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Listeriosis as a cause of maternal death: An obstetric complication of the acquired immunodeficiency syndrome (AIDS)
I
OBSTETRICS
Listeriosis as a cause of maternal death: An abstetric complication of the acquired immunodeficiency syndrome (AIDS) Charles
V. Wetli,
M.D., Eneida
0. Roldan,
M.D.,
and Rita M. Fojaco,
M.D.
Miami, Florida A case of maternal death due to Lisferia monocyfogenes bacteremia, with survival of the prematurely delivered infant, is presented. Lymphopenia and a Haitian origin suggest that the fatal OutCOme was related to the acquired immunodeficiency syndrome (AIDS). To our knowledge, this is the first’recorded instance of a maternal death due to listeriosis. (AM. J. OBSTET. GYNECOL. 147:7, 1983.)
Listeriosis is a recognized cause of neonatal death.’ Also, adults with cancer or who are immunosuppressed may die of Listeti bacteremia.2* 3 Reported here is the case of a previously healthy Haitian woman who died of Listeria bacteremia 3% hours after giving birth. The premature infant boy remained clinically well despite the maternal death and placental lesions typical of listeriosis. To our knowledge, no maternal deaths have been previously attributed to listeriosis. The case reported here is thought to be a manifestation of the acquired immunodeficiency syndrome (AIDS).
Case report A 27-year-old Haitian woman, at 32 weeks’ gestation, was admitted to the hospital because of fever, a sore neck, and a slight cough of 1 week’s duration. A maculopapular rash of the lower extremities which appeared a month earlier had subsequently become excoriated. The patient had come to the United States from Haiti 4 years earlier. She had no medical problems. While in Haiti she was delivered of a baby at 4 months’ gestation; the infant subsequently died of prematurity-related complications. A year before the current hospital admission, she was delivered of twins who also died of prematurity-related complications. That hospiFrom the Department of Pathology, Uniumity of Miami School of Medicine, and the Departments of Pathology and Pediatric Pathology, Jackson Memorial Hospital, and the Dade Counly Medical Examiner’s Office. Received for publication April 22, 1983. Accepted June 14, 1983. Reprint requests: Dr. Charles V. Wetli, Deputy Chief Medical Examiner, Medical Examiner’s Office, 1050 N. W. I9 St., Miami, Florida 33136.
tal course was complicated by a persistent fever of unknown origin (complete workup, including malarial smears, was negative) and a transient psychosis, which was thought to be related to a hypoxic episode during parturition. Both the fever and the psychosis spontaneously resolved after 3 werks of hospitalization. Interestingly, she was noted to have “dry skin sores” at that time (these were not further described). Upon admission she was alert but disoriented, with a temperature of 102” F, a pulse of 84 bpm, a respiratory rate of 20/min, and a blood pressure of 86154 torr. Physical examination revealed only excoriated cutaneous lesions of the legs and :I normal 32-week pregnancy. A chest roencgenogram was within normal limits. Hemoglobin was 11 gm/lOO ml and hematocrit was 32%. The white blood cell count was 5,000/mm’i with 60% band forms and 13% lymphocytes (650/ mms). Cerebrospinal fluid obtained by lumbar puncture was clear with an opening pressure of 200 mm H,O and four red blood cells per cubic millimeter with no white blood cells or bacteria observed. Urinalysis disclosed five to 10 white blood cells per high-power field. Serologic tests for syphilis and cryptococcal antigen were negative. Other routine laboratory studies were normal except for an elevated bilirubin (4.5 mg/dl; normal, 0 to 1 mg/dl) and serum glutamic oxaloacetic transaminase (77 U/L; normal, 3 to 20 U/L). Cultures of spinal fluid, blood, cervix, and urine were obtained, and treatment with penicillin and tobramycin was begun. About 15 hours aftqr admission she was delivered precipitately of a 1,681o gm male infant in bed. The placenta was delivered spontaneously 10 minutes later. The temperature remained elevated up to 102” F. She had a fatal cardiac arrest 3% hours after delivery.
8 Wetli, Roldan, and Fojaco
September Am. J. Obstet.
Fig. 1. Multifocal villitis in the placenta, typical of listeriosis. (Hematoxylin magnification X 100.) The postmortem examination revealed 75 ml of yellow serous Huid in each pleural space and 500 ml of similar Huid in the peritoneal cavity. The lungs were slightly congested and edematous. Except for a right parietal subdural ecchymosis, no abnormalities were present grossly or microscopically. No evidence of infection or sottrce of bacteremia was found. Histologic examination of the excoriated skin lesions of the legs revealed only a nonspecific acute and chronic in Hammation with tibrosis. No organisms were demonstrated with a tissue Gram stain. ‘L‘hc 300 gm placenta was considered to be preterm. L1icroscopic examination revealed the presence of sevcrc multifocal villitis (Fig. 1) and numerous grampositive bacilli consistent with Listericr. Cultures of blood, cervix and placenta which had beeri taken shortly before death all grew Licteria monnc~toge:rne.s, The infant, although premature, remained clinically well and was subsequently discharged from the hospital.
Comment Liaterrcl monocytogetw.t has been considered one of the main etiologic factors in repeated and habitual abortion since RabinoviU and associates’ described it in 1959. Maternal infection with Listeria monocytogenes follows one of two characteristic courses.‘. ’ The first is an asymptomatic maternal infection followed by delivery of an affected infant. The second course is that of an
1, I983 Gynecol.
and eosin. Original
acutely ill mother who enters labor prematurely and is delivered of a stillborn or severely infected baby. However, a review of the literature failed to reveal any instance of maternal death due to Listeria monocytogenes bacteremia. Also, adult deaths from Listeriu bacteremia are associated with severe immunologic debilitation as may be seen in cancer patients or with immunosuppression.“. ” The clinical course of this patient has features which, when analyzed together, indicate that AIDS predisposed this patient to fatal Lktrria bacteremia. AIDS was hrst recognized more than 2 years ago as a disease at least moderately predictive of a defect in cellular immunity occurring in a person with no known cause for diminished resistance to that disease.“, d It has a mortality rate of 70%. Most reported cases are of homosexual men or parenteral drug abusers who contracted Kaposi’s sarcoma and/or a variety of opportunistic infections7 A small percentage of AIDS cases occur in heterosexual Haitian immigrants who die of cerebral toxoplasmosis.’ Subsequent investigations have revrealed that these patients have impaired cellular immunity manifested by lymphopenia and an inverted ratio of T-helper to T-suppressor lymphocytes.7 The patient described in this report had an infection with Listeriu monocytogenes which is not particularly uncommon during pregnancy. However, the fatal outcome was unexpected and indicates that her response
Volume Number
Listeriosis
147 1
to the infection was deficient despite adequate treatment. Indeed, a review of the clinical data revealed a profound lymphopenia upon admission (650 lymphocytes per cubic millimeter as compared with a normal adult lymphocyte count of 1,500imm:‘). Impaired immunocompetence during pregnancy is believed to be important in preventing rejection of the fetus.” However, the degree of immunologic impairment is never below the confidence limit for the normal population. The fact that the patient described here was Haitian (a high-risk population for AIDS) and had a severe lymphopenia explains the difference between her response and that of other pregnant women with Listeria monocytogenes infection. It seems paradoxical that the premature infant delivered by this patient did not also contract listeriosis. Therefore, it must be presumed that the fetus remained immunocompetent and that the fetal cord lymphocytes retained their cytotoxic activity.Y Subsequent development of lymphocyte abnormalities or of opportunistic infection in this infant may suggest placental transmission of the etiologic agent for AIDS, which has an incubation period of up to 2 years.’ Recent reports, ‘O however, suggest that the offspring of Haitian women without this syndrome may be at increased risk for AIDS during infancy. Further observations are needed to clarify this issue. The case reported here indicates that Listeria monocytogenes infection may be fatal in an apparently healthy mother. It is recommended that healthy pregnant women in a high-risk population for AIDS (particularly intravenous drug abusers and women of Haitian ori-
as cause
of maternal
death
9
gin) be closely monitored for infection and aggressively treated, particularly if lymphopenia is present. Close follow-up of the offspring of’these women for immune deficiency states is also recommended.
REFERENCES 1.
2. 3. 4. 5. 6. 7. 8.
9.
10.
Ortel, S.: In Thalhammer, 0.. editor: Intrauterine Listeriosis Infection in Prenatal Infections, International Symposium of Vienna, September, 1970. New York, 1971, Grune & Stratton, Inc.. pp. 1-8. Nieman. R.. and Lorber. B.: Listeriosis in adults: A changing pattern. Report ot’ei ht cases and review of the literature. 1968-1978. Rev. In Bect. DIS. . 2:207. 1980. Skidmore; A. G.: Listeriosis at Vancouver General Hospital, 1965-1979, Can. Med. Assoc. J. 125:1217. 1981. Rabinovitz, M., Toass, R., and Krochik, N.: Genital listeriosis as a cause oFrepeated abortion, Harefuah 57:276. 1959. Durack, D. T.: Opportunistic infections and Kaposi’s sarcoma in homosexual men. New Engl. J. Med. 305:1465, 1981. Centers for Disease Control: Update on acquired immunodeficiency syndrome (Al DS)-United States, MMWR 31:507, 513, 1982. Curran, J. W., Evatt, B. L.,. and Lawerence, D. N.: Acquired immunodeficiency syndrome: The past as prologue, Ann. Intern. Med. 98:401, 1983. Pitchenik, A. E., Fische, M. A., Dickinson, G. M., et al.: Opportunistic infection and Kaposi’s sarcoma among Haitians: Evidence of a net%’acquired immunodeficiency state, Ann. Intern. Med. 98:277, 1983. Baines, M. G., Pross, H. F., and Millar, K. G.: Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells, AM. J. OBSTET. GYNECOL. 130: 174 1, 1978. Joncas, J. H, Delage, G., ant1 Chad, Z.: Acquired (or congenital) immunodeficiency syndrome in infants born of Haitian mothers, N. Engl. J. Med. 308~842, 1983.
OBSTETRICS
Listeriosis as a cause of maternal death: An abstetric complication of the acquired immunodeficiency syndrome (AIDS) Charles
V. Wetli,
M.D., Eneida
0. Roldan,
M.D.,
and Rita M. Fojaco,
M.D.
Miami, Florida A case of maternal death due to Lisferia monocyfogenes bacteremia, with survival of the prematurely delivered infant, is presented. Lymphopenia and a Haitian origin suggest that the fatal OutCOme was related to the acquired immunodeficiency syndrome (AIDS). To our knowledge, this is the first’recorded instance of a maternal death due to listeriosis. (AM. J. OBSTET. GYNECOL. 147:7, 1983.)
Listeriosis is a recognized cause of neonatal death.’ Also, adults with cancer or who are immunosuppressed may die of Listeti bacteremia.2* 3 Reported here is the case of a previously healthy Haitian woman who died of Listeria bacteremia 3% hours after giving birth. The premature infant boy remained clinically well despite the maternal death and placental lesions typical of listeriosis. To our knowledge, no maternal deaths have been previously attributed to listeriosis. The case reported here is thought to be a manifestation of the acquired immunodeficiency syndrome (AIDS).
Case report A 27-year-old Haitian woman, at 32 weeks’ gestation, was admitted to the hospital because of fever, a sore neck, and a slight cough of 1 week’s duration. A maculopapular rash of the lower extremities which appeared a month earlier had subsequently become excoriated. The patient had come to the United States from Haiti 4 years earlier. She had no medical problems. While in Haiti she was delivered of a baby at 4 months’ gestation; the infant subsequently died of prematurity-related complications. A year before the current hospital admission, she was delivered of twins who also died of prematurity-related complications. That hospiFrom the Department of Pathology, Uniumity of Miami School of Medicine, and the Departments of Pathology and Pediatric Pathology, Jackson Memorial Hospital, and the Dade Counly Medical Examiner’s Office. Received for publication April 22, 1983. Accepted June 14, 1983. Reprint requests: Dr. Charles V. Wetli, Deputy Chief Medical Examiner, Medical Examiner’s Office, 1050 N. W. I9 St., Miami, Florida 33136.
tal course was complicated by a persistent fever of unknown origin (complete workup, including malarial smears, was negative) and a transient psychosis, which was thought to be related to a hypoxic episode during parturition. Both the fever and the psychosis spontaneously resolved after 3 werks of hospitalization. Interestingly, she was noted to have “dry skin sores” at that time (these were not further described). Upon admission she was alert but disoriented, with a temperature of 102” F, a pulse of 84 bpm, a respiratory rate of 20/min, and a blood pressure of 86154 torr. Physical examination revealed only excoriated cutaneous lesions of the legs and :I normal 32-week pregnancy. A chest roencgenogram was within normal limits. Hemoglobin was 11 gm/lOO ml and hematocrit was 32%. The white blood cell count was 5,000/mm’i with 60% band forms and 13% lymphocytes (650/ mms). Cerebrospinal fluid obtained by lumbar puncture was clear with an opening pressure of 200 mm H,O and four red blood cells per cubic millimeter with no white blood cells or bacteria observed. Urinalysis disclosed five to 10 white blood cells per high-power field. Serologic tests for syphilis and cryptococcal antigen were negative. Other routine laboratory studies were normal except for an elevated bilirubin (4.5 mg/dl; normal, 0 to 1 mg/dl) and serum glutamic oxaloacetic transaminase (77 U/L; normal, 3 to 20 U/L). Cultures of spinal fluid, blood, cervix, and urine were obtained, and treatment with penicillin and tobramycin was begun. About 15 hours aftqr admission she was delivered precipitately of a 1,681o gm male infant in bed. The placenta was delivered spontaneously 10 minutes later. The temperature remained elevated up to 102” F. She had a fatal cardiac arrest 3% hours after delivery.
8 Wetli, Roldan, and Fojaco
September Am. J. Obstet.
Fig. 1. Multifocal villitis in the placenta, typical of listeriosis. (Hematoxylin magnification X 100.) The postmortem examination revealed 75 ml of yellow serous Huid in each pleural space and 500 ml of similar Huid in the peritoneal cavity. The lungs were slightly congested and edematous. Except for a right parietal subdural ecchymosis, no abnormalities were present grossly or microscopically. No evidence of infection or sottrce of bacteremia was found. Histologic examination of the excoriated skin lesions of the legs revealed only a nonspecific acute and chronic in Hammation with tibrosis. No organisms were demonstrated with a tissue Gram stain. ‘L‘hc 300 gm placenta was considered to be preterm. L1icroscopic examination revealed the presence of sevcrc multifocal villitis (Fig. 1) and numerous grampositive bacilli consistent with Listericr. Cultures of blood, cervix and placenta which had beeri taken shortly before death all grew Licteria monnc~toge:rne.s, The infant, although premature, remained clinically well and was subsequently discharged from the hospital.
Comment Liaterrcl monocytogetw.t has been considered one of the main etiologic factors in repeated and habitual abortion since RabinoviU and associates’ described it in 1959. Maternal infection with Listeria monocytogenes follows one of two characteristic courses.‘. ’ The first is an asymptomatic maternal infection followed by delivery of an affected infant. The second course is that of an
1, I983 Gynecol.
and eosin. Original
acutely ill mother who enters labor prematurely and is delivered of a stillborn or severely infected baby. However, a review of the literature failed to reveal any instance of maternal death due to Listeria monocytogenes bacteremia. Also, adult deaths from Listeriu bacteremia are associated with severe immunologic debilitation as may be seen in cancer patients or with immunosuppression.“. ” The clinical course of this patient has features which, when analyzed together, indicate that AIDS predisposed this patient to fatal Lktrria bacteremia. AIDS was hrst recognized more than 2 years ago as a disease at least moderately predictive of a defect in cellular immunity occurring in a person with no known cause for diminished resistance to that disease.“, d It has a mortality rate of 70%. Most reported cases are of homosexual men or parenteral drug abusers who contracted Kaposi’s sarcoma and/or a variety of opportunistic infections7 A small percentage of AIDS cases occur in heterosexual Haitian immigrants who die of cerebral toxoplasmosis.’ Subsequent investigations have revrealed that these patients have impaired cellular immunity manifested by lymphopenia and an inverted ratio of T-helper to T-suppressor lymphocytes.7 The patient described in this report had an infection with Listeriu monocytogenes which is not particularly uncommon during pregnancy. However, the fatal outcome was unexpected and indicates that her response
Volume Number
Listeriosis
147 1
to the infection was deficient despite adequate treatment. Indeed, a review of the clinical data revealed a profound lymphopenia upon admission (650 lymphocytes per cubic millimeter as compared with a normal adult lymphocyte count of 1,500imm:‘). Impaired immunocompetence during pregnancy is believed to be important in preventing rejection of the fetus.” However, the degree of immunologic impairment is never below the confidence limit for the normal population. The fact that the patient described here was Haitian (a high-risk population for AIDS) and had a severe lymphopenia explains the difference between her response and that of other pregnant women with Listeria monocytogenes infection. It seems paradoxical that the premature infant delivered by this patient did not also contract listeriosis. Therefore, it must be presumed that the fetus remained immunocompetent and that the fetal cord lymphocytes retained their cytotoxic activity.Y Subsequent development of lymphocyte abnormalities or of opportunistic infection in this infant may suggest placental transmission of the etiologic agent for AIDS, which has an incubation period of up to 2 years.’ Recent reports, ‘O however, suggest that the offspring of Haitian women without this syndrome may be at increased risk for AIDS during infancy. Further observations are needed to clarify this issue. The case reported here indicates that Listeria monocytogenes infection may be fatal in an apparently healthy mother. It is recommended that healthy pregnant women in a high-risk population for AIDS (particularly intravenous drug abusers and women of Haitian ori-
as cause
of maternal
death
9
gin) be closely monitored for infection and aggressively treated, particularly if lymphopenia is present. Close follow-up of the offspring of’these women for immune deficiency states is also recommended.
REFERENCES 1.
2. 3. 4. 5. 6. 7. 8.
9.
10.
Ortel, S.: In Thalhammer, 0.. editor: Intrauterine Listeriosis Infection in Prenatal Infections, International Symposium of Vienna, September, 1970. New York, 1971, Grune & Stratton, Inc.. pp. 1-8. Nieman. R.. and Lorber. B.: Listeriosis in adults: A changing pattern. Report ot’ei ht cases and review of the literature. 1968-1978. Rev. In Bect. DIS. . 2:207. 1980. Skidmore; A. G.: Listeriosis at Vancouver General Hospital, 1965-1979, Can. Med. Assoc. J. 125:1217. 1981. Rabinovitz, M., Toass, R., and Krochik, N.: Genital listeriosis as a cause oFrepeated abortion, Harefuah 57:276. 1959. Durack, D. T.: Opportunistic infections and Kaposi’s sarcoma in homosexual men. New Engl. J. Med. 305:1465, 1981. Centers for Disease Control: Update on acquired immunodeficiency syndrome (Al DS)-United States, MMWR 31:507, 513, 1982. Curran, J. W., Evatt, B. L.,. and Lawerence, D. N.: Acquired immunodeficiency syndrome: The past as prologue, Ann. Intern. Med. 98:401, 1983. Pitchenik, A. E., Fische, M. A., Dickinson, G. M., et al.: Opportunistic infection and Kaposi’s sarcoma among Haitians: Evidence of a net%’acquired immunodeficiency state, Ann. Intern. Med. 98:277, 1983. Baines, M. G., Pross, H. F., and Millar, K. G.: Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells, AM. J. OBSTET. GYNECOL. 130: 174 1, 1978. Joncas, J. H, Delage, G., ant1 Chad, Z.: Acquired (or congenital) immunodeficiency syndrome in infants born of Haitian mothers, N. Engl. J. Med. 308~842, 1983.