For Review Only
 
 
 
 
 
 
Management of Ocular Human Herpesvirus 1 Infection in a 
White-faced Saki Monkey (Pithecia pithecia) 
 
 
Journal: Comparative Medicine 
Manuscript ID CM-17-000119.R1 
Manuscript Type: Case Reports 
Date Submitted by the Author: 11-Jan-2018 
Complete List of Authors: Bauer, Kendra; Smithsonian Institution National Zoological Park, 
Smithsonian Conservation Biology Institute, Animal Care Sciences 
Steeil, James; Smithsonian Institution National Zoological Park, 
Smithsonian Conservation Biology Institute, Animal Care Sciences 
Adkins, Elizabeth; Hope Advanced Veterinary Center 
Childress, April; University of Florida, College of Veterinary Medicine, 
Department of Small Animal Clinical Sciences 
Wellehan, James; University of Florida, College of Veterinary Medicine, 
Department of Comparative, Diagnostic, and Population Medicine 
Kerns, Kenton; Smithsonian Institution National Zoological Park, 
Smithsonian Conservation Biology Institute, Animal Care Sciences 
Sarro, Steven; Smithsonian Institution National Zoological Park, 
Smithsonian Conservation Biology Institute, Animal Care Sciences 
Holder, Kali; Smithsonian Institution National Zoological Park, Smithsonian 
Conservation Biology Institute, Animal Care Sciences 
Keywords: 
Herpes viruses < Infectious organisms, Nonhuman primates < Animal 
species 
  
 
 
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Management of Ocular Human Herpesvirus 1 Infection in a White-faced 
Saki Monkey (Pithecia pithecia) 
 
Kendra L. Bauer
1
, James C. Steeil
1
, Elizabeth A. Adkins
2
, April L. Childress
3
, 
James F. X. Wellehan Jr.
3
, Kenton L. Kerns
1
, Steven J. Sarro
1
, Kali A. Holder
1 
 
1Smithsonian Institution National Zoological Park, Smithsonian Conservation Biology 
Institute, Animal Care Sciences, 3001 Connecticut Avenue, Washington, DC; 2Hope 
Advanced Veterinary Center, 140 Park Street SE, Vienna, VA; 3Department of Small 
Animal Clinical Sciences, Comparative, Diagnostic, and Population Medicine, College of 
Veterinary Medicine, University of Florida, 2015 SW 16th Avenue, Gainesville, Florida.  
 
*Corresponding author: Kendra Bauer. Email: bauer.kendra@gmail.com  
 
Human Herpesvirus 1 in a Saki Monkey 
 
Abstract 
A 20-year-old male intact white-faced saki monkey (Pithecia pithecia) presented 
with acute ocular disease of the right eye. Clinical signs included periocular 
swelling, conjunctivitis, and anisocoria with a miotic right pupil. Conjunctival swabs 
were positive for Human herpesvirus 1 (HHV1) by PCR with sequencing. Initial 
clinical signs resolved with supportive treatment, and the animal was managed 
chronically with intermittent acyclovir (5 mg/kg PO twice daily) during flare-ups. 
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After more than 2 years, progression of clinical disease led to enucleation of the 
right eye. Two months later, an acute presentation of severe neurologic signs, 
including ataxia and blindness, resulted in euthanasia. Histopathology, PCR, and 
sequencing results were consistent with viral encephalitis from HHV1, with 
coinfection with Pithecia pithecia lymphocryptovirus 1 also identified. This is the 
first case of managed HHV1 infection in a platyrrhine primate and the first case of 
HHV1 in a white-faced saki monkey that was not rapidly fatal. 
 
Abbreviations and acronyms: 
Human herpesvirus 1 (HHV1) 
  
Introduction 
Human herpesvirus 1 (HHV1) is an alphaherpesvirus in the genus 
SimplexirusSimplexvirus with high pathogenicity in non-human primates and other 
Euarchontoglires. In the endemic host, humans (Homo sapiens), HHV1 infection is 
lifelong and usually causes subclinical infection, with a prevalence over 98% in normal 
adults 
1314
. However, cold sores may occur in some individuals, and severe fatal 
encephalitis is possible in otherwise healthy neonates 
1819
. The virus host range is 
widespread across the Euarchontoglires, the mammalian superorder containing primates, 
rabbits, and rodents 2122. A diverse array of nonhuman Euarchontoglires are susceptible to 
systemic HHV1 disease (typically encephalitis), especially in the case of young or 
immunocompromised animals 11, 1412, 15, 16, 29, 3017, 31, 32. The parvorder Catarrhini, 
containing contains humans, are often large and aggressive, and humans are unlikely to 
deliberately come into direct contact with other catarrhinesprimates native to the old 
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world. The other clade in the infraorder Simiiformes, the parvorder Platyrrhini, contains 
the primates native to the new world. Platyrrhini are heavily represented in the pet trade 
and in literature regarding nonhuman HHV1 disease. Rapidly fatal disease associated 
with acute encephalitis has been reported in black howler monkeys (Alouatta caraya), 
owl monkeys (Aotus spp.), marmosets (Callithrix spp.), and white-faced saki monkeys 
(Pithecia pithecia) 
2, 9, 17, 19, 22
.
10, 18, 20, 24
. However, some reports of HHV1 in platyrrhines 
have indicated differences in susceptibility among species and individuals 
7, 278, 29
. 
Experimental corneal infection with HHV1 in capuchin monkeys (Cebus apella) and 
squirrel monkeys (Saimiri sciureus) produced corneal disease in both species, but 
subsequent systemic disease was not reported 
7, 278, 29
.  Interestingly, capuchin monkeys 
have also been reported to be asymptomatically infected with Macacine herpesvirus 1, 
another Simplexvirus endemic in a catarrhine host, the rhesus macaque (Macaca mulatta) 
56
. In a naturally occurring outbreak of HHV1 in owl monkeys, some monkeys developed 
rapidly fatal encephalitis while others showed only mild signs limited to dyscoria and 
posterior synechia 910. All monkeys that did not die in the outbreak were euthanized, so 
the long-term outcome was not determined 
910
. Longer term management of a case of 
HHV1 disease in a platyrrhine has not been reported.  
Case Report 
 A 20-year-old male, intact, captive white-faced saki monkey (Pithecia pithecia) 
with an acute history of right periocular swelling and lethargy was anesthetized for a 
complete physical examination. This animal’s prior medical history included chronic 
proteinuria and diarrhea, which were managed with treatments of benazepril (0.5 mg/kg 
PO daily, Diamondback Drugs, Scottsdale, AZ), flax seed oil (50 mg/kg PO daily, 
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Puritan’s Pride, Holbrook, NY), and metronidazole (5 mg/kg PO daily, Wedgewood 
Village Pharmacy LLC, Swedesboro, NY).  
 On initial physical examination under anesthesia, findings included right-sided 
periocular lid swelling, conjunctival hyperemia and edema, mucoid discharge, corneal 
edema, a 3 mm × 2 mm central corneal ulcer, and anisocoria with a miotic right pupil.  
Oral examination revealed erythematous gingiva and two thick, off-white plaques on the 
tip of the tongue. A low body condition score (3/9) and 15% weight loss from the 
animal’s typical weight 19 days prior was noted.  
 Complete blood count, serum biochemistry, and urine analysis revealed 
leukocytosis (19.8 k/µl; reference range, 3.7–19.11 k/µl), neutrophilia (13.9 k/µl; 
reference range, 1.5–11.96 k/µl), monocytosis (4.4 k/µl, reference range 0.053–1.211 
k/µl), hypoalbuminemia (2.2 g/dL, reference range, 2.4–5.9 g/dL), proteinuria (4+ 
protein, UPC 9.97), hematuria (0–2 RBC/hpf), pyuria (1–3 WBC/hpf), and mild 
bacteriuria 
25
.
27
. Liver enzymes including ALT (3 U/L, reference range 3–37 U/L), AST 
(45 U/L, reference range 20-123 U/L), and GGT (31 U/L, reference range 7-61 U/L) 
were unremarkable 27. However, total bilirubin was not included in the chemistry panel. 
A urine culture was negative. Whole body radiographs, abdominal ultrasound, cytology 
of a scraping of the tongue, and lead II electrocardiography were unremarkable. 
Treatment administered at the time of the examination included lactated Ringer’s solution 
(45 ml/kg SC, Hospira, Lake Forest, IL), penicillin G benzathine and penicillin G 
procaine (PPG, 22,000 IU/kg SC, Bimeda, La Sueur, MN), ivermectin (0.4 mg/kg SC, 
Merial Limited, Duluth GA), meloxicam (0.2 mg/kg SC, Norbrook Laboratories Limited, 
Northern Ireland), ceftiofur crystalline free acid (10 mg/kg SC, Zoetis, Kalamazoo, MI), 
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and neomycin, polymyxin B sulfates, and bacitracin zinc ophthalmic ointment (topically 
on right eye, Bausch & Lomb, Tampa FL). Treatment courses of tramadol (1.2 mg/kg PO 
twice daily for 9 days, Diamondback Drugs) and azithromycin (10 mg/kg PO daily for 7 
days, Greenstone LLC, Peapack, NJ) were initiated, and ciprofloxacin (10 mg/kg PO 
twice daily for 24 days, Bayer HealthCare, Whippany, NJ) was initiated 5 days later.  
  A recheck examination under anesthesia 10 days after the initial presentation 
revealed persistent ocular abnormalities, including a 3 mm × 5 mm corneal ulcer of the 
right eye. Mucoid discharge was also present from the left eye. A complete temporary 
tarsorrhaphy of the right eye to promote corneal healing was performed using 5-0 PDS in 
a horizontal mattress pattern. In addition, exudative abrasions and ulcerations were noted 
on the right arm and the face above each eye, on the chin, and on the right cheek. 
Cytological evaluation of impression smears of the affected areas revealed severe 
neutrophilic and histiocytic inflammation. Treatments during the examination included 
penicillin G benzathine and penicillin G procaine (22,000 IU/kg SC), meloxicam (0.2 
mg/kg SC), gentamicin (0.05 ml, 100 mg/ml, subconjunctival right eye, VetOne, Boise, 
ID), lactated Ringer’s solution (30 ml/kg SC), and nystatin-neomycin sulfate-
thiostrepton-triamcinolone ointment (Animax, topically on right wrist, Dechra, Overland 
Park, KS), and the scabs and wounds were clipped and cleaned with chlorhexidine 
solution (Vétoquinol USA, Fort Worth, TX). Due to concern about an underlying viral 
infection, serum was submitted for serology to VRL Laboratories (San Antonio, TX); the 
results were negative for cytomegalovirusSaimiriine herpesvirus 4, Saimiriine 
herpesvirus 2, Saimiriine herpesvirus 1, HHV1, Human herpesvirus 2, HHV1 IgM, 
Human herpesvirus 2 IgM, and Measles, determined by previously reported methods 1011. 
Formatted: Font: Italic
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A swab collected from the corneal and subconjunctival surfaces of the right eye was 
positive for HHV1 by PCR with sequencing at the University of Tennessee utilizing 
previously reported methods 2628. Treatment courses of Animax (topically on right 
carpus, twice daily for 5 days), cephalexin (22 mg/kg PO twice daily for 17 days, 
Hospira), meloxicam (0.1 mg/kg PO once daily for 10 days), and acyclovir (5 mg/kg PO 
twice daily for 24 days, Diamondback Drugs) were initiated. Additional treatments at a 
recheck examination 8 days later included removal of the temporary tarsorrhaphy sutures, 
gentamicin (0.1 ml subconjunctival in right eye with 0.05 ml in lower lid and 0.05 ml in 
upper lid), meloxicam (0.2 mg/kg IM), ceftiofur sodium crystalline free acid (7.5 mg/kg 
SC), and lactated Ringer’s solution (30 ml, kg SC). Additional medications included l-
lysine (12.5 mg/kg PO daily, Carlson, Arlington Heights, IL) and continued acyclovir, 
cephalexin, ciprofloxacin, and meloxicam.  
A recheck examination 25 days after the initial presentation showed no evidence 
of corneal ulceration. At that time, the right eye was considered non-visual, and there was 
evidence of mild corneal degeneration, a narrow anterior chamber, and an active 
pupillary light response. Oral administration of l-lysine was continued. The skin lesions 
had also resolved at that time.  
There were no additional concerns until 6 months after the initial presentation 
when a recheck exam showed moderate conjunctival hyperemia of the left eye. A swab of 
this eye was positive for HHV1 on PCR, indicating viral shedding at this time. Acyclovir 
treatment was then reinitiated. Three additional flare-ups of periocular pruritus and 
conjunctivitis were treated with courses of acyclovir over the 2 years and 3 months 
following the initial presentation. 
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Approximately 2 years and 4 months after initial presentation, enucleation of the 
right eye was performed due to concerns of recurring ocular disease. L-lysine was 
discontinued approximately 1 week later, because of removal of the affected eye and 
worsening patient compliance. Histology of the affected eye revealed chronic, erosive 
keratoconjunctivitis; mild to moderate, chronic, lymphohistiocytic iridocyclitis with 
multiple synechia; and chronic retinal degeneration and detachment. No viral inclusions 
were found. 
Two months later, this animal became acutely ataxic, obtunded, and blind. 
Euthanasia was elected owing to suspected progression of HHV1 associated disease. 
Histopathology confirmed disseminated disease consistent with herpesvirus, including 
severe, multifocal to coalescing necrohemorrhagic meningoencephalitis with neuronal 
intranuclear inclusion bodies (Figure 1, Figure 2). The optic and trigeminal nerves and 
the left eye were infiltrated by lymphocytes and plasma cells. Other findings included 
mild lymphohistiocytic hepatitis, mild lymphoplasmacytic interstitial nephritis, mild 
lymphocytic gastroenteritis, moderate mucopurulent to lymphocytic laryngitis, mild 
lymphocytic conjunctivitis of the left eye, and granulomatous inflammation of the 
enucleation site of the right eye.  
Brain tissue was submitted to the University of Florida for confirmation of HHV1 
via PCR and sequencing. DNA was extracted from brain tissue (DNeasy, Qiagen, 
Valencia, CA). Blank extractions were used as negative controls. A nested PCR 
amplification was performed using previously described consensus primers for the 
herpesviral DNA-dependent DNA polymerase gene 
2628
. The PCR amplicon was resolved 
in a 1.5% agarose gel, excised, and purified using a QIAquick gel extraction kit (Qiagen), 
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then sequenced via the Sanger method, using a Big-Dye™ Terminator Kit (Applied 
Biosystems, Foster City, CA) and analyzed on ABI 3130 automated DNA sequencers.  
Sequencing completed at Genewiz (South Plainfield, NJ) resulted in dual peaks at most 
nucleotides, consistent with mixed sequence (Figure 3). The sequence obtained was 
compared with sequences in the databases of GenBank (National Center for 
Biotechnology Information, Bethesda, Maryland, USA), EMBL (Cambridge, UK), and 
the Data Bank of Japan (Mishima, Shizuoka, Japan) using BLASTN 
1
. The BLASTN 
search found closest sequence homology with HHV1 (GenBank accession # KX424525).  
When peaks matching HHV1 were subtracted, the sequence of the remaining peaks 
showed 100% homology with Pithecia pithecia lymphocryptovirus 1 (PpLCV1; GenBank 
accession # AY139025), previously reported from the lung of a captive white-faced saki 
monkey in Germany 
67
. Use of fluorescence peak heights associated with different 
nucleotides to assess nucleotide polymorphisms has been validated, and the dominance of 
HHV1 suggests it was likely present in greater copy numbers than PpLCV1 1213. This 
confirmed HHV1 in this saki monkey’s brain tissue.  
 
Discussion 
 This is the first report of the management of a platyrrhine with HHV1, and the 
first report of HHV1 in a white-faced saki monkey that was not rapidly fatal. Treatment 
for the animal in this case was aimed at reducing shedding and consisted of acyclovir 
given during times of suspected increased shedding. L-lysine was also administered, but 
has not been found efficacious for control of herpesviral disease and is considered 
unlikely to have played a role in this case 
3, 45
. Oral acyclovir and oral valacyclovir have 
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both been shown to be effective for treatment of HHV1, although the long-term efficacy 
of these therapies is uncertain 45. A survival time of 2.5 years has not been previously 
reported in this species or in other platyrrhines; this may be related to lack of antemortem 
diagnostics in previous cases.  Previous reports have identified infection without rapid 
fatality in platyrrhines 
7, 9, 278, 10, 29
. Antemortem diagnostic investigation is indicated in 
platyrrhines with ocular inflammatory disease. 
 Proteinuria detected at the time of the saki monkey’s initial presentation was 
similar to previous findings in this individual due to suspected glomerular protein loss 
first diagnosed three years prior to the ocular findings. An ultrasound with a consulting 
radiologist at the time of initial diagnosis of proteinuria revealed mild pyelectasia 
bilaterally and prominent vasculature in the left renal pelvis (5 mm diameter). Clinical 
response to benazepril and flax seed oil was varied over the clinical course, but ultimately 
did not completely control protein loss. Chronic renal disease was further confirmed on 
necropsy findings. Other causes of proteinuria such as due to low grade herpes meningitis 
cannot be completely ruled out, as no spinal tap was performed.       
 At the time of serological testing in this animal, there was no evidence of 
seroconversion. Previous cases of HHV1 in white-faced saki monkeys have also been 
negative for antibodies to HHV1 
24
. The negative serologic response may be due to lack 
of cross-species serologic reactivity when utilizing anti-human secondary antibodies to 
detect white-faced saki monkey antibodies. Some other Platyrrhini have shown evidence 
of serologic response, but it is unknown if this is due to species differences or due to 
variation in serologic testing 
8, 10
. Testing in this case utilized a rapid dot immunobinding 
assay, while other reported tests that have yielded positive results in Platyrrhini have 
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utilized serum neutralization or ELISA 
8, 10, 11
. It is also possible that seroconversion 
occurred later in this case, but additional serological testing was not done.  
It is unknown what triggered the final progression of the disease in this case. 
While it is possible that low-level meningitis was present earlier, the hemorrhage and 
necrosis observed on histopathology indicated acute progression, and it is consistent with 
the observed normal mentation and mobility until immediately prior to death. While 
white-faced saki monkeys have been documented to live up to 36 years of age, a more 
typical lifespan in the wild is 15 years 2830. At 22 years of age, this animal was geriatric. 
Reactivation, and reactivation of HHV1 has been associated with age and coinfection 
with other herpesviruses 
23
. 
25
.  
The role of Pithecia pithecia lymphocryptovirus 1 in this case is unknown;. 
Lymphocryptoviruses are gammaherpesviruses, and,unique lymphocryptoviruses have 
been identified in at least 42 species of non-human primates. These viruses are generally 
considered to be host-adapted; however, fatal lymphoproliferative disease was associated 
with the lymphocryptovirus Callitrichine herpesvirus 3 in a group of common marmosets 
(Callithrix jacchus) 
21, 23
. In addition, intranuclear inclusions similar to those seen in this 
case have been identified in rhesus macaques infected with Macacine herpesvirus 4, 
another lymphocryptovirus 
4
. However, there has been no investigation of the role of this 
virus in disease 
20
Pithecia Pithecia lymphocryptovirus 1 in disease 
21
. The repeated 
positive PCR tests for HHV1 during the course of this animal’s disease and the 
similarities in final clinical course to other cases of white-faced saki monkeys also 
suggest that HHV1 was the cause of ocular disease and ultimate meningoencephalitis in 
this case 
18, 24
. 
Formatted: Not Superscript/ Subscript
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Reactivation of HHV1 has also been associated with coinfection with other 
herpesviruses, so it is possible that the presence of the lymphocryptovirus indirectly 
contributed to worsening of clinical disease 
25
. Central nervous system coinfection with 
HHV1 and the human lymphocryptovirus, Human herpesvirus 4, has been reported 
2426
. 
Coinfection with HHV1 and Human herpesvirus 4 results in significantly altered 
production of cytokines by cultured lymphocytes in comparison to single infection with 
either virus 
89
. Cytokines have a significant effect on the course of infectious disease. 
At the time of the initial presentation, the saki monkey in this case report shared 
an enclosure with a female white-faced saki monkey and two golden lion tamarins 
(Leontopithecus rosalia). Because of concern about their exposure to HHV1, these 
animals were subsequently housed separately from the male saki monkey and underwent 
examinations for diagnostic testing. All three animals were negative for HHV1 by 
serology and PCR and never exhibited clinical signs of disease consistent with HHV1. 
While it is assumed that these exhibit-mates are susceptible to the disease, it is possible 
that the close contact required for transmission did not occur. In another case, a family of 
white-faced saki monkeys with HHV1 resulted in the death of all three saki monkeys, but 
five white-lipped tamarins (Saguinus labiatus) in the same enclosure never developed 
clinical illness 
1718
. 
When deciding to treat a captive platyrrhine for HHV1, it is important to consider 
the health of other animals in the collection because the disease has been reported to 
affect multiple animals 9, 17, 19, 22.10, 18, 20, 24. In this case, the decision was made to house 
this saki monkey separately to reduce risk to other animals. However, housing a social 
primate alone has long-term implications for quality of life. Such concerns may be 
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partially mitigated by allowing visual contact with other primates or providing additional 
enrichment. This decision should be made on a case by case basis for each individual. 
  
Acknowledgements 
The authors thank Drs. Nancy Boedeker, Katharine Hope, Samantha Sander, and 
Jessica Siegal-Willott for their contributions in managing this case and Dr. Megan 
Partyka for her contributions to the preparation of this manuscript. The authors also thank 
the keepers of the Small Mammal House for the high quality of care provided to the saki 
monkey in this case. 
 
References 
 
1. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search 
tool. J Mol Biol. 215:403-410. 
 
2. Barnes KJ, Garner MM, Wise AG, Persiani M, Maes RK, Kiupel M. 2016. Herpes simplex 
encephalitis in a captive black howler monkey (Alouatta caraya). J Vet Diagn Invest. 28:76-78.  
 
3. Bol S, Bunnik EM. 2015. Lysine supplementation is not effective for the prevention or treatment 
of feline herpesvirus 1 infection in cats: a systematic review. BMC Vet Res. 11:284. 
 
4. Carville A, Mansfield KG. 2008. Comparative pathobiology of macaque lymphocryptoviruses. 
Comp Med, 58:57–67. 
 
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5.6. Coulibaly C, Hack R, Seidl J, Chudy M, Itter G, Plesker R. 2004. A natural asymptomatic 
herpes B virus infection in a colony of laboratory brown capuchin monkeys (Cebus apella). Lab 
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6.7. Ehlers B, Ochs A, Leendertz F, Goltz M, Boesch C, Mätz-Rensing K. 2003. Novel simian 
homologues of Epstein-Barr virus. J Virol. 77:10695-10699. 
 
7.8. Felsburg PJ, Heberling RL, Kalter SS. 1973. Experimental corneal infection of the Cebus 
monkey with herpesvirus hominis type 1 and type 2. Arch Virol, 40:350-358. 
 
8.9. Gosselin J, Flamand L, D'Addario M, Hiscott J, Stefanescu I, Ablashi DV, Gallo RC, 
Menezes J. 1992. Modulatory effects of Epstein-Barr, herpes simplex, and human herpes-6 viral 
infections and coinfections on cytokine synthesis. A comparative study. J Immunol. 149:181-187. 
 
9.10. Gozalo AS, Montoya EJ, Weller RE. 2008. Dyscoria associated with herpesvirus 
infection in owl monkeys (Aotus nancymae). J Am Assoc Lab Anim Sci. 47:68-71.  
 
10.11. Heberling RL,  Kalter SS. 1986. Rapid dot-immunobinding assay on nitrocellulose for 
viral antibodies. J Clin Microbiol. 23:109–113. 
 
11.12. Heldstab A, Rüedi D, Sonnabend W, Deinhardt F. 1980. Spontaneous generalized 
Herpesvirus hominis infection of a lowland gorilla (Gorilla gorilla gorilla). J Med Primatol. 
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populations of malaria parasites by sequencing: validation and applications. 
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13.14. Kaufman HE, Azcuy AM, Varnell ED, Sloop GD, Thompson HW, Hill JM. 2005. 
HSV-1 DNA in tears and saliva of normal adults. Invest Ophthalmol Vis Sci. 46:241-247. 
 
14.15. Kemp GE, Losos GL, Causey OR, Emmons RW, Golding RR. 1972. Isolation of 
Herpesvirus hominis from lemur: a naturally occurring epizootic at a zoological garden in Nigeria. 
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15.16. Kik MJ, Bos JH, Groen J, Dorrestein GM. 2005. Herpes simplex infection in a 
juvenile orangutan (Pongo pygmaeus pygmaeus). J Zoo Wildl Med. 36:31-134. 
 
16.17. Landolfi JA, Wellehan JF, Johnson AJ, Kinsel MJ. 2005. Fatal human herpesvirus 
type 1 infection in a white-handed gibbon (Hylobates lar). J Vet Diagn Invest. 17:369-371. 
 
17.18. Lapid R, Eshar D. 2017. Fatal herpes simplex virus 1 (HSV-1) infection in a group of 
zoo-kept white-faced saki monkeys (Pithecia pithecia) in Israel. Isr J Vet Med. 72:51-55. 
 
18.19. Leas BF, Umscheid CA. 2015. Neonatal herpes simplex virus type 1 infection and 
Jewish ritual circumcision with oral suction: a systematic review. J Pediatric Infect Dis Soc. 
4:126-131. 
 
19.20. Mätz-Rensing K, Jentsch KD, Rensing S, Langenhuyzen S, Verschoor E, Niphuis H, 
Kaup FJ. 2003. Fatal Herpes simplex infection in a group of common marmosets (Callithrix 
jacchus). Vet Pathol. 40:405-411. 
 
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future, p. 385-405. In: Münz C, editor. Epstein Barr virus, vol 2. Cham, Switzerland: Springer 
International Publishing. 
 
21.22. Murphy WJ, Pringle TH, Crider TA, Springer MS, Miller W. 2007. Using genomic 
data to unravel the root of the placental mammal phylogeny. Genome Res. 17:413-421. 
 
23. Ramer JC, Garber RL, Steele KE, Boyson JF, O'Rourke C, Thomson JA. 2000. Fatal 
lymphoproliferative disease ass ciated with a novel gammaherpesvirus in a captive population of 
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22.24. Schrenzel MD, Osborn KG, Shima A, Klieforth RB, Maalouf GA. 2003. Naturally 
occurring fatal herpes simplex virus 1 infection in a family of white‐faced saki monkeys (Pithecia 
pithecia pithecia). J Medical Primatol. 32:7-14.  
 
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virus type 1 is associated with cytomegalovirus and age. J Med Virol. 84:1797-802. 
 
24.26. Tang YW, Espy MJ, Persing DH, Smith TF. 1997. Molecular evidence and clinical 
significance of herpesvirus coinfection in the central nervous system. J Clin Microbiol. 35:2869-
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25.27. Teare JA, editor. 2013. Pithecia_pithecia_No_selection_by_gender__All_age 
s_combined_Conventional_American_units__2013_CD.html. In: Species360 Physiological 
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Formatted: List Paragraph
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TM. 1996. Detection and analysis of diverse herpesviral species by consensus primer PCR. J Clin 
Microbiol. 34:1666-71. 
 
27.29. Varnell ED, Kaufman HE, Hill JM, Wolf RH. 1987. A primate model for acute and 
recurrent herpetic keratitis. Curr Eye Res. 6:277-279. 
 
28.30. Weigl R. 2005. Longevity of mammals in captivity; from the living collections of the 
world. Kleine Senckenberg-Reihe 48. Stuttgart, Germany: Schweizerbart Science Publishers.  
 
29.31. Weissenbock H, Hainfellner JA, Berger J, Kasper I, Budka H. 1997. Naturally 
occurring herpes simplex encephalitis in a domestic rabbit (Oryctolagus cuniculus). Vet Pathol. 
34:44–47. 
 
30.32. Wohlsein P, Thiele A, Fehr M, Haas L, Henneicke K, Petzold D, Baumgärtner W. 
2002, Spontaneous human herpes virus type 1 infection in a chinchilla (Chinchilla lanigera f. 
dom.). Acta Neuropathol 104:674–678. 
 
Figure Legends 
Figure 1.  Photomicrograph of the frontal cerebrum of a 22-y-old saki monkey, showing marked expansion 
of the leptomeninges by mixed inflammatory cells, with lymphocytes predominating. Inflammatory 
infiltrates extend into the cerebrum forming perivascular cuffs. Vasculature is congested, and there is 
frequent perivascular hemorrhage into the neuropil with attendant necrosis, vacuolation, and inflammation. 
Hematoxylin and eosin stain; magnification 40x. 
 
Figure 2. Photomicrograph of the frontal cerebrum of a 22-y-old saki monkey, showing degenerate 
neutrophils and karyorrhectic debris surrounding vessels and infiltrating the neuropil. Neuronal nuclei 
contain indistinct basophilic (open arrows) or distinct eosinophilic (solid arrow) inclusions with 
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margination of chromatin. Morphology of the inclusions is characteristic of herpesvirus. Hematoxylin and 
eosin stain; magnification 400x. 
 
Figure 3. Representative region of DNA sequence chromatogram of pan-herpesviral DNA polymerase 
gene PCR product from the brain tissue of a 22-y-old saki monkey Guanine is in black, adenine is in green, 
cytosine is in blue, and thymine is in red.  Sequences for Human herpesvirus 1 (GenBank accession # 
KX424525) and Pithecia pithecia lymphocryptovirus 1 (GenBank accession # AY139025) are below the 
chromatogram.  It can be seen that when one sequence is subtracted from the chromatogram, the other is 
present. 
 
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Photomicrograph of the frontal cerebrum of a 22-y-old saki monkey, showing marked expansion of the 
leptomeninges by mixed inflammatory cells, with lymphocytes predominating. Inflammatory infiltrates 
extend into the cerebrum forming perivascular cuffs. Vasculature is congested, and there is frequent 
perivascular hemorrhage into the neuropil with attendant necrosis, vacuolation, and inflammation. 
Hematoxylin and eosin stain; magnification 40x.  
 
88x66mm (300 x 300 DPI)  
 
 
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Photomicrograph of the frontal cerebrum of a 22-y-old saki monkey, showing degenerate neutrophils and 
karyorrhectic debris surrounding vessels and infiltrating the neuropil. Neuronal nuclei contain indistinct 
basophilic (open arrows) or distinct eosinophilic (solid arrow) inclusions with margination of chromatin. 
Morphology of the inclusions is characteristic of herpesvirus. Hematoxylin and eosin stain; magnification 
400x.  
 
88x66mm (300 x 300 DPI)  
 
 
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Representative region of DNA sequence chromatogram of pan-herpesviral DNA polymerase gene PCR 
product from the brain tissue of a 22-y-old saki monkey Guanine is in black, adenine is in green, cytosine is 
in blue, and thymine is in red.  Sequences for Human herpesvirus 1 (GenBank accession # KX424525) and 
Pithecia pithecia lymphocryptovirus 1 (GenBank accession # AY139025) are below the chromatogram.  It 
can be seen that when one sequence is subtracted from the chromatogram, the other is present.  
 
187x40mm (300 x 300 DPI)  
 
 
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