VSC 443/543 (U of A) Diseases of Nonhuman Primates Diseases of Nonhuman Primates
 

DISEASES OF NONHUMAN PRIMATES

RESEARCH ANIMAL METHODS
VSC 443/543 - Fall 2007

Lecture notes for November 14, 2007

Michael S. Rand, Assistant Director, University Animal Care
University of Arizona - Tucson, AZ

TABLE OF CONTENTS

Viral Diseases

Measles

Herpesvirus tamarinus and Herpesvirus simplex

Bacterial Diseases

Tuberculosis

Streptococcus pneumoniae

Shigellosis

Campylobacteriosis

Parasitic Diseases

Gastrointestinal protozoal agents

Nematodes

Arthropods

Reproductive Conditions

Endometriosis

Dystocia

Miscellaneous Conditions

Traumatic injuries

Dental conditions

Behavioral disorders

Hypothermia

Hypoglycemia

Acute gastric dilatation/bloat

Scurvy

Reference


Common clinical problems

In general, the most common health problems encountered in a nonhuman primate colony involve bacterial enteritis, bacterial pneumonia, and traumatic injuries.  The clinical conditions presented are categorized as viral, bacterial, parasitic, reproductive, or miscellaneous.  Where appropriate, a brief discussion of the etiology, clinical signs, diagnostic procedures, and treatment recommendations are included. A preventive health program, as well as good husbandry and sanitation practices, will limit the occurrence of many of the clinical conditions described.

Viral Diseases

Measles

  • A human Morbillivirus causes measles.
  • It has been reported in New and Old World species, and the great apes.
  • The primary route of transmission of measles is through inhaled aerosols from infected animals or humans.
  • In macaques and most Old World species, the disease is usually mild or asymptomatic unless the animal is stressed or immunosuppressed.  Clinical signs most frequently seen include nasal discharge, conjunctivitis, facial edema, blepharitis, a papular skin rash, and in severe cases, pneumonia.
  • In marmosets and owl monkeys, measles causes a gastroenterocolitis with a mortality rate approaching 100%.  These animals present with diarrhea and lack the characteristic rash and upper respiratory signs seen in Old World species.
  • There is no specific treatment for measles other than supportive care.
  • Immunizing susceptible populations of animals and limiting contact with humans can prevent measles outbreaks.

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Herpesvirus tamarinus and Herpesvirus simplex 

  • Herpesvirus tamarinus (herpes T) and Herpesvirus simplex cause very similar disease conditions in New World species.
  • Squirrel, spider, and capuchin monkeys serve as asymptomatic reservoir hosts of herpes T, whereas humans are the reservoir host of herpes simplex.
  • Transmission is through contact with asymptomatic carriers shedding the virus and/or contact with infected bodily secretions.
  • Herpes T is not typically associated with clinical signs in carrier species, although on occasion it has been associated with oral ulcerative lesions.
  • In susceptible species (owl monkeys, marmosets, and tamarins), herpes T and herpes simplex can cause a fatal disease process characterized by anorexia, dermatitis, pruritus, depression, and ulcerative lesions of the oral cavity and the gastrointestinal tract.
  • There is no specific treatment for herpes T and herpes simplex in susceptible species other than supportive care.
  • Herpes T and herpes simplex outbreaks can be minimized by preventing contact of susceptible species with carrier species and humans with active herpes simplex lesions.

Bacterial Diseases

Tuberculosis

  • Tuberculosis is one of the most important bacterial diseases of nonhuman primates.  Most reported cases are caused by the acid-fast bacillus Mycobacterium tuberculosis or Mycobacterium bovis.
  • Susceptibility of nonhuman primates varies, with Old World species considered more susceptible to infection than New World species.
  • The primary route of transmission of tuberculosis is through inhaled aerosols from infected animals.  Animals with tuberculosis of the gastrointestinal tract can shed the organism in their feces.
  • In nonhuman primates, tuberculosis classically involves the respiratory system and clinical signs may include coughing, labored breathing, and exercise intolerance.  Because tuberculosis can involve a multitude of organ systems, signs vary, depending, on the system affected. Some additional nonspecific signs associated with infection include chronic weight loss, diarrhea, and enlarged lymph nodes with or without draining tracts.
  • The tuberculin skin test is the primary method used in the antemortem diagnosis of tuberculosis.
  • Due to the inherent risk a nonhuman primate infected with tuberculosis poses to the colony and staff, it is recommended that animals infected with or suspected of being infected with tuberculosis be euthanatized.  For valuable animals or special circumstances, tuberculosis-positive animals can be successfully treated with a regimen of isoniazid, ethambutol, and rifampin. 
  • Tuberculosis in a colony can be prevented/minimized by establishing a preventive health program that includes obtaining animals from reputable sources, tuberculin skin testing animals in quarantine and the conditioned colony, annual (minimum frequency) tuberculin skin testing of staff that come in contact with nonhuman primates, and limiting nonessential human access to the colony.

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Streptococcus pneumoniae

  • Streptococcus pneumoniae is a Gram-positive coccoid bacterium usually found in pairs or chains.
  • It can be carried in the respiratory tract of asymptomatic nonhuman primates as well as other species, including humans.
  • The primary route of transmission is through inhaled aerosols from infected animals.
  • Most reported clinical cases in nonhuman primates involve macaques and the great apes.  Active disease is often associated with stress-related factors such as shipment, quarantine, and viral respiratory infections.
  • Animals infected with this agent typically present with clinical signs consistent with pneumonia, such as cough, dyspnea, and exercise intolerance.  In addition, this agent may cause bacterial meningitis. These animals will present with central nervous signs such as ataxia, head tilt/head press, paralysis, and seizures.
  • Clinical pneumonia has been effectively treated using long-acting penicillins; whereas clinical disease associated with meningitis has been effectively treated with cephalosporins.
  • Other bacterial agents that cause pneumonia in nonhuman primates include Klebsiella pneumoniae and Bordetella bronchiseptica.

Shigellosis

  • Shigellas are rod shaped, Gram-negative bacteria.  The most common isolate in nonhuman primates is Shigella flexneri.
  • It is one of the more common enteric bacterial pathogens isolated from nonhuman primates, occurring in New and Old World species and the great apes.
  • The fecal-oral route spreads infection and asymptomatic carriers may exist within colonies.
  • Clinical signs associated with shigellosis include depression, anorexia, dehydration, weakness, and diarrhea containing variable amounts of blood and mucus.  Abdominal pain is often evident and affected animals may sit in a hunched posture with hands and arms folded across their abdomen. Marked gingivitis has also been associated with nonenteric shigella infections.
  • Shigellosis has been successfully treated using enrofloxacin.  Supportive care, including fluid and electrolyte administration, may be necessary in severe cases.

Campylobacteriosis

  • Campylobacter are curved, slender, Gram-negative bacteria.  The most common isolates of nonhuman primates are Campylobacter jejuni and Campylobacter coli.
  • It is one of the more common enteric bacterial pathogens isolated from nonhuman primates, occurring in New and Old World species.
  • The fecal-oral route spreads infection and asymptornatic carriers may exist within colonies.
  • Clinical signs associated with campylobacter infections include watery diarrhea with or without blood, dehydration, and weight loss.  In some cases, an animal may present with chronic or intermittent diarrhea.
  • Campylobacteriosis has been successfully treated using oral erythromycin.  Many infections are self-limiting and animals may only require supportive care (fluid and electrolyte administration).

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Parasitic Diseases

Gastrointestinal protozoal agents

  • Nonhuman primates are frequently infected with gastrointestinal protozoal agents.  Agents associated with clinical disease include Giardia spp., Trichomonas spp.,Cryptosporidium spp., Entamoeba histolytica, and Balantidium coli.
  • These agents are transmitted through the fecal-oral route, direct contact with infected animals and their excretions, and contaminated food and water.
  • The clinical signs associated with these agents can vary from an asymptomatic carrier state to severe diarrhea and dehydration.  Specifically, Cryptosporidiurn infections have been associated with intractable diarrhea and dehydration in infants and immunosuppressed animals, whereas Balantidium coli has been associated with severe ulcerative enterocolitis and death in great apes. Entamoeba histolytica has been reported to cause more significant disease, including marked diarrhea with blood and mucus, in young and immunosuppressed animals, and New World species. Giardia causes greasy diarrhea and vomiting in all species.  Trichomonads cause diarrhea in callitrichids (e.g., marmosets).
  • Giardia spp., Trichomonas spp., Entamoeba histolytica and Balantidium coli have been successfully treated using metronidazole.  Cryptosporidium infections are usually self-limiting and most animals can be effectively treated by providing supportive care, including fluid and electrolyte administration.

Nematodes

  • Oesophagostomum spp., or nodular worms, is the most common nematode parasite found in Old World species and the great apes.  Infection is usually asymptomatic: however, heavy burdens can cause diarrhea, weight loss, and abdominal adhesions. The parasite produces firm, smooth, black or white nodules in the wall of the colon.  Oesophagostomum eggs resemble hookworm eggs.  Thiabendazole and ivermectin have been used to treat animals infected with this parasite.
  • Strongyloides cebus and Strongy1oides fulleborni are commonly found to infect New and Old World species, respectively.  Infection is usually asymptomatic; however, severe infections can cause diarrhea. Other clinical signs associated with larval migration include cough, dyspnea, and dermatitis.  Thiabendazole and ivermectin have been used to treat animals infected with this parasite.

Arthropods

Lung mites, Pneumonyssus spp., are the most important arthropod found in Old World monkeys.  The most commonly encountered member of this species is Pneumonyssus simicola, which is found in rhesus monkeys.  Animals with lung mites are usually asymptomatic; however, coughing and pulmonary lesions have been associated with infestation. Pulmonary lesions typically consist of small, pale yellow to gray/tan cystic foci throughout the lungs. In addition, fibrous adhesions between the lungs and the pleural cavity may be present.  Ivermectin has been reported to be effective in eliminating lung mite infestations in nonhuman primates.

Reproductive Conditions

Endometriosis

Endometriosis is one of the most common reproductive disorders seen in rhesus and cynomolgus macaques.  In addition to infertility, suggestive clinical signs of endometriosis include cyclical abdominal pain, anorexia, weight loss, depression, and a decrease or absence of feces as well as the presence of a mass in the caudal abdomen. Infrequently, prolonged menstrual bleeding coupled with mild anemia may be observed. Pathologic findings are typically associated with the reproductive tract and include the presence of cystic structures containing a characteristic brown ("chocolate-like") fluid as well as localized to extensive adhesions involving the bladder and colon.  Endometriosis can be managed medically with danazol, leuprolide, or medroxyprogesterone, or surgically via ovarlohysterectomy.  In severe cases of endometriosis, marked adhesions may preclude surgical management.

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Dystocia

Dystocia occurs in nonhuman primates and is considered relatively common in squirrel monkeys and marmosets.  Predisposing factors include the size, presentation, and position of the fetus as well as maternal pelvic abnormalities. Squirrel monkeys are particularly prone to dystocia because of the infant's relatively large head size and high birth weight, 15 to 17% of the mother's weight for male infants and 5 to 8% for female infants.

Typically, nonhuman primates give birth at night or during the early morning while in a squat or upright position.  Uncomplicated labor usually lasts I to 4 hours, and the vast majority of babies are delivered head first. Signs indicating that a nonhuman primate is having difficulty giving birth and may require manual or surgical assistance include:

  • A weak, depressed animal lying down in the cage
  • Labor that fails to progress during a 2-hour period or that lasts for more than 4 or 5 hours.
  • Evidence of fetal malpresentation during delivery (i.e., the presence of a limb(s) or tail in the pelvic canal or exiting the vagina)

Note: Dystocia should be considered a life-threatening condition for both the mother and the unborn infant, and a veterinarian should be contacted immediately should an animal appear to be having difficulty giving birth.

Miscellaneous Conditions 

Traumatic injuries

Traumatic injuries are commonplace in nonhuman primate facilities.  Most injuries occur as a result of fighting. The most frequently encountered injuries typically involve the hands, feet, or tail.  These injuries can be quite extensive and may require amputation of digits and/or portions of the tail. Fresh lacerations/wounds with minimal contamination can be managed by thoroughly cleaning/lavaging the site with a 0.05% chlorhexidine solution before suture repair.  In addition to thorough cleaning, old contaminated or infected lacerations/wounds may require the use of wet-to-dry bandages, drains, or surgical debridement.

In group-housed animals, fighting may result in crushing injuries.  Crushing injuries are characterized by areas of marked soft tissue damage (bruising). The significance of these injuries is deceptive and they are often difficult to detect because of the length of an animal's hair as well as the lack of a major laceration and external hemorrhage. Various factors released from the damaged soft tissue can induce acute renal failure; therefore, animals with crush-like injuries should be treated aggressively with intravenous fluids.

The management of nonhuman primates with wounds can be challenging because of their intelligence, dexterity, and inclination to pick at wounds and suture lines.  If bandages are used, they should be checked frequently to make sure they are clean, intact, and have not slipped in such a manner as to occlude the venous return of the respective limb.

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Dental conditions

In addition to the accumulation of dental tartar and associated gingivitis and periodontal disease, one of the more frequently encountered dental conditions in a nonhuman primate colony is tooth root abscess.  Tooth root abscesses can develop subsequent to severe periodontal disease, technical failure of canine disarming methods, and traumatic injuries to teeth from chewing on cages, sticks, and other manipulanda. They typically present as a draining fistulous tract in either the oral cavity or on the face of an animal.  A root canal procedure or extraction of the affected tooth is the treatment of choice for an abscessed tooth.  

Behavioral disorders

Abnormal behavior in nonhuman primates often takes the form of stereotypic behavior, that is, a repetitive action that does not appear to serve any apparent biologic purpose.  Examples of stereotypic behaviors include pacing, back flipping, bouncing and rocking, as well as digit sucking, self-clasping, and excessive grooming. Nonhuman primates can also exhibit self-injurious behaviors such as hair-plucking, head banging, and self-biting. A variety of factors have been proposed as being associated with the development of aberrant behavior, including rearing method, social isolation, and environmental complexity. Animals reared in total or partial isolation not only frequently develop a variety of stereotypes, but also may lack the social skills necessary to be pair or group housed as adults.

Hypothermia

Hypothermia is a frequently encountered clinical condition in nonhuman primate facilities.  Animals most prone to develop hypothermia include the smaller New World monkeys, as well as the young, old, debilitated, and anesthetized nonhuman primates of all species.  The clinical presentation of hypothermia includes lethargy, huddling, recumbency, and/or an increase in anesthetic recovery time. Body temperatures of nonhuman primates can readily be assessed using mercury rectal, digital, or tympanic membrane thermometers.  Hypothermia generally occurs secondary to some other underlying process; therefore, after initiating measures to treat an animal's hypothermia, the animal should be assessed to determine possible causes such as hypoglycemia, debilitating systemic disease, or anesthesia/chemical restraint.  Below is a list of some methods to minimize further heat loss as well as provide supplemental heat.

  • Direct contact with metal surfaces, such as found in cages and on examination tables, should be eliminated because these surfaces can serve as heat sinks.  Simply placing insulating material between the animal’s body and the metal surface can do this.
  • Animals should be removed from drafty locations such as positions near supply or exhaust ducts.
  • Animal room temperatures should be checked and, where appropriate, increased.
  • Heat lamps are frequently used to provide supplemental heat to nonhuman primates; however, care must be taken to minimize thermal burns.  Heat lamps should not be placed any closer than 4 feet from an animal or cage. When using a heat lamp on an animal in a cage, it should be directed only on a portion of the cage so that the animal can self-regulate his/her exposure to the heat source. Halogen lamps should never be used as a supplemental heat source.
  • Warm water recirculating blankets, nontoxic heat solution packs that use an exothermic reaction, and warm bags of saline can be used to provide supplemental heat to anesthetized or recumbent animals.  A towel or other linen-like material should be placed between the animal's body and the heat source. Warm air blankets can also be used to provide supplemental heat to anesthetized or recumbant animals. An electric heating pad should not be used as a supplemental heat source due to the potential for thermal burns and electric shock.
  • Hypothermic animals can also be maintained in incubators or incubator-type cages.

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Hypoglycemia

Hypoglycemia is another condition frequently encountered in nonhuman primate facilities.  Animals at risk for developing a hypoglycemic crisis include small New World species, anorectic or fasted animals, animals receiving insulin, and the young of all species, in particular squirrel monkey infants.  The clinical presentation of hypoglycernia includes lethargy, weakness, ataxia, recumbency, and hypothermia.

A hypoglycemic animal that is conscious can be treated by orally administering a 20% dextrose solution, Gatorade, or Pedialyte.  Administering intravenously 2 to 4 ml/kg of a 50% dextrose solution can treat a hypoglycemic animal that is unconscious.  Subsequent administration of a high caloric liquid diet such as Ensure by stomach tube will minimize potential relapse. In addition, most unconscious/recumbent animals will be hypothermic and will require heat supplementation. Upon recovery, animals should be offered their favorite food items, monitored for a relapse, and assessed to determine the underlying cause of the hypoglycermic episode.

Acute gastric dilatation/bloat

Acute gastric dilatation/bloat occurs in both Old World and New World species.  The cause of bloat in most cases is associated with the rapid production of gas in the gastrointestinal tract by clostridial organisms. Predisposing factors implicated in the disease include a sudden change in diet, excessive water intake, prolonged broad-spectrum antibiotic therapy, anesthesia, shipping, and fasting followed by free-choice feeding.

Bloat is a rapidly progressive disease process that can result in death in a matter of hours. Clinical signs include abdominal distension, restlessness, lying down in the cage, rapid shallow respiratory pattern, increased heart rate, pale/gray mucous membranes, and a prolonged capillary refill time. At necropsy, animals have markedly distended stomachs and distended and congested intestines. In some cases, the stomach may rupture. In addition, subcutaneous hemorrhage, edema, and emphysema may be present, as well as rectal and vaginal prolapse.

If clinical signs consistent with acute gastric dilatation are noted, a veterinarian should be contacted immediately. Treatment consists of passing a stomach tube to relieve gastric gas and excess fluid buildup. Supportive therapy, including fluid therapy, antibiotics, analgesics, and corticosteroids for shock, should also be initiated. The occurrence of bloat can be decreased by limiting feed intake after fasting and anesthesia, changing diets gradually, feeding animals multiple times during the day, and the judicious use of broad-spectrum antibiotics that affect the gut flora.  

Scurvy

Nonhuman primates develop scurvy if they do not receive adequate amounts of dietary vitamin C. Typical clinical signs include joint swelling and joint pain, lameness, anemia, and gingival and subcutaneous hemorrhage.  Cephalohematoma is a common finding in squirrel monkeys with scurvy. Treatment for vitamin C deficiency consists of ascorbic acid injections; 25 mg/kg given intramuscularly twice daily for 5 days. Feeding an appropriately stored commercial nonhuman primate diet within 3 months of milling can prevent Vitamin C deficiency.

Reference

  1. Fortman, J.D., Hewett, T.A., and Bennett, B.T.  The Laboratory Nonhuman Primate.  CRC Press, Boca Raton, FL, 2002.

  2. Fox, J.G., Anderson, L.C., Loew, F.M., et all.  Laboratory Animal Medicine. Academic Press, San Diego, CA, 2002.

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