Rational use of azithromycin in the control of trachoma : using quantitative PCR to assess distribution of infection and impact of treatment

Doctoral thesis English OPEN
Solomon, Anthony William

Trachoma is a chronic keratoconjunctivits caused by ocular infection with\ud Chlamdydia trachomatis (CT). It is a major cause of blindness. This thesis addresses\ud issues important for the rational use of the antibiotic azithromycin, one of the\ud cornerstones of WHO's strategy for trachoma elimination.\ud An entire sub-village in Rombo District, Tanzania was invited to participate.\ud Consenting individuals were examined and had swabs taken for quantitative PCR\ud (directed against the single-copy CT gene ompl), at baseline (before treatment). and\ud two, six, twelve and eighteen months after, mass distribution of single-dose\ud azithromycin. At the time of drug distribution, both weight and height of each treated\ud individual was recorded.\ud Four findings are highlighted. (1) Before treatment, and at each post-treatment time\ud point, children below the age of ten years harboured the bulk of the community's ocular\ud CT. Control programmes should view this age group as their principal target in\ud antibiotic distribution campaigns.\ud (2) Signs of active trachoma were much less useful than age thresholds for\ud predicting population subsets with heavy infections.\ud (3) Based on a summary statistic referred to as the community ocular CT load, or\ud COCTL, the overall community burden of organism fell dramatically following\ud azithromycin distribution, and stayed low for the entire eighteen months of follow-up.\ud The COCTL was 13% of its baseline level at two months. 8% of baseline at six months,\ud and 4% at both twelve and eighteen months. This may have been due to the high\ud treatment coverage (98%) achieved.\ud (4) In the population studied, height was a good proxy for weight for determining\ud azithromycin dose.\ud These studies contribute new information about the epidemiology of ocular CT\ud infection, provide dramatic evidence of the potential effect of azithromycin when uptake\ud is high, and should help to streamline azithromycin distribution efforts by simplifying\ud determination of dose in the field.
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