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    Dogged pursuit

    Dermatologist first to diagnose monkeypox


    The child, bitten by a prairie dog, had secondary lesions adjacent to the primary inoculation site. Photographs courtesy of the Marshfield Clinic.
    Washington, D.C. - The rash was like nothing John Melski, M.D., had ever seen before and he had reason to be alarmed. Bitten by a prairie dog, his 3-year-old patient had been hospitalized with a fever that raged for days despite intravenous antibiotics. Meanwhile, her parents became sick as well. It took Dr. Melski nine days of high-tech sleuthing to find out he was the first dermatologist in the Western Hemisphere to diagnose monkeypox in humans.

    "It was a very exciting time," said Dr. Melski, who will describe his encounter with the disease when he speaks at the American Academy of Dermatology annual meeting here Feb. 6-11.

    When Dr. Melski of Wisconsin's Marshfield Clinic first examined the patient on May 25, 2003, the lesions had already spread from prairie dog bites on the girl's right forefinger and left hand to her trunk and feet. They were domed edematous papules, dimpled in the center. Lesions in the advanced stages had a hemorrhagic crust.

    Searching the literature, Dr. Melski ruled out plague, anthrax and most other bacterial diseases because a broad spectrum of oral and intravenous antibiotics had not helped. That led him to conclude some sort of virus must be at work. And since some of the lesions were in places the patient could not easily reach, he decided the virus must be blood-borne. Suspecting herpes, he started the child on intravenous acyclovir.

    At the same time, he biopsied the lesions and sent samples to pathology, asking to process them immediately. It was a Sunday, the day before Memorial Day, but by 9 p.m., Dr. Melski had the results back and they supported his theory that a virus was to blame.

    But what virus? All of Dr. Melski's assays came back negative - including those for herpes - leading him to suspect a poxvirus. He searched the literature intensively for references to pox in prairie dogs, but found nothing that could be passed to a human being.

    Talking to the child's family was just as confusing; in addition to two prairie dogs - one by now dead from the disease, another recovering - the family owned 13 cats, 20 dogs, seven horses, four goats, and three donkeys. "With this menagerie of other animals, I wasn't sure who gave what to whom!"

    And now the child's mother was sick as well, with a sore throat, drenching sweats, fever, malaise and, at the site of a cat scratch, vesicles and erythema. Dr. Melski took biopsies from the mother and sent them to Dr. Kurt Reed, Marshfield infectious disease pathologist, for electron microscopy. By that Friday, the results confirmed the presence of a poxvirus, and Dr. Reed began to further isolate the virus using a negative staining technique.

    The outbreak would have been dire indeed, except that the girl had begun to recover, and her mother's illness was brief. They were both feeling well by the time the father fell ill that weekend, one week after the girl first came to Dr. Melski.

    Finally, that Tuesday, everything came together. Not only did Dr. Reed identify the culprit as an orthopox - the class of pox viruses that includes monkeypox - but Dr. Melski also learned that the prairie dogs had been near an African Gambian rat, known to be susceptible to monkeypox. "That was the epiphany," he said. "That was the 'Eureka!' moment."

    That same day, similar clinical cases with prairie dog exposure were reported from the Milwaukee area, prompting notification of the U.S. Centers for Disease Control and Prevention. The virus was quickly sequenced and found to be monkeypox. CDC officials traced the illness to a single distributor of prairie dogs in Illinois - who himself was the first person to become sick in the outbreak - and found others affected.


    The mother of the patient showed disseminated umbilicated vesicles, and reported sweats and a sore throat.
    "We were able to find a number of residences that had prairie dogs as pets," says Mark Sotir, Ph.D., a CDC epidemiologist who, along with Inger K. Damon, M.D., Ph.D., chief of the agency's pox virus section, presented his findings at the Infectious Diseases Society of America annual meeting in San Diego. A federal ban on the import of African rodents to the U.S. swiftly followed.

    Altogether, Dr. Damon reported 22 suspect, 12 probable, and 37 confirmed cases of monkeypox along with 87 "persons of special interest" from Wisconsin, Indiana, Illinois, Missouri, Kansas, Ohio, Texas, New Jersey, Iowa, and Michigan. Those with confirmed cases experienced symptoms similar to those of Dr. Melski's patients: rash (97 percent), fever (86 percent), lymphadenopathy (73 percent), and sweats (67 percent). Thirty-seven percent were hospitalized, but the illness was mild for most patients, and none died.

    The 3-year-old who first came to Dr. Melski's attention, however, will have surgery to treat a lacrymal duct obstruction that resulted from conjunctivitis associated with the illness.

    In Africa, the virus has killed between one and 10 percent of its human victims. Investigators theorized that the patients fared better in this outbreak - the first ever in the United States - either because they were in better health than Africans on average, or because this was a weaker strain of the virus.

    There is no established treatment for monkeypox. Cidofovir has been shown to attack monkeypox viruses in animal and in vitro studies, but no one knows whether the drug will benefit a patient with a serious monkeypox infection. It can cause severe adverse reactions.

    Some studies suggest that the smallpox vaccine is more than 85 percent effective in preventing monkeypox, according to a CDC report. But the data is limited and it is unclear whether the vaccine can be used to treat monkeypox after exposure, though it does help in treating smallpox.

    In the 2003 U.S. outbreak, 88 people were given the smallpox vaccine, according to Dr. Damon. Melski was not among them; by the time the option was made available, he decided it was too late for the vaccine to be useful. Marshfield Clinic lab personnel were vaccinated.

    Dr. Melski did change his approach to handling patients after making the diagnosis, though. Since monkeypox may spread through large respiratory droplets as well as intimate contact, he began using a mask with a positive pressure breathing apparatus and seeing patients in a negative-pressure room.

    One lesson from the episode, Dr. Melski says, is that dermatologists should be consulted more promptly when primary care and emergency-room physicians encounter an unusual disease involving symptoms of the skin. "We have all the tools to understand pathological processes in the skin. Our colleagues don't necessarily have that. But it was not until after the child failed antibiotics that I was called in."

    The monkeypox proved one of the biggest surprises of Dr. Melski's career. "If you had asked me if I would ever see monkeypox in my time, I would have said, 'no.'"

    But the case proves that dermatologists today have to be prepared for anything, says Janet Fairley, MD, a Medical College of Wisconsin dermatology professor who saw the prairie dog distributor a few days after Dr. Melski's patients came to him. "It demonstrates how small our world has become and how something that used to be confined to Africa can come up in Wisconsin, of all places."

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