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3. Identifying Infectious Hazards Associated with the Use of Nonhuman Primates in Research
Pages 21-58

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From page 21...
... This potential risk increases the importance of identifying infectious hazards for persons working with nonhuman primates or their blood or tissue. Pathogenic organisms can be acquired by exposure to blood or body fluids by any route including needle inoculation, animal bites and scratches, splashes, accidental ingestion, mucous membrane contamination, contaminated caging and equipment, or even infectious aerosols.
From page 22...
... Information relevant to each agent is presented in four categories: disease profile in nonhuman primates, mode of transmission, incubation period and clinical signs, and diagnosis and prevention. It should be clarified that not all of the agents listed have been recognized as causes of any illness or other untoward effect in human beings to date.
From page 23...
... Detailed considerations for the design and implementation of an OHSP relative to infectious and non-infectious hazards are presented in Chapter 7 of this report. VIRAL DISEASES Several virus classes are chronic or latent infections of a given species of nonhuman primate and are discussed below or listed in Table 3-1.
From page 24...
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From page 25...
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From page 26...
... B virus is also known to be highly pathogenic in other species of nonhuman primates including colobus monkeys, pates monkeys, DeBrazza's monkeys, capuchins, and marmosets in contact with infected macaques or after experimental inoculation with the agent (Loomis and others 1981; Thompson and others 2000; Weigler 1992; Wilson and others 1990~. Mode of Transmission B virus exposures in humans have resulted from animal bites and scratches, splashes, needle stick injuries (although this virus is not considered a bloodborne pathogen)
From page 27...
... B virus infection in humans has been documented on at least 50 occasions and has led to at least 23 deaths (Palmer 1987; Cohen and others 2002~. When exposure is not evaluated promptly and there is no specific antiviral therapy, case fatality rate exceeds 80% (Hilliard, personal observations; Palmer 1987~; thus B virus is the most significant infectious occupational health hazard in the conduct of nonhuman-primate research.
From page 28...
... and the pathologic and clinical patterns that follow SIV infections in macaques have given them an extremely important role as experimental models of AIDS biology (Mansfield and King 1998~. In experimentally infected macaques, the incubation period can vary from weeks to months, depending on the model.
From page 29...
... Mode of Transmission To date, three individuals have been infected with SIV, these occupational exposures occurred through splashes of infectious material onto mucous membranes, contamination of open cuts or abrasions on the skin, and needle stick injuries (Essex 1994; Khabbaz and others 1994; Sotir and others 1997~. Incubation Period and Clinical Signs The incubation period for human cases is undefined, as no clinical signs of disease have occurred in exposed persons.
From page 30...
... Mode of Transmission The mode of transmission to humans is unknown but presumed to be via contaminated saliva and possibly via bites and invasive research or veterinary procedures involving the oral cavity and respiratory tract of infected animals. Incubation Period and Clinical Signs No illness has been described as a result of spumavirus infections of human or nonhuman-primate origin.
From page 31...
... Incubation Period and Clinical Signs The incubation period for these agents in humans is unknown. There have been no clinical signs in association with small numbers of Ebola-R infections in humans.
From page 32...
... Monkeypox can experimentally infect a wide variety of Old World and New World nonhuman-primate species (Downie 1974; Heberling and Kalter 1971~. Although antibodies may be found in wild populations of guenons, arboreal squirrels are thought to be the natural mammalian reservoirs in endemic regions of Africa (Khodakevich and others 1986)
From page 33...
... Molluscum contagiosum, a skin infection caused by the only member of the Molluscipoxvirus genus, causes umbilicated papules on the skin (genital area, face, and upper body) that can persist for up to 2 years.
From page 34...
... Molluscum contagiosum is spread by close direct contact between humans and potentially through close contact with an infected chimpanzee. Incubation Period and Clinical Signs The incubation period for monkeypod in humans is thought to be about 3 weeks.
From page 35...
... , and accidental exposures with needle sticks or other sharp instruments are a continuing possibility, especially during quarantine of animals after receipt from endemic areas. Incubation Period and Clinical Signs After an incubation period of 3-6 days, the human disease can present with variable severity, including mild, inapparent infections in endemic areas.
From page 36...
... Diagnosis and Prevention Diagnosis is through serologic testing and virus isolation assays. Prevention is by maintaining effective quarantine programs, especially after receipt of animals from endemic areas, eliminating or destroying potential larval habitats of Aedes mosquito vectors, and protecting against mosquito bites.
From page 37...
... Incubation Period and Clinical Signs The incubation period of LCMV in humans is around 8-13 days. A biphasic febrile illness has most often been reported in association with LCMV infection from rodents.
From page 38...
... Mode of Transmission Transmission of hepatitis A to human beings is usually by a fecal-oral route, although transmission via parenteral inoculation is possible. Incubation Period and Clinical Signs The incubation period of human hepatitis A (potentially retransmitted through nonhuman primates)
From page 39...
... Mode of Transmission No cases of transmission of HBV of nonhuman primate origin to humans has been documented, though these agents could presumably be spread by percutaneous inoculation, permucosal exposure to infective material, or vertically via mother to child in the case of human-to-human HBV. Incubation Period and Clinical Signs The incubation period of human HBV averages about 2-3 months.
From page 40...
... for the protection of persons involved in research work on this agent and should be considered as well for all persons who work with chimpanzees or their blood, organs, or other tissues. BACTERIAL DISEASES Tuberculosis Disease Profile in Nonhuman Primates Mycobacterium tuberculosis and M
From page 41...
... Diagnosis and Prevention Intradermal skin tests with mammalian old tuberculin, accompanied by pathologic examination as necessary, are the mainstay of tuberculosis surveillance in nonhuman-primate colonies. An enzyme immunoassay for detection of tuberculosis infection in various species of nonhuman primates via measurement of gamma interferon release from stimulated lymphocytes is also available (Desem and Tones 1998~.
From page 42...
... Shigellosis Disease Profile in Nonhuman Primates Shigella appears to be acquired by nonhuman primates in captivity from contact with infected humans, and various species of Shigella, most commonly S flexneri, have been found in association with a variety of nonhuman-primate species, including macaques, baboons, squirrel monkeys, marmosets, tamarins, and apes (Gibson 1998; fuan-Salles and others 1999; Miller and others 1990; Muchmore 1987; Wolfensohn 1998~.
From page 43...
... Mode of Transmission Transmission is by the fecal-oral route in humans and nonhuman primates. Incubation Period and Clinical Signs In humans, the incubation period averages 1-4 days.
From page 44...
... Incubation Period and Clinical Signs The incubation period is typically 2-5 days in humans. Diarrhea, abdominal pain, fever, nausea; and vomiting have been seen; stools sometimes contain blood or mucus.
From page 45...
... Good hygiene, barrier methods of protection, and safe-handling procedures are warranted to minimize likelihood of exposure from infected animals. Antibiotic therapy has been discouraging in nonhuman primates because of bacterial resistance.
From page 46...
... Mode of Transmission The exact mode of transmission is not well established, though it is suspected that most human infections are acquired via inhalation. Incubation Period and Clinical Signs Months to years follow exposure before onset of clinical signs in humans.
From page 47...
... Incubation Period and Clinical Signs The incubation period is variable but typically ranges from 2 to 4 weeks. Many infections are asymptomatic, but acute or fulminating dysentery with fever, chills, and hemorrhagic or catarrhal diarrhea may occur.
From page 48...
... Good hygiene, barrier methods of protection, and safe-handling procedures are indicated. Balantidiasis Disease Profile in Nonhuman Primates Balantidium cold is reported in macaques, baboons, squirrel monkeys, guenons, and chimpanzees (Ghandour and others 1995; Hubbard and others 1991; Knezevich 1998; Levine 1970; Munene and others 1998; Muriuki and others 1998; Nakauchi 1999~.
From page 49...
... Incubation Period and Clinical Signs The incubation period is likely to be 1-12 days. Abdominal cramping, watery diarrhea, nausea, and vomiting are described for human infection.
From page 50...
... Mode of Transmission Human cases acquired directly from nonhuman primates are rare; accidental exposures through penetrating injuries from needles and other medical sharps are possible as is transmission through a mosquito bite. Incubation Period and Clinical Signs The incubation period in humans is typically 1-4 weeks after the bite of an infective female mosquito of the genus Anopheles, which may be followed by fever, chills, sweating, headache, and nausea.
From page 51...
... Safe blood-handling practices and effective control programs for involved vector species are indicated in work with infected animals. METAZOAN PARASITES Hymenolepiasis Disease Profile in Nonhuman Primates The cestode Hymenolepis nana has been reported in many species of nonhuman primates, including macaques, baboons, squirrel monkeys, and chimpanzees (Ghandour and others 1995; Muchmore 1987; Toft and Eberhard 1998~.
From page 52...
... Incubation Period and Clinical Signs The incubation period is poorly defined but is probably weeks to months. Abdominal pain and tenderness, appendicitis, and nodular inflammation of the intestinal wall have been described.
From page 53...
... Fecal examination or sigmoidoscopy of the lower colon can also be done. Good hygiene, barrier methods of protection, and safe-handling procedures are indicated, and infected animals should be treated appropriately with anthelmintics.
From page 54...
... Incubation Period and Clinical Signs The incubation period is uncertain, but probably 2-4 weeks. Abdominal pain, nausea, diarrhea, and anemia are reported symptoms of Strongyloides infection in humans.
From page 55...
... Good hygiene, barrier methods of protection, and safehandling procedures are indicated, and infected animals should be treated appropriately with anthelmintics. OTHER AGENTS Because of the diversity of species involved and shared susceptibilities to common pathogens, many other infectious agents occasionally found in nonhuman primates are of potential or documented risk to persons who work with them.
From page 56...
... Both handlers had sustained occupational exposure to different species of nonhuman primates during their careers, and both remained healthy despite infection. Use of barrier methods of protection and safe-handling procedures, including prompt disinfecting and flushing of wound sites as warranted because of B virus hazards, should help to minimize transmission in occupational settings.
From page 57...
... The agent has been associated with outbreaks of abortion and stillbirth in baboons and abortion and peracute death in squirrel monkeys, but overt disease in other cases of infection has been inapparent. Leptospira organisms can be acquired via ingestion, mucous membrane exposure, or skin abrasion; nonhuman primates carrying them could represent a hazard for humans, even if they are not the primary vertebrate reservoir.
From page 58...
... Whether these infections can be sustained in research-colony settings depends on the species of nonhuman primate, the biology of the agent, systems of husbandry and veterinary care, and the presence of competent invertebrate vectors. Likewise, the potential for occupational exposure to the agents varies with the collection of species, the type of research use, systems of husbandry and veterinary care, and contact with other vertebrate and invertebrate species at each institution.


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