Postexposure Prophylaxis Instructions for Monkey B Virus and Training 2

RULES TO PREVENT B VIRUS INFECTION IN PRIMATE HANDLERS 1. Know the safe methods for handling monkeys and sharps to prevent injuries. 2. Cleanse wounds thoroughly and without delay. 3. Collect specimens from both worker and monkey after an injury and ship promptly to the NIH B Virus Resource Laboratory. 4. Report all injuries and know the symptoms of B virus infection. The evidence from previous human infections suggests that patients survive if they are treated early before advanced symptoms develop. 5. Provide post-exposure prophylaxis if indicated. (see table 5 and 6 for risk assessment and PEP. Appendix 4 Herpes Virus Simiae (B Virus) Infection – Questions and Answers Q. What is B-Virus? A. Virus is a member of the herpes group of viruses that occurs naturally in Macaque monkeys and possibly in other Old World monkeys. B virus infects ≥70% to 100% of surveyed captive adult macaques, but not other nonhuman primates (NHPs). Like humans infected with Herpesvirus simplex virus, monkeys infected with B virus have a lifelong infection, with intermittent reactivation and shedding of the virus in saliva, conjunctival fluid, or urogenital secretions. Although virus shedding is more frequent during the mating season (roughly March to June) and when an animal is ill, under stress, or immunosuppressed, there are often no signs of shedding. Macaques should always be regarded as potentially infectious. Infection with B virus produces very mild disease in the monkey. Most have no obvious evidence of infection. Some monkeys may have vesicles (small blisters) which progress to ulcers in the mouth, on the face, lips, or genitals and/or eye infection. These lesions spontaneously heal after a few days, but the virus resides permanently in the monkey, and may reactivate and cause ulcerative lesions periodically. These relapses are especially likely to occur when the monkey is “stressed” (like cold sores or fever blisters in humans). During these periods, the virus is shed by the monkey to the environment; however, the virus may also be shed by monkeys without visible lesions or symptoms. Q. How does transmission of the B virus from monkeys to humans occur? A. Transmission to humans occurs by exposure to eye, mouth or genital secretions or neurologic tissue from rhesus, cynomolgus or other macaque monkeys. Previously reported human infections usually have been attributed to macaque bites or scratches, injuries from needles used near a macaque’s mucous membranes or central nervous system, or contact with infectious products from the macaques. The first fatal case of B virus infection due to mucosal splash exposure was reported in 1998. Incubation periods may be as short as 2 days, but more commonly they are 2 to 5 weeks. Most documented infections have occurred among biomedical research employees who worked with macaques. Laboratory workers handling only infected central nervous system or primary monkey kidney cell lines have also been exposed and, in at least one instance, infected. One case of person-to-person transmission has been reported. Q. Who is at risk for infection with B virus? A. Those at risk include animal caretakers, laboratory personnel, or anyone who is exposed to monkeys or monkey tissues. Persons who are immunosuppressed because of medication or underlying medical conditions may be at higher risk for infection. The risk of acquiring B virus infections from macaques is probably very low. Thousands of persons who have handled macaques since human infection with B-virus infection was first reported over 50 years ago. There have been approximately 50 known cases of fatal human B virus infection described in the English language literature. About 26 of these cases have been well documented. Q. Can there be serious complications from B virus infection? A. In humans, B virus infections most commonly present as rapidly ascending encephalomyelitis after a prodrome characterized by nonspecific febrile malaise and variably accompanied by herpetic blisters and/or peripheral neurasthenias. Bites to the head and neck are more dangerous because of their proximity to the central nervous system. A B virus infection occurring after these bites would be less likely than distal bites to present with early warning signs such as extremity paresthesias. Q. How can I protect myself from infection? A. Proper work practices markedly reduce the chances of infection. When working with non-human primates: 1. Exercise caution at all times, remembering these are wild animals. They can and will bite and are capable of transmitting to humans several diseases as well as B virus. 2. Wear appropriate, protective clothing, and eye and splash protection. 3. Work together with at least one other person when handling awake primates. Minimize direct handling. 4. Report any observed facial, lip, or oral lesions in primates to a staff veterinarian. 5. Report exposures to oral, genital or ocular secretions or neurologic tissues involving a macaque monkey or scratches with cages or equipment that might be contaminated with their secretions immediately to the Occupational and Environmental Medicine clinic. If the injury occurs after clinic hours first aid should promptly be initiated at the worksite and then go to the Hospital’s Emergency Department. The first aid provided at either of these locations should follow the wound care instructions posted in your work area. Immediately clean wound by soaking or scrubbing exposure site with soap or detergent for at least 15 minutes, then rinse well with water. Rinse eyes and mucus membranes with sterile saline/flowing water. Q. What are the signs and symptoms of B-virus infection in humans? A. B virus related disease is characterized by a variety of signs and symptoms, which generally occur within one month of exposure. These include: Q. What is the purpose of the serum specimen drawn from all new monkey handlers and placed in frozen storage? A. These serum specimens are held in reserve to help in the interpretation a patient’s serum antibody levels following an exposure or illness. About half of the human population possesses antibodies to human herpes simplex virus that cross-react to with B virus. By using special techniques, the lab can reduce, but not entirely eliminate the frequency of false positive results. Clinical manifestations suggesting active infection with B virus. Early manifestations (inconsistently present) 1. Vesicular eruptions or ulcerations at or near the exposure site 2. Severe pain or itching at the exposure site 3. Regional lymphadenopathy Intermediate manifestations (inconsistently present) 1. Fever 2. Numbness, paresthesia, or other neurasthenias at or near the exposure site, with or without proximal progression. 3. Muscle weakness or paralysis in the exposed extremity 4. Conjunctivitis 5. Persistent hiccups Late manifestations (avoidable with early therapy) 1. Sinusitis 2. Neck stiffness 3. Headache lasting > 24 hours 4. Nausea and vomiting 5. Brain-stem findings: diplopia, dysarthria, dysphagia, dizziness, cross hemiparesis, cerebellar signs with ataxia, crossed sensory loss, cranial nerve palsies, or drop attacks 6. Altered mentation Other signs compatible with CNS impairment or viral encephalitis including urinary retention, respiratory failure, convulsions, twitching, hemiparesis, hemiplegia, other localized neurological signs, progressive ascending paralysis, or coma. SIGNS AND SYMPTOMS SUGGESTING POSSIBLE INFECTION WITH B VIRUS To Employees Working with Macaque Monkeys: The following signs or symptoms should be reported immediately, especially if they occur after sustaining a macaque monkey bite or scratch. Early manifestations (inconsistently present) 1. Small blister-like eruptions (vesicles) or ulcerations at or near the exposure site 2. Severe pain or itching at the exposure site 3. Inflamed lymph nodes, especially if they occur in the armpit or elbow of the injured arm Intermediate manifestations (inconsistently present) 1. Fever 2. Numbness or tingling at or near the exposure site, with or without progression toward the center of the body 3. Muscle weakness or paralysis in the exposed extremity 4. Eye redness and inflammation (conjunctivitis) 5. Persistent hiccups Late manifestations (avoidable with early therapy) 1. 2. 3. 4. 5. Sinusitis Neck stiffness Headache lasting more than 24 hours Nausea and vomiting Double vision, difficulty speaking, difficulty swallowing, dizziness, muscle weakness or partial paralysis on either side, or other symptoms of brain stem dysfunction (cerebellar signs with ataxia, crossed sensory loss, cranial nerve palsies, or drop attacks) 6. Altered mental activity 7. Other signs compatible with an infection of the central nervous system, including urinary retention, respiratory failure, convulsions, hemiplegia (paralysis on one side of the body), other localized neurological signs, progressive ascending paralysis, or coma. (Adapted from Table 1 in Guidelines for the Prevention and Treatment of B-Virus Infections in Exposed Persons by Gary Holmes, et al.) Employee Instructions: MACAQUE MONKEY BITE/SCRATCH POSTEXPOSURE PROCEDURES An exposure is not limited to a bite or scratch directly from the monkey. An exposure also includes a cut or scrape from primate cages, a needle stick, or saliva contamination of an existing wound or ocular exposure. Exposure can also occur at necropsy (e.g., a cut from a scalpel blade used to perform the monkey necropsy). If you are exposed, take the following steps: 1. For wounds or scratches, thoroughly scrub or irrigate the wound or exposed area for a minimum of 15 minutes with a disinfectant solution that should be available at a sink in or near the monkey room. THIS IS THE MOST IMPORTANT STEP! DO NOT DELAY! Wound cleansing should be started as soon as possible or within two to five minutes after the injury. (It has been shown that a similar virus, the human herpes simplex virus, can enter host cells within five minutes of exposure.) 2. A concentrated soap or detergent such as povidone-iodine (Betadine Scrub), or chlorhexidine (Nolvasan Scrub) is recommended for skin exposures. The B virus is readily killed by most detergent soaps and disinfectants. The mechanical scrubbing or flushing action is reportedly the most effective means of removing the virus. Consider initial spray of 0.25% hypochlorite solution on wounds, scratches or area of contact except for eyes or mucous membranes, prior to washing. For ocular exposures, the eye should be copiously flushed at the eye wash station or with an eye solution such as Dacriose or sterile normal saline for a minimum of 15 minutes. Never use any soap or disinfectants in the eyes. 3. After the immediate wound cleansing, contact the supervisor and the veterinarian on duty to report the incident. (The veterinarian will coordinate the collection of blood and virology samples from the involved monkey.) Your supervisor will direct you to go the occupational health clinic during normal working hours for blood and wound virology sample collection. You will bring all sections of this information packet and give it to the treating physician. You should ask for the First Aid section back as it contains follow-up instructions. 4. After normal working hours, BMC holidays and weekends, the emergency department will handle exposures by providing appropriate wound care and collecting a wound virology sample and a blood sample. 5. The clinic or emergency department will repeat 15 more minutes of cleaning as described above. The provider will notify the Microbiology Laboratory (H 406) and tube the specimens to pneumatic tube station #2. The specimens may include viral culture swabs collected from the wound or exposed area after disinfecting as described above. Also a blood sample will be drawn and sent to the Microbiology laboratory. Specimens must be refrigerated or frozen and shipped to the NIH B Virus Resource Laboratory. Viral specimens should be frozen prior to shipment and the serum from the blood sample should be stored in a refrigerator or frozen. Forms are included in this packet and include specific directions on how to obtain and handle specimens. QUIZ WORKING SAFELY WITH NONHUMAN PRIMATES 1) The disease carried by rhesus, cynomolgus, and other macaques that is most feared by humans as a possibly fatal disease is called. a. b. c. d. 2) What are the common routes of contact with monkey body fluids that may cause infection of humans with B-virus? a. b. c. d. 3) Shigellosis and Chicken Pox Measles and Tuberculosis Amoebic Dysentery and Measles Tuberculosis and Influenza It is generally stated that protective clothing is your first line of defense against injury and disease transmission. That being the case, then it is especially important that: a. b. c. d. 6) Moving cages Washing cages Needle stick All of the above Which of the following diseases are particularly important in the management of a nonhuman primate colony because they can be transmitted to nonhuman primates from infected humans? a. b. c. d. 5) Scratch by a monkey Bite by a monkey Splash by a monkey All of the above Which of the following injury situations, not involving direct contact with a monkey, are potential risks for exposure to B-virus? a. b. c. d. 4) Tuberculosis (TB) Shigellosis (Bacterial Diarrhea) Cercopithecine Herpesvirus-1 (B-virus) Rubeola (Measles) You disinfect gloves before entering an animal room You have protective equipment custom fitted You have no gaps between sleeves and gloves You must have hearing protection with you at all times Who has the primary responsibility for assuring that appropriate training is provided for students and trainees and they have demonstrated competency in performing all activities associated with any nonhuman primates? a. Principal Investigators b. Facility Managers c. Facility Veterinarians d. Animal Care-givers 7) The primary function of the Animal Exposure Surveillance Program (AESP) is to: a. b. c. d. 8) Register you as a user of laboratory animals Comply with NIH health policy Satisfy your Animal Care and Use Committee Protect your health and well-being Nonhuman primates are broadly classified as either Old World or New World based on the original homeland of the species. Which of the groups include the species that are potential carriers of Herpes B Virus? a. New World b. Old World c. Great Apes 9) Which of the following is not classified as Old World monkeys? a. b. c. d. Rhesus monkeys Squirrel monkeys Cynomolgus monkeys Pig-tailed monkeys 10) In order to protect yourself from injury it is critically important that you be able to recognize the level of arousal and the likelihood of aggressive behavior in nonhuman primates. Which of the following combinations of behaviors represents the highest level of arousal in macaques? a. b. c. d. 11) The risk of you being bitten or scratched is greatest under which of the following circumstances? a. b. c. d. 12) Calling, jumping around, and ear flapping Scratching, yawning, and grooming Direct stare, sneezing, and raising eyebrows Open mouth threat, reaching out, and erect tail Any time your hands are near an occupied cage When you are offering treats for good behavior Transferring an animal from its home cage to a transport cage All of the above If you are bitten, scratched, or exposed to body fluids on a cage it is important that you take action within five minutes after the accident. What should you do first? a. b. c. d. Call Occupational Medical Service for instructions Notify your supervisor and fill out an incident report Scrub the injured area for 15 minutes Culture the animal that injured you 13) If you are bitten, scratched, or exposed to body fluids by a splash in your eye when the Occupational Medical Service (OMS) is closed (evenings, holidays, and weekends) who do you contact before going to the hospital for follow-up? a. b. c. d. 14) BUSM Security Office Your supervisor Your personal health care provider BMC ENC Emergency Department Where is the bite/scratch kit located in your work area? Fill in the blank____________________________________________________________. Answer Key 1) c, 2) d, 3) d, 4) b, 5) c, 6) a, 7) d, 8) b, 9) b, 10) d, 11) d, 12) c, 13) d, 14) The answer is facility specific. Personal Protective Equipment for NHP handlers Hair coverBouffant Cap required Face shield must provide splash protection from top and sides required (Surgical masks with attached eye shields are NOT an acceptable substitute). Face mask-required • Surgical mask or dust/mist mask are acceptable • Protects the monkeys from TB • Protects you from inadvertently touching your mouth with contaminated hands. Goggles must be worn to protect to protect against eye exposure to B-virus. Scrubs and disposable Lab coat or Tyvek or equivalent jumpsuit if wearing street clothes, (long-sleeved)–required Long sleeves protect arms against scratches. 2 pairs of Gloves are required If performing cage change in a macaque holding room Tyvek jumpsuit or equivalent is required. Shoe covers–required Shoe covers–required Shoe covers minimize the risk that you will track monkey feces home. Personal Protective Equipment For Personnel Working with Non–human Primates Equipment Lab coat or surgical gown with long sleeves, Tyvek or jumpsuit Gloves Mask Eye Protection, and Face shield with splash protection from top and sides and Goggles with splash protection For Entry To handle animals/cages ; ; Tyvek jumpsuit or equivalent ; ; ; ; ; ; Shoe covers Or dedicated monkey shoes. Required Do you want to track monkey feces into your car or home? Bouffant Hair cover Required