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DNA fingerprinting by restriction-fragment–length polymorphism (RFLP) analysis can be useful in identifying unusual routes of transmission of M. tuberculosis that may not be detected by conventional contact investigations.3,4 We report two cases of tuberculosis in which the M. tuberculosis isolates were identical on DNA fingerprinting. The only known contact between the affected patients occurred at the time of embalming. Information about Patient 1 was obtained by reviewing the medical record. Information about Patient 2 was obtained by reviewing the medical record and by interviewing the patient.
Case Reports
Patient 1
Patient 1 was a 35-year-old man with the acquired immunodeficiency syndrome (AIDS) who was hospitalized after presenting with fever and a cough. A chest radiograph showed infiltrates in the upper and middle portions of both lungs. A tuberculin skin test performed two years before admission had shown reactivity. Preventive therapy with isoniazid was started at that time, but the patient discontinued it after three months. During his hospitalization, a sputum sample was obtained for staining for acid-fast bacteria and culture, but the patient died on the day it was obtained. After the patient's death, the acid-fast smear was reported to be positive, and the culture grew M. tuberculosis. Blood cultures for mycobacteria were not performed. The patient's only close contacts were four family members, of whom one had had a positive result on prior tuberculin skin testing. Of the other three family members, two had negative tuberculin tests, and one declined testing. None of the close contacts had evidence of active tuberculosis.
Patient 2
Patient 2 was a 45-year-old man who worked as an embalmer. He had a history of hypertension and chronic renal insufficiency (serum creatinine level, 1.4 mg per deciliter [123.8 µmol per liter]). A test for antibodies to the human immunodeficiency virus (HIV), performed two years before presentation, had reportedly been negative. The patient did not have a history of tuberculosis and had not undergone tuberculin skin testing. He had been an embalmer for 15 years and could not remember ever embalming a cadaver that he knew had active tuberculosis. He performed at least 300 embalmings per year, always wearing gloves and usually wearing a mask. He had no history of percutaneous exposure to blood or of chronic skin lesions.
A chest radiograph obtained on routine health screening 31 months after Patient 1 had died showed right paratracheal and hilar adenopathy and an infiltrate in the left lung. A computed tomographic scan revealed extensive mediastinal adenopathy, minimal hilar adenopathy, and mild interstitial thickening in the lingula and both bases. A tuberculin skin test resulted in a 14-mm induration with vesiculation. After being told of the radiographic findings, the patient reported that he had had shortness of breath during the previous four to six months, without fever, chills, night sweats, cough, hemoptysis, weight loss, or fatigue. Treatment with isoniazid, rifampin, pyrazinamide, and ethambutol was started. Culture of a biopsy specimen from the right paratracheal lymph node grew M. tuberculosis. Sputum cultures were all negative. The patient declined an HIV test. Treatment was continued for six months without incident.
Methods
As part of an ongoing study of the epidemiology of tuberculosis, DNA fingerprinting was performed with M. tuberculosis isolates from more than 90 percent of patients in Baltimore who had received a diagnosis of tuberculosis, confirmed by culture, between January 1994 and December 1998.5 Patients 1 and 2 were part of this study. M. tuberculosis isolates were cultivated on Lowenstein–Jensen medium, harvested, and heat-killed. Genomic DNA was isolated, and RFLP analysis was performed according to a standardized method,6 with the use of a 245-bp, right-sided probe (IS6110) and BioImage Whole Band Analyzer software, version 3.0 (Genomic Solutions, Ann Arbor, Mich.).
Results
RFLP analysis showed that the M. tuberculosis isolates from Patient 1 and Patient 2 had an identical 10-band fingerprint pattern (Figure 1). Because of the large number of bands after analysis with IS6110, testing with secondary probes (e.g., pTBN12) was not performed.7 Drug-susceptibility testing showed that both isolates were susceptible to all first-line antituberculosis agents.
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A retrospective chart review showed that Patient 2 had signed the death certificate of Patient 1. The two men had resided in different parts of Baltimore and had had no known contact before the embalming. Hence, there was no evidence that the transmission of tuberculosis from Patient 1 to Patient 2 had occurred before the embalming.
The embalming process included the aspiration of blood and other body fluids from the cadaver's hollow organs and the infusion of preservatives and disinfectants into the arteries under 1.4 to 2.3 kg (3 to 5 lb) of pressure. The aspirated body fluids and perfused liquids were then emptied into drains. Either part of the process may have resulted in the generation of aerosols. The frothing of fluids through the cadaver's nose and mouth or the release of trapped air bubbles through these orifices during cadaveric spasms may also have generated aerosols.
Patient 2 embalmed Patient 1 without assistance from other persons. No other employees of the funeral home contracted active tuberculosis. Patient 2 had no other known exposure to persons or other cadavers infected with M. tuberculosis.
Discussion
Using molecular epidemiologic methods, we confirmed the transmission of M. tuberculosis from a cadaver to an embalmer, probably during the process of embalming. It was possible to obtain proof of transmission because active tuberculosis developed in Patient 2 and the organism could therefore be cultured for DNA fingerprinting.
The increased risk of M. tuberculosis infection among funeral-home employees was recently demonstrated in a large study with the use of tuberculin skin testing.2 The employees who embalmed cadavers were twice as likely to have reactivity on tuberculin skin testing as those who did not perform embalming; this association was strongest among the persons who had worked as embalmers for the greatest number of years. However, the study did not include persons with active tuberculosis. Another study found that the rate of active tuberculosis was higher among funeral directors than in the general population, but the route of transmission was not determined.1
Although it was initially reported that tubercle bacilli from embalmed cadavers used for medical-school anatomy classes were not infectious,8 a subsequent study showed that M. tuberculosis organisms remain viable and therefore infectious for at least 24 to 48 hours after an infected cadaver has been embalmed.9 M. tuberculosis has been transmitted from cadavers to persons working in autopsy rooms,10,11 but to our knowledge, there have been no reports of transmission to embalmers. The mode of transmission in this case was probably the inhalation of infectious aerosols generated during the embalming process. Although mycobacterial blood cultures were not obtained from Patient 1, who had AIDS, bacteremia with M. tuberculosis is more common in patients who have AIDS than in those who do not, and the presence of bacteremia may have increased the likelihood that aerosols generated during embalming were infectious.
The risk of transmission of M. tuberculosis has been thought to be lower during the embalming process than during an autopsy because embalming is less invasive. The guidelines established by the Centers for Disease Control and Prevention12 and by the Occupational Safety and Health Administration13 to prevent nosocomial transmission of M. tuberculosis have not been specifically applied to funeral homes.
The strong epidemiologic and molecular link between the two cases of tuberculosis reported here, as well as the absence of other plausible epidemiologic links, supports the hypothesis that M. tuberculosis was transmitted from the cadaver to the embalmer during the embalming process. Given these findings, efforts should be made to prevent the transmission of M. tuberculosis in funeral homes.
Supported by the Baltimore City Health Department and grants from the Centers for Disease Control and Prevention (cooperative agreement U300466-10) and the National Institutes of Health (AI40605).
We are indebted to Nancy Hooper, at the Mycobacteriology Laboratory of the Maryland Department of Health and Mental Hygiene, for her assistance, and to the staff of the Eastern Chest Clinic of the Baltimore City Health Department.
Source Information
From the Division of Infectious Diseases (T.R.S., W.R.B., R.E.C.) and the Department of Pathology (S.H.), Johns Hopkins University School of Medicine; the Baltimore City Health Department Eastern Chest Clinic (T.R.S., D.S.P., R.E.C.); and the Departments of Epidemiology (T.R.S., D.S.P., R.E.C.), International Health (W.R.B., R.E.C.), and Environmental Health Sciences (R.R.G.), Johns Hopkins University School of Public Health — all in Baltimore.
Address reprint requests to Dr. Sterling at the Division of Infectious Diseases, 1830 E. Monument St., Rm. 444, Baltimore, MD 21287, or at tsterls{at}jhmi.edu.
References
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