Host Factors Impacting the Development and Transmission of Bovine Digital Dermatitis

This review provides insight on potential host-specific factors that increase individual susceptibility to infection and transmission of bovine digital dermatitis. Digital dermatitis is increasing in prevalence within herds worldwide and yields economic losses for producers and welfare issues for animals. A total of 34 relevant studies were reviewed based on the inclusion criteria. A decrease in susceptibility to disease was found in animals with specific genomic and hoof characteristics, thus citing the importance of sire selection when designing a breeding program. Animals with superior health status that lacked co-morbidities and mounted immune responses to infection were less likely to develop disease. Primiparous cattle and those in peak production were more likely to develop lesions, as were over-or-under-conditioned Holstein–Friesian breeds. Cattle with superior hoof conformation and gait were poor hosts for bacteria and therefore less likely to develop and spread infection. The lowest risk of transmission of digital dermatitis occurred during the dry period and post peak lactation and cattle with advanced lesions contributed to the persistence of the disease within a herd. It is hoped that this review will help producers design breeding and management programs for their herds, and help veterinarians advise clients on the subject.

Household secondary attack rates of SARS-CoV-2 by variant and vaccination status: an updated systematic review and meta-analysis

We previously reported a household secondary attack rate (SAR) for SARS-CoV-2 of 18.9% through June 17, 2021. To examine how emerging variants and increased vaccination have affected transmission rates, we searched PubMed from June 18, 2021, through January 7, 2022. Meta-analyses used generalized linear mixed models to obtain SAR estimates and 95%CI, disaggregated by several covariates. SARs were used to estimate vaccine effectiveness based on the transmission probability for susceptibility (VE_S,p), infectiousness (VE_I,p), and total vaccine effectiveness (VE_T,p). Household SAR for 27 studies with midpoints in 2021 was 35.8% (95%CI, 30.6%-41.3%), compared to 15.7% (95%CI, 13.3%-18.4%) for 62 studies with midpoints through April 2020. Household SARs were 38.0% (95%CI, 36.0%-40.0%), 30.8% (95%CI, 23.5%-39.3%), and 22.5% (95%CI, 18.6%-26.8%) for Alpha, Delta, and Beta, respectively. VE_I,p, VE_S,p, and VE_T,p were 56.6% (95%CI, 28.7%-73.6%), 70.3% (95%CI, 59.3%-78.4%), and 86.8% (95%CI, 76.7%-92.5%) for full vaccination, and 27.5% (95%CI, -6.4%-50.7%), 43.9% (95%CI, 21.8%-59.7%), and 59.9% (95%CI, 34.4%-75.5%) for partial vaccination, respectively. Household contacts exposed to Alpha or Delta are at increased risk of infection compared to the original wild-type strain. Vaccination reduced susceptibility to infection and transmission to others.

Characterizing the transmission patterns of seasonal influenza in Italy: lessons from the last decade

Background Despite thousands of influenza cases annually recorded by surveillance systems around the globe, estimating the transmission patterns of seasonal influenza is challenging. Methods We develop an age-structured mathematical model to influenza transmission to analyze ten consecutive seasons (from 2010 to 2011 to 2019–2020) of influenza epidemiological and virological data reported to the Italian surveillance system. Results We estimate that 18.4–29.3% of influenza infections are detected by the surveillance system. Influenza infection attack rate varied between 12.7 and 30.5% and is generally larger for seasons characterized by the circulation of A/H3N2 and/or B types/subtypes. Individuals aged 14 years or less are the most affected age-segment of the population, with A viruses especially affecting children aged 0–4 years. For all influenza types/subtypes, the mean effective reproduction number is estimated to be generally in the range 1.09–1.33 (9 out of 10 seasons) and never exceeding 1.41. The age-specific susceptibility to infection appears to be a type/subtype-specific feature. Conclusions The results presented in this study provide insights on type/subtype-specific transmission patterns of seasonal influenza that could be instrumental to fine-tune immunization strategies and non-pharmaceutical interventions aimed at limiting seasonal influenza spread and burden.

Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19

: The incidence of infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for coronavirus disease 2019 (COVID-19), has dramatically escalated following the initial outbreak in China in late 2019, resulting in a global pandemic with millions of deaths. Although the majority of infected patients survive, and the rapid advent and deployment of vaccines have afforded increased immunity against SARS-CoV-2, long term sequelae of SARS-CoV-2 infection have become increasingly recognized. These include, but are not limited to, chronic pulmonary disease, cardiovascular disorders, and proinflammatory-associated neurological dysfunction that may lead to psychological and neurocognitive impairment. A major component of cognitive dysfunction is operationally categorized as “brain fog” which comprises difficulty with concentration, forgetfulness, confusion, depression, and fatigue. Multiple parameters associated with long-term neuropsychiatric sequelae of SARS-CoV-2 infection have been detailed in clinical studies. Empirically elucidated mechanisms associated with the neuropsychiatric manifestations of COVID-19 are by nature complex, but broad based working models have focused on mitochondrial dysregulation leading to systemic reductions of metabolic activity and cellular bioenergetics within CNS structures. Multiple factors underlying the expression of brain fog may facilitate future pathogenic insults leading to repetitive cycles of viral and bacterial propagation. Interestingly, diverse neurocognitive sequelae associated with COVID-19 are not dissimilar from those observed in other historical pandemics, thereby providing a broad and integrative perspective on potential common mechanisms of CNS dysfunction subsequent to viral infection. Poor mental health status may be reciprocally linked to compromised immune processes and enhanced susceptibility to infection by diverse pathogens. By extrapolation, we contend that COVID-19 may potentiate the severity of neurological/neurocognitive deficits in patients afflicted by well-studied neurodegenerative disorders such as Alzheimer's disease and Parkinson’s disease. Accordingly, the prevention, diagnosis, and management of sustained neuropsychiatric manifestations of COVID-19 are pivotal health care directives and provide a compelling rationale for careful monitoring of infected patients, as early mitigation efforts may reduce short- and long-term complications.

Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms

Since the appearance of the coronavirus disease 2019 (COVID-19) and its announcement as a global pandemic, the search for prophylactic and therapeutic options have become a priority for governments and the scientific community. The approval of several vaccines against SARS-CoV-2 is being crucial to overcome this situation, although the victory will not be achieved while the whole population worldwide is not protected against the virus. This is why alternatives should be studied in order to successfully support the immune system before and during a possible infection. An optimal inflammatory and oxidative stress status depends on an adequate diet. Poor levels of several nutrients could be related to an impaired immune response and, therefore, an increased susceptibility to infection and serious outcomes. Vitamins exert a number of anti-microbial, immunomodulatory, anti-inflammatory, and antioxidant activities, which can be of use to fight against this and several other diseases (especially vitamin D and C). Even though they cannot be considered as a definitive therapeutic option, in part owing to the lack of solid conclusions from well-designed clinical trials, currently available evidence from similar respiratory diseases may indicate that it would be rational to deeply explore the use of vitamins during this global pandemic.

Endosymbiotic male-killing Spiroplasma affect the physiological and behavioural ecology of Macrocheles - Drosophil a interactions

While many arthropod endosymbionts are vertically transmitted, phylogenetic studies reveal repeated introductions of hemolymph-dwelling Spiroplasma into Drosophila . Introductions are often attributed to horizontal transmission via ectoparasite vectors. Here, we test if mites prefer to infect Spiroplasma poulsonii MSRO infected flies, and if MSRO infection impairs fly resistance against secondary mite ( Macrocheles subbadius ) attack. First we tested if mites prefer MSRO+ or MSRO– flies using pair-wise-choice tests across fly ages. We then tested whether mite preferences are explained by changes in fly physiology, specifically increased metabolic rate (measured as CO 2 production). We hypothesize that this preference is due in part to MSRO+ flies expressing higher metabolic rates. However, our results showed mite preference depended on an interaction between fly age and MSRO status: mites avoided 14-days old MSRO+ flies relative to MSRO– flies (31% infection), but prefered MSRO + flies (64% infection) among 26-day old flies. Using flow-through respirometry, we found 14 day-old MSRO + flies had higher CO 2 emissions than MSRO– flies (32% greater), whereas at 26 days old the CO 2 production among MSRO+ flies was 20% lower than MSRO– flies. Thus, mite preferences for high metabolic rate hosts did not explain the infection biases in this study. To assess changes in susceptibility to infection, we measured fly endurance using geotaxis assays. Older flies had lower endurance consistent with fly senescence, and this effect was magnified among MSRO+ flies. Given the biological importance of male-killing Spiroplasma, potential changes in the interactions of hosts and potential vectors could impact the ecology and evolution of host species. Importance Male-killing endosymbionts are transmitted mother to daughter and kill male offspring. Despite these major ecological effects, how these endosymbionts colonize new host species is not always clear. Mites are sometimes hypothesized to transfer these bacteria between hosts/host species. Here we test if 1) if mites prefer to infect flies that harbour Spiroplasma poulisoni MSRO and 2) if flies infected with MSRO are less able to resist mite infection. Our results show that flies infected with MSRO have weaker anti-mite resistance but the mite preference/aversion for MSRO+ flies varied with fly age. Given the fitness and population impacts of male-killing Spiroplasma , changes in fly-mite interactions have implications for the ecology and evolution of these symbioses.

Altered expressions of CXCR4 and CD26 on T-helper lymphocytes in hereditary hemorrhagic telangiectasia

Background Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype (muco-cutaneous telangiectases, arteriovenous malformations), a specific risk of infection is suggested by case series of severe and atypical infections as well as by reports of decreased T and natural killer (NK) lymphocyte counts. As some evidence supports a dysregulation of the CXCR4/CXCL12 chemotactic axis of HHT endothelial cells, we hypothesized that a similar phenomenon could occur on lymphocytes. Methods Eighteen HHT patients with history of severe infection (HSI) were matched in age and sex with 18 HHT without HSI and 18 healthy control subjects (HC). We assessed the cell count and the surface expression of CXCR4 and CD26 (CXCL12 inactivating peptidase) of circulating T-helper and T-cytotoxic lymphocytes (including naive, memory and activated subsets) and NK cells. Results The overall HHT group of 36 patients exhibited a reduction of circulating T-helper lymphocytes compared to HC (median: 517 vs. 1026 cells/mm3, p < 0.0001), correlated with age (r = − 0.46, p = 0.005), requirement of intravenous iron or blood transfusions (median: 291 vs. 627 cells/mm3, p = 0.03) and CXCR4 surface expression (r = 0.353, p = 0.0345). CXCR4 and CD26 membrane expression were both decreased on HHT T-helper lymphocytes (median MFI ratio: 4.49 vs. 5.74 for CXCR4 and 3.21 vs. 4.33 for CD26, p = 0.03 and 0.0018 respectively) with an unchanged CXCR4/CD26 ratio. The HHT group with HSI had a higher CXCR4/CD26 ratio on the total T-lymphocyte population, as well as on the T-helper population and its naive subset (median on naive T-helper cells: 2.34 vs. 1.32, p = 0.0002). Conclusions Our findings support a dysregulation of the CXCL12/CXCR4 chemotaxis of T-helper lymphocytes in HHT patients, potentially linked to their T-helper lymphopenia and susceptibility to infection.

Proposed protocol for treatment of severe periodontitis without platelet transfusion in patients with aplastic anemia: a case report

Background Aplastic anemia is an intractable disease characterized by pancytopenia, susceptibility to infection, and difficulty in achieving hemostasis. In patients with severe periodontal disease and aplastic anemia, spontaneous bleeding from the gingival tissue due to thrombocytopenia and during brushing is common, which may further exacerbate dental issues. Comprehensive periodontal treatment for patients with aplastic anemia is highly challenging and requires collaboration with a hematologist. Here, we discuss the case of a patient with aplastic anemia and severe periodontitis who was successfully treated in collaboration with our hematology department. Case presentation A 36-year-old Japanese woman with chief complaints of spontaneous gingival bleeding, pain, and increasing tooth mobility consulted our department. She had developed pancytopenia at age 11 years and was later diagnosed with aplastic anemia, making her susceptible to infection due to leukopenia. The results of the initial periodontal examination led to a diagnosis of severe generalized periodontitis (generalized stage IV grade C periodontitis) caused by leukopenia and poor oral hygiene. We adopted a comprehensive treatment plan, including invasive dental procedures. The patient exhibited no postoperative bleeding due to aplastic anemia-induced thrombocytopenia and experienced a good outcome. Conclusions Both physicians and dentists should be aware that immunocompromised patients with aplastic anemia are at risk of developing severe periodontitis with severe alveolar bone resorption if the condition is combined with poor oral hygiene. Even in the presence of aplastic anemia, patients with severe periodontitis can undergo comprehensive dental treatment, including dental extraction and periodontal surgery, if bleeding and susceptibility to infection are controlled. This requires the cooperation of the patient and hematologists and can ultimately contribute to improving the patient’s quality of life.

A novel IL-10 – DEL-1 axis promotes granulopoiesis and sepsis survival in early life

Newborns’ susceptibility to infection is mainly attributed to decreased neutrophil bone marrow reserves and peripheral blood neutropenia. However, the regulation of neonatal neutrophil kinetics in sepsis remains poorly understood. We demonstrate herein that the developmental endothelial locus (DEL-1) is elevated in early life and is integral to a protective host response in neonates, by supporting emergency granulopoiesis. DEL-1-deficient neonate mouse pups subjected to sepsis displayed diminished bone marrow numbers of neutrophils and granulocyte-macrophage progenitors, leading to neutropenia, exaggerated bacteremia, and increased mortality; defects that were rescued by DEL-1 administration. Contrary to adult mice, DEL-1 was not downregulated upon neonatal sepsis. The sustained production of DEL-1 under newborn sepsis was attributed to a high IL-10/IL-17A ratio, as we IL-10 upregulated DEL-1. The expression of DEL-1 and its effect in emergency granulopoiesis in neonates was diminished by anti-IL-10-Receptor blockage. Consistent with the mouse findings, DEL-1 and neutrophil numbers were higher in septic human adult and neonate patients with high IL-10/IL-17A ratio. Furthermore, septic patients with high DEL-1 exhibited lower mortality rates compared to patients with low DEL-1. These findings highlight the role of a hitherto unappreciated IL-10–DEL-1 axis in supporting emergency granulopoiesis, preventing neutropenia and promoting sepsis survival in early life.

The Role of GM-CSF Autoantibodies in Infection and Autoimmune Pulmonary Alveolar Proteinosis: A Concise Review

Autoantibodies to multiple cytokines have been identified and some, including antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), have been associated with increased susceptibility to infection. High levels of GM-CSF autoantibodies that neutralize signaling cause autoimmune pulmonary alveolar proteinosis (aPAP), an ultrarare autoimmune disease characterized by accumulation of excess surfactant in the alveoli, leading to pulmonary insufficiency. Defective GM-CSF signaling leads to functional deficits in multiple cell types, including macrophages and neutrophils, with impaired phagocytosis and host immune responses against pulmonary and systemic infections. In this article, we review the role of GM-CSF in aPAP pathogenesis and pulmonary homeostasis along with the increased incidence of infections (particularly opportunistic infections). Therefore, recombinant human GM-CSF products may have potential for treatment of aPAP and possibly other infectious and pulmonary diseases due to its pleotropic immunomodulatory actions.