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

OBJECTIVES:This study examined R. typhi infection patients in Lao People's Democratic Republic (Lao PDR) to; 1) investigate humoral immune dynamics; 2) determine the differences in reference diagnostic results and recommend appropriate cut-offs; 3) determine differences in immune response after different antibiotic treatments; and 4) determine appropriate diagnostic cut-off parameters for the indirect immunofluorescence assay (IFA). METHODS:Sequential serum samples from 90 non-pregnant, adult patients were collected at 7 time points (days 0, 7, 14, 28, 90,180, 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal endpoint titers against R. typhi and PCR. RESULTS:For all 90 patients, reciprocal R. typhi IgM and IgG antibody titers ranged from <400 to ≥3,200. The median half-life of R. typhi IgM was 126 (IQR 36-204) days and IgG was 177 (IQR 134-355) days. Overall median patient titers for R. typhi IgM and IgG were significantly different (p<0.0001) and at each temporal sample collection point (range p <0.0001-0.0411). Using Bayesian LCM 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 and 89.9%; 95% CI, 62.5-100 specificity), and for IFA IgG 1,600 (77.3%; 95% CI, 68.2-87.6sensitivity and 99%; 95% CI, 95-100 specificity). CONCLUSIONS:This study suggests suitable diagnostic cut-offs for local diagnostic laboratories and other endemic settings and highlight antibody persistence following acute infection. Further studies are required to validate and to define cut-offs in other geographically diverse locations.