Refine
Year of publication
Document Type
- Article (44) (remove)
Has Fulltext
- yes (44)
Is part of the Bibliography
- no (44)
Keywords
- HIV (4)
- COVID-19 (3)
- Opportunistic infections (2)
- SARS-CoV-2 (2)
- AA-amylodosis (1)
- Acute coronary syndrome (1)
- Antibody avidity (1)
- Antigens (1)
- Antiretroviral therapy (1)
- Assay variation (1)
- Atrial fibrillation (1)
- B cell subpopulations (1)
- BPTF (1)
- Blood groups (1)
- COBAS Taqman (1)
- CVID (1)
- Cancer (1)
- Cancer genetics (1)
- Cancer genomics (1)
- Cardiac troponin (1)
- Cardiovascular biology (1)
- Cerebral toxoplasmosis HIV (1)
- Chemorefractory advanced gastric cancer (1)
- Children (1)
- Chronic kidney disease (1)
- Culture positive (1)
- De-isolation (1)
- Decision trees (1)
- Diagnosis (1)
- Diagnostic markers (1)
- Europe (1)
- European Society for Immunodeficiencies (ESID) (1)
- FAPI PET (1)
- FOLFIRI (1)
- Filariosis (1)
- First-line combination antiretroviral therapy (1)
- First-line regimen (1)
- Forschung (1)
- GIIb/IIIa-receptor (1)
- Genomic instability (1)
- German PID-NET registry (1)
- HCV (1)
- HIV protease inhibitors (1)
- HIV-RNA (1)
- HNO (1)
- HSP (hereditary spastic paraplegia) (1)
- Hals-Nasen-Ohren-Heilkunde (1)
- Haplotypes (1)
- Hemophilia A (1)
- Human genetics (1)
- IVDU (1)
- IgG substitution therapy (1)
- KLHL11 (1)
- Late presentation (1)
- Lehre (1)
- Loa loa (1)
- Methicillin-resistant Staphylococcus aureus (1)
- Microfilaremia (1)
- Migrant health (1)
- Molecular medicine (1)
- Mycobacteria (1)
- Mycobacterium avium complex (1)
- Myocardial infarction (1)
- N471D strumpellin knock-in mice (1)
- NTDs (1)
- NURF (1)
- Neglected tropical diseases (1)
- Nontuberculous mycobacteria (1)
- ORL (1)
- Open pulmonary tuberculosis (1)
- Otorhinolaryngology (1)
- PAC-1 (1)
- PCP (1)
- PID prevalence (1)
- Persistence SARS-CoV-2 antibodies (1)
- Phylogenetic analysis (1)
- Pneumocystis jirovecii (1)
- Pre-treatment drug resistance mutations (1)
- Protease inhibitor therapy (1)
- RealTime (1)
- Research (1)
- Residency (1)
- Respiratory infections (1)
- SARS-CoV‑2 pandemic (1)
- SARS-CoV‑2-Pandemie (1)
- SPG8 (1)
- Sensitivity (1)
- Specialist training (1)
- Specificity (1)
- Sputum smear-negative (1)
- Sunitinib (1)
- T cell response (1)
- TB-therapy (1)
- Teaching (1)
- Treatment (1)
- Treatment modification (1)
- Trees (1)
- Tyrosine kinase inhibitor (1)
- University hospitals (1)
- Universitätskliniken (1)
- VEGF (1)
- Viral load (1)
- Virological failure (1)
- WASH complex subunit 5 (1)
- Weiterbildung (1)
- animal experiments (1)
- anti-retroviral agents (1)
- autoimmunity (1)
- biomarker (1)
- blood hiv rna (1)
- booster (1)
- cART (1)
- cardiac magnetic resonance (1)
- cd4 count determination procedure (1)
- chronic kidney disease (1)
- cirrhosis (1)
- clinical immunology (1)
- cohort study (1)
- death rates (1)
- decision aids (1)
- enterobacter infections; pseudomonas aeruginosa; epidemiology (1)
- epidemiology (1)
- exponential model (1)
- fibrosis imaging (1)
- flow cytometry (1)
- guidelines (1)
- hemodialysis (1)
- hiv (1)
- human immunodeficiency virus (1)
- immunosuppression (1)
- infection (1)
- intranasal administration (1)
- leucocytes (1)
- liver transplantation (1)
- lymphocytes (1)
- mRNA-1273 (1)
- medical risk factors (1)
- mice (1)
- monoclonal antibody (1)
- mortality risk (1)
- myocardial fibrosis (1)
- neutralization (1)
- neutralizing antibody (1)
- non-ST-segment elevation acute coronary syndrome (1)
- nuclear cardiology (1)
- perinatal HIV infection (1)
- platelets (1)
- pneumocystis (1)
- pneumocystis carinii (1)
- pneumocystis pneumonia (1)
- pneumonia (1)
- prevention (1)
- primary immunodeficiency (PID) (1)
- prophylaxis (1)
- pseudomonas aeruginosa (1)
- reference values (1)
- registry for primary immunodeficiency (1)
- renal transplantation (1)
- risk factors (1)
- scar (1)
- seroconversion (1)
- strumpellin (1)
- survival (1)
- topical administration (1)
- transduction (1)
- transplantation (1)
- vaccination (1)
- virological failure (1)
- virus (1)
- young people (1)
Institute
- Medizin (44) (remove)
A 24-year-old patient from Cameroon presented to our hospital because of a foreign structure in her left eye. To our knowledge, for the first time, fluorescent microscopy revealed motile microfilariae, and the diagnosis of loiasis was established. Despite substantial microfilaremia, eosinophilia only unmasked after the initiation of antiparasitic therapy.
Highlights
• Open pulmonary tuberculosis patient discharge policy was not reviewed for decades.
• After smear-negativity conversion, substantial cultural positivity may remain.
• It remains unclear, whether smear-negative patients still may be infective.
• The clinical relevance of this finding warrants further investigation.
Abstract
Objectives: Patients with open pulmonary tuberculosis (opTB) are subject to strict isolation rules. Sputum smear microscopy is used to determine infectivity, but sensitivity is lower than for culture. This study aimed to investigate the clinical relevance of this mismatch in contemporary settings.
Methods: Differential results between microscopy and culture were determined at the time of microscopic sputum conversion, from all patients with opTB between 01/2013 and 12/2017. In addition, data on HIV, multi/extensive drug-resistant TB status, time to smear- and cultural-negativity conversion were analyzed; and a Kaplan-Meier curve was developed.
Results: Of 118 patients with opTB, 58 had demographic data available for microbiological and clinical follow-up analysis; among these, 26 (44.8%) had still at least one positive culture result. Median time from opTB-treatment initiation to full microscopic sputum- or culture conversion, was 16.5 days (range 2-105), and 20 days (1-105), respectively (median difference: +3.5 days). Sixteen days after de-isolation, >90% had converted culturally. HIV- or multi/extensive drug-resistant TB status did not impact conversion time.
Conclusion: When patients with opTB were de-isolated after 3 negative sputum smear microscopy tests, a substantial part still revealed cultural growth of Mycobacterium tuberculosis complex, but it remains unclear, whether smear-negative and culturally-positive individuals on therapy are really infective. Thus, the clinical relevance of this finding warrants further investigation.
The long-term effect of protection by two doses of SARS-CoV-2 vaccination in patients receiving chronic intermittent hemodialysis (CIHD) is an urging question. We investigated the humoral and cellular immune response of 42 CIHD patients who had received two doses of SARS-CoV-2 vaccine, and again after a booster vaccine with mRNA-1273 six months later. We measured antibody levels and SARS-CoV-2-specific surrogate neutralizing antibodies (SNA). Functional T cell immune response to vaccination was assessed by quantifying interferon-γ (IFN-γ) and IL-2 secreting T cells specific for SARS-CoV-2 using an ELISpot assay. Our data reveal a moderate immune response after the second dose of vaccination, with significantly decreasing SARS-CoV-2-specific antibody levels and less than half of the study group showed neutralizing antibodies six months afterwards. Booster vaccines increased the humoral response dramatically and led to a response rate of 89.2% for antibody levels and a response rate of 94.6% for SNA. Measurement in a no response/low response (NR/LR) subgroup of our cohort, which differed from the whole group in age and rate of immunosuppressive drugs, indicated failure of a corresponding T cell response after the booster vaccine. We strongly argue in favor of a regular testing of surrogate neutralizing antibodies and consecutive booster vaccinations for CIHD patients to provide a stronger and persistent immunity.
Despite the recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of the SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2, retains full activity against the variant of concern (VOC) B.1.1.7 and still neutralizes the VOC B.1.351, although with reduced potency. Importantly, not only systemic but also intranasal application of DZIF-10c abolished the presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology when administered prophylactically. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies.
Objectives: Rising prevalence of multidrug-resistant organisms (MDRO) is a major health problem in patients with liver cirrhosis. The impact of MDRO colonization in liver transplantation (LT) candidates and recipients on mortality has not been determined in detail.
Methods: Patients consecutively evaluated and listed for LT in a tertiary German liver transplant center from 2008 to 2018 underwent screening for MDRO colonization including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria (MDRGN), and vancomycin-resistant enterococci (VRE). MDRO colonization and infection status were obtained at LT evaluation, planned and unplanned hospitalization, three months upon graft allocation, or at last follow-up on the waiting list.
Results: In total, 351 patients were listed for LT, of whom 164 (47%) underwent LT after a median of 249 (range 0–1662) days. Incidence of MDRO colonization increased during waiting time for LT, and MRDO colonization was associated with increased mortality on the waiting list (HR = 2.57, p<0.0001. One patients was colonized with a carbapenem-resistant strain at listing, 9 patients acquired carbapenem-resistant gram-negative bacteria (CRGN) on the waiting list, and 4 more after LT. In total, 10 of these 14 patients died.
Conclusions: Colonization with MDRO is associated with increased mortality on the waiting list, but not in short-term follow-up after LT. Moreover, colonization with CRGN seems associated with high mortality in liver transplant candidates and recipients.
Background: Using data from the COHERE collaboration, we investigated whether primary prophylaxis for pneumocystis pneumonia (PcP) might be withheld in all patients on antiretroviral therapy (ART) with suppressed plasma human immunodeficiency virus (HIV) RNA (≤400 copies/mL), irrespective of CD4 count.
Methods: We implemented an established causal inference approach whereby observational data are used to emulate a randomized trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤200 cells/µL in line with existing recommendations. We compared the following 2 strategies for stopping prophylaxis: (1) when CD4 count was >200 cells/µL for >3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio (HR) to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring.
Results: A total of 4813 patients (10 324 person-years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as an endpoint, the adjusted HR (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared with the existing guidelines (aHR, .8; 95% confidence interval, .6–1.1; P = .2).
Conclusions: This study suggests that primary PcP prophylaxis might be safely withheld in confirmed virologically suppressed patients on ART, regardless of their CD4 count.
Introduction Disseminated infection due to non-tuberculous mycobacteria has been a major factor of mortality and comorbidity in HIV patients. Until 2018, U.S. American guidelines have recommended antimycobacterial prophylaxis in patients with low CD4 cell counts, a practice that has not been adopted in Europe. This study aimed at examining the impact of disseminated NTM disease on clinical outcome in German HIV patients with a severe immunodeficiency. Materials and methods In this retrospective case control study, HIV patients with disseminated NTM disease were identified by retrospective chart review and matched by their CD4 cell counts to HIV patients without NTM infection in a 1:1 alocation. Primary endpoints were mortality and time to first rehospitalisation. In addition, other opportunistic diseases, as well as antimycobacterial and antiretroviral treatments were examined. Results Between 2006 and 2016, we identified 37 HIV patients with disseminated NTM disease. Most of them were suffering from infections due to M. avium complex (n = 31, 77.5%). Time to event analysis showed a non-significant trend to higher mortality in patients with disseminated NTM disease (p = 0.24). Rehospitalisation took place significantly earlier in patients with disseminated NTM infections (median 40.5 days vs. 109 days, p<0.0001). Conclusion In this retrospective case control study, we could demonstrate that mortality is not significantly higher in HIV patients with disseminated NTM disease in the ART era, but that they require specialised medical attention in the first months following discharge.
Objectives: We explore the importance of SARS-CoV-2 sentinel surveillance testing in primary care during a regional COVID-19 outbreak in Austria.
Design: Prospective cohort study.
Setting: A single sentinel practice serving 22 829 people in the ski-resort of Schladming-Dachstein.
Participants: All 73 patients presenting with mild-to-moderate flu-like symptoms between 24 February and 03 April, 2020.
Intervention: Nasopharyngeal sampling to detect SARS-CoV-2 using real-time reverse transcriptase-quantitative PCR (RT-qPCR).
Outcome measures: We compared RT-qPCR at presentation with confirmed antibody status. We split the outbreak in two parts, by halving the period from the first to the last case, to characterise three cohorts of patients with confirmed infection: early acute (RT-qPCR reactive) in the first half; and late acute (reactive) and late convalescent (non-reactive) in the second half. For each cohort, we report the number of cases detected, the accuracy of RT-qPCR, the duration and variety of symptoms, and the number of viral clades present.
Results: Twenty-two patients were diagnosed with COVID-19 (eight early acute, seven late acute and seven late convalescent), 44 patients tested SARS-CoV-2 negative and 7 were excluded. The sensitivity of RT-qPCR was 100% among all acute cases, dropping to 68.1% when including convalescent. Test specificity was 100%. Mean duration of symptoms for each group were 2 days (range 1–4) among early acute, 4.4 days (1–7) among late acute and 8 days (2–12) among late convalescent. Confirmed infection was associated with loss of taste. Acute infection was associated with loss of taste, nausea/vomiting, breathlessness, sore throat and myalgia; but not anosmia, fever or cough. Transmission clusters of three viral clades (G, GR and L) were identified.
Conclusions: RT-qPCR testing in primary care can rapidly and accurately detect SARS-CoV-2 among people with flu-like illness in a heterogeneous viral outbreak. Targeted testing in primary care can support national sentinel surveillance of COVID-19.
Background: Antibody detection of SARS-CoV-2 requires an understanding of its variation, course, and duration.
Methods: Antibody response to SARS-CoV-2 was evaluated over 5–430 days on 828 samples across COVID-19 severity levels, for total antibody (TAb), IgG, IgA, IgM, neutralizing antibody (NAb), antibody avidity, and for receptor-binding-domain (RBD), spike (S), or nucleoprotein (N). Specificity was determined on 676 pre-pandemic samples.
Results: Sensitivity at 30–60 days post symptom onset (pso) for TAb-S/RBD, TAb-N, IgG-S, IgG-N, IgA-S, IgM-RBD, and NAb was 96.6%, 99.5%, 89.7%, 94.3%, 80.9%, 76.9% and 92.8%, respectively. Follow-up 430 days pso revealed: TAb-S/RBD increased slightly (100.0%); TAb-N decreased slightly (97.1%); IgG-S and IgA-S decreased moderately (81.4%, 65.7%); NAb remained positive (94.3%), slightly decreasing in activity after 300 days; there was correlation with IgG-S (Rs = 0.88) and IgA-S (Rs = 0.71); IgG-N decreased significantly from day 120 (15.7%); IgM-RBD dropped after 30–60 days (22.9%). High antibody avidity developed against S/RBD steadily with time in 94.3% of patients after 430 days. This correlated with persistent antibody detection depending on antibody-binding efficiency of the test design. Severe COVID-19 correlated with earlier and higher antibody response, mild COVID-19 was heterogeneous with a wide range of antibody reactivities. Specificity of the tests was ≥99%, except for IgA (96%).
Conclusion: Sensitivity of anti-SARS-CoV-2 assays was determined by test design, target antigen, antibody avidity, and COVID-19 severity. Sustained antibody detection was mainly determined by avidity progression for RBD and S. Testing by TAb and for S/RBD provided the highest sensitivity and longest detection duration of 14 months so far.