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

Vora, Neil M.; Orciari, Lillian A.; Bertumen, J Bradford; Damon, Inger K.; Ellison, James A.; Fowler, Vance G.; Franka, Richard; Petersen, Brett W.; Satheshkumar, Panayampalli S.; Schexnayder, Stephen M.; Smith, T.; Wallace, Ryan M.; Weinstein, Susan P.; Williams, Carl J.; Yager, Pamela A.; Niezgoda, Michael

doi:10.15585/mmwr.mm6705a3

Cited by 7 publications

(4 citation statements)

References 8 publications

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“…IVIG is produced from the plasma of healthy donors, and it contains high IgG levels. Abs to viruses (eg, HBsAb, HBcAb, HTLV-1/2 Ab, rabies Ab), bacteria and autoimmune Abs present in IVIG products have resulted in false reactive serological results, 16-26 thus, reactive Ab results shortly after IVIG may represent passive Ab infusion rather than endogenous Ab production in response to infection or vaccination. Positive results of anti-HLA Abs shortly after IVIG administration should be interpreted cautiously because they might show passive transfer instead of true infection or immunity derived from vaccination.…”

Section: Discussionmentioning

confidence: 99%

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin

Takamatsu

Yamada

Tsuji

et al. 2021

Transplantation Direct

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Section: Discussionmentioning

confidence: 99%

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin

Takamatsu

Yamada

Tsuji

et al. 2021

Transplantation Direct

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“…Results of serological assays have to be interpreted with caution when the test is performed on a single CSF or serum sample, especially when the history of vaccination is unavailable or unreliable. Recent intravenous immune globulin (IVIG) administration is known to confound serologic diagnosis of rabies [27]. Though the presence of specific antibodies in CSF is considered diagnostic of rabies irrespective of vaccination status [28], breach in blood brain barrier due to any other infectious or non-infectious etiology or a traumatic tap can give false-positive results in vaccinated individuals.…”

Section: Discussionmentioning

confidence: 99%

Utility of rabies neutralizing antibody detection in cerebrospinal fluid and serum for ante-mortem diagnosis of human rabies

2019

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BackgroundEarly ante-mortem laboratory confirmation of human rabies is essential to aid patient management and institute public health measures. Few studies have highlighted the diagnostic value of antibody detection in CSF/serum in rabies, and its utility is usually undermined owing to the late seroconversion and short survival in infected patients. This study was undertaken to examine the ante-mortem diagnostic utility and prognostic value of antibody detection by rapid fluorescent focus inhibition test (RFFIT) in cerebrospinal fluid (CSF)/serum samples received from clinically suspected human rabies cases from January 2015 to December 2017.Methodology/Principal findingsSamples collected ante-mortem and post-mortem from 130 and 6 patients with clinically suspected rabies respectively, were received in the laboratory during the study period. Ante-mortem laboratory confirmation was achieved in 55/130 (42.3%) cases. Real time PCR for detection of viral nucleic acid performed on saliva, nuchal skin, brain tissue and CSF samples could confirm the diagnosis in 15 (27.2%) of the 55 laboratory confirmed cases. Ante-mortem diagnosis could be achieved by RFFIT (in CSF and/or serum) in 45 (34.6%) of the 130 clinically suspected cases, accounting for 81.8% of the total 55 laboratory confirmed cases. The sensitivity of CSF RFFIT increased with the day of sample collection (post-onset of symptoms) and was found to be 100% after 12 days of illness. Patients who had received prior vaccination had an increased probability of a positive RFFIT and negative PCR result. Patients who were positive by RFFIT alone at initial diagnosis had longer survival (albeit with neurological sequelae) than patients who were positive by PCR alone or both RFFIT and PCR.Conclusions/SignificanceDetection of antibodies in the CSF/serum is a valuable ante-mortem diagnostic tool in human rabies, especially in patients who survive beyond a week. It was also found to have a limited role as a prognostic marker to predict outcomes in patients.

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“…Current immunization schedules include 12 vaccines, many of which contain antigens against multiple different viruses or serotypes of bacteria, 28 so that at least 40 different responses could be studied, but space allows review of selected examples only. Additional data on antibodies for which there are vaccines, including measles virus, 29 varicella-zoster virus, 30 tick-borne encephalitis virus, 31 and rabies lyssa virus 32 ; as well as data on titers in sera from immune-deficient patients receiving IgG replacement therapy, [33][34][35][36] and a comparison of antibody titers in IgG preparations and patient sera against bacteria for which vaccines are not available 37 are published elsewhere. Table 1 presents data on antibodies to bacterial antigens from several studies of multiple lots of products produced in the US, UK, and EU.…”

Section: Antibodies Against Common Bacterial Pathogens and Toxinsmentioning

confidence: 99%

Antibodies to vaccine antigens in pooled polyclonal human IgG products

Berger¹

2018

Transfusion

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Immune‐deficient patients depend on the antibodies in pooled human immunoglobulin G (IgG) preparations to remain free from serious infections. The potency of IgG preparations is therefore an ongoing concern. The use of pooled IgG to prevent infection is based on the concept that healthy adults have recovered from infections earlier in life and maintain relatively high antibody titers. In general, vaccine‐induced immunity is less robust or long‐lasting than immunity after natural infection, and many infectious diseases which were formerly widely prevalent have become much less common due to improved hygiene and vaccines. This raises questions as to the adequacy of protective antibodies in current IgG preparations. This paper reviews available data on antibodies against selected bacterial and virus vaccine antigens in current IgG products. Most products contain sufficient antibody to yield levels above minimal protective concentrations to a broad range of pathogens and toxins. Illustrative examples of effects of vaccines on antibody content of IgG products are also discussed: antibody titers to hepatitis A virus in donor plasma pools in both the US and EU are dropping due to decreased natural infection, but they are still sufficient to provide robust protection. Increasing seroprevalence of hepatitis B virus as a result of immunization suggests that antibody titers against this virus may actually be increasing. Finally, serial studies suggest that pooled IgG provides protection against seasonal influenza viruses despite year‐to‐year antigenic drift, and is also likely to provide at least some protective antibody against potentially pandemic strains.

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

Cited by 7 publications

References 8 publications

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin

Utility of rabies neutralizing antibody detection in cerebrospinal fluid and serum for ante-mortem diagnosis of human rabies

Antibodies to vaccine antigens in pooled polyclonal human IgG products

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