Chandler, Abbigail MD; Oehler, Richard L. MD, FACP
HISTORY OF PRESENT ILLNESS
A 58-year-old animal handler presented to the emergency department one evening with report of having sustained a bite injury at a local civic auditorium. The patient, who was tending 2 rhesus macaque monkeys during a live circus event, was unexpectedly bitten on both the left and right hands by 1 of the 2 primates. The monkey had become startled by the spontaneous explosion of a small toy circus balloon. The patient sustained deep lacerations to the dorsal aspect of his left hand as well as a smaller superficial laceration on the palmar surface of the right hand. The patient was unable to receive first aid for his injuries until the conclusion of the performance. He received minor first aid to his injury at the circus venue before packing up his animals and driving his truck to a local hospital.
The patient was a professional animal handler from Indianapolis, Iowa, who had more than 40 years of experience handling rhesus macaque (Macaca mulatta) monkeys. He admitted to keeping rhesus monkeys since the age of 14 years and had been bitten several times before, but had not previously sought medical treatment.
"Scooter" (Fig. 1), one of the 2 monkeys owned by the bite victim, was a shy but loyal animal. Easily startled, he had bitten his master reflexively, apparently not of malice but simply due to fear. He was an 8-year-old macaque originally born in the United States whose parents were laboratory animals. He and his sister "Grace" had been the near constant companions of the patient for approximately 4 years. Both were previously healthy and had received regular medical care through an exotic animal veterinarian in Indiana.
When seen in the emergency department on a Sunday evening, the patient's wound was irrigated and dressed, and he was sent home with a prescription for levofloxacin and instructions to follow-up at an orthopedic clinic on the following morning. Overnight, however, the patient noticed the relatively rapid onset of increased swelling and fluctuance at the site of the bite injury (Fig. 2). He also noticed subjective fever and chills. Upon presentation to the orthopedic hand specialist on the following morning, he was afebrile with otherwise normal vital signs. His left hand was noted to be markedly swollen, and there were 3 to 4 distinct puncture areas on the dorsolateral portion of his hand. The longest laceration measured approximately 3 cm in length. Functionally, he appeared neurologically intact with no sensory loss noted in any of his digits. He had impaired flexion of his second through fifth digits in the left hand, which he attributed to discomfort and swelling. Bite marks were also visible on the lateral plantar surface, but less swelling and erythema were seen on this side. A small superficial laceration was also found at the hypothenar eminence of the right palm (Fig. 3), which the patient had sustained when he was attempting to remove the animal's jaws from the opposite hand.
An outpatient incision-and-drainage procedure was quickly performed, resulting in the prompt drainage of a small quantity of semipurulent material which was submitted for Gram stain and culture. The patient experienced immediate relief from his discomfort with drainage of the wound fluid. His wound was dressed, and a hard cast was placed. The patient was offered immediate admission to the hospital, but initially declined because he did not have surrogate caretaker to watch his animals. He temporarily left the medical facility to drive his unattended animals to the safety of another animal handler's home and then returned for admission to the hospital. Blood cultures and a baseline serum sample for herpes B virus were obtained, and he was initially started on broad-spectrum antibiotics with intravenous tigecycline, levofloxacin, and acyclovir. On the following day, the patient was taken to the operating room for incision and debridement, extensive wound exploration, irrigation, and plaster casting. The patient returned to the operating room again on postoperative day 1, and good initial evidence of wound healing was seen. Although blood cultures were negative, initial wound cultures soon were positive for Streptococcus mitis/Streptococcus oralis, and his antibacterials were changed to intravenous ceftriaxone and oral clindamycin. He was monitored closely during his hospitalization for signs of disorientation or the onset of encephalopathy, but did not experience mental status change during his inpatient stay. He received 2 more operative dressing changes and remained hospitalized for 14 days, and was then discharged home to complete a total of 3 weeks' intravenous therapy with ceftriaxone plus oral clindamycin. When seen again 2 weeks later (Fig. 4), the infection had completely subsided, and his wound was almost completely closed.
A swab of the patient's wound obtained at the time of presentation was submitted to the National B Virus Resource Lab in Atlanta, Ga, for culture. The swab tested negative for herpes B virus. Serological testing of the involved animal had last been performed 4 years earlier, when he was acquired by his current handler. At that time, Scooter tested negative for herpes B virus, herpes simplex virus (HSV) 1 antibodies, measles, and simian immunodeficiency virus (SIV) antibody. Because of the potential risk of encephalitis to the patient associated with exposure to herpes B virus, repeat serological testing of the rhesus macaque was pursued. Obtaining the animal's serum was more difficult than anticipated, however, because of the owner's feeling that the animal would cooperate more completely only if his regular Indiana veterinarian drew the sample. It also proved difficult to find an exotic animal veterinarian locally who would obtain the specimen. As a result, repeat serological testing of the monkey could not be immediately performed, although he successfully completed a 2-week course of oral valacyclovir for prophylaxis.
Primate bites, although rare, can result in a significant, even fatal, outcome for an exposed patient. A bite injury may transmit potentially pathogenic bacteria, but viral pathogens may also present significant risks. Risk factors for the transmission of pathogenic viruses may vary based on the severity of exposure and the primate species involved. The likely organisms isolated from infected simian bites frequently parallel those seen with human bite wounds. The bacterial flora appears to be similar across many primate species, with no species-specific association noted in previous case reports.1
The actual number of monkey bites reported is likely a very small percentage of those that actually occur.2 Monkeys may be kept as personal pets, as commercial animals for exhibition, or in laboratory settings. Owners and handlers are often uneducated about the risks of a bite or scratch. They may be harboring the exotic animal without a license, which is required in most states, and fear losing the animal if they seek medical treatment. They may even falsely identify the cause of the trauma as due to some other common domestic pet or from mechanical trauma. Exposures may also occur from infectious tissues or fluids of monkeys, including ocular, oral, or genital secretions. Cerebrospinal fluid and central nervous system (CNS) tissue are also a source for potential infection.3
The oral flora of nonhuman primates is very similar to that of humans. It includes gram-positive bacteria, such as Streptococcus salivarius, Streptococcus sanguis, and Streptococcus mutans; gram-negative bacteria, such as Veillonella sp; and anaerobes such as Bacteroides sp, Lactobacillus sp, Leptotrichia sp, and Fusobacterium sp.4 The animal, depending on its origin, age, and current habitat, may also be shedding HSV-1, measles virus, SIV, simian retrovirus, or herpes B virus. Nonhuman primates are not natural reservoirs for HSV-1 or measles virus. Both must be transferred from human contact and then may be transmitted to other monkeys or back to humans. Neither SIV nor simian retrovirus is known to cause disease in humans.5
Because of the spectrum of bacterial pathogens associated with these exposures, empiric antibiotic therapy should include coverage for streptococci, staphylococci (including methicillin-resistant Staphylococcus aureus), enterococci, Eikenella, anaerobes, and Enterobacteriaceae.1 Oral regimens for less severe exposures might include doxycycline plus ampicillin-sulbactam, clindamycin plus an oral fluoroquinolone (levofloxacin or ciprofloxacin), or possibly clindamycin plus trimethoprim/sulfamethoxazole. For more serious infections, suggested intravenous regimens might include vancomycin plus ampicillin/sulbactam, vancomycin plus a carbapenem, or monotherapy with tigecycline. Linezolid and daptomycin are also reasonable alternatives to vancomycin in the above-mentioned combinations.
Cercopithecine herpesvirus 1 (B virus) is one of 35 herpesviruses identified in nonhuman primates. It is the only one that is known to be pathogenic to humans.6 Old World monkeys, including rhesus macaques (M. mulatta), pit-tailed macaques, cynomolgus monkey, and other macaques, are known to be infected with the virus.3 B virus is a large, double-stranded DNA α-herpesvirus that is very similar to HSV-1 and HSV-2.6 Usually by 2 to 4 years of age or sexual maturity, monkeys are seropositive.6 Exposure of mucosa or skin to oral or genital secretions results in the initial infection which is often asymptomatic.3 They may develop oral or genital lesions. The virus then becomes dormant in the sensory ganglia. It may reactivate asymptomatically, with shedding of the virus, similar to human herpesviruses, often during times of stress or immunosuppression.6 Antibody seropositivity to B virus in captive adult macaques ranges from 73% to 100%. Unfortunately, the titer cannot confirm nor eliminate the possibility of shedding at the time of the bite.2
B virus infection in humans usually involves direct contact of the patient with the monkey, such as a bite, scratch, or mucosal contact with body fluid or tissue. 6 The first documented human case was in 1932. A researcher was bitten on the hand and died of encephalomyelitis 15 days later. 6 One case documented human-to-human transmission after a woman acquired B virus by caring for another patient's open wound.7 The mortality of patients before antiviral therapy was greater than 70%.1 The incubation period of herpes B virus may be as short as 2 days, but usually is 4 to 5 weeks.3 Vesicular lesions are commonly found at the site of exposure, and the patient may also have involvement of the peripheral nervous system at that site.6 Systemic symptoms are often very general, including fever, myalgias, headache, and fatigue. With spread to the CNS, hyperesthesias, ataxia, diplopia, agitation, and ascending flaccid paralysis may develop. Death is often secondary to the respiratory failure associated with the paralysis. Those who do survive will likely have long-term serious neurological sequelae.6
Recommendations for persons exposed to B virus were originally published in 1995 and then again in 20023(Table 1). Within minutes of an exposure, the skin or any mucosal surfaces potentially in contact with infected material should be cleansed for 15 minutes using sterile saline solution for mucosal or eye exposure or chlorhexidine or detergent soap for all other areas. The exposure should be reported to a health care provider who has knowledge about B virus. The potentially infected area should be cleaned again by the provider, and a thorough history should be taken to detail the events of the exposure. If possible, the monkey's medical history and testing should be obtained, and the monkey should be examined for signs of active B virus. All this information will aid in the decision to test and treat the human prophylactically for B virus. Bacterial infections and rabies and tetanus vaccines should also be considered and administered accordingly.3
According to Cohen et al,3 4 variables need to be assessed before starting prophylaxis: (1) source of exposure; (2) timeliness and adequacy of first aid to the wound; (3) type, depth, and location of the wound, and (4) nondirect exposure to materials that have come in contact with the animals. Macaques are the only known primates to transmit B virus. Wounds are more likely to become infected if cleaned poorly. Deep puncture wounds are more difficult to adequately clean. Exposures closer to the CNS (head, torso, or neck) are of higher risk, similar to rabies virus exposures. Needle punctures that contain material from CNS, eyelids, or mucosa are high risk. Postexposure medications should be given from within hours to up to 5 days after the exposure if it is deemed necessary.3
Current recommendations suggest 3 oral agents (Table 2), although none are approved by the US Food and Drug Administration, for postexposure prophylaxis. These include acyclovir, valacyclovir, and famciclovir. Valacyclovir (1 g orally every 8 hours for 14 days) is the drug of choice both for compliance purposes and higher serum levels of acyclovir. Acyclovir (800 mg orally 5 times per day for 14 days) is the alternative regimen and is also recommended for pregnant women. The lack of available animal studies with famciclovir is of some concern to some clinicians with respect to its usefulness as a prophylaxis agent. After 14 days, prophylaxis medications can be discontinued if the patient has developed no symptoms of B virus infection and cultures are negative. Drugs do need to be adjusted for renal insufficiency.3
Intravenous acyclovir (12.5-15 mg/kg every 8 hours) is the drug of choice for patients with B virus infection, presenting with symptoms or with a positive culture. If CNS symptoms are present, ganciclovir (5 mg/kg intravenously every 12 hours) should be considered, as B virus is more susceptible to ganciclovir than acyclovir. Renal toxicity and bone marrow suppression may occur secondary to the medication. Once symptoms have resolved and 2 sets of cultures are negative, therapy may be discontinued or changed to the oral prophylaxis regimen, which is preferred. No good data exist according to the current recommendations.3
The Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health maintain an online monograph available at http://www.cdc.gov/niosh/hid5.html. Further information is also available at http://www.haz-mzp.com/Macaque.htm. In addition, a wealth of resources regarding exposures and diagnostic testing can be referenced at the National B Virus Resource Center at http://www2.gsu.edu/∼wwwvir/index.html. The site includes sample submission forms and related information, answers to FAQs, and a link to a copy of the 2002 guidelines.3
© 2008 Lippincott Williams & Wilkins, Inc.