Lack of Tularemia Among Health Care Providers With Close Contact With Infected Patients—A Case Series

Abstract

Francisella tularensis has a low infectious dose and can infect laboratory staff handling clinical specimens. The risk to health care providers exposed during patient care is poorly defined. We describe 9 examples of health care providers who did not develop tularemia after significant exposures to infected patients.

Francisella tularensis, a tier 1 bioterrorism select agent, can be transmitted to humans via inhalation, direct contact with infected animals, or arthropod bite and has a low infectious dose. Clinical manifestations of tularemia depend on the route of transmission and include respiratory, ulceroglandular, and oropharyngeal disease [1, 2]. Laboratory workers can become infected while handling specimens and most often develop respiratory tularemia after inhaling aerosolized bacteria [4, 5]. F. tularensis subspecies tularensis (type A) is limited to North America; subspecies holarctica (type B) occurs in North America and Eurasia and typically causes milder symptoms than type A [1, 3].

Health care providers (HCPs) can be exposed to F. tularensis during routine patient care or when performing aerosol-generating procedures such as bronchoscopy, intubation and extubation, or cardiopulmonary resuscitation [6]. Existing guidelines recommend that HCPs use standard precautions when caring for patients with tularemia; isolation of patients with tularemia or use of additional respiratory protection (eg, N95 mask) by HCPs is not recommended [2]. However, in some cases HCPs have been counseled to take doxycycline or ciprofloxacin for postexposure prophylaxis or perform fever watch as a precautionary measure after exposure to a patient with unrecognized tularemia at the time care was provided. These situations understandably spark concern among HCPs who have been exposed and the public health practitioners who advise them. There is minimal evidence on the actual risk to HCPs during exposure to an infected patient, appropriate personal protective equipment (PPE) use, and the proper course of action thereafter.

Human-to-human transmission of tularemia has been clearly documented only twice—from an infected organ donor to organ recipients and from a deceased patient to a medical examiner during autopsy [7, 8]. An unconfirmed report from 1924 also described a mother who pricked her thumb while tending to an ulcer on her son’s ear and subsequently developed glandular tularemia [9]. Curiously, human-to-human transmission from an infected, living person to others has not been reported in recent history. The reasons for this are unclear.

Characterizing the risk to close contacts of patients with tularemia would help inform recommendations for PPE use, postexposure prophylaxis, and bioterrorism preparedness. The objective of this investigation was to collect detailed information on exposures to F. tularensis in the health care setting and describe outcomes of HCPs who did not take antimicrobial prophylaxis after exposure.

METHODS

HCPs who cared for patients with tularemia were identified during public health investigations of US tularemia cases from 2017 to 2019. Nine HCPs who were considered to have substantial patient exposures were invited to complete a brief questionnaire; all agreed. Participating HCPs provided information on the nature of their exposure, PPE worn during the exposure, and any signs or symptoms of illness experienced during the 2 weeks after exposure. HCPs who elected to take antimicrobial prophylaxis following exposure were not invited to participate in this investigation.

This investigation was reviewed by the Centers for Disease Control and Prevention’s Human Subjects Research Advisors and determined to be nonresearch as a public health case series.

RESULTS

We interviewed 9 HCPs with exposure to F. tularensis in the clinical setting (Table 1). Six were male, 3 were female; age ranged from 29 to 60 years. Total duration of exposure ranged from 40 minutes to 5 hours.

Table 1.

Characteristics and Outcomes of Health Care Provider Exposures to Patients With Tularemia

HCP No.	Description of Infected Patient	F. tularensis Characterization	HCP Role	Preexisting Conditions	No. of Exposure Episodesa	Total Duration of Exposure, h:min	Nature of Exposure	Procedures Performed During Exposure	PPE Worn During Exposure	Postexposure Management	Postexposure Signs or Symptoms of Tularemia
1	Kidney transplant recipient from donor with unrecognized F. tularensis infection at time of death. Kidney recipient developed severe tularemia and septic shock, then recovered. F. tularensis was isolated from the patient’s blood, dialysate, and other clinical specimens.	F. tularensis subspecies tularensis (type A)	Resident physician: Anesthesiology	None	4	2:20	Provided anesthesia, patient transport	Endotracheal intubation, bronchoscopy	Facemask, gloves	None, unaware of exposure	None
2			Nurse practitioner: Transplant surgery	Exercise-induced asthma	1	0:40	Performed physical examination, patient transport	None	None	Fever watch	None
3			Physician: Transplant surgery	None	4	5:00	Performed renal transplant surgery and post-transplant examination of recipient	Preparation of donor organ, kidney transplantation	During surgery: Facemask, glasses, gown, gloves During examination: Gloves	Fever watch	None
4			Physician fellow: Infectious diseases	None	11	3:25	Performed physical examination (patient coughing during examination)	None	Gloves	Fever watch	None
5	Elderly patient with respiratory tularemia with productive cough, pleural effusions, and pulmonary nodule. F. tularensis was isolated from pulmonary nodule. Developed respiratory failure and died.	F. tularensis subspecies tularensis (type A)b	Registered nurse: Surgery	None	1	1:15	Transferred patient from stretcher to operating table, circulated in operating room	None	Facemask, gloves	None, unaware of exposure	None
6			Physician: Thoracic surgery	Eczema	1	1:00	Performed thoracic surgery	Bronchoscopy, mediastinoscopy	Facemask, gown, gloves	Fever watch	None
7			Physician: Pulmonology & intensive care	None	2	0:25	Performed endotracheal intubation and directed cardiopulmonary resuscitation from foot of bed	Endotracheal intubation	During endotracheal intubation: Facemask, gloves During cardiopulmonary resuscitation: None	Fever watch	None
8	Patient underwent second total knee replacement due to persistent swelling. F. tularensis was isolated from joint fluid collected during surgery.	F. tularensis subspecies holarctica (type B)	Physician: Anesthesiology	None	1	1:33	Provided anesthesia	Endotracheal intubation	Facemask, gloves	Fever watch	None
9			Physician: Anesthesiology	None	1	3:15	Provided anesthesia, performed physical examination	Endotracheal intubation	Facemask, glasses, gloves	Fever watch	None

Abbreviations: HCP, health care provider; PPE, personal protective equipment.

^aExposure episode = present within 3 feet of patient with tularemia or infected organ.

bSubspecies was inferred by location, as only subspecies tularensis is endemic to the area where the patient was infected.

Exposed HCPs 1–4 cared for a patient who received a kidney transplant from a donor with unrecognized F. tularensis infection at the time of death. After transplant, the kidney recipient developed fulminant tularemia, respiratory failure, and septic shock but eventually recovered. F. tularensis was isolated from the donor spleen and recipient blood, dialysate, peritoneal dialysis catheter tip, and biliary fluid [7]. Exposed HCPs 5–7 were exposed to a patient with respiratory tularemia who had a productive cough, pleural effusions, and a pulmonary nodule. The patient underwent bronchoscopy with bronchoalveolar lavage and biopsies of hilar lymph nodes and the pulmonary nodule; F. tularensis was isolated from the pulmonary nodule sample. The patient developed respiratory failure and died despite intubation and attempted cardiopulmonary resuscitation. Exposed HCPs 8 and 9 cared for a patient with persistent swelling after previous knee replacement who underwent repeat total knee replacement surgery. The procedure involved bone sawing and drilling to remove the existing joint; cavitary bone loss was noted in the central femur. F. tularensis was isolated from joint fluid collected during surgery. For all of the patients involved in this investigation, F. tularensis infection was unrecognized for the majority of the time that care was provided.

There were no known breaches in infection prevention protocols during surgical procedures. However, some HCPs did not wear masks during interaction with the patients, including a physician who examined the kidney transplant recipient during coughing episodes and a physician who directed cardiopulmonary resuscitation of the patient with respiratory tularemia. None of the HCPs developed signs or symptoms of tularemia within 2 weeks of the exposures.

DISCUSSION

In this descriptive series, we demonstrate no occurrence of tularemia among HCPs who had substantial exposures to F. tularensis–infected patients and organs. Exposures included aerosol-generating procedures such as bronchoscopy, intubation, and bone sawing during replacement of an infected joint. Although F. tularensis transmission from patients to HCPs is theoretically possible, the risk appears to be low. This information can be used by infection control practitioners, HCPs, and public health practitioners when counseling persons after exposure to patients with tularemia and for planning bioterrorism response.

There are several caveats to interpretation of these findings. All of the HCPs interviewed were relatively healthy, aged 60 years or younger, and not pregnant, which limits interpretability. HCPs with immune compromise, other medical conditions, or pregnancy may be at greater risk for contracting F. tularensis from infected patients. Furthermore, although we describe in this series a variety of exposures, we did not capture all potential exposure mechanisms. Procedures such as nebulized medication administration or bone sawing during autopsy could generate more aerosols and potentially create higher risk for HCPs [6]. Lastly, as HCPs did not undergo serologic testing, we cannot rule out transmission of F. tularensis to HCPs that led to subclinical infection.

Based on the available data, the current recommendation for HCPs to use standard precautions when caring for patients with tularemia is still appropriate [2]. Patients with pulmonary tularemia do not need to be placed on droplet or airborne precautions, nor do they need to be placed in an airborne isolation room. In cases of unintended PPE breach or heightened concern after exposure to a patient with tularemia, HCPs may choose to perform fever watch or take antimicrobial prophylaxis in consultation with an infectious diseases physician. Currently there is no solid evidence, however, to suggest that antimicrobial prophylaxis after exposure to a patient with tularemia is necessary.

Additional surveillance and research on potential human-to-human transmission of F. tularensis could help further our understanding of the risk to HCPs and first responders caring for infected patients in the aftermath of a bioterrorism attack.

Acknowledgments

We wish to thank the HCPs who participated in the questionnaire and the hospital and public health staff who assisted with tularemia case investigations. We also thank Tracy Woodall and Jennifer House from the Colorado Department of Public Health and Environment for providing tularemia case information; Amy Schwartz and Grace Marx from the Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, for assistance with case follow-up; and Clifford McDonald and David Kuhar from the Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, for supporting development of the HCP questionnaire.

Financial support. No external funding sources were used for this work.

Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).

Potential conflicts of interest. All authors: no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.