14
Patient 1
SHORT REPORTS
A 61-year-old microbiologist was admitted to hospital on July 18, 1988, after fevers, myalgias, and arthraigias had developed in late June, 1988, followed by intractable back pain at the mid-thoracic
level. Findings on admission were beats/min, and respiratory rate 18/min.
Person-to-person transmission of Brucella melitensis
Human brucellosis is primarily an occupational hazard in the USA; in the Middle East and Africa ingestion of contaminated dairy products is an important route of infection. Whether human beings can become infected via person-to-person spread is uncertain. During an investigation of a commonsource, laboratory-associated outbreak due to Brucella melitensis, biotype 3, the wife of a microbiologist with serologically proven brucellosis Her blood isolate was became infected. indistinguishable from the epidemic strain. In the absence of other risk factors, we suggest that sexual intercourse is a possible means of transmission.
In the
USA, transmission of brucellosis to man is primarily occupational hazard affecting people who work with infected animals or their tissues, or laboratory personnel exposed to clinical isolates or the live vaccine.! an
Percutaneous or mucous membrane contamination of open wounds is the usual route of infection. Inhalation of infectious aerosols2 and consumption of contaminated dairy products3 (especially in the Middle East and Africa) are also important vehicles of spread. Opinions differ about whether brucellosis can be transmitted from person to person.4-7 There have been cases of brucellosis after blood transfusions or bone-marrow transplants,8 and in newborn babies.9 During an investigation of a common-source, laboratory-associated outbreak, we were able to demonstrate transmission of Brucella melitensis from an infected worker to his spouse. From May, 1988, to September, 1988, brucellosis developed in eight hospital microbiologists. The outbreak, due to B melitensis, biotype 3, followed inadvertent aerosolisation of a clinical specimen in late March, 1988. Brucellosis was confirmed by the isolation of the organism from the blood of five employees and by four-fold changes in antibodies in an additional three employees. All isolates were indistinguishable biochemically and serologically, and all had the same antibiograms. One of the affected employees, described
below, infected his
spouse.
fever (395°C), pulse 96 Rales were heard in his left lower lung fields and he had point tenderness at the T7 to T 10 level without neurological impairment. Total leucocyte count was 6600/ul and haemoglobin was 12-9 g/dl. An X-ray film showed a patchy infiltrate in the left lower lung field with a small pleural effusion. Serological studies were not done. Blood and urine cultures were negative and sputum culture yielded normal flora. There were no abnormalities in his thoracic spine (thoracic spine films, computed tomography, and technetium bone scan). The patient improved on intravenous doxycycline (100 mg/12 h), defervescing over 3 days; he was discharged on July 24. 2 days later, while on oral doxycycline, he became febrile (39°C) and had intensified back pain (which radiated to his chest) and shortness of breath. On readmission to hospital, his physical and laboratory indices were unchanged with the exception of haemoglobin (11-2 g/dl) and a residual small pleural effusion. Blood cultures were negative. He was given intravenous doxycycline and his fever subsided on the day of admission. He was discharged 6 days later on analgesics but no further antibiotics. His back pain responded to intensive physiotherapy; he returned to work in late September, 1988. After confirmation of the outbreak of brucellosis, the patient was reexamined. He had active discitis of the T7-T8 interspace with
contiguous osteomyelitis as judged by computed tomography. Blood cultures were negative but brucella antibody titre by tube agglutination was 640. He was treated with co-trimoxazole (trimethoprim/sulphamethoxazole, 480 mg/2400 mg per day) and rifampicin 900 mg per day for 3 months with complete resolution. Subsequent serological testing demonstrated a fall in brucella antibodies to 80. All blood cultures obtained during and after treatment remained negative. Patient 2 In February, 1989, fevers, chills, headache, and myalgias developed in the 61-year-old wife of patient 1. Her examination was unremarkable but blood cultures were positive for B melitensis. Cultures of urine, cervix, and saliva were negative for brucella. She responded promptly to parenteral doxycycline (100 mg/12 h plus gentamicin 1-7 mg/kg per day) for the initial 2 weeks followed by oral doxycycline (100 mg/12 h) alone for 2 additional weeks. Initial brucella antibody titre was 80 (peak 320), with a four-fold decline several months later. She denied having visited the microbiology laboratory in years and had no other risk factors for brucellosis. She and her husband had infrequent sexual relations during his acute illness (June-September), but they did have occasional sexual
intercourse before he had received treatment for brucellosis in October, 1988. Cultures of her husband’s sperm, prostatic fluid, urine, and saliva were negative for brucella in February, 1989. Her blood isolate was confirmed as B melitensis, biotype 3 (Centers for Disease Control), and was indistinguishable from the epidemic strain.
We have provided evidence of person-to-person transmission of brucellosis. Since patient 1 was definitely exposed during a proven laboratory outbreak of brucellosis, we were able to exclude another occult environmental focus for his infection. However, the exact mechanism of transmission to his wife remains speculative. Coital transmission of brucellosis in animals is well known. In man, as many as half of individuals with systemic brucellosis will periodically excrete organisms in the urine. The testicle is the most common genitourinary organ affected.10 Brucella has also been isolated from vaginal swabs from Maltese prostitutes (1907 report of Commission for the Investigation of Mediterranean Fever). Our findings add to the evidence of Goossens et al’ that brucellosis may be a sexually transmitted disease. Sexual partners of infected cases should
15
closely for evidence of infection and it would prudent to abstain from unprotected intercourse until
be monitored seem
infection has been eradicated. REFERENCES MD, Kaufman AF. Brucellosis in the United States, 1965-1974. J Infect Dis 1977; 136: 312-16. 2. Kaufman AF, Fox MD, Boyce JM, et al. Airborne Spread of Brucellosis. Ann NY Acad Sci 1980; 353: 105-14. 3. Young EF, Suvannoparrat V. Brucellosis attributed to ingestion of unpasteurised goat cheese. Arch Intern Med 1975; 135: 240-43. 4. Brucellosis. In: Benenson AS, ed. Control of Communicable Diseases in Man. 15th ed. Washington, DC: American Public Health Association 1. Fox
1990: 66-69.
5. Brucellosis. In: Peter G, ed. Report of the Committee on Infectious Diseases. 21st ed. Elk Grove, Illinois: American Academy of Pediatrics, 1988: 140-42. 6. Stantic-Pavlinic M, Cec V, Mehle J. Brucellosis in spouses and the possibility of interhuman infection. Infection 1983; 11: 313-14. 7. Goossens H, Marcelis L, DeKeyser P, Butzler JP. Brucella melitensis: person-to-person transmission? Lancet 1983; i: 773. 8. Naparstek E, Block CS, Slavin S. Transmission of brucellosis by bone marrow transplantation. Lancet 1982; i: 574-75. 9. Lubani MM, Dudin KI, Sharda DC, et al. Neonatal brucellosis. Eur J Pediatr 1988; 147: 520-22. 10. Forbes KA, Lowry EC, Gibson TE, Soanes WA. Brucellosis of the genitourinary tract: review of the literature and report of a case in a child. Urol Surveys 1954; 4: 391-412.
ADDRESSES Division of Infectious Diseases (B Ruben, MD, J. D. Band, MD, P Wong, MD) and the Department of Microbiology (J Colville, MD) William Beaumont Hospital, Royal Oak, Michigan 48073, USA. Correspondence to Dr J. Band
Familial
leg ulcers of juvenile onset
unremarkable. Physical examinations of eighteen family members (ten males and eight females) revealed less severe leg ulcers in seven males. None had trophic changes. Leg ulcerations were reported on the medical charts of three other male relatives. The propositus’ father had also had this disorder. The risk factors for leg ulcers found in the eleven males were smoking in three, diabetes mellitus in two, and varicose veins in eight. Glucose-6-phosphate dehydrogenase activity was deficient in four of the affected males
(only seven studied).**
Arteriography and venography were done in the propositus but were not indicated in the other seven affected
Chronic ulceration of the legs was found in the propositus and in ten male relatives in a family of Iraqi Jews. All eleven males had juvenile onset of symptoms. Venous lesions with ulceration were found in two of the propositus’ brothers and without ulceration in his three sisters. The findings suggest an autosomal dominant sex-limited genetic defect.
Chronic ulceration of the legs affects about 1 % of European populations. The common forms are ischaemic, static, and neurotrophic ulcers; less frequent causes include trauma, infection, and metabolic, haematological, and autoimmune disorders. Females are more often affected than males and the disease is more prevalent from age 30. We report eleven related males with unexplained chronic leg ulceration that first appeared in childhood. A 27-year-old man of Jewish-Iraqi descent (propositus) was referred to us with bilateral, recurrent, lateral and medial malleolar leg ulcers that had first appeared when he was 11 years old. The lesions had not responded to medical and surgical treatment. The patient had smoked 40 cigarettes a day for 10 years. The family history revealed chronic leg ulcers developing in childhood in eleven male relatives (figure). The propositus had a shallow 45 x 5.5 cm ulcer on the right medial malleolus and superficial varicose veins on both thighs. He had no trophic changes. Arterial pulses were easily palpable and the neurological examination was
males. Non-invasive vascular studies were done in his two affected brothers and in his three sisters. On arteriography the propositus had patent arteries down to the ankle with a soft-tissue blush on the right leg, prominent at the medial malleolus. Below the ankle only the anterior tibial artery and dorsalis pedis artery were patent. The arterial circulation in the two brothers and three sisters was assessed by doppler ultrasound and with a pulse volume recorder. Good pulsatility was found in all five and in the propositus. Venography in the propositus revealed patency of deep veins in both legs with superficial venous filling via the calf perforators. No stasis of contrast material was observed. * A detailed table is obtainable from The Lancet.
NON-INVASIVE VASCULAR STUDIES
*SFJ = saphenofemoral
junction, SSPJ =short saphenopopliteal junction, Results as - (venous incompetence), - (normal
PPGphotoplethysmography venous
flow), for R, L
Patient 1
SHORT REPORTS
A 61-year-old microbiologist was admitted to hospital on July 18, 1988, after fevers, myalgias, and arthraigias had developed in late June, 1988, followed by intractable back pain at the mid-thoracic
level. Findings on admission were beats/min, and respiratory rate 18/min.
Person-to-person transmission of Brucella melitensis
Human brucellosis is primarily an occupational hazard in the USA; in the Middle East and Africa ingestion of contaminated dairy products is an important route of infection. Whether human beings can become infected via person-to-person spread is uncertain. During an investigation of a commonsource, laboratory-associated outbreak due to Brucella melitensis, biotype 3, the wife of a microbiologist with serologically proven brucellosis Her blood isolate was became infected. indistinguishable from the epidemic strain. In the absence of other risk factors, we suggest that sexual intercourse is a possible means of transmission.
In the
USA, transmission of brucellosis to man is primarily occupational hazard affecting people who work with infected animals or their tissues, or laboratory personnel exposed to clinical isolates or the live vaccine.! an
Percutaneous or mucous membrane contamination of open wounds is the usual route of infection. Inhalation of infectious aerosols2 and consumption of contaminated dairy products3 (especially in the Middle East and Africa) are also important vehicles of spread. Opinions differ about whether brucellosis can be transmitted from person to person.4-7 There have been cases of brucellosis after blood transfusions or bone-marrow transplants,8 and in newborn babies.9 During an investigation of a common-source, laboratory-associated outbreak, we were able to demonstrate transmission of Brucella melitensis from an infected worker to his spouse. From May, 1988, to September, 1988, brucellosis developed in eight hospital microbiologists. The outbreak, due to B melitensis, biotype 3, followed inadvertent aerosolisation of a clinical specimen in late March, 1988. Brucellosis was confirmed by the isolation of the organism from the blood of five employees and by four-fold changes in antibodies in an additional three employees. All isolates were indistinguishable biochemically and serologically, and all had the same antibiograms. One of the affected employees, described
below, infected his
spouse.
fever (395°C), pulse 96 Rales were heard in his left lower lung fields and he had point tenderness at the T7 to T 10 level without neurological impairment. Total leucocyte count was 6600/ul and haemoglobin was 12-9 g/dl. An X-ray film showed a patchy infiltrate in the left lower lung field with a small pleural effusion. Serological studies were not done. Blood and urine cultures were negative and sputum culture yielded normal flora. There were no abnormalities in his thoracic spine (thoracic spine films, computed tomography, and technetium bone scan). The patient improved on intravenous doxycycline (100 mg/12 h), defervescing over 3 days; he was discharged on July 24. 2 days later, while on oral doxycycline, he became febrile (39°C) and had intensified back pain (which radiated to his chest) and shortness of breath. On readmission to hospital, his physical and laboratory indices were unchanged with the exception of haemoglobin (11-2 g/dl) and a residual small pleural effusion. Blood cultures were negative. He was given intravenous doxycycline and his fever subsided on the day of admission. He was discharged 6 days later on analgesics but no further antibiotics. His back pain responded to intensive physiotherapy; he returned to work in late September, 1988. After confirmation of the outbreak of brucellosis, the patient was reexamined. He had active discitis of the T7-T8 interspace with
contiguous osteomyelitis as judged by computed tomography. Blood cultures were negative but brucella antibody titre by tube agglutination was 640. He was treated with co-trimoxazole (trimethoprim/sulphamethoxazole, 480 mg/2400 mg per day) and rifampicin 900 mg per day for 3 months with complete resolution. Subsequent serological testing demonstrated a fall in brucella antibodies to 80. All blood cultures obtained during and after treatment remained negative. Patient 2 In February, 1989, fevers, chills, headache, and myalgias developed in the 61-year-old wife of patient 1. Her examination was unremarkable but blood cultures were positive for B melitensis. Cultures of urine, cervix, and saliva were negative for brucella. She responded promptly to parenteral doxycycline (100 mg/12 h plus gentamicin 1-7 mg/kg per day) for the initial 2 weeks followed by oral doxycycline (100 mg/12 h) alone for 2 additional weeks. Initial brucella antibody titre was 80 (peak 320), with a four-fold decline several months later. She denied having visited the microbiology laboratory in years and had no other risk factors for brucellosis. She and her husband had infrequent sexual relations during his acute illness (June-September), but they did have occasional sexual
intercourse before he had received treatment for brucellosis in October, 1988. Cultures of her husband’s sperm, prostatic fluid, urine, and saliva were negative for brucella in February, 1989. Her blood isolate was confirmed as B melitensis, biotype 3 (Centers for Disease Control), and was indistinguishable from the epidemic strain.
We have provided evidence of person-to-person transmission of brucellosis. Since patient 1 was definitely exposed during a proven laboratory outbreak of brucellosis, we were able to exclude another occult environmental focus for his infection. However, the exact mechanism of transmission to his wife remains speculative. Coital transmission of brucellosis in animals is well known. In man, as many as half of individuals with systemic brucellosis will periodically excrete organisms in the urine. The testicle is the most common genitourinary organ affected.10 Brucella has also been isolated from vaginal swabs from Maltese prostitutes (1907 report of Commission for the Investigation of Mediterranean Fever). Our findings add to the evidence of Goossens et al’ that brucellosis may be a sexually transmitted disease. Sexual partners of infected cases should
15
closely for evidence of infection and it would prudent to abstain from unprotected intercourse until
be monitored seem
infection has been eradicated. REFERENCES MD, Kaufman AF. Brucellosis in the United States, 1965-1974. J Infect Dis 1977; 136: 312-16. 2. Kaufman AF, Fox MD, Boyce JM, et al. Airborne Spread of Brucellosis. Ann NY Acad Sci 1980; 353: 105-14. 3. Young EF, Suvannoparrat V. Brucellosis attributed to ingestion of unpasteurised goat cheese. Arch Intern Med 1975; 135: 240-43. 4. Brucellosis. In: Benenson AS, ed. Control of Communicable Diseases in Man. 15th ed. Washington, DC: American Public Health Association 1. Fox
1990: 66-69.
5. Brucellosis. In: Peter G, ed. Report of the Committee on Infectious Diseases. 21st ed. Elk Grove, Illinois: American Academy of Pediatrics, 1988: 140-42. 6. Stantic-Pavlinic M, Cec V, Mehle J. Brucellosis in spouses and the possibility of interhuman infection. Infection 1983; 11: 313-14. 7. Goossens H, Marcelis L, DeKeyser P, Butzler JP. Brucella melitensis: person-to-person transmission? Lancet 1983; i: 773. 8. Naparstek E, Block CS, Slavin S. Transmission of brucellosis by bone marrow transplantation. Lancet 1982; i: 574-75. 9. Lubani MM, Dudin KI, Sharda DC, et al. Neonatal brucellosis. Eur J Pediatr 1988; 147: 520-22. 10. Forbes KA, Lowry EC, Gibson TE, Soanes WA. Brucellosis of the genitourinary tract: review of the literature and report of a case in a child. Urol Surveys 1954; 4: 391-412.
ADDRESSES Division of Infectious Diseases (B Ruben, MD, J. D. Band, MD, P Wong, MD) and the Department of Microbiology (J Colville, MD) William Beaumont Hospital, Royal Oak, Michigan 48073, USA. Correspondence to Dr J. Band
Familial
leg ulcers of juvenile onset
unremarkable. Physical examinations of eighteen family members (ten males and eight females) revealed less severe leg ulcers in seven males. None had trophic changes. Leg ulcerations were reported on the medical charts of three other male relatives. The propositus’ father had also had this disorder. The risk factors for leg ulcers found in the eleven males were smoking in three, diabetes mellitus in two, and varicose veins in eight. Glucose-6-phosphate dehydrogenase activity was deficient in four of the affected males
(only seven studied).**
Arteriography and venography were done in the propositus but were not indicated in the other seven affected
Chronic ulceration of the legs was found in the propositus and in ten male relatives in a family of Iraqi Jews. All eleven males had juvenile onset of symptoms. Venous lesions with ulceration were found in two of the propositus’ brothers and without ulceration in his three sisters. The findings suggest an autosomal dominant sex-limited genetic defect.
Chronic ulceration of the legs affects about 1 % of European populations. The common forms are ischaemic, static, and neurotrophic ulcers; less frequent causes include trauma, infection, and metabolic, haematological, and autoimmune disorders. Females are more often affected than males and the disease is more prevalent from age 30. We report eleven related males with unexplained chronic leg ulceration that first appeared in childhood. A 27-year-old man of Jewish-Iraqi descent (propositus) was referred to us with bilateral, recurrent, lateral and medial malleolar leg ulcers that had first appeared when he was 11 years old. The lesions had not responded to medical and surgical treatment. The patient had smoked 40 cigarettes a day for 10 years. The family history revealed chronic leg ulcers developing in childhood in eleven male relatives (figure). The propositus had a shallow 45 x 5.5 cm ulcer on the right medial malleolus and superficial varicose veins on both thighs. He had no trophic changes. Arterial pulses were easily palpable and the neurological examination was
males. Non-invasive vascular studies were done in his two affected brothers and in his three sisters. On arteriography the propositus had patent arteries down to the ankle with a soft-tissue blush on the right leg, prominent at the medial malleolus. Below the ankle only the anterior tibial artery and dorsalis pedis artery were patent. The arterial circulation in the two brothers and three sisters was assessed by doppler ultrasound and with a pulse volume recorder. Good pulsatility was found in all five and in the propositus. Venography in the propositus revealed patency of deep veins in both legs with superficial venous filling via the calf perforators. No stasis of contrast material was observed. * A detailed table is obtainable from The Lancet.
NON-INVASIVE VASCULAR STUDIES
*SFJ = saphenofemoral
junction, SSPJ =short saphenopopliteal junction, Results as - (venous incompetence), - (normal
PPGphotoplethysmography venous
flow), for R, L
