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1.
J Virol ; 98(4): e0191223, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38501661

RESUMEN

The corona virus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) spurred a worldwide race for the development of an efficient vaccine. Various strategies were pursued; however, the first vaccines to be licensed presented the SARS-CoV-2 spike protein either in the context of a non-replicating adenoviral vector or as an mRNA construct. While short-term efficacies have extensively been characterized, the duration of protection, the need for repeated boosting, and reasonable vaccination intervals have yet to be defined. We here describe the adaptive immune response resulting from homologous and heterologous vaccination regimen at 18 months after primary vaccination. To that extent, we monitored 176 healthcare workers, the majority of whom had recovered from previous SARS-CoV-2 infection. In summary, we find that differences depending on primary immunization continue to exist 18 months after the first vaccination and these findings hold true irrespective of previous infection with the virus. Homologous primary immunization with BNT162b2 was repeatedly shown to produce higher antibody levels and slower antibody decline, leading to more effective in vitro neutralization capacities. Likewise, cellular responses resulting from in vitro re-stimulation were more pronounced after primary immunization involving BNT162b2. In contrast, IL-2 producing memory T helper and cytotoxic T cells appeared independent from the primary vaccination regimen. Despite these differences, comparable infection rates among all vaccination groups suggest comparable real-life protection.IMPORTANCEVaccination against the severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) was shown to avert severe courses of corona virus disease 2019 (COVID-19) and to mitigate spreading of the virus. However, the duration of protection and need for repeated boosting have yet to be defined. Monitoring and comparing the immune responses resulting from various vaccine strategies are therefore important to fill knowledge gaps and prepare for future pandemics.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Inmunidad Celular , Inmunidad Humoral , ARN , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus
2.
Retina ; 43(11): 1951-1959, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37535933

RESUMEN

PURPOSE: To analyze the annual prevalence of ocular vascular occlusion in relation to COVID-19 infection and vaccination status in a prospective study. METHODS: All patients were examined for an active severe acute respiratory syndrome coronavirus 2 infection by RNA detection and for a previous infection by virus-specific antibody detection, and their vaccination status was documented. Data from pandemic year 2020 and previous years, before COVID-19 (2019, 2018, 2017), were retrospectively analyzed. RESULTS: In 2021, a total of 103 patients with the first diagnosis of ocular vascular occlusion were treated. Most frequent subdiagnoses were central retinal vein occlusion (20.4%), nonarteritic anterior ischemic optic neuropathy (18.4%), central retinal artery occlusion (13.6%), and branch retinal artery occlusion (12.6%). Thereof, only three patients (2.9%) presented with virus-specific severe acute respiratory syndrome coronavirus 2 antibodies, and none was PCR positive. Patients with preceded severe acute respiratory syndrome coronavirus 2 vaccination (59.2%) presented with comparable characteristics as unvaccinated patients with vascular occlusion regarding age, gender distribution, systemic risk factors, duration of symptoms, visual acuity, and the present subdiagnoses ( P > 0.05). The total number of cases in 2021 (103 cases) was comparable with the pandemic year 2020, at which no vaccination was available (114 cases), and to earlier years 2017, 2018, and 2019 without COVID-19 pandemic (100, 120, and 119 cases). Furthermore, we did not reveal any differences between pandemic and reference years regarding patients' characteristics ( P > 0.05). CONCLUSION: Our study did not reveal an increased annual prevalence of ocular vascular occlusions during COVID-19 pandemic years 2020 and 2021. Patients with previous COVID-19 vaccination did not present differences regarding the risk profile nor symptoms, compared with unvaccinated individuals.


Asunto(s)
COVID-19 , Oclusión de la Arteria Retiniana , Humanos , SARS-CoV-2/genética , ARN Viral/genética , COVID-19/epidemiología , COVID-19/complicaciones , Prevalencia , Estudios Prospectivos , Pandemias , Estudios Retrospectivos , Vacunas contra la COVID-19 , Oclusión de la Arteria Retiniana/diagnóstico , Oclusión de la Arteria Retiniana/epidemiología , Oclusión de la Arteria Retiniana/etiología
3.
BMC Med ; 20(1): 29, 2022 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-35042529

RESUMEN

BACKGROUND: While vaccination programs against the severe acute respiratory syndrome virus 2 (SARS-CoV-2) are globally ongoing, disparate strategies for the deployment of spike antigen show varying effectiveness. METHODS: In order to explore this phenomenon, we sought to compare the early immune responses against AZD1222 and BNT162b2. SARS-CoV-2 seronegative participants received a single dose of either vaccine and were analyzed for immune cell, effector T cell, and antibody dynamics. RESULTS: AZD1222 induced transient leukopenia and major changes among innate and adaptive subpopulations. Both vaccines induced spike protein-specific effector T cells which were dominated by type 1 helper T cell responses following AZD1222 vaccination. A significant reduction of anti-inflammatory T cells upon re-stimulation was also restricted to AZD1222 vaccinees. While IgM and IgG were the dominant isotypes elicited by AZD1222, BNT162b2 led to a significant production of IgG and IgA. CONCLUSIONS: Our results suggest that the strategy for spike protein delivery impacts on how and to what extent immune priming against the main SARS-CoV-2 antigen proceeds.


Asunto(s)
COVID-19 , ChAdOx1 nCoV-19 , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , Humanos , Inmunoglobulina A , SARS-CoV-2 , Vacunación
4.
Haematologica ; 107(4): 947-957, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35045692

RESUMEN

Vector-based SARS-CoV-2 vaccines have been associated with vaccine- induced thrombosis with thrombocytopenia syndrome (VITT/TTS), but the causative factors are still unresolved. We comprehensively analyzed the ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Johnson and Johnson) vaccines. ChAdOx1 nCoV-19 contains significant amounts of host cell protein impurities, including functionally active proteasomes, and adenoviral proteins. A much smaller amount of impurities was found in Ad26.COV2.S. Platelet factor 4 formed complexes with ChAdOx1 nCoV-19 constituents, but not with purified virions from ChAdOx1 nCoV-19 or with Ad26.COV2.S. Vascular hyperpermeability was induced by ChAdOx nCoV-19 but not by Ad26.COV2.S. These differences in impurities together with EDTAinduced capillary leakage might contribute to the higher incidence rate of VITT associated with ChAdOx1 nCoV-19 compared to Ad26.COV2.S.


Asunto(s)
COVID-19 , Vacunas , Ad26COVS1 , Vacunas contra la COVID-19/efectos adversos , ChAdOx1 nCoV-19 , Humanos , SARS-CoV-2
5.
Wien Med Wochenschr ; 172(11-12): 280-286, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34581968

RESUMEN

BACKGROUND: The influenza season 2017-2018 of the northern hemisphere was the highest since 2001 and was caused predominantly by influenza B virus. METHODS: We performed a retrospective analysis of all patients in a university hospital in northern Germany with laboratory-confirmed influenza during the winter season 2017-2018 and analyzed underlying conditions, complications, and outcome. RESULTS: A total of 272 cases of influenza were diagnosed: 70 influenza A (25.7%), 201 influenza B (73.9%), and 1 co-infection. Of 182 adults, 145 were hospitalized, 73 developed pneumonia, 11 developed myocardial infarction, two a transient ischemic attack, one a stroke, and one perimyocarditis. Eleven of the 145 hospitalized adult patients (7.6%) died, ten of them because of pneumonia. All of them had preexisting diseases. Pneumonia was associated with a mortality of 13.7%. Underlying cardiac insufficiency was correlated with higher mortality (7/51 with versus 4/126 patients without cardiac insufficiency; p < 0.05). Ninety cases of influenza were diagnosed in 89 children (30 A, 60 B), one child had first influenza B, then influenza A. Twenty-eight children (31%) were hospitalized, 15 children developed one or more complications (lower respiratory tract infections, meningeal irritations, febrile seizures, otitis media, myositis). No child died. Influenza vaccination status was known in 149 adult patients, pneumonia occurred more frequently in non-vaccinated individuals (43/90; 47.8%) than in vaccinated patients (18/59; 30.5%, p < 0.05). CONCLUSION: Patients with influenza should be monitored for secondary pneumonia and myocardial infarction, and vaccination should be enforced especially in patients with coronary heart disease and cardiac insufficiency.


Asunto(s)
Insuficiencia Cardíaca , Gripe Humana , Infarto del Miocardio , Neumonía , Adulto , Niño , Hospitalización , Hospitales Universitarios , Humanos , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Neumonía/complicaciones , Neumonía/epidemiología , Estudios Retrospectivos , Estaciones del Año
6.
Parasitol Res ; 120(1): 209-221, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33263166

RESUMEN

Schistosomiasis is one of the most devastating parasitic disease in the world. Schistosoma spp. survive for decades within the vasculature of their human hosts. They have evolved a vast array of mechanisms to avoid the immune reaction of the host. Due to their sexual dimorphism, with the female worm lying within the gynecophoric canal of the male worm, it is the male that is exposed to the immediate environment and the soluble parts of the host's immune response. To understand how the worms are so successful in fending off the immune attacks of the host, comparative analyses of both worm sexes in human serum (with or without Praziquantel) were performed using scanning electron microscopy, transmission electron microscopy, and immunohistochemistry. Further, gene expression analyses of tegument-specific genes were performed. Following the incubation in human serum, males and females out of pairs show morphological changes such as an altered structure of the pits below the surface and an increased number of pits per area. In addition, female schistosomes presented a marked tuft-like repulsion of their opsonized surface. The observed resistance of females to Praziquantel seemed to depend on active proteins in the human serum. Moreover, different expression profiles of tegument-specific genes indicate different functions of female_single and male_single teguments in response to human serum. Our results indicate that female schistosomes developed different evasion strategies toward the host's immune system in comparison to males that might lead to more robustness and has to be taken into account for the development of new anti-schistosomal drugs.


Asunto(s)
Antihelmínticos/farmacología , Proteínas del Helminto/metabolismo , Praziquantel/farmacología , Schistosoma/efectos de los fármacos , Suero/fisiología , Animales , Resistencia a Medicamentos , Femenino , Proteínas del Helminto/genética , Humanos , Evasión Inmune , Masculino , Schistosoma/metabolismo , Schistosoma/ultraestructura , Factores Sexuales
7.
Gesundheitswesen ; 83(11): 890-893, 2021 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-34571553

RESUMEN

BACKGROUND: The current risk of infection with SARS-CoV-2 in schools continues to be a subject of controversy. METHODOLOGY: "schugi-MV" collects data on the incidence of infection, hygiene management and other factors in structured inspections of schools in Mecklenburg-Western Pomerania. Recommendations for safe teaching are to be derived from the results. This article presents information on the first 10 schools visited between 18.12.2020 and 20.01.2021. RESULTS: At the schools visited, the ratio of the number of index cases among adults and children was 1:1.25. The inspections showed a great heterogeneity of schools and school buildings and the resulting possibilities for implementing infection control measures. CONCLUSION: Based on the present preliminary results, hygiene and infection control measures at schools in Mecklenburg-Western Pomerania cannot be standardised, but should leave room for design.


Asunto(s)
COVID-19 , Adulto , Niño , Alemania/epidemiología , Humanos , Pandemias/prevención & control , SARS-CoV-2 , Instituciones Académicas
8.
Lancet ; 392(10165): 2718-2727, 2019 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-30409443

RESUMEN

BACKGROUND: Chikungunya fever is an emerging viral disease and substantial threat to public health. We aimed to assess the safety, tolerability, and immunogenicity of a live-attenuated, measles-vectored chikungunya vaccine (MV-CHIK). METHODS: In this double-blind, randomised, placebo-controlled and active-controlled phase 2 trial, we enrolled healthy volunteers aged 18-55 years at four study sites in Austria and Germany. Participants were randomly assigned to receive intramuscular injections with MV-CHIK (5 × 104 or 5 × 105 50% tissue culture infectious dose), control vaccine, or measles prime and MV-CHIK, in two different administration regimens. Randomisation was done by use of three-digit randomisation codes in envelopes provided by a data management service. The participants and investigators were masked to treatment assignment, which was maintained by use of sterile saline as a placebo injection. The primary endpoint was immunogenicity, defined as the presence of neutralising antibodies against chikungunya virus, at day 56, which is 28 days after one or two immunisations. The primary endpoint was assessed in all participants who completed the study without major protocol deviations (per-protocol population) and in all randomised participants who received at least one study treatment (modified intention-to-treat population). The safety analysis included all participants who received at least one study treatment. This trial is registered with ClinicalTrials.gov (NCT02861586) and EudraCT (2015-004037-26) and is completed. FINDINGS: Between Aug 17, 2016, and May 31, 2017, we randomly assigned 263 participants to receive control vaccine (n=34), MV-CHIK (n=195), or measles prime and MV-CHIK (n=34). 247 participants were included in the per-protocol population. Neutralising antibodies against chikungunya virus were detected in all MV-CHIK treatment groups after one or two immunisations, with geometric mean titres ranging from 12·87 (95% CI 8·75-18·93) to 174·80 (119·10-256·50) and seroconversion rates ranging from 50·0% to 95·9% depending on the dose and administration schedule. Adverse events were similar between groups, with solicited adverse events reported in 168 (73%) of 229 participants assigned to MV-CHIK and 24 (71%) of 34 assigned to control vaccine (p=0·84) and unsolicited adverse events in 116 (51%) participants assigned to MV-CHIK and 17 (50%) assigned to control vaccine (p=1·00). No serious adverse events related to the vaccine were reported. INTERPRETATION: MV-CHIK showed excellent safety and tolerability and good immunogenicity, independent of pre-existing immunity against the vector. MV-CHIK is a promising candidate vaccine for the prevention of chikungunya fever, an emerging disease of global concern. FUNDING: Themis.


Asunto(s)
Fiebre Chikungunya/prevención & control , Virus Chikungunya/inmunología , Vacunas Virales/inmunología , Adolescente , Adulto , Anticuerpos Antivirales/biosíntesis , Anticuerpos Antivirales/sangre , Relación Dosis-Respuesta Inmunológica , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Masculino , Vacuna Antisarampión/administración & dosificación , Vacuna Antisarampión/efectos adversos , Vacuna Antisarampión/inmunología , Virus del Sarampión/inmunología , Persona de Mediana Edad , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/efectos adversos , Adulto Joven
9.
Radiologe ; 60(10): 893-898, 2020 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-32865603

RESUMEN

Until July 31, 2020, about 17.6 million SARS-CoV­2 infections and 680,000 deaths from COVID-19 were reported. SARS-CoV­2 is most likely transmitted by droplets and probably by aerosols. Patients become infectious 2-3 days before the onset of symptoms, and persons with asymptomatic infections are also infectious. COVID-19 affects the upper respiratory tract, lungs (pneumonia, acute respiratory distress syndrome [ARDS]), heart, liver, gastrointestinal tract, and other organs. SARS-CoV­2 uses ACE2 a receptor to enter host cells. Vasculitis, endothelial damage, thromboembolic events and organ failure are accompanied by a massive cytokine response. Elderly people and those with pre-existing diseases are particularly vulnerable. An efficient antiviral therapy is not yet available. Severely ill patients may benefit from dexamethasone and early treatment of complications. Candidate vaccines are currently being tested in clinical studies.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , COVID-19 , Infecciones por Coronavirus/epidemiología , Humanos , Neumonía Viral/epidemiología , SARS-CoV-2
10.
Emerg Infect Dis ; 25(2): 321-324, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30666932

RESUMEN

During 2013-2016, a total of 32 patients were treated for Crimean-Congo hemorrhagic fever in Prishtina, Kosovo; 11 died. In the 11 patients who died, findings included viral loads >1 × 108.5/mL, lactate dehydrogenase >2,700 U/mL, bleeding, and impaired consciousness. Ribavirin therapy had no noticeable effect in this small patient sample.


Asunto(s)
Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea/epidemiología , Fiebre Hemorrágica de Crimea/virología , Adolescente , Adulto , Anciano , Biomarcadores , Niño , Preescolar , Femenino , Geografía , Fiebre Hemorrágica de Crimea/historia , Historia del Siglo XXI , Humanos , Lactante , Recién Nacido , Kosovo/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Carga Viral , Adulto Joven
11.
Infection ; 47(1): 105-109, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30298473

RESUMEN

Vaccination is an essential tool in reducing the impact of seasonal influenza infections. The viral strains responsible for seasonal outbreaks vary annually, and preventive vaccines have to be adapted accordingly. The aim of this study was to evaluate the safety, clinical tolerability and the antibody response to each of the three influenza vaccine antigens after vaccination with a cell-derived, trivalent, surface antigen, inactivated influenza vaccine (TIVc), as measured by single radial haemolysis (SRH) or haemagglutination inhibition (HI) assay in accordance with European Union licensing guidelines in place for years 2013/2014. This phase 3, open-label, single-arm study enrolled 126 healthy adults divided into two age groups (63 subjects aged 18 to ≤ 60 years and 63 subjects aged ≥ 61 years). Antibody titres were measured before and 21 days after vaccination. Adverse events were determined using diary cards, interviews and reviews of the available medical records. One subject was lost to follow-up and three subjects had protocol deviations. Following vaccination, protective HI antibody titres (≥ 1:40) were detected in 100%, 97%, and 94% of the younger adults (18-≤ 60 years) and in 97%, 95%, and 80% of the older adults (≥ 61 years) against the A (H1N1), A (H3N2), and B influenza strains respectively. The antibody response licensing criteria were met in both age groups. Solicited adverse events were reported by 57% subjects 18 to ≤ 60 years and 35% subjects ≥ 61 years. Among the younger adults 51% had local and 27% had systemic adverse events, whereas of the older subjects 29% had local and 13% had systemic adverse events (mainly injection site pain or headache in both age groups). Unsolicited adverse events at least possibly related to the vaccine were mild and detected in 3% of the younger adults and none of the older adults. Overall, the trivalent, surface antigen, inactivated subunit influenza virus vaccine produced in mammalian cell culture proved to be safe and immunogenic in younger and older healthy adults.


Asunto(s)
Antígenos Virales/inmunología , Inmunogenicidad Vacunal/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Adulto , Anciano , Femenino , Alemania , Pruebas de Inhibición de Hemaglutinación , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
12.
Infection ; 47(1): 129-133, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30259307

RESUMEN

A 22-year-old HIV-negative man from Ghana was diagnosed with severe hemophagocytic lymphohistiocytosis (HLH) induced by multiorgan tuberculosis with peritoneal, hepatic, pericardial, myocardial, pleural, pulmonary, and bone manifestation. His body mass index was 12.9 m2/kg. Bioptic material of a peritoneal biopsy grew M. tuberculosis, sensitive to all first-line antituberculous drugs. HLH resolved with antituberculous therapy, without additional anti-inflammatory therapy being given. The initial CT scan of his brain was normal. After 5 months of antituberculous treatment, he developed a paralysis of the left arm. A cerebral MRT showed ring-enhanced lesions. Blood cultures and lumbar puncture revealed Cryptococcus neoformans var. grubi. The HIV test was repeatedly negative. Antituberculous treatment was continued for a total of 9 months, and additional treatment with antifungal therapy was established. He recovered fully after 14 months of antifungal treatment.


Asunto(s)
Criptococosis/diagnóstico , Cryptococcus neoformans/aislamiento & purificación , Síndrome Inflamatorio de Reconstitución Inmune/diagnóstico , Linfohistiocitosis Hemofagocítica/diagnóstico , Tuberculosis/complicaciones , Antifúngicos/administración & dosificación , Antituberculosos/administración & dosificación , Encéfalo/diagnóstico por imagen , Encéfalo/microbiología , Encéfalo/patología , Criptococosis/diagnóstico por imagen , Criptococosis/tratamiento farmacológico , Criptococosis/microbiología , Alemania , Ghana/etnología , Seronegatividad para VIH , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/diagnóstico por imagen , Síndrome Inflamatorio de Reconstitución Inmune/microbiología , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/microbiología , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/tratamiento farmacológico , Adulto Joven
13.
Retina ; 44(9): e59-e60, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39167586

Asunto(s)
Humanos
14.
Rheumatol Int ; 39(2): 345-351, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30607506

RESUMEN

This report presents a case of co-occurrence of Takayasu arteritis (TA) and multiorgan tuberculosis (TB) in a 20-year-old female and provides a review of 18 previously reported cases of co-occurring TA and TB. All patients were between 9 and 24 years of age. Most reports describe a concomitant diagnosis of active TB and TA. TB lymphadenitis was described in 11 cases (57.9%), and microbiologically confirmed in 4 of these. All patients received antituberculous therapy and most received corticosteroids (89.5%). In our and two other cases, TA relapses necessitating additional immunosuppressive therapy were observed.


Asunto(s)
Arteritis de Takayasu/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Adulto , Antituberculosos/uso terapéutico , Femenino , Humanos , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/diagnóstico por imagen , Tuberculosis/complicaciones , Tuberculosis/diagnóstico por imagen
16.
J Hepatol ; 62(4): 871-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25463533

RESUMEN

BACKGROUND & AIMS: Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects of 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-) mice with cholestatic liver injury and biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven liver fibrosis in S. mansoni infection. METHODS: Adult NMRI mice were infected with 50 S. mansoni cercariae and after 12 weeks received either norUDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4 weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of norUDCA on primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro. RESULTS: UDCA as well as norUDCA attenuated the inflammatory response in livers of S. mansoni infected mice, but exclusively norUDCA changed cellular composition and reduced size of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo. Moreover, norUDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro, whereas UDCA had no effect. CONCLUSIONS: This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of norUDCA compared to UDCA in S. mansoni induced liver injury, and indicates that norUDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro. Therefore, norUDCA represents a promising drug for the treatment of this important cause of liver fibrosis.


Asunto(s)
Granuloma , Cirrosis Hepática , Esquistosomiasis mansoni , Ácido Ursodesoxicólico/análogos & derivados , Animales , Colagogos y Coleréticos/metabolismo , Colagogos y Coleréticos/farmacología , Modelos Animales de Enfermedad , Monitoreo de Drogas , Granuloma/tratamiento farmacológico , Granuloma/inmunología , Granuloma/patología , Inmunohistoquímica , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Cirrosis Hepática/inmunología , Cirrosis Hepática/patología , Cirrosis Hepática/fisiopatología , Activación de Linfocitos/efectos de los fármacos , Ratones , Esquistosomiasis mansoni/complicaciones , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/patología , Esquistosomiasis mansoni/fisiopatología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Resultado del Tratamiento , Ácido Ursodesoxicólico/metabolismo , Ácido Ursodesoxicólico/farmacología
17.
Dtsch Med Wochenschr ; 149(8): 454-457, 2024 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-38565119

RESUMEN

HISTORY: A 42-year-old female presented with a two-day history of vomiting, diarrhea, fever and chills. Two weeks before she had returned to Germany from a Safari in Tanzania. She had disregarded the recommendation to take antimalarial chemoprophylaxis. CLINICAL FINDINGS AND DIAGNOSIS: The thin blood film showed Plasmodium falciparum-parasitized erythrocytes, and Plasmodium falciparum malaria was diagnosed. The full blood count showed thrombocytopenia and ultrasound imaging revealed splenomegaly. Initially the criteria for complicated malaria were not fulfilled. THERAPY AND COURSE: We started oral therapy with atovaquone/proguanil. The patient vomited the tablets twice. Therefore therapy was switched to intravenous artesunate. Subsequently, parasitemia dropped from 2.8 to 1.0 % within 22 hours. After 3 days of artesunate i. v., treatment could then be completed with oral atovaquone/proguanil, and the symptoms resolved. CONCLUSIONS: Patients with malaria and persistent vomiting should be treated intravenously and monitored closely, as severe gastrointestinal symptoms may reflect impending organ failure. We therefore propose including persistent vomiting in the list of criteria for complicated malaria.


Asunto(s)
Antimaláricos , Malaria Falciparum , Malaria , Femenino , Humanos , Adulto , Proguanil/uso terapéutico , Atovacuona/uso terapéutico , Artesunato/uso terapéutico , Antimaláricos/uso terapéutico , Malaria/tratamiento farmacológico , Malaria Falciparum/complicaciones , Malaria Falciparum/diagnóstico , Malaria Falciparum/tratamiento farmacológico , Combinación de Medicamentos , Vómitos/etiología
18.
Front Immunol ; 15: 1359475, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562927

RESUMEN

Background: After licensing of the protein-based vaccine NVX-CoV2373, three technically different vaccines against the SARS-CoV-2 became available for application to the human population - and for comparison of efficacies. Methods: We here recruited 42 study participants who had obtained one initial dose of NVX-CoV2373 and analyzed their immune responses in contrast to 37 study participants who had obtained either the vector vaccine AZD1222 or the mRNA vaccine BNT162b2 a year earlier. 32 participants also donated blood before first vaccination to serve as a vaccine-naive control. In detail, we investigated and quantified at day 21 and approximately six months after primary immunization the amounts of vaccine-specific antibodies produced, their neutralization capacity, their quality in terms of binding different epitopes and their efficiency in inducing various isotypes. Cellular immunity and intracellular cytokine production following in vitro re-stimulation with BNT162b2 vaccine was analyzed via ELISpot or via flow cytometry. Results: Our results show that even though vaccination including the mRNA vaccine yielded best results in almost any aspect of antibody levels and binding efficiency, the neutralization capacities against the wild-type Wuhan strain and the Omicron BA.1 variant early and at six months were comparable among all three vaccination groups. As for the T cells, we observed a prevailing CD8 response at three weeks which turned into a predominant CD4 memory at six months which has not yet been observed for AZD1222 and BNT162b2. While additional infection with SARS-CoV-2 resulted in a boost for the humoral response, T cell memory appeared rather unaffected. Conclusion: Whether any of these differences translate into real world protection from infection, mitigation of severe disease courses and prevention of long/post COVID will need to be investigated in the future.


Asunto(s)
Vacuna BNT162 , Vacunas contra la COVID-19 , Vacunas de ARNm , Humanos , ChAdOx1 nCoV-19 , Inmunidad Celular , ARN Mensajero/genética
19.
Vaccines (Basel) ; 12(5)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38793732

RESUMEN

Influenza pandemics pose a serious risk to the global population, with the potential for high morbidity and mortality. An adjuvanted H5N1 vaccine (aH5N1) has been approved for prophylaxis against the avian influenza virus H5N1, which is a likely cause of future pandemics. In this phase-III, stratified, randomized, controlled, observer-blind, multicenter study, we evaluated the safety and immunogenicity of aH5N1 in four separate groups of adults: adults 18-60 years of age who were healthy or had high-risk medical conditions and older adults ≥61 years of age who were healthy or had high-risk medical conditions. Subjects were randomly assigned to aH5N1 or the comparator, adjuvanted trivalent seasonal influenza vaccine (aTIV). Antibody responses to aH5N1 were increased in all four subgroups and, within each age stratum, largely consistent between healthy subjects and those with medical conditions. Injection-site pain was reported by 66-73% of younger and 36-42% of older-aH5N1 recipients, and fatigue and myalgia were reported by 22-41% of subjects across age and health subgroups. No serious adverse events or deaths were considered related to the study vaccine. In conclusion, aH5N1 increased antibody responses regardless of age or health status and demonstrated a clinically acceptable safety and tolerability profile.

20.
Front Bioeng Biotechnol ; 12: 1367366, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737540

RESUMEN

Introduction: The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable. Methods: In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6 h) and long-term (10 days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6 h and 10 days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10 days. Results: The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6 h, but it markedly diminished after 10 days. After 10 days, capsule formations were observed around the materials without visible inflammatory cells. Discussion: For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry.

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