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The monkeypox virus outbreak

Reflections from the frontlines
      The day began as a rather typical Friday morning on May 30, 2003. The infection control practitioners were reviewing their telephone messages and preparing for the weekly staff meeting with both the hospital epidemiologist and the Chairman of the Froedtert Hospital Infection Control Committee, who was engaged in a discussion with one of our staff emergency department (ED) physicians about a veterinarian who was seeking treatment in the ED for a skin lesion and swollen lymph nodes. The veterinarian had a history of recent exposure to an ill pet prairie dog. At the time, little did we know that a series of events would set into motion a full scale epidemiologic investigation encompassing our own hospital in addition to local, state, and federal health agencies, entirely because of a smallpox-like virus that had never been seen before in the Western hemisphere.
      • Centers for Disease Control and Prevention
      Multistate Outbreak of Monkeypox—Illinois, Indiana, and Wisconsin, 2003.

      The learning curve

      Before the events of late May and early June, few infection control practitioners were familiar with a viral agent that is known as monkeypox. Monkeypox, an orthopoxvirus, was first recognized in 1970 as producing a sporadic smallpox-like zoonotic viral exanthem in persons in Central and Western Africa.
      • Landyl IN
      • Ziegler P
      • Kim A
      A human infection caused by monkeypox virus in Basankusa Territory, Democratic Republic of the Congo (DRC).
      In 1996, this agent was responsible for an outbreak in Zaire, involving 71 clinical cases in a total of 13 villages.
      • Centers for Disease Control and Prevention
      Human monkeypox— Kasai Oriental, Zaire, 1996-1997.
      The outbreak was notable in that the case-fatality rate was 8.4% and person-to-person spread was viewed as a potential mechanism for disease transmission. Several subsequent outbreaks investigated in the Democratic Republic of the Congo were reported to have a case-fatality rate ranging from 4% to 33%, with young children as the principal victims.
      • Jezek Z
      • Marennikova SS
      • Mutumbo M
      • Nakano JH
      • Paluku KM
      • Szczeniowski M
      Human monkeypox: a study of 2510 contacts of 214 patients.
      • Meyers H
      • Perrichot M
      • Stemmler M
      • Emmerich P
      • Schmitz H
      • Varaine F
      • et al.
      Outbreak of disease suspected of being due to human monkeypox virus infection in the Democratic Republic of Congo in 2001.
      This background information was not lost on those of us challenged with dealing with this outbreak, nor was it unknown to the phalanx of media-types who viewed this as a news-worthy if not apocalyptic event. Monkeypox is not smallpox, and as such does not have the high mortality rate usually associated with the more virulent viral disease. Whereas there is no cure, the disease must progress through a series of clinical stages including fever, generalized aches and pains, headache, swollen lymph nodes, and rash. The presentation may be highly variable from patient to patient. The great unknown however, was the communicability of the agent, and this was our impetus for immediate action.
      On June 3, a patient was admitted to our hospital with fever, rash, and a recent history of close exposure to prairie dogs. The next morning the admitting physician received a telephone call from a veterinary epidemiologist from the Wisconsin Division of Public Health, informing her of the possible linkage between an outbreak of a pox-like viral infection in humans and exposure to sick prairie dogs. The patient with the rash was immediately placed in contact and airborne isolation precautions. Subsequent telephone conversations with other state officials eventually led to extending an invitation to Epidemic Intelligence Service (EIS) officers from the Centers for Disease Control and Prevention to visit Froedtert Hospital on June 6 to review our current cases, which at that time included 3 hospitalized patients. Blood and tissue samples were dispatched to the Centers for Disease Control and Prevention in Atlanta, where the diagnosis of monkeypox was confirmed by polymerase chain reaction (PCR) analysis. Electron microscopic (EM) studies conducted on tissues sent to our pathology department documented the presence of an intracellular pox-like virus suggestive of an orthopoxvirus. These particles were identical to a pox-like entity reported in EM studies conducted by investigators at the Marshfield Clinic approximately 7 days earlier. The Marshfield Clinic EM studies were important because these results were available days before PCR analysis and, in combination with the corresponding epidemiologic data, suggested we were dealing with a disease that was relatively new to the Western hemisphere.
      From the very beginning of this outbreak, all of us have been involved in a steep learning curve, which can best be characterized as intense and collaborative. Although none of the team has received specific training to identify and manage patients or persons exposed to monkeypox, our fundamental training in the recognition, management, and epidemiology of other communicable diseases has been our foundation for action. It can be stated that infection control practitioners, infectious disease physicians, medical epidemiologists, and other public health officials train to practice the routine but in reality should be prepared for any possibility.

      Lessons from the past

      Although this experience may involve a novel infectious agent, it does not represent our first encounter with a major outbreak involving an unusual microorganism. In 1993, thousands of Milwaukee, Wisconsin residents experienced an infection involving a small protozoan parasite called Cryptosporidium, a microorganism normally found in the intestines of farm animals, which contaminated the city water supply via runoff of agricultural waste. Tragically, that event was associated with several deaths in immunosuppressed and other high-risk patient populations.
      • MacKenzie WR
      • Schell WL
      • Blair KA
      • Addiss DG
      • Peterson DE
      • Hoxie NJ
      • et al.
      Massive outbreak of waterborne cryptosporidium infection in Milwaukee, Wisconsin: recurrence of illness and risk of secondary infection.
      Another smaller but just as serious outbreak involved a highly virulent strain of Escherichia coli that produced severe systemic disease, especially in young children. It was later determined that individuals acquired the organism at a local restaurant when employees cross-contaminated a salad bar after handling contaminated beef. Last year residents in Wisconsin were introduced to a new potential threat, Chronic Wasting Disease in the native deer population, and the nation as a whole is bracing itself for another episode of West Nile virus, which infects birds and is passed to persons through mosquitos.
      • Joly DO
      • Ribie CA
      • Langenberg JA
      • Beheler K
      • Batha CA
      • Dhuey BJ
      • et al.
      Chronic wasting disease in free-ranging Wisconsin white-tailed deer.
      • Centers for Disease Control and Prevention
      Provisional surveillance summary of West Nile Virus epidemic—United States, January-November 2002.
      Our current response to monkeypox virus has, in part, been governed by past experiences and highlights the importance of cooperation between local, state, and other public health professionals, so as to detect these diseases in their earliest phases and interrupt the transmission process using traditional and, at times, innovative strategies.

      A question of public trust and leadership

      Local and national media have justifiably taken a keen interest in the current monkeypox virus outbreak. Questions have focused on clinical symptoms, transmission issues, and whether the public is safe. Throughout the outbreak, close attention has been placed on identifying possible secondary cases associated with person-to-person contact. To date, we have managed 18 patients with suspected monkeypox virus infection; most have reported direct contact with ill animals. However, some of our suspected cases, which are yet to be confirmed, reported no such direct contact and are being evaluated as possible human-to-human transmissions. Because of the unresolved issue of secondary transmission, local, state, and federal authorities are actively monitoring any persons who may have had unprotected or protected contact with active or suspected patients. Local, state, and national public health professionals are vested with the responsibility of protecting the health and well-being of it's citizens, therefore the management of this viral outbreak involves not only protecting the public's safety but also providing accurate information and presenting a correct perspective of the illness and its potential impact on the population.
      Within 24 hours of recognizing that we were dealing with a unique infectious disease process, members of the Froedtert Infection Control Team were meeting with patient care directors, physicians, and nurses in a effort to identify their concerns and reinforce the importance of our heightened infection control efforts. Information pertaining to laboratory and clinical features of monkeypox infection was placed on both the Froedtert Hospital and the Medical College of Wisconsin Web sites. As is often the case in human nature, several staff members expressed concern over the timeliness of the periodic updates, however our knowledge of this disease process was rapidly evolving and therefore, as we climbed the “learning curve,” so did our physicians and nurses. Whereas it is true that hospital-based infection control practitioners in general do not carry the same partisan responsibilities as our public health colleagues, we are obliged within our professional realm to assume a mantle of leadership when addressing the concerns of our clinical colleagues and their patients.

      Some final thoughts and considerations for the future

      At some point this outbreak will become a historical reference, but before that occurs we still have much to learn. For instance, we need to understand how the virus actually found it's way into the prairie dog population and what other exotic animal species may have been involved in the transmission process. We also need to clarify whether the current outbreak is solely the result of animal-to-human transmission (zoonotic) or whether the infection can be spread between humans, as it appears to happen in Africa. It is obvious that in the post–monkeypox virus climate, the risk and prevention of rare zoonotic diseases will take on a greater meaning of importance within the infection control community. For most infection control practitioners, zoonotic infections and their role in the healthcare environment is a somewhat murky topic. Therefore, we need to invest more educational time and effort in preparing our colleagues for a whole smorgasbord of new emerging pathogens that can effectively leap from animal to man.
      • Weber DJ
      • Rutala WA
      Risk and prevention of nosocomial transmission of rare zoonotic diseases.
      It would appear that as a first-line defensive strategy, our primary emphasis on adherence to a policy of strict isolation precautions was valid in the face of this new viral entity.
      • Garner JS
      Guidelines for isolation precautions in hospitals.
      Because of initial uncertainties concerning the anticipated route of transmission of monkeypox virus, suspected patients were screened in a recently constructed ED decontamination (negative pressure) suite. Whereas development of this facility required (with some discussion) a significant capital expenditure, its intrinsic benefit during this outbreak was obvious, allowing suspected patients to be circuited in and out of the institution with minimal patient-staff exposure.
      The experiences of the past several weeks have been a major departure from our usual myriad of infection control activities. It was obvious from the beginning that our efforts to evaluate and manage suspected monkeypox cases involved a much broader public health initiative, encompassing a different “command” and “control” structure, and requiring rapid communication between all members of the public and private health care establishment. The monkeypox virus outbreak clearly demonstrated that an exquisite collegiality must exist between both public and private health care practitioners if we are to effectively deal with future exotic infections. As for present considerations, we have already planned a series of “look-back” discussions, in which we will review our own institutional efforts in response to the monkeypox virus outbreak and foremost on the agenda will be, “What constitutes an effective communication strategy, especially when dealing with a rapidly (and poorly understood) infectious process?”
      One cannot leave this topic without some mention of the human toll often associated with selected disease processes. Several persons were furloughed to home quarantine because they fell within the realm of case definition based on selected clinical findings and/or suspected exposure. For some, this created a potential financial crisis because eligibility criteria for Workman's Compensation was initially unresolved. This was, in part, exacerbated by the fact that there was no easy, rapid diagnostic test for this “new infectious process.” It is obvious from both a public health and patient management perspective that resources need to be directed toward providing accurate and rapid diagnostic testing for these emerging (exotic) diseases.
      In the final analysis, the present system worked reasonably well, patients received competent and compassionate care, and the risk to other patients and staff was minimized. That is a “good thing”—because there is always another day.

      References

      References

        • Centers for Disease Control and Prevention
        Multistate Outbreak of Monkeypox—Illinois, Indiana, and Wisconsin, 2003.
        MMWR Morb Mortal Wkly Rep. 2003; 52: 537-540
        • Landyl IN
        • Ziegler P
        • Kim A
        A human infection caused by monkeypox virus in Basankusa Territory, Democratic Republic of the Congo (DRC).
        Bull World Health Organ. 1972; 46: 593-597
        • Centers for Disease Control and Prevention
        Human monkeypox— Kasai Oriental, Zaire, 1996-1997.
        MMWR Morb Mortal Wkly Rep. 1997; 46: 304-307
        • Jezek Z
        • Marennikova SS
        • Mutumbo M
        • Nakano JH
        • Paluku KM
        • Szczeniowski M
        Human monkeypox: a study of 2510 contacts of 214 patients.
        J Infect Dis. 1986; 154: 551-555
        • Meyers H
        • Perrichot M
        • Stemmler M
        • Emmerich P
        • Schmitz H
        • Varaine F
        • et al.
        Outbreak of disease suspected of being due to human monkeypox virus infection in the Democratic Republic of Congo in 2001.
        J Clin Microbiol. 2002; 40: 2919-2921
        • MacKenzie WR
        • Schell WL
        • Blair KA
        • Addiss DG
        • Peterson DE
        • Hoxie NJ
        • et al.
        Massive outbreak of waterborne cryptosporidium infection in Milwaukee, Wisconsin: recurrence of illness and risk of secondary infection.
        Clin Infect Dis. 1995; 21: 63-64
        • Joly DO
        • Ribie CA
        • Langenberg JA
        • Beheler K
        • Batha CA
        • Dhuey BJ
        • et al.
        Chronic wasting disease in free-ranging Wisconsin white-tailed deer.
        Emerg Infect Dis. 2003; 9: 599-601
        • Centers for Disease Control and Prevention
        Provisional surveillance summary of West Nile Virus epidemic—United States, January-November 2002.
        MMWR Morb Mortal Wkly Rep. 2002; 51: 1129-1133
        • Weber DJ
        • Rutala WA
        Risk and prevention of nosocomial transmission of rare zoonotic diseases.
        Clin Infect Dis. 2001; 32: 446-456
        • Garner JS
        Guidelines for isolation precautions in hospitals.
        Infect Control Hosp Epidemiol. 1996; 17: 53-80