Treatment of Tularemia in Pregnant Woman, France

Charlotte Dentan, Patricia Pavese, Isabelle Pelloux, Sandrine Boisset, Jean-Paul Brion, Jean-Paul Stahl, and Max Maurin

Author affiliations: Centre Hospitalier Universitaire de Grenoble, Grenoble, France (C. Dentan, P. Pavese, I. Pelloux, S. Boisset, J.-P. Brion, J.-P. Stahl, M. Maurin); Université Joseph Fourier–Grenoble 1, Grenoble (S. Boisset, J.-P. Stahl, M. Maurin)

Abstract

A pregnant woman who had oropharyngeal tularemia underwent treatment with azithromycin and lymph node resection and recovered without obstetrical complication or infection in the child. Azithromycin represents a first-line treatment option for tularemia during pregnancy in regions where the infecting strains of Francisella tularensis have no natural resistance to macrolides.

Tularemia is a bacterial zoonotic disease caused by a gram-negative coccobacillus, Francisella tularensis; the most virulent subspecies, tularensis (type A), is found in North America, but subspecies holarctica (type B) occurs throughout the Northern Hemisphere (1–4). In France, human cases are most often sporadic and occur predominantly in the eastern, southeastern, and western parts of the country (1).
F. tularensis has several animal reservoirs, including rodents and lagomorphs (hares and rabbits). Domestic animals may be infected with F. tularensis through contact with the wildlife fauna and, occasionally, transmit the disease to humans. Human contamination occurs following direct contact with infected animals, through contaminated environments or arthropod bites (2).We describe the diagnosis and treatment of tularemia in a pregnant woman in France.

The Case

In late February 2006, a 27-year-old pregnant woman, at 6 weeks’ gestation, was referred to Grenoble University Hospital, Grenoble, France, for investigation of persistent left cervical lymphadenopathy with fever. She had no history of severe infection or underlying illness. The patient lived in a farm in the French Alps. The lymphadenopathy occurred 3 weeks earlier, along with a sore throat, and persisted despite 10 days’ treatment with amoxicillin (3 g daily).
At admission, the patient was febrile (38°C) and had a tender, swollen, submaxillary cervical lymph node on the left side. Examination of the oral cavity showed no abnormalities. Magnetic resonance imaging of the left cervical region showed a large mass extending from the parotid region to the submandibular region, with hypo- and hypersignals in T1- and T2-weighted imaging, respectively.
Lymph node tissue was obtained by needle aspiration, and examination revealed nonspecific lesions of lymphadenitis. Laboratory test results showed moderate inflammatory syndrome (C-reactive protein 67 mg/L). Serologic results were negative for HIV, hepatitis B and C viruses, rubella virus, Treponema pallidum (syphilis), Coxiella burnetii (Q fever), and Borrelia, Bartonella, Brucella, and Legionella spp. and showed only residual IgG-type antibodies against cytomegalovirus, Epstein-Barr virus, herpes simplex virus, parvovirus, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
Because we suspected severe Streptococcus pyogenes infection, a second course of amoxicillin was administered for 13 additional days. After initial clinical improvement, the patient relapsed, and the lymphadenopathy evolved to suppuration and necrosis. In March 2006, a large amount of pus was surgically drained from the site, and inflamed lymph nodes were removed. These unusual clinical features led us to suspect tularemia.
The patient denied receiving any tick bite but reported that she regularly fed domestic rabbits in cages. Her symptoms began a few days after she killed and skinned rabbits, which were then kept frozen but not eaten by the family.
Examination of the removed lymph node samples confirmed the presence of nonspecific lymphadenitis. Routine cultures and mycobacterial cultures remained sterile, but F. tularensis DNA was detected in lymph node samples by using specific real-time PCR targeting the gene encoding a 23-kDa surface protein (5). PCR amplification and sequencing of the 16S rDNA–23S rDNA intergenic spacer region (5) directly from lymph node tissue confirmed the presence of DNA from F. tularensis subsp. holarctica. Serum samples collected in late February and on March 15, 2006, were tested by using an immunofluorescence assay and a homemade F. tularensis antigen (5). Both samples were positive, with IgM and IgG titers of 320 (cutoff titers of >160).
Because the patient was pregnant and tularemia in France has been caused only by biovar 1 strains of F. tularensis subsp. holarctica (2), which are naturally susceptible to macrolides, she was treated with azithromycin (500 mg/d for 6 weeks). She recovered, with no complications for herself or her baby.
The patient reported that the rabbits were reared outdoors, in floor-level, wire-mesh cages; therefore, we suspected the animals were infected with F. tularensis through contact with wild fauna. Attempts to detect F. tularensis in pieces of the frozen rabbits by culture and PCR tests were unsuccessful. All family members of the patient also tested negative for F. tularensis.