The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients.
Phakhounthong K., Mukaka M., Dittrich S., Tanganuchitcharnchai A., Day NPJ., White LJ., Newton PN., Blacksell SD.
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.