CT694 and pgp3 as serological tools for monitoring trachoma programs

PLoS Negl Trop Dis. 2012;6(11):e1873. doi: 10.1371/journal.pntd.0001873. Epub 2012 Nov 1.

Abstract

Background: Defining endpoints for trachoma programs can be a challenge as clinical signs of infection may persist in the absence of detectable bacteria. Antibody-based tests may provide an alternative testing strategy for surveillance during terminal phases of the program. Antibody-based assays, in particular ELISAs, have been shown to be useful to document C. trachomatis genital infections, but have not been explored extensively for ocular C. trachomatis infections.

Methodology/principal findings: An antibody-based multiplex assay was used to test two C. trachomatis antigens, pgp3 and CT694, for detection of trachoma antibodies in bloodspots from Tanzanian children (n = 160) collected after multiple rounds of mass azithromycin treatment. Using samples from C. trachomatis-positive (by PCR) children from Tanzania (n = 11) and control sera from a non-endemic group of U.S. children (n = 122), IgG responses to both pgp3 and CT694 were determined to be 91% sensitive and 98% specific. Antibody responses of Tanzanian children were analyzed with regard to clinical trachoma, PCR positivity, and age. In general, children with more intense ocular pathology (TF/TI = 2 or most severe) had a higher median antibody response to pgp3 (p = 0.0041) and CT694 (p = 0.0282) than those with normal exams (TF/TI = 0). However, 44% of children with no ocular pathology tested positive for antibody, suggesting prior infection. The median titer of antibody responses for children less than three years of age was significantly lower than those of older children. (p<0.0001 for both antigens).

Conclusions/significance: The antibody-based multiplex assay is a sensitive and specific additional tool for evaluating trachoma transmission. The assay can also be expanded to include antigens representing different diseases, allowing for a robust assay for monitoring across NTD programs.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Bacterial / blood*
  • Antigens, Bacterial / immunology*
  • Azithromycin / therapeutic use
  • Bacterial Proteins / immunology*
  • Child
  • Child, Preschool
  • Drug Monitoring / methods*
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Infant
  • Lymphogranuloma Venereum / diagnosis
  • Lymphogranuloma Venereum / drug therapy*
  • Male
  • Sensitivity and Specificity
  • Tanzania

Substances

  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • CT694 protein, Chlamydia trachomatis
  • Immunoglobulin G
  • pgp3 protein, Chlamydia
  • Azithromycin

Grant support

Funding for this study was obtained in part from USAID (No. OGH11-12021) through an inter-agency agreement with the Centers for Disease Control and Prevention. The study also received operational support from Trachoma Control Programs in Tanzania and was funded in part by the Bill and Melinda Gates Foundation. Dr. West is the recipient of a Senior Scientific Investigator award from Research to Prevent Blindness. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.