Faecal transplantation for the treatment of Clostridium difficile infection in a marmoset.

BACKGROUND: The common marmoset has been used as an experimental animal for various purposes. Because its average weight ranges from 250 to 500 g, weight loss quickly becomes critical for sick animals. Therefore, effective and non-stressful treatment for chronic diseases, including diarrhoea, is essential. CASE PRESENTATION: We report a case in which faecal microbiota transplantation (FMT) led to immediate recovery from chronic and recurrent diarrhoea caused by Clostridium difficile infection. A male common marmoset experienced chronic diarrhoea after antibiotic treatments. The animal experienced severe weight loss, and a faecal sample was confirmed to be C. difficile-positive but was negative for protozoa. Metronidazole was partially effective at the first administration but not after the recurrence of the clinical signs. Then, oral FMT was administered to the subject by feeding fresh faeces from healthy individuals mixed with the marmoset's usual food. We monitored the faeces by categorization into four groups: normal, loose, diarrhoea, and watery. After the first day of FMT treatment, the marmoset underwent a remarkable recovery from diarrhoea, and after the fourth day of treatment, a test for C. difficile was negative. The clinical signs did not recur. The marmoset recovered from sinusitis and bilateral dacryocystitis, which also did not recur, as a by-product of the improvement in its general health caused by the cessation of diarrhoea after the FMT. CONCLUSION: This is the first reported case of successful treatment of a marmoset using oral FMT. As seen in human patients, FMT was effective for the treatment of recurrent C. difficile infection in a captive marmoset.

Diagnoses and Treatment of Dental Disorders in a Research Colony of Macaca fascicularis: A Case Series.

During daily routine oral examinations in a research colony of nonhuman primates (NHPs, Macaca fascicularis), a variety of oral-dental lesions were identified. A dental care program was established based on these findings. Based on the presence of dental clinical signs and their severity, 31 animals were triaged to be examined and treated by a veterinarian. Clinical examination consisted of visual inspection using a periodontal probe/explorer and full or partial mouth dental radiographs. Treatment was performed during the same procedure. Some animals had a follow-up examination including radiographs months later. Four common dental diseases were diagnosed: periodontal disease, caries, tooth fracture, and tooth attrition. Less frequent were dental abscess, enamel hypomineralization, gingival hyperplasia, hypercementosis, tooth luxation, tooth dysplasia, root resorption, abrasion. Less severe periodontal disease was treated conservatively. If severely affected, teeth were extracted. Well-circumscribed caries without endodontic involvement were treated by composite restoration. Teeth with extensive caries and pulp involvement were extracted. Teeth with exposed pulp were treated via extraction or orthograde root canal treatment. In this case series, 27 (87%) of 31 NHPs exhibited at least 1 moderate to severe dental lesion that required treatment. The presumable improvement in welfare and weight of oral/dental lesions for the overall health status in research NHPs encourages us to continue this program prospectively.

RETROSPECTIVE ANALYSIS OF ADULT-ONSET CARDIAC DISEASE IN FRANÇOIS' LANGURS (TRACHYPITHECUS FRANCOISI) HOUSED IN U.S. ZOOS.

Cardiac disease is a common condition in captive primates, and multiple cases in François' langurs ( Trachypithecus francoisi ) were noted on review of the Species Survival Plan studbook. To determine the prevalence of cardiac disease in this species, surveys were distributed to current and previous holding institutions (n = 23) for the U.S. studbook population (n = 216). After exclusion of stillbirths (n = 48), animals less than 1 yr of age (n = 8), and animals housed internationally (n = 2), a study group (n = 158) was identified for this analysis. Robust data was received for 98.7% (n = 156) of the study group and antemortem and postmortem cardiac abnormalities were reported for 25.3% (n = 40) of these animals. Eight animals were reported as medically managed for clinical cardiac disease, and three of these were alive at the time of survey. Six of 11 animals with radiographic cardiac silhouette enlargement antemortem were noted with cardiomegaly on postmortem examination. Of 102 deceased animals in the study group, four were identified with dilated cardiomyopathy, and varying degrees of myocardial fibrosis was observed in 18 animals. Langurs with cardiac fibrosis were found to be significantly older than langurs without cardiac fibrosis (P = 0.003) and more commonly were male (P = 0.036). Screening tests for cardiac disease, such as thoracic radiographs and echocardiography, are recommended to diagnose affected animals earlier, to monitor progression of disease, and to guide treatment, although they should be interpreted with caution because of apparent insensitivity when compared with pathologic results.

DIAGNOSIS AND MANAGEMENT OF BENIGN PROSTATIC HYPERPLASIA IN A PIED TAMARIN (SAGUINUS BICOLOR).

An intact male pied tamarin (Saguinus bicolor) presented with a hunched posture while moving, dysuria, pollakiuria, and hematuria. After diagnostic imaging assessment and prostate biopsy, benign prostatic hyperplasia was diagnosed. Treatments with delmadinone acetate and osaterone caused clinical signs and hematuria to resolve temporarily for a variable period of time. Because of frequent recurrence, elective surgical castration was performed, leading to resolution of the clinical signs.

Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.

Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T(H)2 response following helminth treatment that was associated with a decrease in activated CD4(+) Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in T(H)1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.

Outbreak of pathogenic Escherichia coli in an outdoor-housed non-human primate colony.

BACKGROUND: Pathogenic Escherichia coli has been identified as an etiologic agent in humans causing acute diarrhea or even death but has been rarely reported in non-human primates (NHP). An outbreak of diarrhea occurred in an outdoor-housed NHP colony over a period of 2 months with an attack rate of 29%. METHODS: Bacterial culture and PCR were performed on the fecal specimens to identify enteroinvasive E. coli (EIEC) and Enterohemorrhagic E. coli (EHEC) in the NHPs. RESULTS: By random sampling of 10% of fecal samples of diarrheal cases, four cases of EIEC in rhesus macaques and two cases of EHEC in cynomolgus macaques were confirmed. CONCLUSION: This is the first time EIEC and EHEC have been reported in NHPs associated with diarrhea. The primary source of infection could not be determined.

Multifocal Cryptococcus neoformans var. neoforms: infection, treatment, and monitoring by serial computed tomography in a Schmidt's red-tailed guenon (Cercopithecus ascanius schmidti).

A 9-yr-old, female, intact Schmidt's red-tailed guenon (Cercopithecus ascanius schmidti) presented with an acute swelling, consistent with an abscess over the right hip. Cytology, culture, and polymerase chain reaction (PCR) results from material within the abscess and serum titers were all indicative of a Cryptococcus neoformans infection. Thoracic radiographs and computed tomography (CT) revealed a consolidated right caudal lung lobe associated with an endobronchial mass. Pulmonary Cryptococcus infection and systemic disease was confirmed with positive brush cytology and bronchoalveolar lavage (BAL). Culture and sensitivity, minimum inhibitory concentration values, and serum fluconazole level results were used to develop and monitor treatment efficacy for this animal. Sequential thoracic radiographs, CT images, bronchoscopy, BAL, and serology were used to monitor response to therapy. Five months after initial diagnosis, pregnancy was confirmed and the frequency of immobilizations for recheck serology and diagnostic imaging was decreased to lessen radiation exposure and physiologic stress to the dam and fetus. Long-term administration of oral fluconazole was well accepted and effective at treating the multifocal C. neoformans infection. No long-term adverse effects of therapy were observed, and repeated diagnostics were well tolerated. Advanced imaging modalities and serum drug levels were critical to the assessment, monitoring, and treatment of infection in this animal and should be considered for other cases.

Alopecia: possible causes and treatments, particularly in captive nonhuman primates.

Alopecia (hair loss) occurs in some nonhuman primates housed in captivity and is of concern to colony managers and veterinarians. Here we review the characteristics, potential causes, and treatments for this condition. Although we focus on nonhuman primates, relevant research on other mammalian species is discussed also, due to the relative paucity of studies on alopecia in the primate literature. We first discuss the cycle of hair growth and explain how this cycle can be disrupted to produce alopecia. Numerous factors may be related to hair loss and range from naturally occurring processes (for example, seasonality, aging) to various biologic dysfunctions, including vitamin and mineral imbalances, endocrine disorders, immunologic diseases, and genetic mutations. We also address bacterial and fungal infections, infestation by parasites, and atopic dermatitis as possible causes of alopecia. Finally, we examine the role of psychogenic factors, such as stress. Depending on the presumed cause of the hair loss, various treatment strategies can be pursued. Alopecia in nonhuman primates is a multifaceted disorder with many potential sources. For this reason, appropriate testing for various disease conditions should be completed before alopecia is considered to be related to stress.

Acute Abdominal Distension Due to Disseminated Peritoneal Neoplasia in a Rhesus Macaque (Macaca mulatta).

This report describes the clinical, radiographic, and pathologic findings in a female rhesus macaque that presented with acute abdominal distension and tympany. The macaque was euthanized after evidence of severe colonic distension on radiography and observation of widespread peritoneal adhesions on exploratory laparotomy. Gross and histopathologic evaluation revealed extensive entrapment of gastrointestinal and reproductive tracts by serosal fibrovascular proliferative tissue containing foci of endometriosis. The diagnosis of endometrial stromal sarcoma was supported by expression of CD10, Wilm tumor 1, estrogen receptor, and progesterone receptor and failure to express immunohistochemical markers characteristic of a range of differential diagnoses. In humans, this relatively uncommon neoplasm can arise from sites of endometriosis and often presents clinically as intestinal obstruction, similar to the presentation in this macaque.

An Alternative Treatment Against Acanthocephala ( Prosthenorchis elegans) in Captive Squirrel Monkeys ( Saimiri sciureus) in Mexico.

We provide the first report of Acanthocephala ( Prosthenorchis elegans) in Mexican non-human primates. There has been no known treatment against this parasite except for surgical removal, and this has been relatively ineffective because of the small juveniles. We report the presence of P. elegans in a captive breeding colony of squirrel monkeys ( Saimiri sciureus) in Mexico, and we describe a successful treatment protocol. Treatment involved 2 steps: oral administration of the drugs loperamide chlorhydrate (0.5 mg/0.9 kg/3 days) and niclosamide (0.2 mg/0.9 kg/3 days) followed by surgical removal of adult worms from the intestine. Fecal examination during treatment revealed live adults but no living juveniles and no eggs. Surgery after 1 wk of treatment revealed the presence of adults and an absence of juvenile parasites. All adults were physically extracted during the surgery. All subjects recovered from surgery within 1 wk.

Canine tooth root infection as a cause of facial abscess in the common marmoset (Callithrix jacchus).

Facial abscesses in a colony of common marmosets were found to be caused by abscessation of an upper canine tooth root. Trauma to the upper canine, resulting in exposure of the pulp cavity, was thought to be the mode of infection. Radiography was the most useful diagnostic aid in establishing the nature and extent of the lesion. Antibiotic therapy alone was inadequate, and provision of drainage by extracting the tooth, in conjunction with antibiotics, proved the most effective treatment.

Cardiopulmonary resuscitation in the nonhuman primate.

Seventeen adult male Cynamolgus monkeys were subjected to potassium chloride-induced cardiopulmonary arrests of 10 to 12 minutes. Pupils became dilated and fixed at a mean interval of 30 +/- 11 seconds, and the electroencephalogram became isoelectric at a mean interval of 34 +/- 13 seconds. The monkeys were resuscitated by means of oxygen, external cardiac message, epinephrine, calcium, and bicarbonate. The mean time required to resuscitate the monkeys was 140 +/- 70 seconds. After resuscitation, the monkeys were kept in an intensive care unit. Pupillary responsiveness and electroencephalographic activity were slow to return, with mean intervals of 90 +/- 85 and 108 +/- 36 minutes, respectively. Although all 17 monkeys were resuscitated, only 9 survived 96 hours or more. Of the 9 survivors, 2 appeared neurologically normal, 3 were moderately impaired, and 4 were severely impaired.

Urolithiasis in cynomolgus monkey (Macaca fascicularis): a case report.

Only a few cases of urinary calculi have been reported in cynomolgus monkeys. The adult male Macaca fascicularis presented here had two calculi, both of which were 100% calcium carbonate. Similar calculi occur in humans.

Tuberculosis in laboratory animals.

Tuberculosis can cause great losses in captive colonies of various animal species. In South Africa the culprit is the human type of tubercle bacillus. Interspecific transmission of tuberculosis infection amongst laboratory animals, notably primates, is known to occur, and often handlers and caretakers act as the source of infection. The need for preventive measures in laboratory colonies and procedures for case finding and treatment of tuberculous animals are discussed. Indiscriminate destruction of diseased animals is opposed. The South African situation as revealed by questionnaire survey is described.

[Intestinal microflora of monkeys, normal and in pathology, and its correction by preparations of live bacteria from human biocenosis (coli bacteria, bifikol and bifidum bacterin)]. / Mikroflora kishechnika obez'ian v norme i pri patologii i ee korrektsiia preparatami iz zhivykh bakterii obligatnogo biotsenoza cheloveka (koli-bakterii, bifikol, bifidum-bakterin).

The study of the qualitative and quantitative composition of intestinal microflora in 15 anthropoid apes, 60 lower primates and 72 monkeys with clinically pronounced dysbacteriosis was made, which revealed the prevalence of microorganisms belonging to the genus Proteus, a decrease in the biological activity of normal Escherichia coli and in the content of bifido- and lactobacteria. The treatment of 39 rhesus and pig-tailed macaques with the preparations of live bacteria occurring in normal human microflora led to clinical convalescence and the normalization of the bacteriocenosis, while in 33 control animals no positive shifts in clinical and bacteriological data were observed. The essential similarity of the composition of intestinal microflora in higher and lower primates and in man makes it possible to use these animals as models for testing the effectiveness of new biological preparations and determines the expediency of using bacterial therapy for the treatment of monkeys at the period of acclimatization.

[The principles of the therapy of glanders in monkeys]. / Printsipy terapii sapa u obez'ian.

The effect of pathogenetic therapy in the normalization of homeostasis disturbances in monkeys has been shown under experimental conditions. Data on the possibility of using hemosorption in the treatment of severe forms of glanders are presented. The conclusion on the necessity of using complex treatment for the effective therapy of glanders in humans has been made.

Ménétrier's disease-like hypertrophic gastritis in two red-capped mangabeys (Cercocebus torquatus).

Chronic lymphoplasmacytic gastritis in two red-capped mangabeys (Cercocebus torquatus) at a zoological facility progressed to severe hypertrophic gastropathy similar to Ménétrier's disease that affects humans. Clinical signs included emesis, diarrhea, hunched posture consistent with abdominal pain, anemia, and hypoproteinemia. Large gastric masses were present and in one case created a gastric outflow obstruction. Both cases were positive for simian immunodeficiency virus and Helicobacter spp. were variably isolated, although the association with the hypertrophic gastropathy is unclear. Medical treatment had varying success and included sucralfate, H2 receptor antagonists, proton pump inhibitors, diet manipulations, and antibiotic therapies targeting Helicobacter spp. Surgical resection of a large portion of the stomach resulted in some palliative improvement in one case. Overall, this disease presented many challenges regarding identification, confirmation of diagnosis, and clinical management. Both aggressive medical and surgical treatments were unrewarding for long-term management of hypertrophic gastropathy in this pair of red-capped mangabeys and resulted in a poor prognosis in these cases.

Correction of refractive errors in rhesus macaques (Macaca mulatta) involved in visual research.

Macaques are the most common animal model for studies in vision research, and due to their high value as research subjects, often continue to participate in studies well into old age. As is true in humans, visual acuity in macaques is susceptible to refractive errors. Here we report a case study in which an aged macaque demonstrated clear impairment in visual acuity according to performance on a demanding behavioral task. Refraction demonstrated bilateral myopia that significantly affected behavioral and visual tasks. Using corrective lenses, we were able to restore visual acuity. After correction of myopia, the macaque's performance on behavioral tasks was comparable to that of a healthy control. We screened 20 other male macaques to assess the incidence of refractive errors and ocular pathologies in a larger population. Hyperopia was the most frequent ametropia but was mild in all cases. A second macaque had mild myopia and astigmatism in one eye. There were no other pathologies observed on ocular examination. We developed a simple behavioral task that visual research laboratories could use to test visual acuity in macaques. The test was reliable and easily learned by the animals in 1 d. This case study stresses the importance of screening macaques involved in visual science for refractive errors and ocular pathologies to ensure the quality of research; we also provide simple methodology for screening visual acuity in these animals.

Efficacy of oral fecal bacteriotherapy in rhesus macaques (Macaca mulatta) with chronic diarrhea.

Chronic diarrhea remains the principal burden in providing health care for nonhuman primates in biomedical research facilities. Although the exact etiology continues to puzzle nonhuman primate clinicians, recent research in humans has shown that restoring the indigenous microbial diversity may be successful in resolving cases of chronic diarrhea when other treatment modalities have failed. The process of restoring this microbial balance, known as fecal bacteriotherapy, uses the complete flora from a normal donor as a therapeutic probiotic mixture. In the current study, Indian-origin rhesus macaques were randomized into treatment (n=7) and control (n=6) groups to determine whether orally administered fecal bacteriotherapy would reduce the overall incidence of chronic diarrhea during a 60-d follow-up period in the treatment group compared with control macaques, which received a placebo. Although the treatment effect, determined by comparing the baseline fecal scores of the treatment and control groups, did not reach statistical significance, preprocedure and postprocedure fecal scores in the treatment group differed significantly. These findings are encouraging, and we hope that our study will motivate larger studies evaluating the use of fecal bacteriotherapy in nonhuman primates.