Selection of Diagnostic Cutoffs for Murine Typhus IgM and IgG Immunofluorescence Assay: A Systematic Review

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Dhawan, Sandhya
Robinson, Matthew T
Stenos, John
Graves, Stephen R
Wangrangsimakul, Tri
Newton, Paul N
Day, Nicholas PJ
Blacksell, Stuart D
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2020
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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.

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American Journal of Tropical Medicine and Hygiene
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© 2020 American Society of Tropical Medicine and Hygiene. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
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Biomedical and clinical sciences
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Dhawan, S; Robinson, MT; Stenos, J; Graves, SR; Wangrangsimakul, T; Newton, PN; Day, NPJ; Blacksell, SD, Selection of Diagnostic Cutoffs for Murine Typhus IgM and IgG Immunofluorescence Assay: A Systematic Review, American Journal of Tropical Medicine and Hygiene, 2020, 103 (1), pp. 55-63
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