Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin

Abstract

Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

FIGURE 1

Timeline of events for a patient with autoimmune encephalitis who met Council of State and Territorial Epidemiologists criteria for diagnosis of human rabies and had recently received intravenous immune globulin Abbreviations: CSF = cerebrospinal fluid; IgG = immunoglobulin G; IgM = immunoglobulin M; IVIG = intravenous immune globulin; RLNA = Rabies lyssavirus neutralizing antibody. * By number of days after illness onset.

FIGURE 2

Timeline of events for a patient with Eastern equine encephalitis virus infection who had no history of rabies vaccination, but in whom Rabies lyssavirus neutralizing antibodies were detected after receiving intravenous immune globulin Abbreviations: CSF = cerebrospinal fluid; IgG = immunoglobulin G; IgM = immunoglobulin M; IVIG = intravenous immune globulin; RLNA = Rabies lyssavirus neutralizing antibody. * By number of days after illness onset.