Choosing the right animal model for infectious disease research.

A complex biological system is often required to study the myriad of host-pathogen interactions associated with infectious diseases, especially since the current basis of biology has reached the molecular level. The use of animal models is important for understanding the very complex temporal relationships that occur in infectious disease involving the body, its neuroendocrine and immune systems and the infectious organism. Because of these complex interactions, the choice of animal model must be a thoughtful and clearly defined process in order to provide relevant, translatable scientific data and to ensure the most beneficial use of the animals.

Common Challenges in Safety: A Review and Analysis of AAALAC Findings.

The 8th edition of the Guide for the Care and Use of Laboratory Animals (Guide) is clear in its requirement for each institution to establish and maintain an occupational health and safety (OHS) program as an essential part of the overall program of animal care and use. For over 30 years, AAALAC International has utilized a variety of methods to evaluate this component of OHS programs as part of the accreditation process. AAALAC International began collecting data on site visit findings over 20 years ago using the Guide as a template for establishing the categories and subcategories to which findings are assigned.

Using Telemetry Data to Refine Endpoints for New Zealand White Rabbits Challenged with .

We used a continuous-monitoring digital telemetry system to investigate temperature response in New Zealand White rabbits after inhalation or subcutaneous challenge with Bacillus anthracis. Two spore preparations of B. anthracis Ames A2084 were evaluated by using a nose-only inhalation model, and 2 strains, B.

Challenges and Opportunities in Implementation: The AAALAC International Perspective.

In spite of the increasing trend for local authorities and international organization to follow the same ethical principles, the regulatory framework on the protection, care, and use of research animals is still heterogeneous. Differences across geopolitical areas exist not only at the legal level but, more important, also at the level of implementation of the existing regulations. In this diverse landscape, AAALAC International uses performance standards to assure harmonization of accredited animal care and use programs globally.

Disaster preparedness in biocontainment animal research facilities: developing and implementing an incident response plan (IRP).

Preparing for the wide variety of disasters that can occur is challenging for any animal research facility, but the level of concern for human and animal health rises significantly when infectious agents and toxins are part of the scenario. Federal regulations provide detailed requirements for the development of an incident response plan (IRP) when select agents and toxins (SATs) are used. In addition to the usual issues associated with disaster planning, the IRP must address concerns associated with the potential theft, loss, or release of SATs that may affect both institutional personnel and the surrounding community.

Ebola hemorrhagic fever: evaluation of passive immunotherapy in nonhuman primates.

The survival of 7 of 8 patients with Ebola virus (EBOV) infection after transfusions of convalescent-phase blood during a 1995 outbreak of EBOV infection is frequently cited as evidence that passive immunotherapy is a viable treatment option. To test whether whole-blood transfusions were more efficacious than passively administered immunoglobulins or monoclonal antibodies, we transfused convalescent-phase blood from EBOV-immune monkeys into naive animals shortly after challenge with EBOV. Although passively acquired antibody titers comparable to those associated with effective vaccination were obtained, all monkeys that had received transfusions succumbed to infection concurrently with control monkeys.

Simultaneous deficiency in CD28 and STAT6 results in chronic ectoparasite-induced inflammatory skin disease.

A mouse lacking CD28, a T-cell costimulatory molecule, and STAT6, a transcription factor that mediates interleukin-4 (IL-4) signaling, was developed from parental CD28- and STAT6-deficient mice. STAT6/CD28(-/-) BALB/c mice that were 8 weeks old had a normal phenotype, and IL-4 production was induced following infection with nematode parasites. Unexpectedly, when they were between 4 and 8 months old, all mice examined spontaneously developed severe chronic dermatitis associated with pronounced numbers of Demodex ectoparasites.

The pathology of experimental aerosolized monkeypox virus infection in cynomolgus monkeys (Macaca fascicularis).

Cynomolgus monkeys (Macaca fascicularis) were exposed by fine-particle aerosol to lethal doses of monkeypox virus, Zaire strain. Death, attributable to fibrinonecrotic bronchopneumonia, occurred 9 to 17 days postexposure. Lower airway epithelium served as the principal target for primary infection.

Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections.

A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation.

Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses.

A commercially available immunoglobulin G (IgG) from horses, hyperimmunized to Ebola virus, was evaluated for its ability to protect cynomolgus monkeys against disease following i.m. inoculation with 1 000 PFU Ebola virus (Zaire '95 strain).

Neurotoxicity in animals due to arteether and artemether.

Several artemisinin (qinghaosu) derivatives have been developed and are in use as antimalarial drugs but scant animal or human toxicity data are available. We noted a progressive syndrome of clinical neurological defects with cardio-respiratory collapse and death in 5/6 dogs dosed daily for 8 d with intramuscular arteether (AE) at 20 mg/kg/d in a pharmacokinetic study. Neurological findings included gait disturbances, loss of spinal reflexes, pain response reflexes and prominent loss of brain-stem and eye reflexes.

Evaluation of butorphanol tartrate and buprenorphine hydrochloride on the inflammatory reaction of the Sereny Test.

Invasion of the ocular epithelia of guinea pigs by virulent Shigella organisms, eliciting keratoconjunctivitis, is the basis of the Sereny Test (ST). This test has been used to ascertain the virulence of Shigella strains and more recently to screen candidate Shigella vaccines for efficacy. This test undoubtedly causes pain in test animals; however, recommendation for use of local analgesics/anesthetics has not been accepted because of concern that these topical agents may affect the ability of the Shigella organisms to invade the ocular epithelia or have a physiologic effect on the inflammatory process.

A surgical technique for bilateral cochleotomy in the Long-Evans rat.

A bilateral cochleotomized surgical rat model, needed for a study involving microwave effects, was developed, standardized, and assessed for reproducibility. After a review of the literature concerning attempts and approaches with various species, a technique involving an approach through the external auditory canal was chosen and modified. Using a stereomicroscope, a cutaneous incision in the intertragic notch was made and extended medially along the ventral aspect of the external auditory canal to the depth of the external auditory meatus.