Ocular pathologic response elicited by Chlamydia organisms and the predictive value of quantitative modeling

Abstract

Background: Chlamydia organisms are a significant cause of ocular and genital tract disease worldwide. Acute inflammatory responses are largely responsible for pathologic changes.

Methods: Guinea pigs were inoculated in the conjunctiva with various infectious doses of Chlamydia caviae. We developed a predictive model and thresholds of the ocular pathologic response, on the basis of measurements of the pathologic response and chlamydial inclusion-forming unit (ifu) loads, using statistical and mathematical techniques. We validated the predictions by modifying the pathologic response with the use of a lytic chlamydiaphage.

Results: If the area under the inclusion-forming unit curve reaches approximately 4x10(5) "ifu-days," then it is likely that an ocular pathologic response will develop and that a serious pathologic finding can develop quickly. The earlier that a pathologic response arises, the longer it will remain. A 2-log10 reduction in the peak inclusion-forming unit load reduces the chance of any pathologic finding emerging from 81% to 32%, and it reduces the chance of a serious pathologic finding emerging from 33% to 2%. A reduction in the peak chlamydial load also substantially reduces the duration of the pathologic response.

Conclusions: Our predictive model can be used to evaluate the likely effect of interventions that modify the course of chlamydial infection. It suggests that, to be effective in preventing or mitigating pathologic responses, an intervention is required to change the chlamydial time course before the peak inclusion-forming unit load is reached.