Rainer Weber

University Hospital Zürich, Zürich, Zurich, Switzerland

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Publications (227)1741.6 Total impact

  • PLoS ONE 09/2015; 10(9):e0138838. DOI:10.1371/journal.pone.0138838 · 3.23 Impact Factor
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    ABSTRACT: Background: Children travelling are potentially exposed to a wide spectrum of illness, which includes mild self-limiting disease, but also severe illness requiring hospitalization. Risk factors for hospitalization need to be analysed to inform prevention- and treatment strategies for travel-related disease, to make travelling for children - from a medical perspective - more secure. Methods: We performed a cross-sectional analysis on children with travel-related disease presenting at the Emergency Room of University of Zurich Children's Hospital between July 2007 and December 2012. The profile of children being hospitalized was compared to that of children treated as outpatients. Results: 801 children (57.4% male) were included in the study. 83 children (10.4%) were treated as inpatients. Compared to outpatients, inpatients were significantly more likely to be male, to have travelled to Southern Asia, to have a diagnosis of Salmonella typhi or paratyphi(3.6 % vs. 0.1%, p < 0.0001), pyogenic abscess (3.6% vs. 0.1 %, p < 0.0001) or malaria (1.4 % vs. 0.2%, p = 0.0384). Neurologic diagnoses (such as seizure disorder: 3.6% vs. 0.4%, p < 0.0001) were diagnosed more often among inpatients. Furthermore, inpatients presented more often with non-specific findings such as dehydration (8.5% vs. 0.6%, p < 0.0001): No correlation with inpatient care was seen for VFR/immigrant travel. Conclusions: Children acquire a wide spectrum of travel-related illness. A careful, detailed travel history is important in children presenting in the Emergency Room with symptoms suggesting infectious disease.
    The Pediatric Infectious Disease Journal 09/2015; DOI:10.1097/INF.0000000000000890 · 2.72 Impact Factor
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    ABSTRACT: Paper-based interventions have been shown to stimulate switching from intravenous (i.v.) to oral (p.o.) antibiotic therapies. Shorter i.v. durations are associated with a lower risk of iatrogenic infections as well as reduced workload and costs. The purpose of this study was to determine whether automated electronic reminders are able to promote earlier switching. In this controlled before-and-after study, an algorithm identified patients who were eligible for i.v.-to-p.o. switch 60h after starting i.v. antimicrobials. Reminders offering guidance on the re-assessment of initial i.v. therapy were displayed within the electronic health records in 12 units during the intervention period (year 2012). In contrast, no reminders were visible during the baseline period (2011) and in the control group (17 units). A total of 22863 i.v. antibiotic therapies were analysed; 6082 (26.6%) were switched to p.o. In the intervention group, 757 courses of i.v. antibiotics were administered for a mean±standard deviation duration of 5.4±8.1 days before switching to p.o. antibiotics in the baseline period, and 794 courses for 4.5±5.5 days in the intervention period (P=0.004), corresponding to a 17.5% reduction of i.v. administration time. In contrast, in the control group the duration increased; 2240 i.v. antibiotics were administered for a mean duration of 4.0±5.9 days in the baseline period, and 2291 for 4.3±5.8 days in the intervention period (P=0.03). Electronic reminders fostered earlier i.v.-to-p.o. switches, thereby reducing the duration of initial i.v. therapies by nearly a day. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
    International journal of antimicrobial agents 07/2015; DOI:10.1016/j.ijantimicag.2015.06.013 · 4.30 Impact Factor
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    ABSTRACT: We identified 10 patients with disseminated Mycobacterium chimaera infections subsequent to open-heart surgery at three European Hospitals. Infections originated from the heater-cooler unit of the heart-lung machine. Here we describe clinical aspects and treatment course of this novel clinical entity. Interdisciplinary care and follow-up of all patients was documented by the study team. Patients' characteristics, clinical manifestations, microbiological findings, and therapeutic measures including surgical reinterventions were reviewed and treatment outcomes are described. The 10 patients comprise a 1-year-old child and nine adults with a median age of 61 years (range 36-76 years). The median duration from cardiac surgery to diagnosis was 21 (range 5-40) months. All patients had prosthetic material-associated infections with either prosthetic valve endocarditis, aortic graft infection, myocarditis, or infection of the prosthetic material following banding of the pulmonary artery. Extracardiac manifestations preceded cardiovascular disease in some cases. Despite targeted antimicrobial therapy, M. chimaera infection required cardiosurgical reinterventions in eight patients. Six out of 10 patients experienced breakthrough infections, of which four were fatal. Three patients are in a post-treatment monitoring period. Healthcare-associated infections due to M. chimaera occurred in patients subsequent to cardiac surgery with extracorporeal circulation and implantation of prosthetic material. Infections became clinically apparent after a time lag of months to years. Mycobacterium chimaera infections are easily missed by routine bacterial diagnostics and outcome is poor despite long-term antimycobacterial therapy, probably because biofilm formation hinders eradication of pathogens. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
    European Heart Journal 07/2015; DOI:10.1093/eurheartj/ehv342 · 15.20 Impact Factor
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    ABSTRACT: Background: The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV) infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR) using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group. Methodology: Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir) for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin. Results: We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR) HCV-RNA decline after silibinin therapy was 2.65 (2.1-2.8) log10 copies/mL. Fifteen of sixteen patients (94%) had undetectable HCV RNA at weeks 4 and 12, eleven patients (69%) showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48), and ten patients (63%) reached SVR at week 12 (SVR 12). Six of the sixteen patients (37%) did not reach SVR 12: One patient had rapid virologic response (RVR) (i.e., undetectable HCV-RNA at week 4) but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete treatment period. No serious adverse events and no significant drug-drug interactions were associated with silibinin. Conclusion: A lead-in with silibinin before triple-therapy was safe and highly effective in difficult-to-treat HIV/HCV coinfected patients, with a pronounced HCV-RNA decline during the lead-in phase, which translates into 63% SVR. An add-on of intravenous silibinin to standard of care HCV treatment is worth further exploration in selected difficult-to-treat patients. Trial registration: ClinicalTrials.gov NCT01816490.
    PLoS ONE 07/2015; DOI:10.1371/journal.pone.0133028 · 3.23 Impact Factor
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    ABSTRACT: Background. Although acquired immune deficiency syndrome-associated morbidity has diminished due to excellent viral control, multimorbidity may be increasing among human immunodeficiency virus (HIV)-infected persons compared with the general population. Methods. We assessed the prevalence of comorbidities and multimorbidity in participants of the Swiss HIV Cohort Study (SHCS) compared with the population-based CoLaus study and the primary care-based FIRE (Family Medicine ICPC-Research using Electronic Medical Records) records. The incidence of the respective endpoints were assessed among SHCS and CoLaus participants. Poisson regression models were adjusted for age, sex, body mass index, and smoking. Results. Overall, 74 291 participants contributed data to prevalence analyses (3230 HIV-infected; 71 061 controls). In CoLaus, FIRE, and SHCS, multimorbidity was present among 26%, 13%, and 27% of participants. Compared with nonsmoking individuals from CoLaus, the incidence of cardiovascular disease was elevated among smoking individuals but independent of HIV status (HIV-negative smoking: incidence rate ratio [IRR] = 1.7, 95% confidence interval [CI] = 1.2–2.5; HIV-positive smoking: IRR = 1.7, 95% CI = 1.1–2.6; HIV-positive nonsmoking: IRR = 0.79, 95% CI = 0.44–1.4). Compared with nonsmoking HIV-negative persons, multivariable Poisson regression identified associations of HIV infection with hypertension (nonsmoking: IRR = 1.9, 95% CI = 1.5–2.4; smoking: IRR = 2.0, 95% CI = 1.6–2.4), kidney (nonsmoking: IRR = 2.7, 95% CI = 1.9–3.8; smoking: IRR = 2.6, 95% CI = 1.9–3.6), and liver disease (nonsmoking: IRR = 1.8, 95% CI = 1.4–2.4; smoking: IRR = 1.7, 95% CI = 1.4–2.2). No evidence was found for an association of HIV-infection or smoking with diabetes mellitus. Conclusions. Multimorbidity is more prevalent and incident in HIV-positive compared with HIV-negative individuals. Smoking, but not HIV status, has a strong impact on cardiovascular risk and multimorbidity.
    07/2015; DOI:10.1093/ofid/ofv108
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    ABSTRACT: Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood. HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA <20 IU/mL) and the influence of HBV genotypes were determined. 143 HIV/HBV-coinfected participants with detectable HBV DNA were identified. The predominant HBV genotypes were A (82 patients, 57 %); and D (35 patients, 24 %); 20 patients (14 %) were infected with multiple genotypes (3 % A + D and 11 % A + G); and genotypes B, C and E were each present in two patients (1 %). TDF completely suppressed HBV DNA in 131 patients (92 %) within 6 months; and in 12 patients (8 %), HBV DNA suppression was delayed. No HBV resistance mutations to TDF were found in patients with delayed response, but all were infected with HBV genotype A (among these, 5 patients with genotype A + G), and all had previously been exposed to lamivudine. In HIV/HBV-coinfected patients, infection with multiple HBV genotypes was more frequent than previously reported. The large majority of patients had an undetectable HBV viral load at six months of TDF-containing ART. In patients without viral suppression, no TDF-related resistance mutations were found. The role of specific genotypes and prior lamivudine treatment in the delayed response to TDF warrant further investigation.
    BMC Gastroenterology 07/2015; 15(1):79. DOI:10.1186/s12876-015-0308-0 · 2.37 Impact Factor
  • Clinical Infectious Diseases 06/2015; 61(7). DOI:10.1093/cid/civ515 · 8.89 Impact Factor
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    ABSTRACT: Condomless sex is a key driver of sexually transmitted diseases. In this study, we assess the long-term changes (2000–2013) of the occurrence of condomless sex among human immunodeficiency virus (HIV)-infected individuals enrolled in the Swiss HIV Cohort study. The frequencies with which HIV-infected individuals reported condomless sex were either stable or only weakly increasing for 2000–2008. For 2008–2013, these rates increased significantly for stable relationships among heterosexuals and men who have sex with men (MSM) and for occasional relationships among MSM. Our results highlight the increasing public health challenge posed by condomless sex and show that condomless sex has been increasing even in the most recent years.
    06/2015; 2(2). DOI:10.1093/ofid/ofv077
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    ABSTRACT: Background: Prospectively and systematically collected data on frequency and spectrum of unexpected clinical manifestations during primary human immunodeficiency virus (HIV) infection (PHI) have not been published. Methods: We prospectively enrolled 290 patients with documented PHI in the Zurich Primary HIV Infection Study. Typical acute retroviral syndrome (ARS) was defined as fever plus at least 1 symptom or sign typically considered to be associated with ARS; in absence of fever, presence of 2 or more ARS symptoms or signs. Atypical ARS was defined as lack of symptoms or signs, a single symptom or sign only and absence of fever, presence of symptoms or signs that are not considered typically associated with ARS, or occurrence of an opportunistic disease. Time to diagnosis was calculated based on estimated date of infection and first positive HIV test. Results: We analyzed 290 patients (271 males). PHI manifested with typical ARS in 202 (70%) and with atypical ARS in 88 (30%) patients. Patients with atypical ARS were hospitalized 4 times more often compared with typical ARS (43% vs 11%; P < .001). The gastrointestinal tract was the most frequent organ system affected in patients with atypical manifestations. Only in 112 (38%) patients was HIV infection suspected during the first medical attendance. Patients with typical ARS were diagnosed slightly earlier compared with atypical ARS, but this difference was not significant (P = .3). Conclusions: Unexpected clinical presentations occurred in a large fraction of patients with PHI and were associated with substantial morbidity. Universal HIV testing may be mandatory in high-risk groups.
    Clinical Infectious Diseases 05/2015; 61(6). DOI:10.1093/cid/civ398 · 8.89 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the clinical value of positron emission tomography/computed tomography with (18)F-fluorodeoxyglucose (FDG-PET/CT) for therapy control in patients with prosthetic vascular graft infections (PVGI). In this single-centre, observational, prospective cohort study, 25 patients with a median age of 66 years (range: 48-81) were included who had a proven PVGI. Follow-up FDG-PET/CT was performed at a median time interval of 170 days (range: 89-249) after baseline examination. Two independent and blinded readers measured maximum standardized uptake values (SUV max.) to quantify metabolic activity and analysed whole body datasets for secondary diagnosis (i.e., infectious foci not within graft vicinity). The metabolic activity of the graft was correlated with clinical information and two laboratory markers (C-reactive protein (CRP) and white blood cell count (WBC)). FDG-PET/CT had an impact on management in all patients. In 19 of 25 patients (76%) antibiotic treatment was continued due to the results of follow-up FDG-PET/CT. Antibiotic treatment was stopped or changed in 8% and 16% of patients, respectively. In eight patients (32%) additional incidental findings were detected on follow-up FDG-PET/CT which had further impact on patient management. Only in a subgroup of patients with PVGI and no other sites of infection, a significant correlation between the difference in CRP at the time of baseline and follow-up FDG-PET/CT and the difference in SUV max. was found (n = 11; r = 0.84; P = 0.001). FDG-PET/CT represents a useful tool in therapy monitoring of PVGI and impacts on patient management. By providing quantitative data on the course of the graft infection and whole body imaging data, PET/CT differentiates between response of therapy to PVGI and other infectious foci. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 05/2015; 56(7). DOI:10.2967/jnumed.115.156265 · 6.16 Impact Factor
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    ABSTRACT: The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV-therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. Over the last 13 years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 04/2015; 63(3). DOI:10.1016/j.jhep.2015.04.019 · 11.34 Impact Factor
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    ABSTRACT: Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channelling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient years). In a conventional Cox model, recent - but not cumulative - exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past four years increased the risk of a CVD event (hazard ratio 2.06, 95% confidence interval 1.43-2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6 to 36 months caused the greatest increase in risk. Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2015; Publish Ahead of Print(4). DOI:10.1097/QAI.0000000000000662 · 4.56 Impact Factor
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    ABSTRACT: With the aging of the population living with HIV, the absolute risk of cardiovascular disease (CVD) is increasing. There is a need to further facilitate the identification of persons at elevated risk in routine practice. Prospective information was collected on 32,663 HIV-positive persons from 20 countries in Europe and Australia, who were free of CVD at entry into the Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Cox regression models (full and reduced) were developed that predict the risk of a global CVD endpoint. The predictive performance of the D:A:D models were compared with a recent CVD prediction model from the Framingham study, which was assessed recalibrated to the D:A:D dataset. A total of 1010 CVD events occurred during 186,364.5 person-years. The full D:A:D CVD prediction model included age, gender, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, high-density lipoprotein, CD4 lymphocyte count, cumulative exposure to protease- and nucleoside reverse transcriptase-inhibitors, and current use of abacavir. A reduced model omitted antiretroviral therapies. The D:A:D models statistically significantly predicted risk more accurately than the recalibrated Framingham model (Harrell's c-statistic of 0.791, 0.783 and 0.766 for the D:A:D full, D:A:D reduced, and Framingham models respectively; p < 0.001). The D:A:D models also more accurately predicted five-year CVD-risk for key prognostic subgroups. An updated, easily recalibrated, global CVD-risk equation tailored to HIV-positive persons was developed using routinely collected CVD risk parameters and incorporating markers on immune function (CD4 lymphocyte count), and exposure to antiretroviral therapies. The estimated CVD risk can be used to quantify risk and to guide preventive care. © The European Society of Cardiology 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    04/2015; DOI:10.1177/2047487315579291
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    ABSTRACT: Background: Invasive Mycobacterium chimaera infections were diagnosed in 2012 in 2 heart surgery patients on extracorporeal circulation. We launched an outbreak investigation to identify the source and extent of the potential outbreak and to implement preventive measures. Methods: We collected water samples from operating theaters, intensive care units, and wards, including air samples from operating theaters. Mycobacterium chimaera strains were characterized by randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was performed based on archived histopathology samples and M. chimaera isolates since 2006, and the patient population at risk was prospectively surveyed. Results: We identified 6 male patients aged between 49 and 64 years with prosthetic valve endocarditis or vascular graft infection due to M. chimaera, which became clinically manifest with a latency of between 1.5 and 3.6 years after surgery. Mycobacterium chimaera was isolated from cardiac tissue specimens, blood cultures, or other biopsy specimens. We were able also to culture M. chimaera from water circuits of heater-cooler units connected to the cardiopulmonary bypass, and air samples collected when the units were in use. RAPD-PCR demonstrated identical patterns among M. chimaera strains from heater-cooler unit water circuits and air samples, and strains in 2 patient clusters. Conclusions: The epidemiological and microbiological features of this prolonged outbreak provided evidence for the airborne transmission of M. chimaera from contaminated heater-cooler unit water tanks to patients during open-heart surgery.
    Clinical Infectious Diseases 03/2015; 61(1). DOI:10.1093/cid/civ198 · 8.89 Impact Factor
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    ABSTRACT: BACKGROUND: Travel is important in the acquisition and dissemination of infection. We aimed to assess European surveillance data for travel-related illness to profile imported infections, track trends, identify risk groups, and assess the usefulness of pre-travel advice. METHODS: We analysed travel-associated morbidity in ill travellers presenting at EuroTravNet sites during the 5-year period of 2008-12. We calculated proportionate morbidity per 1000 ill travellers and made comparisons over time and between subgroups. We did 5-year trend analyses (2008-12) by testing differences in proportions between subgroups using Pearson's χ(2) test. We assessed the effect of the pre-travel consultation on infection acquisition and outcome by use of proportionate morbidity ratios. FINDINGS: The top diagnoses in 32 136 patients, ranked by proportionate morbidity, were malaria and acute diarrhoea, both with high proportionate morbidity (>60). Dengue, giardiasis, and insect bites had high proportionate morbidity (>30) as well. 5-year analyses showed increases in vector borne infections with significant peaks in 2010; examples were increased Plasmodium falciparum malaria (χ(2)=37·57, p<0·001); increased dengue fever (χ(2)=135·9, p<0·001); and a widening geographic range of acquisition of chikungunya fever. The proportionate morbidity of dengue increased from 22 in 2008 to 36 in 2012. Five dengue cases acquired in Europe contributed to this increase. Dermatological diagnoses increased from 851 in 2008 to 1102 in 2012, especially insect bites and animal-related injuries. Respiratory infection trends were dominated by the influenza H1N1 pandemic in 2009. Illness acquired in Europe accounted for 1794 (6%) of all 32 136 cases-mainly, gastrointestinal (634) and respiratory (357) infections. Migration within Europe was associated with more serious infection such as hepatitis C, tuberculosis, hepatitis B, and HIV/AIDS. Pre-travel consultation was associated with significantly lower proportionate morbidity ratios for P falciparum malaria and also for acute hepatitis and HIV/AIDS. INTERPRETATION: The pattern of travel-related infections presenting in Europe is complex. Trend analyses can inform on emerging infection threats. Pre-travel consultation is associated with reduced malaria proportionate morbidity ratios and less severe illness. These findings support the importance and effectiveness of pre-travel advice on malaria prevention, but cast doubt on the effectiveness of current strategies to prevent travel-related diarrhoea. FUNDING: European Centre for Disease Prevention and Control, University Hospital Institute Méditerranée Infection, US Centers for Disease Control and Prevention, and the International Society of Travel Medicine.
    The Lancet Infectious Diseases 12/2014; DOI:10.1016/S1473-3099(14)71000-X · 22.43 Impact Factor
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    ABSTRACT: Introduction A recent meta-analysis of 4 RCTs showed an increased rate of suicidality events (suicidal ideation or attempted/completed suicide) associated with efavirenz (EFV) compared to other regimens, but only a trend towards a higher rate of completed/attempted suicides, as only 17 events occurred. We investigated the association between EFV use and completed suicide. Materials and Methods All D:A:D participants were followed from study entry to the first of death, last study visit or 1 February 2013. Deaths are centrally validated using cause of death methodology, which assigns underlying, immediate and up to four contributing causes of death. Two endpoints were considered: 1) suicide or psychiatric disease as the underlying cause, and 2) suicide or psychiatric disease mentioned as an underlying, immediate or contributing cause of death (anywhere). Adjusted rate ratios were calculated using Poisson regression. Results A total of 4420 deaths occurred in 49,717 people over 371,333 person-years (PY) (rate 11.9 per 1000 PY; 95% CI 11.6–12.3). A total of 193 deaths (rate 0.52; 0.45–0.59) had an underlying cause of suicide or psychiatric disease, and 482 deaths (1.30; 1.18–1.41) had suicide or psychiatric disease mentioned anywhere. A strong association with current CD4 count was seen: for suicide or psychiatric disease mentioned anywhere, rates were: 3.18 (2.55–3.80) for <200 cells/uL, 1.60 (1.29–1.90) for 201–350 cells/uL, 1.07 (0.86–1.29) for 351–500 cells/uL, 0.95 (0.80–1.09) for >500 cells/uL and 1.30 (1.18–1.41) for unknown. Highest rate of suicide or psychiatric deaths were seen in ART-experienced people currently off ART, but no differences were seen according to current ART regimen, which remained after adjustment (Table 1). Consistent results were obtained when considering additional endpoints of suicide alone as the underlying cause and death from suicide or any possibly related cause (psychiatric disease, drug overdose, alcohol related, accidental or violent), as well as considering recent EFV use in the previous 3 and 6 months. Conclusions The finding of no higher death rates from suicide amongst those receiving EFV is reassuring. However, there is likely confounding by indication in our observational study. In light of conflicting results from RCTs, this potentially could suggest that in clinical practice EFV may be less frequently prescribed in those with underlying psychiatric conditions.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19512. DOI:10.7448/IAS.17.4.19512 · 5.09 Impact Factor
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    ABSTRACT: Introduction According to reports from observational databases, classic AIDS-defining opportunistic infections (ADOIs) occur in patients with CD4 counts above 500/µL on and off cART. Adjudication of these events is usually not performed. However, ADOIs are often used as endpoints, for example, in analyses on when to start cART. Materials and Methods In the database, Swiss HIV Cohort Study (SHCS) database, we identified 91 cases of ADOIs that occurred from 1996 onwards in patients with the nearest CD4 count >500/µL. Cases of tuberculosis and recurrent bacterial pneumonia were excluded as they also occur in non-immunocompromised patients. Chart review was performed in 82 cases, and in 50 cases we identified CD4 counts within six months before until one month after ADOI and had chart review material to allow an in-depth review. In these 50 cases, we assessed whether (1) the ADOI fulfilled the SHCS diagnostic criteria (www.shcs.ch), and (2) HIV infection with CD4 >500/µL was the main immune-compromising condition to cause the ADOI. Adjudication of cases was done by two experienced clinicians who had to agree on the interpretation. Results More than 13,000 participants were followed in SHCS in the period of interest. Twenty-four (48%) of the chart-reviewed 50 patients with ADOI and CD4 >500/µL had an HIV RNA <400 copies/mL at the time of ADOI. In the 50 cases, candida oesophagitis was the most frequent ADOI in 30 patients (60%) followed by pneumocystis pneumonia and chronic ulcerative HSV disease (Table 1). Overall chronic HIV infection with a CD4 count >500/µL was the likely explanation for the ADOI in only seven cases (14%). Other reasons (Table 1) were ADOIs occurring during primary HIV infection in 5 (10%) cases, unmasking IRIS in 1 (2%) case, chronic HIV infection with CD4 counts <500/µL near the ADOI in 13 (26%) cases, diagnosis not according to SHCS diagnostic criteria in 7 (14%) cases and most importantly other additional immune-compromising conditions such as immunosuppressive drugs in 14 (34%). Conclusions In patients with CD4 counts >500/ µL, chronic HIV infection is the cause of ADOIs in only a minority of cases. Other immuno-compromising conditions are more likely explanations in one-third of the patients, especially in cases of candida oesophagitis. ADOIs in HIV patients with high CD4 counts should be used as endpoints only with much caution in studies based on observational databases.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19621. DOI:10.7448/IAS.17.4.19621 · 5.09 Impact Factor
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    ABSTRACT: Antiretroviral therapy to treat HIV, as we know it today, is nothing less than a huge success story in modern medical history. What used to be an almost certain death-sentence was transformed into a very manageable chronic disease by means of highly efficient und mostly well tolerated drugs. Today, HIV-infected patients treated according to international recommendations have a very good chance to outgo the negative effects of HIV-1 and are therefore able to reach an almost normal life expectancy. Furthermore, patients successfully treated with antiretroviral drugs are no longer infectious, which is an essential aspect of global strategies to overcome the pandemic. Nevertheless, due to the complexity of HIV, physicians treating patients with antiretroviral therapy require profound knowledge of aspects such as viral resistance mechanisms and immune reconstitution, as well as drug-toxicity und drug-drug-interactions. Many other aspects such as long-term side-effects of antiretroviral drugs are still unknown. Strict adherence to treatment is of utmost importance.
    Therapeutische Umschau 08/2014; 71(8):461-468. DOI:10.1024/0040-5930/a000538
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    ABSTRACT: Incidence as well as morbidity and mortality of opportunistic infections (OI) have declined remarkably since the availability of antiretroviral treatment (ART). Nearly half of all persons infected with HIV however do not know their HIV-status, and the diagnosis of an OI may be the first manifestation of their HIV infection. Therefore, knowledge of the presentation of OIs as well as their management should remain an essential part of clinicians' expertise. After starting ART the immune system will improve; in this context OI may be unmasked or the clinical presentation of known OI may worsen. Before starting ART therefore, it is essential to rule out any asymptomatic or latent OI. For the same reason, in the case of a known OI, the start of ART must often be deferred for some weeks after the start of OI treatment. Treatment of OIs is complex and often results in a large pill-burden for the patient with the potential for multiple drug-drug-interactions, particularly once ART has to be started. Many of the OI treatments are also associated with frequent drug side-effects and allergies. OIs can be prevented with specific antimicrobial agents once the CD4 have decreased below a defined threshold. However, the main prevention of OI is the timely recognition of HIV infection and an early start of ART before complications of OI appear.
    Therapeutische Umschau 08/2014; 71(8):475-82. DOI:10.1024/0040-5930/a000540

Publication Stats

12k Citations
1,741.60 Total Impact Points


  • 1996–2015
    • University Hospital Zürich
      Zürich, Zurich, Switzerland
  • 1991–2015
    • University of Zurich
      • • Division of Infectuous Dieseases
      • • Institute of Parasitology
      Zürich, Zurich, Switzerland
  • 2008
    • Hospital for Tropical Diseases, Ho Chi Minh City
      Thành phố Hồ Chí Minh, Ho Chi Minh City, Vietnam
    • Azienda Ospedaliera San Paolo - Polo Universitario
      Milano, Lombardy, Italy
  • 2007
    • National Institute of Allergy and Infectious Diseases
      Maryland, United States
  • 1999–2007
    • University of Lausanne
      • • Institute of Microbiology
      • • Division of Infectious Diseases
      Lausanne, Vaud, Switzerland
    • University of Bristol
      • School of Social and Community Medicine
      Bristol, England, United Kingdom
  • 2004–2005
    • University Hospital of Lausanne
      • Institute of Microbiology (IMUL)
      Lausanne, Vaud, Switzerland
  • 2003–2004
    • Universitätsspital Basel
      • Institute for Clinical Epidemiology and Biostatistics (CEB)
      Bâle, Basel-City, Switzerland
  • 1992
    • Centers for Disease Control and Prevention
      • Division of Parasitic Diseases and Malaria
      Atlanta, MI, United States