological Research (ILTER) network and the Group on Earth Observations Biodiversity Observation Network (GEO BON), we propose merging the frameworks behind these initiatives, namely ecosystem integrity and essential biodiversity variables, to serve as an improved guideline for future site-based long-term research and monitoring in terrestrial, freshwater and coastal ecosystems. We derive a list of specific recommendations of what and how to measure at a monitoring site and call for an integration of sites into co-located site networks across individual monitoring initiatives, and centered on ecosystems. This facilitates the generation of linked comprehensive ecosystem monitoring data, supports synergies in the use of costly infrastructures, fosters cross-initiative research and provides a template for collaboration beyond the ILTER and GEO BON communities.
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http://dx.doi.org/10.1016/j.scitotenv.2017.08.111DOI Listing
February 2018

Incidental Findings on Coronary Computed Tomography Angiography in Human Immunodeficiency Virus (HIV)-Positive and HIV-Negative Persons.

Open Forum Infect Dis 2018 May 20;5(5):ofy084. Epub 2018 Apr 20.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich, University of Zurich, Switzerland.

Background: Incidental findings on coronary computed tomography angiography (CCTA) have a great impact on the benefits and costs of testing for cardiovascular disease. The number of incidental findings might be increased in human immunodeficiency virus (HIV)-positive individuals compared with the general population. Data are limited regarding the association between incidental findings and HIV infection.

Methods: We assessed the prevalence and factors associated with incidental findings among HIV-positive and HIV-negative participants ≥45 years undergoing CCTA. Logistic regression was performed to evaluate the factors associated with incidental findings in the HIV-positive and HIV-negative groups. For the analysis of the HIV effect, a propensity score-matched dataset of HIV-positive/HIV-negative participants was used.

Results: We included 553 participants, 341 with and 212 without HIV infection. Incidental findings were observed in 291 of 553 (53%) patients. In 42 of 553 (7.6%) participants, an incidental finding resulted in additional workup. A malignancy was diagnosed in 2 persons. In the HIV-positive group, age (1.31 per 5 years, 1.10-1.56) and smoking (2.29, 1.43-3.70) were associated with incidental findings; in the HIV-negative group, age (1.26, 1.01-1.59) and a CAC score >0 (2.08, 1.09-4.02) were associated with incidental findings. Human immunodeficiency virus seropositivity did not affect the risk of incidental findings.

Conclusions: Incidental findings were highly prevalent among HIV-positive and HIV-negative persons. Human immunodeficiency virus infection was not associated with an increased risk of incidental findings.
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http://dx.doi.org/10.1093/ofid/ofy084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952950PMC
May 2018

N-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure-Activity Relationships, and Pharmacokinetic Profiling.

J Med Chem 2018 05 10;61(10):4528-4560. Epub 2018 May 10.

Institut für Radiopharmazeutische Krebsforschung , Helmholtz-Zentrum Dresden-Rossendorf , Bautzner Landstraße 400 , 01328 Dresden , Germany.

Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M s, which resulted in comprehensive structure-activity relationships. Structure-activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.
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http://dx.doi.org/10.1021/acs.jmedchem.8b00286DOI Listing
May 2018

Commonly Prescribed Antiretroviral Therapy Regimens and Incidence of AIDS-Defining Neurological Conditions.

J Acquir Immune Defic Syndr 2018 01;77(1):102-109

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.

Background: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown.

Setting: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration.

Methods: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics.

Results: Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age.

Conclusion: Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings.
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http://dx.doi.org/10.1097/QAI.0000000000001562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720915PMC
January 2018

Erratum to 'Intestinal colonisation with extended-spectrum cephalosporin- and colistin-resistant Enterobacteriaceae in HIV-positive individuals in Switzerland: molecular features and risk factors' [International Journal of Antimicrobial Agents 49/4 (2017) 519-521].

Int J Antimicrob Agents 2017 08 5;50(2):276. Epub 2017 Jun 5.

Institute for Infectious Diseases (IFIK), University of Bern, Friedbühlstrasse 51, Bern CH-3001, Switzerland; Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.ijantimicag.2017.05.002DOI Listing
August 2017

Human papillomavirus antibody response following HAART initiation among MSM.

AIDS 2017 02;31(4):561-569

aInternational Agency for Research on Cancer, Lyon, FrancebInstitute of Social and Preventive Medicine, University of Bern, BerncDivision of Infectious Diseases, University Hospital Lausanne, LausannedDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, BaseleDepartment of Infectious Diseases, Bern University Hospital, University of Bern, BernfHIV/AIDS Unit, Infectious Disease Service, Geneva University Hospital, GenevagDivision of Infectious Diseases, Cantonal Hospital St. Gallen, St. GallenhDivision of Infectious Diseases, Regional Hospital Lugano, LuganoiDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of ZurichjInstitute of Medical Virology, University of Zurich, Zurich, SwitzerlandkInfection and Cancer Program, German Cancer Research Center, Heidelberg, Germany.

Objective: To describe effects of HAART on high-risk human papillomavirus (HPV) antibody response in HIV-positive MSM and the meaning of this response for subsequent HPV-related cancer risk.

Design: Prospective seroepidemiological study of 281 HIV-positive MSM initiating HAART between 1995 and 2004 in the Swiss HIV Cohort Study.

Methods: For each individual, two serum samples, one at HAART initiation (pre-HAART) and another 24 months later (post-HAART), were tested for L1 antibodies to HPV6, 11, 16, 18, 31, 33, 35, 45, 52 and 58, as well as HPV16-E6 antibodies, using a multiplex serology assay. Identification of HPV-related cancer included data linkage with Swiss cancer registries.

Results: Pre-HAART, 45.2% were seropositive for any high-risk HPV-L1 and 32.4% for HPV16-L1. Sexual intercourse during the last 6 months was the only evaluated factor associated with L1 seropositivity pre-HAART. Seropositivity increased post-HAART to 60.5% for any high-risk HPV-L1 [prevalence ratio versus pre-HAART = 1.34, 95% confidence interval (CI) 1.14-1.57] and 48.0% for HPV16-L1 (prevalence ratio versus pre-HAART = 1.48, 95% CI 1.20-1.83), and seroconversion was significantly associated with both lower CD4 cell count and CD4/CD8 ratio (P < 0.01). Only one individual was HPV16-E6-seropositive pre-HAART, but two more seroconverted post-HAART. Anal cancer incidence among the three HPV16-E6-positives post-HAART was significantly increased compared with HPV16-E6-negatives (incidence rate ratio = 63.1, 95% CI 1.1-1211).

Conclusion: HAART-related immune reconstitution increases HPV-specific antibody responses, which may discriminate future anal cancer risk in this high-risk population.
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http://dx.doi.org/10.1097/QAD.0000000000001354DOI Listing
February 2017

[Vaccinations for immunocompromised hosts – focussing on patients after a hematological stem cell or organ transplantation, with HIV or with functional or anatomical asplenia].

Ther Umsch 2016 ;73(5):281-9

1 Universitätsklinik für Infektiologie, Inselspital Bern.

Patients with an acquired immune deficiency, for example due to HIV-infection, after a solid organ or haematological stem cell transplantation or due to functional or anatomical asplenia, have a greater risk to experience severe complications or a chronic course of infection compared to healthy individuals. Vaccinations would pose an ideal primary preventive method. However, their efficacy is reduced if applied during the immunosuppressed period. Therefore, whenever possible, vaccinations should be administered before the period of immunosuppression starts – or caught up later during the period of minimal possible immunosuppression. Nevertheless, the benefit conveyed through vaccines is undisputed, particularly if indications regarding dosing of vaccines (amount and frequency of doses) are optimized according to the given state of immunosuppression. Live attenuated vaccines are contraindicated during severe immunosuppression. Serologies should still be analysed and documented however, since these vulnerable patients require passive immunization through specific or standard intravenous immunoglobulins in case of relevant exposure to the respective antigens. For all patients therefore, careful documentation and communication of previous vaccinations and serologies (protective or not) among the various medical specialties is required to optimize patient management. For all immunosuppressed patients the efficacy of polysaccharide vaccines (such as the pneumococcal and meningococcal vaccines PSV-23 and MPV-ACWY) is strongly reduced compared to the conjugated ones (PCV13 and MCV-ACWY). Therefore, contrary to most other national guidelines, the Swiss guidelines recommend to use only the conjugated versions in primary vaccination series as well as in boosters – this applies strongly for immunosuppressed patients, but is recommended also for the general population in Switzerland. Another common management recommendation specific for transplant patients is the indication to control vaccine efficacy by measuring titers. This is also indicated for hepatitis B in HIV-positive patients, but not required for any vaccine in asplenic patients. In summary, vaccines pose an important opportunity for primary and secondary prevention for vulnerable patients at highest risk of experiencing the worst forms of the diseases to be prevented.
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http://dx.doi.org/10.1024/0040-5930/a000793DOI Listing
August 2016

Serotype/serogroup-specific antibiotic non-susceptibility of invasive and non-invasive Streptococcus pneumoniae, Switzerland, 2004 to 2014.

Euro Surveill 2016 May;21(21)

Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern, Switzerland.

Concurrent analysis of antibiotic resistance of colonising and invasive Streptococcus pneumoniae gives a more accurate picture than looking at either of them separately. Therefore, we analysed 2,129 non-invasive and 10,996 invasive pneumococcal isolates from Switzerland from 2004 to 2014, which spans the time before and after the introduction of the heptavalent (PCV7) and 13-valent (PCV13) conjugated pneumococcal polysaccharide vaccines. Serotype/serogroup information was linked with all antibiotic resistance profiles. During the study period, the proportion of non-susceptible non-invasive and invasive isolates significantly decreased for penicillin, ceftriaxone, erythromycin and trimethoprim/sulfamethoxazole (TMP-SMX). This was most apparent in non-invasive isolates from study subjects younger than five years (penicillin (p = 0.006), erythromycin (p = 0.01) and TMP-SMX (p = 0.002)). Resistant serotypes/serogroups included in PCV7 and/or PCV13 decreased and were replaced by non-PCV13 serotypes (6C and 15B/C). Serotype/serogroup-specific antibiotic resistance rates were comparable between invasive and non-invasive isolates. Adjusted odds ratios of serotype/serogroup-specific penicillin resistance were significantly higher in the west of Switzerland for serotype 6B (1.8; 95% confidence interval (CI): 1.4-4.8), 9V (3.4; 95% CI: 2.0-5.7), 14 (5.3; 95% CI: 3.8-7.5), 19A (2.2; 95% CI: 1.6-3.1) and 19F (3.1; 95% CI: 2.1-4.6), probably due to variations in the antibiotic consumption.
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http://dx.doi.org/10.2807/1560-7917.ES.2016.21.21.30239DOI Listing
May 2016

Multiplex Real-Time PCR Assay with High-Resolution Melting Analysis for Characterization of Antimicrobial Resistance in Neisseria gonorrhoeae.

J Clin Microbiol 2016 08 25;54(8):2074-81. Epub 2016 May 25.

Institute for Infectious Diseases, University of Bern, Bern, Switzerland

Resistance to antibiotics used against Neisseria gonorrhoeae infections is a major public health concern. Antimicrobial resistance (AMR) testing relies on time-consuming culture-based methods. Development of rapid molecular tests for detection of AMR determinants could provide valuable tools for surveillance and epidemiological studies and for informing individual case management. We developed a fast (<1.5-h) SYBR green-based real-time PCR method with high-resolution melting (HRM) analysis. One triplex and three duplex reactions included two sequences for N. gonorrhoeae identification and seven determinants of resistance to extended-spectrum cephalosporins (ESCs), azithromycin, ciprofloxacin, and spectinomycin. The method was validated by testing 39 previously fully characterized N. gonorrhoeae strains, 19 commensal Neisseria species strains, and an additional panel of 193 gonococcal isolates. Results were compared with results of culture-based AMR determination. The assay correctly identified N. gonorrhoeae and the presence or absence of the seven AMR determinants. There was some cross-reactivity with nongonococcal Neisseria species, and the detection limit was 10(3) to 10(4) genomic DNA (gDNA) copies/reaction. Overall, the platform accurately detected resistance to ciprofloxacin (sensitivity and specificity, 100%), ceftriaxone (sensitivity, 100%; specificity, 90%), cefixime (sensitivity, 92%; specificity, 94%), azithromycin (sensitivity and specificity, 100%), and spectinomycin (sensitivity and specificity, 100%). In conclusion, our methodology accurately detects mutations that generate resistance to antibiotics used to treat gonorrhea. Low assay sensitivity prevents direct diagnostic testing of clinical specimens, but this method can be used to screen collections of gonococcal isolates for AMR more quickly than current culture-based AMR testing.
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http://dx.doi.org/10.1128/JCM.03354-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963482PMC
August 2016

Successful Prevention of Transmission of Integrase Resistance in the Swiss HIV Cohort Study.

J Infect Dis 2016 08 29;214(3):399-402. Epub 2016 Apr 29.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Institute of Medical Virology, University of Zurich.

The prevalence of integrase strand transfer inhibitor (INSTI)-transmitted drug resistance (TDR) may increase with the increasing use of INSTIs. We analyzed the prevalence of INSTI TDR in the Swiss HIV Cohort Study (2008-2014). In 1 of 1316 drug-naive samples (0.1%), a major INSTI TDR mutation was detected. Prevalence was stable, although INSTIs were increasingly used. We showed that this is in contrast to the introduction of previous drug classes, in which more treatment failures with resistant strains occurred and TDR was observed more rapidly. We demonstrated on a population-level that it is possible to avoid TDR to a new drug class for years.
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http://dx.doi.org/10.1093/infdis/jiw165DOI Listing
August 2016