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PubMed2006

Detection of monkeypox virus with real-time PCR assays.

BACKGROUND: Human monkeypox, a zoonotic disease, was first reported outside of Africa during the 2003 US outbreak. OBJECTIVES: We present two real-time PCR assays critical for laboratory diagnosis of monkeypox during the 2003 US outbreak. STUDY DESIGN: A TaqMan-based assay (E9L-NVAR) targets the orthopoxvirus DNA polymerase gene and detects Eurasian orthopoxviruses other than Variola. A hybridization assay, utilizing a MGB Eclipsetrade mark (Epoch Biosciences) probe, targets an envelope protein gene (B6R) and specifically detects monkeypox virus (MPXV). Assays were validated using coded orthopoxvirus DNA samples and used to evaluate lesion samples from five confirmed US monkeypox cases. RESULTS: E9L-NVAR did not detect variola (48 strains), North American orthopoxviruses (2), or DNA derived from non-poxviral rash illnesses. The assay reproducibly identified various concentrations of 13 Eurasian orthopoxvirus strains and was sensitive to 12.5 vaccinia genomes. The B6R assay recognized 15 different MPXV strains, while other orthopoxvirus (9) and bacteria (15) strains did not cross-react. Of the 13 human samples tested from confirmed cases, both assays identified 100% as containing MPXV DNA. CONCLUSIONS: E9L-NVAR and B6R assays demonstrate 100% specificity for non-variola Eurasian orthopoxvirus and MPXV, respectively. Using two discrete viral gene targets, these assays together provide a reliable and sensitive method for quickly confirming monkeypox infections.

Adult↗

PubMed2004

Human monkeypox: an emerging zoonosis.

Human monkeypox is a rare viral zoonosis endemic to central and western Africa that has recently emerged in the USA. Laboratory diagnosis is important because the virus can cause disease that is clinically indistinguishable from other pox-like illnesses, particularly smallpox and chickenpox. Although the natural animal reservoir of the monkeypox virus is unknown, rodents are the probable source of its introduction into the USA. A clear understanding of the virulence and transmissibility of human monkeypox has been limited by inconsistencies in epidemiological investigations. Monkeypox is the most important orthopoxvirus infection in human beings since the eradication of smallpox in the 1970s. There is currently no proven treatment for human monkeypox, and questions about its potential as an agent of bioterrorism persist.

Adult↗

PubMed2005

Extended interhuman transmission of monkeypox in a hospital community in the Republic of the Congo, 2003.

This report describes the first reported outbreak of human monkeypox in the Republic of Congo. Eleven confirmed and probable monkeypox cases were observed during this outbreak, all were less than 18 years old, and most resided on the grounds of the Government Hospital in Impfondo. Molecular, virologic, and serologic, and diagnostic assays were used to detect evidence of monkeypox (or orthopox) virus infection in individuals with striking dermatologic and other clinical manifestations. The majority of cases in this outbreak experienced significant, symptomatic illnesses; there was one death, possibly involving secondary complications, and one instance of profound sequelae. Up to six sequential transmissions of monkeypox virus from person to person are hypothesized to have occurred, making this the longest uninterrupted chain of human monkeypox fully documented to date. The pattern of sustained human-to-human transmission observed during this outbreak may influence our current perception of the capacity for this zoonotic virus to adapt to humans.

Adolescent↗

PubMed2005

Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox.

Approximately 50% of the US population received smallpox vaccinations before routine immunization ceased in 1972 for civilians and in 1990 for military personnel. Several studies have shown long-term immunity after smallpox vaccination, but skepticism remains as to whether this will translate into full protection against the onset of orthopoxvirus-induced disease. The US monkeypox outbreak of 2003 provided the opportunity to examine this issue. Using independent and internally validated diagnostic approaches with >or=95% sensitivity and >or=90% specificity for detecting clinical monkeypox infection, we identified three previously unreported cases of monkeypox in preimmune individuals at 13, 29 and 48 years after smallpox vaccination. These individuals were unaware that they had been infected because they were spared any recognizable disease symptoms. Together, this shows that the US monkeypox outbreak was larger than previously realized and, more importantly, shows that cross-protective antiviral immunity against West African monkeypox can potentially be maintained for decades after smallpox vaccination.

Animals↗

PubMed2005

Reemergence of monkeypox: prevalence, diagnostics, and countermeasures.

Human monkeypox is a viral zoonotic disease that occurs mostly in the rain forests of central and western Africa. However, the disease recently emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation very similar to that of ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. Given this clinical spectrum, differential diagnosis to rule out smallpox is very important. There are no licensed therapies for human monkeypox; however, the smallpox vaccine can protect against the disease. The discontinuation of general vaccination in the 1980s has given rise to increasing susceptibility to monkeypox virus infection in the human population. This has led to fears that monkeypox virus could be used as a bioterrorism agent. Effective prevention relies on limiting the contact with infected patients or animals and limiting the respiratory exposure to infected patients.

Animals↗

PubMed1988

The transmission potential of monkeypox virus in human populations.

Data on monkeypox in Zaire over the five years 1980-1984 are analysed to assess the protection imparted by past smallpox vaccination and the transmission potential of the virus in unvaccinated communities. Attack rates in individuals with and without vaccination scars indicated that smallpox vaccination (discontinued in 1980) imparted approximately 85% protection against monkeypox. It is predicted that monkeypox virus will continue to be introduced into human communities from animal sources, and that the average magnitude and duration of monkeypox epidemics will increase as vaccine-derived protection declines in the population. On the other hand, current evidence indicates that the virus is appreciably less transmissible than was smallpox, and that it will not persist in human communities, even in the total absence of vaccination. The findings thus support the recommendation of the Global Commission for the Certification of Smallpox Eradication to cease routine smallpox vaccination in monkeypox endemic areas, but to encourage continued epidemiological surveillance.

Democratic Republic of the Congo↗

PubMed1994

Evidence for recent genetic variation in monkeypox viruses.

DNA from isolates of monkeypox virus, when digested with the endonuclease PstI, gave fragment-size profiles which correlated with the geographic area from which the isolate originated. Although some of the differences were located subterminally in the genome, others mapped to the central conserved region. Further differentiation of the viral genomes was sought by analysis of a short region within the central conserved part of the genome that appeared to be a partially deleted counterpart of an intact 1024 bp open reading frame (ORF) present in variola and vaccinia virus genomes. We reasoned that this region would not be conserved by functional selection and would therefore be likely to show more variation between isolates of monkeypox virus. The deletions found in monkeypox virus isolates from Liberia and from Benin were almost the same as that which we had previously found in the Denmark strain. A much shortened ORF, potentially coding for a product of 133 amino acids, was retained in all three West African isolates, but three Zairean isolates each showed an identical series of small insertions and deletions which effectively abolish the ORF. Three deletions, present in all isolates, must pre-date the geographical separation of monkeypox virus lineages; other, presumably more recent, changes differ between the Zairean and West African isolates. In contrast, the base similarity was found to be more than 99% when all the monkeypox virus sequences were appropriately aligned. This, in a disrupted and presumably nonfunctional gene also indicates that the changes described are recent. It is suggested that insertions and deletions occur regularly during poxvirus DNA replication, but are preserved only in sequences that are not required for continued transmission in the natural host.

Africa, Western↗

PubMed2002

Outbreaks of disease suspected of being due to human monkeypox virus infection in the Democratic Republic of Congo in 2001.

Seven outbreaks of disease characterized by a pustular rash and suspected to have been caused by human monkeypox virus were investigated. The outbreaks occurred between February and August 2001 in the province of Equateur in the Democratic Republic of Congo. The outbreaks involved a total of 31 persons and caused five deaths. Specimens from 14 patients were available and were analyzed by electron microscopy, virus isolation, and PCR assays specific for monkeypox virus and varicella-zoster virus. We provide evidence that two outbreaks were indeed caused by monkeypox virus (16 cases, with four deaths), that in two outbreaks both monkeypox and varicella-zoster virus were involved (seven cases, with one death), and that two outbreaks were cases of chickenpox caused by infection with varicella-zoster virus (six cases, with no deaths). In one outbreak, no evidence for either monkeypox or chickenpox was found (two cases, with no deaths).

Adult↗

PubMed1987

The role of squirrels in sustaining monkeypox virus transmission.

When the research on the ecology of monkeypox virus entered the latest stage in 1984, three groups of animals were considered priority candidates for maintenance of virus circulations in nature because of their relatively higher population density: terrestrial rodents, squirrels, and gregarious bats. Following the isolation of the virus from a wild squirrel in 1985 another survey was carried out in Bumba zone of Zaïre in January-February 1986, which included collection of animal samples, later on tested by WHO collaborating laboratories. No antibodies were found in 233 rodents tested. A high prevalence of monkeypox-specific antibodies (24.7%) found in 320 squirrels of Funisciurus anerythrus species suggested that these animals sustain virus transmission in the areas surrounding human settlements. A consistently high level of antibody prevalence found among squirrels Heliosciurus rufobrachium suggested that this species is also steadily involved in the transmission. The squirrels, the only mammals frequently infected by monkeypox in the areas of human activities, which are frequently trapped by the population, are obviously a major source of infection for human beings. Out of 39 primates collected during the survey from the primary forest, three were found seropositive for monkeypox. At the moment, however, it is difficult to say whether the primates play an important role in sustaining virus transmission in nature, or (like human beings) that they are an occasional host of the virus. Possibilities are discussed of monkeypox virus transmission being sustained by squirrels outside the areas of major human activities.

Animals↗

PubMed1988

Human monkeypox: secondary attack rates.

Data on human monkeypox collected in Zaire during the six years 1981-86 were analysed to assess the extent of interhuman transmission of monkeypox virus. Among the 2278 persons who had close contact with 245 monkeypox patients infected from an animal source, 93 fell ill and were presumed to have been infected from the known human source: 69 of these were spread in the first generation, 19 in the second generation, and the remaining five cases in the third and fourth generation.The secondary attack rates were correlated with the age, sex, place of residence, and vaccination status of the contacts. There was an overall 3% probability of becoming ill following infection from a known human source. The affected household was the main focal point for interhuman transmission of monkeypox virus. The highest attack rate (11.7%) occurred among unvaccinated household contacts in the age group 0-4 years. However, the majority of susceptible persons who had been close to patients in the confined space of poorly ventilated huts failed to develop illness. There was no evidence of an increase in the secondary attack rate between 1970-80 and 1981-86.The inefficient spread from person to person, even in conditions of maximum exposure, supports the concept that monkeypox virus is poorly adapted for sustained transmission between humans and that such transmission does not pose a significant health problem.

Adolescent↗

PubMed1988

Monkeypox virus: ecology and public health significance.

Recent investigations have revealed that monkeypox virus infections occur with a high prevalence in several species of squirrels belonging to the genus Funisciurus, less frequently in squirrels of the genus Heliosciurus, and rarely in forest-dwelling primates. These squirrels commonly inhabit the secondary forests around human settlements in the rural areas of Zaire, especially where oil palms are grown, and are rare in the primary rain forest.Human infection with monkeypox virus occurs most frequently in the 5-9-year-old age group, particularly in small villages where the children hunt and eat squirrels and other small mammals. As the populations are now increasing in number and can no longer feed on wild life alone for their animal protein requirements, the development of animal husbandry as a source of meat will certainly decrease the risk and the incidence of human monkeypox, even in areas where monkeypox virus is present in the local population of squirrels.Although population growth and economic development in western and central Africa will probably reduce the risk of human infection with monkeypox virus, visitors to these areas who are likely to come into contact with wild animals should be offered smallpox vaccination as a protection.

Animals↗

PubMed1997

Human monkeypox--Kasai Oriental, Zaire, 1996-1997.

Monkeypox is an orthopoxvirus with enzootic circulation in rainforests of central and western Africa; the virus can be transmitted to humans and cause a syndrome clinically similar to smallpox (e.g., pustular rash, fever, respiratory symptoms, and in some cases, death). From February through August 1996, a total of 71 clinical cases of monkeypox, including six deaths, occurred in 13 villages in Africa in the Katako-Kombe health zone (1996 combined population: 15,698), Sankuru subregion, Kasai Oriental, Zaire. During the initial investigation of this cluster of human cases, specimens of serum and/or crusted scab or fluid from vesicles were collected from 11 patients, and monkeypox virus infection was confirmed in all 11 patients by the World Health Organization (WHO) Collaborating Center for Smallpox and Other Poxvirus Infections at CDC. Preliminary DNA phylogenetic studies of this strain of virus indicated only minor genetic variation compared with other strains of monkeypox virus from Zaire collected during 1970-1979. Because of reports by local public health officials of ongoing disease transmission, the Zaire Ministry of Health and WHO organized a follow-up investigation in February 1997 to characterize the magnitude of the outbreak. This report summarizes the preliminary results of the ongoing multidisciplinary investigation, which suggest that person-to-person transmission accounted for most monkeypox cases investigated in 1996 and 1997; in contrast, during previous years, reports were primarily for sporadic cases that resulted from animal-to-human transmission.

Cluster Analysis↗

PubMed1997

Human monkeypox -- Kasai Oriental, Democratic Republic of Congo, February 1996-October 1997.

Human monkeypox is a severe smallpox-like illness caused by monkeypox virus (MPV); monkeypox occurs in sporadic outbreaks, and infection is enzootic among squirrels and monkeys in the rainforests of western and central Africa. In 1996, cases of monkeypox were reported from villages in the Katako-Kombe Health Zone, Kasai Oriental, Zaire (i.e., Democratic Republic of Congo). The World Health Organization (WHO), in collaboration with CDC, investigated this outbreak and identified 92 suspected cases with onset during February 1996-February 1997, and isolated MPV from lesions of active cases. Cases continued to be reported, and a new investigation was initiated by WHO and CDC in October 1997. This report summarizes the results of the field investigation, which indicate that this is the largest human monkeypox outbreak ever recorded.

Democratic Republic of the Congo↗

PubMed2004

Monkeypox transmission and pathogenesis in prairie dogs.

During May and June 2003, the first cluster of human monkeypox cases in the United States was reported. Most patients with this febrile vesicular rash illness presumably acquired the infection from prairie dogs. Monkeypox virus was demonstrated by using polymerase chain reaction in two prairie dogs in which pathologic studies showed necrotizing bronchopneumonia, conjunctivitis, and tongue ulceration. Immunohistochemical assays for orthopoxviruses demonstrated abundant viral antigens in surface epithelial cells of lesions in conjunctiva and tongue, with less amounts in adjacent macrophages, fibroblasts, and connective tissues. Viral antigens in the lung were abundant in bronchial epithelial cells, macrophages, and fibroblasts. Virus isolation and electron microscopy demonstrated active viral replication in lungs and tongue. These findings indicate that both respiratory and direct mucocutaneous exposures are potentially important routes of transmission of monkeypox virus between rodents and to humans. Prairie dogs offer insights into transmission, pathogenesis, and new vaccine and treatment trials because they are susceptible to severe monkeypox infection.

Animals↗

PubMed1972

Outbreaks of monkeypox and serological surveys in nonhuman primates.

In connexion with the recent detection of cases of monkeypox in man in West and Central Africa, the frequency of monkeypox outbreaks in monkeys since 1958, when the disease was first recognized in captive animals, has been investigated. Special incidence surveys were made for this purpose. During the last 3 years, a serological survey has been conducted to find natural foci of monkeypox virus, and a total of 2 242 sera from monkeys of different species from various parts of Africa and Asia have been examined for poxvirus antibodies. The survey failed to detect any significant indication of poxvirus infections. The observations suggest that although a few human cases of monkeypox have been identified, monkeypox in the natural environment is not widespread and is perhaps localized in small areas.

Africa↗

PubMed2006

Clinical manifestations of human monkeypox influenced by route of infection.

BACKGROUND: In April 2003, an outbreak of monkeypox occurred in the United States following the importation of monkeypox virus (MPXV)-infected animals in a consignment of exotic pets from West Africa. Transmission of the virus to non-African captive species, including prairie dogs, preceded human disease. METHODS: We evaluated the influence of the route of infection on clinical illness for persons with confirmed and probable cases of human monkeypox. Exposures were categorized as being "noninvasive" (e.g., the person touched an infected animal, cleaned an infected animal's cage, and/or stood within 6 feet of an infected animal) or "complex" (e.g., invasive bite or scratch from an ill prairie dog plus potential noninvasive exposure), and associations between exposure, illness manifestation, and illness progression (i.e., elapsed time from first exposure to an ill prairie dog through various benchmarks of illness) were assessed. RESULTS: Patients with complex exposures were more likely than patients with noninvasive exposures to have experienced pronounced signs of systemic illness (49.1% vs. 16.7%; P=.041) and to have been hospitalized during illness (68.8% vs. 10.3%; P<.001). Complex exposures were also associated with shorter incubation periods (9 days for complex exposures vs. 13 days for noninvasive exposures) and the absence of a distinct febrile prodrome. CONCLUSIONS: The findings of this study indicate that route of infection can influence monkeypox illness manifestations.

Animals↗

PubMed2005

A tale of two clades: monkeypox viruses.

Human monkeypox was first recognized outside Africa in 2003 during an outbreak in the USA that was traced to imported monkeypox virus (MPXV)-infected West African rodents. Unlike the smallpox-like disease described in the Democratic Republic of the Congo (DRC; a Congo Basin country), disease in the USA appeared milder. Here, analyses compared clinical, laboratory and epidemiological features of confirmed human monkeypox case-patients, using data from outbreaks in the USA and the Congo Basin, and the results suggested that human disease pathogenicity was associated with the viral strain. Genomic sequencing of USA, Western and Central African MPXV isolates confirmed the existence of two MPXV clades. A comparison of open reading frames between MPXV clades permitted prediction of viral proteins that could cause the observed differences in human pathogenicity between these two clades. Understanding the molecular pathogenesis and clinical and epidemiological properties of MPXV can improve monkeypox prevention and control.

Animals↗

PubMed2004

Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox.

Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.

Animals↗