Contact Tracing and Exposure Investigation in Response to the First Case of Monkeypox Virus Infection in the United States During the 2022 Global Monkeypox OutbreakFREE
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Visual Abstract. Contact Tracing and Exposure Investigation in Response to Monkeypox.
After the first U.S. case of monkeypox was identified, contact tracing and exposure investigations were done statewide in multiple health care facilities and community settings in Massachusetts. This article reports on the application of a risk assessment and stratification framework for contacts in community and health care settings.
Abstract
Background:
In May 2022, the first case of monkeypox virus (MPXV) infection in the United States in the current global outbreak was identified. As part of the public health and health care facility response, a contact tracing and exposure investigation was done.
Objective:
To describe the contact tracing, exposure identification, risk stratification, administration of postexposure prophylaxis (PEP), and exposure period monitoring for contacts of the index patient, including evaluation of persons who developed symptoms possibly consistent with MPXV infection.
Design:
Contact tracing and exposure investigation.
Setting:
Multiple health care facilities and community settings in Massachusetts.
Participants:
Persons identified as contacts of the index patient.
Intervention:
Contact notification, risk stratification, and symptom monitoring; PEP administration in a subset of contacts.
Measurements:
Epidemiologic and clinical data collected through standard surveillance procedures at each facility and then aggregated and analyzed.
Results:
There were 37 community and 129 health care contacts identified, with 4 at high risk, 49 at intermediate risk, and 113 at low or uncertain risk. Fifteen health care contacts developed symptoms during the monitoring period. Three met criteria for MPXV testing, with negative results. Two community contacts developed symptoms. Neither met criteria for MPXV testing, and neither showed disease progression consistent with monkeypox. Among 4 persons with high-risk exposures offered PEP, 3 elected to receive PEP. Among 10 HCP with intermediate-risk exposures for which PEP was offered as part of informed clinical decision making, 2 elected to receive PEP. No transmissions were identified at the conclusion of the 21-day monitoring period, despite the delay in recognition of monkeypox in the index patient.
Limitation:
Descriptions of exposures are subject to recall bias, which affects risk stratification.
Conclusion:
In a contact tracing investigation involving 166 community and health care contacts of a patient with monkeypox, no secondary cases were identified.
Primary Funding Source:
None.
Since the beginning of the global outbreak of monkeypox virus (MPXV) in May 2022, contact tracing, exposure investigation, risk assessment, and symptom monitoring of exposed persons have been critically important to our evolving understanding of the epidemiology of monkeypox and to breaking chains of transmission (1).
This process involves close collaboration between public health authorities and clinicians. We describe the actions and results after the identification of the first case of monkeypox diagnosed in the United States as part of the 2022 outbreak (2).
In this case, a 31-year-old man with recent travel to Canada in late April 2022 and contacts with male partners there presented over several days to multiple health care facilities in Massachusetts with progressive and evolving skin lesions, followed by severe proctitis with rectal bleeding, fevers, chills, sweats, and inguinal lymphadenopathy. These symptoms prompted hospital admission for additional evaluation and management. For the first 5 days of admission, monkeypox was not suspected because other infectious diagnoses were pursued, and the patient was not isolated. At the time, the potential for community spread of monkeypox through sexual networks in nonendemic countries was not understood. In fact, it was during the period that this patient was being evaluated that non–travel-related cases were first reported through public health authorities in Europe (3)
This case presented complexities due to multiple interactions with several health care facilities and delayed recognition of the cause, which resulted in exposures to persons in both community and health care settings. Although community (4, 5) and nosocomial (6) transmission have been reported in endemic countries, only a single case of nosocomial transmission and 2 cases due to household spread among travel-related cases have been reported outside endemic countries before the current global outbreak (7).
We report on the application of a risk assessment and stratification framework for contacts in community and health care settings to assist in decision making on whether to offer and administer postexposure prophylaxis (PEP), as well as on the associated outcomes. At the conclusion of this investigation, no secondary cases were identified, prompting reconsideration of risk assessment for identified exposures.
Methods
Identification of Contacts
Community Contacts
Community contacts were considered to be anyone who had close contact with the patient during the symptomatic period in any venue other than the patient's health care settings. Both household and workplace contacts were identified. Persons who interacted with the index patient were identified through multiple interviews done by epidemiologists at the Massachusetts Department of Public Health (MDPH). Workplace contacts were identified through review of company records and employee schedules maintained by the workplace.
Health Care Facility Contacts
The index patient received care at 4 health care facilities (A, B, C, and D) during illness. Facility A is an urgent care center, facility B a hospital-based laboratory affiliated with facility A, and facility C a primary care practice within a tertiary care center; all 3 are part of the same health care system. Facility D is a separate tertiary care facility where the patient was seen in an outpatient infectious diseases practice and the emergency department and was eventually admitted.
Facilities A, B, and C
Health care personnel (HCP) were identified through routine contact tracing done by infection preventionists using medical record review and interviews with the manager of each work area the index patient had visited. A list of potentially exposed HCP was created that included all persons who had had contact with the index patient or the care environment, provided direct care, or handled laboratory specimens at any of the 3 facilities. Employee occupational health staff spoke with each HCP by telephone to determine if they had had contact with the index patient or items in the environment (such as bed sheets or clothing) and what personal protective equipment (PPE) was worn.
Lists of patient visits were reviewed by infection preventionists and unit managers for the time period overlapping with the index patient's visit at each facility to determine if any patients or visitors were exposed.
Facility D
Heath care personnel were initially identified as possibly exposed through preestablished standard processes used for contact tracing and exposure investigations at the institution. This process begins with a trace in the electronic health record to identify persons who accessed the medical record of the index patient. The query was expanded to include any HCP with links to the medical records of the index patient's hospital roommates, because HCP would have entered the shared room to care for the roommates. This approach identified persons who never interacted with the index patient or his environment (that is, those doing only medical record review) and also failed to identify persons who interacted with him or his environment but did not access the medical record (such as nutrition and food services or environmental services). Once the initial list was generated, to better identify contacts, managers for the specific care locations reviewed the list to add or remove persons. Additional interviews with infection preventionists and employee occupational health services resulted in the final comprehensive trace list. Health care personnel on this list were contacted through direct calls from a nursing labor pool established for this purpose or through a REDCap survey (8–10) to determine if they had had contact with the index patient.
Exposed patients were identified using a similar process to trace patients in the electronic health record. Interviews with the index patient's care team and review of the medical record were used to identify visitors to the index patient or his roommates.
Risk Assessment and Stratification
An initial framework for risk assessment and stratification was developed in collaboration with the MDPH (Table 1) and used by them as the basis for risk assessments in the first part of the outbreak. This risk assessment was based on the Centers for Disease Control and Prevention (CDC) approach but provided greater discrimination for each category of exposure (11). Of note, at the time of this exposure and contact tracing investigation, this framework considered all HCP interacting with the infected person's care environment using appropriate PPE (gown, gloves, N95 respirator, and eye protection) to be exposed at low or uncertain risk. The study team augmented the CDC framework with additional detail to describe specific types of contact (both direct and indirect) separate from exposure to respiratory secretions and to stratify by PPE use. The increase in specificity permitted standard application to HCP across multiple types of facilities and provided common exposure scenarios in both the health care setting and the community (Table 1).
Assignment of contacts to each risk category was done by MDPH epidemiologists for household and community contacts and by occupational health staff in consultation with MDPH epidemiologists at the index patient's workplace. In the health care facilities, a combination of employee occupational health services, infection prevention and control, and other clinicians assisted in the assignment of HCP, patients, and visitors to risk categories. At facility D, an electronic survey approach was used and supplemented by one-on-one discussions with HCP who were at high or intermediate risk to confirm risk categorization. Contacts with more than 1 exposure risk were assigned to the highest of their risk categories (8).
Symptom diaries were not used for persons identified as contacts requiring 21-day monitoring.
Indications for PEP
Persons who were categorized as having high risk were recommended to receive PEP with 2 doses of modified vaccinia Ankara vaccine (JYNNEOS [Bavarian Nordic]), 28 days apart. Those who met criteria for the intermediate 2 exposure risk category were provided counseling, with recommendations for PEP on a case-by-case basis. Postexposure prophylaxis was provided only if contacts were within 14 days of their last known exposure.
Monitoring During the Exposure Period and Evaluation of Symptomatic Contacts
Persons in all risk categories were monitored for symptoms during the 21-day period after their last exposure. Epidemiologists at the MDPH explained that contacts should monitor for development of any new symptoms with a particular focus on rash (even single lesions), fever or chills, and lymphadenopathy. They checked in directly with household and personal contacts approximately 3 times per week; contacts were instructed to call a continuously staffed line when they had questions or observed symptoms. Workplace occupational health staff monitored workplace contacts daily, 7 days a week. In facilities A, B and C, monitoring was done twice daily—once by direct observation (either in person or virtual) and once by home self-assessment with results recorded on a paper form. Each monitoring session included a temperature check, as well as questions about symptoms.
In facility D, symptom monitoring was initially twice daily and later transitioned to once daily. Health care personnel completed a daily symptom monitoring survey delivered by e-mail and text message, with supporting direct telephone calls from a call center for facility D. Those who had not completed their symptom survey by noon each day were contacted by the call center to confirm that they remained asymptomatic (8).
During the 21-day monitoring period, all 4 facilities remained in close contact with the MDPH, including about assessment of reported symptoms, to determine if MPXV testing was warranted. When indicated, polymerase chain reaction testing for orthopoxvirus was done and processed at the MDPH, following protocols in place at the time.
The work presented here represents routine infection control and occupational health services and does not meet the regulatory definition of human subjects research per 45 C.F.R. §46.102(l).
Role of the Funding Source
This study received no funding.
Results
Identification of Contacts
During the index patient's infectious period, interactions in the community and 4 health care settings took place over 18 days (Figure 1). A total of 166 contacts were identified across all locations (Figure 2). As part of the community exposure investigation, because of some initial uncertainty about the symptom onset date, the initial list of possible contacts included 41 people, 4 of whom were eventually determined to have interacted with the index patient before symptom onset. Of the remaining 37, two were household contacts and 35 were workplace contacts. Across the health care facilities, 129 exposed persons were identified: 5 in facility A, 1 in facility B, 18 in facility C, and 105 in facility D.
Figure 2. Flow diagram of contact tracing and exposure investigation.
Total counts of contacts of the index patient in the community and health care facilities A, B, C, and D are noted. HCP = health care personnel.
* For facility D, a single visitor identified as exposed was also an HCP and is counted in the HCP total.
Exposure Risk Assessment and Stratification
The exposure assessment and risk stratification tool (Table 1) was applied to persons identified as contacts.
No high-risk exposures were identified among community contacts. Both household community contacts were identified as intermediate-risk exposures. There were 35 contacts in the index patient's workplace, all of which were identified as low- or uncertain-risk exposures. All 5 contacts in facility A were identified as intermediate-risk exposures. A single contact in facility B was identified as a low- or uncertain-risk exposure. Among 18 contacts in facility C, exposure risk was identified as high, intermediate, and low or uncertain in zero, 3, and 15 contacts, respectively. Among 105 contacts (102 HCP, 2 patients, and 1 visitor) in facility D, the corresponding numbers were four, 39, and 62 contacts, respectively. The visitor identified was also an HCP at facility D and was tabulated among HCP, bringing the total number of exposed HCP to 103 (Table 2).
PEP
No community contacts met exposure criteria for PEP.
One HCP at facility A and 1 at facility C would have been eligible to receive PEP on the basis of the type of exposure but were outside the 14-day window. No contacts at facility B met criteria for PEP. At facility D, PEP was offered to 14 persons (12 HCP and 2 patients), of whom 5 (4 HCP and 1 patient) accepted and received PEP (Table 2). The 4 HCP received their first dose on day 9, day 11, day 12, and day 13 after exposure, and 3 received their second dose per the protocol; 1 HCP declined the second dose. The patient who received PEP, 9 days after last exposure, declined the second dose of the vaccine offered 28 days after the first dose.
Follow-up of Contacts During the 21-Day Exposure Period
All contacts were recommended for 21-day symptom monitoring. Symptom screening protocols are provided for the health care facilities (Supplement). Fifteen HCP developed symptoms, of whom 3 met criteria for testing and were tested for MPXV. Both patient contacts developed symptoms and were tested for MPXV. All MPXV test results were negative (Table 3).
Discussion
In a large contact tracing and exposure investigation involving a total of 166 contacts across community settings and 4 health care facilities, 4 high-risk, 49 intermediate-risk, and 113 low- or uncertain-risk exposures were identified. Three contacts with high-risk exposures and 2 with intermediate-risk exposures received PEP, all more than 4 days but within 9 to 13 days after exposure. In addition, of the 4 community contacts who interacted with the index patient during the presymptomatic period, none developed monkeypox, consistent with the current understanding that transmission risk begins during a person's symptomatic period. No transmission events were identified in any setting among exposed persons in this investigation.
Such extensive investigations as these are resource intensive. At facility D, activation of the Hospital Incident Command System was necessary to identify and deploy resources given the size of the event and time-sensitive nature of follow-up. Most important, the time and clinical expertise required to establish exposure risk are substantial, involving one-on-one discussions with HCP and community contacts. Exposed persons were asked to recall interactions from several days or weeks prior and to recall specific details related to distance, PPE worn, and types of interactions. The process was further complicated by the need to conduct a risk assessment, in the case of facility D, related to HCP and visitors not of the index patient but of his 2 roommates. Despite the challenges, conducting and reporting on such investigations is critical to ensure appropriate management of exposed persons in community and health care settings and to advance our understanding of transmission risk.
Among those who received PEP, administration occurred in all cases more than 4 days after exposure because of the delay in diagnosis of the index patient. Because of the time lag, we would not expect vaccination to prevent the development of infection, but rather to reduce the severity of illness. Thus, the fact that no infection was observed among those with exposures that qualified for PEP supports the overall low risk for transmission of MPXV.
On the basis of this initial experience and a review of relevant literature, we conclude that HCP using all appropriate PPE, in the absence of a recognized breach, should not be considered to have sustained an exposure. The MDPH adopted this approach in most cases and recommended self-monitoring of symptoms for those HCP. During the 2022 outbreak, the occurrence of MPXV infection in HCP after occupational exposure was extremely limited (12), and the most recently updated guidance from the CDC for both community (13) and health care (14) exposures endorses the approach used in this investigation. One of the challenges of implementing the CDC guidelines for exposure risk assessment in health care settings was the inclusion of distance and time variables (for example, within 6 feet for ≥3 hours). However, in community settings, the MDPH has found these criteria useful in assessing exposures. Since this exposure investigation was done, the CDC has modified their classification of exposure risk, including considering persons who interacted with a patient with monkeypox with all appropriate PPE not to be in the low- or uncertain-risk category but in fact to be not exposed. Our facilities and the MDPH also made this change, before the CDC modification, based on our experiences with this investigation and subsequent exposure investigations. The exposure definition that continues to be implemented in our facilities includes a higher level of detail than the CDC version to facilitate implementation by our occupational health and infection prevention and control teams.
Until the case patient was identified as a person under investigation for monkeypox, he received care in many locations without specific precautions. Once identified as at risk for monkeypox, he was transferred to a general medicine unit in facility D, where HCP had previously received dedicated training in infection control protocols related to the care of patients with high-consequence infectious diseases. Thus, most care provided to the patient was during a time when monkeypox was not suspected and on units and care locations not included in dedicated training programs about high-consequence infectious diseases.
In summary, in this large contact investigation that included a period for potential exposures lasting longer than 2 weeks because of delayed recognition of MPXV infection, no secondary cases were observed across community and health care settings. The creation of a framework for assessing specific risk scenarios permitted ease of application by employee occupational health staff and application across various settings. Public health authorities and health care facilities should consider how these findings may inform revised estimates of exposure risk, requirements for monitoring, and recommendations for PEP. Although preexposure prophylaxis was not specifically evaluated in this study, the lack of secondary transmission suggests that this strategy may not be indicated for most HCP. Similar investigations in response to cases identified globally are likely to be informative.
Supplemental Material
References
1.
Kraemer MUG, Tegally H, Pigott DM, et al. Tracking the 2022 monkeypox outbreak with epidemiological data in real-time [Letter]. Lancet Infect Dis. 2022;22:941-942. [PMID: 35690074] doi: 10.1016/S1473-3099(22)00359-0
2.
Basgoz N, Brown CM, Smole SC, et al. Case 24-2022: a 31-year-old man with perianal and penile ulcers, rectal pain, and rash. N Engl J Med. 2022;387:547-556. [PMID: 35704401] doi: 10.1056/NEJMcpc2201244
3.
World Health Organization. Monkeypox - United Kingdom of Great Britain and Northern Ireland. 18 May 2022. Accessed at www.who.int/emergencies/disease-outbreak-news/item/2022-DON383 on 14 October 2022.
4.
Hutin YJ, Williams RJ, Malfait P, et al. Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997. Emerg Infect Dis. 2001;7:434-8. [PMID: 11384521]
5.
Nolen LD, Osadebe L, Katomba J, et al. Extended human-to-human transmission during a monkeypox outbreak in the Democratic Republic of the Congo. Emerg Infect Dis. 2016;22:1014-21. [PMID: 27191380] doi: 10.3201/eid2206.150579
6.
Nakoune E, Lampaert E, Ndjapou SG, et al. A nosocomial outbreak of human monkeypox in the Central African Republic. Open Forum Infect Dis. 2017;4:ofx168. [PMID: 29732376] doi: 10.1093/ofid/ofx168
7.
Zachary KC, Shenoy ES. Monkeypox transmission following exposure in healthcare facilities in nonendemic settings: low risk but limited literature. Infect Control Hosp Epidemiol. 2022;43:920-924. [PMID: 35676244] doi: 10.1017/ice.2022.152
8.
Simpson LA, Macdonald K, Searle EF, et al. Development and deployment of tools for rapid response notification of monkeypox exposure, exposure risk assessment and stratification, and symptom monitoring. Infect Control Hosp Epidemiol. 2022;43:963-967. [PMID: 35815416] doi: 10.1017/ice.2022.167
9.
Harris PA, Taylor R, Minor BL, et al; REDCap Consortium. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208. [PMID: 31078660] doi: 10.1016/j.jbi.2019.103208
10.
Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377-81. [PMID: 18929686] doi: 10.1016/j.jbi.2008.08.010
11.
Centers for Disease Control and Prevention. Monitoring people who have been exposed. Updated 22 May 2022. Accessed at www.cdc.gov/poxvirus/monkeypox/clinicians/monitoring.html on 29 May 2022.
12.
Thy M, Peiffer-Smadja N, Mailhe M, et al. Breakthrough infections after post-exposure vaccination against monkeypox. medRxiv. Preprint posted online 4 August 2022. doi: 10.1101/2022.08.03.22278233
13.
Centers for Disease Control and Prevention. Monitoring and risk assessment for persons exposed in the community. Updated 11 August 2022. Accessed at www.cdc.gov/poxvirus/monkeypox/clinicians/monitoring.html on 19 August 2022.
14.
Centers for Disease Control and Prevention. Infection prevention and control of monkeypox in healthcare settings. Updated 11 August 2022. Accessed at www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.html on 19 August 2022.
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Published In
Annals of Internal Medicine
Volume 175 • Number 12 • December 2022
Pages: 1639 - 1647
History
Published online: 8 November 2022
Published in issue: December 2022
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© 2022 American College of Physicians.
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Contact Tracing and Exposure Investigation in Response to the First Case of Monkeypox Virus Infection in the United States During the 2022 Global Monkeypox Outbreak. Ann Intern Med.2022;175:1639-1647. [Epub 8 November 2022]. doi:10.7326/M22-2721
Contact Tracing and Exposure Investigation in Response to the First Case of Monkeypox Virus Infection in the United States During the 2022 Global Monkeypox Outbreak. Ann Intern Med.2022;175:1639-1647. [Epub 8 November 2022]. doi:10.7326/M22-2721
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