emerging and reemerging infections. All authors have no other conflict of interest to declare. a Institute of Clinical Medicine, University of Aarhus, Palle Juul-Jensens Boulevard 82, Aarhus N DK-8200, Denmark; b The Royal Hospital, Muscat, Oman; c European Society for Clinical Microbiology and Infectious Diseases, Task Force for Emerging Infections, Basel, Switzerland; d Inflammation Center, Helsinki University Hospital and Helsinki University, Stenba¨ ckinkatu 9, PO BOX 100, Helsinki FI-00029 HUS, Finland; e Viroscience Department, Erasmus Medical Centre, Postbus 2040, Rotterdam 3000 CA, the Netherlands; f Department of Public Health, College of Medicine, Ambrose Alli University, Ekpoma, Nigeria; g Department of Public Health, and Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria; h Nigeria Centre for Disease Control, Plot 801, Ebitu Ukiwe Street, Jabi, Abuja, Nigeria; i Division of Infection and Immunity, Center for Clinical Microbiology, University College London, The National Institute of Health Research Biomedical Research Centre at UCL Hospitals, Gower Street, London WC1E 6BT, UK * Corresponding author. Directorate General for Communicable Disease Surveillance and Control, Ministry of Health, 18th November Street, 101 Muscat, Sultanate of Oman. E-mail address: eskild.petersen@gmail.com KEYWORDS Monkeypox Smallpox West Africa Epidemic KEY POINTS Human monkeypox is a zoonosis caused by the monkeypox virus (MPXV), a doublestranded DNA virus of the family Poxviridae. The frequency and geographic distribution of human monkeypox cases across West and Central Africa have increased in recent years. Continued Infect Dis Clin N Am - (2019) -–- https://doi.org/10.1016/j.idc.2019.03.001 id.theclinics.com 0891-5520/19/ª 2019 Elsevier Inc. All rights reserved. INTRODUCTION Human monkeypox virus (MPXV) is a double-stranded DNA virus of the Orthopoxvirus genus of the family Poxviridae.1–4 Two genetic clades of the monkeypox virus have been characterized: West African and Central African. MPXV is one of the 4 orthopoxvirus species pathogenic for humans, the other 3 being (1) variola major virus (VARV), the causative agent of smallpox, now eradicated, (2) variola minor virus, and (3) cowpox virus (CPXV). There is a range of animal poxviruses, several of which have zoonotic potential. Infections in humans have been described for vaccinia virus, cowpox virus, buffalopox virus, and sporadic cases of camelpox.5,6 Monkeypox infects a wide range of mammalian species, but its natural host reservoir remains unknown. PUBLIC HEALTH IMPORTANCE Thought to be a rare and self-limiting disease,7 monkeypox has not attracted much attention since its discovery 70 years ago. The frequency and geographic distribution of human monkeypox cases have increased in recent years in a specific region of Africa (Fig. 1),8 and monkeypox has been recognized as an increasing public health threat, particularly in regions in West Africa where there is close interaction between humans and wild animal reservoirs and in particular where there is evidence that the infection attack rate is increasing. The clinical presentation of monkeypox is similar to that of smallpox2 in terms of symptom onset, timing of rash occurrence, and rash distribution,7 but generally less severe than smallpox in terms of complication rate, case fatality rate, and levels of scarification. Recently, concern has been raised about the emergence of MPXV as well as the resemblance of its clinical presentation to that of smallpox, a deadly disease globally eradicated by vaccination 40 years ago.9 During outbreaks, it has been challenging to clinically distinguish monkeypox from chickenpox, an unrelated herpesvirus infection. However, sporadic zoonotic infections with other orthopoxviruses also call for vigilance. Outbreaks of buffalopox have occurred with multiple human cases in India.10 Similarly, during outbreaks of vaccinia virus infection in cattle in Brazil, there is documented evidence of human infections.11 Cross-Immunity and Protection Various orthopoxvirus species share genetic and antigenic features,12–14 and an infection by any of these species may confer substantial protection against infection by the others.15 Vaccination with vaccinia virus protects against disease caused by VARV, MPXV, or CPXV.16 The immunologic mechanisms underlying cross-protection by immunization with vaccinia virus seem to be diverse, with neutralizing antibodies among the principal components.17 Consistent with the ability of smallpox vaccine to provide Continued The clinical presentation of monkeypox is similar to that of smallpox, in terms of symptom onset, timing of rash occurrence, and rash distribution, but generally less severe than smallpox with lower fatality rate and scarification. Most confirmed Monkeypox cases are younger than 40 years with a median age of 31 years, a population born only after discontinuation of the smallpox vaccination campaign, and thus may reflect a lack of cross-protective immunity. 2 Petersen et al cross-protection for humans against monkeypox, monkeys can be protected against monkeypox by immunization with the human smallpox vaccine.18,19 Ever since smallpox vaccinations were discontinued in 1978, cross-protective immunity to various