a spread of monkeypox-infected animals and increased their interaction with humans across West and Central Africa. Monkeypox Cases in the United States Monkeypox remained an ignored global public health threat and was only given international attention when the first cases outside Africa were detected in the United States in 2003.48 After several Midwesterners developed fever, rash, respiratory symptoms, and lymphadenopathy, outbreak investigation linked the symptoms to exposure to pet prairie dogs (Cynomys species), and monkeypox virus was identified as a causative agent.48 It spread rapidly. Monkeypox cases were reported from 6 states—Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin—during the outbreak.49 Molecular investigations identified a monkeypox virus of the West African genetic group (clade). Epidemiologic studies concluded that the virus had been imported into the United States, more specifically to Texas, from Ghana on April 9, 2003, with a shipment of small mammals of 9 different species, including 6 genera of African rodents.50 These comprised rope squirrels (Funiscuirus sp.), tree squirrels (Heliosciurus sp.), African giant pouched rats (Cricetomys sp.), brush-tailed porcupines (Atherurus sp.), dormice (Graphiurus sp.), and striped mice (Lemniscomys sp.). Some of the infected animals were housed in close proximity to prairie dogs later sold as pets. Monkeypox Cases in the United Kingdom and Israel In September 2018, monkeypox again drew the attention of global media, politicians, and scientists when 3 individual patients in the United Kingdom were diagnosed with monkeypox.51 The first 2 had recently traveled in Nigeria, a country with an ongoing outbreak of the disease,52 and both were symptomatic during their flight home. The third case of monkeypox in the United Kingdom was diagnosed in a health care worker caring for 1 of these first 2 patients. As the clinical picture of the 3 patients’ disease raised a concern over an exotic disease, special infection control measures were taken well before monkeypox was suspected. One of the primary cases reported contact with a person with suspected rash at a family gathering, and the consumption of bushmeat.52 Secondary and tertiary human-tohuman transmission of monkeypox does occur in endemic areas.53,54 Of note, definitive confirmation of human-to-human transmission in endemic areas is somewhat problematic, because even the secondary and tertiary cases may have been exposed to infected animals. The disease contracted by the British health care worker provides indisputable evidence of human-to-human transmission from an infected patient. In October 2018, Israel reported a monkeypox case imported from Nigeria.55 It is well known that travelers can act as sentinels of infectious disease epidemics in the region visited. Not consistent with the reports of low levels of transmission in Nigeria, 3 cases imported to other countries from there within a couple of months should raise the concern of health authorities.56 Human Monkeypox 5 Ongoing Monkeypox Outbreak in West Africa On September 22, 2017, the Nigeria Center for Disease Control (NCDC) commenced an outbreak investigation following the identification of a suspected case of monkeypox in an 11-year-old child.57 The data available indicate that the current outbreak is either a multisource outbreak or one stemming from previously undetected endemic transmission, because the cases were not epidemiologically linked.28,58–60 The exact zoonotic origin and role of environmental and ecologic factors in the Nigerian outbreak are not yet known. New cases of monkeypox continue to be detected in the country. Since the beginning of the outbreak on September 22, 2018, as of January 1, 2019 there have been 311 suspected cases reported from 26 states (132 confirmed cases affecting children and adults of all ages) and 7 deaths reported.60 Most of the confirmed monkeypox patients are aged between 21 and 40 years, with a median age of 31 years, similar to the observed age range in DRC.42 It is noteworthy that all were born after 1978, when the global vaccination programs for smallpox were discontinued. MODES OF TRANSMISSION OF MONKEYPOX VIRUS TO HUMANS The exact mode of MPXV transmission to humans remains unknown. Primary animalto-human infection is assumed to occur when handling monkeypox-infected animals, through direct (touch, bite, or scratch) or indirect contact, although the exact mechanism(s) remains to be defined. The virus is assumed to enter the body through broken skin, respiratory tract, or the mucous membranes (eyes, nose, or mouth). Secondary human-to-human transmission is considered common,37,53,61 presumably through large respiratory droplets or direct or indirect contact with body fluids, lesion material, and contaminated surfaces or other material, such as clothing or linens. Prolonged contact with patients renders hospital staff and family members at greater risk of infection. Nosocomial transmission has been described.38 There is no evidence to date that human-to-human transmission alone can sustain monkeypox infections in the human population. There have only been a few genomic studies of the origins of monkeypox outbreaks. Human-to-human