Oesophageal and oral ulcer tuberculous associated with human T-cell lymphotropic virus type 1 (HTLV-1) and SARS-CoV-2 infection

Oesophageal involvement due to tuberculosis (TB) and coinfection with HTLV-1 is rare and can be complicated by the presence of other infections that affect the mucosa of the upper respiratory tract, such as COVID-19. We present the case of a 27-year-old male patient, with 3 months of illness, weight loss, dysphagia, and ulcers in the oral cavity. Tomography showed oesophageal perforation and after oesophageal ulcer biopsy, TB was diagnosed, in addition to infection by HTLV-1 and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The patient responded satisfactorily to antituberculous treatment and corticosteroids. Considering the association between rare extrapulmonary tuberculosis and other immunosuppressive pathologies, it is crucial to identify these pathologies in such patients.

19th Seminar on Tropical Pathology and Public Health 12th Biotechnology Week 1st Physical Therapy Week, Virtual, 23-25 November 2022

These proceedings comprise 85 articles spanning diverse fields such as bacteriology, molecular biology, biotechnology, dermatology, infectious and parasitic diseases, epidemiology, physiotherapy, immunology, mycology, parasitology, pathology, collective health, and virology. The articles delve into a wide range of research topics, from repurposing drugs for Mycobacterium abscessus complex infections to utilising artificial intelligence for SARS-CoV-2 diagnosis. In bacteriology, investigations explore the correlation between smoking and Helicobacter pylori infection in gastric adenocarcinoma patients, as well as the resistance profiles of Staphylococcus aureus and Pseudomonas aeruginosa in tracheostomised children. Molecular biology studies focus on gene polymorphisms related to diseases like paracoccidioidomycosis. Biotechnology research emphasises bioactive molecules in species like Croton urucurana and the development of computational models for cytotoxicity prediction. Dermatology articles address stability characterisation in vegetable oil-based nanoemulsions. The section on infectious and parasitic diseases encompasses studies on COVID-19 vaccine response in pregnant women and the impact of infection prevention measures in rehabilitation hospitals. Epidemiology investigations analyse trends in premature mortality, tuberculosis in diabetic patients, and public adherence to non-pharmacological COVID-19 measures. Physiotherapy research covers topics such as telerehabilitation through a developed game and the prevalence of congenital anomalies. Immunology studies explore immune responses in HIV and Leishmaniasis, whilst mycology investigates the biotechnological potential of fungi from the cerrado biome. Parasitology research evaluates treatment efficacy against vectors parasites such as Aedes aegypti and Toxoplasma gondii. Pathology articles discuss intentional intoxication in cattle and the influence of curcumin on acute kidney injury therapy. Collective health studies focus on intervention plan development in healthcare settings and pesticide use in horticulture. Lastly, virology research investigates parvovirus occurrence in hospitalised children during the COVID-19 pandemic, hidden hepatitis B virus infection in inmates, and the prevalence of HPV and HTLV-1/2 infections in specific populations.

Sotrovimab retains activity against SARS-CoV-2 omicron variant BQ.1.1 in a non-human primate model.

The SARS-CoV2 Omicron variants have acquired new Spike mutations leading to escape from the most of the currently available monoclonal antibody treatments reducing the options for patients suffering from severe Covid-19. Recently, both in vitro and in vivo data have suggested that Sotrovimab could retain partial activity against recent omicron sub-lineage such as BA.5 variants, including BQ.1.1. Here we report full efficacy of Sotrovimab against BQ.1.1 viral replication as measure by RT-qPCR in a non-human primate challengemodel.

Covid-19: A Multi-Host Pandemic

SARS-CoV-2, the causal agent of the COVID-19 pandemic, is related to a group of viruses (Sarbecovirus) that circulate in horseshoe bats. Its origin is still uncertain, as there is lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2. Irrespective of its origin, SARS-CoV-2 has been shown to replicate in many mammalian species. So far, over forty species have been found to be susceptible to SARS-CoV-2 infection, and natural infections have been documented in at least 23 species of distant mammalian orders, including Primata, Rodentia, Carnivora, and Arthiodactyla. In two of those species, minks and white tailed deer, continued transmission among conspecifics occurred following introduction of SARS-CoV-2 from humans, at a rate which makes mink farms and deer populations suitable compartments where the virus may be maintained and evolve, and then perhaps spill back to humans or other animals as a new variant, as suggested by molecular evidence. Considering the above, what is truly unique about this pandemic, and adds a major obstacle to attain its control, is its multi-host nature. This is another compelling example of the relevance of the 'One Health' approach. This approach recognizes the inextricable links between people and nature, and visualizes the health and disease phenomenon from an integrative perspective. The COVID-19 pandemic urges us to acknowledge the interconnection between people and the remaining forms of life, and with the environments they share, and demonstrates that the improvement of global health needs a collaborative, multisectoral, and transdisciplinary approach, acting at the local, regional and global levels. This concept becomes paramount when taking into account that most diseases affecting humans in the last decades -not only COVID-19 - have been caused by pathogens originated in animals.Copyright © 2023

Zooanthropogenic potential of SARS-CoV-2 virus: Implications for vaccine-mediated immunity

The human pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in December, 2019 is still continuing in various parts of the world. The SARS-CoV-2 has evolved through sporadic mutations and recombination events and the emergence of alternate variants following adaptations in humans and human-to-animal transmission (zooanthraponosis) has raised concerns over the efficacy of vaccines against new variants. The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV- 2-related viruses in bats and pangolins. A recent report of back-andforth transmission of SARS-CoV-2 between humans and minks on mink farms in the Netherlands has sparked widespread interest in zooanthroponotic transmission of SARS-CoV-2 followed by reemergence to infect human populations. The risk of animal to human transmission depends on virus-host interaction in susceptible species that may be short-term or long term risks. The short term risk might be due to infection to humans during the viremic stage in susceptible animals. The long term risk might be either due to persistence of the virus at population level or latency of infection leading to risk of evolution and re-emergence of the virus. Experimental studies have identified a range of animals that are susceptible and permissive to SARS-CoV-2 infection viz. cats, ferrets, hamsters, mink, non-human primates, tree shrews, raccoon dogs, fruit bats, and rabbits. The health impacts of SARS-CoV-2 infection in animals are unknown and it is likely that other susceptible species have not been discovered yet. Apart from farmed animals, stray cats and rodents have been identified as a potential opportunity for ongoing transmission in intense farming situations. Recognizing animal species that are most susceptible to infection is the first step in preventing ongoing transmission from humans. Minimizing the risk of zooanthraponosis requires multi-sectoral coordination that includes implementation of strict biosecurity measures such as controlled access to farms that house susceptible animals, bio-secure entry and exit protocols, disinfection protocols in farm, down time for animal transport vehicles and daily assessments of human handlers for exposure to SARS-CoV- 2. Hence, active surveillance in animal species that are prioritized based on risk assessment need to be initiated in coordination with health and environment sectors for early identification of emerging and re-emerging variants of SARS-CoV-2 virus in animals.

Primate play during COVID-19

For more information see: 'Play Signals, Play Moves: A Gorilla Critique of Play Theory' International Journal of Play, Nov 2018. https://doi.org/10.1080/21594937.2018.1532681

The Isolation and In Vitro Differentiation of Primary Fetal Baboon Tracheal Epithelial Cells for the Study of SARS-CoV-2 Host-Virus Interactions.

The mucociliary airway epithelium lines the human airways and is the primary site of host-environmental interactions in the lung. Following virus infection, airway epithelial cells initiate an innate immune response to suppress virus replication. Therefore, defining the virus-host interactions of the mucociliary airway epithelium is critical for understanding the mechanisms that regulate virus infection, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Non-human primates (NHP) are closely related to humans and provide a model to study human disease. However, ethical considerations and high costs can restrict the use of in vivo NHP models. Therefore, there is a need to develop in vitro NHP models of human respiratory virus infection that would allow for rapidly characterizing virus tropism and the suitability of specific NHP species to model human infection. Using the olive baboon (Papio anubis), we have developed methodologies for the isolation, in vitro expansion, cryopreservation, and mucociliary differentiation of primary fetal baboon tracheal epithelial cells (FBTECs). Furthermore, we demonstrate that in vitro differentiated FBTECs are permissive to SARS-CoV-2 infection and produce a potent host innate-immune response. In summary, we have developed an in vitro NHP model that provides a platform for the study of SARS-CoV-2 infection and other human respiratory viruses.

Cynomolgus Macaque Model for COVID-19 Delta Variant.

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

"Natural Laboratory Complex" for novel primate neuroscience.

We propose novel strategies for primate experimentation that are ethically valuable and pragmatically useful for cognitive neuroscience and neuropsychiatric research. Specifically, we propose Natural Laboratory Complex or Natural Labs, which are a combination of indoor-outdoor structures for studying free moving and socially housed primates in natural or naturalistic environment. We contend that Natural Labs are pivotal to improve primate welfare, and at the same time to implement longitudinal and socio-ecological studies of primate brain and behavior. Currently emerging advanced technologies and social systems (including recent COVID-19 induced "remote" infrastructures) can speed-up cognitive neuroscience approaches in freely behaving animals. Experimental approaches in natural(istic) settings are not in competition with conventional approaches of laboratory investigations, and could establish several benefits at the ethical, experimental, and economic levels.

Elevated soluble urokinase plasminogen activator receptor is associated with renal dysfunction in a Chlorocebus atheiops COVID-19 model.

Increases of soluble urokinase plasminogen activator receptor (suPAR) were measured in both urine and plasma of a Chlorocebus aethiops (African green monkey; AGM) mucosal infected with SARS-CoV-2. The data indicate that elevated suPAR may be associated with renal dysfunction and pathology in the context of COVID-19.

One Health Perspectives on New Emerging Viral Diseases in African Wild Great Apes.

The most recent emerging infectious diseases originated in animals, mainly in wildlife reservoirs. Mutations and recombination events mediate pathogen jumps between host species. The close phylogenetic relationship between humans and non-human primates allows the transmission of pathogens between these species. These pathogens cause severe impacts on public health and impair the conservation of habituated or non-habituated wild-living apes. Constant exposure of great apes to human actions such as hunting, deforestation, the opening of roads, and tourism, for example, contributes to increased interaction between humans and great apes. In spite of several studies emphasizing the risks of pathogen transmission between animals and humans, outbreaks of the reverse transmission of infectious agents threatening wildlife still occur on the African continent. In this context, measures to prevent the emergence of new diseases and conservation of primate species must be based on the One Health concept; that is, they must also ensure the monitoring of the environment and involve political and social aspects. In this article, we review and discuss the anthropological aspects of the transmission of diseases between people and wild primates and discuss new anthropozoonotic diseases in great apes in Africa from studies published between 2016 and 2020. We conclude that the health of great apes also depends on monitoring the health of human populations that interact with these individuals.

Primate play during COVID-19

For more information see: 'Play Signals, Play Moves: A Gorilla Critique of Play Theory' International Journal of Play, Nov 2018. https://doi.org/10.1080/21594937.2018.1532681

FDA and industry collaboration: Identifying opportunities to further reduce reliance on nonhuman primates for nonclinical safety evaluations.

The nonhuman primate (NHP) has always been a limited resource for pharmaceutical research with ongoing efforts to conserve. This is due to their inherent biological properties, the growth in biotherapeutics and other modalities, and their use in small molecule drug development. The SARS-CoV-2 pandemic has significantly impacted the availability of NHPs due to the immediate need for NHPs to develop COVID-19 vaccines and treatments and the China NHP export ban; thus, accelerating the need to further replace, reduce and refine (3Rs) NHP use. The impact of the NHP shortage on drug development led DruSafe, BioSafe, and the United States (U.S.) Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) to discuss this issue at their 2021 annual meeting. This meeting identified areas to further the 3Rs in NHP use within the current nonclinical safety evaluation regulatory framework and highlighted the need to continue advancing alternative methods towards the aspirational goal to replace use of NHPs in the long term. Alignment across global health authorities is necessary for implementation of approaches that fall outside existing guidelines. This article captures the proceedings from this meeting highlighting current best practices and areas for 3Rs in NHP use.

Human-animal spillover of SARS-CoV-2: Implications for public health

COVID-19 pandemic caused by the recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a significant public health catastrophe in a century. While the precise origin of SARS-CoV-2, and its mode of introduction into the human population, is not yet fully resolved, there is evidence that SARS-CoV-2 originated from bats. As zoonotic viruses infecting humans can spill back into susceptible animal hosts, SARS-CoV-2 has demonstrated the ability to infect many nonhuman animal host species. The list of animal species susceptible to SARS-CoV-2 infection continues to grow and includes domestic animals, primates, pet animals, and zoo animals. In addition, based on the ability of the spike protein to bind to the ACE-2 receptor, computational predictions have identified dozens of additional possible animal hosts for SARS-CoV-2. In addition, there are multiple reports of human infections from SARS-CoV-2 infected animals. We discovered widespread natural infection of wild white-tailed deer with SARS-CoV-2 in the USA, suggesting their role as a potential SARS-CoV-2 reservoir. Establishing an animal reservoir could facilitate the continued circulation of SARS-CoV-2 independent of circulation in humans. In addition, deer could pass on the infection to other susceptible wild animals such as rodents, foxes, and raccoons resulting in the establishment of SARS-CoV-2 enzootic transmission cycles. Such a scenario could result in virus adaptation and the emergence of novel variants that could escape the protection of current human SARS-CoV-2 vaccines. This presentation will discuss our recent findings on natural SARS-CoV-2 infection of deer and the long-term implications of human-animal-human spillover of SARS-CoV-2.

The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion.

ARNSTEN, A.F.T., M.K.P. Joyce and A.C. Roberts. The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion. NEUROSCI BIOBEHAV REV XXX-XXX, 2022. The symptoms of major-depressive-disorder include psychic pain and anhedonia, i.e. seeing the world through an "aversive lens". The neurobiology underlying this shift in worldview is emerging. Here these data are reviewed, focusing on how activation of subgenual cingulate (BA25) induces an "aversive lens", and how higher prefrontal cortical (PFC) areas (BA46/10/32) provide top-down regulation of BA25 but are weakened by excessive dopamine and norepinephrine release during stress exposure, and dendritic spine loss with chronic stress exposure. These changes may generate an attractor state, which maintains the brain under the control of BA25, requiring medication or neuromodulatory treatments to return connectivity to a more flexible state. In line with this hypothesis, effective anti-depressant treatments reduce the activity of BA25 and restore top-down regulation by higher circuits, e.g. as seen with SSRI medications, ketamine, deep brain stimulation of BA25, or rTMS to strengthen dorsolateral PFC. This research has special relevance in an era of chronic stress caused by the COVID19 pandemic, political unrest and threat of climate change.

Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model.

Molnupiravir (EIDD-2801) is a prodrug of a ribonucleoside analogue that is currently being used under a US FDA emergency use authorization for the treatment of mild to moderate COVID-19. We evaluated molnupiravir for efficacy as an oral treatment in the rhesus macaque model of SARS-CoV-2 infection. Twenty non-human primates (NHPs) were challenged with SARS-CoV-2 and treated with 75 mg/kg (n = 8) or 250 mg/kg (n = 8) of molnupiravir twice daily by oral gavage for 7 days. The NHPs were observed for 14 days post-challenge and monitored for clinical signs of disease. After challenge, all groups showed a trend toward increased respiration rates. Treatment with molnupiravir significantly reduced viral RNA levels in bronchoalveolar lavage (BAL) samples at Days 7 and 10. Considering the mild to moderate nature of SARS-CoV-2 infection in the rhesus macaque model, this study highlights the importance of monitoring the viral load in the lung as an indicator of pharmaceutical efficacy for COVID-19 treatments. Additionally, this study provides evidence of the efficacy of molnupiravir which supplements the current ongoing clinical trials of this drug.

Prevelance of self medication with pain killers during COVID 19 pandemic among dental students of Kashmir

Introduction: Self medication may be defined as the practice of use of medication for the treatment of any disease on their own without consulting concerned health care professional. If the practice is not correctly done due to lack of knowledge in students pursuing medical studies without evaluation by the trained medical professionals it can lead to ineffective treatment which can result in unnecessary expenses and drug dependence over a period of time. AIM: This study was conducted to find out self medication behaviour and its associated factors amongst dental students of Government Dental College and Hospital, Srinagar. Materials and methodology: A cross sectional study was conducted on 100 dental students and interns from Government Dental College And Hospital, Srinagar, Jammu and Kashmir between the month of September 2021 to November 2021 after ethical clearance was taken from said institution under order no GDC/Pedo/1677. A convenience sampling technique was used and survey consisting of 11 questions was be distributed amongst the dental students which included the questions of demographic variables and information related self medication with painkillers during the COVID times of 2020-2021 for any painful ailment and to evaluate awareness about side effects and loop holes of self medication. Data was collected and was statistically analysed using Statistical Package for Social Sciences (SPSS) version 21.

A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2.

The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague-Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster.

Metagenomic Next-Generation Sequencing Reveals the Profile of Viral Infections in Kidney Transplant Recipients During the Covid-19 Pandemic

Purpose: To study the clinical application of metagenomic next-generation sequencing (mNGS) in the detection of viral infections in kidney transplant recipients (KTRs) during the COVID-19 pandemic. Method(s): Using mNGS techniques, 50 human fluid samples of KTRs were detected in Henan Province People's Hospital between May 2020 to May 2021, including 20 bronchoalveolar lavage fluid (BALF) samples, 21 urine samples and 9 blood samples. The detected nucleic acid sequences were compared and analyzed with the existing viral nucleic acid sequences in the database, and the virus infection spectrum of KTRs was drawn. Result(s): The viral nucleic acids of 15 types of viruses were detected in 96.00% (48/50) of the samples, of which 11 types of viruses were in BALF (95.00%, 19/20), and the dominant viruses were torque teno virus (TTV) (65.00%;13/20), cytomegalovirus (CMV) (45.00%;9/20) and human alphaherpesvirus 1 (25.00%;5/20). 12 viruses (95.24%, 20/21) were detected in the urine, and the dominant viruses were TTV (52.38%;11/21), JC polyomavirus (52.38%;11/21), BK polyomavirus (42.86%;9/21), CMV (33.33%;7/21) and human betaherpesvirus 6B (28.57%;6/21). 7 viruses were detected in the blood (100.00%, 9/9), and the dominant virus was TTV (100.00%;9/9). Four rare viruses were detected in BALF and urine, including WU polyomavirus, primate bocaparvovirus 1, simian virus 12, and volepox virus. Further analysis showed that TTV infection with high reads indicated a higher risk of acute rejection (P<0.05). Conclusion(s): mNGS detection reveals the rich virus spectrum of infected persons after kidney transplantation, and improves the detection rate of rare viruses. TTV may be a new biomarker for predicting rejection. (Figure Presented).