FLOWCHART

Diseases / List of Viral Diseases / Disease description:

Herpesvirus hominis (simplex) Infection

Disease Summary

Alternative Names (Synonyms)

• Herpes hominis infection
• Herpes simplex infection.
• Human herpesvirus 1 infection
• Human herpesvirus 2 infection

Disease Type

 Viral

Infectious/Non-Infectious Agent (directly associated with the Disease)

• In a survey of samples submitted to a virus reference laboratory in San Antonio, Texas, for chimpanzees (Pan troglodytes - Chimpanzee and Pan paniscus - Pygmy chimpanzee) 13/56 (23%) were positive for HSV-1 and 6/51 (12%) were positive for HSV-2; Gorilla gorilla - Gorilla, 39/63 (62%) were positive for HSV-1 and 13/62 (21%) were positive for HSV-2; in Pongo pygmaeus - Orang-utan, 4/36 (11%) were positive for HSV-1 and only 1/34 (3%) for HSV-2. (J495.47.w6)
• Possibly also closely-related viruses specific to great apes - see discussion in Herpesviridae- Herpesvirus hominis (simplex) Virus - Viral Type Diversity

Species/Taxa

• Herpesviridae- Herpesvirus hominis (simplex) Virus

Chemical

• --

Physical

• --

References

Disease Author

Referee

References

• --

Incubation Period, Time Course and Persistence of Disease

1) INCUBATION PERIOD:

• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)), infected experimentally by corneal scarification of one eye, conjunctivitis, blepharitis and lacrimation developed in the inoculated eye after five days. (J495.19.w2)
• In experimentally inoculated White-handed gibbons - Hylobates lar (Hylobatidae - Gibbons (Family)), lesions first appeared two days after intradermal inoculation of virus. (N38.1968.w1)
  • In an experimentally infected White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), recrudescence of lesions developed starting five days after injection with epinephrine (adrenaline). (N38.1969.w1)
• In Cebus albifrons - Brown pale-fronted capuchin (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2, the first signs (vaginal inflammation and discharge, vulval vesicles) were noted three days post inoculation. (J39.139.w1)
• In Cebus albifrons - Brown pale-fronted capuchin (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2, lesions first appeared seven days post-inoculation. (J547.37.w1)
• In Cebus apella - Black-capped capuchin (Cebidae - New-world monkeys (Family)) with experimental ocular infection, ocular lesions appeared in the infected eye starting 4 - 6 dpi with Herpesvirus hominis type 1 and after 12 - 14 days (eight days in one individual) with Herpesvirus hominis type 2. Lesions developed in the contralateral eye about 14 days post inoculation. (J71.40.w1)
• In experimentally inoculated Callithrix jacchus - Common marmosets, shorter incubation following intracerebral than following intravenous or subcutaneous inoculation, but time not stated. (J100.128.w1)
• In naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)), less than eight days (captured 7 - 8 days before arrival in the laboratory; clinical signs present on arrival). (J495.22.w2)
• In humans: 2 - 12 days; mean about four days. (B560.67.w67)

2) DISEASE DURATION (TO RECOVERY OR DEATH) IN INDIVIDUAL ANIMALS:

• In humans, recurrent lesions usually last about 5 - 10 days. (J495.19.w1)
• In one male Pan troglodytes - Chimpanzee and two female bonobos (Pan paniscus - Pygmy chimpanzee), 15 - 21 days. (J495.30.w4)
• In a group of chimpanzees, two to three weeks. (J223.87.w1)
• In one 13-day old Gorilla gorilla - Gorilla at Basel Zoo, only five hours from the onset of overt clinical signs to death. (J543.10.w1)
• In a six-month-old female Pongo pygmaeus - Orang-utan, at Ouwehands Zoo, nine days from first signs to death. (J2.36.w5)
• In a group of White-handed gibbons - Hylobates lar (Hylobatidae - Gibbons (Family)), oral lesions healed in less than one week. In individuals developing signs of encephalitis, disease lasted one to six days before euthanasia in terminal coma. (J100.120.w1)
• In a one-year-old pet male White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), four days to death. (J71.31.w1)
• In a 44-year-old female White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), three days from initial signs to euthanasia. (J212.17.w3)
• In experimentally inoculated White-handed gibbons - Hylobates lar (Hylobatidae - Gibbons (Family)), skin lesions healed within three weeks [the time at which oral and conjunctival lesions healed was not stated]. (N38.1968.w1)
• In a two-year-old male Mountain agile gibbon - Hylobates agilis agilis (Hylobatidae - Gibbons (Family)), four days from the first signs to death. (J2.29.w6)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)), in Davis, California, signs lasted four to seven days before death. (J495.19.w2)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)), infected experimentally by corneal scarification of one eye, death occurred died after one or two days of illness. (J495.19.w2)
• Experimentally inoculated Aotis trivirgatus - Owl monkeys (Cebidae - New-world monkeys (Family)) and Saguinus oedipus - Cotton-top tamarin died within 7 - 9 days of inoculation. (B581.w8)
• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)), one to four days from first clinical signs to death. (J543.32.w1)
• In experimentally infected Cebus apella - Black-capped capuchin (Cebidae - New-world monkeys (Family)), following intravaginal inoculation, lesions healed within 14 days: (J71.39.w1)
• In Cebus albifrons - Brown pale-fronted capuchin (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2, virus was isolated at 3 - 16 days post inoculation [the length of time for which lesions were visible was not given]. (J39.139.w1)
• In Cebus albifrons - Brown pale-fronted capuchin (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2, lesions started to regress by 15 days post inoculation (J39.139.w1)
• In Cebus albifrons - Brown pale-fronted capuchin (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2, lesions resolved by 21 days after they appeared. (J547.37.w1)
• In Cebus apella - Black-capped capuchin (Cebidae - New-world monkeys (Family)) with experimental ocular infection, ocular lesions lasted for about 8 - 14 days. (J71.40.w1)
• In Callithrix jacchus - Common marmoset, one to two days from the onset of clinical signs to death or euthanasia. (J26.40.w2)
• In Callithrix jacchus - Common marmoset, three days in two individuals (twins, six months old), four days in another individual at a separate location. (J212.9.w1)
• In a two-year-old pet Callithrix jacchus - Common marmoset, death after eight days. (J84.8.w17)
• In a group of five Callithrix jacchus - Common marmoset, four to six days from first signs to euthanasia in two juveniles, seven days from initial signs to sudden death in an adult male. The time course of illness the third juvenile was not stated; illness in the adult female (which survived) was described as "a short episode."(J2.35.w4)
• In experimentally inoculated Callithrix jacchus - Common marmosets, death about eight dpi following intracerebral inoculation, about 10.5 dpi following intravenous inoculation and about 18 dpi following subcutaneous inoculation. (J100.128.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)), varied from two days to five months from first signs to death. (J546.3.w1)
• In humans: two to three weeks with clinical primary gingivostomatitis. Recurrent lesions on the lips generally heal in 8 - 10 days. With primary genital herpes, about three weeks (average); this is reduced to about two weeks when the initial genital infection occurs in an individual with preexisting antibodies, and recurrent genital lesions last about 7 - 10 days. (B560.67.w67)

3) TIME COURSE / PERSISTENCE OF DISEASE IN A SUSCEPTIBLE POPULATION:

• In one Pan troglodytes - Chimpanzee, lesions recurred five months after the initial outbreak. (J495.30.w4)
• In a group of chimpanzees, two to three weeks. (J223.87.w1)
• In a group of Gorilla gorilla - Gorilla at Basel Zoo, lesions were seen in adults about a month after death of a 13-day-old infant. (J543.10.w1)
• In White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), disease occurred over a period of eight months. (J100.120.w1)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)), deaths occurred over a period of eight to 36 days in two outbreaks. In Davis, California, 45 of fifty animals were affected over a period of five weeks, with most cases (30) occurring in the first two weeks. (J495.19.w2)
• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)), six days from the first clinical signs to the last death. (J543.32.w1)
• In a family group of eight Callithrix jacchus - Common marmosets, two days. (J26.40.w2)
• In a group of five Callithrix jacchus - Common marmoset, about four weeks from the first signs to the last death. (J2.35.w4)
• In three adult Callithrix jacchus - Common marmoset, deaths occurred over a period of ten days. (J552.8.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)), seven months from the first signs to the last death. (J546.3.w1)
• In naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)), deaths occurred over a period of ten days. (J495.22.w2)
• In humans: ubiquitous, permanent infection in populations. (B560.67.w67)

Mortality / Morbidity / Susceptibility / Life stage affected

1) NUMBER OF DEATHS

• No deaths in a group of two male Pan troglodytes - Chimpanzees and three female bonobos (Pan paniscus - Pygmy chimpanzee). (J495.30.w4)
• None. (J223.87.w1)
• In a group of Gorilla gorilla - Gorilla at Basel Zoo, one individual, a 13-day-old infant, died; no deaths occurred in other animals adults in the group. (J543.10.w1)
• No deaths in five affected Eastern gorillas (Gorilla beringei spp.) (P3.2007b.w2)
• In Pongo pygmaeus - Orang-utan at Ouwehands Zoo, one six-month-old female died. (J2.36.w5)
• In two-year-old lowland gorillas (Gorilla gorilla - Gorilla), severe infection in six individuals; one female died. (J4.167.w6)
• One male white-handed gibbon - Hylobates lar [no data given on whether other gibbons were in contact.] (J4.181.w6)
• In a colony of White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), four individuals developed fatal encephalitis. There were about 80 gibbons on the premises. (J100.120.w1, N38.1968.w1)
• A single pet male 2.5-year-old White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)). (J71.31.w1)
• A 44-year-old female White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)); her 19-year-old daughter was not affected. (J212.17.w3)
• One two-year-old male Mountain agile gibbon - Hylobates agilis agilis (Hylobatidae - Gibbons (Family)). (J2.29.w6)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)), in Davis, California, 45 of fifty animals were affected; all affected individuals died. (J495.19.w2)
• In Pithecia pithecia pithecia - White-faced saki monkeys (Cebidae - New-world monkeys (Family)), all three individuals (pair and their offspring) infected died. (J543.32.w1)
• In Cebus albifrons - Brown pale-fronted capuchin (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2, no deaths. (J547.37.w1)
• In Callithrix jacchus - Common marmoset, three described infections were fatal [a fourth fatal case was also described but a different (unidientified) herpesvirus, not HSV, was considered responsible]. (J212.9.w1)
• Fatal infection in one two-year-old pet Callithrix jacchus - Common marmoset. (J84.8.w17)
• In a family group of eight Callithrix jacchus - Common marmosets, all animals died. Other groups kept at the same location but without direct contact, were unaffected. (J26.40.w2)
• In a group of five Callithrix jacchus - Common marmoset, four individuals died. (J2.35.w4)
• Three adult Callithrix jacchus - Common marmosets. (J552.8.w1)
• In experimentally inoculated Callithrix jacchus - Common marmosets, 22 of 24 inoculated marmosets died, including all 12 inoculated intracerebrally or intravenously; the two survivors were 2/12 inoculated subcutaneously. (J100.128.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)), six or seven lemurs died; all affected animals died (one infant disappeared and was not confirmed either affected or uninfected; an additional infant was aborted). (J546.3.w1)
• In naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)), eight of 13 animals died; herpesvirus infection confirmed or probable in five. (J495.22.w2)

2) NUMBER OF ANIMALS AFFECTED

• In a group of two male Pan troglodytes - Chimpanzees and four bonobos (Pan paniscus - Pygmy chimpanzee), three individuals (one male Pan troglodytes - Chimpanzees and two female bonobos (Pan paniscus - Pygmy chimpanzee) developed genital and/or oral herpetic lesions, an additional Pan troglodytes - Chimpanzee developed fever (and Streptococcus tonsillitis) and all five of the animals for which paired serum samples were available seroconverted. (J495.30.w4)
• Signs developed in five chimpanzees from one group at the same time. (J223.87.w1)
• In a group of Gorilla gorilla - Gorilla at Basel Zoo, a 13-day-old infant died and vesicular eruptions were seen on two adults; illness [not definitely related] was also seen in the mother of the infant, a week before illness in the infant. (J543.10.w1)
• In a group of orphaned Eastern gorillas (Gorilla beringei spp.) in Rwanda, five of seven individuals affected. (P3.2007b.w2)
• In Pongo pygmaeus - Orang-utan, at Ouwehands Zoo, only one individual, a six-month-old infant, affected. (J2.36.w5)
• Six two-year-old lowland gorillas (Gorilla gorilla - Gorilla). (J4.167.w6)
• One male white-handed gibbon - Hylobates lar [no data given on whether other gibbons were in contact.] (J4.181.w6)
• In a colony of White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), oral lesions occurred on six animals and encephalitis in four individuals (including one which had previously had oral lesions). There were about 80 gibbons on the premises. (J100.120.w1, N38.1968.w1)
• A 44-year-old female White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)); her 19-year-old daughter was not affected. (J212.17.w3)
• One two-year-old male Mountain agile gibbon - Hylobates agilis agilis (Hylobatidae - Gibbons (Family)). (J2.29.w6)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)), in Davis, California, 45 of fifty animals were affected. The other five animals were not infected, as shown by lack of measurable antibodies (CF or neutralizing antibodies) and absence of virus in tissues. (J495.19.w2)
• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)), three individuals (pair and their offspring). (J543.32.w1)
• In Cebus albifrons - Brown pale-fronted capuchin (Cebidae - New-world monkeys (Family)) experimentally infected by intravaginal inoculation with Herpesvirus hominis type 2, all individuals developed lesions. (J22.171.w1)
• In Cebus albifrons - Brown pale-fronted capuchin (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2, all individuals developed lesions. (J547.37.w1)
  • On reinfection: lesions developed in 3/10 individuals. (J547.37.w1)
• In a family group of eight Callithrix jacchus - Common marmosets, all eight individuals were affected. (J26.40.w2)
• In Callithrix jacchus - Common marmoset, three fatal infections with HSV were described [a fourth fatal case was also described but a different (unidientified) herpesvirus, not HSV, was considered responsible]. (J212.9.w1)
• Fatal infection in one two-year-old pet Callithrix jacchus - Common marmoset. (J84.8.w17)
• In a group of five Callithrix jacchus - Common marmoset, all were affected. (J2.35.w4)
• Three adult Callithrix jacchus - Common marmosets died; there was no information regarding the size of the group. (J552.8.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)), six or seven individuals were affected (plus one infant disappeared and was not confirmed either affected or uninfected). (J546.3.w1)
• In naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)), eight of 13 animals died; herpesvirus infection confirmed or probable in five. (J495.22.w2)

3) EFFECTS OF AGE, SEX AND REPRODUCTIVE STATUS

• Both male and female chimpanzees affected. (J223.87.w1)
• In a group of Gorilla gorilla - Gorilla at Basel Zoo, the only death was in a 14-day-old infant; only mild signs (vesicular eruptions, listlessness, anorexia) were seen in adults. (J543.10.w1)
• In Eastern gorillas (Gorilla beringei spp.) the affected animals were all orphans [presumably juveniles]. (P3.2007b.w2)
• In Pongo pygmaeus - Orang-utan, at Ouwehands Zoo, a six-month-old female died but no illness was reported in other individuals. (J2.36.w5)
• In humans, infection may occur in all ages. Generalised disease, with high mortality, is most common in neonates and young children. (J495.19.w1)
• In humans, while disease is generally localised (gingivostomatitis), generalised disease with high mortality can occur in infants and young children. Meningoencephalitis with a high fatality rate also can occur in adult humans. (J495.19.w1)
• Fatal infection in one five-year-old male white-handed gibbon - Hylobates lar [no data given on whether other gibbons were in contact.] (J4.181.w6)
• In a colony of White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), two individuals, one which developed only oral lesions and the other which developed oral lesions and later encephalitis, were described as "young adult"; the ages of the other affected individuals were not stated. (J100.120.w1)
• Fatal infection occurred in a 2.5-year-old pet male White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)). (J71.31.w1)
• In a 44-year-old female White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), advanced age was considered to be a factor in development of probable recrudescence of latent infection. (J212.17.w3)
• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)), an adult male, adult female and their juvenile offspring were all fatally affected. (J543.32.w1)
• In a family group of eight Callithrix jacchus - Common marmosets, males and females, one to nine years of age, were affected. (J26.40.w2)
• In Callithrix jacchus - Common marmoset, the animals were "young"; two were noted to be six months old. (J212.9.w1)
• Fatal infection in one two-year-old pet Callithrix jacchus - Common marmoset. (J84.8.w17)
• In a group of five Callithrix jacchus - Common marmoset, four nine-month old individuals and one adult male died while an adult female survived. (J2.35.w4)
• Three adult Callithrix jacchus - Common marmosets. (J552.8.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)), adults and possibly an infant (which disappeared and was not confirmed either affected or uninfected) were affected; another infant was aborted. (J546.3.w1)

4) EFFECTS OF BODY CONDITION AND OTHER DISEASES

Stress/stressors in general appear to increase susceptibility to the development of clinical signs associated with herpes hominis (simplex) virus. 

• In humans, reactivation may be associated with a variety of triggers including fever, colds, fatigue, emotional distress, menstruation and some foods. (B564.13.w13)
• In one of five experimentally-infected White-handed gibbons - Hylobates lar (Hylobatidae - Gibbons (Family)), intramuscular injection of epinephrine (adrenaline) resulted in recrudescence of herpetic lesions on the oral mucosa and skin. (N38.1968.w1, N38.1969.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)), it was considered possible that the stress of being moved to a new enclosure (which required catching), and stress from closeness to the public in their new location, may have increased susceptibility. (J546.3.w1)
• Naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)) had been recently captured and transported. (J495.22.w2)

Clinical Signs (by physiological system)

Specific lesions seen in individual great apes are generally vesicles and ulcers of mucosae; these may include oral and pharyngeal ulcers, ulcers and vesicles on the gingiva and at the mucocutaneous junction of the lips, vesicles on the lips and nose, conjunctival lesions and pustulovesicular and/or ulcerated lesions of the genitalia. Other signs have included general listlessness and anorexia. In two fatal cases in infants, diarrhoea and vomiting occurred in a six-month old Pongo pygmaeus - Orang-utan) and laboured breathing as well as vesicle in a 13-day-old Gorilla gorilla - Gorilla. In other, more susceptible, nonhuman primates, conjunctival, oral and cutaneous lesions (vesicles to ulcers), general weakness, depression and anorexia, excessive salivation and serous nasal discharge, and neurological signs including aggression, ataxia and seizures.

• In a group of two male Pan troglodytes - Chimpanzees and four bonobos (Pan paniscus - Pygmy chimpanzee), variable depression and anorexia, plus lesions: (J495.30.w4)
  • One male Pan troglodytes - Chimpanzee initially developed a 4 mm diameter, circular, pustulovesicular lesion mid-shaft on the penis; by five days later, this was about 10 - 12 mm wide, extending around the penis shaft. Additional lesions (vesicular) were seen on the gingiva and tongue. (J495.30.w4)
    • Genital and oral lesions recurred five months later. (J495.30.w4)
  • One female bonobo (Pan paniscus - Pygmy chimpanzee) developed pustulovesicular and ulcerated lesions on the inner labial fold. (J495.30.w4)
  • One female bonobo developed oral lesions [details not given]. (J495.30.w4)
  • One male Pan troglodytes - Chimpanzee did not develop visible herpetic lesions but did develop fever (39.8 °C) and exudative tonsillitis (beta-haemolytic Streptococcus isolated); it was not clear whether this was related to herpesvirus infection. (J495.30.w4)
• In a five-year-old female Pan troglodytes - Chimpanzee, oral (including tongue) and pharyngeal ulcers, whitish in colour, with red borders. In four other individuals in the same group, similar oral lesions were observed at the same time. (J223.87.w1)
• In a group of Gorilla gorilla - Gorilla at Basel Zoo. (J543.10.w1)
  • In a 13-day-old infant, laboured breathing, development of numerous vesicles on the face (hairless regions) and death five hours after the first signs were seen. (J543.10.w1)
  • In adults: vesicles, mainly on the upper lip and nose, in two individuals; the male remained otherwise normal while the female was listless and anorectic. Listlessness and tremors had also been noted in an adult female (mother of the infant) a week before the infant became ill, but it is not known whether this was related. (J543.10.w1)
• In one gorilla, at least one labial lesion [no details given]. (J93.27.w2)
• In five affected orphaned Eastern gorillas (Gorilla beringei spp.) lethargy, anorexia and development of large ulcerated lesions on the lips at the mucocutaneous junction. Clinical examination revealed multiple clear, fluid-filled vesicles, up to 2 cm diameter, on the mucosa of the gingiva and lips. It was noted that disease severity and progression varied between individuals. (P3.2007b.w2)
• In a six-month-old female Pongo pygmaeus - Orang-utan at Ouwehands Zoo: (J2.36.w5)
  • Diarrhoea and vomiting. (J2.36.w5)
• In six two-year-old lowland gorillas (Gorilla gorilla - Gorilla): (J4.167.w6)
  • On the lips (oral), "deep, extensive, and apparently painful" lesions. 
  • In one female, "generalised herpetic lesions in conjunctival, nasal, oral, vaginal, and rectal skin." (J4.167.w6)
• In humans: (J495.19.w1)
  • Initial infection, acute gingivostomatitis. (J495.19.w1)
  • Recurrent: usually on the lip (mucocutaneous junction), sometime the external nares, oral mucosa, skin, conjunctiva, oesophagus, external genitalia, vagina or cervix, small clusters of vesicles; these rupture and the resultant erosions or ulcers. Local hyperaesthesia and/or neuralgia may occur starting before visible lesions appear and may continue after visible lesions have healed. (J495.19.w1)
• In one male White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)). (J4.181.w6)
  • Generalised ataxia and seizure activity. Initially focal seizure-like activity of the face - every five seconds, a grimacing expression. By six hours later, seizures affected the head, neck and pectoral limbs. The following day, clonic contractions affecting the whole body every five seconds, and depression. By the third day, coma and continuing convulsions. Death. (J4.181.w6)
• In a colony of White-handed gibbons - Hylobates lar (Hylobatidae - Gibbons (Family)). (J100.120.w1)
  • Oral lesions: at the mucocutaneous junction on the lateral commisures of the lips, lesions described as superficial denuded areas/prominent excoriated areas in three individuals with healed within one week, and in three other individuals, "small, well circumscribed vesicles that ulcerated rapidly, became necrotic, and healed slowly". (J100.120.w1)
  • Neurological signs: initial docility (in normally aggressive individuals) and lethargy, anorexia, ataxia, excessive salivation, convulsive seizures, paralysis of the lips, tongue and throat, hemiplegia (usually), blindness (sometimes) and descending paralysis developing to coma. (J100.120.w1)
• In a 2.5-year-old pet male White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)). (J71.31.w1)
  • Fever, chills, nasal discharge, irritability and aggression. Facial muscle twitching, progressive weakness of the extremities. Death in less than four days. (J71.31.w1)
• In a 44-year-old female White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)): (J212.17.w3)
  • Weakness, disorientation and ataxia, thought to be post-seizure (due to a history of previous seizures). Further examination revealed paresis, altered mentation and severe hypothermia. Over the next three days the gibbon remained weak, poorly responsive, and unable to thermoregulate, therefore was euthanased. (J212.17.w3)
• In experimentally infected White-handed gibbons - Hylobates lar (Hylobatidae - Gibbons (Family)) (inoculated intradermally on the back, submucosally in the labial surface of the lips and by light scarification of one eye): (N38.1968.w1)
  • Cutaneous: initial red, raised lesions after two days, developing ulcerated centres by day four, then starting to regress before becoming enlarged and inflamed on days 6 - 7 (reaching up to 35 mm diameter); secondary vesicles appeared two days later; all lesions had healed by three weeks post inoculation. (N38.1968.w1)
  • Oral: vesicles developed at 3 - 4 days, increased in size and spread, affecting other areas of the mouth, including the tongue, with large areas sloughing and necrotic by eight days post inoculation. (N38.1968.w1)
  • Ocular: conjunctivitis developed four to six days post inoculation; by two days later extensive exudative keratoconjunctivitis and palpebral oedema was noted, with corneal ulceration by 9 - 10 days post inoculation. (N38.1968.w1)
• In a two-year-old male Mountain agile gibbon - Hylobates agilis agilis (Hylobatidae - Gibbons (Family)). (J2.29.w6)
  • Initially wrist folding and myoclonus, worsening. By the second day, unable to walk, and salivating profusely. Progressing to semi-comatose, and by the third day, still salivating constantly and profusely, unable to lift its head; the gibbon died on the fourth day. (J2.29.w6)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)), in Davis, California, conjunctivitis, coryza and lethargy. (J495.19.w2)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)), infected experimentally by corneal scarification of one eye, conjunctivitis, blepharitis and lacrimation developed in the inoculated eye after five days. The monkeys became lethargic and anorectic, remained on the floor of their cage, and died after one or two days of illness. (J495.19.w2)
• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)): (J495.32.w1)
  • Nasal discharge, depression and anorexia, pyrexia (103  -109 °F), dehydration and oral ulcers.
  • In the adult male only, also tonic-clonic seizures.

  (J543.32.w1)

• In experimentally infected Cebus apella - Black-capped capuchin (Cebidae - New-world monkeys (Family)), following intravaginal inoculation with Herpesvirus hominis 1 or Herpesvirus hominis 2: (J71.39.w1)
  • Vulval labia, vulvar and vaginal mucosa: vesicular lesions, progressing to ulcerated, persisting for five to seven days and healed or healing by 14 days post inoculation. (J71.39.w1)
• In Cebus albifrons - Brown pale-fronted capuchins (Cebidae - New-world monkeys (Family)) experimentally infected by intravaginal inoculation with Herpesvirus hominis type 2: (J22.171.w1)
  • Vaginal and cervical inflammation; on the vulva, vesicles or ulcers, and sometimes perineal and finger lesions (type not specified). (J22.171.w1)
  • With repeated infection, 6 - 12 weeks later, discrete vulval vesicles. (J22.171.w1)
• In Cebus albifrons - Brown pale-fronted capuchins (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2: (J39.139.w1)
  • Vaginal inflammation and purulent vaginal discharge; later (by eight days post inoculation) vesicular lesions on the mucosa; on the vulval labia, vesicular lesions developing to ulcerated. Lesions started to regress by 15 days. (J39.139.w1)
• In Cebus albifrons - Brown pale-fronted capuchins (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2: (J547.37.w1)
  • On the vulval labia, introitus and lower vagina, small vesicles, 1 - 3 mm diameter appearing seven days post inoculation, coalescing and eroding to form ulcers which often exceeded 1 cm, with inflammation, oedema of the labai and apparent marked pruritis; over 3 - 4 days the lesions became purulent and necrotic, then slowly healed over a further 7 - 14 days (healed by 28 days post-inoculation). (J547.37.w1)
  • Upper vagina and cervix: moderately severe inflammation but no vesicles or ulceration. (J547.37.w1)
  • Face, distal fingers and lips: in five of 10 individuals, small discrete vesicles, 1 - 2 mm diameter, and ulcers, developing 4 - 5 days after the onset of genital lesions, healing after 3 - 5 days without development of purulence or necrosis. (J547.37.w1)
  • On reinfection: in 3/10 individuals, vulval labial vesicles, remaining discrete, ulcerating and healing in 5 - 8 days. (J547.37.w1)
• In Cebus apella - Black-capped capuchins (Cebidae - New-world monkeys (Family)) with experimental ocular infection: (J71.40.w1)
  • Initially follicular conjunctivitis, with later development of superficial ulcerative keratitis (corneal ulceration) and disciform keratitis. (J71.40.w1)
• In a family group of eight Callithrix jacchus - Common marmosets: (J26.40.w2)
  • Apathy/depression, anorexia and weakness; excessive salivation and serous nasal discharge; ulceration of the oral cavity and lips (vesicular to ulcerative gingivitis) and in three individuals "lesions covered with fibrinonecrotic exudate at the mucocutaneous junctions." (J26.40.w2)
• In Callithrix jacchus - Common marmosets: (J212.9.w1)
  • In one individual, depression and anorexia, serous nasal and ocular discharges and vesicular to ulcerative dermatitis and stomatitis. (J212.9.w1)
  • In two six-month-old twin marmosets, depression, anorexia and oral ulceration. (J212.9.w1)
  • [Seizures were the presenting sign in a fourth individual, with a history of previous scrotal ulceration, but the infection was found to be due to a different (unidentified) herpesvirus]. (J212.9.w1)
• In a two-year-old pet Callithrix jacchus - Common marmoset. (J84.8.w17)
  • Severe necrotising stomatitis, anorexia and vomiting. Death after eight days. (J84.8.w17)
• In a group of five Callithrix jacchus - Common marmoset. (J2.35.w4)
  • In two nine-month old individuals, anorexia, depression, severe ulcerative gingivitis and stomatitis, enlarged mandibular lymph nodes. In an adult pair, a short period of depression and reluctance to feed, followed a week later by sudden death of one of the animals (male). (J2.35.w4)
• In experimentally inoculated Callithrix jacchus - Common marmosets: (J39.139.w1)
  • Females inoculated intravaginally with Herpesvirus hominis type 2 developed severe lesions on the vulva, vagina and cervix [necrotic lesions indicated at necropsy] and died after 8 - 19 days. (J39.139.w1)
  • A male inoculated with Herpesvirus hominis type 2 by intranasal and ocular installation became moribund on the seventh day. (J39.139.w1)
• In one of three adult Callithrix jacchus - Common marmosets (signs were not described for the other two animals). (J552.8.w1)
  • Lesions (vesicles and ulcers) on the tongue and the commisures of the lips, preventing eating.
• In experimentally inoculated Callithrix jacchus - Common marmosets: (J100.128.w1)
  • Anorexia, diarrhoea, dehydration, terminal hypothermia (35 °C) and usually death. (J100.128.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)), non-specific and central nervous signs: (J546.3.w1)
  • Lemur 1: Listlessness and odd posture before death.
  • Lemur 2: Excess salivation, extreme weakness before death.
  • Lemur 3: Excess salivation, abortion, head tilt, slow, careful movements with greatly reduced jumping, and general dullness.
  • Lemur 5: Initial lethargy and unsteadiness; six weeks later lethargic and lying on the ground, head tilt, loss of equilibrium, weakness and inability to jump before death.
  • Lemur 6: Lethargic, becoming more listless in the following weeks before death.
  • Lemur 8: Apparent abortion, lethargy and lying on the ground, developing to extreme weakness before death.
  • An infant (offspring of one of the affected females) was small and developed slowly but was apparently normal before disappearing overnight.

  (J546.3.w1)

• In naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)): (J495.22.w2)
  • Inactive and emaciated.
  • Conjunctivitis and clear ocular discharge.

  (J495.22.w2)

• In humans: 
  • Primary oral: variable from asymptomatic to "combinations of fever, sore throat, ulcerative and vesicular lesions, gingivostomatitis, edema, localized lymphadenopathy, anorexia, and malaise." Most commonly, asymptomatic. (B560.67.w67)

Experimental infections without clinical signs:

• Attempts to infect Saimiri sciurea - Squirrel monkeys (Cebidae - New-world monkeys (Family)) by intravaginal inoculation with Herpesvirus hominis type 2 were unsuccessful. (J22.171.w1, J547.37.w1)
  • No clinical signs/lesions, no virus isolated, no antigen detected by immunofluresence, and no seroconversion. (J547.37.w1)
• Attempts to infect Macaca mulatta - Rhesus macaque by intravaginal inoculation with Herpesvirus hominis type 2 were unsuccessful. (J22.171.w1, J547.37.w1)
  • Mild inflammation of the vagina and cervix on first inoculation, no virus isolation (except immediately after removal of the swab used for inoculation), and possible fluorescence of a few cells (immunofluorescence test for antigen) from the cervical smear of one of five individuals. No seroconversion. (J547.37.w1)
• Papio cynocephalus - Yellow baboons (Cercopithecidae - Old-world monkeys (Family)) inoculated with Herpesvirus hominis type 2 by the intravaginal, intramuscular, intravenous or intranasal route seroconverted but did not develop any lesions; females inoculated intravaginally did shed virus for a period of 3 - 5 days post inoculation. (J39.139.w1)

Clinical Pathology (Testing Samples incl. Serology)

Seroconversion is generally apparent in affected individuals and high antibody titres may persist for years after infection. However, individuals dying of acute infection have not always seroconverted. Serum biochemistry and blood counts have generally been unremarkable, although abnormal values indicative of dehydration together with raised liver enzymes were noted in one White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), and dehydration plus mild leukopaenia in two Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)).

• In an affected five-year-old female chimpanzee, blood biochemistry parameters normal. (J223.87.w1)
• Serology: nine of 21 sera from the group of chimpanzees were positive for an alphaherpesvirus of the herpes simplexvirus group, by ELISA, reacting with HSV-1, HSV-2 and HVP2 (herpesvirus papio 2) antigen. (J223.87.w1)
  • Competition ELISAs showed that two sera from chimpanzees in this group, and serum from another, USA zoo-housed, chimpanzee previously tested, were probably infected with the same virus: soluble ChHV antigen completely inhibited reactivity of the chimpanzee sera with solid-phase HSV2 antigen (while only partially competing reactivity of HSV-2 positive human serum with solid-phase HSV-2 antigen). In contrast, soluble HSV-2 antigen efficiently competed reactivity of human HSV-2 positive serum with solid-phase ChHV antigen and only partially competed reactivity of chimpanzee sera with solid-phase ChHV antigen. (J223.87.w1)
• In orphaned Eastern gorillas (Gorilla beringei ssp.), serological samples taken. (P3.2007b.w2)
  • In sera taken before the outbreak, all affected individuals were HSV-1 negative and sera from the remaining two unaffected individuals were seropositive. (P3.2007b.w2)
• Serum of the mother of a six-month-old female Pongo pygmaeus - Orang-utan which died from generalised herpesvirus infection at Ouwehands Zoo was positive for HSV-1 (IgG antibodies, 1.61; also level of 3.97 in serum collected three years earlier). (J2.36.w5)
• In a 44-year-old female White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)): (J212.17.w3)
  • Prerenal azotaemia and hypernatraemia, suggesting dehydration. Also elevated liver enzymes (aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase. (J212.17.w3)
• In experimentally infected White-handed gibbons - Hylobates lar (Hylobatidae - Gibbons (Family)), high titre serum neutralization antibodies developed by three weeks after inoculation with Herpesvirus hominis. (N38.1968.w1)
  • [Note: SN antibodies did not develop in two gibbons inoculated with a strain of Herpesvirus hominis isolated from a gibbon with encephalitis; these animals also did not develop lesions. However, lesions did develop on re-inoculation with the same strain or with human strain herpes virus hominis several months later; the simplest explanation is that through a laboratory error the gibbons were not inoculated with live virus on the first occasion.]
• Following the death of a two-year-old male Mountain agile gibbon - Hylobates agilis agilis (Hylobatidae - Gibbons (Family)), testing of 15 gibbons for antibodies using Western blot and virus neutralisation tests detected antibodies to the gibbon herpesvirus isolate and HSV1 in four individuals, including the sister of the affected gibbon, an unrelated, wild-born female housed with the affected gibbon, a gibbon housed at the same location but not in contact, and a gibbon from another location. Three of the gibbons were also positive for HSV2 antibodies. (J2.29.w6)
• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)), dehydration and mild leukopaenia (WBC count 5,300/µL in the adult male, 8,600/µL in the adult female, 4,600 /µL in the juvenile). (J543.32.w1)
• In experimentally infected Cebus apella - Black-capped capuchin (Cebidae - New-world monkeys (Family)), following intravaginal inoculation with Herpesvirus hominis 1 or Herpesvirus hominis 2, serum neutralizing antibodies developed. (J71.39.w1)
• In Cebus albifrons - Brown pale-fronted capuchins (Cebidae - New-world monkeys (Family)) infected by intravaginal inoculation with Herpesvirus hominis type 2: (J547.37.w1)
  • Virus antigen detected by immunofluresence testing in cervical smears of three of five individuals, with specific virus immunofluorescence during the period 3 - 8 dpi and in one individual to 16 dpi.
  • Virus isolated from skin lesions of four of five individuals.
  • Significant increase in neutralising antibody titre in all 10 inoculated monkeys (from < 1:4 increasing to at least 1:16)

  (J547.37.w1)

• In Cebus apella - Black-capped capuchins (Cebidae - New-world monkeys (Family)) with experimental ocular infection, development of low-level serum neutralising antibodies (1:4 to 1:16 by one to two weeks post inoculation. (J71.40.w1)
• In experimentally inoculated Callithrix jacchus - Common marmosets: (J100.128.w1)
  • No significant rises in antibody titre (FAT or seum neutralisation test) in marmosets dying from the infection.
  • In two marmosets which survived inoculation, preexisting FAT of 1:32 and 1:61 (SN <4) increasing to FAT 1:512 by day 32.

  (J100.128.w1)

• In a group of five Callithrix jacchus - Common marmoset, the surviving adult female was positive for complement fixation antibodies to HSV (titre 1:320) and was still positive at the same titre four years after initial examination. Two offspring tested at nine months of age were seronegative (titre < 1:10). Titres of three individuals at another location were <1:10, 1:10 and 1:40 - all titres which would be considered seronegative in humans. (J2.35.w4)

• Biopsy samples were taken of genital lesions of one male Pan troglodytes - Chimpanzees and one female bonobo (Pan paniscus - Pygmy chimpanzee). (J495.30.w4)
• Biopsy of tongue lesions from a five-year-old female chimpanzee. (J223.87.w1)
• in five affected orphaned Eastern gorillas (Gorilla beringei spp.), biopsy samples of one lesion and swabs from lesions. (P3.2007b.w2)
• Samples of affected oral mucosa from a two-year-old pet Callithrix jacchus - Common marmoset. (J84.8.w17)

See also:

• Herpesviridae: Herpesvirus hominis (simplex) Virus - Virus Detection and Identification Techniques

Pathological Findings (by anatomical system)

Pathological lesions are variable and may include: multifocal vesicular and necrotising dermatitis, particularly on the face; gingivitis and stomatitis; hepatomegaly, sometimes with mottling, congestion or necrotic foci; splenomegaly, splenic congestion; pulmonary oedema with froth in the trachea; lymphadenopathy, lymph node petechiation; ocular lesions (conjunctivitis, eyelid swelling, ulcers); sometimes adrenal enlargement, necrosis or haemorrhage; CNS lesions (e.g. oedema, punctate haemorrhages, focal softening and necrosis, congested meninges.

GROSS PATHOLOGY

• In a 13-day-old Gorilla gorilla - Gorilla at Basel Zoo: (J543.10.w1)
  • Cutaneous: on the hairless area of the face in particular, but also the chest, arms, legs and soles of the feet, numerous slightly raised vesicles. (J543.10.w1)
  • Pulmonary: lungs distended, deep red, with a narrow zone of emphysema marginally. (J543.10.w1)
  • Hepatic: liver enlarged and yellow brown, with many 0.5 mm sharply-defined yellow foci especially in the lateral lobes. (J543.10.w1)
  • Splenic: spleen congested.
  • GIT: Many mucosal erosions and ulcerations. (J543.10.w1)
• In a six-month-old female Pongo pygmaeus - Orang-utan at Ouwehands Zoo: (J2.36.w5)
  • General: petechiae on peritoneal and serosal membranes; fair body condition.
  • Cutaneous: petechiae in the pectoral region and upper arms.
  • Cardiac: pericardium fluid-filled (clear fluid), myocardium pale, with petechiae.
  • Pulmonary: foam in trachea; lungs oedematous and hyperaemic.
  • Hepatic: liver enlarged, mottled.
  • Spleen: enlarged, hyperaemic.
  • Stomach: empty.
  • Small intestine: filled with bile-stained mucus.
  • Large intestine: proximally full of yellowish viscous chyme; descending colon full of thick, solid material.
  • Renal: Kidneys pale brown.

  (J2.36.w5)

• In one male white-handed gibbon - Hylobates lar. (J4.181.w6)
  • Hepatic: Congestion.
  • Pulmonary: froth in trachea, pulmonary oedema.
  • CNS: "grey matter of the brain was moderately edematous, with diffuse punctate hemorrhages."

  (J4.181.w6)

• In a colony of White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)). (J100.120.w1)
  • CNS: brain oedema and hyperaemia, meningeal opacification. In three of four animals, in the cerebrum, focal softening and necrosis, particularly affecting the temporal lobe, also in the frontal, parietal and occipital lobes. In two individuals, swelling and slight oedema of the cerebellum and brain stem. (J100.120.w1)
  • Renal: kidney small and fibrotic in one individual. (J100.120.w1)
  • Hepatic: liver large and friable in one individual. (J100.120.w1)
• In a 44-year-old female White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)), no gross lesions. (J212.17.w3)
• In a two-year-old male Mountain agile gibbon - Hylobates agilis agilis (Hylobatidae - Gibbons (Family)). (J2.29.w6)
  • Cardiac: In the left ventricular septum, a large endocardial eccymotic haemorrhage. (J2.29.w6)
  • CNS: meninges intensely congested. (J2.29.w6)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)): (J495.19.w2)
  • Tongue (animals at the New England Primate Research Centre, but not those in Davis, California): On the dorsal and lateral surfaces, necrotic plaques and ulcers, varying in size. Plaques were grey to yellow, with dead tissue clinging to the base, while ulcers, which were depressed, were red.
  • Liver: necrotic foci, seen as grey-white lesions 1 mm diameter, or larger, more irregular and often confluent red areas, on both the capsular surface and cut surfaces.
  • Pulmonary: in the lungs of six individuals, 0.2 - 0.5 cm red patches (two or three such patches).
  • Adrenals: enlarged with cortices mottled red and grey.
  • Lymph nodes: often petechiated.
  • Ocular: 
    • In the experimentally infected individuals, swollen eyelid, congested conjunctival vessels, conjunctival sac contained granular debris, corneal surface rough.
    • In one naturally-infected individual, similar findings but in both eyes.

  (J495.19.w2)

• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)): (J543.32.w1)
  • Oral and oesophagus: ulcers.
  • Nasal turbinates: areas of mucosa dark red.
  • Hepatic: irregular disseminated tan areas.

  (J543.32.w1)

• In a family group of eight Callithrix jacchus - Common marmosets: (J26.40.w2)
  • Oral: acute gingivitis and stomatitis, with multifocal/coalescing lingual erosions, 0.5 - 1.0 cm diameter, with rough borders. In three individuals, some lesions were considered to be ulcers and were covered with a fibrinopurulent exudate.
  • Splenic: mild enlargement of the spleen.
  • Lymph nodes: severe regional lymph node lymphadenopathy.

  (J26.40.w2)

• In Callithrix jacchus - Common marmosets: (J212.9.w1)
  • In one individual: (J212.9.w1)
    • Ventral abdomen: a 2 x 1 cm cutaneous ulcer with a fibrinonecrotic exudate covering the ulcer;
    • Mucocutaneous junction of the lower lip: a similar lesion, 2 mm diameter. 
    • Tongue: an ulcer 3 mm deep. 
    • Oronasal skin, lips and eyelids: erythema, small erosions and ulcers, coalescing.
    • Spleen: mild splenomegaly.
  • In two six-month-old twins: multifocal fibrinoulcerative stomatitis. (J212.9.w1)
• In a group of five Callithrix jacchus - Common marmosets. (J2.35.w4)
  • In three juveniles (nine months old):
    • Oral: ulcerative stomatitis and glossitis.
    • Cutaneous: In one juvenile, multiple forehead skin erosions, circumscribed.
    • CNS: Meningoencephalitis.
  • In one adult male, no gross lesions.

  (J2.35.w4)

• In three adult Callithrix jacchus - Common marmosets. (J552.8.w1)
  • Oral: Lesions on the tongue, commisures of the lips, and deeper in the mouth, including intact vesicles and ulcers. (J552.8.w1)
• In experimentally infected female Callithrix jacchus - Common marmosets inoculated intravaginally with Herpesvirus hominis type 2: (J39.139.w1)
  • Genital: vulval necrotic lesions, severe. In the vagina, viscous purulent exudate filling the vagina; in the mucosa, areas of petechiae. Cervix showed variable necrotic lesions.
  • Bladder: distended, haemorrhagic. Neck of urethra necrotic and containing clotted blood.
  • Adrenals: enlarged, with focal areas of necrosis on the surface.
  • Splenic: necrotic foci present.
  • Pulmonary: lung consolidation in two of four individuals.

  (J39.139.w1)

• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)): (J546.3.w1)
  • Few gross lesions. In one individual (Lemur 10, mild keratitis. In another (Lemur 2), faecal soiling of the hindquarters, and hyperaemia of the small intestine mucosa. No gross lesions in two other lemurs examined. (J546.3.w1)
• In naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)): (J495.22.w2)
  • General: emaciation, dehydration.
  • Hepatic: Fatty change. In 2/8, extensive haemorrhage and necrosis.
  • Adrenal: in the cortex of 2/8, extensive haemorrhage and necrosis.
  • Ocular: in 1/8, conjunctivitis; periorbital congestion and oedema, erosion of periorbital superficial epithelium.

  (J495.22.w2)

HISTOPATHOLOGY

Cutaneous lesions include ballooning degeneration, erosions and necrosis with associated inflammatory infiltrate, syncytial cells and intranuclear inclusion bodies. Pulmonary lesions of oedema, emphysema and haemorrhagic necrotic foci, with eosinophilic intranuclear inclusions and syncytial cells. Focal necrosis and Cowdry type A intranuclear inclusions in other organs (e.g. spleen, liver). Multifocal meningoencephalitis with multifocal nonsuppurative perivascular cuffing), necrosis, gliosis and generally eosinophilic intranuclear inclusion bodies. 

Electron microscopy reveals virus particles, generally about 100 nm diameter (reported 80-150 nm), often with a hexagonal capsid morphology typical of herpes viruses, particularly intranuclear but also intracytoplasmic; both enveloped and unenveloped virus particles may be detected. 

• Biopsy samples of genital lesions of one male Pan troglodytes - Chimpanzees and one female bonobo (Pan paniscus - Pygmy chimpanzee). (J495.30.w4)
  • In the epidermis, prominent necrosis and infiltration of inflammatory cells, mainly polymorphonuclear leucocytes but also some mononuclear cells. Adjacent to the necrotic areas, ballooning degeneration and a few syncytial-type multinucleated giant cells. In the margins of the necrotic areas, and particularly in the multinucleated calls, intranuclear inclusion bodies were found. (J495.30.w4)
  • Electron microscopy: numerous intranuclear herpesvirus nucleocapsids - including "capsids without nucleoids, capsids with slightly osmiophilic nucleoids, and capsids with strongly osmiophilic nucleoids." A distinctly hexagonal configuration to the virus particles was noted commonly. In areas of cell disruption, enveloped particles were found. Enveloped particles measured 150 - 220 nm (external diameter) while intranuclear particles were 80 - 100 nm diameter; in both types, the nucleid was 40 - 60 nm. No intranuclear filamentous tubular formations were found. (J495.30.w4)
• In a 13-day-old Gorilla gorilla - Gorilla at Basel Zoo: 
  • Cardiac, hepatic, renal, splenic, adrenals, brain: focal necrosis, presence of Cowdry type A intranuclear inclusions. (J543.10.w1)
  • Pulmonary: Focal and coalescing necrosis, intranuclear inclusions. Around the necrotic areas, macrophages, also alveoli containing fibrin, and general congestion. (J543.10.w1)
  • Cutaneous: in the epithelial calls, localised ballooning degeneration and resultant thickening of the skin; in some areas, associated superficial erosion. Abundant polykaryocytes and slight neutrophil infiltration. (J543.10.w1)
  • Upper GIT: in the epithelial calls, localised ballooning degeneration and resultant thickening; in some areas, associated superficial erosion. Abundant polykaryocytes and slight neutrophil infiltration. Gastric mucosa, small intestine and large intestine, also numerous necrotic foci. (J543.10.w1)
  • Electron microscopy: intranuclear and intracytoplasmic virus particles with a hexagonal capsid morphology typical of herpes viruses. (J543.10.w1)
  • FAT: herpes simplex virus 1 antigen detected in various tissues; lesser reaction to herpes B virus. (J543.10.w1)
• In a biopsy sample from an orphaned Eastern gorillas (Gorilla beringei spp.) in Rwanda: (P3.2007b.w2)
  • Intracellular oedema, marked ballooning degeneration, numerous epithelial syncytial cells, smudgy intranuclear inclusion bodies. [additional data given during conference]
  • Electron microscopy: naked virus in nucleus [additional data given during conference]. 
• In a six-month-old female Pongo pygmaeus - Orang-utan at Ouwehands Zoo: (J2.36.w5)
  • Pulmonary: alveolar oedema and emphysema. Many haemosiderin-laden macrophages present. In the parenchyma, necrotic foci, with haemorrhages. In the epithelial lining of the alveoli, many eosinophilic intranuclear inclusion bodies. Also, focal syncitial giant cells in the alveoli. (J2.36.w5)
  • Splenic: periarteriolar lymphoid sheaths and red pulp, neutrophil, peripheral macrophage and plasma cell infiltrate. In the periarteriolar lymphatic sheaths, focal lymphocyte necrosis. In the red pulp endothelial cells, eosinophilic intranuclear inclusion bodies. (J2.36.w5)
  • Mesenteric lymph nodes: neutrophil infiltrate in the sinuses and cords, while in the subcapsular and medullary sinuses, occasional macrophages, also with eosinophilic intranuclear inclusions. (J2.36.w5)
  • Hepatic: hepatocytes vacuolated, partly filled with denatured protein, many eosinophilic intranuclear inclusion bodies.
  • EM: intranuclear inclusions were made up of virus particles about 100 nm diameter, electron dense, with cores electroluscent; morphologically these were consistent with herpesvirus particles. (J2.36.w5)
• In one male white-handed gibbon - Hylobates lar. (J4.181.w6)
  • CNS: 
    • At the level of the corpus striatum, adjacent to the lateral ventricles, minimial lymphocytic perivascular infiltration.
    • In cerebral cortical grey matter and the lenticular nucleus, many intranuclear Cowdry type A inclusion bodies, without any associated cellular response. (J4.181.w6)
    • EM: In cellular nuclei and cytopasmic vesicles, immature herpesvirus virions, 94 - 114 nm diameter; also margination of nuclear chromatin. (J4.181.w6)
• In a colony of White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)). (J100.120.w1)
  • CNS: acute meningoencephalitis, with cortical and subcortical necrosis and reactive gliosis (more prominent in two of the gibbons). Cerebral cortex and pons showed the greatest destructive lesions. Type A intranuclear inclusions were most common in the two individuals with the more prominent histopathological lesions, rarer in a third individual and were not seen in the fourth. 
  • Hepatic, renal: degenerative changes (necrosis) in some individuals
  • Cardia: focal myocardial haemorrhage in two individuals.
  • Pulmonary: pneumonitis in two individuals.
  • Virus isolated from three of the four animals.

  (J100.120.w1)

• In experimentally inoculated White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)): biopsy of affected areas of skin (taken 11 days post inoculation) revealed that epithelial cells contained typical type A inclusion bodies. (N38.1968.w1)
• In a 44-year-old female White-handed gibbon - Hylobates lar (Hylobatidae - Gibbons (Family)): (J212.17.w3)
  • CNS: in the cerebral leptomeninges, small to moderate lymphocyte accumulations, with lesser numbers of plasma cells. In the cererum and midbrain, cuffing of scattered vessels with lymphocytes and plasma cells (small numbers only). A few neurons were hypereosinophilic, shrunken and angular, occasionally with three to six glial cells flanking the neuron. Astrocyte nuclei often contained intranuclear inclusions, 2 - 5 µm, eosinophilic with a clear halo and marginated chromatin. Less commonly in astrocytes and some neurons, eosinphilic to amphoteric inclusions, 5 - 8 um, smudgy and pale, extending to the edges of the nucleus. (J212.17.w3)
  • Other organs: No significant lesions. (J212.17.w3)
• In a two-year-old male Mountain agile gibbon - Hylobates agilis agilis (Hylobatidae - Gibbons (Family)). (J2.29.w6)
  • Cardiac: Acute endocardial necrosis with neutrophil infiltrate. (J2.29.w6)
  • CNS: In the brain and spinal cord, multifocal nonsuppurative perivascular cuffing, associated extensive necrosis and degeneration of cortical neurons. In the brain stem, scattered glial nodules. In meninges and parenchyma occasional large foci of haemorrhage. In the pyriform lobe, large area of malacia and gliosis. In the cerebral cortex frequent intranuclear inclusion bodies, mainly eosinophilic and filling the nuclei; chromatin marginated. (J2.29.w6)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)): (J495.19.w2)
  • Multiple tissues (tongue, oesophagus, trachea, lung, liver, spleen, lymph node, Peyer's patches, tonsil, adrenal cortex, conjunctiva, cornea, eyelid skin: necrosis and haemorrhages, widespread. Intranuclear inclusion bodies typical of herpesvirus infection, varying fgrom acidophilic with a clear halo surrounding, to amphoteric and filling the nucleus.
  • Tongue and oesophagus: additionally, in and next to the necrotic areas, multinucleated giant cells.
  • CNS (in two individuals from the New England Primate Research Centre; brain was not examined in individuals from Davis, California): encephalitis, with neuronal necrosis of the thalamus and the grey matter of the cerebral cortex. In many affected neurons, intranuclear inclusion bodies present. Other neurons were rounded with the nuclei karyorrhetic and the cytoplasm being more eosinophilic than normal. Additionally, astrocyte karyorrhexis and focal gliosis. In some vessels, hypertrophy and hyperplasia of the endothelial linings.

  (J495.19.w2)

• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)): (J543.32.w1)
  • Oral and oesophagus: well-demarcated ulcers; in the submucosa, cellular infiltration (neutrophils, mononuclear leucocytes), oedema, haemorrhage and karrhyorretic debris. In the adjacent mucosal epithelium, karyomegaly of cells, intranuclear inclusions (eosinophilic or amphoteric), ocasional multinucleated syncitial cells.
  • Hepatic: loss of hepatocytes, accumulations of "Haryorrhetic and karyopyknotic debris, neutrophils, fibrin, and red blood cells. In hepatocytes adjacent to these areas, intranuclear inclusions (eosinophilic).
  • Splenic: In the periarterioral lymphoid areas, lymphocyte cytolysis (in both males).
  • GIT: Small intestine and colon (juvenile male only), multifocal epithelial cytolysis.
  • CNS: 
    • Adult male: mild meningoencephalitis. In the meninges, haemorrhages and associated cellular infiltrate (mainly mononuclear leucocytes, also neutrophils); also in the superficial molecular layer (distal frontal, parietal, temporal lobes, and diencephalic and mesencephalic brain stem). In the grey matter, perivascular mononuclear leucocyte cuffing. Rarely, eosinophilic or amphoteric intranuclear inclusion in neurons. In some areas nuclear pyknosis and cytoplasmic eosinophilia with no or mild inflammation. 
    • Juvenile male: mild haemorrhages of the cerebrocortical meninges.
  • EM: In hepatocyte nuclei, numerous viral capsids, 100 - 110 nm diameter, with an electron-dense core and surrounding tegument; in the cytoplasm, enveloped viruses, 140 - 150 nm diameter.
  • In situ hybridization with HSV-1-specific oligonucleotides: virus in cells in oral lesions, liver, occasional neurons of the brain, rarely in mononuclear leucocytes in the spleen, and in the intestinal mucosal epithelium and lamina propria (scattered cells, juvenile male only). 
  • PCR: Adult male serum and juvenile male oral lesions and liver, positive for herpesvirus terminase and DNA polymerase genes. DNA sequencing: 99.7% identity with HSV-1 for 370 base pairs of the terminase gene; 100% identity for 177 base pairs of the polymerase gene.

  (J543.32.w1)

• In a family group of eight Callithrix jacchus - Common marmosets: (J26.40.w2)
  • Oral mucosa (tongue): severe vacuolation and ulceration of the squamous epithelium; acanthosis, parakeratosis, coagulation necrosis and polykaryocytosis. Variable degeneration and necrosis of epithelial cells at the margins of the ulcers. Paricularly at the ulcer borders and vesicle borders, intranuclear inclusions, either surrounded by a clear halo or filling the nucleus. In the submucosa underlying the ulcers, marked cellular infiltration, neutrophilic and lymphohistiocytic.
  • Adrenals: mild mixed cellular infiltrate in the cortex.
  • Hepatic: in three individuals, mild interstitial hepatitis - multifocal lymphohistiocytic infiltration.
  • EM: in nuclei of epithelial cells, viral nucleocapsids, empty or filled with electron-dense material, 80 - 100 nm diameter. In the cytoplasm of epithelial cells, and in intercellular spaces, numerous enveloped virions, about 150 nm diameter or larger. Many of the particles had the characteristic hexagonal configuration seen with herpesviruses. (J26.40.w2)

  (J26.40.w2)

• In Callithrix jacchus - Common marmosets: (J212.9.w1)
  • In one individual: (J212.9.w1)
    • Tongue, eyelid, lip and skin: "full thickness coagulative necrosis with fibrin deposition and balloning and htdropic degeneration." Also, particularly on the eyelids and abdomen, prominent subcorneal pustules with acantholytic cells. Associated perivascular to diffuse, mild to moderate cellular infiltrate (neutrophils, plasma cells, lymphocytes). Sebaceous gland and hair follicle necrosis; mild mixed periadnexal inflammation. Keratinocytes at the margins of the ulcers occasionally contained eosinophilic inclusion bodies.
    • CNS: neuronophagia throughout the brain (particularly frontal cortex, also temporal lobes, hypothalamus, also perivascular cuffing with mononuclear cells and small aggregates/diffuse infiltrates of macrophages, lymphocytes and glial cells (some neutrophils also). Moderate meningitis, nonsuppurative. Neutrophil infiltrate in the choroid plexus.
    • Adrenals: at the zona fasciculata, moderate lymphocyte and plasma cell infiltrate.
    • PCR: 120 bp product

    (J212.9.w1)

  • In one of two six-month-old twins (no histology of the other due to autolysis): (J212.9.w1)
    • Tongue: "severe coagulative epithelial necrosis" with underlying moderate mixed, mainly neutrophil, infiltrate.
    • CNS: perivascular cuffing (mononuclear), multifocal gliosis and neuronophagia; temporal lobes particularly affected, as well as the thalamus and hypothalamus, medulla oblongata, white matter of the cerebellum, and around the third ventricle. In neurons and glial cells, many intranuclear inclusions, either eosinophilic with a surrounding halo, or basophilic and filling the nucleus.
    • PCR: 120 base pair (bp) and 194 bp products.

    (J212.9.w1)

  • Samples of affected oral mucosa from a two-year-old pet Callithrix jacchus - Common marmoset: (J84.8.w17)
    • Severe necrotising stomatitis, purulent inflammation with bacterial colonisation of debris. (J84.8.w17)
• In a group of five Callithrix jacchus - Common marmoset. (J2.35.w4)
  • Oral mucosa and tongue: ulceration. Necrosis, deposition of fibrin, neutrophiol, histiocyte and plasma cell inflammatory infiltrate. At ulcer margins, epithelial cells showed mild ballooning degeneration and a few intranuclear inclusions, eosinophilic to basophilic, filling the nucleus, were found. (J2.35.w4)
  • CNS: Mild multifocal to severe diffuse nonsuppurative meningoencephalitis. Lesions of the medulla oblongata, brain stem and cerebrum, with mononuclear (mainly lymphocytic) infiltrates in the meninges and similar perivascular cuffing. In neurons and a few glial cells, intranuclear inclusions, eosinophilic, filling the nucleus and surrounded by a clear halo. (J2.35.w4)
  • Additional lesions described in two juveniles: (J2.35.w4)
    • Renal: mild chronic multifocal lymphohistiocytic interstitial nephritis.
    • Spleen: mild to moderate follicular hyperplasia.
    • Hepatic: mild lymphohistiocytic periportal infiltration.

    (J2.35.w4)

• In three adult Callithrix jacchus - Common marmosets. (J552.8.w1)
  • "Typical lesions were seen with inclusions in nucleus and cytoplasm." (J552.8.w1)
  • Electron microscopy: Virus particles both with and without envelopes in the nucleus and reticulum; these were sometimes in aggregates. (J552.8.w1)
• In experimentally infected female Callithrix jacchus - Common marmosets inoculated intravaginally with Herpesvirus hominis type 2: (J39.139.w1)
  • Genital: vagina contained areas of coagulation necrosis and haemorrhage. Endometrial focal and diffuse necrosis
  • Bladder: In the mucosa and submucosa, focal to diffuse necrosis, sometimes with haemorrhage.
  • Uterus: subserosal necrosis.
  • Small and large intestines: subserosal necrosis.
  • Hepatic: necrotic foci.
  • Adrenals: necrotic foci.
  • Mesenteric lymph nodes: necrotic foci.
  • Typical herpesvirus intranuclear inclusions were present in cells in and around areas of necrosis.

  (J39.139.w1)

• In experimentally inoculated Callithrix jacchus - Common marmosets: (J100.128.w1)
  • Liver, spleen, lymph node, kidney, adrenal, lung, heart and brain: "cellular proliferation, degeneration, and necrosis." (J100.128.w1)
  • Virus isolated from liver, spleen, lymph node, kidney, adrenal, lung, heart, cerebrum, cerebellum and medulla. (J100.128.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)): (J546.3.w1)
  • Lemur 1: CNS - diffuse encephalitis with neuronal necrosis and glial nodules. Mononuclear perivascular infiltration; endothelial cells hyperplastic and hypertrophic. Meningitis: mononuclear infiltration.
  • Lemur 2: 
    • CNS - diencephalon: localised encephalitis with perivascular mononuclear cell cuffing, endothelial cell swelling and proliferation, and glial nodules present near blood vessels. Also in areas of malacia, glial astrocytes contained intranuclear inclusions with a clear halo.
    • Pulmonary: bronchopneumoni with neutrophils in some bronchi; surrounding interalveolar septae thickened and collapsed  due to septal cell swelling and neutrophil infiltration.
  • Lemur 5: Hepatic: bile duct epithelium hypertrophied and hyperlastic.
  • Lemur 8: no lesions detected.

  (J546.3.w1)

• In naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)): (J495.22.w2)
  • Liver: 
    • 2/8 with gross changes haemorrhage and necrosis, widespread. Intranuclear includion bodies: central with a clear halo surrounding, or completely filling the nucleus; associated chromatin margination. 
    • 1/8, necrotic foci but no definite inclusions.
  • Adrenal: 
    • 2/8 with gross changes haemorrhage and necrosis, widespread. Intranuclear includion bodies: central with a clear halo surrounding, or completely filling the nucleus; associated chromatin margination.
    • Two with no gross lesions, in the cortex, foci of necrosis and haemorrhage; intranuclear inclusions in one of these.
  • Pancreas: foci of necrosis in 1/8.
  • Ocular: (1/8): superficial epithelium, areas of necrosis, with acute inflammation reaching into subcutaneous tissue. At the margins of necrotic areas, intranuclear inclusions.
  • Other: In two animals, tongue or oesophageal candidiasis,
  • Electron microscopy: In 2/5 liver sections examined, numerous herpes-type intranuclear virions, about 90 - 110 micrometers diameter. Occasionally in the perinuclear cisterna, enveloped virus particles, 110 - 160 µm diameter; in both enveloped and unenveloped particles, nucleoid 35 - 45 µm. Virus particles often with typical herpesvirus hexagonal configuration. Intranuclear particles included empty capsids (no nucleoid), capsid with slightly osmiophilic nucleoid, and capsid with strongly osmiophilic, very dark nucleoid. Occasional virus particle budding/being extruded through the nuclear membrane.

  (J495.22.w2)

• In humans: (J495.19.w1)
  • Recurrent lesions (e.g. mucocutaneous junction of the lips): "ballooning degeneration, necrosis, intercellular edema, multinucleated giant cells, and intranuclear inclusion bodies". (J495.19.w1)
  • Generalised and severe disease: focal necrosis, intranuclear inclusion bodies. (J495.19.w1)

VIRUS ISOLATION

• In chimpanzees: virus isolation in cell culture, confirmed by serum neutralization to be herpesvirus hominis type 2. (J495.30.w4)
• In a two-year-old male Mountain agile gibbon - Hylobates agilis agilis (Hylobatidae - Gibbons (Family)). (J2.29.w6)
  • Virus isolated in Vero cells from 10% brain suspension. Rapid (under 48 hours) cpe, with many minute foci initially, merging to involve the whole monolayer. EM showed typical herpesvirus particles. Restriction endonuclease analyses and infected cell polypeptide profiles indicated a virus strain closely related to, but not identical with, HSV1. Plaques produced in Vero cell culture were smaller than those produced by HSV1. (J2.29.w6)
• In Aotus trivirgatus - Owl monkey (Cebidae - New-world monkeys (Family)): virus isolated from oral, nasal and anal orifices as well as from the eye. (J495.19.w2)
• In Pithecia pithecia pithecia - white-faced saki monkeys (Cebidae - New-world monkeys (Family)): (J543.32.w1)
  • Herpes simplex virus 1 isolated from tongue, liver and spleen of the adult female (frozen tissue specimens). (J543.32.w1)
• In Cebus apella - Black-capped capuchins (Cebidae - New-world monkeys (Family)) with experimental ocular infection,v irus was isolated from the inoculated eye (lachrimal secretions) and detected in throat swabs from as early as 2 dpi to as late as 12 dpi in the throat and 19 dpi in the eye. (J71.40.w1)
• In a group of five Callithrix jacchus - Common marmoset. (J2.35.w4)
  • Virus was cultured from the brain (isolated in Vero, A549 and MRC-5 cells). The results of a MicroTrack® HSV-1/2 culture identification/typing test (Behring, Marburg, Germany) which distinguishes between HSV-1 and HSV-2 based on antigenic differences in glyoprotein G, suggested the isolated virus was HSV-1. (J2.35.w4)
• In experimentally infected Callithrix jacchus - Common marmosets, female inoculated intravaginally with Herpesvirus hominis type 2, virus was isolated from the adrenals and spleens of all three individuals, from the vagina and bladder of the two individuals from which isolation was attempted and from the lung of the one individual in which this tissue was tested; no virus was isolated from the liver or kidney. In a male inoculated with the same virus intranasally and into the eye, virus was isolated from the adrenal, spleen, kidney, lung, bladder and testis, but not from the liver. (J39.139.w1)
• In a group of Lemur catta - Ring-tailed lemurs (Lemuridae - Large lemurs (Family)), virus isolated from two of five lemurs tested and confirmed as Herpesvirus hominis. (J546.3.w1)
• In naturally infected Tupaia glis - Tree shrews (Tupaiidae - Treeshrews (Family)): (J495.22.w2)
  • Virus isolation: virus isolated from the liver of the first individual, producing a cpe in both rabbit kidney and squirrel monkey fetus lung cell cultures, with cells becoming round and swollen, gathering in clumps, development of syncitia and presence of Type A inclusion bodies. CPE was inhibited by Herpesvirus hominis antiserum; it was not inhibited by herpesvirus simiae or Herpesvirus tamarinus antisera. (J495.22.w2)