Abstract
Limited knowledge is available regarding tularemia in pregnancy. A total of seven tularemia cases in pregnant women have been published in the literature. This report presents three new cases. Two of these cases improved without any treatment. The third case was treated with gentamicin. All three pregnancies reached full term without complication for either mother or child.
Introduction
T
Cases
Case 1
A 23-year-old female in her fourth week of pregnancy presented with a 2-month history of high fever, chills, fatigue, and a swollen neck. On physical examination, a lymphadenopathy was detected in the right cervical area. Neck ultrasonography revealed a 38-×22-mm lymphadenopathy in the right cervical area surrounded by small reactive lymph nodes. The patient routinely consumed natural spring water, and mice populations were known to dwell around her residence. A serological test was performed for tularemia, and the microagglutination test was positive with a 1/320 titer. Gentamicin therapy was prescribed by our clinic, but was refused by the patient because she was in the first trimester of her pregnancy. On follow-up visits to our clinic, her lymphadenopathy regressed significantly, and her fever and fatigue improved. Delivery occurred without complications and the baby was healthy. The baby remained healthy during follow-up over a 1-year period.
Case 2
A 33-year-old female in her 22nd week of pregnancy presented with a 3-day history of high fever, sore throat, chills, fatigue, myalgia, arthralgia, and a swollen lymph node in the right submandibular area. On physical examination, a tender and red lymphadenopathy was found in the right submandibular area. Neck ultrasonography revealed a 48-×50-mm lymphadenopathy compatible with lymphadenitis. Her epidemiological history consisted of natural spring water consumption. Microagglutination testing for tularemia demonstrated a titer of 1/320. The patient refused antibiotic treatment for the tularemia. On her follow-up, the lymph node had suppurated spontaneously and all of her other symptoms, including fever, were improved. On her 9-month follow-up, there was only a lymphadenopathy measuring 10×15 mm. The baby was delivered without complication and remained healthy during the 1-year follow-up.
Case 3
A 22-year-old female in her 20th week of pregnancy presented with a 4-week history of fever, fatigue, myalgia, arthralgia, and chills. On physical examination, there were painful and mobile lymphadenopathies in the left cervical and occipital areas. Her neck ultrasonography revealed a 32-×19-mm lymphadenopathy compatible with lymphadenitis in the left upper cervical submandibular area. A few more lymphadenopathies were also detected around this lesion and in the occipital region. Among these, the biggest lymph node measured 25×11 mm. Her epidemiological history consisted of natural spring water consumption. The F. tularensis microagglutination test returned a titer of 1/320. Gentamicin was administered at 5 mg/kg for 10 days. One week after the therapy, the lymph node suppurated. On her follow-up, the lymph node regressed and her symptoms improved. The pregnancy continued without complication and the baby was healthy.
Before availability of antimicrobials.
Imported from the United States.
Patient refused to use antibiotics.
USA, United States of America; NA, not available; IFA, immunofluorescence assay; PCR, polymerase chain reaction; GM, gentamicin; CIP, ciprofloxacin; ELISA, enzyme-linked immunosorbent assay; Ig, immunoglobulin; PR, present report.
Discussion
Tularemia is a zoonosis occurring in the Northern Hemisphere. The predominant form seen in Turkey is oropharyngeal tularemia (Akalin et al. 2009, Penn 2010). Due to immune system suppression during pregnancy, infectious diseases during pregnancy may follow a more severe course. Limited information is available in the literature with respect to the effect of tularemia on the human fetus during pregnancy. In our search of the literature, we identified seven past cases of tularemia in pregnant patients (Bricker 1931, Dudley and Don 1936, Charles et al. 2008, Yeşilyurt et al. 2012). Five of these patients received antibiotic therapy, whereas the other two did not. One of the untreated cases resulted in an abortion and the second case resulted in a premature delivery (Bricker 1931, Dudley and Don 1936). Of the five cases that received treatment, one patient from France suffered from an ulceroglandular form of tularemia. This patient was given doxycycline and josamycin therapy, and the pregnancy continued without complication and ended with the delivery of a healthy baby (Charles et al. 2008). The remaining four cases receiving antibiotic treatment were from Turkey. These four patients were each treated with gentamicin [intramuscular (i.m.)] at 5 mg/kg per day for 10 days. Because no visible regression of the lesions was observed, or new lymph nodes appeared, gentamicin was discontinued and ciprofloxacin b.i.d. 500 mg was administered for 10–15 days (Yeşilyurt et al. 2012).
In the current case series, the first and the second patients were informed about their tularemia and the treatment options, but both of them refused treatment. The symptoms of the first case started 4 weeks before pregnancy. She presented to our clinic on the second month of her symptoms and in the first trimester of her pregnancy. Even though she refused the treatment, her lesions regressed during pregnancy. The second case was diagnosed at the end of her second trimester. Although she refused the treatment, no complications occurred. When the third case presented, the patient was in her 20th week of pregnancy and was given a 10-day gentamicin treatment.
When the cases in the literature were reviewed, it was thought that the abortion and preterm delivery might be due to tularemia. In our case series, no complications were detected during the pregnancies or with the babies when they were born and during follow-up. Because of that, serological investigation was not conducted for the babies. For pregnant tularemia patients, antibiotics have to be chosen carefully due to the teratogenic effects of some antibiotics on the fetus. Unfortunately, the choice of antibiotics for pregnant patients is very limited and there are no antibiotics in the B class. The US Food and Drug Administration (FDA) has not approved the use of gentamicin or ciprofloxacin for pregnant patients, but gentamicin is recommended in the guidelines as the first-line treatment (WHO Guidelines on Tularemia 2007, Health Protection Agency 2009). The World Health Organization (WHO) recommends ciprofloxacin and gentamicin for the treatment of these cases (WHO Guidelines on Tularemia 2007).
In conclusion, even though treatment was not given in two pregnant cases, with one of them in the first trimester, all three tularemia cases during pregnancy were followed without complication for either the mother or the child. The authors think that this might be due to the low virulence of the tularemia subspecies seen in Turkey.
Footnotes
Author Disclosure Statement
No competing financial interests exist.