Penciclovir pharmacokinetics after oral and rectal administration of famciclovir in African elephants (Loxodonta africana) shows that effective concentrations can be achieved from rectal administration, despite lower absorption.

OBJECTIVE: To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta africana). ANIMALS: 15 African elephants (6 males and 9 females) of various ages. METHODS: Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling. RESULTS: Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (tmax; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 µg·h/mL), maximum observed concentration (Cmax; 3.73 µg/mL), and absorption half-life (t1/2; 0.65 hours). Following rectal administration, the values were: tmax, 0.65 hours; AUC, 15.62 µg·h/mL; Cmax, 2.52 µg/mL; and absorption t1/2, 0.13 hours. CONCLUSIONS: Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration. CLINICAL RELEVANCE: African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.

Treatment and Outcomes of Tusk Fractures in Managed African Savanna and Asian Elephants (Loxodonta africana and Elephas maximus) across Five Continents.

Elephant tusk fractures are a clinical challenge that can impact the overall health of the animal, particularly when they result in pulp exposure. An international survey was sent to veterinarians to understand individual fracture characteristics and management strategies as they relate to outcomes, with the goal of better informing treatment procedures. The data set consisted of 79 fractures from 64 elephants (including Asian and African males and females), 44.3% of which were Class III fractures with pulpal involvement. Of this subset, pulp canal exposures of >0.5 cm were 23.8-fold more likely to develop pulpitis than fractures with <0.5 cm exposed, though canal size did not impact healing versus extraction outcome. Odds ratios showed that treatments including endodontics were 12.0-fold more likely to heal than tusks treated exclusively with medical management, though no association was observed in reducing the risk of pulpitis. Further, pulpitis was 7.58-fold more likely to develop when tap water was used to rinse exposed pulpal tissue; a finding that merits further investigation. The use of endodontic treatment versus medical management alone was significantly associated with improved recovery outcomes (i.e., reduced risk of extraction) in tusk fractures with pulpal involvement.

ACUTE HEMORRHAGIC DISEASE DUE TO ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 3A INFECTION IN FIVE AFRICAN ELEPHANTS (LOXODONTA AFRICANA) AT ONE NORTH AMERICAN ZOOLOGICAL INSTITUTION.

Acute hemorrhagic disease caused by elephant endotheliotropic herpesvirus (EEHV) infection is well recognized as a major threat to young Asian elephants (Elephas maximus) but has been less frequently documented in African elephants (Loxodonta africana). This report describes five sequential cases of EEHV3A infection in African elephants in managed care at one institution. All elephants developed disease within a 4-mo period. The first two cases were 6.5- and 7.5-yr-old females that presented with depressed mentation, anorexia, hematuria, and diarrhea. Both elephants died within 48-72 hr of the onset of illness despite treatment. Postmortem findings included widespread edema, ascites, and extensive petechiae and ecchymoses on the heart, liver, and spleen and within the gastrointestinal and urogenital tracts. Histologic examination identified disseminated vascular necrosis with edema, hemorrhage, and rare endothelial cell intranuclear inclusions typical of herpesvirus in multiple organs. The third and fourth cases were a 13-yr-old male and a 12-yr-old female that presented with minimal to no clinical signs, but with marked changes in hematologic parameters and high viremia detected by quantitative polymerase chain reaction (qPCR). Both elephants survived the infection with early and aggressive treatment. The fifth case was a 37-yr-old female that presented with lethargy and a decreased appetite. Low viremia was detected by qPCR, and mild to moderate hematologic changes were noted. Early treatment resulted in a successful outcome. This case series documents the first known reports of clinical disease and fatality associated with EEHV3A in African elephants.

NAÏVE-POOLED PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID AFTER SINGLE INTRAMUSCULAR ADMINISTRATION IN SMOOTH DOGFISH (MUSTELUS CANIS).

Pharmacokinetics study of ceftiofur crystalline free acid (CCFA) was conducted in 14 adult captive smooth dogfish (Mustelus canis). A single dose of CCFA at 6.6 mg/kg was administered intramuscularly. Blood samples were collected prior to treatment and at 1, 2, 6, 12, 24, 32, 48, 72, 96, 120, 144, and 168 hr posttreatment. Naïve pooling of data from four sharks was used to generate the average plasma drug concentration at each time point. After concluding the study, additional blood samples were opportunistically collected from five randomly selected sharks at 1,920 hr. Plasma ceftiofur and desfuroylceftiofur metabolite concentrations were determined using reversed-phase high performance liquid chromatography (HPLC). Pharmacokinetic analysis was performed using a noncompartmental technique. Peak plasma concentration (Cmax) was 3.75 µg/ml with a time to Cmax (Tmax) of 96 hr. Ceftiofur plasma concentrations were maintained above 2 µg/ml for at least 168 hr and were still quantifiable at 1,920 hr.

SURGICAL MANAGEMENT OF UTERINE LESIONS IN TWO CAPTIVE ORANGUTANS ( PONGO SPP.).

Uterine lesions in two orangutans were effectively managed with surgical intervention. A 26-year-old hybrid orangutan ( Pongo spp.) was diagnosed with uterine adenomyosis based on advanced imaging. Histologic evaluation identified multifocal myometrial endometriosis, a variant of adenomyosis. A 27-year-old Bornean orangutan ( Pongo pygmaeus) was diagnosed with a focal uterine fibroid based on histologic examination. The animals were housed at separate institutions and initially presented with dysmenorrhea and menorrhagia. Both animals were treated intermittently for episodes of dysmenorrhea, with recurrence of clinical signs after each treatment. Due to the lack of consistent response to medical management, an ovariohysterectomy in the hybrid orangutan and a myomectomy in the Bornean orangutan were performed and resulted in complete resolution of clinical signs. Surgical management of adenomyosis and neoplasia has previously been reported in nonhuman primates. These cases are the first known documentation of surgical management of multifocal myometrial endometriosis and a fibroid in orangutans.

Thyroid hormone concentrations in relation to age, sex, pregnancy, and perinatal loss in bottlenose dolphins (Tursiops truncatus).

This study evaluated circulating concentrations of thyroid hormones in relation to age, sex, pregnancy status, and perinatal loss in bottlenose dolphins (Tursiops truncatus) under human care. A total of 373 blood samples were collected from 60 individual dolphins housed at nine aquariums/oceanariums. Serum concentrations of total and free thyroxine (T4) and triiodothyronine (T3) were analyzed with commercial RIA kits validated for use with dolphins. While the effect of age was indicated by higher (P<0.0001) concentrations of total and free T4 and T3 in juveniles than adults, the effect of sex on thyroid hormones was inconclusive. The effect of pregnancy was indicated by higher (P<0.035) total and free T4 and T3 during early pregnancy compared to non-pregnancy. For both successful and unsuccessful pregnancy outcomes, maternal concentrations of thyroid hormones were highest during early, intermediate during mid, and lowest during late pregnancy (P<0.07 to P<0.0001). Compared to live and thriving births, concentrations of total and free T4 and total T3 were lower (P<0.08 to P<0.001) in dolphins with perinatal loss. Lower concentrations ranged from 10% to 14% during early, 11% to 18% during mid, and 23% to 37% during late pregnancy. In conclusion, the effects of age, reproductive status and stage of pregnancy on thyroid hormone concentrations are necessary factors to take into account when assessing thyroid gland function. Since perinatal loss may be associated with hypothyroidism in dolphins, analysis of serum T4 and T3 should be considered for those dolphins that have a history of pregnancy loss.

Semen characteristics and artificial insemination in rockhopper penguins (Eudyptes chrysocome chrysocome).

This work was performed as part of a multi-year study to determine the cause of the low fertility in captive rockhopper penguins (Eudyptes chrysocome chrysocome) and attempt to increase the fertility through artificial insemination (AI). Semen collection and characterization was performed on 14 male rockhopper penguins. The samples were evaluated for volume, sperm concentration, and sperm quality (motility, forward motility, viability, and morphology). There was a large variation between individuals and between collections for each individual. Mean volume of ejaculate was 0.24 ml. Mean concentration was 47.09 × 10(6) sperm/ml. Mean number of sperm per collection was 6.57 × 10(6). The mean motility was 49.4%. Mean forward motility was 1.7. Mean percentage of living sperm was 88.9%. Mean percentage of sperm with normal morphology was 69.4%. AI was performed on a total of 10 females using pooled semen samples. The birds were also allowed to naturally mate. Ten eggs were laid and three fertile eggs were produced, one of them hatched but died within 24 hr. Paternity testing was performed using 12 microsatellite loci, but unfortunately due to insufficient variability, the paternity of the chick and two embryos could not be determined.

Hematologic, plasma biochemistry, and select nutrient values in captive smooth dogfish (Mustelus canis).

The Indianapolis Zoo maintains a large collection of smooth dogfish (Mustelus canis). During the first several years of captivity, there was a period of high mortality in adult, wild-caught sharks in the collection. Smooth dogfish with superficial abrasions would rapidly succumb to infection and death, regardless of the treatment approach. Although the sharks did successfully produce viable offspring, there was an elevated pup mortality rate, with 0% of the pups reaching 1 yr of age during the same period of high mortality in adult sharks. This poor response to captivity prompted interest in the physiologic response of these animals to illness. The objective of this investigation was to establish a preliminary data set of hematologic and plasma chemistry reference intervals, along with select nutrient parameters specific to wild-caught adults maintained in prolonged captivity (i.e., greater than 22 mo). Blood samples were collected from 20 clinically healthy, male (n = 10) and female (n = 10) dogfish sharks at the Oceans facility at the Indianapolis Zoo. Although gender differences in mortality rate were not apparent, complete blood cell counts, plasma biochemical profiles, and select nutrient analyses were performed and analyzed accordingly. Statistically significant differences (P < or = 0.05) specific to sex were determined for parameters including packed cell volume (PCV), absolute and relative fine eosinophilic granulocytes, relative percentage of coarse eosinophilic granulocytes, globulins, the albumin/globulin ratio, total protein, phosphorus, iron, selenium and copper. White blood cell counts appear to be lower in this species compared to other captive elasmobranchs. Further research into appropriate hematology standards including nutritional parameters appears warranted.

Phaeohyphomycosis of the carapace in an Aldabra tortoise (Geochelone gigantea).

An adult male Aldabra tortoise (Geochelone gigantea) presented with a deep flaking area of the carapace, and histologic examination of biopsies from this area revealed phaeohyphomycosis of the superficial keratinized layers. The disease progressed rapidly and spread to numerous sites on the carapace. After several weeks of regular debridement, deep bone involvement was evident and was confirmed through histologic examination. Fungal culture was attempted but was unsuccessful at isolating the infectious agent. Polymerase chain reaction analysis of extracted DNA from the fixed tissue block identified the fungus as Exophiala oligosperma. Initial treatment included weekly debridement and oral and topical antifungal agents. A nuclear scintigraphy bone scan was performed to determine the extent and status of the infection. Multiple foci of uptake of the radiopharmaceutical marker were present within the carapace, indicating active lesions. The tortoise was maintained on oral antifungal treatment, and lesions resolved over several months. A repeat bone scan performed 1 yr after initial presentation showed reduction in marker uptake, indicating a response to treatment in the deeper lesions. Phaeohyphomycosis should be considered as a differential diagnosis for cases of shell lesions in chelonians.

Semen collection and characterization in rockhopper penguins (Eudyptes chrysocome chrysocome).

Low egg fertility and hatchability is a common problem in captive populations of rockhopper penguins (Eudyptes chrysocome chrysocome). These conditions make sustaining a captive population challenging. A method for collecting and evaluating semen from rockhopper penguins was developed to assist in the evaluation of low egg fertility found in one captive population. Six adult male rockhopper penguins were conditioned to allow semen collection once a week from the start of breeding season until ejaculates no longer contained sperm. A total of 59 ejaculates was collected between 17 September and 31 December 2004. Forty-five of these samples were evaluated for volume, pH, sperm concentration, and sperm quality (motility, viability, and morphology). There was a large variation between individuals and between collections for each individual. The mean motility was 34.5% (+/- 22%). Mean volume of ejaculate was 0.23 ml (+/- .31 ml). Mean concentration was 16.9 x 10(6) sperm/ml (+/- 48.7 x 10(6) sperm/ml). Mean number of sperm per collection was 1.7 x 10(6) (+/- 4.2 x 10(6)). Mean percentage of living sperm was 82.9% (+/- 18.1%). Mean percentage of sperm with normal morphology was 82.1% (+/- 18.8%). Mean pH was 6.47 (+/- 0.49). During this season, only one of these males paired with a female. The pair produced one fertile egg, but the embryo died early in incubation. Male rockhopper penguins had low sperm concentration and low motility indicating that low male fertility may be contributing to the poor egg fertility rate. This work represents the first step in an ongoing study to improve captive breeding of rockhopper penguins.