Ocular immune responses, Chlamydia trachomatis infection and clinical signs of trachoma before and after azithromycin mass drug administration in a treatment naïve trachoma-endemic Tanzanian community

Abstract

Background Trachoma, caused by Chlamydia trachomatis , remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C . trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points. Methodology A cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C . trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines. Findings The prevalence of C . trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C . trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C . trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment. Conclusion Conjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure.

Immunopathogenesis of Progressive Scarring Trachoma: Results of a 4-Year Longitudinal Study in Tanzanian Children

“…A detailed description of the longitudinal study design and primary outcomes has been published elsewhere (4,9,10). Briefly, of the 666 eligible children, 616 were enrolled in the cohort study.…”

DjinniChip: Evaluation of a novel molecular rapid diagnostic device for the detection of Chlamydia trachomatis in trachoma-endemic areas

“…Timepoint 14 (August 2015) was selected for this evaluation and 428 children were seen, 9 months after the last mass community treatment with antibiotic as detailed by the SAFE strategy. Conjunctival swabs were collected as previously described using sterile polyester-tipped swabs [7,8]. The rst swab was collected into 250µl RNA later and was used elsewhere [7][8][9], whilst the second swab was collected dry and stored at -80°C until used in this study.…”

“…Conjunctival swabs were collected as previously described using sterile polyester-tipped swabs [7,8]. The rst swab was collected into 250µl RNA later and was used elsewhere [7][8][9], whilst the second swab was collected dry and stored at -80°C until used in this study. 0.5% of swabs collected were 'air' control swabs in order to test for eld and laboratory contamination.…”

DjinniChip: Evaluation of a novel molecular rapid diagnostic device for the detection of Chlamydia trachomatis in trachoma-endemic areas

“…Time-point 14 (August 2015) was selected for this evaluation and 428 children were seen, 9 months after the last mass community treatment with antibiotic as detailed by the SAFE strategy. Conjunctival swabs were collected as previously described using sterile polyester-tipped swabs [7,8]. The rst swab was collected into 250 ml RNA later and was used elsewhere [7][8][9], whilst the second swab was collected dry and stored at -80 °C until used in this study.…”

“…Conjunctival swabs were collected as previously described using sterile polyester-tipped swabs [7,8]. The rst swab was collected into 250 ml RNA later and was used elsewhere [7][8][9], whilst the second swab was collected dry and stored at -80 °C until used in this study. 0.5% of swabs collected were 'air' control swabs in order to test for eld-and laboratory contamination.…”