Moxidectin toxicity in senescence-accelerated prone and resistant mice.

Moxidectin has been used safely as an antiparasitic in many animal species, including for the eradication of the mouse fur mite, Mycoptes musculinus. Although no side effects of moxidectin have previously been reported to occur in mice, 2 strains of the senescence-accelerated mouse (SAMP8 and SAMR1) sustained considerable mortality after routine prophylactic treatment. To investigate the mechanism underlying this effect, moxidectin toxicosis in these mice was evaluated in a controlled study. Moxidectin was applied topically (0.015 mg), and drug concentrations in both brain and serum were analyzed by using HPLC coupled with mass spectrometry. The moxidectin concentration in brain of SAMP8 mice was 18 times that in controls, and that in brain of SAMR1 mice was 14 times higher than in controls, whereas serum moxidectin concentrations did not differ significantly among the 3 strains. Because deficiency of the blood-brain barrier protein P-glycoprotein leads to sensitivity to this class of drugs in other SAM mice, Pgp immunohistochemistry of brain sections from a subset of mice was performed to determine whether this commercially available analysis could predict sensitivity to this class of drug. The staining analysis showed no difference among the strains of mice, indicating that this test does not correlate with sensitivity. In addition, no gross or histologic evidence of organ toxicity was found in brain, liver, lung, or kidney. This report shows that topically applied moxidectin at a standard dose accumulates in the CNS causing toxicosis in both SAMP8 and SAMR1 mice.

Gastric trichobezoars in a rhesus macaque (Macaca mulatta).

On physical examination, a 5 x 10-cm abdominal mass was found in an eight-year-old female rhesus macaque. Radiography revealed an opaque mass in the cranial portion of the abdomen, displacing the stomach craniad. Percutaneous biopsy obtained hair with little tissue, confirming a diagnosis of trichobezoar. Initially, the hairball was medically managed by oral administration of lubricants. Medical management proved unsuccessful, the macaque began to lose weight, and two gastric trichobezoars were subsequently removed surgically. Normal appetite and activity were regained within one week. Gastric trichobezoars may lead to severe clinical illness, and should be considered in the differential diagnosis for anorexia and/or weight loss in any nonhuman primate. Trichobezoars may also be detected and treated prior to development of illness.

Cutaneous acariasis in the African clawed frog (Xenopus laevis).

Increased mortality was observed in a single colony of 50 Xenopus laevis. The frogs were used as oocyte donors in developmental biology studies. Necropsy findings included dermal erythema and petechiation consistent with red leg syndrome; dermal ulcerations and white, filamentous growths on the skin were consistent with Saprolegnia sp. Microscopic evaluation of the skin and fungus revealed an astigmatid mite similar to those of the genus Rhizoglyphus. The mite was also found in the water and the biological filter of the tanks housing the frogs. This mite is considered not to be a parasite of X. laevis; instead, it feeds off moss, fungi, and detritus. Subsequent evaluation of the sphagnum moss used for shipping the frogs from the supplier revealed the same mite in the moss. Our hypothesis is that the mite was introduced into the tank with the shipment of new frogs in sphagnum moss. The mites lived within the biological filter, and were only found after the growth of Saprolegnia sp. attracted the mites to the frogs. Laboratory animal care and veterinary personnel should consider non-pathogenic species of mites in the differential diagnosis of acariasis in Xenopus frogs.

Urolithiasis associated with experimental lymphocytic choriomeningitis virus inoculation in Lewis rats.

A high frequency of struvite urolithiasis, hydronephrosis, and other urinary tract lesions developed in a group of Lewis rats inoculated intracranially with lymphocytic choriomeningitis virus (LCMV). Initially, clinically ill rats were referred to necropsy: 30 rats over 3 years. These rats had high frequency of urolithiasis (8/30, 27%), hydronephrosis (12/30, 40%), cystitis (9/30, 30%), transitional cell carcinoma (4/30, 13%), and pyelonephritis (19/30, 63%). Lesions were more common in LCMV-inoculated rats. After this trend was noted, all rats on this protocol were necropsied as part of a cohort study (n = 144). Although the apparent frequency of disease was lower due to increased sampling, there still was a high number of urolithiasis (9/144, 6%) and hydronephrosis (40/144, 28%) cases. All cases of urolithiasis developed in rats inoculated with LCMV (9/44, 20%), as did most cases of hydronephrosis (31/44, 70%). Although sham-injected and uninoculated control rats also had high frequency of hydronephrosis (6/57 [11%] and 3/43 [7%], respectively), LCMV-inoculated rats had a significantly higher frequency of disease than did sham inoculated (P < 0.0001) and uninoculated (P < 0.0001) controls. These results suggest that Lewis rats may be predisposed to developing lesions of the urinary tract, and that intracranial inoculation of rats with LCMV augments this tendency, leading to formation of struvite calculi and associated urinary tract disease.

Survey of laboratory animal technicians in the United States for Coxiella burnetii antibodies and exploration of risk factors for exposure.

Little is known about the prevalence of zoonotic infections among laboratory animal care technicians (LAT). Q fever, a disease caused by Coxiella burnetii, is a known occupational hazard for persons caring for livestock. We sought to determine the seroprevalence of C. burnetii antibodies among LAT and to identify risk factors associated with C. burnetii seropositivity. A survey was administered and serum samples collected from a convenience sample of 97 LAT. Samples were screened by using a Q fever IgG ELISA. Immunofluorescent antibody assays for phase I and phase II IgG were used to confirm the status of samples that were positive or equivocal by ELISA; positive samples were titered to endpoint. Antibodies against C. burnetii were detected in 6 (6%) of the 97 respondents. In our sample of LAT, seropositivity to C. burnetii was therefore twice as high in LAT as compared with the general population. Age, sex, and working with sheep regularly were not associated with seropositivity. Risk factors associated with seropositivity included breeding cattle within respondent's research facility, any current job contact with waste from beef cattle or goats, and exposure to animal waste during previous jobs or outside of current job duties. Only 15% of responding LAT reported being aware that sheep, goats, and cattle can transmit Q fever. Research facilities that use cattle or goats should evaluate their waste-management practices and educational programs in light of these findings. Additional efforts are needed to increase awareness among LAT regarding Q fever and heightened risk of exposure to infectious materials. Physicians should consider the risk of infection with C. burnetii when treating LAT with potential occupational exposures.

Analgesic effects of meloxicam, morphine sulfate, flunixin meglumine, and xylazine hydrochloride in African-clawed frogs (Xenopus laevis).

We evaluated analgesic use and analgesiometry in aquatic African-clawed frogs (Xenopus laevis). We used the acetic acid test (AAT) to assess the analgesic potential of systemic xylazine hydrochloride, meloxicam, flunixin meglumine, and morphine sulfate after injection into the dorsal lymph sac. Flunixin meglumine provided better analgesia than did the other drugs, most evident at 5 and 9 h after administration. Because the AAT was associated with the development of dermal lesions, we discontinued use of this assay and chose the Hargreaves test as an alternative method of measuring nociception in Xenopus. This assay is commonly performed in rodents, but its efficacy in an aquatic species such as Xenopus was unknown prior to this study. We found that the Hargreaves test was an effective measure of nociception in Xenopus, and we used it to evaluate the effectiveness of the nonopiod agents xylazine hydrochloride, meloxicam, and flunixin meglumine both in the absence of surgery and after surgical oocyte harvest. Similar to findings from the AAT, flunixin meglumine provided better analgesia in the Hargreaves test than did the other agents when analyzed in the absence of surgical intervention. Results were equivocal after oocyte harvest. Although surgical oocyte harvest is a common procedure in Xenopus, and currently there are no published recommendations for analgesia after this invasive surgery. Future studies are needed to clarify the efficacy of nonsteroidal antiinflammatory drugs for that purpose.

Isoflurane waste anesthetic gas concentrations associated with the open-drop method.

The open-drop technique is used frequently for anesthetic delivery to small rodents. Operator exposure to waste anesthetic gas (WAG) is a potential occupational hazard if this method is used without WAG scavenging. This study was conducted to determine whether administration of isoflurane by the open-drop technique without exposure controls generates significant WAG concentrations. We placed 0.1, 0.2, or 0.3 ml of liquid isoflurane into screw-top 500 or 1000 ml glass jars. WAG concentration was measured at the opening of the container and 20 and 40 cm from the opening, a distance at which users likely would operate, at 1, 2, or 3 min WAG was measured by using a portable infrared gas analyzer. Mean WAG concentrations at the vessel opening were as high as 662 +/- 168 ppm with a 500 ml jar and 122 +/- 87 ppm with a 1000 ml jar. At operator levels, WAG concentrations were always at or near 0 ppm. For measurements made at the vessel opening, time was the only factor that significantly affected WAG concentration when using the 500 ml jar. Neither time nor liquid volume were significant factors when using 1000 ml jar. At all liquid volumes and time points, the WAG concentration associated with using the 500 ml container was marginally to significantly greater than that for the 1000 ml jar.

Use of selamectin and moxidectin in the treatment of mouse fur mites.

A breeding colony consisting of 250 different strains of mice was treated with the topical acaricide selamectin for the mouse fur mite Myocoptes musculinus, with no apparent ill effect, suggesting that this drug is safe for use in mice. To further evaluate their efficacy in treating Myocoptes spp., we compared selamectin with another acaricide, moxidectin, in a controlled manner. Infested mice were treated with selamectin or moxidectin at the time of cage change, and a subset of mice was retreated 10 d later. Mice underwent routine cellophane tape examination of the pelage for 1 y. Although no adult mites were found in any group at 1 mo after treatment, egg casings were found in the selamectin treatment group as late as 6 mo after treatment, prompting concern about its effectiveness. Moxidectin used in combination with cage changing was effective in eradicating mites, with mice negative for traces of mites on cellophane tape examination of the pelage from months 2 through 12 after treatment.

Investigation of appropriate sanitization frequency for rodent caging accessories: evidence supporting less-frequent cleaning.

The Guide for the Care and Use of Laboratory Animals states that sanitization of caging accessories (for example, filter tops and wire-bar lids) should be done every 2 wk. In this study we tested the hypothesis that organic contamination measured by the presence of ATP associated with organic material (measured with luciferase test swabs) and the number of bacterial colony-forming units (as determined by use of replicate organism detection and counting plates) on caging accessories did not differ significantly at 2 wk versus several months of use. The study evaluated 4 groups: mouse and rat ventilated and static wire-bar cages with or without filter tops (n = 10 per group). The cages were evaluated at several time points from 2 wk to 6 mo. For every cage type, ATP levels did not differ significantly between 14 and 90 d and, in most cases, between 14 and 180 d. In addition the number of bacterial colonies did not differ significantly between 14 and 120 d (and, in some cases, between 14 and 180 d). This study provides data relevant to establishing a validated frequency for sanitization of rodent caging accessories while controlling, and potentially decreasing, costs associated with sanitization.