Abstract

Background. After a case of rabies, healthcare workers (HCWs) had fear of contagion from the infected patient. Although transmission of rabies to HCWs has never been documented, high-risk exposures theoretically include direct contact of broken skin and/or mucosa with saliva, tears, oropharyngeal secretions, cerebrospinal fluid, and neural tissue. Urine/kidney exposure posed a concern, as our patient's renal transplant was identified as the infection source.

Methods. Our risk assessment included (1) identification of exposed HCWs; (2) notification of HCWs; (3) risk assessment using a tool from the local health department; (4) supplemental screening for urine/kidney exposure; and (5) postexposure prophylaxis (PEP) when indicated.

Results. A total of 222 HCWs including diverse hospital staff and medical trainees from university affiliates were evaluated. Risk screening was initiated within 2 hours of rabies confirmation, and 95% of HCWs were assessed within the first 8 days. There were 8 high-risk exposures related to broken skin contact or mucosal splash with the patient's secretions, and 1 person without high-risk contact sought and received PEP outside our hospital. Nine HCWs (4%) received PEP with good tolerance. Due to fear of rabies transmission, additional HCWs without direct patient contact required counseling. There have been no secondary cases after our sentinel rabies patient.

Conclusions. Rabies exposure represents a major concern for HCWs and requires rapid, comprehensive risk screening and counseling of staff and timely PEP. Given the lack of human-to-human rabies transmission from our own experience and the literature, a conservative approach seems appropriate for providing PEP to HCWs.

Rabies is extremely rare in the United States, with an estimated rate of 1–5 cases per year, and virtually always leads to fatal human infection [1]. A renal transplant recipient who was hospitalized for 23 days on our medical and intensive care units had antemortem serum and tissue results that were suspicious for rabies; this was confirmed from postmortem brain examination [2]. An extensive investigation led to the subsequent discovery that the transplant donor was the source of our sentinel patient's rabies infection and allowed for successful rabies prophylaxis for the remaining 3 transplant recipients [2].

On the basis of a 1912 report, the risk of animal-to-human transmission has been estimated at 0.1% from open wound or mucous membrane contact with saliva from rabid wolves, dogs, or cats in persons who did not receive any preventive measures [3]. Fomite transmission of rabies has not been reported [4]. Unusual nonbite transmission routes leading to human infections from rabies have included contamination of mucous membranes, aerosol exposure from spelunking or laboratory activities, transplanted organs, and improperly inactivated vaccines [5, 6]. There has been no documented human-to-human transmission of rabies, and only a single anecdotal report of transmission from a child to his mother in Ethiopia [7].

Transmission of rabies has been documented in cases of organ and/or tissue transplant [8]. Similar to our case, there have been 2 other reports of rabies transmission to multiple solid organ transplant recipients from single undiagnosed donors in the United States [9] and Germany [10]. However, there has been no reported transmission to healthcare workers (HCWs) during their care of patients with rabies [11]. Theoretically, high-risk exposures to HCWs include broken skin and/or mucosal contact with saliva, tears, respiratory secretions, cerebrospinal fluid, and neural tissue from a patient with rabies [12–14]. We describe our risk assessment and postexposure prophylaxis (PEP) for HCWs, and provide a comprehensive review of the literature, after a sentinel case of rabies was diagnosed at our teaching hospital.

METHODS

Plans for our risk assessment were developed in collaboration with the Maryland Department of Health and Mental Hygiene (MDHMH) and the Centers for Disease Control and Prevention (CDC) after confirmation of rabies in our patient and the discovery of the renal transplant as the source of his infection. Our assessment program included 5 steps: (1) identification of potentially exposed HCWs; (2) prompt notification of these HCWs; (3) risk assessment by staff from infection control, infectious diseases, or occupational health using an instrument provided by the MDHMH (Supplementary Data 1); (4) supplemental assessment for urine and/or kidney tissue exposure (Supplementary Data 2) before CDC guidance was given; and (5) PEP given by occupational health when indicated.

The period of potential transmission was 14 days prior to our patient's onset of symptoms to the time of his death. We used our electronic medical record to identify HCWs from different services who documented care for our sentinel patient during his outpatient visits and hospitalization on the medical ward and medical intensive care unit. During his hospitalization, the patient was on standard precautions. Staff from dietary service, facility management, and pharmacy working in these clinical areas were also considered for potential exposure. We also used information during our screening interviews to identify additional HCWs on work teams who were not documented in our electronic medical record.

Immediately after confirmation of rabies in our sentinel patient on a Friday afternoon, all hospital department chiefs were advised to notify their employees to report for risk assessments. As our teaching hospital is also staffed by trainees from 4 affiliated universities, the 4 academic program directors were advised to send all trainees who may have been exposed to our patient during their rotations at our medical center to our rabies risk screening clinic. Our rabies risk screening clinic was promptly organized and began to interview staff within 2 hours of rabies confirmation on Friday afternoon. This risk screening clinic was staffed by 4 infection control nurses and 2 infectious diseases senior staff physicians to interview and counsel exposed HCWs. Using the risk assessment instrument provided by the MDHMH (Supplementary Data 1), specific high-risk rabies exposures included direct contact with our patient's saliva, respiratory secretions, tears, cerebrospinal fluid, or laboratory specimens without personal protective equipment. Our rabies screening clinic was held for 8 consecutive days from 7 am to 5 pm to accommodate all work tours. Remaining HCWs who did not come to the screening clinic during these first 8 days were contacted in person or by telephone for risk assessment by infectious diseases staff physicians.

When information emerged that the source of our sentinel patient's rabies was his renal transplant [2], urine and kidney tissue exposures posed additional concerns, as both urine [15] and kidney [9] have been known to harbor rabies antigen and virus. We identified HCWs at potential risk to be from the nursing, laboratory, interventional radiology, and nephrology services. Prior to receiving official guidance from the CDC regarding the transmission risk from urine and kidney tissue, we developed our own risk assessment instrument and implemented supplemental screening for urine and/or kidney tissue exposure (Supplementary Data 2).

Persons identified as having high-risk exposure(s) or concerns for transmission risks were referred to the occupational health clinic. Specific risks were readdressed with these HCWs. PEP was recommended to those with high-risk exposures and given at this medical center using rabies immune globulin and rabies vaccine on day 0, and further doses of rabies vaccine on days 3, 7, and 14 for persons not previously vaccinated and days 0 and 3 for persons previously vaccinated [16]. PEP was not recommended to those who were not at high risk. Additional extensive counseling was provided to HCWs who had fear of rabies transmission.

A literature review for 1978 through 2013 was conducted on PubMed using the terms “rabies” and “healthcare workers” or “hospital” or “prophylaxis” or “postexposure prophylaxis.” Additional searches for and verification of rabies cases were made using the CDC human rabies surveillance website at http://www.cdc.gov/rabies/location/usa/surveillance/human_rabies.html.

RESULTS

Our medical center is a tertiary care teaching hospital with trainees from 4 local universities in the greater metropolitan area of Washington, District of Columbia. These trainees from our 4 academic affiliates include third- and fourth-year medical students, interns, residents, and subspecialty fellows. Our own hospital staff includes approximately 2200 persons; there are an estimated 250 trainees. During his 4-day stay on the medical ward and 20-day stay in the medical intensive care unit, our patient had interactions with many HCWs from diverse services throughout the hospital.

As shown in Table 1, 222 persons provided care to our sentinel patient with confirmed rabies, and thus were potentially exposed to rabies. Of these, 167 HCWs were identified via documentation in the electronic medical record and 55 through discussions during screening interviews. All 222 underwent risk assessment using the MDHMH instrument. Of 113 persons with potential exposure to the patient's urine and/or kidney tissue, 95 reported such an exposure and had supplemental screening for these exposures, although rabies was not subsequently detected in our patient's transplanted kidney or his urine.

Table 1.

Number of Risk Assessments, Supplemental Urine/Kidney Exposure Risk, and Postexposure Prophylaxis for Healthcare Workers, by Hospital Department

Hospital Department Risk Assessment Urine/Kidney Risk PEP Given 
Chaplain 
Dietary 
Emergency department (total) 
 Administrator   
 Health technician   
 Physicians  
Facility management 
Laboratory (total) 
 Technologists  
 Pathologist  
 Pathology residents  
Medical (total) 55 
 Staff physicians 19  
 Subspecialty fellows  
 Residents 19  
 Medical students  
Neurology (total) 15 
 EEG technician   
 Staff physicians  
 Residents  3a 
 Medical students  1b 
Nursing (total) 91 75 
 Emergency department  
 Outpatient clinics 12  
 Medical ward 62 52  
 Intensive care unit 12 
Pharmacy 
Radiology (total) 15 
 Technicians 13  
 Interventional radiology nurse  
 Interventional radiologist  
Respiratory therapy 10 
Social work 
Surgery (total) 
 Physician's assistant   
 Surgeons   
 Surgical resident   
Total 222 95 
Hospital Department Risk Assessment Urine/Kidney Risk PEP Given 
Chaplain 
Dietary 
Emergency department (total) 
 Administrator   
 Health technician   
 Physicians  
Facility management 
Laboratory (total) 
 Technologists  
 Pathologist  
 Pathology residents  
Medical (total) 55 
 Staff physicians 19  
 Subspecialty fellows  
 Residents 19  
 Medical students  
Neurology (total) 15 
 EEG technician   
 Staff physicians  
 Residents  3a 
 Medical students  1b 
Nursing (total) 91 75 
 Emergency department  
 Outpatient clinics 12  
 Medical ward 62 52  
 Intensive care unit 12 
Pharmacy 
Radiology (total) 15 
 Technicians 13  
 Interventional radiology nurse  
 Interventional radiologist  
Respiratory therapy 10 
Social work 
Surgery (total) 
 Physician's assistant   
 Surgeons   
 Surgical resident   
Total 222 95 

Specific numbers of staff members are given in the indented sections under department headings.

Abbreviations: EEG, electroencephalography; PEP, postexposure prophylaxis.

a One trainee sought and received PEP outside our hospital despite no reported high-risk exposure.

b One trainee with high-risk exposure received his PEP outside of our medical center as he traveled outside our area.

Screenings were conducted in person at our medical center by 4 infection control nurses, 2 infectious diseases section staff physicians, and an occupational health staff physician, who addressed all questions and concerns about personal acquisition of rabies from anxious HCWs. For HCWs not at the medical center, telephone interviews using the MDHMH instrument with extensive counseling were conducted by the 2 infectious diseases section staff physicians. Every HCW with high-risk exposure or the potential need for PEP was discussed between a senior infectious diseases physician and the occupational health physician before the final treatment decision. Additional help in screening was provided by outside physicians administering the MDHMH risk assessment instrument for 3 medical students outside our hospital. Table 2 outlines the staff roles and time expenditure in screening, counseling, PEP administration, and coordination with local health departments and CDC, including the education and counseling provided to HCWs during their interviews. A total of 346 person-hours was expended for our efforts in risk assessment, PEP provision, and education, nearly the equivalent of 9 staff members working a 40-hour week.

Table 2.

Summary of Staff Time for Risk Assessment After a Sentinel Case of Rabies

Service Staff Time, h Role 
Infection control 4 nurses 183 Identification of staff at risk 
   Notification of service chiefs 
   Notification of healthcare workers 
   Perform risk assessments 
   Participate in rabies teleconferences 
Infectious diseases 3 physicians 106.25 Coordinate risk assessment efforts 
   Perform risk assessments 
   Counsel healthcare workers 
   Participate in rabies teleconferences 
Occupational health 1 physician 21.25 Counsel healthcare workers 
 3 nurses 35.5 Discuss prophylaxis 
   Approve prophylaxis 
   Administer prophylaxis 
   Maintain records and documentation 
   Participate in rabies teleconferences 
Total 11 staff 346  
Service Staff Time, h Role 
Infection control 4 nurses 183 Identification of staff at risk 
   Notification of service chiefs 
   Notification of healthcare workers 
   Perform risk assessments 
   Participate in rabies teleconferences 
Infectious diseases 3 physicians 106.25 Coordinate risk assessment efforts 
   Perform risk assessments 
   Counsel healthcare workers 
   Participate in rabies teleconferences 
Occupational health 1 physician 21.25 Counsel healthcare workers 
 3 nurses 35.5 Discuss prophylaxis 
   Approve prophylaxis 
   Administer prophylaxis 
   Maintain records and documentation 
   Participate in rabies teleconferences 
Total 11 staff 346  

As seen in Figure 1, the time course of our screening program allowed for the prompt evaluation of HCWs, as a screening clinic was set up on Friday afternoon, within 2 hours of rabies confirmation. Our response resulted in assessment and PEP of 65% of HCWs within the first 3 days and 95% within the first 8 days. Screening was completed 32 days after rabies confirmation, when a trainee notified us of his exposure.

Figure 1.

Time to completion of rabies risk screening for all exposed healthcare workers.

Figure 1.

Time to completion of rabies risk screening for all exposed healthcare workers.

As shown in Table 1, 9 persons received PEP, of whom 8 were considered high risk and 1 not high risk. No HCWs sustained any bites from our patient. The specific high-risk exposures included broken skin contact with patient's respiratory secretions or tears by 2 neurology trainees during their examinations; handling soiled instruments by 1 nurse with chapped hands; mucosal splashes during examination by 1 staff physician and 1 medical student; and mucosal splashes during intubation or suctioning by 3 medical residents. None of the 95 HCWs who received supplemental screening for urine and/or kidney tissue exposure reported any direct contact with the patient's samples. Seven HCWs with high-risk exposure received PEP at this medical center; another person with high-risk exposure was given PEP at another hospital, where he was stationed for an elective outside of our area. An additional person did not recall a specific high-risk exposure, but sought and received PEP outside of our hospital. Eight HCWs who were previously unvaccinated had PEP using rabies immune globulin and the 4-dose vaccine series, whereas 1 HCW who had prior vaccination required the 2-dose vaccine series. All persons reported good tolerance of PEP with none of the adverse reactions described previously with other vaccine preparations [17, 18]. There have been no secondary cases or reports of adverse effects from PEP to date, now >21 months after our sentinel patient's presentation, which is the same amount of time as our patient presented after receiving his undiagnosed infected renal transplant.

Table 3 provides a review of available information for general and HCW risk assessment and provision of PEP from the literature of rabies cases from 1978 to 2013, both in the transplant [19–27] and nontransplant [28–60; Supplementary References 61–81] settings. For nontransplant settings, if the source was known, most exposures were related to animal bite or contact, both in the United States and abroad. Data on persons assessed and given PEP were sometimes combined for the personal contacts and HCWs in the transplant [19, 25] and nontransplant [41] settings. However, numbers of total exposed persons or total HCWs assessed and given PEP were often not stated. Several reports documented that PEP was given to persons with high risk and to those with no high risk reported, in both the transplant [27] and nontransplant [29, 32, 37, 41; Supplementary References 72, 73, 76–78] settings.

Table 3.

Literature Review for Postexposure Prophylaxis and Healthcare Worker Exposure After Human Rabies

Referencea Year of Illness Location of Illnessb Exposure Time of Diagnosis PEP Given/All Assessed PEP Given/HCWs Assessed 
Transplant exposure      
 [191978 US (ID) Cornea Postmortem 93/unknown  
 [20     71/161 (44%) 
 [211979 France Cornea Postmortem Unknown Unknown 
 [221981 Thailand 2 cornea Postmortem Unknown Unknown 
 [231987 India 1 cornea Postmortem  1/1 (100%) 
1 cornea Antemortem 
 [241994 Iran 2 corneas Antemortem  15/15 (100%) 
 [25, 262004 US (AL, AK, OR, TX) Kidneys + liver Postmortem 174/917 (19%) Unknown 
 [272005 Germany Cornea, lung, kidney, liver, pancreas Antemortem  128/176 (73%) 
 Our case 2013 US (DC) Kidney Antemortem Unknown 9/222 (4%) 
Nontransplant exposure      
 [281981 US (OK) Unknown Postmortem 102/unknown 98/unknown 
 [291981 US (AZ) Dog in Mexico Antemortem 41/unknown 32/unknown 
 [301983 US (MA) Dog in Nigeria Antemortem 28/132 (21%) 26/unknown 
 [311983 US (MI) Possible bat Antemortem  54/254 (21%) 
 [32     47/209 (20%) 
 [331984 US (TX) Unknown Antemortem 142/unknown 123/unknown 
 [341984 US (PA) Unknown Antemortem Unknown Unknown 
 [351984 US (CA) Dog in Guatemala Postmortem 179/unknown  
 [361985 US (TX) Unknown Postmortem  85/140 (61%) 
 [371987 US (CA) Unknown Postmortem 87/unknown 75/177 (42%) 
 [381989 US (OR) Unknown Postmortem 9/unknown 2/unknown 
 [391990 US (TX) Bat Postmortem 67/100 (67%)  
 [401992 US (CA) Dog in India Antemortem 17/unknown 14/unknown 
 [411992 France Possible dog in Algeria Antemortem 143/unknown unknown 
 [421993 US (NY) Unknown Postmortem 55/unknown 40/unknown 
 [431993 US (TX) Unknown Postmortem 58/unknown 55/110 (50%) 
US (CA) Dog in Mexico Antemortem 25/unknown 20/unknown 
 [441994 US (CA) Unknown Postmortem 26/unknown 25/unknown 
 [451994 US (FL) Unknown Postmortem Unknown 16/unknown 
 [461994 US (AL) Bat Postmortem 99/unknown 87/unknown 
  US (TN) Unknown Antemortem 47/unknown 35/unknown 
  US (TX) Dog Antemortem 54/unknown 38/unknown 
 [471994 US (WV) Bat Antemortem 48/unknown 37/unknown 
 [481995 US (WA) Bat Antemortem 72/unknown 16/unknown 
 [491995 US (CT) Bat Antemortem 83/unknown 46/unknown 
 [501995 US (CA) Bat Antemortem 12/unknown 1/unknown 
  US (CA) Unknown Postmortem 76/unknown 72/unknown 
 [511996 US (FL) Dog Antemortem Unknown 4/unknown 
 [521996 US (NH) Dog in Nepal Antemortem Unknown 1/unknown 
 [531996 US (KY) Possible bat Antemortem 87/unknown 82/unknown 
 1996 US (MT) Possible bat Antemortem 26/unknown 23/unknown 
 [541997 US (MT) Bat Postmortem 60/unknown 58/unknown 
 1997 US (WA) Unknown Postmortem 55/unknown 54/unknown 
 [551997 US (TX) Bat Antemortem 46/unknown 42/unknown 
 1997 US (NJ) Bat Antemortem 50/unknown 42/unknown 
 [561998 US (VA) Unknown Antemortem 48/unknown 16/unknown 
 [572000 US (CA) Bat Antemortem 37/unknown 33/unknown 
  US (GA) Bats Postmortem 71/unknown 70/unknown 
  US (MN) Bat Postmortem 20/unknown 20/unknown 
  US (NY) Dog in Ghana Antemortem 24/unknown 23/unknown 
  US (WI) Bats Postmortem 27/unknown 18/unknown 
 [582002 US (CA) Bat Antemortem 46/unknown 28/unknown 
 [592002 US (IA) Unknown Antemortem 124/unknown 71/unknown 
 [602003 US (VA) Raccoon Postmortem 8/298 (2.6%) 3/173 (2%) 
 [61] 2003 US (CA) Bat Antemortem 6/44 (14%) 2/40 (5%) 
 [62] 2004 US (WI) Bat Antemortem 37/95 (39%) 5/35 (14%) 
 [63] 2005 US (MS) Bat Postmortem 55/unknown 32/79 (41%) 
 [64] 2006 US (TX) Bat Antemortem Unknown Unknown 
 [65] 2006 US (IN) Bat Antemortem 66/unknown 28/unknown 
 2006 US (CA) Possible dog in Philippines Antemortem 24/64 (38%) 11/51(22%) 
 [66] 2007 Canada (Alberta) Bat Antemortem 19/unknown 16/unknown 
 [67] 2007 US (MN) Bat Antemortem 54/538 (10%) 51/524 (10%) 
 [182008 French Guiana Unknown Postmortem 90/160 (56%) 48/100 (48%) 
 [68] 2008 US (CA) Dog not in US Postmortem 20/29 (69%) 4/9 (44%) 
 [69] 2008 US (MO) No Antemortem 5/unknown 1/40 2.5%) 
 [70] 2009 US (TX) Bat Antemortem 1/unknown 0 (0%) 
 [71] 2009 US (KY+IN) Possible bat Antemortem 18/159 (11%) 14/147 (10%) 
 [72] 2009 US (MI) Bat Antemortem 18/194 (9%) 6/180 (3%) 
 [73] 2009 US (VA) Dog in India Antemortem 32/174 (18%) 24/70 (34%) 
 [74] 2010 US (LA) Bat in Mexico Antemortem 95/204 (47%) 68/unknown 
 [75] 2010 US (WI) Bats Antemortem 7/unknown 5/178 (2.8%) 
 [76] 2011 US (NJ) Dog in Haiti Antemortem 14/unknown 10/246 (4%) 
 [77] 2011 US (CA) Cats Antemortem 27/208 (13%) 17/unknown 
 [78] 2011 US (NY) Dog in Afghanistan Antemortem 29/240 (12%) 9/unknown 
 [79] 2011 Italy Dog in India Antemortem 1/unknown 0/unknown 
 [80] 2011 US (SC) Bats Antemortem 22/188 (12%) 18/unknown 
 [81] 2012 UAE
Switzerland 
Bat in US (CA) Antemortem 23/59 (39%) 15/36 (42%) 
Referencea Year of Illness Location of Illnessb Exposure Time of Diagnosis PEP Given/All Assessed PEP Given/HCWs Assessed 
Transplant exposure      
 [191978 US (ID) Cornea Postmortem 93/unknown  
 [20     71/161 (44%) 
 [211979 France Cornea Postmortem Unknown Unknown 
 [221981 Thailand 2 cornea Postmortem Unknown Unknown 
 [231987 India 1 cornea Postmortem  1/1 (100%) 
1 cornea Antemortem 
 [241994 Iran 2 corneas Antemortem  15/15 (100%) 
 [25, 262004 US (AL, AK, OR, TX) Kidneys + liver Postmortem 174/917 (19%) Unknown 
 [272005 Germany Cornea, lung, kidney, liver, pancreas Antemortem  128/176 (73%) 
 Our case 2013 US (DC) Kidney Antemortem Unknown 9/222 (4%) 
Nontransplant exposure      
 [281981 US (OK) Unknown Postmortem 102/unknown 98/unknown 
 [291981 US (AZ) Dog in Mexico Antemortem 41/unknown 32/unknown 
 [301983 US (MA) Dog in Nigeria Antemortem 28/132 (21%) 26/unknown 
 [311983 US (MI) Possible bat Antemortem  54/254 (21%) 
 [32     47/209 (20%) 
 [331984 US (TX) Unknown Antemortem 142/unknown 123/unknown 
 [341984 US (PA) Unknown Antemortem Unknown Unknown 
 [351984 US (CA) Dog in Guatemala Postmortem 179/unknown  
 [361985 US (TX) Unknown Postmortem  85/140 (61%) 
 [371987 US (CA) Unknown Postmortem 87/unknown 75/177 (42%) 
 [381989 US (OR) Unknown Postmortem 9/unknown 2/unknown 
 [391990 US (TX) Bat Postmortem 67/100 (67%)  
 [401992 US (CA) Dog in India Antemortem 17/unknown 14/unknown 
 [411992 France Possible dog in Algeria Antemortem 143/unknown unknown 
 [421993 US (NY) Unknown Postmortem 55/unknown 40/unknown 
 [431993 US (TX) Unknown Postmortem 58/unknown 55/110 (50%) 
US (CA) Dog in Mexico Antemortem 25/unknown 20/unknown 
 [441994 US (CA) Unknown Postmortem 26/unknown 25/unknown 
 [451994 US (FL) Unknown Postmortem Unknown 16/unknown 
 [461994 US (AL) Bat Postmortem 99/unknown 87/unknown 
  US (TN) Unknown Antemortem 47/unknown 35/unknown 
  US (TX) Dog Antemortem 54/unknown 38/unknown 
 [471994 US (WV) Bat Antemortem 48/unknown 37/unknown 
 [481995 US (WA) Bat Antemortem 72/unknown 16/unknown 
 [491995 US (CT) Bat Antemortem 83/unknown 46/unknown 
 [501995 US (CA) Bat Antemortem 12/unknown 1/unknown 
  US (CA) Unknown Postmortem 76/unknown 72/unknown 
 [511996 US (FL) Dog Antemortem Unknown 4/unknown 
 [521996 US (NH) Dog in Nepal Antemortem Unknown 1/unknown 
 [531996 US (KY) Possible bat Antemortem 87/unknown 82/unknown 
 1996 US (MT) Possible bat Antemortem 26/unknown 23/unknown 
 [541997 US (MT) Bat Postmortem 60/unknown 58/unknown 
 1997 US (WA) Unknown Postmortem 55/unknown 54/unknown 
 [551997 US (TX) Bat Antemortem 46/unknown 42/unknown 
 1997 US (NJ) Bat Antemortem 50/unknown 42/unknown 
 [561998 US (VA) Unknown Antemortem 48/unknown 16/unknown 
 [572000 US (CA) Bat Antemortem 37/unknown 33/unknown 
  US (GA) Bats Postmortem 71/unknown 70/unknown 
  US (MN) Bat Postmortem 20/unknown 20/unknown 
  US (NY) Dog in Ghana Antemortem 24/unknown 23/unknown 
  US (WI) Bats Postmortem 27/unknown 18/unknown 
 [582002 US (CA) Bat Antemortem 46/unknown 28/unknown 
 [592002 US (IA) Unknown Antemortem 124/unknown 71/unknown 
 [602003 US (VA) Raccoon Postmortem 8/298 (2.6%) 3/173 (2%) 
 [61] 2003 US (CA) Bat Antemortem 6/44 (14%) 2/40 (5%) 
 [62] 2004 US (WI) Bat Antemortem 37/95 (39%) 5/35 (14%) 
 [63] 2005 US (MS) Bat Postmortem 55/unknown 32/79 (41%) 
 [64] 2006 US (TX) Bat Antemortem Unknown Unknown 
 [65] 2006 US (IN) Bat Antemortem 66/unknown 28/unknown 
 2006 US (CA) Possible dog in Philippines Antemortem 24/64 (38%) 11/51(22%) 
 [66] 2007 Canada (Alberta) Bat Antemortem 19/unknown 16/unknown 
 [67] 2007 US (MN) Bat Antemortem 54/538 (10%) 51/524 (10%) 
 [182008 French Guiana Unknown Postmortem 90/160 (56%) 48/100 (48%) 
 [68] 2008 US (CA) Dog not in US Postmortem 20/29 (69%) 4/9 (44%) 
 [69] 2008 US (MO) No Antemortem 5/unknown 1/40 2.5%) 
 [70] 2009 US (TX) Bat Antemortem 1/unknown 0 (0%) 
 [71] 2009 US (KY+IN) Possible bat Antemortem 18/159 (11%) 14/147 (10%) 
 [72] 2009 US (MI) Bat Antemortem 18/194 (9%) 6/180 (3%) 
 [73] 2009 US (VA) Dog in India Antemortem 32/174 (18%) 24/70 (34%) 
 [74] 2010 US (LA) Bat in Mexico Antemortem 95/204 (47%) 68/unknown 
 [75] 2010 US (WI) Bats Antemortem 7/unknown 5/178 (2.8%) 
 [76] 2011 US (NJ) Dog in Haiti Antemortem 14/unknown 10/246 (4%) 
 [77] 2011 US (CA) Cats Antemortem 27/208 (13%) 17/unknown 
 [78] 2011 US (NY) Dog in Afghanistan Antemortem 29/240 (12%) 9/unknown 
 [79] 2011 Italy Dog in India Antemortem 1/unknown 0/unknown 
 [80] 2011 US (SC) Bats Antemortem 22/188 (12%) 18/unknown 
 [81] 2012 UAE
Switzerland 
Bat in US (CA) Antemortem 23/59 (39%) 15/36 (42%) 

The reference, year and location of illness, transplant and nontransplant exposure, and time of rabies diagnosis are provided. The location of illness is given as the country (state/province) where the patient had clinical manifestations of rabies. Numbers of all persons given PEP and total assessed, as well as numbers of HCWs given PEP and total HCWs assessed, are given, as reported. PEP rates are calculated as percentages (%), if both number of those given PEP and those assessed are given.

Abbreviations: HCW, healthcare worker; PEP, postexposure prophylaxis; UAE, United Arab Emirates; US, United States.

a References [61–81] can be found in the Supplementary Data.

b US states: AK, Alaska; AL, Alabama; AZ, Arizona; CA, California; CT, Connecticut; DC, District of Columbia; FL, Florida; GA, Georgia; IA, Iowa; ID, Idaho; IN, Indiana; KY, Kentucky; LA, Louisiana; MA, Massachusetts; MI, Michigan; MN, Minnesota; MO, Missouri; MS, Mississippi; MT, Montana; NH, New Hampshire; NJ, New Jersey; NY, New York; OK, Oklahoma; OR, Oregon; PA, Pennsylvania; SC, South Carolina; TN, Tennessee; TX, Texas; VA, Virginia; WA, Washington; WI, Wisconsin; WV, West Virginia.

DISCUSSION

After confirmation of rabies in our patient, our infection control, infectious diseases, and occupational health staff screened 222 HCWs at potential risk, and 9 of these persons received PEP. Eight persons had high-risk exposures and 1 HCW without high risk sought PEP outside our hospital. Because the specific high-risk exposures included broken skin or mucosal contact with the patient's secretions, some of these exposures were avoidable had HCWs practiced standard precautions [11] when handling bodily fluids or contaminated medical equipment or had they used personal protective equipment.

Rates of PEP after hospitalized cases of rabies have varied widely, ranging from 0% to 100% of those exposed (Table 3). During 1980–1996, the CDC reported that after potential exposure to rabies, PEP was given to a mean of 64.6 persons per case (SD, 40.8 persons per case) [51]. For HCWs, PEP is warranted after specific risk exposures and not simply after routine healthcare delivery [Supplementary Reference 62]. Early rabies consideration in the differential diagnosis, proper use of personal protective barriers with adherence to Advisory Committee on Immunization Practices guidelines during the care of the patient [50], and prompt, thorough risk assessment of exposed persons [Supplementary Reference 76] can help to avoid providing unnecessary PEP.

In our hospital, 4% of our screened HCWs received PEP. Our rate was relatively low compared with provision of PEP to 44%–100% of HCWs in previous reports describing similar settings after transplant exposure to rabies [19–27]. As seen in the section on transplant exposures in Table 3, PEP was given to 44% of HCWs after the first corneal transplant exposure described in the United States in 1978 [20] and 73% for multiple solid organ transplants in Germany in 2005 [27]. For settings with few exposed HCWs, PEP was given to all HCWs after rabies confirmation in the transplanted corneas, such as the single surgeon who performed both operations in India [23] and all HCWs who were involved in Iran [24].

As shown in the section for nontransplant settings in Table 3 [28–60; Supplementary References 61–81], although PEP was recommended for HCWs with high-risk exposures, some with low or no risk received PEP as well [29, 32; Supplementary References 73, 76, 77]. In a report of 2 cases from California during the same year, the provision of PEP varied greatly, with 1 HCW receiving PEP for the patient who was diagnosed antemortem, and 72 HCWs receiving PEP for the patient who was diagnosed postmortem [50]. Low rates of giving PEP at 2.6% for non-HCWs and 2% for HCWs were credited to the careful risk assessments undertaken after postmortem diagnosis of rabies from a raccoon exposure in Virginia [60]. There was a single report of preexposure prophylaxis for 3 pathologists performing the autopsy on a patient whose rabies was diagnosed antemortem [30].

Because rabies usually leads to neurologic complications and fatal infection, fear of transmission among HCWs who cared for patients with rabies may lead to excessive use of PEP [Supplementary References 82, 83] and inappropriate deviations from PEP guidelines [Supplementary References 84, 85]. In addition, decisions for PEP provision may be subjective based on perceived risk [Supplementary Reference 86]. Our relatively low rate of giving PEP likely resulted from the close collaboration of our staff with local health departments, the use of the MDHMH tool to objectively standardize our risk assessment, and compliance with PEP guidelines by the evaluating physicians. Additionally, we addressed all concerns raised by HCWs in a timely and objective manner, and provided extensive education regarding rabies transmission risks and the use of PEP for all involved HCWs.

This investigation allowed for rapid mobilization of staff from infection control, infectious diseases, and occupational health, totaling 346 person-hours from 4 physicians and 7 nurses (Table 2). Our estimated pharmacy cost of providing PEP for 7 persons at our medical center was US$4454; 2 persons received PEP outside this facility. A rapid and complete investigation with specialized dedicated staff such as ours or broad provision of PEP [27] are likely more difficult in settings outside the United States and Europe with limited personnel and resources.

In summary, after confirmation of a sentinel case of acute rabies, a coordinated effort by staff from infection control, infectious diseases, and occupational health resulted in a prompt risk assessment of all potentially exposed HCWs including trainees rotating at our teaching hospital. Our staff evaluated and counseled 222 potentially exposed HCWs to allay their fears regarding the nosocomial risk of rabies transmission. Within the first 3 days, 65% were evaluated, and within 8 days of our screening program, 95% were assessed. A total of 9 (4%) HCWs received PEP. Our relatively low rate of provision of PEP was likely due to HCWs' use of standard precautions during patient care and to the extensive education and counseling regarding rabies transmission risk to HCWs. There have been no secondary cases now >21 months after our sentinel rabies patient. Given the lack of human-to-human transmission of rabies from the literature, as well as our own experience, a conservative approach seems appropriate for determining which HCWs should receive PEP after caring for a patient with rabies.

Supplementary Data

Supplementary materials are available at Clinical Infectious Diseases online (http://cid.oxfordjournals.org). Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.

Notes

Acknowledgments. The authors thank Katherine A. Feldman, DVM, MPH, State Public Health Veterinarian at the Center for Zoonotic and Vector-borne Diseases, Prevention and Health Promotion Administration, Maryland Department of Health and Mental Hygiene, Baltimore, Maryland, for her assistance with our patient's specimens for rabies detection and subsequent risk assessment.

Disclaimer. The findings and views expressed in this report are those of the authors and do not represent the official position of the Department of Veterans Affairs.

Potential conflicts of interest. All authors: No reported conflicts.

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.

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Supplementary data

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