BIOSAFETY

1. BIOSAFETY

2. Exposure • There are four major types of exposures to potential health hazards within a nonhuman primate facility:

4. BITES AND SCRATCHES • All bites and scratches should be considered serious. • Nonhuman primates, both wild caught and domestically bred, are wild animals and tend to react aggressively to restraint and handling. Most of them have large, sharp teeth and strong jaws, which they will use to inflict puncture wounds or lacerations as they attempt to either escape or resist handling.

5. Toenails • The animals also have sharp fingernails and toenails that can scratch and abrade the skin of handlers

6. Infectious Agents • In addition to the immediate injury, broken skin provides easy entry for infectious agents carried by the animal. Secondary infection may occur as a result of exposure to a variety of aerobic and anaerobic bacteria from the animal, including Pasteurella multocida and Clostridium tetani. Clostridium tetani causes tetanus, a painful disease that acts upon the central nervous system to cause sustained muscular contractions. Therefore, it is important that all persons working with nonhuman primates have current tetanus immunization status • A more serious, but less frequent, sequel to bites and scratches is exposure to zoonotic viral infections carried by the nonhuman primates, such as herpesvirus simiae and rabies virus

7. Herpesvirus simiae • Herpesvirus simiae (herpes B virus) is the most serious of the zoonotic viruses. In monkeys, it may be subclinical or cause mouth lesions resembling cold sores. But in humans it can result in fatal encephalitis, usually following an incident of a bite or scratch, as the virus is shed in saliva and lacrimal secretions. • Cases have also been reported following exposure to monkey tissues. Each animal care facility should have on-call medical care personnel who are knowledgeable about the hazards of Herpesvirus simiae, as well as its symptoms and treatment

8. Herpes B virus • Caused by a virus carried in non-human primates. • Most feared infection of non-human primate handlers. • Over thirty cases have been reported in the last forty years in persons who have had contact with macaque monkeys • First reported case in 1932 (W.B.) 23 additional cases through 1972. • Most recent cases include 4 in Florida in 1987, 1 in Texas in 1991, and 1 at Yerkes in Georgia in December 1997.

9. Reservoir and Incidence • Naturally occurs in rhesus, cynomolgous, pig-tail, and other Asiatic monkeys of macaque genus. • Young monkeys can be infected by adult carriers once they loose maternal antibody protection. • Virus can be found in asymptomatic seropositive animals.

10. Transmission • Occurs via bites, scratches, splashes, or improper handling of contaminated monkey tissues. • Virus has been found in saliva, blood, urine, feces, and kidney tissue cultures of infected monkeys. • ALL MACAQUES SHOULD BE CONSIDERED TO BE INFECTIOUS

11. Herpes B virus • Disease in Non-Human Primates • May be completely asymptomatic. • Virus may cause mild cold sore type lesions of mucous membranes, base of tongue, lips or face. • Mild conjunctivitis or nasal discharge.

12. Herpes B virus • Disease in Humans • Variety of symptoms which occur within a month of exposure. • Vesicular (blister-like) lesions at or near the site of exposure. • Localized neurological symptoms (numbness, tingling, pain). • Ascending paralysis. • Ultimately encephalitis (infection of brain)

13. Herpes B virus • Disease in Humans • Death usually occurs 3 to 21 days after the appearance of symptoms. • Two of the four patients in the Florida case exhibited mild disease after receiving Acyclovir early in the course of the disease. • They became culture negative and lesions resolved during therapy.

14. Herpes B virus • Guidelines for Prevention • Macaques used only when indicated. • Use B-virus free animals. • Minimize direct handling. • Universal Precautions • Educating and training personnel. • Occupational health program should be established

15. Herpes B virus • Health Program • Employee serum samples collected and banked annually. • All bite, scratch, and splash incidents should be tended to immediately (washed for 20 minutes). • All bites and scratches should be reported and documented. • Follow-up.

16. Rabies virus • Rabies infection is rare in nonhuman primates in laboratory settings, but several cases have been reported in newly captured New World primates. For this reason, rabies vaccinations should be considered for everyone who works with unconditioned monkeys and all bites should be evaluated for rabies potential

17. Rabies virus • Transmission • Virus laden saliva via bite, scratch, or abrasion. • Tissues and fluids in the laboratory. • Rabid animal may shed virus in saliva 1 to 14 days before showing signs

18. Rabies virus • Prevention and Control • Virus destroyed rapidly at greater than 50°C. • Survives no more than a few hours at room temperature. • Vigorous first aid for bite wounds. • Consult health authority

19. ACCIDENTAL INOCULATIONSNeedle stick • Most accidental inoculations occur as the result of needle sticks when performing veterinary procedures such as chemical restraint, tuberculin testing, or collection of blood samples. Lacerations and scratches from equipment with sharp edges can also result in accidental inoculation

20. Filoviruses • All of the zoonotic diseases carried by nonhuman primates can be transmitted by accidental inoculation; however, filoviruses deserve special consideration as a potential complication. • In 1967, 31 humans became ill and 7 died following exposure to the tissues of apparently healthy African Green Monkeys. The incident, which affected personnel in West Germany and Yugoslavia, became known as the Marburg incident, and the virus was named the Marburg virus. A related disease, Ebola fever, has been transmitted from human to human in Africa via needles. Viruses belonging to the Marburg-Ebola family (filoviruses) were implicated in the 1989-90 outbreaks of fatal febrile-hemorrhagic disease in cynomolgus monkeys that had been recently imported into the U.S.

21. Retroviruses • Retroviruses, particularly those of type D morphology, have been implicated in causing neoplasia, immunosuppression, anemia, and other problems in nonhuman primates. Simian immunodeficiency virus is closely related to HIV virus, which causes human AIDS. There has been no evidence of humans contracting disease from these simian agents. • However, when working with animals infected with a retrovirus, the same safety precautions are followed as when working with animals infected with hepatitis B: prevent exposing mucous membranes and unprotected skin to materials that may be contaminated with the virus, and particularly, prevent accidental

22. Other diseases • Other diseases that could be sequelae to accidental inoculation are the pox viruses (monkey pox and yaba-like disease), and Trypanosoma cruzi, a blood-borne flagellated protozoan. This is a manifestation of yaba-like disease in a human

23. Experimental agents • Accidental inoculation is even more serious when the inoculum contains infectious agents or tissues from animals that have been experimentally infected with agents such as hepatitis B virus, hepatitis C virus, or malaria.

24. Needle disposal • Needles and other sharp objects must be carefully discarded, preferably into specially designed containers. Needles should never be placed directly into trash containers where other persons could unknowingly harm themselves. To avoid unintentional injury, needles should never be recapped by hand.

25. Follow-up care • All needle stick or puncture wounds should be reported for follow-up medical care and monitored for disease sequelae

26. AIRBORNE DISEASE TRANSMISSION • There are several diseases that ran be transmitted between nonhuman primates and humans via the airborne route, including tuberculosis and measles. It is probable that other pathogens causing respiratory disease can also be transmitted by air

27. Tuberculosis • Tuberculosis is a disease that can progress very rapidly and is often fatal in Old World Primates. Transmission from nonhuman primates to humans has been documented in only a few cases; however, it is not uncommon for persons to convert from a negative to positive tuberculin test after working with nonhuman primates or following an outbreak of disease in a colony.

28. Tuberculosis • TB caused by a bacteria of the Mycobacterium genera. • Three most common species: • M. Bovis (cattle) • M. Avium (birds) • M. Tuberculosis (humans and non-human primates)

29. Tuberculosis • Disease in Non-Human Primates • Anorexia and lethargy • Sudden death • Diarrhea • Suppuration of lymph nodes • Ulcerative skin lesions • Paralysis of the hind limbs

30. Diagnosis of TB • Intradermal TB test (Mammalian Tuberculin) • Chest radiograph • Gastric wash • Acid fast stained sputum smear

31. Prevention and Control • Personnel education. • Universal Precautions • Regular health surveillance programs for human and non-human primates. • Rapid euthanasia and careful disposal of infected animals. • Facility directors may consider denying entry to individuals who are skin-test positive, as they could become active spreaders of the disease to nonhuman primates.

32. Measles (Rubeola Virus) • Measles is the other major zoonotic disease transmitted by the airborne route. • Respiratory disease and skin rash seen in monkeys imported from both Asia and South America has been attributed to human measles virus. Therefore, it is important for persons working with nonhuman primates to have current immunization status.

33. MEASLES • Human population serve as a reservoir. • Highly contagious. Can spread from human to non-human primate or non-human primate to human. • Virus is excreted from the mucous membranes of the eye and throat and later from the respiratory/urinary tracts.

34. MEASLES • Prevention and Control • Vaccinate personnel working with NHP if they do not have history of previous exposure. • Universal Precautions • Consider vaccination of susceptible population of NHP where contact with humans cannot be adequately controlled.

35. CONTACT DISEASE TRANSMISSION • Nonhuman primates and their environment are potentially contaminated with a host of bacterial and viral pathogens associated with saliva, hair coat, lacrimal secretions and excrement. In addition, humans and nonhuman primates also share common parasites

36. Caretaker • Only minimal contact is required. Traces of biological materials are easily transferred from an animal, cage, or cage pan to the clothing or hands of an animal caretaker or investigator, and from there to the mouth. Animal tissues are also a source of contact disease transmission.

37. Diarrhea • Diarrheal disease caused by enteric bacteria or parasites is perhaps the most common ailment in captive nonhuman primates that can be transmitted to personnel

38. Salmonella • Gram negative bacteria. • 1600 recognized serotypes, most common in lab animals are: • S. Typhimurium • S. Enteritidus

39. Salmonella • Reservoir and Incidence • Inhabits the intestinal tract of many animals. • Indirect transmission via contaminated food and water are the most common sources. • Animal feeds containing animal by-products continues to be a source. • Common contaminant of sewage

40. SHIGELLOSIS • Gram negative, non spore forming, bacteria. • Common organism causing problems: • S. Flexneri • S. Sonnei • S. Dysenteriae • Considered a significant zoonotic disease that has frequently been transmitted from non-human primate to man.

41. SHIGELLOSIS • Reservoir and Incidence • Most commonly identified causes of diarrhea in NHP. • Asymptomatic carriers are common. • Difficult to eliminate all carriers. • Prevention and Control • Prevention is aimed at improving sanitation and personal hygiene. • Universal Precautions

42. Amebiasis, Balantidiasis, Giardiasis • Agents include: • Entamoeba hystolytica • Balantidium coli • Giardia duodenalis • Reservoir and Incidence • Worldwide distribution. • Non-human primates can serve as reservoir.

43. Amebiasis, Balantidiasis, Giardiasis • Transmission • Ingestion of infective cysts. • Disease in man and non-human primates • Diarrhea or dysentery. • Abdominal pain. • Anorexia. • Weight loss. • Prevention • PRACTICE GOOD HYGIENE. • UNIVERSAL PRECAUTIONS

44. Human hepatitis A • Human hepatitis A is transmitted mainly by the fecal to oral route. This may occur when an animal caretaker handles soiled materials and then touches the mouth directly or even indirectly - for example, later while eating. This disease has been seen in humans who have been in contact with newly imported nonhuman primates, including chimpanzees, the gorilla, siamang, celebes black ape, patas monkey and woolly monkey.

45. Ringworm • Ringworm is also spread by direct contact with infected nonhuman primates. Early signs of the disease are redness and flaking of the skin, with subsequent focal hair loss. Any such lesion should be examined by a medical clinician for possible treatment.

46. REDUCING RISKS • The risk of exposure to both airborne and contact pathogenic agents is reduced by correct use of protective clothing, adherence to hygiene practices and an effective animal health surveillance program. • Everyone entering a nonhuman primate area for any reason should wear protective clothing. • The minimum protection acceptable is a surgical mask, gown and gloves. Long sleeves should be worn by anyone handling animals.

48. All protective clothing should be removed upon leaving the animal room or facility. Contaminated items should be bagged for incineration or autoclaving.

49. Laundry worker • An on-site laundry encourages the use of clean garments by animal care persons, and therefore, enhances the safety of the work environment. But remember that personnel handling potentially contaminated garments must themselves use increased safety practices.

50. Personal hygiene • The second important safeguard against potential exposure to pathogenic agents is adherence to hygiene practices. • Each nonhuman primate holding area should be equipped with a hand washing sink, soap and paper towels. Personnel should wash thoroughly each time they leave the holding area, even though they have been wearing protective gloves.