- Email: [email protected]
Q fever in animal laboratory workers: An outbreak and its investigation
BRiEC REPORTS
Q fever in animal laboratory wwkers: An outbreak and its investigation Charles J. Graham, MD Terry Yamauchi, MD Paul Rountree, MD Little Rock, Arkansas
Q fever is an acute febrile illness caused by the rickettsial organism Coxiella burnetti. Animals such as sheep, cattle, and goats are the source of human infection.‘s2 The infection, first described by Derrick? initially occurred among slaughterhouse workers in 1937. The microorganism is highly infectious; only one inhaled organism is capable of causing infection.“ Outbreaks of the disease have been reported in abattoir workers3s5 and in personnel employed in animal research laboratories6-” The purpose of this report is to describe two cases of Q fever in workers in a perinatal research laboratory and the subsequent epidemiologic investigation. MATERIAL
AND METNODS
C. bumetti exists in two antigenic forms, referred to as phase I and phase II. Antibody titers to either antigen can be measured in serum. Elevation of phase II titers are typical of most cases of acute self-limited Q fever, whereas elevations of phase I titers are more characteristic of patients with chronic Q fever or Q fever endocarditis. Blood samples taken during this investigation from patients and laboratory workers were obtained and sent to the University Clinical Laboratory. Serum was obtained and sent to the reference laboratory. In May through October 1985, the Nichols Institute in San Juan Capistrano, Calif., was used as the reference laboratory. Complement fixation titers to both From the University Children’s Reprint Hospital,
Departments of Arkansas Hospital.
of Pediatrics for Medical
and Clinical Toxicology, Sciences, and Arkansas
requests: Terry Yamauchi, MD, Arkansas 800 Marshall St., Little Rock, AR 72202.
17/47/13921
Children’s
phase I and phase II antigens were measured. After October 1985 the University Clinical Laboratory changed reference laboratories for these serologic studies, and the services of the State of California Viral and Rickettsial Disease Laboratory in Berkeley, Calif., were used. This laboratory performed studies to ascertain complement fixation phase II titers and IgG immunofluorescence phase II titers. A complement fixation titer of 1: 8 or greater or an immunofluorescence titer of 1: 32 or greater was reported as positive. THE
OUTBREAK
AND ITS INVESTlQITtON
The index case was that of a 60-year-old white man employed as an animal caretaker in the university’s perinatal research laboratory. He became ill in May 1985 with weakness, anorexia, and fever up to 39.4” C. He was seen in a local emergency room where his diagnosis was viral illness, and he was treated with oral cephalexin. Three days later he came to the University Employee Health Center with worsening symptoms and suggested the possibility of Q fever. He was afebrile and the physical examination showed normal findings. Studies to determine Q fever titers were performed at the Nichols Institute. The initial studies on the index case revealed a complement fixation phase I titer of 1: 8192 and a complement fixation phase II titer of greater than 1: 8192. The patient’s symptoms gradually resolved. Repeated serologic testing was performed at the State of California Viral and Rickettsial Disease Laboratory at Berkeley in December 1985 and revealed a complement fixation phase II titer of 1: 256 and an IgG immunofluorescence phase II titer of greater than 1: 32. The second case in the laboratory was that of 345
Americari
346
Graham
et al.
Table 1. Serologic
INFEWION
findings
worker No.
in workers
with positive
phase
1:64
10 12 13
of
It Q fever titers
ca+mfmttim
8 9
Jotmat CONTROL
a 34-year-old white male employee who came to the University Employee Health Center in October 1985 with complaints of subjective fever, malaise, numbness of hands and feet, and light-headedness. Results of his physical examination were normal. Titers of sera revealed Q fever, and the patient was treated with oral tetracycline, 500 mg four times a day; subsequently his symptoms improved. The initial serologic studies were performed at the Nichols Institute and revealed a complement fixation titer for phase I of 1: 16 and for phase II of 1: 102.4. Subsequent serologic testing performed at Berkeley in December 1985 revealed a complement fixation phase II titer of 1:256 and an IgG immunofluorescence phase II titer of greater than 1: 32. Because two cases of Q fever were found in workers in the same laboratory, sera from the other 29 university employees in the laboratory were obtained in December 1985 and January 1986. Both complement fixation and immunofluorescence phase II titers were performed at the Berkeley laboratory. A complement fixation titer of 1: 8 or greater or an immunofluorescence titer of 1: 32 or greater was considered a positive finding. Thirteen of the workers had at least one positive phase II titer for Q fever. The serologic data of workers with titers positive for Q fever are listed in Table 1. The titers of 16 workers were negative for Q fever. None of the workers surveyed recalled symptoms compatible with Q fever between May and December 1985.
>132 cl:8 >I:32 >1:32 >1.32 >1.32 ->1:32 >132 11.32 >I 32 I:32 1.32 1.32
Subsequent investigation revealed that the laboratory had purchased three ewes from a source in Tennessee approximately 3 weeks before the illness in the index case. The ewes were pregnant and delivered in the laboratory sometime in April or May 1985. Two of the animals subsequently died of endometritis and .were studied at the National Animal Disease Laboratory, where serum from one of the animals was positive for Q fever antibody.
In spite of reports of epidemics of ~Q-fever in animal laboratory workers, outbreaks of the disease continue to occur. The organism can be found in the animal’s urine, feces, and in particularly high concentrations in birth products. The placentas of sheep can harbor as many as lo9 organisms per gram of tissue.12 Workers in animal laboratories, particularly those involved in perinatal research in which sheep are used, can be exposed and infected with the microorganism. Q fever is prevalent in certain animals; for example, as many as 80% of dairy animals have been found to be infected in enzooticm areas.‘” The infection is commonly subclinical in animals, and an animal can give birth to offspring that appear healthy in spite of high numbers of organisms present in birth products.‘4 The infected animals may become chronic carriers of the organism. Because of the asymptomatic nature of the illness, the identification of infected animals can be difficult. In an attempt to pre-
Volume December
17 Number
6
Q fever in animal laboratov workers
1989
vent transmission, efforts have been made in some laboratories to use serologic tests to identify infected animals. Some investigators have found a greater risk of contracting the disease from seropositive animals than seronegative animals, although a direct correlation between shedding and seropositivity has not been confirmed.14 In addition, transmission from seronegative animals has been documented.* Studies presently are evaluating the use of vaccine in sheep in attempt to produce Q fever-free flocks.‘S In the present study two clinical cases of Q fever and serologic evidence of infection in 13 others occurred in a laboratory where perinatal sheep research was in progress. A specific infection control protocol was not in place before the outbreak. It is likely that the workers contracted the illness in the laboratory from the ewes or their birth products. Serologic survey of nonlaboratory workers was not performed in this study; however, previous reports have noted a seropositivity rate between 0.6% and 4.5% in control subjects with no known sheep contact .6,7 This compares with the 45% seropositivity rate in the reported laboratory worker group. The fact that the index case suggested the diagnosis is evidence that at least some of the workers were aware of the risk of infection. In spite of this knowledge, appropriate steps to prevent transmission were not taken. The specific mode of transmission in this situation is not known because of the laboratory personnel’s multiple exposures to laboratory sheep. Specific infection control procedures subsequently were instituted in the laboratory. These procedures include periodic serologic testing of laboratory employees, use of protective clothing and masks, disinfection of contaminated surfaces and equipment with bleach or phenol solution, use of biohazard containers, and incineration of contaminated materials from the laboratory. The laboratory is marked as a biohazard area. Research animals are transported to the laboratory in enclosed chambers to reduce the possibility of outside contamination. Employees in the laboratory receive training in these infection control procedures, as well as in signs and symptoms of Q fever.
347
Several recommendations have been made for infection control in sheep research laboratories.‘4-‘6 First, physically separate facilities are important to isolate these animals from those not associated with the research. There have been at least two reports7J of spread of infection outside the specific laboratory where the sheep research was conducted. The laboratory should be marked as a biohazard area, and those not associated with the ongoing research should be restricted from access. To protect support personnel outside the laboratory such as laundry workers, materials from the laboratory should be decontaminated in the laboratory or placed in impenetrable containers before removal. Instruments used in the research should be autoclaved or chemically disinfected. Personnel in the facility should wear protective clothing, and an adequate handwashing protocol should be observed. Disposable surgical masks should be used when laboratory workers attend pregnant sheep or perform surgical procedures. Persons who have valvular heart disease (particularly those with prosthetic valves) should consider avoiding exposure to these animals because of the risk of Q fever endocarditis. In addition, theoretically there are increased risks for those who are pregnant or immunocompromised. Laboratory administrators should inform these groups of the possible risks and consider limiting exposure. Routine serologic testing of workers is recommended to identify those who have been exposed to the infection. In spite of reports of outbreaks of Q fever in animal research laboratories and recommendations for its control, outbreaks continue to occur. Outbreaks have been reported in laboratories using sheep and goats as research animals, although other species can be infected.’ Infection control practitioners in institutions where animal research (particularly that involved with sheep or goats) is in progress should be aware of this disease, and an active infection control program should be instituted to prevent transmission. References 1. Sawyer concepts.
LA, Fishbein Rev Infect
DE, McDade JE. Q fever: Dis 1987;9:935-46.
current
American
348
Graham et al.
2. Kaplan K. Q fever. Infect Dis Practice 1987;10:1-6. 3. Derrick EH. “Q” fever, a new fever entity: clinical features, diagnosis, and laboratory investigation. Med J Aust 1937;2:281-99. 4. Ormsbee R, Peacock M, Gerloff R, et al. Limits of rickettsial infectivity. Infect Immun 1978;19:239-45. 5. Spelman DW. Q fever: a study of 111 consecutive cases. Med J Aust 1982;1:547-53. 6. Simor AE, Brunton JL, Salit IE, et al. Q fever: hazard from sheep used in research. Can Med Assoc J 1984; 130:1013-6. 7. Meiklejohn G, Reimer LG, Graves PS, et al. Cryptic epidemic of Q fever in a medical school. J Infect Dis 1981;144:107-13. 8. Hall CJ, Richmond SJ, Caul EO, et al. Laboratory outbreak of Q fever acquired from sheep. Lancet 1982; 1:1004-6. 9. Schachter 3. Sung M, Meyer KF. Potential danger of Q fever in a university hospital environment. J Infect Dis 1971;123:301-4. 10. Curet LB, Paust JC. Transmission of Q fever from ex-
INFECTlO&
11.
12.
13.
14.
15. 16.
Journal
of
CONTROL
perimental sheep to laboratory personnel. Am J Obstet Gynecol 1972;114:566-8. Spinelli JS, Ascher MS, Brooks DL, et al. Q fever crisis in San Francisco: controlling a sheep zoonosis in a lab facility. Lab Anim 1981;15:24-7. Welsh HH, Lennette EH, Abinanti FR, et al. Airborne transmission of Q fever: the role of parturition in the generation of infectious aerosols. Ann NY Acad Sci 1958;70:528-40. Biberstein EL, Behymer DE, Bushnett R, et al. A survey of Q fever (Coxiella burnetti) in California dairy cows. Am J Vet Res 1974;35:1577-82. Singh SB, Lang CM. Q fever serologic surveillance program for sheep and goats at a research animal facility. Am J Vet Res 1985;46:321-5. Grant CC, Ascher MS, Bernard KW, et al. Q fever and experimental sheep. Infect Control 1985;6:122-123. Bernard KW, Parham CL, Winkler G, et al. Q fever control measures: recommendations for research facilities using sheep. Infect Control 1982;3:461-4.
Q fever in animal laboratory wwkers: An outbreak and its investigation Charles J. Graham, MD Terry Yamauchi, MD Paul Rountree, MD Little Rock, Arkansas
Q fever is an acute febrile illness caused by the rickettsial organism Coxiella burnetti. Animals such as sheep, cattle, and goats are the source of human infection.‘s2 The infection, first described by Derrick? initially occurred among slaughterhouse workers in 1937. The microorganism is highly infectious; only one inhaled organism is capable of causing infection.“ Outbreaks of the disease have been reported in abattoir workers3s5 and in personnel employed in animal research laboratories6-” The purpose of this report is to describe two cases of Q fever in workers in a perinatal research laboratory and the subsequent epidemiologic investigation. MATERIAL
AND METNODS
C. bumetti exists in two antigenic forms, referred to as phase I and phase II. Antibody titers to either antigen can be measured in serum. Elevation of phase II titers are typical of most cases of acute self-limited Q fever, whereas elevations of phase I titers are more characteristic of patients with chronic Q fever or Q fever endocarditis. Blood samples taken during this investigation from patients and laboratory workers were obtained and sent to the University Clinical Laboratory. Serum was obtained and sent to the reference laboratory. In May through October 1985, the Nichols Institute in San Juan Capistrano, Calif., was used as the reference laboratory. Complement fixation titers to both From the University Children’s Reprint Hospital,
Departments of Arkansas Hospital.
of Pediatrics for Medical
and Clinical Toxicology, Sciences, and Arkansas
requests: Terry Yamauchi, MD, Arkansas 800 Marshall St., Little Rock, AR 72202.
17/47/13921
Children’s
phase I and phase II antigens were measured. After October 1985 the University Clinical Laboratory changed reference laboratories for these serologic studies, and the services of the State of California Viral and Rickettsial Disease Laboratory in Berkeley, Calif., were used. This laboratory performed studies to ascertain complement fixation phase II titers and IgG immunofluorescence phase II titers. A complement fixation titer of 1: 8 or greater or an immunofluorescence titer of 1: 32 or greater was reported as positive. THE
OUTBREAK
AND ITS INVESTlQITtON
The index case was that of a 60-year-old white man employed as an animal caretaker in the university’s perinatal research laboratory. He became ill in May 1985 with weakness, anorexia, and fever up to 39.4” C. He was seen in a local emergency room where his diagnosis was viral illness, and he was treated with oral cephalexin. Three days later he came to the University Employee Health Center with worsening symptoms and suggested the possibility of Q fever. He was afebrile and the physical examination showed normal findings. Studies to determine Q fever titers were performed at the Nichols Institute. The initial studies on the index case revealed a complement fixation phase I titer of 1: 8192 and a complement fixation phase II titer of greater than 1: 8192. The patient’s symptoms gradually resolved. Repeated serologic testing was performed at the State of California Viral and Rickettsial Disease Laboratory at Berkeley in December 1985 and revealed a complement fixation phase II titer of 1: 256 and an IgG immunofluorescence phase II titer of greater than 1: 32. The second case in the laboratory was that of 345
Americari
346
Graham
et al.
Table 1. Serologic
INFEWION
findings
worker No.
in workers
with positive
phase
1:64
10 12 13
of
It Q fever titers
ca+mfmttim
8 9
Jotmat CONTROL
a 34-year-old white male employee who came to the University Employee Health Center in October 1985 with complaints of subjective fever, malaise, numbness of hands and feet, and light-headedness. Results of his physical examination were normal. Titers of sera revealed Q fever, and the patient was treated with oral tetracycline, 500 mg four times a day; subsequently his symptoms improved. The initial serologic studies were performed at the Nichols Institute and revealed a complement fixation titer for phase I of 1: 16 and for phase II of 1: 102.4. Subsequent serologic testing performed at Berkeley in December 1985 revealed a complement fixation phase II titer of 1:256 and an IgG immunofluorescence phase II titer of greater than 1: 32. Because two cases of Q fever were found in workers in the same laboratory, sera from the other 29 university employees in the laboratory were obtained in December 1985 and January 1986. Both complement fixation and immunofluorescence phase II titers were performed at the Berkeley laboratory. A complement fixation titer of 1: 8 or greater or an immunofluorescence titer of 1: 32 or greater was considered a positive finding. Thirteen of the workers had at least one positive phase II titer for Q fever. The serologic data of workers with titers positive for Q fever are listed in Table 1. The titers of 16 workers were negative for Q fever. None of the workers surveyed recalled symptoms compatible with Q fever between May and December 1985.
>132 cl:8 >I:32 >1:32 >1.32 >1.32 ->1:32 >132 11.32 >I 32 I:32 1.32 1.32
Subsequent investigation revealed that the laboratory had purchased three ewes from a source in Tennessee approximately 3 weeks before the illness in the index case. The ewes were pregnant and delivered in the laboratory sometime in April or May 1985. Two of the animals subsequently died of endometritis and .were studied at the National Animal Disease Laboratory, where serum from one of the animals was positive for Q fever antibody.
In spite of reports of epidemics of ~Q-fever in animal laboratory workers, outbreaks of the disease continue to occur. The organism can be found in the animal’s urine, feces, and in particularly high concentrations in birth products. The placentas of sheep can harbor as many as lo9 organisms per gram of tissue.12 Workers in animal laboratories, particularly those involved in perinatal research in which sheep are used, can be exposed and infected with the microorganism. Q fever is prevalent in certain animals; for example, as many as 80% of dairy animals have been found to be infected in enzooticm areas.‘” The infection is commonly subclinical in animals, and an animal can give birth to offspring that appear healthy in spite of high numbers of organisms present in birth products.‘4 The infected animals may become chronic carriers of the organism. Because of the asymptomatic nature of the illness, the identification of infected animals can be difficult. In an attempt to pre-
Volume December
17 Number
6
Q fever in animal laboratov workers
1989
vent transmission, efforts have been made in some laboratories to use serologic tests to identify infected animals. Some investigators have found a greater risk of contracting the disease from seropositive animals than seronegative animals, although a direct correlation between shedding and seropositivity has not been confirmed.14 In addition, transmission from seronegative animals has been documented.* Studies presently are evaluating the use of vaccine in sheep in attempt to produce Q fever-free flocks.‘S In the present study two clinical cases of Q fever and serologic evidence of infection in 13 others occurred in a laboratory where perinatal sheep research was in progress. A specific infection control protocol was not in place before the outbreak. It is likely that the workers contracted the illness in the laboratory from the ewes or their birth products. Serologic survey of nonlaboratory workers was not performed in this study; however, previous reports have noted a seropositivity rate between 0.6% and 4.5% in control subjects with no known sheep contact .6,7 This compares with the 45% seropositivity rate in the reported laboratory worker group. The fact that the index case suggested the diagnosis is evidence that at least some of the workers were aware of the risk of infection. In spite of this knowledge, appropriate steps to prevent transmission were not taken. The specific mode of transmission in this situation is not known because of the laboratory personnel’s multiple exposures to laboratory sheep. Specific infection control procedures subsequently were instituted in the laboratory. These procedures include periodic serologic testing of laboratory employees, use of protective clothing and masks, disinfection of contaminated surfaces and equipment with bleach or phenol solution, use of biohazard containers, and incineration of contaminated materials from the laboratory. The laboratory is marked as a biohazard area. Research animals are transported to the laboratory in enclosed chambers to reduce the possibility of outside contamination. Employees in the laboratory receive training in these infection control procedures, as well as in signs and symptoms of Q fever.
347
Several recommendations have been made for infection control in sheep research laboratories.‘4-‘6 First, physically separate facilities are important to isolate these animals from those not associated with the research. There have been at least two reports7J of spread of infection outside the specific laboratory where the sheep research was conducted. The laboratory should be marked as a biohazard area, and those not associated with the ongoing research should be restricted from access. To protect support personnel outside the laboratory such as laundry workers, materials from the laboratory should be decontaminated in the laboratory or placed in impenetrable containers before removal. Instruments used in the research should be autoclaved or chemically disinfected. Personnel in the facility should wear protective clothing, and an adequate handwashing protocol should be observed. Disposable surgical masks should be used when laboratory workers attend pregnant sheep or perform surgical procedures. Persons who have valvular heart disease (particularly those with prosthetic valves) should consider avoiding exposure to these animals because of the risk of Q fever endocarditis. In addition, theoretically there are increased risks for those who are pregnant or immunocompromised. Laboratory administrators should inform these groups of the possible risks and consider limiting exposure. Routine serologic testing of workers is recommended to identify those who have been exposed to the infection. In spite of reports of outbreaks of Q fever in animal research laboratories and recommendations for its control, outbreaks continue to occur. Outbreaks have been reported in laboratories using sheep and goats as research animals, although other species can be infected.’ Infection control practitioners in institutions where animal research (particularly that involved with sheep or goats) is in progress should be aware of this disease, and an active infection control program should be instituted to prevent transmission. References 1. Sawyer concepts.
LA, Fishbein Rev Infect
DE, McDade JE. Q fever: Dis 1987;9:935-46.
current
American
348
Graham et al.
2. Kaplan K. Q fever. Infect Dis Practice 1987;10:1-6. 3. Derrick EH. “Q” fever, a new fever entity: clinical features, diagnosis, and laboratory investigation. Med J Aust 1937;2:281-99. 4. Ormsbee R, Peacock M, Gerloff R, et al. Limits of rickettsial infectivity. Infect Immun 1978;19:239-45. 5. Spelman DW. Q fever: a study of 111 consecutive cases. Med J Aust 1982;1:547-53. 6. Simor AE, Brunton JL, Salit IE, et al. Q fever: hazard from sheep used in research. Can Med Assoc J 1984; 130:1013-6. 7. Meiklejohn G, Reimer LG, Graves PS, et al. Cryptic epidemic of Q fever in a medical school. J Infect Dis 1981;144:107-13. 8. Hall CJ, Richmond SJ, Caul EO, et al. Laboratory outbreak of Q fever acquired from sheep. Lancet 1982; 1:1004-6. 9. Schachter 3. Sung M, Meyer KF. Potential danger of Q fever in a university hospital environment. J Infect Dis 1971;123:301-4. 10. Curet LB, Paust JC. Transmission of Q fever from ex-
INFECTlO&
11.
12.
13.
14.
15. 16.
Journal
of
CONTROL
perimental sheep to laboratory personnel. Am J Obstet Gynecol 1972;114:566-8. Spinelli JS, Ascher MS, Brooks DL, et al. Q fever crisis in San Francisco: controlling a sheep zoonosis in a lab facility. Lab Anim 1981;15:24-7. Welsh HH, Lennette EH, Abinanti FR, et al. Airborne transmission of Q fever: the role of parturition in the generation of infectious aerosols. Ann NY Acad Sci 1958;70:528-40. Biberstein EL, Behymer DE, Bushnett R, et al. A survey of Q fever (Coxiella burnetti) in California dairy cows. Am J Vet Res 1974;35:1577-82. Singh SB, Lang CM. Q fever serologic surveillance program for sheep and goats at a research animal facility. Am J Vet Res 1985;46:321-5. Grant CC, Ascher MS, Bernard KW, et al. Q fever and experimental sheep. Infect Control 1985;6:122-123. Bernard KW, Parham CL, Winkler G, et al. Q fever control measures: recommendations for research facilities using sheep. Infect Control 1982;3:461-4.