The Effect of Multiple Rounds of Mass Drug Administration on the Association between Ocular Chlamydia trachomatis Infection and Follicular Trachoma in Preschool-Aged Children

Abstract

PurposeTo examine the relationship between ocular Chlamydia trachomatis infection and follicular trachoma (TF) in children prior to and following multiple rounds of annual mass drug administration (MDA) with azithromycin.Methodology/principal findingsThirty-two communities with endemic trachoma in Kongwa District, Tanzania, were offered annual MDA as part of a district-wide trachoma control program. Presence of ocular C. trachomatis infection and TF were assessed in 3,200 randomly sampled children aged five years and younger, who were examined prior to each MDA. Infection was detected using the Amplicor CT/NG assay and TF was identified by clinical examination using the World Health Organization (WHO) simplified grading system. The association between chlamydial infection and TF in children was evaluated at baseline prior to any treatment, and 12 months after each of three annual rounds of mass treatment. Factors associated with infection were examined using generalized estimating equation models.At baseline, the overall prevalence of chlamydial infection and TF was 22% and 31%, respectively. Among children with clinical signs of TF, the proportion of those with infection was 49% prior to treatment and declined to 30% after three MDAs. The odds of infection positivity among children with clinical signs of TF decreased by 26% (OR 0.74, 95% CI 0.65 to 0.84, p = <0.01) with each MDA, after adjusting for age. For children aged under one year, who did not receive treatment, the relationship was unchanged.Conclusions/significanceThe association between ocular C. trachomatis infection and TF weakened in children with each MDA, as both infection and clinical disease prevalence declined. However, there was still a significant proportion of TF cases with infection after three rounds of MDA. New strategies are needed to assess this residual infection for optimal treatment distribution.

Immunofibrogenic Gene Expression Patterns in Tanzanian Children with Ocular Chlamydia trachomatis Infection, Active Trachoma and Scarring: Baseline Results of a 4-Year Longitudinal Study

“…This is consistent with earlier studies which found a stronger correlation as the underlying prevalence of infection increased (Ramadhani et al, 2016b ). However, in common with many other studies reporting the relationship between disease and infection, a minority (36%) of individuals with TF had detectable infection, probably due to the shorter duration of infection episodes relative to disease (Grassly et al, 2008 ; Burton et al, 2011a , c ; Lee et al, 2014 ). With increasing severity of both TF and TP scores, there was an increasing proportion with infection and increasing loads of infection.…”

“…Genes that were most strongly associated with active trachoma in the absence of C. trachomatis infection were enriched for pathways of leukocyte transendothelial migration, TNF receptors, MMP activation, collagen formation and assembly (Table 6 ). Active trachoma signs often persist after the clearance of C. trachomatis infection (Grassly et al, 2008 ; Burton et al, 2011a , c ; Lee et al, 2014 ) and inflammation is linked to progressive scarring (Ramadhani et al, 2016a ). We found that TP but not infection was associated with TS in the multivariable model (Table 3 ).…”

Evidence for contamination with C. trachomatis in the household environment of children with active Trachoma: A cross-sectional study in Kongwa, Tanzania

“…Ideally, we would have had a rapid test of infection to decide which households to visit, but there was not one available at the time of the study. We have shown the correlation of trachoma and infection even in low prevalence settings which justified the use of this purposeful sampling approach [22]; 3) imprecise sampling area of the object being sampled. We tried to sample the area indicated by the caretaker, but this could be imprecise and subject to recall bias.…”

The impact of a single round of community mass treatment with azithromycin on disease severity and ocular Chlamydia trachomatis load in treatment-naïve trachoma-endemic island communities in West Africa

“…It is likely that repeated episodes of infection are reduced following MDA due to a decrease in circulating C. trachomatis and subsequently reduced transmission. Moreover, in populations undergoing MDA there is evidence that clinical signs of trachoma become less specific for C. trachomatis infection [ 36 , 37 ], suggesting that only the more severe phenotypes remain predictive of C. trachomatis infection. Azithromycin exhibits immunomodulatory effects that may be associated with reduced levels of inflammation [ 38 ], although at one year after a single dose this effect is unlikely to play a major role.…”