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.

FIRST DETECTION OF CLINICAL DISEASE DUE TO ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 7A IN TWO AFRICAN ELEPHANTS (LOXODONTA AFRICANA) IN HUMAN CARE.

Multiple species of elephant endotheliotropic herpesvirus (EEHV) have caused fatal hemorrhagic disease in African (Loxodonta africana) and Asian (Elephas maximus) elephants. To date, EEHV7 has been detected only in benign pulmonary and skin nodules and in saliva of African elephants and has not been associated with clinical illness. Low-level viremia due to EEHV7A was detected via qPCR in two subadult African elephants during routine surveillance. Hematologic changes were noted in both elephants, including leukopenia, lymphopenia, monocytopenia, and band heterophilia. Treatment was initiated with famciclovir, antimicrobials, and rectal fluids, and one elephant received plasma transfusions due to a progressive decrease in platelet count. Both elephants remained asymptomatic throughout the viremias, with rapid resolution of hematologic abnormalities. These cases add to the current understanding of the epidemiology of EEHV in African elephants; to the authors' knowledge, they represent the first documentation of clinical disease due to EEHV7 infection in any elephant.

USE OF HYSTEROSCOPIC MORCELLATION WITH A MYOSURE® DEVICE FOR REMOVAL OF UTERINE FOREIGN MATERIAL IN AN ORANGUTAN (PONGO SP.).

A 36-yr-old female intact hybrid orangutan (Pongo sp.) presented with evidence of chronic bacterial cystitis with no response to treatment with multiple systemic antibiotics. Abnormalities were identified within the reproductive tract on CT scan, and hysteroscopy was pursued based on the recommendation of an obstetrician-gynecologist. Hysteroscopic examination revealed a large amount of intrauterine foreign material consistent with wood wool from the orangutan's bedding. A hysteroscopic morcellator (MyoSure®) was used to remove the foreign material. Histologic examination of endometrial biopsies showed severe suppurative to pyogranulomatous endometritis with intralesional foreign (wood) fibers and bacteria. The orangutan was treated with antibiotics, but evidence of bacterial cystitis persisted. After 15 wk, additional wood wool was identified within the uterus by hysteroscopic examination and was removed similarly. Five months later, there was no recurrence of foreign material on hysteroscopy or CT. This report describes the first documentation of intrauterine foreign material in a nonhuman primate. Hysteroscopic morcellation is a useful technique for noninvasive removal of intrauterine foreign material in great apes.

Pharmacokinetics of robenacoxib after a single intramuscular dose in smooth dogfish (Mustelus canis).

OBJECTIVE: To determine the pharmacokinetics of robenacoxib after a single intramuscular dose (4.0 mg/kg) in smooth dogfish (Mustelus canis). ANIMALS: 8 healthy adult male smooth dogfish in human care within the same habitat. METHODS: All sharks received a single intramuscular dose of robenacoxib (4.0 mg/kg) in the right caudolateral epaxial musculature. Blood samples were collected under manual restraint from the ventral tail vessel at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours after drug administration. Plasma drug concentrations were determined by HPLC followed by noncompartmental pharmacokinetic analysis of the data. RESULTS: A maximum plasma concentration of 1.24 µg/mL was reached at a mean time of 30 minutes following robenacoxib administration with a plasma elimination half-life of 3.79 hours. Plasma concentrations did not fall below the lower limit of quantification (0.1 µg/mL) at the time points sampled in this study. CLINICAL RELEVANCE: Intramuscular administration of a single dose (4.0 mg/kg) of robenacoxib in smooth dogfish resulted in rapid absorption to a maximum concentration at approximately 30 minutes after administration and persisted above levels considered to be therapeutic in domestic species for at least 8 hours.

Biochemical and molecular confirmation of alkaptonuria in a Sumatran orangutan (Pongo abelii).

A 6-yr-old female orangutan presented with a history of dark urine that turned brown upon standing since birth. Repeated routine urinalysis and urine culture were unremarkable. Urine organic acid analysis showed elevation in homogentisic acid consistent with alkaptonuria. Sequence analysis identified a homozygous missense variant, c.1081G>A (p.Gly361Arg), of the homogentisate 1,2-dioxygenase (HGD) gene. Familial studies, molecular modeling, and comparison to human variant databases support this variant as the underlying cause of alkaptonuria in this orangutan. This is the first report of molecular confirmation of alkaptonuria in a nonhuman primate.

HEALTH ASSESSMENT OF PAINTED TURTLES (CHRYSEMYS PICTA) IN A RESTORED WETLAND HABITAT IN NORTHWESTERN INDIANA, USA.

Freshwater turtles are sensitive to environmental changes and can serve as sentinel species for ecosystem health assessments. The Efroymson Restoration at Kankakee Sands in northwestern Indiana, USA has been restored in the past 25 yr from primarily agricultural land to a mosaic of prairie and wetland habitats. Health assessments of 40 free-ranging painted turtles (Chrysemys picta) at Kankakee Sands were performed in May 2021 to evaluate overall health status, screen for infectious diseases, and obtain baseline clinical pathology values in this population. Assessment of each turtle included a physical examination, complete blood count, plasma biochemistry panel, blood lactate level, venous blood gas analysis, serum trace mineral panel, serum vitamin D3 level, and plasma protein electrophoresis. Oral and cloacal swabs were tested for adenoviruses, herpesviruses, frog virus 3, and Mycoplasmopsis species by PCR in 39 painted turtles. Four turtles were positive for adenovirus, which shared 100% homology to Sulawesi tortoise adenovirus. Two turtles were herpesvirus-positive with 100% homology to emydid herpesvirus 1. No Mycoplasmopsis spp. or frog virus 3 was detected. Female turtles had significantly higher manganese, prealbumin, uric acid, triglycerides, and ionized calcium levels, while male turtles had significantly higher cholesterol, glutamate dehydrogenase, and CO2 levels. These baseline data can be used for future research into freshwater turtle health in restored wetland habitats.

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.

CONGENITAL HYPOTHYROIDISM IN A BORNEAN ORANGUTAN (PONGO PYGMAEUS) AND A SUMATRAN ORANGUTAN (PONGO ABELII).

Congenital hypothyroidism (CH) in humans is most commonly caused by disruption of thyroid gland development (dysgenesis) or an inherited defect in thyroid hormone biosynthesis (dyshormonogenesis). CH has not been previously documented in great apes. This report describes the clinical presentation, diagnosis, and treatment of CH in a 9-mo-old male Bornean orangutan (Pongo pygmaeus) and a 6-wk-old female Sumatran orangutan (Pongo abelii). Primary CH due to thyroid dysgenesis was confirmed in the Bornean orangutan using sonography and radioisotope scintigraphy. Although commercial thyroid immunoassays are not validated for use in orangutans, in comparison to age-matched controls, thyroid-stimulating hormone level was markedly elevated, and serum thyroxine (T4) and free T4 levels were markedly decreased in both cases. Oral supplementation with levothyroxine sodium resulted in noticeable clinical improvement in both orangutans within 30 days of initiating treatment.

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.