title: Metabolomics of cerebrospinal fluid from humans treated for rabies.
abstract: Rabies is a rapidly progressive lyssavirus encephalitis that is statistically 100% fatal. There are no clinically effective antiviral drugs for rabies. An immunologically naïve teenager survived rabies in 2004 through improvised supportive care; since then, 5 additional survivors have been associated with use of the so-called Milwaukee Protocol (MP). The MP applies critical care focused on the altered metabolic and physiologic states associated with rabies. The aim of this study was to examine the metabolic profile of cerebrospinal fluid (CSF) from rabies patients during clinical progression of rabies encephalitis in survivors and nonsurvivors and to compare these samples with control CSF samples. Unsupervised clustering algorithms distinguished three stages of rabies disease and identified several metabolites that differentiated rabies survivors from those who subsequently died, in particular, metabolites related to energy metabolism and cell volume control. Moreover, for those patients who survived, the trajectory of their metabolic profile tracked toward the control profile and away from the rabies profile. NMR metabolomics of human rabies CSF provide new insights into the mechanisms of rabies pathogenesis, which may guide future therapy of this disease.
authors.affiliation: Department of Food Science and Technology, University of California, Davis, California 95616, United States.
authors.forename: Aifric
authors.initials: A
authors.lastname: O'Sullivan
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Willoughby
authors.forename: Darya
authors.initials: D
authors.lastname: Mishchuk
authors.forename: Brisa
authors.initials: B
authors.lastname: Alcarraz
authors.forename: Cesar
authors.initials: C
authors.lastname: Cabezas-Sanchez
authors.forename: Rene Edgar
authors.initials: RE
authors.lastname: Condori
authors.forename: Dan
authors.initials: D
authors.lastname: David
authors.forename: Rafael
authors.initials: R
authors.lastname: Encarnacion
authors.forename: Naaz
authors.initials: N
authors.lastname: Fatteh
authors.forename: Josefina
authors.initials: J
authors.lastname: Fernandez
authors.forename: Richard
authors.initials: R
authors.lastname: Franka
authors.forename: Sara
authors.initials: S
authors.lastname: Hedderwick
authors.forename: Conall
authors.initials: C
authors.lastname: McCaughey
authors.forename: Joanne
authors.initials: J
authors.lastname: Ondrush
authors.forename: Andres
authors.initials: A
authors.lastname: Paez-Martinez
authors.forename: Charles
authors.initials: C
authors.lastname: Rupprecht
authors.forename: Andres
authors.initials: A
authors.lastname: Velasco-Villa
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Slupsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000134:cerebrospinal fluid / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D055432:Metabolomics; D011818:Rabies / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011819:Rabies Vaccines / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D011820:Rabies virus / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000998:Antiviral Agents; D011819:Rabies Vaccines