Clinical Characteristics of Human Monkeypox, and Risk Factors for Severe Disease

University of Illinois at Chicago, Chicago, Illinois, United States
Clinical Infectious Diseases (Impact Factor: 8.89). 12/2005; 41(12):1742-51. DOI: 10.1086/498115
Source: PubMed


Human monkeypox is an emerging smallpox-like illness that was identified for the first time in the United States during an outbreak in 2003. Knowledge of the clinical manifestations of monkeypox in adults is limited, and clinical laboratory findings have been unknown.
Demographic information; medical history; smallpox vaccination status; signs, symptoms, and duration of illness, and laboratory results (hematologic and serum chemistry findings) were extracted from medical records of patients with a confirmed case of monkeypox in the United States. Two-way comparisons were conducted between pediatric and adult patients and between patients with and patients without previous smallpox vaccination. Bivariate and multivariate analyses of risk factors for severe disease (fever [temperature, > or =38.3 degrees C] and the presence of rash [> or =100 lesions]), activity and duration of hospitalization, and abnormal clinical laboratory findings were performed.
Of 34 patients with a confirmed case of monkeypox, 5 (15%) were defined as severely ill, and 9 (26%) were hospitalized for >48 h; no patients died. Previous smallpox vaccination was not associated with disease severity or hospitalization. Pediatric patients (age, < or =18 years) were more likely to be hospitalized in an intensive care unit. Nausea and/or vomiting and mouth sores were independently associated with a hospitalization duration of >48 h and with having > or =3 laboratory tests with abnormal results.
Monkeypox can cause a severe clinical illness, with systemic signs and symptoms and abnormal clinical laboratory findings. In the appropriate epidemiologic context, monkeypox should be included in the differential diagnosis for patients with unusual vesiculopustular exanthems, mucosal lesions, gastrointestinal symptoms, and abnormal hematologic or hepatic laboratory findings. Clinicians evaluating a rash illness consistent with possible orthopoxvirus infection should alert public health officials and consider further evaluation.

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    • "The patients were found to be infected with a West African strain of monkeypox virus caused by close contact with sick pet prairie dogs (Cynomys spp.), which may have been in contact with wild rodents imported from Ghana [7] [8]. There were no deaths during the USA outbreak, but some pediatric patients developed serious complications that could have resulted in death [8]. The disease course is often milder than that of smallpox. "
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    ABSTRACT: The pathogenesis of severe human monkeypox, which causes systemic and fulminant infections, is not clear. This study presents a case repot of fulminant monkeypox with bacterial sepsis after experimental infection with monkeypox virus in a cynomolgus monkey (Macaca fascicularis). In our previous study (Saijo et al., 2009, J Gen Virol), two cynomolgus monkeys became moribund after experimental infection with monkeypox virus Liberia strain, West African strain. One exhibited typical monkeypox-related papulovesicular lesions. The other monkey presented fulminant clinical symptoms with a characteristic flat red rash similar to that found in smallpox, which is associated with extremely high fatality rates. In this study, we found that the monkey with flat red rash had high levels of viremia and neutropenia, as well as high plasma levels of pro-inflammatory cytokines and chemokines compared with the other monkey. Monkeypox virus replicates in epithelial cells and macrophages in various organs. Sepsis due to Gram-positive cocci was confirmed histopathologically in the monkey with flat red rash. The lack of inflammatory response in the lesion suggested that the monkey with sepsis experienced strong immune suppression during the viral infection. The neutropenia and excessive inflammatory cytokine responses indicate that neutrophils play key roles in the pathogenesis of systemic and fulminant human monkeypox virus infections with sepsis.
    Full-text · Article · Aug 2014 · International journal of clinical and experimental pathology
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    • "Monkeypox virus (MPXV), an emerging virus that could cause up to 10% lethality in humans, poses a risk to human health as an infectious agent and as a potential biological weapon. Human MPXV infection resembles, in many aspects, clinical symptoms of smallpox, including fever, weight loss, lesions, and death [1,2]. To fully understand the pathogenesis of MPXV and related orthopoxviruses, such as variola virus, and to provide a model to evaluate countermeasures to these poxviruses, a MPXV non-human primate (NHP) model has been developed [3,4]. "
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    ABSTRACT: Natural killer (NK) cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV) infection is not well characterized. In this intravenous challenge study of MPXV infection in rhesus macaques (Macaca mulatta), we analyzed blood and lymph node NK cell changes in absolute cell numbers, cell proliferation, chemokine receptor expression, and cellular functions. Our results showed that the absolute number of total NK cells in the blood increased in response to MPXV infection at a magnitude of 23-fold, manifested by increases in CD56+, CD16+, CD16-CD56- double negative, and CD16+CD56+ double positive NK cell subsets. Similarly, the frequency and NK cell numbers in the lymph nodes also largely increased with the total NK cell number increasing 46.1-fold. NK cells both in the blood and lymph nodes massively proliferated in response to MPXV infection as measured by Ki67 expression. Chemokine receptor analysis revealed reduced expression of CXCR3, CCR7, and CCR6 on NK cells at early time points (days 2 and 4 after virus inoculation), followed by an increased expression of CXCR3 and CCR5 at later time points (days 7-8) of infection. In addition, MPXV infection impaired NK cell degranulation and ablated secretion of interferon-γ and tumor necrosis factor-α. Our data suggest a dynamic model by which NK cells respond to MPXV infection of rhesus macaques. Upon virus infection, NK cells proliferated robustly, resulting in massive increases in NK cell numbers. However, the migrating capacity of NK cells to tissues at early time points might be reduced, and the functions of cytotoxicity and cytokine secretion were largely compromised. Collectively, the data may explain, at least partially, the pathogenesis of MPXV infection in rhesus macaques.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "Finally, there is also interest in therapeutics for treatment of other poxviruses, such as monkeypox, which is transmitted among rodent populations. A monkeypox outbreak occurred for the first time in the USA in 2003 [5], [6], [7], [8]. "
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    Full-text · Article · Nov 2012 · PLoS ONE
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