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Virology, Immunology and Pathology of Human Rabies During Treatment

Caicedo, Yolanda MD*; Paez, Andres PhD; Kuzmin, Ivan PhD; Niezgoda, Michael MS; Orciari, Lillian A. MS; Yager, Pamela A. BS; Recuenco, Sergio MD, PhD; Franka, Richard DVM, PhD; Velasco-Villa, Andres PhD; Willoughby, Rodney E. Jr. MD

The Pediatric Infectious Disease Journal: May 2015 - Volume 34 - Issue 5 - p 520–528
doi: 10.1097/INF.0000000000000624
Pathogenesis and Host Response

Background: Rabies is an acute fatal encephalitis caused by all members of the Lyssavirus genus. The first human rabies survivor without benefit of prior vaccination was reported from Milwaukee in 2005. We report a second unvaccinated patient who showed early recovery from rabies and then died accidentally during convalescence, providing an unparalleled opportunity to examine the histopathology as well as immune and virological correlates of early recovery from human rabies.

Methods: Case report, rapid fluorescent focus inhibition test, enzyme-linked immunosorbent assay, indirect and direct fluorescent antibody assays, reverse-transcriptase polymerase chain reaction, phylogenetic reconstruction, isolation in tissue culture, pathology and immunohistochemistry.

Results: The 9 year old died 76 days after presenting with rabies of vampire bat phylogeny transmitted by cat bite. Antibody response in serum and cerebrospinal fluid was robust and associated with severe cerebral edema. No rabies virus was cultured at autopsy. Rabies virus antigen was atypical in size and distribution. Rabies virus genome was present in neocortex but absent in brainstem.

Conclusions: Clinical recovery was associated with detection of neutralizing antibody and clearance of infectious rabies virus in the central nervous system by 76 days but not clearance of detectable viral subcomponents such as nucleoprotein antigen or RNA in brain.

From the *Hospital Universitario del Valle, Cali, Colombia; Laboratorio de Virología, Instituto Nacional de Salud (INS), Bogotá D.C., Colombia; Rabies Program, Centers for Disease Control and Prevention, Atlanta, GA; §Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, GA; and Medical College of Wisconsin, Milwaukee, WI.

Accepted for publication September 27, 2014.

Supported, in part, by the Zach Jones Foundation and by the NIH 1RO1AI093369 (R.E.W.). The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Rodney E. Willoughby, Jr., MD, Department of Pediatric Infectious Diseases, Medical College of Wisconsin, C450. P.O. Box 1997, Milwaukee, WI 53201. E-mail:

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