http://www.medscape.com/viewarticle/457247?mpid=15146

June 13, 2003 — Editor's Note: As of June 11, 54 patients in the U.S. with a rash illness are thought to have monkeypox, and nine have been confirmed virologically. These 54 cases are primarily in three Midwest states: 20 in Wisconsin, 10 in Illinois, and 23 in Indiana, as well as one child in New Jersey who had recently traveled to the Midwest.

As the public and the medical community become more aware of this disease, and now that the Centers for Disease Control and Prevention (CDC) has issued a standardized case definition, numbers of reported cases may increase. To deal with the outbreak, the CDC has activated its Emergency Operations Center and deployed teams of medical officers, epidemiologists, and other experts to several states to assist with the investigation.

"This outbreak demonstrates the importance of preparedness for the unexpected," Tommy G. Thompson, Secretary of the Department of Health and Human Services, said in a news release. "State health departments have been actively involved in planning and preparing for the possibility of a bioterrorist event. We are now seeing that this level of preparation can also assist in unexpected, natural outbreaks."

Monkeypox is a rare, zoonotic, orthopox virus initially limited to rain forests in Central and West Africa. It was first identified in African primates in 1958 and in humans in 1970. In addition to nonhuman primates, it typically infects rabbits, squirrels, and some rodents. Human infection is sporadic, with an incubation period of about 12 days (range, 7 - 21 days) and a course of about two to four weeks.

Of the 54 suspected U.S. cases, 14 have been hospitalized, including one child with encephalitis; none have died; and all appear to be in various stages of recovery. Age range in the 33 cases reported as of June 9 was 4 to 48 years. Nearly all have had a characteristic rash progressing through papular, pustular, and crusted stages; most have had fever; more than half had cough or other respiratory symptoms; and some had enlarged lymph nodes. Other symptoms may include chills, sweats, headache, myalgia, malaise, and fatigue.

"This is our first experience with monkeypox in the Western hemisphere, so we're in a learning mode," CDC Deputy Director David Fleming said in a telebriefing on June 11. Although there have been no deaths in U.S. patients, he pointed out that the mortality rate in Africa was between 1% and 10%.

"There are lots of reasons why things may be different here, including improved medical treatment, better nutrition, so in some cases that may be optimistically, a worst-case scenario," Dr. Fleming said. "But we do need to be prepared for the fact that monkeypox can be a fatal disease."

Laboratory evidence of monkeypox in the confirmed U.S. cases includes electron microscopy images consistent with poxvirus, several polymerase chain reaction–based assays, serologic tests, immunohistochemistry, and gene sequencing.

Patients in the U.S. appear to have been infected through bites or other contact with exotic pets, including infected prairie dogs, a Gambian giant rat, and a pet rabbit purchased from a pet store where it may have been exposed to an infected animal. Phil's Pocket Pets, a pet dealership in the Chicago area, was quarantined after an individual with presumed monkeypox reported close contact with exotic animals sold there. Apparently the dealership housed prairie dogs together with a Gambian giant rat which had initially been shipped to Texas from Ghana. That shipment may have contained 800 other small mammals of nine different species that might have been the actual source of monkeypox.

The Illinois distributor sold prairie dogs and the Gambian giant rat to a distributor in Milwaukee, Wisconsin, who sold prairie dogs to two pet shops in the Milwaukee area and to others at a pet swap meet in Wisconsin. Ultimately, animals from this distributor may have been sold in several other states. As of June 12, the CDC has issued an immediate embargo and prohibition of importation, interstate transportation, sale, and release into the environment of certain rodents and prairie dogs.

The CDC is urging owners of pet rodents or others who may have been exposed to similar animals not to release ill animals into the wild, to call ahead to warn veterinarians before seeking care for these animals, and to immediately report rash, fever, or other symptoms of infectious illness. The CDC is also recommending that animals diagnosed with monkeypox be euthanized.

According to the World Health Organization (WHO), humans usually contract monkeypox through contact with an infected animal's blood, body fluids, or lesions, or by being bitten. In an outbreak of monkeypox in the Democratic Republic of Congo in Africa in 1997, most monkeypox cases in humans were in remote African villages near tropical rain forests where villagers could easily encounter infected monkeys and other animals. The case-fatality rate during that outbreak was 9.8% for persons not vaccinated with vaccinia (smallpox) vaccine.

The CDC is continuing to investigate the possibility of person-to-person transmission in the U.S. cases. In the Congo, the secondary transmission rate to other household members that were in very close direct contact with individuals infected from animal exposure was 9.3%.

After several generations of transmission from one individual to another, infectivity appeared not to be sustained. Although investigators in the African outbreak concluded that there was no evidence that person-to-person transmission alone could sustain monkeypox in the local population, they warned that in a population with low herd immunity, person-to-person transmission and repeated introduction of virus from the animal reservoir could lead to more and larger clusters of human monkeypox cases.

However, the CDC points out that outbreaks in one part of the world may not necessarily behave similarly to those in other parts of the world. In any event, monkeypox appears to be much less infectious via the person-to-person route than its relative, the smallpox virus. Possible means of transmission may include contact with large respiratory droplets during direct and prolonged face-to-face contact, with body fluids of an infected person, or with bedding, clothing, or other objects contaminated with the virus.

Because the smallpox vaccine was about 85% efficacious in preventing human monkeypox during the outbreak in rural Africa, the CDC is now recommending smallpox vaccination for individuals investigating monkeypox outbreaks, those involved in caring for infected individuals or animals, and those who have had close or intimate contact with individuals or animals confirmed to have monkeypox. These persons can be vaccinated up to 14 days after exposure. The CDC does not recommend pre-exposure vaccination for unexposed veterinarians, veterinary staff, or animal control officers, unless they are involved in field investigations.

"Monkeypox can be a serious illness, and it has not been previously seen in humans in this hemisphere. CDC and a team of expert advisors carefully weighed the risk of smallpox vaccination against the risks posed by exposure to monkeypox infection in arriving at this important decision," CDC Director Julie Gerberding, MD, said in a news release. "We must do everything we can to protect persons who are exposed to monkeypox in the course of investigating or responding to this outbreak."

Within the narrow constraints outlined above, the CDC is taking an aggressive stance toward vaccination. They recommend vaccination even in pregnant women and children who meet the above criteria, with counseling and decisions on a case-by-case basis for those who are immunocompromised or who have eczema.

"The decision around vaccination is going to be made at the local level in consultation between the state health department, the affected individual, and their private provider, and...all indications are that that is an important discussion but one that it will be fairly easy to arrive at a consensus," Dr. Fleming said.

The CDC is recommending that individuals not needing hospitalization for medical reasons can be cared for at home, provided they remain isolated and infectious precautions are observed until any open lesions scab over. Although there is no specific treatment, antiviral drugs, such as cidofovir, are being evaluated, and the CDC has issued an interim guidance on the use of smallpox vaccine, cidofovir, and vaccinia immune globulin.

"Because of the risks associated with cidofovir use, it's not something that should be considered unless there is a life-threatening illness that the patient is having, and then in that context it should be made on a case by case basis," Dr. Fleming said.

Standard, contact, and airborne precautions should be applied in all healthcare settings involving possible exposure, including hand washing, gown and gloves, eye protection for exposure to splash or spray of body fluids, filtering disposable respirator or surgical masks, negative pressure isolation room or private room, proper disposal of contaminated waste, caution when handling soiled laundry or equipment, and disinfecting environmental surfaces. Other specific recommendations, including surveillance in exposed healthcare workers, are available on the CDC site (http://www.cdc.gov/ncidod/monkeypox/index.htm).

Dr. Fleming was asked to comment on the rapid succession of unusual viral outbreaks in the U.S. — West Nile virus, severe acute respiratory syndrome (SARS), and now monkeypox. Although he first stated that this could be no more than "coincidence" because "things tend to happen in clusters," he also suggested that improved detection related to anti-bioterrorism efforts and increased globalization could be responsible.

"With the investments that have been made in this country, and in other countries, to improve public health infrastructure for detection of bioterrorism events, we should take this as a natural consequence, that we're going to be increasingly efficient and effective in identifying these naturally occurring threats as well.... So, in essence, this is confirmation of, number one, the need to invest in our system, and number two, the effectiveness of that system," he said. "We are living in a world that's increasingly globalized, and so if you look at the amount of travel that's occurring between countries, both of humans and of animals, that's been increasing exponentially. All of these outbreaks are...related to that globalization, and in that context we should expect that these will become more rather than less frequent."

To learn more about monkeypox and how clinicians should respond to this outbreak, Medscape's Laurie Barclay interviewed Cathy Roth, MD, a medical officer and virologist at the WHO in Geneva, Switzerland. Dr. Roth was part of the WHO investigative team in the October 1997 outbreak of monkeypox in the Democratic Republic of Congo, where she took part in both laboratory and epidemiological investigations.

Medscape: What is the significance of the monkeypox outbreak following so closely on the heels of the SARS outbreak? Are there factors related to worldwide travel, increased contact with exotic animals as pets or food sources, and/or bioterrorism that could herald similar outbreaks of unusual viral infections?

Dr. Roth: I think the significance of monkeypox following so rapidly after SARS is simply a matter of chance. However, underlying factors to be considered are the spread of disease in the modern world because of the increased frequency and speed of travel and trade. Over the past 30 to 40 years, we've also had better surveillance and reporting of infectious outbreaks, which improves each time there is a new occurrence. So we're more likely to recognize and publicize outbreaks, although it is true that they probably occur more frequently because of global travel. Sick animals and people can rapidly travel by airplane across the globe.

Medscape: In June of last year, UPI and NewsMax reported that Ken Alibek, a former deputy chief of the Soviet biological weapons program who now is a U.S. bioterrorism expert and advisor, was concerned about the potential use of monkeypox as a bioterror weapon. Do you think, as Dr. Alibek and some United Nations weapons inspectors have intimated, that Russia could have been working on monkeypox as a bioterrorist weapon, and that stocks of monkeypox may have fallen into Iraqi hands?

Dr. Roth: I have no direct knowledge of that. At the WHO we focus solely on public health issues. In the case of monkeypox, we were involved with intensified surveillance in Africa from 1970 to 1986, and with studying the outbreaks in the Democratic Republic of Congo in 1996 amd 1997.

Medscape: Is the monkeypox virus implicated in the U.S. cases the same as that identified in the African outbreaks, or is there any evidence of mutation or biological manipulation?

Dr. Roth: The WHO hasn't seen the U.S. data yet. The CDC is probably trying to characterize the genetic identity of the U.S. monkeypox virus, and then it could be compared with the African strains. But the first priority is confirmation or refutation of all the suspected cases. Genetic characterization could take some time — days or weeks.

Medscape: How effective is transmission via routes of animal-to-person, person-to-person, and from contaminated surfaces?

Dr. Roth: We really have no good data on that. In Africa, sporadic cases were presumed to have been exposed by the animal-to-person route. During the period of intensive surveillance from 1970 to 1986, there were cases of apparent person-to-person transmission, but it appeared to involve quite close contact, for example, those who cared for ill persons in the same household. From laboratory data on survival of viruses on sufaces, we know that orthopox viruses in general are moderately resistant, but we have no real community-based data on how well the monkeypox virus survives on contaminated surfaces.

Medscape: How rapidly is monkeypox spreading, and what can clinicians do to contain its spread?

Dr. Roth: The complete picture is still evolving in the US. In Africa, we still see occasional sporadic cases in those who depend on hunting for their survival, but there have been no confirmed large outbreaks since the one in 1997. What was thought to be a possible outbreak after that turned out to be chickenpox, as those diseases may be easily confused.

Medscape: What is the danger that ill animals already released into the wild may have spread monkeypox to other animals or to humans?

Dr. Roth: Well, I hope that none have been released. The U.S. authorities are encouraging people not to panic and release sick pets into the wild. It's very important not to do that, but to contact the local health authorities instead. If pets infected with monkeypox are released, they could infect wild animals which could in turn infect humans they might contact.

Medscape: Now that there has been a single case of monkeypox reported in New Jersey, what is the likelihood that cases will crop up in other states outside the Midwest?

Dr. Roth: That will depend largely on the export pattern of the affected animals. As time passes, we'll know more.

Medscape: Is there any danger that the monkeypox outbreak could mask an outbreak of smallpox, delaying recognition and isolation if the symptoms, signs, and virological findings in an index of case of smallpox are confused with those of monkeypox?

Dr. Roth: Clinically, the appearance of monkeypox is indistinguishable from that of smallpox, but it's a much milder illness. Now that the public is alerted to monkeypox as well as smallpox, any illness with a rash and other symptoms of infection will be very carefully investigated. The U.S. and some other countries now have very good systems in place to investigate these types of cases, so there should be no significant delays in detecting a smallpox outbreak if one should occur.

Medscape: Now that smallpox vaccination is being recommended in individuals at high risk for exposure to monkeypox, is this likely to cause depletion of the smallpox vaccine supply that could cause problems in the event of a smallpox outbreak?

Dr. Roth: The numbers of individuals who get vaccinated to protect against monkeypox will probably be very small, so it shouldn't have any significant effect in reducing the vaccine supply.

Medscape: What progress is anticipated in terms of treatment?

Dr. Roth: If antiviral drugs are used, careful attention will be given to determine whether or not they are effective. Any progress made in terms of treatment, whether it be in specific supportive care measures or in the efficacy of specific drugs, will be important and useful information for the future. Because the African outbreaks took place in isolated, rural areas, we don't have any experience with the efficacy of modern treatment. These patients just received basic supportive care. In terms of antiviral drugs, even those that are approved for human use in other conditions wouldn't be used empirically in humans with monkeypox. However, laboratory evidence that they would be effective already exists.

Medscape: What role should physicians play in this outbreak, and how can they reassure their patients?

Dr. Roth: Physicians should be alert that they might be seeing this illness, and should consider the diagnosis when they see a patient with a rash. They need to ask the right questions to determine if that patient could have been exposed to monkeypox, and to take samples and alert the public health authorities of suspected cases. Patients should be reassured that anything suspicious for monkeypox or other viral outbreak will be properly investigated. On the other hand, if they haven't been in close contact with rodents or with infected individuals, they are unlikely to have this disease.

Editor's Note: Dr. Roth reports no pertinent financial disclosures.

MMWR 2003;52(23):537-540

Reviewed by Gary D. Vogin, MD

Laurie Barclay, MD Writer for Medscape Medical News Medscape Medical News is edited by Deborah Flapan, a news coordinator at Medscape. Send press releases and comments to news@webmd.net.   Medscape Medical News 2003. © 2003 Medscape