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Journal article

Selection of diagnostic cutoffs for murine typhus IgM and IgG immunofluorescence assay: a systematic review

Abstract:
Murine typhus is a neglected but widespread infectious disease that results in acute fever. The immunofluorescence assay (IFA) is the “gold standard” to identify IgM or IgG antibodies, although there is a lack of standardization in methodologies. The objective of this review is to summarize 1) the differences in published methodologies, 2) the diagnostic cutoff titers, and 3) the justification of diagnostic cutoffs. Searches were performed by combining the following search terms: “murine typhus,” “rickettsia typhi,” “immunofluorescence,” “IFA,” and “serologic” with restrictions (i.e., “rickettsia typhi” or “murine typhus,” and “IFA” or “immunofluorescence,” or “serologic*”). The search identified 78 studies that used IFA or immunoperoxidase assay (IIP) antibody cutoffs to diagnose murine typhus, 39 of which were case series. Overall, 45 studies (57.7%) provided little to no rationale as to how the cutoff was derived. Variation was seen locally in the cutoff titers used, but a 4-fold or greater increase was often applied. The cutoffs varied depending on the antibody target. No consensus was observed in establishing a cutoff, or for a single-value diagnostic cutoff. In conclusion, there is a lack of consensus in the establishment of a single-value cutoff. Further studies will need to be executed at each distinct geographic location to identify region-specific cutoffs, while also considering background antibody levels to distinguish between healthy and infected patients.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.4269/ajtmh.19-0818

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Tropical Medicine
Role:
Author
ORCID:
0000-0003-1187-2712


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Grant:
106698/Z/14/A milestone
106698/B/14/Z milestone


Publisher:
American Society of Tropical Medicine and Hygiene
Journal:
American Journal of Tropical Medicine and Hygiene More from this journal
Volume:
103
Issue:
1
Pages:
55-63
Publication date:
2020-04-06
Acceptance date:
2020-02-18
DOI:
EISSN:
1476-1645
ISSN:
0002-9637
Pmid:
32274984


Language:
English
Keywords:
Pubs id:
1099467
Local pid:
pubs:1099467
Deposit date:
2020-06-01
ARK identifier:

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