Monkeypox: an epidemiologic and clinical comparison of African and US disease.

Department of Dermatology at Aspen Medical Group, Saint Paul, Minnesota, USA.
Journal of the American Academy of Dermatology (Impact Factor: 4.91). 10/2006; 55(3):478-81. DOI: 10.1016/j.jaad.2006.05.061
Source: PubMed

ABSTRACT Monkeypox is a double-stranded DNA virus and a member of the genus Orthopoxvirus. Human monkeypox was first identified in the Democratic Republic of the Congo (formerly Zaire) in 1970. The first outbreak in the western hemisphere occurred in the spring of 2003. Important epidemiologic and clinical differences exist between human monkeypox in the United States and in Africa, including sex distribution, case fatality, morphology of skin lesions, and associated lymphadenopathy. These divergent clinical presentations could be caused by mode of transmission (skin inoculation vs ingestion), the skin color of affected patients, the training backgrounds of those who saw and documented disease outbreaks, the virulence of monkeypox strains involved, nutritional status, access to advanced medical care, and the prevalence of prior smallpox vaccinations.

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    ABSTRACT: Although smallpox has been eradicated, other diseases caused by virulent orthopoxviruses such as monkeypox virus (MPV) remain endemic in remote areas of western and central sub-Saharan Africa, and represent a potential biothreat due to international travel and/or inadvertent exposure. Unfortunately, extensive antigenic cross-reactivity among orthopoxviruses presents a challenge to serological diagnosis. We previously reported a 20mer peptide-based ELISA that identified recent MPV infection with >90% sensitivity and >90% specificity. However, the sensitivity of this approach was not determined with samples obtained at later time points after antibody titers had declined from their peak levels. To improve assay sensitivity for detecting MPV-specific antibodies at later time points, we compared diagnostic 20mer peptides to 30mer peptides. In addition, optimal 30mer peptides were tested in combination or after conjugating selected peptides to a carrier protein (bovine serum albumin) to further improve assay performance. An optimized combination of four unconjugated 30mer peptides provided 100% sensitivity for detecting MPV infection at 2-6 months post-infection, 45% sensitivity for detecting MPV infection at >2 years post-infection, and 99% specificity. However, an optimized combination of two peptide conjugates provided 100% sensitivity for detecting MPV infection at 2-6 months post-infection, 90% sensitivity for detecting MPV infection at >2 years post-infection, and 97% specificity. Peptide-based ELISA tests provide a relatively simple approach for serological detection of MPV infection. Moreover, the systematic approach used here to optimize diagnostic peptide reagents is applicable to developing improved diagnostics to a broad range of other viruses, and may be particularly useful for distinguishing between closely-related viruses within the same genus or family.
    Vector borne and zoonotic diseases (Larchmont, N.Y.) 01/2012; 12(5):400-9. · 2.61 Impact Factor
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    ABSTRACT: The 2003 monkeypox virus (MPXV) outbreak and subsequent laboratory studies demonstrated that the black-tailed prairie dog is susceptible to MPXV infection and that the ensuing rash illness is similar to human systemic orthopoxvirus (OPXV) infection, including a 7-to 9-day incubation period and, likely, in some cases a respiratory route of infection; these features distinguish this model from others. The need for safe and efficacious vaccines for OPVX in areas where it is endemic or epidemic is important to protect an increasingly OPXV-naïve population. In this study, we tested current and investigational smallpox vaccines for safety, induction of anti-OPXV antibodies, and protection against mortality and morbidity in two MPXV challenges. None of the smallpox vaccines caused illness in this model, and all vaccinated animals showed anti-OPXV antibody responses and neutralizing antibody. We tested vaccine efficacy by challenging the animals with 10 5 or 10 6 PFU Congo Basin MPXV 30 days postvaccination and evaluating morbidity and mortality. Our results demonstrated that vaccination with either Dryvax or Acambis2000 protected the animals from death with no rash illness. Vaccination with IMVAMUNE also protected the animals from death, albeit with (modified) rash illness. Based on the results of this study, we believe prairie dogs offer a novel and potentially useful small animal model for the safety and efficacy testing of smallpox vaccines in pre-and postexposure vaccine testing, which is important for public health planning. Although smallpox has been eradicated (5), orthopoxviruses (OPXVs), such as variola virus (VARV) (6, 32), monkeypox virus (MPXV) (3, 10, 57), vaccinia virus (VACV) (4, 76), and others (53, 68, 77), are a continuing public health concern (61, 67). Due to cellular and humoral protective effects (7, 15, 16, 46, 73), the traditional live VACV-based smallpox vaccines provide cross-protection against multiple OPXV threats (48). Unfortunately, the cessation of routine vaccination (37) has left much of the global population fully susceptible to OPXV infections (34), and the adverse effects of first-and second-generation vaccines (78) coupled with increases in the global immunocompromised population (59) underline the need for continued development and testing of safer smallpox vaccines (30). Testing of smallpox vaccines requires the development of relevant animal models. Current smallpox vaccine testing ani-mal models include ectromelia virus (ECTV) infection of mice (75), VACV infection of mice (63), rabbitpox virus (RPXV) and VACV infection of rabbits (1, 18), VARV and MPXV infection of nonhuman primates (NHP) (13, 19, 21, 25, 26, 31), and others (65, 74). Limitations of current models include abbreviated disease incubation periods and/or differences from
    Journal of Virology 01/2011; 85(15):7683-7698. · 5.08 Impact Factor
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