One Health Investigation into Mpox and Pets, United States.

Monkeypox virus (MPXV) is zoonotic and capable of infecting many mammal species. However, whether common companion animals are susceptible to MPXV infection is unclear. During July 2022-March 2023, we collected animal and environmental swab samples within homes of confirmed human mpox case-patients and tested for MPXV and human DNA by PCR.

A cocktail of human monoclonal antibodies broadly neutralizes North American rabies virus variants as a promising candidate for rabies post-exposure prophylaxis.

Human rabies remains a globally significant public health problem. Replacement of polyclonal anti-rabies immunoglobulin (RIG), a passive component of rabies post-exposure prophylaxis (PEP), with a monoclonal antibody (MAb), would eliminate the cost and availability constraints associated with RIG. Our team has developed and licensed a human monoclonal antibody RAB1 (Rabishield), as the replacement for RIG where canine rabies is enzootic.

Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.

Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.

Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model.

Smallpox, caused by (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing.

Laboratory Infection of Novel Akhmeta Virus in CAST/EiJ Mice.

Akhmeta virus is a zoonotic first identified in 2013 in the country of Georgia. Subsequent ecological investigations in Georgia have found evidence that this virus is widespread in its geographic distribution within the country and in its host-range, with rodents likely involved in its circulation in the wild. Yet, little is known about the pathogenicity of this virus in rodents.

IMVAMUNE and ACAM2000 Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model.

The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today's populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios.

Pharmacokinetic Profiles of Gabapentin after Oral and Subcutaneous Administration in Black-tailed Prairie Dogs ().

In veterinary and human medicine, gabapentin (a chemical analog of γ-aminobutyric acid) is commonly prescribed to treat postoperative and chronic neuropathic pain. This study explored the pharmacokinetics of oral and subcutaneous administration of gabapentin at high (80 mg/kg) and low (30 mg/kg) doses as a potential analgesic in black-tailed prairie dogs (; = 24). The doses (30 and 80 mg/kg) and half maximal effective concentration (1.

Magnitude and diversity of immune response to vaccinia virus is dependent on route of administration.

Historic observations suggest that survivors of smallpox maintained lifelong immunity and protection to subsequent infection compared to vaccinated individuals. Although protective immunity by vaccination using a related virus (vaccinia virus (VACV) strains) was the key for smallpox eradication, it does not uniformly provide long term, or lifelong protective immunity (Heiner et al., 1971).

Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro.

Currently, no rabies virus-specific antiviral drugs are available. Ranpirnase has strong antitumor and antiviral properties associated with its ribonuclease activity. TMR-001, a proprietary bulk drug substance solution of ranpirnase, was evaluated against rabies virus in three cell types: mouse neuroblastoma, BSR (baby hamster kidney cells), and bat primary fibroblast cells.

Use of live Variola virus to determine whether CAST/EiJ mice are a suitable surrogate animal model for human smallpox.

Numerous animal models of systemic orthopoxvirus disease have been developed to evaluate therapeutics against variola virus (VARV), the causative agent of smallpox. These animal models do not resemble the disease presentation in human smallpox and most used surrogate Orthopoxviruses. A rodent model using VARV has a multitude of advantages, and previous investigations identified the CAST/EiJ mouse as highly susceptible to monkeypox virus infection, making it of interest to determine if these rodents are also susceptible to VARV infection.

Inactivated Rabies Virus-Based Ebola Vaccine Preserved by Vaporization Is Heat-Stable and Immunogenic Against Ebola and Protects Against Rabies Challenge.

Background: Ebola virus (EBOV) is a highly lethal member of the Filoviridae family associated with human hemorrhagic disease. Despite being a sporadic disease, it caused a large outbreak in 2014-2016 in West Africa and another outbreak recently in the Democratic Republic of Congo. Several vaccine candidates are currently in preclinical and clinical studies but none are stable without cold chain storage.

Inactivated Rabies Virus-Vectored Immunocontraceptive Vaccine in a Thermo-Responsive Hydrogel Induces High and Persistent Antibodies against Rabies, but Insufficient Antibodies against Gonadotropin-Releasing Hormone for Contraception.

Rabies is preventable through vaccination, but the need to mount annual canine vaccination campaigns presents major challenges in rabies control and prevention. The development of a rabies vaccine that ensures lifelong immunity and animal population management in one dose could be extremely advantageous. A nonsurgical alternative to spay/neuter is a high priority for animal welfare, but irreversible infertility in one dose has not been achieved.

Analgesia during Monkeypox Virus Experimental Challenge Studies in Prairie Dogs ().

Because human patients with monkeypox virus (MPXV) infection report painful symptoms, it is reasonable to assume that animals infected with MPXV experience some degree of pain. Understanding whether and how analgesics affect MPXV disease progression is crucial when planning in vivo challenge experiments. In the current study, we challenged prairie dogs with a low dose (4 ×10³ pfu) of MPXV and treated with meloxicam (NSAID) or buprenorphine (opioid); control animals did not receive analgesia or received analgesia without MPXV challenge.

PREVALENCE OF ANTIBODIES TO ORTHOPOXVIRUS IN WILD CARNIVORES OF NORTHWESTERN CHIHUAHUA, MEXICO.

The distribution of orthopoxviruses (OPXVs) across the North American continent is suggested to be widespread in a wide range of mammalian hosts on the basis of serosurveillance studies. To address the question of whether carnivores in northwestern Mexico are exposed to naturally circulating OPXVs, wild carnivores were collected by live trapping within four different habitat types during fall of 2013 and spring of 2014 within the Janos Biosphere Reserve in northwestern Chihuahua, Mexico. A total of 51 blood samples was collected for testing.

Preclinical pharmacokinetic evaluation to facilitate repurposing of tyrosine kinase inhibitors nilotinib and imatinib as antiviral agents.

Background: Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for "repurposing" as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible.

Revisiting rabies virus neutralizing antibodies through infecting BALB/c mice with live rabies virus.

This study investigates the production of rabies virus (RABV) neutralizing antibody after virus infection through a mouse model. The BALB/c mice from different age groups (three, five, seven week old) were intramuscularly inoculated with live rabies virus (TX coyote 323R). Without pre-exposure or post-exposure prophylaxis (PEP), we found there is a decreased fatality with increased age of animals, the mortalities are 60%, 50%, and 30%, respectively.

Retrospective Proteomic Analysis of Serum After Akhmeta Virus Infection: New Suspect Case Identification and Insights Into Poxvirus Humoral Immunity.

Serologic cross-reactivity, a hallmark of orthopoxvirus (OPXV) infection, makes species-specific diagnosis of infection difficult. In this study, we used a variola virus proteome microarray to characterize and differentiate antibody responses to nonvaccinia OPXV infections from smallpox vaccination. The profile of 2 case patients infected with newly discovered OPXV, Akhmeta virus, exhibited antibody responses of greater intensity and broader recognition of viral proteins and includes the B21/22 family glycoproteins not encoded by vaccinia virus strains used as vaccines.

Assessing Monkeypox Virus Prevalence in Small Mammals at the Human-Animal Interface in the Democratic Republic of the Congo.

During 2012, 2013 and 2015, we collected small mammals within 25 km of the town of Boende in Tshuapa Province, the Democratic Republic of the Congo. The prevalence of monkeypox virus (MPXV) in this area is unknown; however, cases of human infection were previously confirmed near these collection sites. Samples were collected from 353 mammals (rodents, shrews, pangolins, elephant shrews, a potamogale, and a hyrax).

Characterization of Eptesipoxvirus, a novel poxvirus from a microchiropteran bat.

The genome of Eptesipoxvirus (EPTV) is the first poxvirus genome isolated from a microbat. The 176,688 nt sequence, which is believed to encompass the complete coding region of the virus, is 67% A+T and is predicted to encode 191 genes. 11 of these genes have no counterpart in GenBank and are therefore unique to EPTV.

Successful strategies implemented towards the elimination of canine rabies in the Western Hemisphere.

Almost all cases of human rabies result from dog bites, making the elimination of canine rabies a global priority. During recent decades, many countries in the Western Hemisphere have carried out large-scale dog vaccination campaigns, controlled their free-ranging dog populations and enforced legislation for responsible pet ownership. This article reviews progress in eliminating canine rabies from the Western Hemisphere.

The history of rabies in the Western Hemisphere.

Before the introduction of control programs in the 20th century, rabies in domestic dogs occurred throughout the Western Hemisphere. However, historical records and phylogenetic analysis of multiple virus isolates indicate that, before the arrival of the first European colonizers, rabies virus was likely present only in bats and skunks. Canine rabies was either rare or absent among domestic dogs of Native Americans, and first arrived when many new dog breeds were imported during the period of European colonization.

Detection and Molecular Characterization of Zoonotic Poxviruses Circulating in the Amazon Region of Colombia, 2014.

During 2014, cutaneous lesions were reported in dairy cattle and farmworkers in the Amazon Region of western Colombia. Samples from 6 patients were analyzed by serologic and PCR testing, and results demonstrated the presence of vaccinia virus and pseudocowpox virus. These findings highlight the need for increased poxvirus surveillance in Colombia.

Pharmacokinetic Profiles of Meloxicam and Sustained-release Buprenorphine in Prairie Dogs ().

In this study, we evaluated the pharmacokinetic profiles of meloxicam and sustained-release (SR) buprenorphine in prairie dogs. The 4 treatment groups were: low-dose meloxicam (0.2 mg/kg SC), high-dose meloxicam (4 mg/kg SC), low-dose buprenorphine SR (0.