Cargando…

1655. Performance of Molecular and Serologic Tests for the Diagnosis of Scrub Typhus

BACKGROUND: Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its nonspecific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial t...

Descripción completa

Detalles Bibliográficos
Autores principales: Varghese, George M, Kannan, Kavitha, Abhilash, Kundavaram, Nithyananth, Alice, David, Thambu, Sathyendra, Sowmya, Hansdak, Samuel, Iyyadurai, Ramya, Prakash, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808676/
http://dx.doi.org/10.1093/ofid/ofz360.1519
_version_ 1783461793028374528
author Varghese, George M
Kannan, Kavitha
Abhilash, Kundavaram
Nithyananth, Alice
David, Thambu
Sathyendra, Sowmya
Hansdak, Samuel
Iyyadurai, Ramya
Prakash, John
author_facet Varghese, George M
Kannan, Kavitha
Abhilash, Kundavaram
Nithyananth, Alice
David, Thambu
Sathyendra, Sowmya
Hansdak, Samuel
Iyyadurai, Ramya
Prakash, John
author_sort Varghese, George M
collection PubMed
description BACKGROUND: Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its nonspecific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluated the diagnostic performance of various tests. METHODS: Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood or eschar were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative PCR using 47 kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil–Felix test (WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT). RESULTS: Among the 302 participants, 152 had confirmed scrub typhus (cases) and 150 were controls. ELISA and RDT detecting IgM antibodies had excellent discriminative potential with sensitivities and specificities of 94%, 93% and 92%, 93%, respectively. False-positive IgM serology was observed with spotted fever and leptospirosis. The sensitivity and specificity of IFA were found to be 80% and 85%, respectively. qPCR exhibited excellent sensitivity (96%) and perfect specificity. CONCLUSION: ELISA and RDT detecting IgM antibodies have excellent sensitivity and specificity while the sensitivity of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories. DISCLOSURES: All authors: No reported disclosures.
format Online
Article
Text
id pubmed-6808676
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-68086762019-10-28 1655. Performance of Molecular and Serologic Tests for the Diagnosis of Scrub Typhus Varghese, George M Kannan, Kavitha Abhilash, Kundavaram Nithyananth, Alice David, Thambu Sathyendra, Sowmya Hansdak, Samuel Iyyadurai, Ramya Prakash, John Open Forum Infect Dis Abstracts BACKGROUND: Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its nonspecific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluated the diagnostic performance of various tests. METHODS: Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood or eschar were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative PCR using 47 kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil–Felix test (WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT). RESULTS: Among the 302 participants, 152 had confirmed scrub typhus (cases) and 150 were controls. ELISA and RDT detecting IgM antibodies had excellent discriminative potential with sensitivities and specificities of 94%, 93% and 92%, 93%, respectively. False-positive IgM serology was observed with spotted fever and leptospirosis. The sensitivity and specificity of IFA were found to be 80% and 85%, respectively. qPCR exhibited excellent sensitivity (96%) and perfect specificity. CONCLUSION: ELISA and RDT detecting IgM antibodies have excellent sensitivity and specificity while the sensitivity of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6808676/ http://dx.doi.org/10.1093/ofid/ofz360.1519 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Varghese, George M
Kannan, Kavitha
Abhilash, Kundavaram
Nithyananth, Alice
David, Thambu
Sathyendra, Sowmya
Hansdak, Samuel
Iyyadurai, Ramya
Prakash, John
1655. Performance of Molecular and Serologic Tests for the Diagnosis of Scrub Typhus
title 1655. Performance of Molecular and Serologic Tests for the Diagnosis of Scrub Typhus
title_full 1655. Performance of Molecular and Serologic Tests for the Diagnosis of Scrub Typhus
title_fullStr 1655. Performance of Molecular and Serologic Tests for the Diagnosis of Scrub Typhus
title_full_unstemmed 1655. Performance of Molecular and Serologic Tests for the Diagnosis of Scrub Typhus
title_short 1655. Performance of Molecular and Serologic Tests for the Diagnosis of Scrub Typhus
title_sort 1655. performance of molecular and serologic tests for the diagnosis of scrub typhus
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808676/
http://dx.doi.org/10.1093/ofid/ofz360.1519
work_keys_str_mv AT varghesegeorgem 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus
AT kannankavitha 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus
AT abhilashkundavaram 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus
AT nithyananthalice 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus
AT davidthambu 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus
AT sathyendrasowmya 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus
AT hansdaksamuel 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus
AT iyyadurairamya 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus
AT prakashjohn 1655performanceofmolecularandserologictestsforthediagnosisofscrubtyphus