PC2123: Tularemia During Pregnancy and the Neonatal Period: A Systematic Literature Review

Background: Tularemia, caused by the gram-negative bacterium Francisella tularensis, is endemic throughout the Northern Hemisphere where outbreaks continue to occur. Tularemia can be transmitted to humans via tick or other arthropod bite, direct contact with infected animals, and ingestion or inhalation of infectious particles. Clinical manifestations can include fever, skin ulcer, lymphadenopathy, pharyngitis, or pneumonia. Globally, rural and impoverished populations are at particular risk for contracting tularemia due to farming, hunting, consumption of game meat, and use of drinking water from wells and other local sources. Aminoglycosides, fluoroquinolones, and doxycycline are used to treat tularemia. Data on tularemia during pregnancy are lacking but could inform best practices for clinical care. We performed a systematic review of tularemia during pregnancy to characterize clinical manifestations and describe maternal, fetal, and neonatal outcomes associated with antimicrobial treatment.

Methods: We searched nine literature databases using terms related to tularemia and pregnancy. Articles reporting cases of tularemia with at least one maternal or fetal outcome were included. We abstracted data on the clinical features of tularemia; antimicrobial treatment; maternal, fetal, and neonatal morbidity and mortality; and placental findings.

Results: Our search identified 4,181 articles, of which 25 articles describing 47 cases of tularemia in pregnant patients were eligible for inclusion. Cases occurred between 1930 and 2021, with 55% reported after 2000. Cases were reported from eight countries; the majority were from Turkey (n=20, 43%), the United States (n=18, 38%), France (n=3, 6%), and Kosovo (n=2, 4%). Among cases with clinical data available, oropharyngeal tularemia was the most common clinical form reported (n=13/22, 59%). Twenty-four (51%) mothers were treated with antimicrobials; 19 received at least one antimicrobial effective against F. tularensis. Four intrauterine fetal deaths (IUFD) occurred, three in untreated pregnancies and one in which the mother received an antimicrobial not considered effective for tularemia. For one IUFD, there was evidence of possible maternal-fetal transmission of F. tularensis on fetal autopsy, with gram-negative coccobacilli consistent with F. tularensis identified in placental villi and macrophages in the spleen. Among 34 reported live births, two births were preterm and one case of hydranencephaly was identified. The mothers of these three infants were not treated with antimicrobials. No maternal or neonatal deaths were reported.

Conclusion: IUFD and preterm birth have been documented in untreated pregnancies with tularemia. However, further research is needed to establish whether these outcomes were attributable to the infection. Possible evidence of F. tularensis in placental and fetal tissues might suggest that tularemia is transmissible from mother to fetus. Prompt recognition and treatment of tularemia during pregnancy is critical to minimize risk for adverse outcomes.