Viruses That Cause Disease in Nonhuman Primates

All macaques are considered potential shedders of Cercopithecine herpesvirus 1 (herpesvirus simiae, also known as B virus). The infection is generally subclinical or mild (conjunctivitis or oral vesicles) in Macaca spp but causes fatal encephalitis and encephalomyelitis in humans.

B virus can be transmitted via a bite, scratch, or contamination of a superficial wound or mucous membranes (eg, conjunctiva) with infectious saliva, conjunctival secretions, or genitourinary secretions. Human fatalities due to B virus encephalitis illustrate the importance of using appropriate precautions and personal protective equipment (clothing that covers the arms, face masks, goggles or face shields, and gloves) to prevent direct or indirect contact with macaque secretions and body fluids.

When a human is exposed to macaque body fluids through a bite, scratch, or mucous membrane exposure, a veterinarian should examine the animals involved in the exposure to look for vesicles, ulcers, or other herpetic lesions. 

Swabs should be taken from multiple mucous membranes (eg, mouth, eyes, urethra, vulva) to test for the virus. A blood sample should also be taken for a baseline herpesvirus titer, and a second sample should be collected approximately 2 weeks later to look for rising titer. The National B Virus Resource Center can provide assistance with diagnostic testing.

For high-risk B virus exposures, if the monkey was found to be shedding virus at the time of the exposure, or if a rising titer is detected indicating an active infection at the time the human was exposed, antiviral prophylaxis for the human might be indicated. Captive-born-and-raised animals should still be screened when first presented in a clinical setting and every year afterward in a private facility.

Saimiriine herpesvirus 1 (herpesvirus T) causes mild herpetic lingual ulcers and stomatitis in squirrel monkeys, but natural transmission to owl monkeys and marmosets has resulted in fatal epizootic diseases. Similarly, human herpes simplex virus 1 causes mild infection in humans and certain other primates, but owl monkeys, gibbons, capuchins, and tree shrews (Tupaia glis) are highly susceptible and can die.

Signs of herpesvirus infection in nonhuman primates include ulcerations of the mucous membrane or skin, conjunctivitis, meningitis, or encephalitis. Human caretakers with oral lesions should be replaced until the infection regresses, and any interaction between nonhuman primates showing signs and the public should be discouraged.

Naturally occurring, clinically silent infections with hepatitis A virus (enterically transmitted hepatitis virus) have been reported in chimpanzees (Pan troglodytes) and macaques. Nonhuman primates infected with hepatitis A virus might exhibit increased AST and ALT values. Humans have contracted infections from chimpanzees.

Rubeola infection (measles) acquired via human contact can cause epizootic outbreaks with high mortality rates. The virus causes a nonpruritic, exanthematous rash on the face, chest, and lower portions of the body. It can also cause interstitial giant-cell pneumonia, rhinitis, conjunctivitis, and, particularly in New World monkeys, gastroenteritis. Marmosets are extremely susceptible to measles, and children should not interact with this species.

There is no specific treatment for rubeola infection in nonhuman primates. Vaccination of infant rhesus monkeys and other macaques with human measles vaccine or a canine vaccine containing distemper-measles is recommended. Modified live measles virus vaccine can cause disease in marmosets and is not recommended.

Mpox (previously called "monkeypox") and other poxvirus infections can occur in nonhuman primate colonies. Mpox is a reportable zoonotic disease characterized by a maculopapular rash and variolous pustules. Affected monkeys usually survive and, after recovery, are immune to challenge.

Immunosuppressive disease in nonhuman primates can be caused by a number of retroviruses, including several orthoretroviruses (formerly called type C and type D oncornaviruses), and several simian immunodeficiency viruses (SIVs). SIVs are lentiviruses closely related to human immunodeficiency virus (HIV-1 and HIV-2). Other unique immunodeficiency viruses have been found in different species of nonhuman primates.

SIVs are of low pathogenicity in their natural hosts (African primate species), and infections are often clinically silent but can cause devastating disease similar to acquired immunodeficiency syndrome (AIDS) in macaques after cross-species transmission. SIV has been demonstrated to infect humans; however, the long-term consequences of infection are unknown.

Infection with orthoretroviruses of the genus Betaretrovirus can cause an immunodeficiency predisposing the animal to a complex of diseases such as fibromatosis, atypical mycobacteriosis, intestinal cryptosporidiosis, pneumocystic pneumonia, disseminated cytomegalovirus infection, and candidiasis in colonies of macaques—similar to that found in infections caused by SIV.

Infection with oncornaviruses of the genus Deltaretrovirus (formerly type C retrovirus) results primarily in lymphoproliferative disease, and rarely T-cell lymphoma, in Old World monkeys and apes. There is great host-interspecies variation in clinical signs and susceptibility from virus to virus. Infection is transmitted between nonhuman primates via direct or indirect contact with infected blood and other body fluids or from dam to offspring.

Human respiratory viral diseases such as the common cold, respiratory syncytial virus infection, and influenza are all transmissible to nonhuman primates. For high-risk situations such as zoos or for geriatric animals, vaccination for viral respiratory diseases should be considered.

Signs of respiratory virus infection range from self-limiting rhinitis to fulminant pneumonia with lethargy. Diagnosis of potential anthropozoonotic agents such as influenza, respiratory syncytial virus (RSV), or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be achieved via commercial PCR assays or ELISAs using nasal swabs or via paired serum titers.

Treatment of viral respiratory diseases in nonhuman primates consists of supportive care and treatment of secondary infections.

GI viruses such as noroviruses, adenoviruses, and rotaviruses are often underrecognized and underreported as a cause of GI upset and diarrhea in nonhuman primates, and they should be differentiated from bacterial or parasitic etiologies.

Hemorrhagic viral zoonoses, such as Ebola or Marburg hemorrhagic fever and mosquito-borne yellow fever, are risks with wild-caught animals. An important differential diagnosis for these zoonoses is simian hemorrhagic fever. This Arterivirus infection is subclinical in African monkeys but is highly contagious and fatal for Asian species. Hemorrhagic necrosis of the proximal duodenum is a pathognomonic lesion. Captive populations that ultimately are housed in private facilities are a low risk.

• Viral Immunology Center, Georgia State University: National B Virus Resource Center

• Centers for Disease Control and Prevention: Clinical Overview of B Virus