Table 1.

Biological and clinical characteristics of Monkeypox, Smallpox and Viral Hemorrhagic Fevers.

Modif. from Ref. [1, 17, 18]

	Monkeypox	Smallpox	Viral hemorrhagic fevers (disease)
Virus/disease	Monkeypox virus	Variola virus	• Filoviruses: Ebola and Marburg virus (Ebola HF, Marburg HF) • Arenaviruses (Lassa HF) • Hantaviruses (Hemorrhagic Fever with renal syndrome), Nairoviruses (Congo-Crimean HF), and Phenuiviruses (Rift Valley fever [RVF]) formerly included in the Bunyaviridae family • Flaviviruses (Dengue, Yellow Fever, Omsk Hemorrhagic Fever)
Transmission	Human–human transmission mainly via sexual contact	Human–human eradicated	• Filoviruses: human–human; also by exposure to sick or dead infected forest animals, or to infected bats • Arenaviruses: rodents exposure • Hantaviruses: rodents exposure • Nairoviruses: bite of infected tick/rarely human- human, mainly in hospital setting • Phenuiviruses: bite of infected mosquitos • Flaviviruses: bite of infected mosquitos
Reservoir	Rodents, prairie dogs, opossums, and several primates	Only humans	• Filoviruses: fruit bats and humans • Arenaviruses: rodents (mainly Mastomys natalensis) • Hantaviruses: rodents • Nairoviruses: Ioxodidae ticks; cattle, goats sheep amplifying hosts • Phenuiviruses: ruminants, rats in some areas, wild animals • Flaviviruses: primates/rodents
Symptoms	Fever Multiple papular, vesiculopustular, and ulcerative lesions on the face and body Lymphadenopathy In the current outbreak, anorectal pain, proctitis with bleeding, and penile edema with balanitis and phimosis	Severe headache, backache, and fever Enanthema over the tongue, mouth, and oropharynx, then cutaneous rash evolving in vesiculopustular and ulcerative lesions followed by umbilication and crusting (pockmarks) Rarely complicated by panophthalmitis and blindness from viral keratitis, encephalitis, pneumonia	Fever Increased vascular permeability with decreased plasma volume Coagulation abnormalities Varying degrees of hemorrhage, up to DIC
Fatality rate	1% (West African clade and reported cases outside Africa) 11% (Central Africa clade)	1% (Variola minor)  > 30% Hemorrhagic Smallpox (HSPX)	From less than 5% (Dengue) up to 90% (Ebola HF)
Hemorrhagic features	Described only in animal models	DIC (only in HSPX, ~ 3% of cases)	DIC
Mechanisms of coagulopathy	Not fully elucidated Extensive liver necrosis with loss of clotting factors Endothelial damage in affected tissues Thrombocytopenia	Not fully elucidated (Smallpox eradicated before availability of modern study methods) Cytokine-induced coagulation activation? Endothelial damage in affected tissues? Thrombocytopenia	Endotheliopathy Tissue factor-induced coagulopathy Complement system activation Cytokine release Vasculitis Capillary leakage

DIC disseminated intravascular coagulation with thrombocytopenia, consumption of clotting factors, increased levels of fibrin degradation products