Abstract
BackgroundDefining 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 FindingsAn 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/SignificanceThe 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.
Highlights
Trachoma, an ocular disease resulting from infection by the bacterium Chlamydia trachomatis, causes an estimated 3.8 million cases of blindness and 5.3 million cases of low vision [1] in Africa and Southeast Asia
As neglected tropical disease (NTD) programs reduce infection prevalence, defining program endpoints is a programmatic priority and challenge. This is true for trachoma where clinical pathology may be observed in the absence of active infection [3] or, in some low-prevalence areas, may be caused by inflammation associated with non-Chlamydial bacteria [4]
Trachoma is an ocular disease caused by repeated infections with the bacteria Chlamydia trachomatis that is observed mostly in children and women
Summary
An ocular disease resulting from infection by the bacterium Chlamydia trachomatis, causes an estimated 3.8 million cases of blindness and 5.3 million cases of low vision [1] in Africa and Southeast Asia. Elimination efforts are based on the components of the SAFE strategy, including Surgery to prevent blindness in those with trichiasis, the use of Antibiotics to treat active infection, the advocacy of Facial hygiene to prevent spread of infection, and Environmental change through sanitation improvements to disrupt transmission. As neglected tropical disease (NTD) programs reduce infection prevalence, defining program endpoints is a programmatic priority and challenge. This is true for trachoma where clinical pathology may be observed in the absence of active infection [3] or, in some low-prevalence areas, may be caused by inflammation associated with non-Chlamydial bacteria [4]. 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
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