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Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam

BACKGROUND: Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteris...

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Autores principales: Katoh, Shungo, Cuong, Ngo Chi, Hamaguchi, Sugihiro, Thuy, Pham Thanh, Cuong, Do Duy, Anh, Le Kim, Anh, Nguyen Thi Hien, Anh, Dang Duc, Sando, Eiichiro, Suzuki, Motoi, Fujita, Hiromi, Yasunami, Michio, Yoshihara, Keisuke, Yoshida, Lay-Myint, Paris, Daniel Henry, Ariyoshi, Koya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917290/
https://www.ncbi.nlm.nih.gov/pubmed/31805053
http://dx.doi.org/10.1371/journal.pntd.0007928
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author Katoh, Shungo
Cuong, Ngo Chi
Hamaguchi, Sugihiro
Thuy, Pham Thanh
Cuong, Do Duy
Anh, Le Kim
Anh, Nguyen Thi Hien
Anh, Dang Duc
Sando, Eiichiro
Suzuki, Motoi
Fujita, Hiromi
Yasunami, Michio
Yoshihara, Keisuke
Yoshida, Lay-Myint
Paris, Daniel Henry
Ariyoshi, Koya
author_facet Katoh, Shungo
Cuong, Ngo Chi
Hamaguchi, Sugihiro
Thuy, Pham Thanh
Cuong, Do Duy
Anh, Le Kim
Anh, Nguyen Thi Hien
Anh, Dang Duc
Sando, Eiichiro
Suzuki, Motoi
Fujita, Hiromi
Yasunami, Michio
Yoshihara, Keisuke
Yoshida, Lay-Myint
Paris, Daniel Henry
Ariyoshi, Koya
author_sort Katoh, Shungo
collection PubMed
description BACKGROUND: Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteristics of ST, we conducted an observational study using multiple diagnostic assays at a national tertiary hospital in Hanoi, Vietnam. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 1,127 patients hospitalized with documented fever between June 2012 and May 2013. Overall, 33 (2.9%) patients were diagnosed with ST by PCR and/or screening of ELISA for immunoglobulin M (IgM) with confirmatory tests: 14 (42.4%) were confirmed by indirect immunoperoxidase assay (IIP), and 19 (57.6%) were by IIP and PCR. Living by farming, conjunctival injection, eschar, aspartate aminotransferase elevation, and alanine aminotransferase elevation were significantly associated with ST cases (adjusted odds ratios (aORs): 2.8, 3.07, 48.8, 3.51, and 4.13, respectively), and having a comorbidity and neutrophilia were significantly less common in ST cases (aORs: 0.29 and 0.27, respectively). The majority of the ST cases were not clinically diagnosed with rickettsiosis (72.7%). Dominant IIP reactions against a single antigen were identified in 15 ST cases, whereas indistinguishably high reactions against multiple antigens were seen in 11 ST cases. The most frequently observed dominant IIP reaction was against Karp antigen (eight cases) followed by Gilliam (four cases). The highest diagnostic accuracy of IgM ELISA in acute samples was 78%. In a phylogenetic analysis of the 56-kDa type-specific antigen gene, the majority (14 cases) were located in the Karp-related branch followed by the Gilliam-related (two cases), Kato-related (two cases), and TA763-related clades (one case). CONCLUSIONS/SIGNIFICANCE: Both the clinical and laboratory diagnoses of ST remain challenging at a tertiary hospital. Implementation of both serological and nucleic acid amplification assays covering endemic O. tsutsugamushi strains is essential.
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spelling pubmed-69172902019-12-27 Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam Katoh, Shungo Cuong, Ngo Chi Hamaguchi, Sugihiro Thuy, Pham Thanh Cuong, Do Duy Anh, Le Kim Anh, Nguyen Thi Hien Anh, Dang Duc Sando, Eiichiro Suzuki, Motoi Fujita, Hiromi Yasunami, Michio Yoshihara, Keisuke Yoshida, Lay-Myint Paris, Daniel Henry Ariyoshi, Koya PLoS Negl Trop Dis Research Article BACKGROUND: Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteristics of ST, we conducted an observational study using multiple diagnostic assays at a national tertiary hospital in Hanoi, Vietnam. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 1,127 patients hospitalized with documented fever between June 2012 and May 2013. Overall, 33 (2.9%) patients were diagnosed with ST by PCR and/or screening of ELISA for immunoglobulin M (IgM) with confirmatory tests: 14 (42.4%) were confirmed by indirect immunoperoxidase assay (IIP), and 19 (57.6%) were by IIP and PCR. Living by farming, conjunctival injection, eschar, aspartate aminotransferase elevation, and alanine aminotransferase elevation were significantly associated with ST cases (adjusted odds ratios (aORs): 2.8, 3.07, 48.8, 3.51, and 4.13, respectively), and having a comorbidity and neutrophilia were significantly less common in ST cases (aORs: 0.29 and 0.27, respectively). The majority of the ST cases were not clinically diagnosed with rickettsiosis (72.7%). Dominant IIP reactions against a single antigen were identified in 15 ST cases, whereas indistinguishably high reactions against multiple antigens were seen in 11 ST cases. The most frequently observed dominant IIP reaction was against Karp antigen (eight cases) followed by Gilliam (four cases). The highest diagnostic accuracy of IgM ELISA in acute samples was 78%. In a phylogenetic analysis of the 56-kDa type-specific antigen gene, the majority (14 cases) were located in the Karp-related branch followed by the Gilliam-related (two cases), Kato-related (two cases), and TA763-related clades (one case). CONCLUSIONS/SIGNIFICANCE: Both the clinical and laboratory diagnoses of ST remain challenging at a tertiary hospital. Implementation of both serological and nucleic acid amplification assays covering endemic O. tsutsugamushi strains is essential. Public Library of Science 2019-12-05 /pmc/articles/PMC6917290/ /pubmed/31805053 http://dx.doi.org/10.1371/journal.pntd.0007928 Text en © 2019 Katoh et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Katoh, Shungo
Cuong, Ngo Chi
Hamaguchi, Sugihiro
Thuy, Pham Thanh
Cuong, Do Duy
Anh, Le Kim
Anh, Nguyen Thi Hien
Anh, Dang Duc
Sando, Eiichiro
Suzuki, Motoi
Fujita, Hiromi
Yasunami, Michio
Yoshihara, Keisuke
Yoshida, Lay-Myint
Paris, Daniel Henry
Ariyoshi, Koya
Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam
title Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam
title_full Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam
title_fullStr Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam
title_full_unstemmed Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam
title_short Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam
title_sort challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern vietnam
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917290/
https://www.ncbi.nlm.nih.gov/pubmed/31805053
http://dx.doi.org/10.1371/journal.pntd.0007928
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