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

https://doi.org/10.1016/j.cmi.2019.10.022Get rights and content
Under a Creative Commons license
open access

Abstract

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.

Keywords

Diagnosis
Dynamics
Humoral immunity
Immunoglobulin G
Immunoglobulin M
Lao PDR
Murine typhus
Rickettsia typhi

Cited by (0)