Poxvirus Zoonoses — Putting Pocks into Context
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《新英格兰医药杂志》
Naturally occurring poxvirus infections affect humans and many species of animals and insects. Smallpox, the dreaded disease caused by the only human-specific orthopoxvirus pathogen, variola, was successfully eradicated in the last century by the induction of cross-protection through vaccination with vaccinia virus, an iatrogenic zoonosis. In the future, cases of smallpox will occur only if there is an accidental or intentional release of smallpox virus into the environment. However, infections of humans with animal poxviruses may be confused with smallpox. The growing popularity of exotic animals as household pets increases the concern about the spread of animal poxviruses to humans, as does rapid international travel, which may permit the global spread of infections that were once confined to well-defined geographic areas.
For the most part, poxviruses other than variola cause self-limited disease in immunocompetent humans. Classically, pocks are cutaneous vesicles that become pustular and evolve over a period of two to three weeks. As a pock dries, it forms a scab, frequently leaving a scar. With the recent concern about and media attention to potential bioterrorism, there is an increased awareness of emerging pox-related diseases, but few physicians have experience in diagnosing and treating these diseases.
Many poxviruses were named after the animal from which they were originally isolated (e.g., cowpox and monkeypox), but the main reservoirs for the viruses may be rodents or other species (see Table). Monkeypox (see Figure) is not readily transmitted from animals to humans or from humans to other humans without direct contact, and outbreaks are controlled with simple infection-control methods. The main vector for monkeypox is thought to be wild rodents; animals such as monkeys or anteaters are incidental hosts.
Table. Poxviruses That Infect Humans and Cause Disease.
Figure. Structure of the Monkeypox Virus.
The incubation period for monkeypox is approximately 5 to 21 days. As Reed et al. report in this issue of the Journal (pages 342–350), monkeypox infection begins with a two-day prodrome, followed by an abrupt onset of rash, often beginning on the face. Prominent features include headache (occurring in 100 percent of patients), fever (in 82 percent), sweats (in 82 percent), chills (in 82 percent), and lymphadenopathy (in 55 percent). The disease is usually mild and self-limited, and recovery is generally complete. The secondary attack rate for monkeypox in African households varies but is approximately 10 percent overall. The mortality rate is typically no more than 10 percent among unvaccinated persons. In comparison, the attack rate for smallpox is approximately 20 percent, and the mortality rate is 30 percent. Vaccination with vaccinia virus is known to provide protection against monkeypox.
Reed et al. report an outbreak of monkeypox in Wisconsin — the first such outbreak that has been recognized in the Western Hemisphere. This zoonosis was epidemiologically tracked to transmission from a rodent imported from Africa. The zoonosis spread to prairie dogs and eventually to humans. All patients with known cases had direct contact with prairie dogs; skin lesions developed in all the patients, and they all had self-limiting disease. Four of the 11 monkeypox-infected persons required hospitalization, but none of the patients required treatment with vaccinia immune globulin. Human-to-human transmission of monkeypox could not be ruled out in two cases. Six of the 11 patients had been vaccinated against smallpox as children. Infection-control procedures were implemented for humans and animals, and the spread of the virus was halted quickly.
Tanapox, a distinct poxvirus belonging to a different genus from that of smallpox and monkeypox, is transmitted to humans by its natural hosts, nonhuman primates, through minor trauma. Human-to-human transmission is considered to be rare. Disease is manifested by mild fever of abrupt onset that lasts three to four days, and the infection is limited to the exposed epidermis, with the formation of one or two pock lesions, although more lesions may occur in some cases. The pock lesions are not pustular, but rather firm and cheesy in appearance. There is no treatment for tanapox, and no protective cross-immunity is expected from vaccinia vaccine.
Dhar et al., also in this issue of the Journal (pages 361–366), present the fifth case of tanapox that has been documented in the United States since the 1960s. Three previously reported cases occurred in laboratory personnel. In the present case, a student from the United States who was working in the Republic of Congo handling orphaned chimpanzees had a classic presentation of tanapox. Because of her fever and the nonspecific nature of her presentation, she was initially treated with antimalarial drugs. Later, an attempt was made to drain what was thought to be an abscess. On further laboratory evaluation, including electron microscopy and polymerase chain reaction performed at the Centers for Disease Control and Prevention (CDC), a diagnosis of tanapox was made. The disease was self-limited and resolved without specific therapy.
Human-to-human transmission of most animal poxviruses is quite rare. Wild rodents are thought to be the principal reservoir for these viruses, although many species act as incidental hosts and expose humans to infection. As immunity to smallpox wanes in the general population and the popularity of exotic pets increases, the risk of human disease from animal orthopoxviruses may increase. It would be of interest to know whether the monkeypox-related illness reported by Reed et al. was milder or shorter in duration in the six patients who had received smallpox vaccine than in those who had not been vaccinated. If it was, that fact might suggest that immunologic memory has a role in limiting the replication of the virus.
Another matter of concern is the introduction of new poxviruses into an animal ecology that has not previously been exposed to them. Now that some prairie dogs have become a new vector for monkeypox, they may provide a useful new animal model for the study of poxvirus pathogenesis. Whether monkeypox virus could have escaped into a North American rodent vector during the outbreak of 2003 is an open question necessitating continued vigilance. At least 11 states were affected by the monkeypox outbreak.
Although disease is generally self-limited, immunocompromised hosts, children, and persons with atopy are at increased risk for poor outcomes. In addition, the clinical picture can be confused with those of other zoonoses, such as anthrax or plague, or other diseases that cause nodular skin formations, such as those caused by mycobacteria and fungi. Historically, varicella was sometimes confused with poxvirus illness, and such confusion may become a problem again, since the advent of vaccination against varicella has meant that younger clinicians have limited experience in identifying varicella infections.
The two current reports of disease caused by poxviruses demonstrate the need for physicians, veterinarians, and animal handlers to be aware of poxvirus infections, as well as the need to have a low threshold for reporting unusual disease presentations to public health authorities. Health care providers and local public health officials have immediate access to Web-based information and diagnostic expertise through the CDC. The CDC can provide assistance in identifying, categorizing, and tracking emerging infections caused by poxviruses. As in the 2003 monkeypox outbreak, humans and animals can then be isolated, and emergency orders issued to limit the transportation of animals, plants, and insects as necessary, in order to halt the spread of the virus.
Dr. Frey reports having received grant support from Acambis. Dr. Belshe reports having received lecture fees from Wyeth and grant support from Acambis and Wyeth.
Source Information
From the Division of Infectious Diseases and Immunology, Saint Louis University, St. Louis.(Sharon E. Frey, M.D., and)
For the most part, poxviruses other than variola cause self-limited disease in immunocompetent humans. Classically, pocks are cutaneous vesicles that become pustular and evolve over a period of two to three weeks. As a pock dries, it forms a scab, frequently leaving a scar. With the recent concern about and media attention to potential bioterrorism, there is an increased awareness of emerging pox-related diseases, but few physicians have experience in diagnosing and treating these diseases.
Many poxviruses were named after the animal from which they were originally isolated (e.g., cowpox and monkeypox), but the main reservoirs for the viruses may be rodents or other species (see Table). Monkeypox (see Figure) is not readily transmitted from animals to humans or from humans to other humans without direct contact, and outbreaks are controlled with simple infection-control methods. The main vector for monkeypox is thought to be wild rodents; animals such as monkeys or anteaters are incidental hosts.
Table. Poxviruses That Infect Humans and Cause Disease.
Figure. Structure of the Monkeypox Virus.
The incubation period for monkeypox is approximately 5 to 21 days. As Reed et al. report in this issue of the Journal (pages 342–350), monkeypox infection begins with a two-day prodrome, followed by an abrupt onset of rash, often beginning on the face. Prominent features include headache (occurring in 100 percent of patients), fever (in 82 percent), sweats (in 82 percent), chills (in 82 percent), and lymphadenopathy (in 55 percent). The disease is usually mild and self-limited, and recovery is generally complete. The secondary attack rate for monkeypox in African households varies but is approximately 10 percent overall. The mortality rate is typically no more than 10 percent among unvaccinated persons. In comparison, the attack rate for smallpox is approximately 20 percent, and the mortality rate is 30 percent. Vaccination with vaccinia virus is known to provide protection against monkeypox.
Reed et al. report an outbreak of monkeypox in Wisconsin — the first such outbreak that has been recognized in the Western Hemisphere. This zoonosis was epidemiologically tracked to transmission from a rodent imported from Africa. The zoonosis spread to prairie dogs and eventually to humans. All patients with known cases had direct contact with prairie dogs; skin lesions developed in all the patients, and they all had self-limiting disease. Four of the 11 monkeypox-infected persons required hospitalization, but none of the patients required treatment with vaccinia immune globulin. Human-to-human transmission of monkeypox could not be ruled out in two cases. Six of the 11 patients had been vaccinated against smallpox as children. Infection-control procedures were implemented for humans and animals, and the spread of the virus was halted quickly.
Tanapox, a distinct poxvirus belonging to a different genus from that of smallpox and monkeypox, is transmitted to humans by its natural hosts, nonhuman primates, through minor trauma. Human-to-human transmission is considered to be rare. Disease is manifested by mild fever of abrupt onset that lasts three to four days, and the infection is limited to the exposed epidermis, with the formation of one or two pock lesions, although more lesions may occur in some cases. The pock lesions are not pustular, but rather firm and cheesy in appearance. There is no treatment for tanapox, and no protective cross-immunity is expected from vaccinia vaccine.
Dhar et al., also in this issue of the Journal (pages 361–366), present the fifth case of tanapox that has been documented in the United States since the 1960s. Three previously reported cases occurred in laboratory personnel. In the present case, a student from the United States who was working in the Republic of Congo handling orphaned chimpanzees had a classic presentation of tanapox. Because of her fever and the nonspecific nature of her presentation, she was initially treated with antimalarial drugs. Later, an attempt was made to drain what was thought to be an abscess. On further laboratory evaluation, including electron microscopy and polymerase chain reaction performed at the Centers for Disease Control and Prevention (CDC), a diagnosis of tanapox was made. The disease was self-limited and resolved without specific therapy.
Human-to-human transmission of most animal poxviruses is quite rare. Wild rodents are thought to be the principal reservoir for these viruses, although many species act as incidental hosts and expose humans to infection. As immunity to smallpox wanes in the general population and the popularity of exotic pets increases, the risk of human disease from animal orthopoxviruses may increase. It would be of interest to know whether the monkeypox-related illness reported by Reed et al. was milder or shorter in duration in the six patients who had received smallpox vaccine than in those who had not been vaccinated. If it was, that fact might suggest that immunologic memory has a role in limiting the replication of the virus.
Another matter of concern is the introduction of new poxviruses into an animal ecology that has not previously been exposed to them. Now that some prairie dogs have become a new vector for monkeypox, they may provide a useful new animal model for the study of poxvirus pathogenesis. Whether monkeypox virus could have escaped into a North American rodent vector during the outbreak of 2003 is an open question necessitating continued vigilance. At least 11 states were affected by the monkeypox outbreak.
Although disease is generally self-limited, immunocompromised hosts, children, and persons with atopy are at increased risk for poor outcomes. In addition, the clinical picture can be confused with those of other zoonoses, such as anthrax or plague, or other diseases that cause nodular skin formations, such as those caused by mycobacteria and fungi. Historically, varicella was sometimes confused with poxvirus illness, and such confusion may become a problem again, since the advent of vaccination against varicella has meant that younger clinicians have limited experience in identifying varicella infections.
The two current reports of disease caused by poxviruses demonstrate the need for physicians, veterinarians, and animal handlers to be aware of poxvirus infections, as well as the need to have a low threshold for reporting unusual disease presentations to public health authorities. Health care providers and local public health officials have immediate access to Web-based information and diagnostic expertise through the CDC. The CDC can provide assistance in identifying, categorizing, and tracking emerging infections caused by poxviruses. As in the 2003 monkeypox outbreak, humans and animals can then be isolated, and emergency orders issued to limit the transportation of animals, plants, and insects as necessary, in order to halt the spread of the virus.
Dr. Frey reports having received grant support from Acambis. Dr. Belshe reports having received lecture fees from Wyeth and grant support from Acambis and Wyeth.
Source Information
From the Division of Infectious Diseases and Immunology, Saint Louis University, St. Louis.(Sharon E. Frey, M.D., and)