Infectious diseases result from the interactions of host, pathogens, and, in the case of vector-borne diseases, also vec- tors. The interactions involve physiological and ecological mechanisms and they have evolved un...Infectious diseases result from the interactions of host, pathogens, and, in the case of vector-borne diseases, also vec- tors. The interactions involve physiological and ecological mechanisms and they have evolved under a given set of environmental conditions. Environmental change, therefore, will alter host-pathogen-vector interactions and, consequently, the distribution, in- tensity, and dynamics of infectious diseases. Here, we review how climate change may impact infectious diseases of aquatic and terrestrial wildlife. Climate change can have direct impacts on distribution, life cycle, and physiological status of hosts, pathogens and vectors. While a change in either host, pathogen or vector does not necessarily translate into an alteration of the disease, it is the impact of climate change on the interactions between the disease components which is particularly critical for altered disease risks. Finally, climate factors can modulate disease through modifying the ecological networks host-pathogen-vector systems are belonging to, and climate change can combine with other environmental stressors to induce cumulative effects on infectious dis- eases. Overall, the influence of climate change on infectious diseases involves different mechanisms, it can be modulated by phenotypic acclimation and/or genotypic adaptation, it depends on the ecological context of the host-pathogen-vector interactions, and it can be modulated by impacts of other stressors. As a consequence of this complexity, non-linear responses of disease sys- tems under climate change are to be expected. To improve predictions on climate change impacts on infectious disease, we sug- gest that more emphasis should be given to the integration of biomedical and ecological research for studying both the physio- logical and ecological mechanisms which mediate climate change impacts on disease, and to the development of harmonized methods and approaches to obtain more comparable results, as this would support the discrimination of case-specific versus gen- eral mechanisms .展开更多
Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent orunregulated proinflammatory cytokine responses are associated with severe disease outcomes. ...Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent orunregulated proinflammatory cytokine responses are associated with severe disease outcomes. Previous work suggested thatmonocyte-derived macrophages (MDMs) are resistant and unresponsive to SARS-CoV-2 infection. Here, we demonstrate that uponphagocytosis of SARS-CoV-2-infected cells, MDMs are activated and secrete IL-6 and TNF. Importantly, activated MDMs in turnmediate strong activation of plasmacytoid dendritic cells (pDCs), leading to the secretion of high levels of IFN-α and TNF.Furthermore, pDC activation promoted IL-6 production by MDMs. This kind of pDC activation was dependent on direct integrinmediated cell‒cell contacts and involved stimulation of the TLR7 and STING signaling pathways. Overall, the present studydescribes a novel and potent pathway of pDC activation that is linked to the macrophage-mediated clearance of infected cells.These findings suggest that a high infection rate by SARS-CoV-2 may lead to exaggerated cytokine responses, which maycontribute to tissue damage and severe disease.展开更多
Background:Fasciola hepatica is a foodborne trematode present worldwide.Definitive hosts are mostly ruminants such as cattle and sheep,as well as humans.In Switzerland,Fasciola infection in humans is rare.Unfortunatel...Background:Fasciola hepatica is a foodborne trematode present worldwide.Definitive hosts are mostly ruminants such as cattle and sheep,as well as humans.In Switzerland,Fasciola infection in humans is rare.Unfortunately,many patients are likely to undergo multiple unnecessary investigations before the parasite is suspected and fascioliasis diagnosed,especially if symptoms are unspecific.Methods:Retrospective analysis of all patients diagnosed with Fasciola hepatica at the University Hospital of Bern between 2005 and 2018.Diagnosis was positive if a positive serology and/or eggs in stool samples correlated with clinical presentation(symptoms and/or imaging).Patients were excluded if serology was weakly positive and another diagnosis more likely.Personal data,laboratory results,imaging,proposed treatment and outcome were collected from patient files.Results:Sixty patients had a positive serology during this time period.Forty-seven of them had a more plausible alternative diagnosis and were not included in the study,leaving 13 patients for analyses;46.2%(6/13)were male,mean age was 45.8 years old(range,17-80 years old).Four patients(4/13,30.8%)were asymptomatic,nine(9/13,69.2%)presented with symptoms ranging from right upper quadrant abdominal pain(44.4%)and generalized pruritus(33.3%)to weight loss and night sweats(33.3%).The mean duration of symptoms until correct diagnosis was 8.9 months(range,1-48 months).Five patients(5/13,38.5%)had documented eosinophilia,four(4/13,30.8%)elevated liver enzymes and seven(7/13,53.8%)elevated cholestasis parameters.Mean antibody level on serology was 88 AU/mL(range,3-134 AU/mL).Ultrasound was used most frequently(7/13,53.8%),followed by magnetic resonance imaging(4/13,30.8%),computed tomography and endoscopic retrograde cholangiopancreatography(3/13,23.1%).The most common findings were bile duct dilatation,followed by hepatic lesions.Treatment consisted of Triclabendazole 10 mg/Kg.One patient needed a second treatment course for persistent disease.There were no recurrences.Conclusions:With a low incidence of Fasciola hepatica in Switzerland,correct diagnosis is often substantially delayed.Raising awareness among Swiss physicians is paramount,and a higher level of suspicion necessary when confronted with unspecific symptoms or liver imaging,thus avoiding a long delay in diagnosis,as well as unnecessary tests.展开更多
In a recent study published in Science,Koenig et al.1 reported on rationally engineered biparatopic nanobodies targeting the receptor-binding domain(RBD)of the spike protein that not only efficiently neutralize SARS-C...In a recent study published in Science,Koenig et al.1 reported on rationally engineered biparatopic nanobodies targeting the receptor-binding domain(RBD)of the spike protein that not only efficiently neutralize SARS-CoV-2,but additionally suppress mutational escape.Population growth,increased travel and climate change foster epidemic and pandemic threats by(re)emerging viruses.展开更多
文摘Infectious diseases result from the interactions of host, pathogens, and, in the case of vector-borne diseases, also vec- tors. The interactions involve physiological and ecological mechanisms and they have evolved under a given set of environmental conditions. Environmental change, therefore, will alter host-pathogen-vector interactions and, consequently, the distribution, in- tensity, and dynamics of infectious diseases. Here, we review how climate change may impact infectious diseases of aquatic and terrestrial wildlife. Climate change can have direct impacts on distribution, life cycle, and physiological status of hosts, pathogens and vectors. While a change in either host, pathogen or vector does not necessarily translate into an alteration of the disease, it is the impact of climate change on the interactions between the disease components which is particularly critical for altered disease risks. Finally, climate factors can modulate disease through modifying the ecological networks host-pathogen-vector systems are belonging to, and climate change can combine with other environmental stressors to induce cumulative effects on infectious dis- eases. Overall, the influence of climate change on infectious diseases involves different mechanisms, it can be modulated by phenotypic acclimation and/or genotypic adaptation, it depends on the ecological context of the host-pathogen-vector interactions, and it can be modulated by impacts of other stressors. As a consequence of this complexity, non-linear responses of disease sys- tems under climate change are to be expected. To improve predictions on climate change impacts on infectious disease, we sug- gest that more emphasis should be given to the integration of biomedical and ecological research for studying both the physio- logical and ecological mechanisms which mediate climate change impacts on disease, and to the development of harmonized methods and approaches to obtain more comparable results, as this would support the discrimination of case-specific versus gen- eral mechanisms .
文摘Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent orunregulated proinflammatory cytokine responses are associated with severe disease outcomes. Previous work suggested thatmonocyte-derived macrophages (MDMs) are resistant and unresponsive to SARS-CoV-2 infection. Here, we demonstrate that uponphagocytosis of SARS-CoV-2-infected cells, MDMs are activated and secrete IL-6 and TNF. Importantly, activated MDMs in turnmediate strong activation of plasmacytoid dendritic cells (pDCs), leading to the secretion of high levels of IFN-α and TNF.Furthermore, pDC activation promoted IL-6 production by MDMs. This kind of pDC activation was dependent on direct integrinmediated cell‒cell contacts and involved stimulation of the TLR7 and STING signaling pathways. Overall, the present studydescribes a novel and potent pathway of pDC activation that is linked to the macrophage-mediated clearance of infected cells.These findings suggest that a high infection rate by SARS-CoV-2 may lead to exaggerated cytokine responses, which maycontribute to tissue damage and severe disease.
文摘Background:Fasciola hepatica is a foodborne trematode present worldwide.Definitive hosts are mostly ruminants such as cattle and sheep,as well as humans.In Switzerland,Fasciola infection in humans is rare.Unfortunately,many patients are likely to undergo multiple unnecessary investigations before the parasite is suspected and fascioliasis diagnosed,especially if symptoms are unspecific.Methods:Retrospective analysis of all patients diagnosed with Fasciola hepatica at the University Hospital of Bern between 2005 and 2018.Diagnosis was positive if a positive serology and/or eggs in stool samples correlated with clinical presentation(symptoms and/or imaging).Patients were excluded if serology was weakly positive and another diagnosis more likely.Personal data,laboratory results,imaging,proposed treatment and outcome were collected from patient files.Results:Sixty patients had a positive serology during this time period.Forty-seven of them had a more plausible alternative diagnosis and were not included in the study,leaving 13 patients for analyses;46.2%(6/13)were male,mean age was 45.8 years old(range,17-80 years old).Four patients(4/13,30.8%)were asymptomatic,nine(9/13,69.2%)presented with symptoms ranging from right upper quadrant abdominal pain(44.4%)and generalized pruritus(33.3%)to weight loss and night sweats(33.3%).The mean duration of symptoms until correct diagnosis was 8.9 months(range,1-48 months).Five patients(5/13,38.5%)had documented eosinophilia,four(4/13,30.8%)elevated liver enzymes and seven(7/13,53.8%)elevated cholestasis parameters.Mean antibody level on serology was 88 AU/mL(range,3-134 AU/mL).Ultrasound was used most frequently(7/13,53.8%),followed by magnetic resonance imaging(4/13,30.8%),computed tomography and endoscopic retrograde cholangiopancreatography(3/13,23.1%).The most common findings were bile duct dilatation,followed by hepatic lesions.Treatment consisted of Triclabendazole 10 mg/Kg.One patient needed a second treatment course for persistent disease.There were no recurrences.Conclusions:With a low incidence of Fasciola hepatica in Switzerland,correct diagnosis is often substantially delayed.Raising awareness among Swiss physicians is paramount,and a higher level of suspicion necessary when confronted with unspecific symptoms or liver imaging,thus avoiding a long delay in diagnosis,as well as unnecessary tests.
文摘In a recent study published in Science,Koenig et al.1 reported on rationally engineered biparatopic nanobodies targeting the receptor-binding domain(RBD)of the spike protein that not only efficiently neutralize SARS-CoV-2,but additionally suppress mutational escape.Population growth,increased travel and climate change foster epidemic and pandemic threats by(re)emerging viruses.
