Longitudinal analysis of antibody responses to trachoma antigens before and after mass drug administration

Abstract

BackgroundBlinding trachoma, caused by the bacteria Chlamydia trachomatis, is a neglected tropical disease targeted for elimination by 2020. A major component of the elimination strategy is mass drug administration (MDA) with azithromycin. Currently, program decisions are made based on clinical signs of ocular infection, but we have been investigating the use of antibody responses for post-MDA surveillance. In a previous study, IgG responses were detected in children lacking clinical evidence of trachoma, suggesting that IgG responses represented historical infection. To explore the utility of serology for program evaluation, we compared IgG and IgA responses to trachoma antigens and examined changes in IgG and IgA post-drug treatment.MethodsDried blood spots and ocular swabs were collected with parental consent from 264 1–6 year olds in a single village of Kongwa District, central Tanzania. Each child also received an ocular exam for detection of clinical signs of trachoma. MDA was given, and six months later an additional blood spot was taken from these same children. Ocular swabs were analyzed for C. trachomatis DNA and antibody responses for IgA and total IgG were measured in dried bloods spots.ResultsBaseline antibody responses showed an increase in antibody levels with age. By age 6, the percentage positive for IgG (96.0%) was much higher than for IgA (74.2%). Antibody responses to trachoma antigens declined significantly six months after drug treatment for most age groups. The percentage decrease in IgA response was much greater than for IgG. However, no instances of seroreversion were observed.ConclusionsData presented here suggest that focusing on concordant antibody responses in children will provide the best serological surveillance strategy for evaluation of trachoma control programs.

Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies

“…Serology has been suggested as a possible alternative to clinical signs and infection testing, as it indicates the cumulative exposure to Ct [19,20], with the potential to assess the impact of intervention efforts [21]. By monitoring the exposure to Ct of the youngest age groups, born after implementation of MDA, serology may prove useful for confirming that transmission has been interrupted [22].…”

“…Serology has recently been used in several studies [19,20,22–24], three of which have taken place in districts that have completed three or more rounds of MDA [22–24]. These studies have used the multiplex bead array platform (Bio-rad, Hercules, California) to detect antibodies against Pgp3 and CT694, antigens thought to be highly immunogenic [25].…”

“…To make serological testing more widely accessible, the Pgp3/CT694 assay used in previous studies [19,20,22–24] has been adapted for use in a simple Pgp3-specific enzyme-linked immunosorbent assay (ELISA). Pgp3 is a Ct-specific 84kDa heterotrimeric protein [27] and is recognised by specific IgG [28].…”

Serology reflects a decline in the prevalence of trachoma in two regions of The Gambia

“…Additionally, further work is needed to determine the half-life of Pgp3 antibodies and seroreversion rates. A previous study that examined a high-prevalence community before and after one round of azithromycin suggested that individual anti-Pgp3 antibody levels decreased slightly six months after drug treatment, but not enough to be considered seroreversion 51 . This is similar to results seen for urogenital Ct infection, where anti-Pgp3 antibody titres decreased over 4–7 years, but patients were still in the seropositive range 52 .…”

Age-specific prevalence of anti-Pgp3 antibodies and severe conjunctival scarring in the Solomon Islands

“…Antibodies to Pgp3 have recently been suggested for monitoring Ct transmission in trachoma programmes 10,29 , but there is still much to learn about the dynamics of these responses. For example, it is not clear whether anti-Pgp3 responses are detectable in all individuals previously infected with Ct, or if multiple exposures are required to develop sustained anti-Ct responses.…”