Infectious Disease Virus Research Articles

Predictive Role of Cluster Bean (Cyamopsis tetragonoloba) Derived miRNAs in Human and Cattle Health.

MicroRNAs (miRNAs) are small non-coding conserved molecules with lengths varying between 18-25nt. Plants miRNAs are very stable, and probably they might have been transferred across kingdoms via food intake. Such miRNAs are also called exogenous miRNAs, which regulate the gene expression in host organisms. The miRNAs present in the cluster bean, a drought tolerant legume crop having high commercial value, might have also played a regulatory role for the genes involved in nutrients synthesis or disease pathways in animals including humans due to dietary intake of plant parts of cluster beans. However, the predictive role of miRNAs of cluster beans for gene-disease association across kingdoms such as cattle and humans are not yet fully explored. Thus, the aim of the present study is to (i) find out the cluster bean miRNAs (cb-miRs) functionally similar to miRNAs of cattle and humans and predict their target genes' involvement in the occurrence of complex diseases, and (ii) identify the role of cb-miRs that are functionally non-similar to the miRNAs of cattle and humans and predict their targeted genes' association with complex diseases in host systems. Here, we predicted a total of 33 and 15 functionally similar cb-miRs (fs-cb-miRs) to human and cattle miRNAs, respectively. Further, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the participation of targeted genes of fs-cb-miRs in 24 and 12 different pathways in humans and cattle, respectively. Few targeted genes in humans like LCP2, GABRA6, and MYH14 were predicted to be associated with disease pathways of Yesinia infection (hsa05135), neuroactive ligand-receptor interaction (hsa04080), and pathogenic Escherichia coli infection (hsa05130), respectively. However, targeted genes of fs-cb-miRs in humans like KLHL20, TNS1, and PAPD4 are associated with Alzheimer's, malignant tumor of the breast, and hepatitis C virus infection disease, respectively. Similarly, in cattle, targeted genes like ATG2B and DHRS11 of fs-cb-miRs participate in the pathways of Huntington disease and steroid biosynthesis, respectively. Additionally, the targeted genes like SURF4 and EDME2 of fs-cb-miRs are associated with mastitis and bovine osteoporosis, respectively. We also found a few cb-miRs that do not have functional similarity with human and cattle miRNAs but are found to target the genes in the host organisms and as well being associated with human and cattle diseases. Interestingly, a few genes such as NRM, PTPRE and SUZ12 were observed to be associated with Rheumatoid Arthritis, Asthma and Endometrial Stromal Sarcoma diseases, respectively, in humans and genes like SCNN1B associated with renal disease in cattle.

Acute infectious viral disease (chikungunya virus): clinical case

The article presents a case of primary infection with the rare chikungunya virus (CHIKV) in the form of somatogenic delirium in the setting of acute reactive pancreatitis and nephrotoxic syndrome.Somato-genic delirium is a fairly common condition that is not often diagnosed by general practitioners and prompts referrals to psychiatrists, where patients are subsequently treated exclusively within the psychiatric nosology register, which can limit the range of diagnostic search and mask the dynamics of symptoms during antipsychotic therapy. It is these patients who require detailed attention at the stage of the admission department, since only the search for the true factor of the disorder of consciousness can lead to the timely provision of appropriate care and prevention of disabling consequences. The relevance of the problem lies in the step-by-step analysis of a clinical case with a detailed explanation of the logic of decision-making at each stage. The unusual clinical picture has led to the emergence of a variety of possibilities for the primary clinical diagnosis: from primary psychiatric pathology to acute cerebrovascular accident. Accordingly, the treatment algorithm should change, which should initially be nonspecific detoxification. The article discusses the sequential process of establishing a diagnosis and differential diagnosis of this disease with other pathological conditions in order to enrich the experience of doctors with possible rare variants of diseases introduced by the possible use of epidemiological warfare tools on the territory of Ukraine.The article will be useful for a wide range of doctors of different profiles, including general practitioners, therapists and neurologists.

Molecular Detection of Avian Poxvirus in Chickens and Pigeons of Diyala Province in Iraq

Fowlpox is an infectious viral disease affecting domestic and wild birds. The current study was conducted using PCR-based molecular detection to determine the avian pox virus (APV) and its genetic sequence. A total of 40 pigeons and 40 chickens suspected of APV were obtained from different bird markets. Following euthanasia, tissue samples were taken from the vents, eyes, wings, and beaks for molecular analysis. DNA extraction was focused on the core protein gene region (pb4). PCR results confirmed the presence of APV in all samples, generating specific cDNA bands of 329 bp. Four GenBank accession codes (OR670580, OR670581, OR670582, and OR670583) represented pigeon pox samples, whereas two GenBank accession numbers (OR619724 and OR619725) represented samples of fowlpox. A significant similarity of 99% was found by genetic analysis between the reference target sequences and the sequenced samples. In viral samples of fowlpox and avipoxvirus, nucleic acid variants (205 C > G and 204 T > C) were found with missense and silent effects on particular proteins (p.101Leu>Val and p.108Pro). Phylogenetic analysis organized the samples into clades representing fowlpox and pigeon pox viruses, showing close relationships with strains from different geographical regions. This study unequivocally demonstrates the susceptibility of both domestic and wild birds to avian pox, highlighting the pivotal role of phylogenetic analysis and molecular detection in elucidating novel perspectives on the genetic landscape of these viruses. Keywords: Fowl pox, Gene, Pigeon pox, Polymerase Chain Reaction

Evaluation of bird-adapted self-amplifying mRNA vaccine formulations in chickens

Each year, millions of poultry succumb to highly pathogenic avian influenza A virus (AIV) and infectious bursal disease virus (IBDV) infections. Conventional vaccines based on inactivated or live-attenuated viruses are useful tools for disease prevention and control, yet, they often fall short in terms of safety, efficacy, and development times. Therefore, versatile vaccine platforms are crucial to protect poultry from emerging viral pathogens. Self-amplifying (replicon) RNA vaccines offer a well-defined and scalable option for the protection of both animals and humans. The best-studied replicon platform, based on the Venezuelan equine encephalitis virus (VEEV; family Togaviridae) TC-83 vaccine strain, however, displays limited efficacy in poultry, warranting the exploration of alternative, avian-adapted, replicon platforms. In this study, we engineered two Tembusu virus (TMUV; family Flaviviridae) replicons encoding varying capsid gene lengths and compared these to the benchmark VEEV replicon in vitro. The TMUV replicon system exhibited a robust and prolonged transgene expression compared to the VEEV replicon system in both avian and mammalian cells. Moreover, the TMUV replicon induced a lesser cytopathic effect compared to the VEEV replicon RNA in vitro. DNA-launched versions of the TMUV and VEEV replicons (DREP) were also developed. The replicons successfully expressed the AIV haemagglutinin (HA) glycoproteins and the IBDV capsid protein (pVP2). To assess the immune responses elicited by the TMUV replicon system in chickens, a prime-boost vaccination trial was conducted using lipid nanoparticle (LNP)-formulated replicon RNA and DREP encoding the viral (glyco)proteins of AIV or IBDV. Both TMUV and VEEV replicon RNAs were unable to induce a humoral response against AIV. However, TMUV replicon RNA induced IBDV-specific seroconversion in vaccinated chickens, in contrast to VEEV replicon RNA, which showed no significant humoral response. In both AIV and IBDV immunization studies, VEEV DREP generated the highest (neutralizing) antibody responses, which underscores the potential for self-amplifying mRNA vaccine technology to combat emerging poultry diseases.

Predictors of mortality among children at a tertiary hospital in Tanzania: a cohort study

BackgroundTanzania is among the countries in sub-Saharan Africa with the highest under-five mortality rate. The leading causes of mortality among these children include vaccine-preventable infections. Strategies for reducing under-five mortality in hospital settings require a good knowledge of driving factors, which are largely unknown in Tanzania. This study was conducted at Muhimbili National Hospital to determine mortality and its predictors among under-five admitted in the general paediatric wards.MethodsWe conducted a prospective cohort study among children aged between 1 and 59 months admitted in the paediatric wards at Muhimbili National Hospital from 2nd October 2017 to 13th April 2018. We recruited eligible children consecutively and followed them up until discharge or death. We calculated the mortality rate as the incidence density rate and determined the causes and predictors of mortality. We analyzed data to identify and quantify predictors of deaths and used Kaplan-Meir and Cox regression analyses to determine predictors of survival. A P-value of < 0.05 was considered statistically significant.ResultsWe recruited 925 children aged 1–59 months with a median age of 13 and (IQR) of (20) months, females constituted 40.8%. The overall mortality rate was 12.2% (95% CI: 10.2%-14.5%). We found septicaemia (27%), malnutrition (12%), congenital heart disease (12%), pneumonia (11%), and Human Immunodeficiency Virus infection (9%) to be leading causes of mortality. More deaths were observed at night, during the first 24 h of admission, and on weekends. Independent factors for mortality were found to be low wealth quintiles (lowest quintile (AOR = 4.0; 95% CI: 1.19–13.51), second quintile (AOR = 5.2; 95% CI: 1.65–16.69) and middle quintile (AOR = 3.6; 95% CI: 1.14–11.33), unconsciousness on admission (AOR = 18; 95% CI: 6.70–56.82), inability to feed (AOR = 5.7; 95% CI: 1.97–16.51), lethargy (AOR = 4.9; 95% CI: 2.32–10.40), severe wasting (AOR = 4.5; 95% CI: 2.49–8.10), and respiratory distress (AOR = 2.6; 95% CI: 1.40–4.97).ConclusionA high mortality rate was noted in this study and low wealth quantile, low parental education, and lack of health insurance were associated with high mortality. Patients had the highest risk of mortality within 24 h of admission, therefore it is important to raise awareness among clinicians regarding the need for improvement in the monitoring of patients, especially within 24 h of admission.

Dengue fever in the state of Paraná in the seasonal period from 2022 to 2023

Dengue is a viral infectious disease that has become a global public health concern. It is transmitted through the bite of the Aedes aegypti mosquito, which is the primary vector in Brazil and the Americas. This study aims to describe the epidemiological characteristics of dengue in the State of Paraná from July 2022 to July 2023, which is the seasonal period for the Epidemiological Report of the Health Department (SESA) of the State of Paraná. This is a bibliographic review that provides a detailed analysis and interpretation of dengue and the data collected by SESA, PR. The results show a high number of confirmed cases during the seasonal period, with the most critical period being in April 2022. A total of 108 deaths were recorded, with the cities of Londrina and Foz do Iguaçu having the highest number of cases. Control and management of urban arbovirus vectors and home care continues to be the main prevention methods for these diseases, including dengue.

The balance between nuclear import and export of NLRC5 regulates MHC class I transactivation

MHC (major histocompatibility complex) class I molecules play an essential role in regulating the adaptive immune system by presenting antigens to CD8 T cells. CITA (MHC class I transactivator), also known as NLRC5 (NLR family, CARD domain-containing 5), regulates the expression of MHC class I and essential components involved in the MHC class I antigen presentation pathway. While the critical role of the nuclear distribution of NLRC5 in its transactivation activity has been known, the regulatory mechanism to determine the nuclear localization of NLRC5 remains poorly understood. In this study, a comprehensive analysis of all domains in NLRC5 revealed that the regulatory mechanisms for nuclear import and export of NLRC5 coexist and counterbalance each other. Moreover, GCN5 (general control non-repressed 5 protein), a member of HATs (histone acetyltransferases), was found to be a key player to retain NLRC5 in the nucleus, thereby contributing to the expression of MHC class I. Therefore, the balance between import and export of NLRC5 has emerged as an additional regulatory mechanism for MHC class I transactivation, which would be a potential therapeutic target for the treatment of cancer and virus-infected diseases.

Factors associated with the worsening of COVID-19 symptoms among cohorts in community- or home-isolation care in southern Thailand.

This study aimed to investigate factors associated with time-to-referral due to worsening symptoms in patients with laboratory-confirmed COVID-19 in southern Thailand. While underlying diseases have been evaluated to assess COVID-19 severity, the influence of vaccinations and treatments is also crucial. A cohort of 8,638 patients quarantined in home or community isolation with laboratory-confirmed COVID-19 was analyzed. Survival analysis and the Cox proportional hazard ratio were employed to assess factors influencing time-toreferral. Age ≥ 60 years, neurologic disorders, cardiovascular disease, and human immunodeficiency virus infection were identified as significant risk factors for severe COVID-19 referral. Patients who received full- or booster-dose vaccinations had a lower risk of experiencing severe symptoms compared to unvaccinated patients. Notably, individuals vaccinated during the Omicron-dominant period had a substantially lower time-to-referral than those unvaccinated during the Delta-dominant period. Moreover, patients vaccinated between 1 and 6 months prior to infection had a significantly lower risk of time-to-referral than the reference group. These findings demonstrate early intervention in high-risk COVID-19 patients and the importance of vaccination efficacy to reduce symptom severity. The study provides valuable insights for guiding future epidemic management strategies and optimising patient care during infectious disease outbreaks.

From digital to quantum epidemiology: The Quantum Data Lake concept for big data related to viral infectious diseases

The development of quantum epidemiology represents the next anticipated phase in epidemiology transformation, driven by the emergence of new quantum technologies. Epidemiology is currently transitioning into the digital era and undergoing a paradigm shift from a data-driven to a value-driven strategy. Epidemiology data are characterized by uncertainty, multidimensionality, and disconnection, thereby correlating with the preferential quantum approach for data exposition, value creation, and modeling. Examples of such complex epidemiology data include the data on DNA viruses with associated symptoms and diseases. The Quantum Data Lake concept is proposed and consists of several layers and quantum tools, including Robson semantic triples, Quantum Universal Exchange Language, Hyperbolic Dirac Net, &amp;ldquo;quantum ribosome&amp;rdquo; structure, quantum random access memory, teleportation, Quantum Query Language, non-Hermitian gates, and tensor networks (e.g., matrix product state, projected entangled pair state, and multiscale entanglement renormalization ansatz [MERA]), alongside PT-symmetry properties. PT-symmetry can serve as an intuitive modeling tool, and PT-symmetry breaking can detect the hidden shift in the information that is permanently updated in the Data Lake. The computational output is presented as PT-symmetry gain/loss equilibrium breaking in the form of a complex number, i.e., two possible variants of epidemic modeling. For MERA, non-Hermiticity with spontaneous PT-symmetry breaking can theoretically appear as a violation of the entanglement monotonicity and local entanglement gain, leading to a non-reversible character of the coarse-graining transformation. The duality of PT-symmetry equilibrium breaking can be compared to, for example, the estimation of the best and worst scenarios simultaneously, or the gain of entanglement can display a significant correlation between some studied parameters embedded into the data. The fundamental difference between digital and quantum epidemiology is the implementation of quantum logic and reliance on a quantum theory.

Construction of recombinant fluorescent LSDV for high-throughput screening of antiviral drugs

Lumpy skin disease virus (LSDV) infection is a major socio-economic issue that seriously threatens the global cattle-farming industry. Here, a recombinant virus LSDV-ΔTK/EGFP, expressing enhanced green fluorescent protein (EGFP), was constructed with a homologous recombination system and applied to the high-throughput screening of antiviral drugs. LSDV-ΔTK/EGFP replicates in various kidney cell lines, consistent with wild-type LSDV. The cytopathic effect, viral particle morphology, and growth performance of LSDV-ΔTK/EGFP are consistent with those of wild-type LSDV. High-throughput screening allowed to identify several molecules that inhibit LSDV-ΔTK/EGFP replication. The strong inhibitory effect of theaflavin on LSDV was identified when 100 antiviral drugs were screened in vitro. An infection time analysis showed that theaflavin plays a role in the entry of LSDV into cells and in subsequent viral replication stages. The development of this recombinant virus will contribute to the development of LSDV-directed antiviral drugs and the study of viral replication and mechanisms of action.

Tunneling nanotubes and tumor microtubes-Emerging data on their roles in intercellular communication and pathophysiology: Summary of an International FASEB Catalyst Conference October 2023.

In the past decade, there has been a steady rise in interest in studying novel cellular extensions and their potential roles in facilitating human diseases, including neurologic diseases, viral infectious diseases, cancer, and others. One of the exciting new aspects of this field is improved characterization and understanding of the functions and potential mechanisms of tunneling nanotubes (TNTs), which are actin-based filamentous protrusions that are structurally distinct from filopodia. TNTs form and connect cells at long distance and serve as direct conduits for intercellular communication in a wide range of cell types in vitro and in vivo. More researchers are entering this field and investigating the role of TNTs in mediating cancer cell invasion and drug resistance, cellular transfer of proteins, RNA or organelles, and intercellular spread of infectious agents, such as viruses, bacteria, and prions. Even further, the elucidation of highly functional membrane tubes called "tumor microtubes" (TMs) in incurable gliomas has further paved a new path for understanding how and why the tumor type is highly invasive at the cellular level and also resistant to standard therapies. Due to the wide-ranging and rapidly growing applicability of TNTs and TMs in pathophysiology across the spectrum of biology, it has become vital to bring researchers in the field together to discuss advances and the future of research in this important niche of protrusion biology.

Global Basic Reproduction Number of African Swine Fever in Wild Boar and a Mental Model to Explore the Disease Dynamics

Basic reproduction number (R0) is a mathematical expression used in epidemiology to address expected number of secondary cases. R0 helps to predict outbreak diffusion and preventive measures. As African swine fever (ASF) is a viral infectious disease, there are significant studies related to R0 of the ASF outbreak, but most of them are investigated in a zonal and geospecific boundary. This study explores the general overview of African swine fever virus (ASFV) R0 based on existing literature and examines for the global scale using a doubling time approach using wild boar outbreaks. Further, a qualitative mental model is developed to explore the ASF disease dynamics. It was found that the average R0 was 3.56 from existing literature. Based on the global scenario, ASFV spread in wild boar was above the threshold line (R0≥1). The recent growth trend (R0=5.87) flagging the very high risk. ASFV is threatening the world. The qualitative mental model highlighted the veterinary services as awareness and R&amp;D support are highlighted as the control measures. This study provides a reference to researchers and veterinarians in setting strategies of developing preventive measures and highlights the importance of awareness programs and R&amp;D support for mitigating the ASFV spread.

Evaluation of D-dimer and prothrombin time in alcohol related liver cirrhosis with comparison of machine learning analyses

ObjectivesLiver cirrhosis (LC) can be caused by obesity, alcohol consumption, viral infection, and autoimmune disease. Early diagnosis and management of LC is important for patient quality of life. Non-invasive diagnostic methods are useful for predicting the current status and mortality risk of LC. The purpose of this study is to identify relevant diagnostic factors measured in routine laboratory test of alcohol-related liver cirrhosis (ALC) patients. MethodsThis study analyzed data from 127 patients with ALC, including their laboratory test results and clinical information, including coagulation parameters, hematologic parameters, and biochemical parameters. These data were used to compare the performance of the prediction models from three machine learning algorithms including K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF). ResultsHigher Model for End-stage Liver Disease (MELD) score were associated with prothrombin time (PT) and D-dimer. Logistic and multiple linear regression analyses revealed significant factors predicting mortality in the MELD group. Machine learning approaches were used to predict death in ALC patients using some laboratory parameters associated with mortality. The prediction model based on SVM exhibited better prediction performance than others. ConclusionPT and D-dimer were the factors that were most strongly associated with 90-day mortality, and machine learning methods can create prediction models with good predictive power.

Parrot Trade and the Potential Risk of Psittacosis as a Zoonotic Disease in Indonesian Bird Markets

Wildlife trade, both legal and illegal, is increasingly recognized as a key factor in the rise of emerging viral infectious diseases, and this is especially apparent in Asia, where large numbers of wildlife are openly offered for sale in bird markets. We here focus on the risk of Psittacosis becoming a zoonotic disease in the wildlife markets of Java and Bali, Indonesia. Psittacosis is particularly prevalent in parrots (hence the name), and the trade in parrots was instrumental in the Great Parrot Fever Pandemic in 1929/1930. Between 2014 and 2023, we conducted 176 surveys of 14 bird markets, during which we recorded 4446 largely wild-caught parrots for sale. On average, each market had nine genera on offer, and the diversity of genera increased with the increasing presence of parrots (up to 16 genera). For most of the bird markets during each survey, parrots from different genera and originating from different parts of the world, were offered for sale alongside each other. Genera offered for sale together did not cluster into natural (geographic) groups. We found no temporal difference in the sale of parrots. We conclude that the omnipresence of wild-caught parrots from various geographic regions in large numbers within the same bird markets increases the risk that psittacosis is present and that this poses a real risk for the zoonotic spread of avian chlamydiosis to humans.

First Case of Highly Pathogenic Avian Influenza H5N1 in Montenegro

Abstract Avian influenza, commonly known as bird flu, is a highly infectious viral disease that affects birds, including wild water birds and poultry. The emergence and spread of highly pathogenic avian influenza (HPAI) strains, such as H5N1, have raised concerns due to their potential to cause severe outbreaks and cross the species barrier, leading to human infections and global public health emergencies. In this study, we report the first case of HPAI H5N1 detection in Montenegro. Twenty-six carcasses of dalmatian pelicans were found in Skadar Lake, Montenegro, and the H5N1 subtype was confirmed through molecular testing in the samples from pelicans. The whole influenza genome was sequenced and belonging to clade 2.3.4.4b was determined.

Neutralization of SARS-CoV-2 BA.2.86 and JN.1 by CF501 adjuvant-enhanced immune responses targeting the conserved epitopes in ancestral RBD

The emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2.86 and JN.1 raise concerns regarding their potential to evade immune surveillance and spread globally. Here, we test sera from rhesus macaques immunized with 3 doses of wild-type SARS-CoV-2 receptor-binding domain (RBD)-Fc adjuvanted with the STING agonist CF501. We find that the sera can potently neutralize pseudotyped XBB.1.5, XBB.1.16, CH.1.1, EG.5, BA.2.86, and JN.1, with 50% neutralization titers ranging from 3,494 to 7,424. We also demonstrate that CF501, but not Alum, can enhance immunogenicity of the RBD from wild-type SARS-CoV-2 to improve induction of broadly neutralizing antibodies (bnAbs) with binding specificity and activity similar to those of SA55, BN03, and S309, thus exhibiting extraordinary broad-spectrum neutralizing activity. Overall, the RBD from wild-type SARS-CoV-2 also contains conservative epitopes. The RBD-Fc adjuvanted by CF501 can elicit potent bnAbs against JN.1, BA.2.86, and other XBB subvariants. This strategy can be adopted to develop broad-spectrum vaccines to combat future emerging and reemerging viral infectious diseases.

Pragmatic Return to Effective Dental Infection Control through Triage and Testing (PREDICT): an observational, feasibility study to improve dental office safety

BackgroundDuring the COVID-19 pandemic, there was a substantial interruption of care, with patients and workers fearful to return to the dental office. As dental practice creates a highly aerosolized environment, the potential for spread of airborne illness is magnified. As a means to increase safety and mitigate risk, pre-visit testing for SARS-CoV-2 has the potential to minimize disease transmission in dental offices. The Pragmatic Return to Effective Dental Infection Control through Testing (PREDICT) Feasibility Study examined the logistics and impact of two different testing mechanisms (laboratory-based PCR viral testing and point-of-care antigen testing) in dental offices.MethodsDental healthcare workers (DHCWs) and patients in four dental offices within the National Dental Practice-based Research Network participated in this prospective study. In addition to electronic surveys, participants in two offices completed POC testing, while participants in two offices used lab-based PCR methods to detect SARS-CoV-2 infection. Analysis was limited to descriptive measures, with median and interquartile ranges reported for Likert scale responses and mean and standard deviation for continuous variables.ResultsOf the total 72 enrolled, 28 DHCWs and 41 patients completed the protocol. Two patients (4.9%) tested positive prior to their visit, while 2 DHCWs (12.5%) tested positive for SARS-CoV-2 infection at the start of the study. DHCWs and patients shared similar degree of concern (69% and 63%, respectively) for contracting COVID-19 from patients, while patients feared contracting COVID-19 from DHCWs less (49%). Descriptive statistics calculations revealed that saliva, tongue epithelial cells, and nasal swabs were the most desirable specimen collection method; both testing (LAB and POC) protocols took similar amounts of total time to complete; and DHCWs and patients reported feeling more comfortable when both groups were tested.ConclusionsWhile a larger-scale, network study is necessary for generalizability of results, this feasibility study suggests that SARS-CoV-2 testing can be effectively implemented into dental practice workflows and positively impact perception of safety for DHCWs and patients. As new virulent infectious diseases emerge, preparing dental personnel to employ an entire toolbox of risk mitigation strategies, including testing, may have the potential to decrease dental practice closure time, maintaining continuity of dental care services for patients.Trial registrationClinicalTrials.gov: NCT05123742.

Benidipine impairs innate immunity converting sublethal to lethal infections in a murine model of spotted fever rickettsiosis.

Spotted fever group rickettsiae are tick-borne obligate intracellular bacteria that infect microvascular endothelial cells. Humans and mammalian infection results in endothelial cell barrier dysfunction and increased vascular permeability. We previously demonstrated that treatment of Rickettsia parkeri-infected cells with the calcium channel blocker benidipine significantly delayed vascular barrier permeability. Thus, we hypothesized that benidipine, known to be safe and effective for other clinical processes, could reduce rickettsia-induced vascular permeability in vivo in an animal model of spotted fever rickettsiosis. Based on liver, lung and brain vascular FITC-dextran extravasation studies, benidipine did not reliably impact vascular permeability. However, it precipitated a deleterious effect on responses to control sublethal R. parkeri infection. Animals treated with benidipine alone had no clinical signs or changes in histopathology and splenic immune cell distributions. Benidipine-treated infected animals had marked increases in tissue and blood bacterial loads, more extensive inflammatory histopathologic injury, and changes in splenic architecture and immune cell distributions potentially reflecting diminished Ca2+ signaling, reduced innate immune cell activation, and loss of rickettsial propagation control. Impaired T cell activation by R. parkeri antigen in the presence of benidipine was confirmed in vitro with the use of NKT cell hybridomas. The unexpected findings stand in stark contrast to recent discussions of the benefits of calcium channel blockers for viral infections and chronic infectious or inflammatory diseases. A role for calcium channel blockers in exacerbation of human rickettsiosis and acute inflammatory infections should be evaluated by a retrospective review of patient's outcomes and medications.

Genomic Regions and Candidate Genes Affecting Response to Heat Stress with Newcastle Virus Infection in Commercial Layer Chicks Using Chicken 600K Single Nucleotide Polymorphism Array.

Heat stress results in significant economic losses to the poultry industry. Genetics plays an important role in chickens adapting to the warm environment. Physiological parameters such as hematochemical parameters change in response to heat stress in chickens. To explore the genetics of heat stress resilience in chickens, a genome-wide association study (GWAS) was conducted using Hy-Line Brown layer chicks subjected to either high ambient temperature or combined high temperature and Newcastle disease virus infection. Hematochemical parameters were measured during three treatment phases: acute heat stress, chronic heat stress, and chronic heat stress combined with NDV infection. Significant changes in blood parameters were recorded for 11 parameters (sodium (Na+, potassium (K+), ionized calcium (iCa2+), glucose (Glu), pH, carbon dioxide partial pressure (PCO2), oxygen partial pressure (PO2), total carbon dioxide (TCO2), bicarbonate (HCO3), base excess (BE), and oxygen saturation (sO2)) across the three treatments. The GWAS revealed 39 significant SNPs (p < 0.05) for seven parameters, located on Gallus gallus chromosomes (GGA) 1, 3, 4, 6, 11, and 12. The significant genomic regions were further investigated to examine if the genes within the regions were associated with the corresponding traits under heat stress. A candidate gene list including genes in the identified genomic regions that were also differentially expressed in chicken tissues under heat stress was generated. Understanding the correlation between genetic variants and resilience to heat stress is an important step towards improving heat tolerance in poultry.

Marmosets as models of infectious diseases.

Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where human trials are not feasible, i.e., for those diseases that occur infrequently in the human population. The common marmoset (Callithrix jacchus), a Neotropical new-world (platyrrhines) non-human primate, has gained increasing attention as an animal model for a number of diseases given its small size, availability and evolutionary proximity to humans. This review aims to (i) discuss the pros and cons of the common marmoset as an animal model by providing a brief snapshot of how marmosets are currently utilized in biomedical research, (ii) summarize and evaluate relevant aspects of the marmoset immune system to the study of infectious diseases, (iii) provide a historical backdrop, outlining the significance of infectious diseases and the importance of developing reliable animal models to test novel therapeutics, and (iv) provide a summary of infectious diseases for which a marmoset model exists, followed by an in-depth discussion of the marmoset models of two studied bacterial infectious diseases (tularemia and melioidosis) and one viral infectious disease (viral hepatitis C).