Comparative pathology of smallpox and monkeypox in man and macaques

Abstract

In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques.

Fig. 1

Primary lesions seen in ordinary (left) and haemorrhagic (right) smallpox and monkeypox in macaques. (A) Haired skin from a macaque with ordinary smallpox showing epidermal hyperplasia and intraepidermal vesiculation (*). A short expanse of normal non-hyperplastic epidermis is visible on the right. HE. Bar, 100um. (B) Haired skin from a macaque with haemorrhagic monkeypox showing focal haemorrhage in the subcutis (*); note the lack of proliferative and necrotizing epidermal lesions. HE. Bar, 200um. (C) Spleen from a macaque with ordinary monkeypox showing mild lymphoid hyperplasia as evidenced by scattered secondary follicles (*). HE. Bar, 200um. (D) Spleen from a macaque with haemorrhagic smallpox showing severe diffuse haemorrhage (red areas) and lymphoid necrosis (*). HE. Bar, 200um. (E) Lymph node from a macaque with ordinary smallpox showing marked lymphoid hyperplasia as evidenced by numerous secondary follicles (*). HE. Bar, 200um. (F) Lymph node from a macaque with haemorrhagic monkeypox showing multifocal follicular lymphoid necrosis (*). HE. Bar, 200um. (G) Bone marrow from a macaque with ordinary monkeypox showing diffuse myeloid hyperplasia. HE. Bar, 20um. (H) Bone marrow from a macaque with haemorrhagic smallpox showing haematopoietic necrosis (*) and haemorrhage (#). HE. Bar, 20um. (I) and (J) Testes from macaques with ordinary and haemorrhagic monkeypox, respectively, showing focal interstitial orchitis (*) and seminiferous tubule degeneration (#). HE. Bars, 100um.