Anthrax during Pregnancy: Case Reports and Review
- 1Departments of Infectious Disease and University of Atatürk, School of Medicine, Erzurum, Turkey
- 2Departments of Obstetrics and Gynecology, University of Atatürk, School of Medicine, Erzurum, Turkey
- Reprints or correspondence: Dr. Ayten Kadanali, A. Türkes Bulvari, Erguvan Konaklari No. 18, 25270 Yildizkent, Erzurum, Turkey (Kadanali{at}atauni.edu.tr).
Abstract
We review, in detail, 2 cases of anthrax during pregnancy, its maternal and perinatal complications, and its management. Patient 1 was a 33-year-old woman at 32 weeks of gestation. She had a submandibular eschar; extensive edema on her face, neck, and upper thorax that inhibited respiratory function; and fever. The patient was treated with penicillin G and prednisolone after the diagnosis of anthrax. She recovered within 10 days but delivered a preterm baby. Patient 2 was a 29-year-old woman at 33 weeks of gestation. Her anthrax lesion was on her right elbow, and therapy consisted of procaine penicillin. She also delivered a preterm baby. These 2 cases show that anthrax during pregnancy can be successfully managed, but preterm delivery could be a complication.
Although anthrax is a disease that dates from 500 BCE, infection by Bacillus anthracis of pregnant women is rare, with only 4 cases reported in the literature [1, 2]. Three of these cases occurred before the availability of antibiotics, and all 3 patients died.
It is still unclear whether the clinical progression of anthrax during pregnancy is same as that in nonpregnant women. The changing body mechanisms of pregnancy may alter the course of the disease. During pregnancy, the total WBC count increases, and T cell levels, especially helper T cells, decrease [3]. Some of the literature suggests that pregnancy appears to be associated with diminished cell-mediated immunity, which could facilitate the immune tolerance of fetal allografts, as well as a variety of other functional impairments of immunity [4].
However, it is important to note that, when providing care for pregnant women with anthrax, there are 2 patients involved—mother and fetus. There is compelling evidence to indicate that infections during pregnancy may cause preterm delivery [5].
Two questions are raised: whether there is a difference in the course of anthrax disease during pregnancy and whether anthrax during pregnancy increases the risk of adverse pregnancy outcomes. The purpose of the present report is to review in detail the rarely seen anthrax infection during in pregnancy, its maternal and perinatal complications, and its management.
Case 1. A 33-year-old pregnant woman at 32 weeks of gestation was admitted to the hospital; she had flayed a dead cow 7 days earlier. The patient had a submandibular eschar with surrounding vesicles that oozed clear yellow fluid; extensive edema on the face, neck, and upper thorax that inhibited respiratory function; and fever (38°C). Obstetric examination confirmed that her pregnancy was normal, and she had no signs or obstetric findings of preterm delivery (uterine contraction and cervical dilatation) at admission. Her WBC count was 28,300 cells/mm3. Direct microscopic examination of vesicle fluid revealed large gram-positive bacilli. Penicillin G and prednisolone therapy was administered immediately, with the presumptive diagnosis of anthrax, and the isolated organism was later identified as B. anthracis. The signs and symptoms of anthrax, except local scarring, disappeared within 10 days of therapy, but the patient delivered a preterm baby on the thirteenth day of her hospital admission. The neonate did not have any evidence of congenital infection.
Case 2. A 29-year-old pregnant woman was hospitalized with a 4-day history of swelling of the right arm and a weeping lesion at the right elbow. The patient was febrile (38.5°C) and had a 2-cm open sore with surrounding erythema and induration that oozed serous fluid. An obstetric examination revealed a 33-week normal pregnancy, without any indications of preterm delivery. The patient's WBC count was 19,600 cells/mm3. Direct microscopic examination of vesicle fluid revealed large gram-positive bacilli, and the isolated organism was later identified as B. anthracis. The patient was treated with procaine penicillin for 7 days. On the day of discharge from the hospital, preterm delivery began that was not prevented with tocolytic therapy, and the patient was delivered of a 34-week preterm baby. The neonate did not have any evidence of congenital infection. B. anthracis was not seen on gram-stained smears and cultures from blood in either case.
Discussion. Anthrax is a disease that dates back to 500 BCE, when it occurred among farmers in Egypt and Mesopotamia. It was considered to be the fifth plague of Egypt. The disease was recorded in Europe in 1613, when an epidemic developed in southern Europe [6].
Infection of pregnant women by B. anthracis is very rare, with only 3 cases reported in the German literature [1]. These cases all occurred before the availability of antibiotics, and all 3 patients died. A case was reported from Iran in 1964, in which the patient developed a cutaneous lesion on her eyelid [2]. The patient was in her ninth month of pregnancy and went into labor within 48 h while in transit to the hospital after the appearance of the lesion. She died shortly after admission to the hospital, on the second day of her illness, from a massive edema of the head and neck that interfered with her breathing. Culture samples from her uterus and vagina were negative for B. anthracis. The neonate did not have any evidence of congenital infection and remained healthy for 3 months after birth.
Two points are important in the management of anthrax during pregnancy: the appropriate clinical management of anthrax and the prevention of adverse pregnancy outcomes, particularly preterm delivery. Like all infectious diseases, anthrax requires specialized knowledge with respect to its impact on a pregnant patient and on her offspring.
Recommendations for the use of drug therapy come from protocols used for nonpregnant patients. Our 2 patients were successfully treated with penicillin, as are nonpregnant patients. β-lactam antibiotics have proved to be the safest antimicrobial agents during pregnancy. Allergic reactions may occur, as they do in the general population, but no specific maternal or fetal adverse effects have been determined. Although second- and third-generation cephalosporins are rather safe during pregnancy (US Food and Drug Administration pregnancy risk category B), B. anthracis is resistant to these antibiotics in vitro, so they should not be used in the treatment of anthrax [7]. Additionally, clinicians must be aware of the increase in plasma volume during pregnancy, particularly during the third trimester, which leads to decreased antibiotic concentration in the blood, if they are used at the same doses as those for nonpregnant women.
Because of terrorist attacks in United States, the Committee on Obstetric Practice of the American College of Obstetricians and Gynecologists (ACOG) recently issued an opinion paper on the management of asymptomatic pregnant or lactating women who have been exposed to anthrax [8]. According to the ACOG committee, anthrax infection is caused by B. anthracis and has 3 clinical manifestations: cutaneous, inhalational, and gastrointestinal. Cutaneous infection is the most common presentation, with mortality rates of 20% among untreated persons and <1% among persons who receive antibiotic therapy. Inhalational anthrax is the most serious presentation: case-fatality estimates are extremely high, even with supportive care and appropriate antibiotic therapy. Gastrointestinal anthrax infection is relatively rare, with fatality estimates of 25%–60%. The effect of early antibiotic therapy on this form of infection is unknown.
The ACOG committee makes the following recommendations for the treatment of exposed asymptomatic pregnant and lactating women:
Prophylaxis should be limited to those who have been exposed to a confirmed environmental contamination or who are exposed to a high-risk source as determined by the local Department of Health.
Prophylaxis should be 500 mg of ciprofloxacin orally every 12 h for 60 days.
Women who are taking ciprofloxacin when they discover that they are pregnant should continue the course of antibiotics for the full 60 days. However, if the bacteria are penicillin sensitive, the patient should be switched to amoxicillin, 500 mg orally 3 times per day for 60 days.
If a woman is allergic to penicillin and ciprofloxacin, she should be treated with doxycycline. Penicillin desensitization should be considered if the organism proves to be sensitive. In such cases, the risks of anthrax would far outweigh the risks of doxycycline to the fetus.
The Working Group on Civilian Biodefense recently recommended that amoxicillin is a suitable alternative if there are contraindications to fluoroquinolones or doxycycline, such as pregnancy, lactation, age <18 years, or antibiotic intolerance [9]. These recommendations are keeping with ACOG committee suggestions.
Our treatment consisted of penicillin, which disagreed with ACOG and Working Group on Civilian Biodefense recommendations about initiating anthrax treatment with penicillin or fluoroquinolones. We believe that penicillin-resistant B. anthracis is the subject of bioterrorist attacks, and both committees' guidelines focused on biodefense against anthrax from bioterrorist attacks. We believe that naturally occurring anthrax is susceptible to penicillin, so it can be used instead of more fetotoxic drugs, such as fluoroquinolones, for the treatment of naturally occurring anthrax.
Our 2 cases resulted in preterm delivery. Among the numerous and diverse maternal characteristics associated with an increased risk for early birth, the importance of an infectious condition, whether viral or bacterial, was recognized as early as the 1940s [10]. There is an increasing body of evidence linking urinary tract infections [11], intrauterine infections [12], and vaginal microflora [13], including bacterial vaginosis [14], with an increased risk of spontaneous preterm birth. This infectious inflammatory response as a cause of preterm birth is particularly worrisome, because it leaves the neonate to struggle with not only the complications of prematurity, such as respiratory distress syndrome and intraventricular hemorrhage, but also the added risk for infection [15, 16].
Animal, in vitro, and human data all provide a consistent picture of how a bacterial infection may result in a spontaneous preterm birth [17–27]. Bacterial invasion of the choriodecidual space activates monocytes in both the decidua and the fetal membranes to produce a number of proinflammatory cytokines, including TNF-α, IL-1α, IL-1β, IL-6, IL-8, and granulocyte colony-stimulating factor [17–27]. Some combination of these cytokines stimulates prostaglandin synthesis and release and initiates a sequence of neutrophil chemotaxis, infiltration, and activation that culminates in the synthesis and release of a number of metalloproteases. The cytokines and prostaglandins stimulate contractions, and the proteases attack the chorioamniotic membranes, leading to rupture. Various proteases also remodel the cervical collagen, resulting in cervical ripening. Although the actual process is certainly more complicated than that described above, the clinical and experimental evidence provides a biologically plausible pathway leading from intrauterine infection to preterm labor and, ultimately, delivery. However, the relevance of these mechanisms in anthrax is unclear. Because anthrax bacteremia results in the death of the mother within hours, there will be no time for such mechanisms. However, the key elements (e.g., proinflammatory cytokines and prostaglandins) of this process can be produced locally, where the anthrax lesion is, and are secreted systematically, causing preterm labor.
The reports in literature and our 2 cases all describe the last trimester of pregnancy. There is a need for reports that describe the progression of anthrax during early pregnancy. Dutz et al. [28] reported a case of primary uterine anthrax by a necrotic endometrium with a massive hemorrhagic parametritis and the rupture of an ovary with massive ascites. The infection resulted from an attempt at abortion with a contaminated stick. Spontaneous abortion is reportedly associated with anthrax in livestock. However, the animal species in question are much more susceptible to anthrax than humans, and the animal uterus and placentation are different than those of humans.
Anthrax during pregnancy is rarely seen, so its management and maternal and perinatal complications are not entirely known. Our 2 cases showed that anthrax during pregnancy can be successfully managed, as it is in nonpregnant women. As was seen in our 2 cases, preterm delivery may be one of the major complications for perinatal outcome. The obstetrician must be aware the probability of this complication, even at the end of the anthrax therapy, and may want to provide early tocolysis in cases of anthrax during pregnancy.
- Received October 11, 2002.
- Accepted January 10, 2003.
- © 2003 by the Infectious Diseases Society of America
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