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Brucella canis
Brucella canis A Cause of Undulant Fever
ROBERT M. BLANKENSHIP, M.D., LT COL. USAF, MC’ JAY P. SANFORD, M.D.+ Dallas, Texas
Brucella canis, recognized In 1987 as a cause of canine abortlon, is an uncommonly reco@zed human pathogen. Our patient, a 48 year old man, probably acquired his infectlon by contact with an infected dog. His clinical course was characterlred by intermittent fever and bacteremia over a 4 month interval. His course, which expands the clinical spectrum of human infections due to Br. canis, is discussed in the context of the other reported instances of community and laboratory acquired cases. Since its discovery in 1967 as a cause of canine abortion [ 11, Brucella canis has infrequently been implicated as a human pathogen. According to the brucella surveillance summary issued in February 1974 [2,3], 10 cases in human subjects are known: 6 in laboratory personnel working with the organism and only 4 in persons wlth a naturally acquired infection. The symptomatic patients have been identified by positive blood cultures and confirmed by serologic tests. We report an additional case, in which the disease presumably was acquired by contact with an infected dog, to further define the clinical features of naturally acquired infection which included a course characterized by intermittent fever and bacteremia over a 4 month interval. CASE REPORT
From the Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical School, Dallas, Texas. Requests for reprints should be addressed to Dr. Jay P. Sanford. Manuscript accepted October 25, 1974. + Present address: Department of Medicine, David Grant USAF Medical Center, Travis AFB, California 94535. + Present address: Uniformed Services University School of Medicine, 6917 Arlington Road, Bethesda, Maryland 20014.
424
September 1975
A 48 year okl man first sought medical attention for this illness in mid-December 1973. At that time he complained of “feeling lousy” for about 1 week. He had a medical history of hypertensive cardiovascular disease with mild congestive heart failure, residuals of an old cerebrovascular accident, a positive tuberculin skin test and a post-traumatic knee problem. His current illness was manifested by chills and subjective fever, decreased appetite and nausea. He denied cough, pain in his chest or abdomen, or any localizing symptoms. On examination his known medical problems were revealed but he had no other abnormaliiis except for an oral temperature of 100.2’F. He was observed on an ambulatory basis to have an undifferentiated febrile illness. Over the ensuing 2 weeks he continued to feel “lousy” wlth decreased appetite and nausea, and then had pain in the dorsum of his right foot which became progressively more severe over the course of a week. He returned to the emergency room because of pain. After a negative orthopedic evaluation he was admitted to the medical service with a documented weight loss of 15 pounds over the 2 week period and with persistent fever (IOl’F orally). Again his examination was noncontributory: specifically, he had no lymphadenopathy, hepatosplenomegaly, or signs of an acute infectious process. During a 3
The American Journal of Yedlclne
Volume 59
BRUCELLA
day hospitalization he spontaneously became afebrile, felt well and was discharged without a specific diagnosis being made. Twelve days after discharge a gram-negative coccobacillus, subsequently identified as Br. canis, was isolated from one of four blood cultures which had been obtained on admission, inoculated into trypticase soy broth (BBLe) and incubated for 14 days with 10 per cent carbon dioxide. The patient was again followed up in March 1974, 3 months after his hospitalization. During this interim he felt reasonably well except for brief relapses of fever and sweats which occurred about once a week. He had returned to work and had regained his appetite and weight. On March 29 the repeat blood culture gave negative results whereas on April 2, prior to institution of empirical tetracycline therapy, a sixth culture again was positive for Br. canis. Laboratory data, except for blood cultures, was unremarkable. Five leukocyte counts were between 6,900 and 9,700/mm3. Differential counts were normal. Liver function tests including bilirubin, serum glutamic oxaloacetic transaminase, alkaline phosphatase and total serum proteins were all normal. Serum electrolytes and renal function tests were normal. “Febrile agglutinins” (including agglutinins against Br. abortus) were not present. Urine cultures gave negative results. A serum protein electrophoresis revealed a marked polyclonal increase in gamma globulin. Epidemiologic investigation was directed toward the patient, 13 household members and the family dog. Blood samples for culture and serologic study were obtained from each person and the dog. The dog, a 2 year old mongrel, had borne two puppies about 2 months prior to our patient’s illness. One puppy was stillborn (the other died shortly after birth), and our patient had disposed of the remains. The dog was confined and examined by a veterinarian but was not apparently ill at the time of evaluation. Blood cultures from all 13 household members and the dog gave negative results. Serologic screening obtained with antigens and antiserums as described by Carmichael and Kenney confirmed the infection in our patient (2-lagglutination at 1:500 serum dilution) and in the dog (2-I at 1:200) [4]. One other household member had a titer of 1:50, which was not diagnostic of Br. canis infection, and the remainder of the titers was less than 1:50. COMMENTS The incidence of Br. canis infection in human beings is not known, but only 10 cases have been recorded [2]. This paucity of cases may reflect the true incidence or may be due, in part, to failure of cross reactivity between Br. canis antibodies and the antigens employed in “febrile agglutinins,” or in routine Brucellosis serologic tests. The reservoir host of Br. canis is the dog. Br. canis was discovered as the agent responsible for epidemic abortion among beagles and has subsequently been identified in many breeds of dogs [S]. Infected dogs may be bacteremic although not overtly ill and also may shed organisms in urine and in the vaginal
CANIS-SLANKENSHIP.
SANFORD
secretion of female dogs [6]. The route by which human infection is acquired is not known, but it is presumably by oral contact, although aerosol exposure is possible, especially in laboratory personnel. The incubation period in natural infection is unknown, but our patient had probable exposure about 8 weeks prior to onset of symptoms. In man the clinical features of Br. canis infections have included fever, chills and malaise. Headache, anorexia, weight loss, loose stools and sore throat have also been reported. Physical findings have been minimal and include fever, adenopathy and occasionally splenomegaly. In the nonlaboratory acquired infections there has been a minimum of adenopathy without splenomegaly. The infrequent but severe complications associated with other forms of brucellosis such as meningitis, endocarditis, orchitis, suppurative splenitis or arthritis have not yet been reported in Br. canis infection. A definitive diagnosis depends upon identification of the organism by blood culture. In the cases available for review, the pattern of bacteremia is variable. Swenson et al. [6] discussed a young woman whose blood cultures (7 of 12) were positive over a 7 day period. The patient mentioned in the Brucellosis summary had 8 blood cultures obtained over an interval of 3 days, all of which were positive. Our patient had two positive cultures (out of 6 blood cultures) spanning a 3 month interval between positive cultures. Lewis et al. [7] recovered the organism from blood, bone marrow and lymph nodes of dogs for intervals of up to 16 weeks after ineffective therapy. Percy et al. [8] experimentally infected monkeys and produced a bacteremic animal model. At necropsy 5 or 10 weeks after inoculation, organisms were isolated from the uterus in one monkey and from the liver and kidneys in another monkey. Although histologic evidence of a granulomatous hepatitis, splenitis and lymphadenitis occurred, organisms were not recovered from these sites. Serologic tests lend support to the diagnosis of Br. canis infection in persons from whom Br. canis is isolated and may be useful in suspicious cases and as an epidemiologic tool. Titers which are considered significant are 11:200 in dogs and 11: 100 in man
[91.” Optimum antimicrobial therapy for Br. canis infections has not been defined. The infection cannot reliably be cured in dogs [7]; however, there is a recent report of favorable results with a two-stage antibiotic regimen in canine infection [lo] in which ampicillin Routine serologic tests for Br. canis are not available. Upon special request, serum samples oan be tested at the Bureau of Laboratories, Center for Disease Control, Atlanta, Ga. l
September 1975
The American Journal of Medicine
Volume 59
425
BRUCELLA CANIS-BLANKENSHIP.
SANFORD
or tetracycline therapy was utilized and followed by a combination of tetracycline and streptomycin therapy. In vitro antimicrobial susceptibility tests suggest that the administration of tetracycline, ampicillin, erythromycin, rifampin, gentamicin and streptomycin might be effective. One patient [2] had positive cultures while receiving ampicillin and subsequently appeared to recover with continued ampicillin therapy. Swenson et al. [6] successfully treated their patient with a combination of ampicillin and streptomycin for 4 weeks. The known spectrum of Br. canis infection is
broadened with our case report to include a relatively miM, chronic relapsing form. Probably when more cases of this rare disease are found, a spectrum similar to other types of Brucellosis will be revealed. ACKNOWLEDGMENT We gratefully acknowledge Dr. Robert S. Mumford, Center for Disease Control, for his critical review and epidemiologic advice. Dr. Ed Beckom, a Dallas County veterinarian, located and examined the dog, and Ms. K. Bateman, a Public Health nurse, obtained blood specimens from the household members.
REFERENCES 1.
Carmichael LE, Bruner DW: Characteristics of a newly recognbed species of brucella responsible for infectious canine abortions. Cornell Vet 58: 579, 1968.
2.
Center for Disease Control: Brucella surveillance summary 1972 (issued February 1974). DHEW Publication No. 75 8186.
3.
Mumford RS, Weaver RE. Patton C, Feely JC, Feldman RA: Human disease caused by Brucella canis. JAMA 231: 1267, 1975.
4.
Carmichael LE, Kenney RM: Canine abortion caused by Brucella canis. J Am Vet f&d Assoc 152: 605, 1968.
5.
Spink WW, Morrisset R: Epidemic canine brucellosis due to a new species. Brucella canis. Trans Am Clin Climatol Assoc 81: 43, 1970.
426
September 1975
The Amerkan
Journal Ot Medklne
6. 7.
8.
9.
10.
Swenson RM. Carmichael LE. Cundy KR: Human infection with Brucella canis. Ann Intern Med 76: 435, 1972. Lewis GE Jr, Crumrine MH, Jennings PB, Farris BL: Therapeutic value of tetracycline and ampicillin in dogs infected wlth Brucella canis. J Am Vet Med Assoc 163: 239, 1973. Percy DH, Egwu IN, Jonas AM: Experimental Bruce@ canis infection in the monkey (Macaca arctoides). Can J Comp Med 36: 221, 1972. Lewis GE Sr, Anderson JK: The incidence of Brucella canis antibodies in sera of military recruits. Am J Public Health 63: 204, 1973. Jennings PB. Crumrine MH, Lewis GE, Farris BL: The effect of a two stage antibiotic regimen on dogs infected with Brucella canis. J Am Vet Med Assoc 164: 513. 1974.
Volume 89
ROBERT M. BLANKENSHIP, M.D., LT COL. USAF, MC’ JAY P. SANFORD, M.D.+ Dallas, Texas
Brucella canis, recognized In 1987 as a cause of canine abortlon, is an uncommonly reco@zed human pathogen. Our patient, a 48 year old man, probably acquired his infectlon by contact with an infected dog. His clinical course was characterlred by intermittent fever and bacteremia over a 4 month interval. His course, which expands the clinical spectrum of human infections due to Br. canis, is discussed in the context of the other reported instances of community and laboratory acquired cases. Since its discovery in 1967 as a cause of canine abortion [ 11, Brucella canis has infrequently been implicated as a human pathogen. According to the brucella surveillance summary issued in February 1974 [2,3], 10 cases in human subjects are known: 6 in laboratory personnel working with the organism and only 4 in persons wlth a naturally acquired infection. The symptomatic patients have been identified by positive blood cultures and confirmed by serologic tests. We report an additional case, in which the disease presumably was acquired by contact with an infected dog, to further define the clinical features of naturally acquired infection which included a course characterized by intermittent fever and bacteremia over a 4 month interval. CASE REPORT
From the Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical School, Dallas, Texas. Requests for reprints should be addressed to Dr. Jay P. Sanford. Manuscript accepted October 25, 1974. + Present address: Department of Medicine, David Grant USAF Medical Center, Travis AFB, California 94535. + Present address: Uniformed Services University School of Medicine, 6917 Arlington Road, Bethesda, Maryland 20014.
424
September 1975
A 48 year okl man first sought medical attention for this illness in mid-December 1973. At that time he complained of “feeling lousy” for about 1 week. He had a medical history of hypertensive cardiovascular disease with mild congestive heart failure, residuals of an old cerebrovascular accident, a positive tuberculin skin test and a post-traumatic knee problem. His current illness was manifested by chills and subjective fever, decreased appetite and nausea. He denied cough, pain in his chest or abdomen, or any localizing symptoms. On examination his known medical problems were revealed but he had no other abnormaliiis except for an oral temperature of 100.2’F. He was observed on an ambulatory basis to have an undifferentiated febrile illness. Over the ensuing 2 weeks he continued to feel “lousy” wlth decreased appetite and nausea, and then had pain in the dorsum of his right foot which became progressively more severe over the course of a week. He returned to the emergency room because of pain. After a negative orthopedic evaluation he was admitted to the medical service with a documented weight loss of 15 pounds over the 2 week period and with persistent fever (IOl’F orally). Again his examination was noncontributory: specifically, he had no lymphadenopathy, hepatosplenomegaly, or signs of an acute infectious process. During a 3
The American Journal of Yedlclne
Volume 59
BRUCELLA
day hospitalization he spontaneously became afebrile, felt well and was discharged without a specific diagnosis being made. Twelve days after discharge a gram-negative coccobacillus, subsequently identified as Br. canis, was isolated from one of four blood cultures which had been obtained on admission, inoculated into trypticase soy broth (BBLe) and incubated for 14 days with 10 per cent carbon dioxide. The patient was again followed up in March 1974, 3 months after his hospitalization. During this interim he felt reasonably well except for brief relapses of fever and sweats which occurred about once a week. He had returned to work and had regained his appetite and weight. On March 29 the repeat blood culture gave negative results whereas on April 2, prior to institution of empirical tetracycline therapy, a sixth culture again was positive for Br. canis. Laboratory data, except for blood cultures, was unremarkable. Five leukocyte counts were between 6,900 and 9,700/mm3. Differential counts were normal. Liver function tests including bilirubin, serum glutamic oxaloacetic transaminase, alkaline phosphatase and total serum proteins were all normal. Serum electrolytes and renal function tests were normal. “Febrile agglutinins” (including agglutinins against Br. abortus) were not present. Urine cultures gave negative results. A serum protein electrophoresis revealed a marked polyclonal increase in gamma globulin. Epidemiologic investigation was directed toward the patient, 13 household members and the family dog. Blood samples for culture and serologic study were obtained from each person and the dog. The dog, a 2 year old mongrel, had borne two puppies about 2 months prior to our patient’s illness. One puppy was stillborn (the other died shortly after birth), and our patient had disposed of the remains. The dog was confined and examined by a veterinarian but was not apparently ill at the time of evaluation. Blood cultures from all 13 household members and the dog gave negative results. Serologic screening obtained with antigens and antiserums as described by Carmichael and Kenney confirmed the infection in our patient (2-lagglutination at 1:500 serum dilution) and in the dog (2-I at 1:200) [4]. One other household member had a titer of 1:50, which was not diagnostic of Br. canis infection, and the remainder of the titers was less than 1:50. COMMENTS The incidence of Br. canis infection in human beings is not known, but only 10 cases have been recorded [2]. This paucity of cases may reflect the true incidence or may be due, in part, to failure of cross reactivity between Br. canis antibodies and the antigens employed in “febrile agglutinins,” or in routine Brucellosis serologic tests. The reservoir host of Br. canis is the dog. Br. canis was discovered as the agent responsible for epidemic abortion among beagles and has subsequently been identified in many breeds of dogs [S]. Infected dogs may be bacteremic although not overtly ill and also may shed organisms in urine and in the vaginal
CANIS-SLANKENSHIP.
SANFORD
secretion of female dogs [6]. The route by which human infection is acquired is not known, but it is presumably by oral contact, although aerosol exposure is possible, especially in laboratory personnel. The incubation period in natural infection is unknown, but our patient had probable exposure about 8 weeks prior to onset of symptoms. In man the clinical features of Br. canis infections have included fever, chills and malaise. Headache, anorexia, weight loss, loose stools and sore throat have also been reported. Physical findings have been minimal and include fever, adenopathy and occasionally splenomegaly. In the nonlaboratory acquired infections there has been a minimum of adenopathy without splenomegaly. The infrequent but severe complications associated with other forms of brucellosis such as meningitis, endocarditis, orchitis, suppurative splenitis or arthritis have not yet been reported in Br. canis infection. A definitive diagnosis depends upon identification of the organism by blood culture. In the cases available for review, the pattern of bacteremia is variable. Swenson et al. [6] discussed a young woman whose blood cultures (7 of 12) were positive over a 7 day period. The patient mentioned in the Brucellosis summary had 8 blood cultures obtained over an interval of 3 days, all of which were positive. Our patient had two positive cultures (out of 6 blood cultures) spanning a 3 month interval between positive cultures. Lewis et al. [7] recovered the organism from blood, bone marrow and lymph nodes of dogs for intervals of up to 16 weeks after ineffective therapy. Percy et al. [8] experimentally infected monkeys and produced a bacteremic animal model. At necropsy 5 or 10 weeks after inoculation, organisms were isolated from the uterus in one monkey and from the liver and kidneys in another monkey. Although histologic evidence of a granulomatous hepatitis, splenitis and lymphadenitis occurred, organisms were not recovered from these sites. Serologic tests lend support to the diagnosis of Br. canis infection in persons from whom Br. canis is isolated and may be useful in suspicious cases and as an epidemiologic tool. Titers which are considered significant are 11:200 in dogs and 11: 100 in man
[91.” Optimum antimicrobial therapy for Br. canis infections has not been defined. The infection cannot reliably be cured in dogs [7]; however, there is a recent report of favorable results with a two-stage antibiotic regimen in canine infection [lo] in which ampicillin Routine serologic tests for Br. canis are not available. Upon special request, serum samples oan be tested at the Bureau of Laboratories, Center for Disease Control, Atlanta, Ga. l
September 1975
The American Journal of Medicine
Volume 59
425
BRUCELLA CANIS-BLANKENSHIP.
SANFORD
or tetracycline therapy was utilized and followed by a combination of tetracycline and streptomycin therapy. In vitro antimicrobial susceptibility tests suggest that the administration of tetracycline, ampicillin, erythromycin, rifampin, gentamicin and streptomycin might be effective. One patient [2] had positive cultures while receiving ampicillin and subsequently appeared to recover with continued ampicillin therapy. Swenson et al. [6] successfully treated their patient with a combination of ampicillin and streptomycin for 4 weeks. The known spectrum of Br. canis infection is
broadened with our case report to include a relatively miM, chronic relapsing form. Probably when more cases of this rare disease are found, a spectrum similar to other types of Brucellosis will be revealed. ACKNOWLEDGMENT We gratefully acknowledge Dr. Robert S. Mumford, Center for Disease Control, for his critical review and epidemiologic advice. Dr. Ed Beckom, a Dallas County veterinarian, located and examined the dog, and Ms. K. Bateman, a Public Health nurse, obtained blood specimens from the household members.
REFERENCES 1.
Carmichael LE, Bruner DW: Characteristics of a newly recognbed species of brucella responsible for infectious canine abortions. Cornell Vet 58: 579, 1968.
2.
Center for Disease Control: Brucella surveillance summary 1972 (issued February 1974). DHEW Publication No. 75 8186.
3.
Mumford RS, Weaver RE. Patton C, Feely JC, Feldman RA: Human disease caused by Brucella canis. JAMA 231: 1267, 1975.
4.
Carmichael LE, Kenney RM: Canine abortion caused by Brucella canis. J Am Vet f&d Assoc 152: 605, 1968.
5.
Spink WW, Morrisset R: Epidemic canine brucellosis due to a new species. Brucella canis. Trans Am Clin Climatol Assoc 81: 43, 1970.
426
September 1975
The Amerkan
Journal Ot Medklne
6. 7.
8.
9.
10.
Swenson RM. Carmichael LE. Cundy KR: Human infection with Brucella canis. Ann Intern Med 76: 435, 1972. Lewis GE Jr, Crumrine MH, Jennings PB, Farris BL: Therapeutic value of tetracycline and ampicillin in dogs infected wlth Brucella canis. J Am Vet Med Assoc 163: 239, 1973. Percy DH, Egwu IN, Jonas AM: Experimental Bruce@ canis infection in the monkey (Macaca arctoides). Can J Comp Med 36: 221, 1972. Lewis GE Sr, Anderson JK: The incidence of Brucella canis antibodies in sera of military recruits. Am J Public Health 63: 204, 1973. Jennings PB. Crumrine MH, Lewis GE, Farris BL: The effect of a two stage antibiotic regimen on dogs infected with Brucella canis. J Am Vet Med Assoc 164: 513. 1974.
Volume 89