Review Cutaneous manifestations of filovirus infections Dieudonne ´ Nkoghe 1,2 , MD, Eric Maurice Leroy 1,3 , VD, PhD, Me ´dard Toung-Mve 2 , MD, and Jean Paul Gonzalez 1 , MD, PhD 1 Centre International de Recherches Me ´ dicales de Franceville (CIRMF), Franceville, Gabon, 2 Ministry of Health, Libreville, Gabon, and 3 MIVEGEC (IRD 224/CNRS 5290/UM1/UM2), Montpellier, France Correspondence Dr Dieudonne ´ Nkoghe, MD Infectious Diseases CIRMF BP 769 Franceville Gabon E-mail: dnkoghe@hotmail.com Conflicts of interest: None Abstract Ebolavirus and Marburgvirus, two filoviruses belonging to the Filoviridae family, are among the most virulent pathogens for humans and non-human primates, causing outbreaks of fulminant hemorrhagic fever (HF) in Central African countries with case fatality rates of up to 90%. Fruit bats are the likely reservoir, and human infection occurs through contact with bats or infected large-animal carcasses or by person-to-person contact (through body fluids, medical care, and burial practices). Schematically, clinical manifestations occur in three successive phases and include general, gastrointestinal, and mucocutaneous disorders. Death usually results from hemorrhagic complications. Cutaneous manifestations rarely make a major contribution to disease severity but can assist with the diagnosis. Rash, the main cutaneous disorder, is nonspecific and cannot guide the differential diagnosis. Immunohistochemical examination of skin biopsy or necropsy specimens can confirm the diagnosis. Introduction Filoviruses belong to the Filoviridae family, order Mono- negavirales, a large group of viruses with single-stranded RNA genomes of negative polarity. 1 The term ‘‘filovirus’’ refers to the elongated filamentous morphology of these pathogens on electron micrographs (Fig. 1). The other three major families of this order, which are genetically closely related to the filoviruses, are Paramyxoviridae (e.g. measles virus), Rhabdoviridae (e.g. rabies virus), and Bornaviridae (bornavirus). Filoviruses are divided into two genera: Marburgvirus (MARV) and Ebolavirus (EBOV). MARV includes a single species (Lake Victoria Marburgvirus), while EBOV is subdivided into five spe- cies: Zaire, Co ˆ te d’Ivoire, Sudan, Reston and Bundibugyo (recently discovered in Uganda). 2 Filoviruses are among the most virulent and hazardous pathogens for humans and non-human primates and are classified as level 4 security agents. Filoviral infections have been described in Africa, Europe, USA, Russia, and Asia. Filoviruses cause outbreaks of fulminant hemor- rhagic fever, mostly in equatorial Africa (Fig. 2) and more rarely in Europe. Since 1967, 23 Ebola outbreaks have been confirmed by virus isolation or by molecular and biological methods, and there have been nine documented outbreaks of Marburg fever. 3 Ebolavirus pathogenicity depends on the species: Zaire ebolavirus is more virulent than the other species, with a case fatality rate of 80–90%, compared with 50–55% with Sudan ebolavirus and 36% with Bundibugyo ebolavirus. Co ˆ te d’Ivoire ebo- lavirus has caused only one documented, non-fatal human case, while Reston ebolavirus has only been described in Asia, in non-human primates. The human lethality of Marburgvirus during the outbreak in Uige province, northern Angola, in 2004–2005, was close to that of Zaire ebolavirus. 4,5 The reservoirs of these viruses are not fully known, but recent studies have identified four fruit bat species (Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata, and Roussetus aegyptiacus) as likely natural reservoir species for EBOV and MARV in Gabon. 6,7 In appropriate physiological and environmental condi- tions, transmission to great apes (gorillas and chimpan- zees) occurs by direct contact with female bat blood and/ or placenta after delivery. 8 Spread within these non- human primates is due to direct contact in the course of fighting and breastfeeding. Human infection can occur in three ways: (i) by direct contact with body fluids of infected non-human primates (during poaching for exam- ple) or while handling infected animal carcasses found in the forest; 9 (ii) direct contact with reservoir species; 8 and (iii) more rarely, by accidental transmission in laboratory facilities. 10 Human–human transmission generally occurs 1037 ª 2012 The International Society of Dermatology International Journal of Dermatology 2012, 51, 1037–1043