and Multi-Jurisdictional Monkeypox Outbreak 2022 – What We Know So Far 5 Singapore) in 2018 and 2019. However, Isidro et al. detected 50 mutations (single nucleotide polymorphisms) in the 2022 outbreak virus compared to those in 2018 and 2019, which suggested that an “evolutionary jump” may have led to a “hypermutated virus”.23 · Epidemiologically, international events have also been implicated in seeding the monkeypox virus worldwide. Contact tracing exercises have traced some cases to the Gran Canarian gay pride festival which had up to 80,000 attendants between May 5 and 15, 2022; at least three cases in Belgium have been traced to a large-scale festival in Antwerp between May 5 and 8; and many cases in Spain have been traced to a single sauna in Madrid.24 At the time of this report, travel history for the 26 Canadian cases was not available.25 · It has also been hypothesized that low-level transmission of monkeypox may not have been detected given the infrequent occurrence and lack of awareness among health care providers.24 Clinical Presentation · Monkeypox is usually self-limiting, lasting for 2–4 weeks.4 Compared to the Central African clade, the West African clade of monkeypox virus is generally associated with less severe disease.26 However, monkeypox may be severe in some individuals, such as children, pregnant women or persons with immune suppression due to other health conditions.1 · Within three days from the onset of the prodrome symptoms which include fever, chills, myalgia, fatigue, headache, backache,3 and sometimes sore throat and cough, a maculopapular rash starts from the site of inoculation and rapidly spreads to other parts of the body. Lesions on oral or ophthalmic mucosa (enanthem) may be present4 and these develop before lesions appear in other parts of the body. Palms and soles are involved in cases of the disseminated rash, which is a characteristic of the disease. Within 12 days, the lesions usually progress simultaneously from macules to papules, vesicles, pustules, crusts and scabs. The lesions may be centrally depressed and can be extremely itchy.27 Monkeypox by the West African clade may have very few lesions.4 Not often seen in smallpox or varicella is lymphadenopathy, which may be generalized or localized to several areas (e.g., neck, armpit, or groin). Lymphadenopathy typically occurs with fever onset, 1–2 days before rash onset, or rarely with rash onset.27 · Data from the 2003 US monkeypox outbreak reported that individuals with exposure to infected animals that resulted in a break in skin (n = 6) may not develop a febrile prodrome.7 The number of cases may limit the generalizability of this finding to other types of exposure (e.g., person-to-person transmission via skin lesions). Disease Severity · The severity of monkeypox can depend upon: · The strain of the infecting virus. The West African clade which circulates from western Cameroon to Sierra Leone seems to cause less severe illness with a case-fatality rate of 3.6% (95% CI: 1.7%–6.8%), compared to the Congo Basin clade which circulates from central and southern Cameroon to the DRC with a case-fatality rate of 10.6% (95% CI: 8.4%–13.3%).28 Multi-Jurisdictional Monkeypox Outbreak 2022 – What We Know So Far 6 · The route of exposure. Data from 47 confirmed and probable cases in the 2003 US outbreak revealed:7 · A higher risk of hospitalization in individuals whose exposure included a break in the skin: 11/17 (68.8%) compared to those whose exposure did not result in a skin break: 3/30 (10.3%); P < 0.001. · A higher risk of experiencing at least six systemic symptoms in individuals whose exposure included a break in the skin: 8/17 (49.1%) compared to those whose exposure did not result in a skin break: 5/30 (16.7%); P < 0.041. · Complications reported in endemic areas include encephalitis, septicemia, secondary skin bacterial infections (from scratching), vomiting, diarrhea, dehydration, conjunctivitis, keratitis, and pneumonia.4,29 In addition, low mood and emotional lability (may be due to monkeypox or being put on isolation), as well as slow healing skin lesions/ulcers were reported in cases in the UK.30 · Data on monkeypox in immunocompromised patients are limited—in the 2017 Nigeria outbreak, 2/8 patients with laboratory investigations tested positive for human immunodeficiency virus (HIV) (n = 2) and they developed > 100 skin lesions associated with genital ulcers. One of the HIV-positive patient had thrombocytopenia. No deaths were reported among HIV-positive patients.31 · Data from 34/37 confirmed monkeypox cases in the 2003 US outbreak noted:32 · No patients died as a result of monkeypox. · 9/34 (26%) required hospitalization > 48 hours, including a patient with hepatitis C who recovered without significant sequelae. · 5/34 (15%) developed severe disease (defined by acuity and burden of fever and rash), including: · A 6-year-old girl in intensive care who was intubated and put on mechanical ventilation for encephalitis. · A 10-year-old girl in intensive care with tracheal airway compromise secondary to a large retropharyngeal abscess and cervical lymphadenopathy. · One patient developed keratitis and corneal ulceration and required corneal replacement. · Pediatric patients (≤ 18 years of age; n = 10) were more likely to require intensive care (P = 0.02) but not