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The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients

OBJECTIVES: This study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cut-offs; (c) determine differences i...

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Autores principales: Phakhounthong, K., Mukaka, M., Dittrich, S., Tanganuchitcharnchai, A., Day, N.P.J., White, L.J., Newton, P.N., Blacksell, S.D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284305/
https://www.ncbi.nlm.nih.gov/pubmed/31678231
http://dx.doi.org/10.1016/j.cmi.2019.10.022
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author Phakhounthong, K.
Mukaka, M.
Dittrich, S.
Tanganuchitcharnchai, A.
Day, N.P.J.
White, L.J.
Newton, P.N.
Blacksell, S.D.
author_facet Phakhounthong, K.
Mukaka, M.
Dittrich, S.
Tanganuchitcharnchai, A.
Day, N.P.J.
White, L.J.
Newton, P.N.
Blacksell, S.D.
author_sort Phakhounthong, K.
collection PubMed
description OBJECTIVES: This study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cut-offs; (c) determine differences in immune response after different antibiotic treatments; and (d) determine appropriate diagnostic cut-off parameters for indirect immunofluorescence assay (IFA). METHODS: Sequential serum samples from 90 non-pregnant, adults were collected at seven time-points (days 0, 7, 14, 28, 90, 180 and 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal end-point titres against R. typhi and PCR. RESULTS: For all 90 individuals, reciprocal R. typhi IgM and IgG antibody titres ranged from <400 to ≥3200. The median half-life of R. typhi IgM was 126 days (interquartile range 36–204 days) and IgG was 177 days (interquartile range 134–355 days). Overall median patient titres for R. typhi IgM and IgG were significantly different (p < 0.0001) and at each temporal sample collection point (range p < 0.0001 to p 0.0411). Using Bayesian latent class model analysis, the optimal diagnostic cut-off reciprocal IFA titer on patient admission for IgM was 800 (78.6%, 95% CI 71.6%–85.2% sensitivity; 89.9%, 95% CI 62.5%–100% specificity), and for IFA IgG 1600 (77.3%; 95% CI 68.2%–87.6% sensitivity; 99%, 95% CI 95%–100% specificity). CONCLUSIONS: This study suggests suitable diagnostic cut-offs for local diagnostic laboratories and other endemic settings and highlights antibody persistence following acute infection. Further studies are required to validate and define cut-offs in other geographically diverse locations.
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spelling pubmed-72843052020-06-17 The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients Phakhounthong, K. Mukaka, M. Dittrich, S. Tanganuchitcharnchai, A. Day, N.P.J. White, L.J. Newton, P.N. Blacksell, S.D. Clin Microbiol Infect Article OBJECTIVES: This study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cut-offs; (c) determine differences in immune response after different antibiotic treatments; and (d) determine appropriate diagnostic cut-off parameters for indirect immunofluorescence assay (IFA). METHODS: Sequential serum samples from 90 non-pregnant, adults were collected at seven time-points (days 0, 7, 14, 28, 90, 180 and 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal end-point titres against R. typhi and PCR. RESULTS: For all 90 individuals, reciprocal R. typhi IgM and IgG antibody titres ranged from <400 to ≥3200. The median half-life of R. typhi IgM was 126 days (interquartile range 36–204 days) and IgG was 177 days (interquartile range 134–355 days). Overall median patient titres for R. typhi IgM and IgG were significantly different (p < 0.0001) and at each temporal sample collection point (range p < 0.0001 to p 0.0411). Using Bayesian latent class model analysis, the optimal diagnostic cut-off reciprocal IFA titer on patient admission for IgM was 800 (78.6%, 95% CI 71.6%–85.2% sensitivity; 89.9%, 95% CI 62.5%–100% specificity), and for IFA IgG 1600 (77.3%; 95% CI 68.2%–87.6% sensitivity; 99%, 95% CI 95%–100% specificity). CONCLUSIONS: This study suggests suitable diagnostic cut-offs for local diagnostic laboratories and other endemic settings and highlights antibody persistence following acute infection. Further studies are required to validate and define cut-offs in other geographically diverse locations. Elsevier 2020-06 /pmc/articles/PMC7284305/ /pubmed/31678231 http://dx.doi.org/10.1016/j.cmi.2019.10.022 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Phakhounthong, K.
Mukaka, M.
Dittrich, S.
Tanganuchitcharnchai, A.
Day, N.P.J.
White, L.J.
Newton, P.N.
Blacksell, S.D.
The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients
title The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients
title_full The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients
title_fullStr The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients
title_full_unstemmed The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients
title_short The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients
title_sort temporal dynamics of humoral immunity to rickettsia typhi infection in murine typhus patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284305/
https://www.ncbi.nlm.nih.gov/pubmed/31678231
http://dx.doi.org/10.1016/j.cmi.2019.10.022
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