Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Clin Infect Dis ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38663013

RESUMO

BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

2.
Infection ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478255

RESUMO

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) offers several key advantages, including enhanced patient quality of life, reduced healthcare costs, and a potential reduction of nosocomial infections. It is acknowledged for its safety and effectiveness. This study provides the first systematic clinical data for Germany, where OPAT has not yet been widely adopted. The aim is to establish a foundational reference point for further research and integration of OPAT into the German healthcare system. METHODS: This prospective observational study descriptively analyses data obtained from a cohort of patients receiving OPAT. Both in- and outpatients from all medical specialties could be recruited. Patients administered the anti-infective medications themselves at home using elastomeric pumps. RESULTS: 77 patients received OPAT, with a median duration of 15 days and saving 1782 inpatient days. The most frequently treated entities were orthopaedic infections (n = 20, 26%), S. aureus bloodstream infection (n = 16, 21%) and infectious endocarditis (n = 11, 14%). The most frequently applied drugs were flucloxacillin (n = 18, 23%), penicillin G (n = 13, 17%) and ceftriaxone (n = 10; 13%). Only 5% of patients (n = 4) reported to have missed more than one outpatient dose (max. 3 per patient). Only one catheter-related adverse event required medical intervention, and there were no catheter-related infections. CONCLUSION: The study demonstrates that OPAT can be safely conducted in Germany. In preparation for its broader implementation, crucial next steps include creating medical guidelines, fostering interdisciplinary and inter-sectoral communication, as well as creating financial and structural regulations that facilitate and encourage the adoption of OPAT. TRIAL REGISTRATION NUMBER: NCT04002453.

3.
Infection ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492196

RESUMO

PURPOSE: The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. METHODS: We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. RESULTS: During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously. CONCLUSION: Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries.

4.
Nature ; 561(7724): 479-484, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30258136

RESUMO

Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg-1 of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/imunologia , Latência Viral/imunologia , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/imunologia , Fármacos Anti-HIV/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Humanizados , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/imunologia , Sítios de Ligação de Anticorpos , Anticorpos Amplamente Neutralizantes , Portador Sadio/tratamento farmacológico , Portador Sadio/imunologia , Portador Sadio/virologia , Combinação de Medicamentos , Farmacorresistência Viral , Feminino , Anticorpos Anti-HIV/administração & dosagem , Anticorpos Anti-HIV/efeitos adversos , Anticorpos Anti-HIV/imunologia , Proteína gp160 do Envelope de HIV/imunologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Estudo Historicamente Controlado , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Filogenia , Viremia/tratamento farmacológico , Viremia/imunologia , Viremia/prevenção & controle , Viremia/virologia , Ativação Viral/imunologia , Adulto Jovem
5.
HIV Med ; 24(7): 785-793, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36883641

RESUMO

OBJECTIVES: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)-based COVID-19 booster vaccination (third dose). METHODS: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT-162b2 or mRNA-1273 between October 2021 and January 2022. We assessed anti-spike receptor-binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID100 ), and T-cell response (using interferon-gamma-release-assay [IGRA]) at baseline and quarterly follow-up visits. Patients with reported COVID-19 during follow-up were excluded. Predictors of serological immune response were analyzed using multivariate regression models. RESULTS: Of 84 people living with HIV who received an mRNA-based booster vaccination, 76 were eligible for analysis. Participants were on effective antiretroviral therapy (ART) and had a median of 670 CD4+ cells/µL (interquartile range [IQR] 540-850). Following booster vaccination, median anti-spike RBD IgG increased by 705.2 binding antibody units per millilitre (BAU/mL) and median VNA titres increased by 1000 ID100 at the follow-up assessment (median 13 weeks later). Multivariate regression revealed that time since second vaccination was a predictor of stronger serological responses (p < 0.0001). No association was found for other factors, including CD4+ status, choice of mRNA vaccine, or concomitant influenza vaccination. In total, 45 patients (59%) had a reactive baseline IGRA, of whom two lost reactivity during follow-up. Of 31 patients (41%) with non-reactive baseline IGRA, 17 (55%) converted to reactive and seven (23%) remained unchanged following booster vaccination. CONCLUSIONS: People living with HIV with ≥500 CD4+ cells/µL showed favourable immune responses to mRNA-based COVID-19 booster vaccination. A longer time (up to 29 weeks) since second vaccination was associated with higher serological responses, whereas choice of mRNA vaccine or concomitant influenza vaccination had no impact.


Assuntos
COVID-19 , Infecções por HIV , Influenza Humana , Humanos , Estudos Retrospectivos , COVID-19/prevenção & controle , Vacinação , RNA Mensageiro , Imunidade , Imunoglobulina G , Anticorpos Antivirais
6.
Infection ; 51(2): 459-464, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35759174

RESUMO

PURPOSE: School closures have been used as part of lockdown strategies to contain the spread of SARS-CoV-2, adversely affecting children's health and education. To ensure the accessibility of educational institutions without exposing society to the risk of increased transmissions, it is essential to establish SARS-CoV-2 testing strategies that are child-friendly, scalable and implementable in a daily school routine. Self-sampling using non-invasive saliva swabs combined with pooled RT-qPCR testing (Lolli-Method) has been proven to be a sensitive method for the detection of SARS-CoV-2. METHODS: We conducted a pilot project in Cologne, Germany, designed to determine the feasibility of a large-scale rollout of the Lolli-Method for testing without any additional on-site medical staff in schools. Over a period of three weeks, students from 22 schools were sampled using the Lolli-Method. At the end of the project, teachers were asked to evaluate the overall acceptance of the project. RESULTS: We analyzed a total of 757 pooled RT-qPCRs obtained from 8,287 individual swabs and detected 7 SARS-CoV-2 infected individuals. The Lolli-Method was shown to be a feasible and accepted testing strategy whose application is only slightly disruptive to the daily school routine. CONCLUSION: Our observations suggest that the Lolli-Method in combination with pooled RT-qPCR can be implemented for SARS-CoV-2 surveillance in daily school routine, applicable on a large scale.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Projetos Piloto , SARS-CoV-2/genética , Teste para COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Instituições Acadêmicas
7.
Emerg Infect Dis ; 28(5): 1050-1052, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35259088

RESUMO

To determine neutralizing activity against the severe acute respiratory syndrome coronavirus 2 ancestral strain and 4 variants of concern, we tested serum from 30 persons with breakthrough infection after 2-dose vaccination. Cross-variant neutralizing activity was comparable to that after 3-dose vaccination. Shorter intervals between vaccination and breakthrough infection correlated with lower neutralizing titers.


Assuntos
COVID-19 , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , SARS-CoV-2 , Vacinação
8.
Clin Microbiol Rev ; 34(1)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33055231

RESUMO

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Doença pelo Vírus Ebola/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/farmacocinética , Monofosfato de Adenosina/farmacologia , Alanina/farmacocinética , Alanina/farmacologia , Antivirais/farmacocinética , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/patogenicidade , COVID-19 , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo/métodos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Esquema de Medicação , Ebolavirus/efeitos dos fármacos , Ebolavirus/crescimento & desenvolvimento , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/patologia , Doença pelo Vírus Ebola/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/crescimento & desenvolvimento , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Segurança do Paciente , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/crescimento & desenvolvimento , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/virologia , Análise de Sobrevida , Resultado do Tratamento
9.
Eur Respir J ; 58(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33574078

RESUMO

BACKGROUND: The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB. METHODS: Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points. RESULTS: 50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9-0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001). CONCLUSION: Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Adulto , Antituberculosos/uso terapêutico , Duração da Terapia , Humanos , Transcriptoma , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico
10.
Infection ; 49(3): 437-445, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33140838

RESUMO

BACKGROUND: With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers. METHODS: The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON®-TB Gold Plus (QFT® Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT® Plus and IP-10 levels. RESULTS: Plasma IP-10 levels were found to be significantly increased (p < 0.001) in patients with extensive disease compared to patients with limited disease (cervical lymph node TB) or healthy controls. In patients with clinically confirmed paradoxical reaction (PR), a further increase of IP-10 was noted. IFN-γ measured by the QFT® Plus test did not decrease significantly during the course of treatment. Of note, in four EPTB patients (20%) without radiographic pulmonary involvement, sputum culture was positive for Mycobacterium tuberculosis. CONCLUSION: Our data demonstrate that IP-10 may be a valuable biomarker for estimation of disease severity in EPTB and monitoring of the disease course in extensive forms. However, IP-10 may be less suitable for diagnosis and monitoring of EPTB patients with limited disease. The QFT® Plus test does not appear to be a suitable marker for therapy monitoring. Sputum should be examined in EPTB patients even in case of normal diagnostic imaging of the chest.


Assuntos
Quimiocina CXCL10/sangue , Tuberculose dos Linfonodos , Humanos , Testes de Liberação de Interferon-gama , Mycobacterium tuberculosis , Índice de Gravidade de Doença , Tuberculose dos Linfonodos/diagnóstico
11.
Infection ; 48(2): 289-293, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31900872

RESUMO

INTRODUCTION: Central nervous system (CNS) tuberculomas are a challenging manifestation of extrapulmonary tuberculosis often leading to neurological complications and post-treatment sequelae. The role of adjunctive corticosteroid treatment is not fully understood. Most guidelines on management of tuberculosis do not distinguish between tuberculous meningitis and CNS tuberculomas in terms of corticosteroid therapy. METHODS: We describe five patients with CNS tuberculomas who required intensified dexamethasone treatment for several months, in two cases up to 18 months. RESULTS: These patients were initially treated with the standard four-drug tuberculosis regimen and adjuvant dexamethasone. Neurological symptoms improved rapidly. However, multiple attempts to reduce or discontinue corticosteroids according to guideline recommendations led to clinical deterioration with generalized seizures or new CNS lesions. Thus, duration of adjunctive corticosteroid therapy was extended eventually leading to clinical cure and resolution of lesions. CONCLUSION: In contrast to tuberculous meningitis, the treatment for CNS tuberculomas appears to require a prolonged administration of corticosteroids. These findings need to be verified in controlled clinical studies.


Assuntos
Antibióticos Antituberculose/administração & dosagem , Dexametasona/administração & dosagem , Tuberculoma/tratamento farmacológico , Tuberculose do Sistema Nervoso Central/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Idoso , Terapia Combinada , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Tuberculoma/diagnóstico por imagem , Tuberculoma/patologia , Tuberculose do Sistema Nervoso Central/diagnóstico por imagem , Tuberculose do Sistema Nervoso Central/patologia
12.
Euro Surveill ; 25(21)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32489176

RESUMO

The coronavirus disease (COVID-19) pandemic has caused tremendous pressure on hospital infrastructures such as emergency rooms (ER) and outpatient departments. To avoid malfunctioning of critical services because of large numbers of potentially infected patients seeking consultation, we established a COVID-19 rapid response infrastructure (CRRI), which instantly restored ER functionality. The CRRI was also used for testing of hospital personnel, provided epidemiological data and was a highly effective response to increasing numbers of suspected COVID-19 cases.


Assuntos
Defesa Civil/organização & administração , Infecções por Coronavirus/epidemiologia , Coronavirus , Surtos de Doenças , Administração dos Cuidados ao Paciente , Pneumonia Viral/epidemiologia , Adulto , Betacoronavirus , COVID-19 , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Pandemias , Medição de Risco , SARS-CoV-2 , Centros de Atenção Terciária , Triagem
13.
Infection ; 47(1): 27-33, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30120718

RESUMO

PURPOSE: Involvement of infectious disease (ID) specialists in the care of hospitalized patients with infections through consultation services improves the quality of care and the outcome of patients. This survey aimed to describe activities and utilization of ID consultations at four German tertiary care hospitals. METHODS: A 1-month (March 2016) retrospective cross-sectional study at four university hospitals (Freiburg, Jena, Cologne and Regensburg) was performed. Only ID consultations with written documentation and bedside patient evaluation were included. Consultations were analyzed with regard to requesting departments, infections, case severity, and diagnostic and therapeutic recommendations. RESULTS: In the study period, 638 ID consultations were performed in 479 patients-corresponding to 3-4 consultations per 100 inpatient cases. Patients were characterized by a high disease complexity-the mean case mix index in patients with consultation was 10.1 compared to 1.6 for all patients. ID consultations were requested by many different specialties, with approximately half of the requests coming from surgical disciplines. ID consultations resulted in revised diagnoses in 34% of the cases, provided recommendations for additional diagnostic procedures in 66%, and for modifications of antimicrobial regimens in 70% of the cases. CONCLUSIONS: Infectious disease consultations were requested for patients with severe and complicated diseases and resulted in recommendations that highly impacted the diagnostic work-up and therapeutic management of patients. The results of this survey may help to estimate requirements for establishment of such services in Germany.


Assuntos
Doenças Transmissíveis/terapia , Hospitais Universitários , Pacientes Internados , Encaminhamento e Consulta/estatística & dados numéricos , Idoso , Controle de Doenças Transmissíveis/estatística & dados numéricos , Estudos Transversais , Feminino , Alemanha , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Especialização/estatística & dados numéricos
14.
Clin Infect Dis ; 65(3): 518-521, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28430999

RESUMO

Nontuberculous mycobacterial infections due to autoantibodies targeting interferon-γ are an emerging medical problem. However, case finding is hampered due to highly complex diagnostic procedures not available in routine laboratories. We show that QuantiFERON assays can be exploited as a simple screening tool that may facilitate adequate and timely treatment.


Assuntos
Anticorpos Neutralizantes/sangue , Autoanticorpos/sangue , Testes de Liberação de Interferon-gama/métodos , Interferon gama/imunologia , Infecções por Mycobacterium não Tuberculosas , Anticorpos Neutralizantes/imunologia , Autoanticorpos/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/imunologia , Micobactérias não Tuberculosas
16.
Infection ; 45(3): 341-347, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28303545

RESUMO

BACKGROUND: Pneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of immunocompromised individuals. A combination of trimethoprim-sulfamethoxazole is widely used for prophylaxis and treatment of PCP. Polymorphisms in the drug targets, the dihydropteroate synthase (DHPS) or the dihydrofolate reductase (DHFR) are presumably a reason for treatment failure. METHODS: We retrospectively examined the prevalence of DHPS and DHFR mutations in Pneumocystis jirovecii isolates obtained from HIV-infected and non-HIV-infected PCP patients. DHFR and DHPS genes were amplified using semi-nested PCR followed by sequencing. Obtained data were correlated with clinical findings. RESULTS: Sequencing of the DHPS gene was achieved in 81 out of 128 isolates (63%), the DHFR-gene was successfully sequenced in 96 isolates (75%). The vast majority of DHFR and DHPS sequences were either wild-type or showed synonymous single nucleotide polymorphisms. Only one sample contained a double mutation at DHPS codon 55 and codon 57 which was associated with treatment failure in some studies. No linkage of treatment failure to a DHFR or DHPS genotype was observed. In our cohort, 35 of 95 Patients (37%) were HIV-positive and 60 (63%) were HIV-negative. The overall mortality rate was 24% with a much higher rate among non-HIV patients. CONCLUSION: DHPS and DHFR mutations exist but are infrequent in our cohort. The contribution of gene polymorphisms to treatment failure needs further research. In immunocompromised HIV-negative patients PCP is associated with high mortality rates. Prophylactic treatment is warranted in this patient subset.


Assuntos
Anti-Infecciosos/farmacologia , Di-Hidropteroato Sintase/genética , Farmacorresistência Bacteriana , Proteínas Fúngicas/genética , Mutação , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/microbiologia , Tetra-Hidrofolato Desidrogenase/genética , Di-Hidropteroato Sintase/metabolismo , Feminino , Proteínas Fúngicas/metabolismo , Alemanha , Infecções por HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/efeitos dos fármacos , Estudos Retrospectivos , Análise de Sequência de DNA , Sulfametoxazol/farmacologia , Tetra-Hidrofolato Desidrogenase/metabolismo , Trimetoprima/farmacologia
17.
Pediatrics ; 153(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38596855

RESUMO

BACKGROUND AND OBJECTIVES: Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess the safety of a test-to-stay screening in daycare facilities. METHODS: 714 daycare facilities and approximately 50 000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-polymerase chain reaction (PCR) screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children after the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions. RESULTS: 219 885 Pool-PCRs and 352 305 Single-PCRs were performed. 6440 (2.93%) Pool-PCRs tested positive, and 17 208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, confidence interval 0.52-1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status. CONCLUSIONS: Our analyses provide evidence that suggest safety of the test-to-stay approach compared with quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.


Assuntos
COVID-19 , Creches , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/diagnóstico , Pré-Escolar , Alemanha/epidemiologia , Lactente , Quarentena , Criança , SARS-CoV-2 , Masculino , Teste de Ácido Nucleico para COVID-19 , Feminino , Programas de Rastreamento/métodos
19.
Viruses ; 15(7)2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37515133

RESUMO

Resistance to multiple antiretroviral drugs among people living with HIV (PLWH) can result in a high pill burden, causing toxicity and drug interactions. Thus, the goal is to simplify treatment regimens while maintaining effectiveness. However, former resistance analysis data may not be current or complete. The use of proviral DNA genotyping may assist in selecting appropriate treatment options. A retrospective study was carried out on individuals belonging to the Cologne HIV cohort with a resistance history to two or more antiretroviral (ARV) classes and on non-standard antiretroviral therapy (ART). Patients required former viral RNA and a recent proviral DNA resistance test to be available prior to the switch to ART. Potential discrepancies between resistance test results obtained through RNA and proviral DNA methods and the consequent virological and clinical outcomes following ART adjustments were analyzed. Out of 1250 patients, 35 were eligible for inclusion in this study. The median length of known HIV infection was 27 years, and the median duration of ART was 22 years. Of the 35 participants, 16 had received all five ARV classes. Based on proviral DNA genotyping results, ART was simplified in 17 patients. At the last follow-up examination after changing therapy, 15 patients had HIV RNA <50 copies/mL (median 202 days, range 21-636). The mean number of pills per day decreased from eight to three, and the median intake frequency decreased from two to one time/day (ranges 1-2). Our study supports the use of proviral DNA genotyping as a safe strategy for switching to simplified ART regimens. However, the lack of extensive research on the advantages of proviral DNA genotyping makes it challenging to fully assess its benefits in terms of treatment selection.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Provírus/genética , Estudos Retrospectivos , Genótipo , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , DNA Viral/genética , RNA Viral/genética , Carga Viral , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética
20.
Front Med (Lausanne) ; 10: 1129288, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168268

RESUMO

Background: Symptoms lasting longer than 12 weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs. Methods: Here, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors. Results: Patients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4+ and CD8+ T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3+) and IL-4 were more abundant in PCS+. Conclusion: This work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA