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Epidemiologic Notes and Reports Update: Ebola-Related Filovirus Infection in Nonhuman Primates and Interim Guidelines for Handling Nonhuman Primates during Transit and Quarantine

In November 1989, infections caused by a filovirus closely related to Ebola virus were detected in cynomolgus (Macaca fascicularis) monkeys imported from the Philippines and held in a primate quarantine facility in Virginia (1). One hundred forty-nine persons who came in contact with infected animals or the blood or tissues of these animals were placed under surveillance for 21 days after their last known exposure, and all were tested for Ebola virus antibody. Active surveillance was discontinued December 25. No illness compatible with that known to be caused by Ebola virus has occurred among these persons, and none had antibody to Ebola virus. Twelve nonhuman primates in two of 12 holding rooms in the Virginia facility were infected; these and all remaining animals in the facility were euthanized, and the building was decontaminated. Extensive investigation at transit points in Amsterdam and New York did not implicate cross-infection of the monkeys by African primates.

In December, a telephone survey of 40 other U.S. primate importers identified another shipment of cynomolgus monkeys that had arrived in Pennsylvania from the Philippines on November 28 and in which a number of unexplained deaths had occurred shortly after arrival. An Ebola-related filovirus was isolated from liver tissue of one of these animals. The specific geographic origin within the Philippines of these animals is being identified, and active surveillance has been initiated at the facility in Pennsylvania to establish whether the virus has spread to other groups of monkeys or to human contacts. No unusual illnesses in staff of the facility have been reported. Animals currently quarantined are being tested for serologic evidence of Ebola virus infection.

Inspection of the four major holding facilities in the Philippines, including the facility that had supplied the monkeys in Virginia, did not identify unusual illness compatible with Ebola virus disease in either workers or nonhuman primates. The infected animals had been captured from widely separated remote areas. Serologic and virologic studies of animals and workers are under way in these and other facilities in the Philippines. Reported by: RK Miller, MD, Fairfax Health District; JY Baumgardner, MAS, CW Armstrong, MD, SR Jenkins, VMD, CD Woolard, MPH, GB Miller, Jr, MD, State Epidemiologist, Virginia State Dept of Health. GG Wrigley, Buckshire Corporation, Perkasie; LD Polk, MD, Bucks County Health Dept; DR Tavris, MD, State Epidemiologist, Pennsylvania State Dept of Health. MEG Miranda, DVM, MM Dayrit, MD, Field Epidemiology Training Program, MC Saniel, MD, Research Institute for Tropical Medicine, Philippine Dept of Health. Div of Quarantine, Center for Prevention Svcs; Div of Global EIS, International Health Program Office; Scientific Resources Program, Div of Viral and Rickettsial Diseases, Center for Infectious Diseases, CDC.

Editorial Note: The episodes documented in Virginia and Pennsylvania are the first known instances of Ebola-related filovirus infection in imported primates in the United States. Numerous infectious agents, including other filoviruses, with a range of pathogenic potential may be circulating in Africa, Asia, and other parts of the world.

The ecology, natural history, and mode of transmission in nature of Ebola virus and the related Marburg virus are unknown. Humans have acquired the disease from nosocomial transmission (often by contaminated needles) and from person-to-person transmission to those in close contact with blood or secretions from seriously ill patients. The only known episode of the transmission of a filovirus from monkeys to humans resulted from direct handling, without protective measures, of blood and tissues from monkeys infected in the wild by Marburg virus. Animal caretakers did not become infected (2).

The lack of human infection in these incidents suggests the effectiveness of the quarantine measures instituted in 1975. Nonetheless, CDC has developed the following interim guidelines that update and modify the procedures used in the transportation and quarantine of nonhuman primates. These guidelines are intended for interim use. A comprehensive set of guidelines will be developed by CDC, with input from organizations and institutions involved in the transport, quarantine, care, and regulation of nonhuman primates.

INTERIM GUIDELINES FOR HANDLING NONHUMAN PRIMATES DURING TRANSIT AND QUARANTINE

All imported nonhuman primates are quarantined for the first 31 days after arrival, including transit time. Nonhuman primates, particularly those recently captured in the wild, may harbor viruses infectious for humans. Although such viruses are usually present in the animal's blood, they may be detected in urine, feces, or saliva. Those at risk for infection include persons working in temporary or long-term holding facilities and persons who transport animals to these facilities (e.g., cargo handlers and inspectors). Although the risk for human infection from these activities is low, guidelines are useful to minimize such risk in persons exposed to nonhuman primates during transport and quarantine.

General Guidelines for Handling Nonhuman Primates during Transit and Quarantine

  1. Management of transportation and quarantine facilities should ensure that personnel are instructed as to the hazards of handling nonhuman primates, that protective apparel is available, and that the need for its use is understood. Management should provide periodic retraining as well as reinforcement of these procedures.
  2. Persons working with nonhuman primates should not drink, eat, or smoke while handling animals, cages, crates, or materials from such animals.
  3. Access to animal holding areas should be restricted to essential personnel. The number of persons involved in the care, transport, and inspection of nonhuman primates should be the minimum necessary to expedite efficient and humane handling.
  4. All staff in direct contact with animals should wear protective clothing (i.e., gloves and surgical masks and gowns) when opening crates, removing foreign materials from crates, feeding the animals, removing dead animals, or handling bedding materials. These persons should remove disposable protective clothing before leaving the animal holding facilities; this clothing should be autoclaved or incinerated. Nondisposable contaminated clothing should be disinfected on site before laundering.
  5. Separate nonglass water bottles should be provided for each nonhuman primate during transit and quarantine. Reusable items should be adequately decontaminated between uses.
  6. All animal waste, bedding, uneaten food, and other possibly contaminated items should be treated with appropriate disinfectant before removal from the animal holding facilities. All cages, feeding bottles, and other possibly contaminated items should be disinfected between each use or before disposal. Glass items should not be used.
  7. A separate disposable needle and syringe (and, if required, infusion equipment) should be used for each animal, then autoclaved or incinerated. A clean needle should be used for any access to multidose vials (e.g., of ketamine) to avoid contamination. After each use on a group of quarantined animals, multidose vials must be autoclaved and discarded. Disposable supplies should be used whenever possible and must not be reused. Nondisposable equipment should be thoroughly disinfected.
  8. Caution must be used to prevent infection from potentially contaminated needles, scalpels, or other sharp instruments, particularly during disposal of needles. Used needles should not be recapped by hand; removed from disposable syringes by hand; or bent, broken, or otherwise manipulated. Only one set of disposable syringes, needles, and scalpels should be used per animal. Used disposable syringes and needles, scalpel blades, and other sharp items should be placed in puncture-resistant containers kept as close to the work site as practical.
  9. Nonquarantined animals should never be placed in, or permitted access to, areas with quarantined animals. This includes unrestrained pets, feral animals, and animals temporarily boarded for overseas travelers or destined for export.
  10. Management should keep records of all serious febrile illnesses (fever >101.3 F ( greater than 38.5 C) for >2 days) in persons having direct contact with nonhuman primates in transit or in quarantine and should promptly notify CDC* if such an illness occurs. Management should ensure that the physician providing care is informed that the patient works with and/or has been exposed to nonhuman primates.

Additional Guidelines for Handling Nonhuman Primates during Transit

  1. Persons who handle crates or pallets containing nonhuman primates should be protected with elbow-length reinforced leather gloves, long-sleeved shirts and trousers of sufficient thickness to resist minor tears, and sturdy waterproof shoes or boots. The gloves should be of a thickness that prevents penetration of splinters or other crating debris. During warm weather, garments may be of lightweight materials to minimize discomfort. Disposable coverall suits can be used for added protection.
  2. Crates should be free of sharp projections that can cause scratches or wounds to workers. Handles should be present on the sides of crates, and mechanical lifting and transporting devices should be used whenever possible.
  3. Crates containing nonhuman primates should be separated by a physical or spatial barrier from all other animals and cargo at all times.
  4. Wherever possible, nonhuman primates should not be handled directly. Live animals should be removed from cages only when staff can be supervised by a qualified veterinarian. Procedures that may result in bites or scratches should be avoided.
  5. Management of holding facilities should maintain records to document the removal of dead animals; documentation should include the date, shipment num ber, country of origin, species, importer, and disposition of the removed animal. The carcass must be placed in waterproof double bags and incinerated. The Division of Quarantine, Center for Prevention Services (CPS), CDC, should be notified.
  6. Temporary holding facilities should document all injections or parenteral infusions administered to nonhuman primates.
  7. If animals are removed from a shipment while in transit, facilities retaining these animals should ensure full compliance with these guidelines and should maintain records on the care and disposition of animals. Temporary facilities holding animals in this way must be registered as importers of nonhuman primates.
  8.  

Additional Guidelines for Care of Nonhuman Primates during Quarantine

  1. Quarantine facilities should be secure, with access limited to authorized, trained, and informed personnel.
  2. Quarantine facilities should be designed to be adequately disinfected. Management and staff should refer to the Guide for the Care and Use of Laboratory Animals (3) and the CDC/National Institutes of Health Biosafety in Microbiological and Biomedical Laboratories, second edition (Animal biosafety level 2, p. 52) (4), for information on design and operation of animal holding facilities. Staff should use protective clothing, gloves, and masks at all times when in the animal holding facilities; these items should be disinfected or disposed of properly.
  3. Staff should use fresh clothing when going from room to room.
  4. Adequate equipment and space should be available for discarding and disinfecting all equipment, clothing, and caging.
  5. Care should be taken to avoid scratches and bites of animals. All handling of individual animals should be done while the animals are anesthetized or tranquilized, and animals should be maintained in squeeze-back cages wherever possible.
  6. Different lots of primates should not be mixed while in quarantine (minimum 31 days).
  7. Management should notify the Division of Quarantine, CPS, CDC, of severe illnesses and deaths in recently imported primates. CDC will advise management on collection of specimens for investigation of cause of death.

References

  1. CDC. Ebola virus infection in imported primates--Virginia, 1989. MMWR 1989;38:831-2,837-8.
  2. Martini GA, Siegert R, eds. Marburg virus disease. Berlin: Springer-Verlag, 1971.
  3. National Institutes of Health. Guide for the care and use of laboratory animals. Bethesda, Maryland: National Institutes of Health, 1985:43-8; document no. 85-23.
  4. CDC/National Institutes of Health. Biosafety in microbiological and biomedical laboratories. 2nd ed. Bethesda, Maryland: US Department of Health and Human Services, Public Health Service, 1988; DHHS publication no. (CDC)88-8395.

*Program Operations Branch, Division of Quarantine, Center for Prevention Services, telephone (404) 639-1437; Special Pathogens Branch, Division of Viral and Rickettsial Diseases (DVRD), Center for Infectious Diseases (CID), telephone (404) 639-1115; Epidemiology Activity Branch, DVRD, CID, telephone (404) 639-3091; and the Animal Resources Branch, Scientific Resources Program, CID, telephone (404) 639-1320.

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