No 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.

Risk factors for the incidence of scarring are needed to inform trachoma control programs in countries hyperendemic for this blinding disease. A cohort of pre-school children with constant, severe trachoma, and an age, sex, and neighborhood matched cohort of children without constant severe trachoma were followed for seven years to determine the incidence of scarring. The incidence of scarring in the children with constant severe trachoma was 29.2% versus 9.6% in the comparison group. In a model adjusting for multiple factors, significant predictors of scarring were increasing age, female, and constant severe trachoma (OR = 4.85, 95% CL = 2.05, 11.40). Infection with C. trachomatis at follow up was also associated with scarring in both groups of children. It is likely that these children have a different host response to infection, and represent a subgroup at high risk for the blinding complications of trachoma. Reducing exposure to infection in the community through antibiotics and changes in hygiene practices is still the most promising control strategy.

Mass distribution of a single dose of oral azithromycin for trachoma was associated with increased circulation of macrolide-resistant S. pneumoniae carriage among young children in the 6 months following treatment. It is crucial that changes in antibiotic resistance patterns and their clinical significance in the treatment of severe pediatric infections be assessed in future MDA trials.

Although most of the chlamydial load in this community resided in children, 10% of the high load resided in adults, most of whom did not have follicular trachoma and in whom the infection would be missed under treatment strategies that focus on clinical disease or children. These data support a mass treatment strategy for hyperendemic communities, at least as a first approach. In addition, treatment of children age < or =2 years should be reexamined, as >30% with high loads at baseline remained infected at 2 months, despite monitored treatment according to weight.