Implementation of a post-exposure tularemia treatment model for pneumonic challenged Fischer rats.

Francisella tularensis is the etiological agent of the potentially fatal disease tularemia. F. tularensis is sensitive to several antibiotic classes; however, the ability to derive antibiotic resistant Francisella strains has been well documented.

Sudan Virus Persistence in Immune-Privileged Organs of Nonhuman Primate Survivors.

After the 2022-2023 Sudan virus (SUDV) disease outbreak in Uganda, we studied SUDV persistence in nonhuman primates that had survived acute infection without therapeutic intervention. We identified SUDV persistence in the vitreous chamber and immediately adjacent tissue in the eyes as well as in the seminiferous tubules in the testes but not in common target organs typically infected during the acute phase of disease. Specifically, SUDV persists primarily in macrophages in the eyes and Sertoli cells in the testes.

Virulence of Burkholderia pseudomallei ATS2021 Unintentionally Imported to United States in Aromatherapy Spray.

In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India.

Anthrax Meningoencephalitis and Intracranial Hemorrhage.

The neurological sequelae of Bacillus anthracis infection include a rapidly progressive fulminant meningoencephalitis frequently associated with intracranial hemorrhage, including subarachnoid and intracerebral hemorrhage. Higher mortality than other forms of bacterial meningitis suggests that antimicrobials and cardiopulmonary support alone may be insufficient and that strategies targeting the hemorrhage might improve outcomes. In this review, we describe the toxic role of intracranial hemorrhage in anthrax meningoencephalitis.

Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus.

The 2022 global human monkeypox outbreak emphasizes the importance of maintaining poxvirus research, including enriching a basic understanding of animal models for developing and advancing therapeutics and vaccines. Intravenous administration of monkeypox virus in macaques is arguably one of the best animal models for evaluating the efficacy of medical countermeasures. Here we addressed one criticism of the model, a requirement for a high-titer administration of virus, as well as improving our understanding of monkeypox virus pathogenesis.

Effect of Monkeypox Virus Preparation on the Lethality of the Intravenous Cynomolgus Macaque Model.

For over two decades, researchers have sought to improve smallpox vaccines and also develop therapies to ensure protection against smallpox or smallpox-like disease. The 2022 human monkeypox pandemic is a reminder that these efforts should persist. Advancing such therapies have involved animal models primarily using surrogate viruses such as monkeypox virus.

Clindamycin Protects Nonhuman Primates Against Inhalational Anthrax But Does Not Enhance Reduction of Circulating Toxin Levels When Combined With Ciprofloxacin.

Background: Inhalational anthrax is rare and clinical experience limited. Expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking.

Methods: Rhesus macaques exposed to an aerosol of Bacillus anthracis spores were treated with ciprofloxacin, clindamycin, or ciprofloxacin + clindamycin after becoming bacteremic.

Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques.

Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule-a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia.

Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure.

Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques.

Unlabelled: Marburg virus (MARV) infection is a lethal hemorrhagic fever for which no licensed vaccines or therapeutics are available. Development of appropriate medical countermeasures requires a thorough understanding of the interaction between the host and the pathogen and the resulting disease course. In this study, 15 rhesus macaques were sequentially sacrificed following aerosol exposure to the MARV variant Angola, with longitudinal changes in physiology, immunology, and histopathology used to assess disease progression.

Niemann-pick C1 is essential for ebolavirus replication and pathogenesis in vivo.

Unlabelled: Recent work demonstrated that the Niemann-Pick C1 (NPC1) protein is an essential entry receptor for filoviruses. While previous studies focused on filovirus entry requirements of NPC1 in vitro, its roles in filovirus replication and pathogenesis in vivo remain unclear. Here, we evaluated the importance of NPC1, and its partner in cholesterol transport, NPC2, by using a mouse model of Ebolavirus (EBOV) disease.

Transient lipopolysaccharide-induced resistance to aerosolized Bacillus anthracis in New Zealand white rabbits.

Previous studies have demonstrated that prior infection by various bacterial pathogens induces nonspecific resistance to subsequent infection by other gram-negative and gram-positive bacterial pathogens. In the present study, we evaluated whether underlying inflammation enhanced host resistance to inhalational Bacillus anthracis infection in New Zealand White rabbits (SPF; Bordetella- and Pasteurella-free). Accordingly, rabbits were pretreated with either the inflammagen bacterial LPS (60,000 EU/kg), a component of the outer membrane of gram-negative bacteria, or saline (vehicle).

Evaluation of Lassa antiviral compound ST-193 in a guinea pig model.

Lassa virus (LASV), a member of the Arenaviridae family, causes a viral hemorrhagic fever endemic to West Africa, where as many as 300,000 infections occur per year. Presently, there are no FDA-approved LASV-specific vaccines or antiviral agents, although the antiviral drug ribavirin has shown some efficacy. A recently identified small-molecule inhibitor of arenavirus entry, ST-193, exhibits submicromolar antiviral activity in vitro.

Alterations in cytokines and effects of dexamethasone immunosuppression during subclinical infections of invasive Klebsiella pneumoniae with hypermucoviscosity phenotype in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques.

Invasive Klebsiella pneumoniae with the hypermucoviscosity phenotype (HMV K. pneumoniae) is an emerging human pathogen that also has been attributed to fatal multisystemic disease in African green monkeys at our institution. Combining a cluster of subclinically infected macaques identified in March and April 2008 and the animals documented during a subsequent survey of more than 300 colony nonhuman primates yielded a total of 9 rhesus macaques and 6 cynomolgus macaques that were subclinically infected.

Rapid real-time PCR assays for detection of Klebsiella pneumoniae with the rmpA or magA genes associated with the hypermucoviscosity phenotype: screening of nonhuman primates.

The relationship of mucoviscosity-associated (magA) and/or regulator of mucoid phenotype (rmpA) genes to the Klebsiella pneumoniae hypermucoviscosity (HMV) phenotype has been reported. We previously demonstrated that rmpA+ K. pneumoniae can cause serious disease in African green monkeys and isolated rmpA+ and magA+ HMV K.

A short course of antibiotic treatment is effective in preventing death from experimental inhalational anthrax after discontinuing antibiotics.

Background: Postexposure prophylaxis of inhalational anthrax requires prolonged antibiotic therapy or antibiotics and vaccination. The duration of treatment for established anthrax is controversial, because retained spores may germinate and cause disease after antibiotics are discontinued. Using rhesus macaques, we determined whether a short course of antibiotic treatment, as opposed to prophylaxis, could effectively treat inhalational anthrax and prevent disease caused by the germination of spores after discontinuation of antibiotics.

Nosocomial infection of Serratia marcescens may induce a protective effect in monkeys exposed to Bacillus anthracis.

This study was originally designed to collect data on the natural history of inhalational anthrax in a new nonhuman primate model. An uncontrollable event created a new experimental condition which allowed us to retrospectively evaluate the power of the innate immune system to protect from an aerosol exposure of B. anthracis.

Corynebacterial necrohemorrhagic cystitis in two female macaques.

We describe severe necrohemorrhagic cystitis in a female rhesus macaque and a female cynomolgus macaque due to colonization of the urinary bladder by Corynebacterium sp. Clinically, both macaques presented with perineal bleeding and depression and, despite extensive and prolonged treatment, succumbed to the disease. At necropsy, the contents of the urinary bladders in both cases were hemorrhagic to greenish black, and the bladder mucosa was necrotic.

Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax.

Prevention of inhalational anthrax after Bacillus anthracis spore exposure requires a prolonged course of antibiotic prophylaxis. In response to the 2001 anthrax attack in the United States, approximately 10,000 people were offered 60 days of antibiotic prophylaxis to prevent inhalational anthrax, but adherence to this regimen was poor. We sought to determine whether a short course of antibiotic prophylaxis after exposure could protect non-human primates from a high-dose spore challenge if vaccination was combined with antibiotics.