Hemorrhagic Pneumonia Research Articles

PMCNA_RS00975 activates NF-κB and ERK1/2 through TLR2 and contributes to the virulence of Pasteurella multocida.

Pasteurella multocida is a pathogenic bacterium known to cause hemorrhagic septicemia and pneumonia in poultry. Reports have indicated that certain proteins, either directly involved in or regulating iron metabolism, are important virulence factors of P. multocida. Therefore, understanding virulent factors and analyzing the role of pro-inflammatory cytokines can help us elucidate the underlying pathogenesis. In this study, the PMCNA_RS00975 protein, a putative encapsuling protein encoded by a gene from a specific prophage island of the pathogenic strain C48-1 of P. multocida, was investigated. To further explore the impact of the PMCNA_RS00975 protein on pathogenicity, a PMCNA_RS00975 gene mutant of P. multocida strain C48-1 was constructed using positive selection technology. Subcellular localization was performed to determine the location of the PMCNA_RS00975 protein within P. multocida. The recombinant protein PMCNA_RS00975 of P. multocida was soluble expressed, purified, and its role in pro-inflammatory cytokines was investigated. The mutant exhibited significantly reduced pathogenicity in the mice model. Furthermore, subcellular localization indicated that the PMCNA_RS00975 protein was located at the outer membrane and expressed during infection of P. multocida. Additionally, our experiments revealed that recombinant PMCNA_RS00975 protein promotes the secretion of the IL-6 pro-inflammatory cytokines triggered by the TLR2 receptor via NF-κB and ERK1/2 signaling pathways in the macrophages. This study identified a novel virulence factor in the C48-1 strain, providing a basis for understanding the pathogenesis and directions for the development of attenuated vaccines against P. multocida.

Streptococcus zooepidemicus in dogs: Exploring a canine pathogen through multilocus sequence typing

Streptococcus equi. subsp. zooepidemicus (S. zooepidemicus) associated diseases in dogs have emerged as a significant concern over recent decades. S. zooepidemicus occurs sporadically in dog populations globally, with increased prevalence in shelters/kennels. This study used multilocus sequence typing (MLST) of 149 independent canine S. zooepidemicus isolates to assess associations between sequence type and breed, country of origin, disease severity, sampling type, year, and behaviour within an outbreak. No clear associations for breed, country, sampling type and year were determined in this study. ST-10 and 123 strains were present within all disease categories, from no clinical signs to severe disease. Assessment of S. zooepidemicus infection in 3 UK outbreaks at the same location found ST-10, 18, 123 strains, and a ST-173 strain in a US outbreak, were associated with haemorrhagic pneumonia and persisted in kennelled populations over time. The ST-173 clonal complex has been noted to have severe virulence capabilities in dogs and other species. S. zooepidemicus seems to thrive in environments with a high risk of transmissibility, overcrowding, stress and naïve populations, particularly for those in shelters/kennels. MLST alone cannot determine the virulence phenotype of S. zooepidemicus in dogs. However, a level of conservancy and diversity within ST allelic loci aids the opportunity to cause severe disease in dogs. Thus, further research into whole genome sequencing and characterising the virulence factors of S. zooepidemicus is warranted in dogs.

Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets

Measles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of pre-existing immune memory by measles virus (MeV), a paramyxovirus of the morbillivirus genus. Therapeutic measles vaccination lacks efficacy, but little is known about preserving immune memory through antivirals and the effect of respiratory disease history on measles severity. We use a canine distemper virus (CDV)-ferret model as surrogate for measles and employ an orally efficacious paramyxovirus polymerase inhibitor to address these questions. A receptor tropism-intact recombinant CDV with low lethality reveals an 8-day advantage of antiviral treatment versus therapeutic vaccination in maintaining immune memory. Infection of female ferrets with influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks pre-CDV causes fatal hemorrhagic pneumonia with lung onslaught by commensal bacteria. RNAseq identifies CDV-induced overexpression of trefoil factor (TFF) peptides in the respiratory tract, which is absent in animals pre-infected with IAV. Severe outcomes of consecutive IAV/CDV infections are mitigated by oral antivirals even when initiated late. These findings validate the morbillivirus immune amnesia hypothesis, define measles treatment paradigms, and identify priming of the TFF axis through prior respiratory infections as risk factor for exacerbated morbillivirus disease.

Hemorrhagic Pneumonia Caused by Stenotrophomonas maltophilia in Patients with Hematologic Malignancies-A Systematic Review and Meta-Analysis.

Background and Objectives: There is a need for information regarding the clinical picture of hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in patients with hematologic malignancies. In this study, we aimed to investigate the risk factors associated with hemorrhagic pneumonia caused by Stenotrophomonas maltophilia. Materials and Methods: A review of the clinical picture of hemorrhagic pneumonia based on reported cases in the literature was performed. In addition, patients with hematologic malignancies who had a Stenotrophomonas maltophilia infection were included in the meta-analysis to evaluate risk factors for hemorrhagic pneumonia. Results: A total of 91 patients had hemorrhagic pneumonia. Acute myeloid leukemia was present in 57 patients (62.6%). Those with bacteremia accounted for 94%, while those with neutropenia accounted for 95% and those with thrombocytopenia accounted for 86.7%. Hemorrhagic pneumonia was a risk factor for mortality of Stenotrophomonas maltophilia infection in patients with hematologic malignancies. Neutropenia and thrombocytopenia were identified as risk factors for hemorrhagic pneumonia. Conclusions: Stenotrophomonas maltophilia bacteremia with hemorrhagic pneumonia in patients with hematologic malignancies is a situation with rapid development and high mortality. Neutropenia and thrombocytopenia were risk factors for hemorrhagic pneumonia in patients with hematologic malignancies and with Stenotrophomonas maltophilia bacteremia; thus, these patients should be managed with caution.

Ranavirus (Frog Virus 3) Infection in Free-Living Three-Toed Box Turtles (Terrapene mexicana triunguis) in Missouri, USA.

Frog virus 3 (FV3) and related ranaviruses are emerging infectious disease threats to ectothermic vertebrate species globally. Although the impact of these viruses on amphibian health is relatively well studied, less is understood about their effects on reptile health. We report two cases of FV3 infection, 11 mo apart, in three-toed box turtles (Terrapene mexicana triunguis) from a wildlife rehabilitation center. Case 1 had upper respiratory signs upon intake but had no clinical signs at the time of euthanasia 1 mo later. Case 2 presented for vehicular trauma, had ulcerative pharyngitis and glossitis, and died overnight. In case 1, we detected FV3 nucleic acid with qPCR in oral swabs, kidney, liver, spleen, and tongue. In case 2, we detected FV3 in an oral swab, an oral plaque, heart, kidney, lung, liver, spleen, and tongue. We also detected FV3 nucleic acid with in situ hybridization for case 2. For both cases, FV3 was isolated in cell culture and identified with DNA sequencing. Histopathologic examination of postmortem tissue from case 1 was unremarkable, whereas acute hemorrhagic pneumonia and splenic necrosis were noted in case 2. The difference in clinical signs between the two cases may have been due to differences in the temporal course of FV3 disease at the time of necropsy. Failure to detect this infection previously in Missouri reptiles may be due to lack of surveillance, although cases may also represent a novel spillover to box turtles in Missouri. Our findings reiterate previous suggestions that the range of FV3 infection may be greater than previously documented and that infection may occur in host species yet to be tested.

Different populations of A(H1N1)pdm09 viruses in a patient with hemolytic-uremic syndrome

Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized.A patient (age group 5–15 years) displaying symptoms of hemolytic uremic syndrome died one day after hospitalization. qPCR, next generation sequencing, virus isolation, antigenic characterization, resistance analysis was performed and virus replication kinetics in well-differentiated airway cells were determined.Autopsy revealed hemorrhagic pneumonia as major pathological manifestation. Lung samples harbored a large population of A(H1N1)pdm09 viruses with the polymorphism H456H/Y in PB1 polymerase. The H456H/Y viruses replicated much faster to high viral titers than upper respiratory tract viruses in vitro. H456H/Y-infected air-liquid interface cultures of differentiated airway epithelial cells did reflect a more pronounced loss of ciliated cells. A different pattern of virus quasispecies was found in the upper airway samples where substitution S263S/F (HA1) was observed.The data support the notion that viral quasispecies had evolved locally in the lung to support high replicative fitness. This change may have initiated further pathogenic processes leading to rapid dissemination of inflammatory mediators followed by development of hemorrhagic lung lesions and fatal outcome.

Multiple Myeloma Patient with Secondary Liver and Tongue Involvement, Complicated by COVID-19-Induced ARDS: An Autopsy Case Report and Literature Review

Background. Liver involvement secondary to multiple myeloma is a rare and uncommon radiologic finding. Such extraosseous secondary lesions as well as tongue involvement require pathohistological confirmation to prevent misdiagnosis. Clinical and laboratory diagnostics are challenging in patients with COVID-19 and underlying multiple myeloma and its secondary lesions, leading to difficulties in treatment and outcomes.
 Case Report. A 64-year-old male patient, not vaccinated against COVID-19, with a history of multiple myeloma presented with symptoms of headache, fatigue, dyspnea, cough, and fever. The patient’s medical history was intricate, involving cholecystectomy and a diagnosis of multiple myeloma, which was subsequently treated with chemotherapy and radiation therapy. Additionally, uncommon liver and tongue involvement secondary to multiple myeloma was found. Upon admission, the patient’s peripheral oxygen saturation was 90%, accompanied by increasing shortness of breath and a respiratory rate of 26 breaths per minute. A positive COVID-19 test was recorded. A lung computed tomography revealed bilateral multifocal areas of ground-glass opacity and consolidation, encompassing the entire pulmonary regions, corresponding to CO-RADS 6. The patient was admitted to the intensive care unit. Despite initiating oxygen support and symptomatic therapy, the patient’s death occurred. Autopsy confirmed the development of severe acute respiratory distress syndrome and bilateral hemorrhagic pneumonia, with multiple myeloma as a contributing factor.
 Conclusions. This case report highlighted the rare occurrence of secondary liver involvement in multiple myeloma, characterized by nodules with distinct imaging features. It underscored the importance of identifying coexisting lesions, such as tongue involvement, and the diagnostic challenges they pose. Additionally, the case emphasized the need for comprehensive clinical assessment in patients with concurrent COVID-19 and underlying multiple myeloma, as it may lead to the development of acute respiratory distress syndrome.

Characterization of Pseudomonas aeruginosa bacteriophages and control hemorrhagic pneumonia on a mice model.

Pseudomonas aeruginosa is one of the most common pathogens causing hemorrhagic pneumonia in Chinese forest musk deer. Multidrug-resistant P. aeruginosa is frequently isolated from the lungs of affected musk deer in Shaanxi Province, China. With the increasing bacterial drug resistance, commonly used antibiotics have shown limited efficacy against drug-resistant P. aeruginosa. Therefore, phages have garnered attention as a promising alternative to antibiotics among researchers. In this study, phages vB_PaeP_YL1 and vB_PaeP_YL2 (respectively referred to as YL1 and YL2) were isolated from mixed sewage samples from a farm. YL1 and YL2 exhibit an icosahedral head and a non-contractile short tail, belonging to the Podoviridae family. Identification results demonstrate good tolerance to low temperatures and pH levels, with minimal variation in potency within 30 min of UV irradiation. The MOI for both YL1 and YL2 was 0.1, and their one-step growth curve latent periods were 10 min and 20 min, respectively. Moreover, both single phage and phage cocktail effectively inhibited the growth of the host bacteria in vitro, with the phage cocktail showing superior inhibitory effects compared to the single phage. YL1 and YL2 possess double-stranded DNA genomes, with YL1 having a genome size of 72,187 bp and a total G + C content of 55.02%, while YL2 has a genome size of 72,060 bp and a total G + C content of 54.98%. YL1 and YL2 are predicted to have 93 and 92 open reading frames (ORFs), respectively, and no ORFs related to drug resistance or lysogeny were found in both phages. Genome annotation and phylogenetic analysis revealed that YL1 is closely related to vB_PaeP_FBPa1 (ON857943), while YL2 is closely related to vB_PaeP_FBPa1 (ON857943) and Phage26 (NC041907). In a mouse model of hemorrhagic pneumonia, phage cocktail treatment showed better control of the disease and significantly reduced lung bacterial load compared to single phage treatment. Therefore, YL1 and YL2 have the potential for the prevention and treatment of multidrug-resistant P. aeruginosa infections.

Baicalin Attenuated PANX-1/P2X7 Axis, P2Y6, and NLRP3/Caspase-1 Signaling Pathways in Peritonitis Induced by Glaesserella parasuis

Glaesserella parasuis (G. parasuis) can cause peritonitis in piglets. However, the pathogenesis of peritonitis remains unclear. Baicalin has been shown to possess anti-inflammatory and anti-oxidant functions. The aim of this study was to investigate the role of the PANX-1/P2X7 axis and the P2Y6 signaling pathway in peritonitis induced by G. parasuis and the effect of baicain on the PANX-1/P2X7 axis and P2Y6 pathway activation triggered by G. parasuis. A G. parasuis serovar 5 isolate SH0165 strain was obtained from the lungs of commercially produced pigs which had the typical symptoms of Glässer’s disease, namely arthritis, fibrinous polyserositis, hemorrhagic pneumonia, and meningitis. Then, 35 piglets were randomly divided into five groups, each group containing seven piglets. The groups consisted of a negative control group, an infection group, a 25 mg/kg baicalin group, a 50 mg/kg baicalin group, and a 100 mg/kg baicalin group. The results showed that G. parasuis could promote PANX-1/P2X7 axis and P2Y6 activation; induce NLRP3/caspase-1, IL-1β and IL-18 expression; trigger PLC/PKC and MLCK/MLC signaling activation; attenuate the expression of tight junction proteins ZO-1, E-cadherin, Occludins, and claudin 1; and stimulate CD14, CD24, CD36, CD47, and CD91 expression in the peritoneum as measured via Western blot (p < 0.01; PLC, p < 0.05). Baicalin could significantly inhibit PANX-1/P2X7 axis, P2Y6, and NLRP3/caspase-1 activation; reduce IL-1β and IL-18 expression; attenuate PLC/PKC and MLCK/MLC activation; promote ZO-1, E-cadherin, occludins, and claudin 1 expression; and reduce CD14, CD24, CD36, CD47, and CD91 expression in the peritoneum induced by G. parasuis as measured via Western blot. Our results deepen the understanding of the mechanism of peritonitis triggered by G. parasuis and provide some novel potential methods of controlling G. parasuis infection.

Diagnosis of a Rabbit Hemorrhagic Disease Virus 2 (RHDV2) and the Humoral Immune Protection Effect of VP60 Vaccine.

Rabbit hemorrhagic disease (RHD) is known as rabbit plague and hemorrhagic pneumonia. It is an acute, septic, and highly fatal infectious disease caused by the Lagovirus rabbit hemorrhagic disease virus (RHDV) in the family Caliciviridae that infects wild and domestic rabbits and hares (lagomorphs). At present, RHDV2 has caused huge economic losses to the commercial rabbit trade and led to a decline in the number of wild lagomorphs worldwide. We performed a necropsy and pathological observations on five dead rabbits on a rabbit farm in Tai'an, China. The results were highly similar to the clinical and pathological changes of typical RHD. RHDV2 strain was isolated and identified by RT-PCR, and partial gene sequencing and genetic evolution analysis were carried out. There were significant differences in genetic characteristics and antigenicity between RHDV2 and classical RHDV strain, and the vaccine prepared with the RHDV strain cannot effectively prevent rabbit infection with RHDV2. Therefore, we evaluated the protective efficacy of a novel rabbit hemorrhagic virus baculovirus vector inactivated vaccine (VP60) in clinical application by animal regression experiment. The result showed that VP60 could effectively induce humoral immunity in rabbits. The vaccine itself had no significant effect on the health status of rabbits. This study suggested that the clinical application of VP60 may provide new ideas for preventing the spread of RHD2.

A novel NADC34-like porcine reproductive and respiratory syndrome virus 2 with complex genome recombination is highly pathogenic to piglets.

The NADC34-like porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) first emerged in China in 2017 and has the potential to become the dominant PRRSV strain in China. Here, a novel PRRSV-2, SCcd2020, was isolated from diseased piglets in Sichuan province, southwest China in 2020. The complete viral genome was determined and analyzed. An ORF5-based phylogenetic analysis showed that SCcd2020 clustered with NADC34-like strains, whereas the genome sequence clustered the isolate with NADC30-like viruses and it contains a discontinuous 131-aa deletion in NSP2 when compared to NADC30 strain. Notably, recombination analyses indicated that SCcd2020 is a multiple recombinant virus from NADC30-like, NADC34-like and JXA1-like strains, which is the first description of Chinese domestic HP-PRRSV involving the recombination event of an NADC34-like strain. Importantly, an animal challenge study in 4-week-old piglets showed that SCcd2020 causes high fever and severe hemorrhagic pneumonia with pulmonary consolidation and edema, and it has a high mortality rate (60%), which indicated that SCcd2020 is a highly pathogenic PRRSV strain. The study reports the emergence of a novel highly pathogenic NADC34-like recombinant strain, and it highlights the importance of monitoring newly emerging PRRSV strains in China.

Stimulation of lipopolysaccharide from Pseudomonas aeruginosa following H9N2 IAV infection exacerbates inflammatory responses of alveolar macrophages and decreases virus replication

H9N2 IAV infection contributed to P. aeruginosa coinfection, causing severe hemorrhagic pneumonia in mink. In this study, the in vitro alveolar macrophage models were developed to investigate the innate immune responses to P. aeruginosa LPS stimulation following H9N2 IAV infection, using MH-S cells. The cytokine levels, apoptosis levels and the viral nucleic acid levels were detected and analyzed. As a result, the levels of IFN-α, IL-1β, TNF-α, and IL-10 in MH-S cells with P. aeruginosa LPS stimulation following H9N2 IAV infection were significantly higher than those in MH-S cells with single H9N2 IAV infection and single LPS stimulation (P < 0.05), exacerbating inflammatory responses. LPS stimulation aggravated the apoptosis of MH-S cells with H9N2 IAV infection. Interestingly, LPS stimulation influences H9N2 IAV replication and indirectly reduced H9N2 IAV replications in in vitro AMs. It implied that LPS should play an important role in the pathogenesis of H9N2 IAV and P. aeruginosa coinfection.

Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial

The risk of death from spontaneous intracerebral haemorrhage is increased for people taking antiplatelet drugs. We aimed to assess the feasibility of randomising patients on antiplatelet drug therapy with spontaneous intracerebral haemorrhage to desmopressin or placebo to reduce the antiplatelet drug effect. DASH was a phase 2, randomised, placebo-controlled, multicentre feasibility trial. Patients were recruited from ten acute stroke centres in the UK and were eligible if they had an intracerebral haemorrhage with stroke symptom onset within 24 h of randomisation, were aged 18 years or older, and were taking an antiplatelet drug. Participants were randomly assigned (1:1) to a single dose of intravenous desmopressin 20 μg or matching placebo. Treatment allocation was concealed from all staff and patients involved in the trial. The primary outcome was feasibility, which was measured as the number of eligible patients randomised and the proportion of eligible patients approached, and analysis was by intention to treat. The trial was prospectively registered with ISRCTN (reference ISRCTN67038373), and it is closed to recruitment. Between April 1, 2019, and March 31, 2022, 1380 potential participants were screened for eligibility. 176 (13%) participants were potentially eligible, of whom 57 (32%) were approached, and 54 (31%) consented and were subsequently recruited and randomly assigned to receive desmopressin (n=27) or placebo (n=27). The main reason for eligible patients not being recruited was the patient arriving out of hours (74 [61%] of 122 participants). The recruitment rate increased after the enrolment period was extended from 12 h to 24 h, but it was then impaired due to the COVID-19 pandemic. Of the 54 participants included in the analysis (mean age 76·4 years [SD 11·3]), most were male (36 [67%]) and White (50 [93%]). 53 (98%) of 54 participants received all of their allocated treatment (one participant assigned desmopressin only received part of the infusion). No participants were lost to follow-up or withdrew from the trial. Death or dependency on others for daily activities at day 90 (modified Rankin Scale score >4) occurred in six (22%) of 27 participants in the desmopressin group and ten (37%) of 27 participants in the placebo group. Serious adverse events occurred in 12 (44%) participants in the desmopressin group and 13 (48%) participants in the placebo group. The most common adverse events were expansion of the haemorrhagic stroke (four [15%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group) and pneumonia (one [4%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group). Our results show it is feasible to randomise patients with spontaneous intracerebral haemorrhage who are taking antiplatelet drugs to desmopressin or placebo. Our findings support the need for a definitive trial to determine if desmopressin improves outcomes in patients with intracerebral haemorrhage on antiplatelet drug therapy. National Institute for Health Research.

Study of Laboratory Diagnosis of Colibasilosis Infection In Local Hen In Surabaya

Background: On November 18, 2022, euthanasia and hen necropsy were conducted (protocol number A-164) in the veterinary pathology laboratory, Faculty Of Veterinary Medicine, Wijaya Kusuma University Surabaya. The hen belongs to a local farmer located at Sawahan, Surabaya. Based on the anamnesis, it is known that the hen was four months old and weighed 1.4 kg. The population consists of eight birds, and one of them was sick, never treated or vaccinated, in a cage made of bamboo, corn fodder, rice bran, and drinking water from tap water. Clinical symptoms show a decreased appetite for the last day, watery eyes, runny nose, lethargy, and diarrhea with feces green mixed with white colors. The initial diagnosis of the chicken was infected with Salmonella sp. with a differential diagnosis of Escherichia coli. Purpose: To diagnose bacterial disease in local chickens with a pathological examination, parasitological examination, microbiological isolation, and clinical pathology for hematology. Result: The results of the anatomic pathology examination showed that the chickens had hemorrhagic tracheitis, hemorrhagic necrotic pneumonia, hemorrhagic necrotic enteritis, hemorrhagic necrotic hepatitis, and hemorrhage in the proventriculus. Parasite identification was found in Raillietina sp. and Ornithonyssus sylviarum. Isolation of bacteria was found in Escherichia coli from the duodenum organ. The chickens had hypoproteinemia, poikilocytosis teardrop and rouleaux, leukocytosis with heterophilia, and monocytosis. Conclusion: Based on the examination associated with the results of anamnesis and examination of clinical symptoms, the chickens were diagnosed with Escherichia coli infection together with Raillietina sp. and Ornithonyssus sylviarum infestations.

Longitudinal analyses using 18F-Fluorodeoxyglucose positron emission tomography with computed tomography as a measure of COVID-19 severity in the aged, young, and humanized ACE2 SARS-CoV-2 hamster models

This study compared disease progression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in three different models of golden hamsters: aged (≈60 weeks old) wild-type (WT), young (6 weeks old) WT, and adult (14–22 weeks old) hamsters expressing the human-angiotensin-converting enzyme 2 (hACE2) receptor. After intranasal (IN) exposure to the SARS-CoV-2 Washington isolate (WA01/2020), 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography with computed tomography (18F-FDG PET/CT) was used to monitor disease progression in near real time and animals were euthanized at pre-determined time points to directly compare imaging findings with other disease parameters associated with coronavirus disease 2019 (COVID-19). Consistent with histopathology, 18F-FDG-PET/CT demonstrated that aged WT hamsters exposed to 105 plaque forming units (PFU) developed more severe and protracted pneumonia than young WT hamsters exposed to the same (or lower) dose or hACE2 hamsters exposed to a uniformly lethal dose of virus. Specifically, aged WT hamsters presented with a severe interstitial pneumonia through 8 d post-exposure (PE), while pulmonary regeneration was observed in young WT hamsters at that time. hACE2 hamsters exposed to 100 or 10 PFU virus presented with a minimal to mild hemorrhagic pneumonia but succumbed to SARS-CoV-2-related meningoencephalitis by 6 d PE, suggesting that this model might allow assessment of SARS-CoV-2 infection on the central nervous system (CNS). Our group is the first to use (18F-FDG) PET/CT to differentiate respiratory disease severity ranging from mild to severe in three COVID-19 hamster models. The non-invasive, serial measure of disease progression provided by PET/CT makes it a valuable tool for animal model characterization.

Lung Expression of Macrophage Markers CD68 and CD163, Angiotensin Converting Enzyme 2 (ACE2), and Caspase-3 in COVID-19.

Background and Objectives: The coronavirus (SARS-CoV-2) damages all systems and organs. Yet, to a greater extent, the lungs are particularly involved, due to the formation of diffuse exudative inflammation in the form of acute respiratory distress syndrome (ARDS) with next progression to pulmonary fibrosis. SARS-associated lung damage is accompanied by the pronounced activation of mononuclear cells, damage of the alveoli and microvessels, and the development of organized pneumonia. To study the expression of macrophage markers (CD68 and CD163), angiotensin-converting enzyme-2 (ACE2), and caspase-3 on the results of two fatal clinical observations of COVID-19. Materials and Methods: In both clinical cases, the female patients died from complications of confirmed COVID-19. Conventional morphological and immunohistochemical methods were used. Results: There was an acute exudative hemorrhagic pneumonia with the formation of hyaline membranes, focal organization of fibrin, stromal sclerosis, stasis, and thrombus formation in the lung vessels. Signs such as the formation of hyaline membranes, organization, and fibrosis were more pronounced in severe disease activity. The activation of CD68+/CD163+ macrophages could cause cell damage at an early stage of pneumonia development, and subsequently cause fibrotic changes in lung tissue. ACE2 expression in lung tissue was not detected in severe pneumonia, while in moderate pneumonia, weak expression was noted in individual cells of the alveolar epithelium and vascular endothelium. Conclusions: This finding could show the dependence of ACE2 expression on the severity of the inflammatory process in the lungs. The expression of caspase-3 was more pronounced in severe pneumonia.

Pathological Characteristics of Domestic Pigs Orally Infected with the Virus Strain Causing the First Reported African Swine Fever Outbreaks in Vietnam.

African swine fever (ASF) is currently Vietnam's most economically significant swine disease. The first ASF outbreak in Vietnam was reported in February 2019. In this study, VNUA/HY/ASF1 strain isolated from the first ASF outbreak was used to infect 10 eight-week-old pigs orally with 103 HAD50 per animal. The pigs were observed daily for clinical signs, and whole blood samples were collected from each animal for viremia detection. Dead pigs were subjected to full post-mortem analyses. All 10 pigs displayed acute or subacute clinical signs and succumbed to the infection between 10 to 27 (19.8 ± 4.66) days post-inoculation (dpi). The onset of clinical signs started around 4-14 dpi. Viremia was observed in pigs from 6-16 dpi (11.2 ± 3.55). Enlarged, hyperemic, and hemorrhagic lymph nodes, enlarged spleen, pneumonia, and hydropericardium were observed at post-mortem examinations.

Yersiniose fatal por Yersinia enterocolitica em um zogue-zogue (Plecturocebus brunneus)

ABSTRACT: We described a case of fatal septicemic yersiniosis in a young adult brown titi monkey (Plecturocebus brunneus) which presented lethargy and severe anemia. Postmortem external assessment revealed marked dehydration and pale pink mucous membranes. The main gross findings included enlarged liver with yellow pinpoints, enlarged spleen with yellow nodules, mucosal ulcerations in the large intestine, enlarged mesenteric lymph nodes, and pulmonary hemorrhage. Histology revealed necrosuppurative hepatosplenitis with intralesional colonies of rod-shaped gram-negative bacteria, ulcerative colitis, reactive lymphoid hyperplasia, and fibrinous and hemorrhagic pneumonia. Bacterial culture and identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry confirmed the diagnosis of yersiniosis by Yersinia enterocolitica. This study indicated that yersiniosis should be considered as a differential diagnosis of death in brown titi monkeys.

Overview of Mink Immunity and Resistance to Pseudomonas aeruginosa

Pseudomonas aeruginosa is one of the most host‐susceptible pathogenic bacteria to cause acute and chronic infections in humans and animals. Notably, its infection can especially cause fatal pathogenic infectious pneumonia in minks. Many previous mink studies have investigated the pathology, pathogenesis, serology, antimicrobial resistance, virulence gene, vaccination, and related diseases of P. aeruginosa. However, the relationship of P. aeruginosa infections with mink immunity and resistance is relatively less studied that needs more elaborations. Therefore, we here provide a comprehensive review about mink immunity and resistance to P. aeruginosa infections and the pathogenesis of mink hemorrhagic pneumonia in four major aspects. They include characterization, infection, immunity, and resistance of P. aeruginosa, and their implication and perspective, which aim to contribute the useful and valuable information to further related research and clinical treatment of P. aeruginosa and to avoid the potential fatal hemorrhagic pneumonia spreading.

Pmorf0222, a Virulence Factor in Pasteurella multocida, Activates Nuclear Factor Kappa B and Mitogen-Activated Protein Kinase via Toll-Like Receptor 1/2.

Pasteurella multocida primarily causes hemorrhagic septicemia and pneumonia in poultry and livestock. Identification of the relevant virulence factors is therefore essential for understanding its pathogenicity. Pmorf0222, encoding the PM0222 protein, is located on a specific prophage island of the pathogenic strain C48-1 of P. multocida. Its role in the pathogenesis of P. multocida infection is still unknown. The proinflammatory cytokine plays an important role in P. multocida infection; therefore, murine peritoneal exudate macrophages were treated with the purified recombinant PM0222, which induced the secretion of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) via the Toll-like receptor 1/2 (TLR1/2)-nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) signaling and inflammasome activation. Additionally, the mutant strain and complemented strain were evaluated in the mouse model with P. multocida infection, and PM0222 was identified as a virulence factor, which was secreted by outer membrane vesicles of P. multocida. Further results revealed that Pmorf0222 affected the synthesis of the capsule, adhesion, serum sensitivity, and biofilm formation. Thus, we identified Pmorf0222 as a novel virulence factor in the C48-1 strain of P. multocida, explaining the high pathogenicity of this pathogenic strain.