Fatal Human Alphaherpesvirus 1 Infection in Free-Ranging Black-Tufted Marmosets in Anthropized Environments, Brazil, 2012-2019

Abstract

Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. The main clinical findings were neurologic signs, necrotizing meningoencephalitis, and ulcerative glossitis; 1 animal had necrotizing hepatitis. Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. PCR confirmed HuAHV1 infection. These findings illustrate how disruption of the One Health equilibrium in anthropized environments poses risks for interspecies virus transmission with potential spillover not only from animals to humans but also from humans to free-ranging nonhuman primates or other animals.

Keywords: Brazil; One Health; PCR; anthropized environments; fatal; histopathology; human alphaherpesvirus 1; immunohistochemistry; marmoset; pathology; transmission electron microscopy; viruses; zoonoses.

Figure 1

Locations of urbanized free-ranging black-tufted marmosets with fatal human alphaherpesvirus 1 infections, Federal District, Goiás, Brazil, 2012–2019. Circles indicate known locations of outbreak 1 (7 animals), outbreak 2 (2 animals), and 3 isolated cases. Insets indicate location of Federal District (black shading) in Goiás state and Goiás state in Brazil. Figure adapted from Google Maps (https://www.google.com.br/maps).

Figure 2

Macroscopic finding in the tongue and lip from a black-tufted marmoset with fatal human alphaherpesvirus 1 infection, Brazil, 2012–2019. A) Erosions and ulcerations on the lip. B) Glossitis with multifocal ulcers and erosions (arrowheads).

Figure 3

Pathologic changes in brain of free-ranging black-tufted marmosets with fatal human alphaherpesvirus 1 infection, Brazil, 2012–2019. A) Necrotizing meningoencephalitis. Hemotoxylin and eosin (H&E) stain; original magnification ×10. B) Neuronal degeneration and glial nodule. H&E stain; original magnification ×40. C) Neuronal necrosis with microglial proliferation and expansion of Virchow–Robbin spaces by lymphocytes, histiocytes, and few plasma cells. Neurons and glial cells show intranuclear inclusion bodies and prominent margination of the nuclear chromatin. H&E stain; original magnification ×63. D) Prominent neutrophilic inflammation accompanies neuronal necrosis and intranuclear inclusion bodies. H&E stain; original magnification ×63. E) Human alphaherpesvirus 1 immunostaining within neurons (immunohistochemistry; original magnification ×40). F) Intranuclear (arrowhead) and cytoplasmic (arrow) herpesvirus particles in gray matter. Transmission electron microscopy; scale bar indicate 500 nm. Inset: cytoplasmic herpesvirus particles (arrow) white matter, myelinated axon (arrowhead); scale bar indicates 200 nm.

Figure 4

Tongue pathology in free-ranging black-tufted marmosets with fatal human alphaherpesvirus 1 infection, Brazil, 2012–2019. A) Severe necrosis of epithelium. Hemotoxylin and eosin (H&E) stain; original magnification ×10. B) Intranuclear inclusion bodies in epithelial cells at the margin of the lesion and multinucleated syncytial cell (arrow). H&E stain; original magnification ×40. C) Human alphaherpesvirus 1 immunostaining within epithelial cells in the area of necrotizing glossitis. Immunihistochemistry; original magnification ×40. D) Epithelial cell containing accumulations of herpesvirus within the cytoplasm. Transmission electron microscopy; scale bar indicates 600 nm. Inset: higher magnification image of herpesvirus particles with well-defined tegument layer in the cytoplasm; scale bar indicates 400 nm.

Figure 5

Liver pathology in free-ranging black-tufted marmosets with fatal human alphaherpesvirus 1 infection, Brazil, 2012–2019. A) Intranuclear inclusion bodies in hepatocytes at the margin of a necrotic focus. Hemotoxylin and eosin (H&E) stain; original magnification ×63. B) Multinucleated syncytial cell (arrow). H&E; original magnification ×63. C) Human alphaherpesvirus 1 immunostaining within hepatocytes in an area of necrotizing hepatitis. Immunihistochemistry; original magnification ×40. D) Herpesvirus in the cytoplasm of a hepatocyte. Transmission electron microscopy; scale bar indicates 400 nm.