The globally important human diseases of trench fever, epidemic typhus, and relapsing fever are vectored by the human louse Pediculus humanus humanus. Although these conditions are epidemically quiescent at present, they persist in socially dysfunctional situations of war, deprivation, and crowding. The taxonomically closely related head louse, Pediculus humanus capitis, does not respect economic or social status and is quite common in most countries. The 2 types of lice are now recognized as conspecific ecotypes of a single species. While the body louse has been adapted for propagation in the laboratory by feeding in vivo on live rabbits, a similar animal model has not been developed for the host-specific head louse. Accordingly, research for treatment and control of the head louse has largely been performed by using laboratory-reared body lice. This review describes methods for the propagation of body lice in the laboratory and outlines at least 4 areas of research that require sufficient numbers of aged body louse cohorts produced in rabbits for use in controlled studies: 1) pediculicide development and resistance, 2) immunity and vaccine potential, 3) endosymbiotic bacteria needed by lice for nutrition, and 4) lice as vectors of human disease. The review concludes with a discussion of several ethical issues involved with the standard method of using unsedated rabbits and recommends consideration of providing sedating anesthetics for rabbits used in louse feeding procedures.
Lymphatic filariasis is a mosquito-borne parasitic infection affecting an estimated 51.4 million people. Brugia malayi and Brugia pahangi are used in research because common nonprimate research species such as Mongolian gerbils (Meriones unguiculatus), cats (Felis catus), and dogs (Canis familiaris) can maintain the life cycle of these species of filarial nematodes. Although overall care and management of animals infected with Brugia spp. is relatively straightforward, there are some unique challenges and special considerations that must be addressed when managing a research colony infected with these parasites. In this review, we discuss our experience, share insight into biosafety and clinical management, and describe the expected clinical signs associated with Brugia infection in gerbils, cats, and dogs.
Leishmaniasis, a disease of global relevance, results from infection with the protozoan parasite, Leishmania, which is transmitted to susceptible hosts through the bite of sand flies. Multiple forms of leishmaniasis may occur, including cutaneous, mucocutaneous, and visceral. Research with animal models remains an important approach to help define basic pathophysiologic processes associated with infection and disease. In this regard, mice and hamsters represent the most commonly used models. The severity of leishmaniasis in animal models depends on several factors, including genotype of the host and parasite and the dose and route of administration of the parasite to the host, and severity of outcome may range from subclinical to severe illness. This review provides basic background on leishmaniasis, relevant animal models, the pathophysiology and clinical signs in animals used as models of leishmaniasis, and general approaches to mitigate risk to personnel.
Genomic sequence analysis of autonomous parvoviruses within the genus Protoparvovirus generates 2 groups that are principally of mouse origin: the minute virus of mice (MVM) strains (MVMp, MVMi, MVMc, MVMm) and the mouse parvovirus (MPV)–like strains (MPV-1, MPV-2, MPV-3, MPV-4, MPV-5, HaPV, LuIII). Baculovirus-expressed recombinant capsid protein (rVP2) from each of these 11 parvovirus strains were produced, purified, and demonstrated to form virus-like particles. Each rVP2 preparation was then used as antigen in a multiplex fluorescent immunoassay and to immunize 5 different strains of mice. Sera from immunized mice, mice experimentally monoinfected with various MVM or MPV isolates, and mice naturally infected with murine parvoviruses were evaluated with the multiplex fluorescent immunoassay rVP2 panel. Results for sera from immunized mice indicate that homologous antigen–antisera interactions produced the strongest seroreactivity. All MVM antigens were highly cross-reactive with heterologous MVM antisera, while more variability was observed in heterologous antigen–antisera reactions among the MPV-like strains. MPV-1, MPV-3, HaPV, and LuIII were highly cross-reactive with each other, MPV-2 and MPV-5 were highly cross-reactive with each other, and MPV-4 displayed modest cross-reactivity with certain MPV-like strains. Serologic cross-reactivity patterns similar to those in immunized mice were observed in mice experimentally infected with MVMp, MVMm, MPV-1, MPV-5, or HaPV, and in sera from mice naturally infected with MVM and MPV. Serologic cross-reactivity spectrums suggest a small panel of rVP2 antigens (MVM, MPV-1, MPV-2, MPV-4) combined with the generic murine parvovirus recombinant nonstructural protein 1 (rNS1) antigen are sufficient for qualitative detection of currently known MVM and MPV-like strains.
Murine fur mites are commonly excluded in modern research animal programs, yet infestations continue to persist due to challenges in detection and control. Because all diagnostic methods and treatment options have limitations, programs must make many operational decisions when trying to eradicate these ectoparasites. The primary aim of this study was to assess various durations of treatment time with an ivermectin-compounded diet in eliminating Radfordia affinis in mice as determined by PCR testing and pelt examination. A shorter treatment duration would be highly advantageous as compared with the current regimen of 8 wk as it would minimize cost and time for animal management programs, impediments to research, and ivermectin drug effects on infested animals. Five experimental groups of R. affinis-positive mice received dietary ivermectin for 0, 2, 4, 6, or 8 wk. A fur mite-negative, naïve mouse was added to each group every 8 wk to perpetuate the infestation and amplify any remaining populations of fur mites. At 16 wk after the respective treatment end, PCR testing was performed for all treated groups in conjunction with the positive control group (no treatment). Visual examination of pelts for mites and eggs via direct microscopy was also performed at each time point. All treated mice were free of R. affinis at 16 wk after the end of treatment as confirmed by both PCR testing and pelt examination. These findings indicate that a dietary ivermectin treatment duration of as little as 2 wk is effective in eliminating R. affinis, making successful eradication initiatives more achievable.
While rodents are used extensively for studying pain, there is a lack of reported direct comparisons of thermal and mechanical pain testing methods in rats of different genetic backgrounds. Understanding the range of interindividual variability of withdrawal thresholds and thermal latencies based on these testing methods and/or genetic background is important for appropriate experimental design. Testing was performed in two common rat genetic backgrounds: outbred Sprague–Dawley (SD) and inbred Fischer 344 (F344). Male and female, 10- to 14-wk-old F344 and SD rats were used to assess withdrawal thresholds in 3 different modalities: the Randall-Selitto test (RST), Hargreaves test (HT), and tail flick test (TFT). The RST was performed by using an operator-controlled handheld instrument to generate a noxious pressure stimulus to the left hind paw. The HT and the TFT used an electronically controlled light source to deliver a noxious thermal stimulus to the left hind paw or tail tip, respectively. Rats of each sex and genetic background underwent one type of test on day 0 and day 7. Withdrawal thresholds and thermal latencies were compared among tests. No significant differences were observed. Our findings can serve as a guide for researchers considering these nociceptive tests for their experiments.
Chinchillas are a relatively novel research model compared with other rodent species. They require special considerations when it comes to their husbandry and daily care. Chinchillas tend to be shy animals that are well adapted to masking clinical signs of illness. These characteristics can make them a difficult species to maintain in a research setting. The authors’ institution has maintained chinchillas and established standardized daily animal care procedures for them. Chinchillas are most commonly used for auditory research. They are often used to study the mechanism of different induced auditory conditions or injuries as well as exploration for potential alleviating treatments. Often, tested therapeutics have demonstrated potentially beneficial effects but have not been applied in the specific condition or injury of interest. The development of new applications for therapeutics can lead to groundbreaking discoveries, but testing of new therapeutic applications is often initially performed in an animal model without knowing how the therapeutic will behave in the species. During testing, unexpected adverse events may manifest that require more focused monitoring and supportive care. This scenario occurred when adverse effects were observed in a chinchilla blast-injury model after receiving an acylated glucagon-like peptide-1 (GLP-1) receptor agonist. The study involved evaluation of this therapeutic over an extended amount of time after inducing a controlled pressurized blast-injury followed by multiple repeated hearing tests under anesthesia. Chinchillas enrolled in the study exhibited several clinical signs including weight loss, lethargy, labored breathing, neurologic abnormalities, decreased appetite or decreased fecal output, and otitis. Five primary abnormalities were reported on pathology: aspiration pneumonia, hepatic steatosis, right ventricular dilation, pancreatitis, and tubulointerstitial nephritis. Initially abnormal clinical signs, early mortality rates, and pathology were attributed to multiple anesthetic events. However, a retrospective analysis evaluating the association of different study variable exposures in a stratified comparison demonstrated that the early mortality rates were actually associated with the therapeutic drug given for the first time in this species. In this study, we describe the detailed findings of the retrospective analysis and explore different strategies that can be incorporated to maintain good animal welfare and decrease early animal loss.
Guanfacine, an α2 adrenoceptor agonist, has been used to successfully treat self-injurious behavior in nonhuman primates, including macaques (Macaca mulatta) and baboons (Papio anubis). It does so by facilitating a correction to the dopaminergic system that mediates a reduction in impulsivity and reactivity. Given this, we assessed the potential efficacy of guanfacine to treat socially directed agonistic behavior in primates with an apparent reactive behavioral phenotype. We present data from 2 pigtail macaques (Macaca nemestrina): an intact adult male housed in a breeding group, and an experimentally naive adult female living in a research setting with her social partner. Baseline behavioral assessments suggested that both macaques showed extreme responses to external stressors that triggered them to aggress social partners often leading to wounding that required veterinary intervention. Both animals were tracked during the course of 1 y. Once treated regularly with guanfacine, both animals showed significant reduction in their agonistic behavior and the rate at which they wounded other animals. Indeed, in the year since the female has been treated with guanfacine she has never wounded her cagemate. By collecting regular and detailed behavioral observations on the male in the breeding colony, we were able to identify triggers for his aggression and to track the behavioral changes evidenced after guanfacine treatment. These data supported our hypothesis that his aggression reflected extreme reactivity to external stressors, rather than general anxiety. Importantly, we saw only a limited and short-lived reduction in the male’s affiliative behavioral rates, and thus guanfacine had no sedative effect, but did successfully reduce his reactivity and resultant agonism and wounding.
The American Association for Laboratory Animal Science (AALAS) currently publishes two journals containing data-driven, peer-reviewed articles. The mission of Comparative Medicine (CM) is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.General