Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory disease: a mathematical modelling study

Abstract

Background: Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms from the vagina and endocervix to the upper genital tract. PID can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of development of PID after the sexually transmitted bacterial infection Chlamydia trachomatis (chlamydia) might affect the impact of screening interventions, but is currently unknown. This study investigates three hypothetical processes for the timing of progression: at the start, at the end, or throughout the duration of chlamydia infection.

Methods: We develop a compartmental model that describes the trial structure of a published randomised controlled trial (RCT) and allows each of the three processes to be examined using the same model structure. The RCT estimated the effect of a single chlamydia screening test on the cumulative incidence of PID up to one year later. The fraction of chlamydia infected women who progress to PID is obtained for each hypothetical process by the maximum likelihood method using the results of the RCT.

Results: The predicted cumulative incidence of PID cases from all causes after one year depends on the fraction of chlamydia infected women that progresses to PID and on the type of progression. Progression at a constant rate from a chlamydia infection to PID or at the end of the infection was compatible with the findings of the RCT. The corresponding estimated fraction of chlamydia infected women that develops PID is 10% (95% confidence interval 7-13%) in both processes.

Conclusions: The findings of this study suggest that clinical PID can occur throughout the course of a chlamydia infection, which will leave a window of opportunity for screening to prevent PID.

Figure 1

Schematic overview of the model framework. The model has a susceptible-infected-susceptible (SIS) framework and allows three hypothetical processes for the timing of progression from chlamydia to PID to be investigated. A woman can become infected at rate λ (force of infection), can clear her infection naturally (rate r), or can be effectively screened and treated (rate α). Numbers indicate when during the chlamydia infection progression to PID could happen: 1) immediate progression, 2) constant progression, and 3) progression at the end of infection. For all three types of progression a certain fraction f of chlamydia-infected women will develop PID. For the constant progression model a woman moves from being infected without PID (I₁) to being infected with PID (I₂) at rate γ, which is set to $\gamma =\frac{f}{1-f}r$. For immediate progression and the progression at the end of infection we set $\gamma =0$ and $\text{I}={\text{I}}_1+{\text{I}}_2$.

Figure 2

Predicted cumulative incidence of chlamydial PID for the three types of timing of progression. Panel A, results for intervention group; panel B, results for control group. Immediate progression (dashed line); constant progression (solid line); progression at the end (dashed-dotted line). The fraction progressing from chlamydia to PID is varied from 0-100% using baseline values for all other model parameters.

Figure 3

Univariable sensitivity analysis, varying the proportion of PID cases due chlamydia in the control group. Panel A, fraction of progression needed in each type of timing of progression: immediate progression (dashed line); constant progression (solid line); and progression at the end (dashed-dotted line). Panels B- D, cumulative incidences of PID cases caused by chlamydia and other microorganisms after one year in the control group (dashed line) and in the intervention group (solid line) for the three types of timing of progression: immediate progression (B); constant progression (C); and progression at the end (D). The baseline value scenario is indicated with a black dot. Proportion of PID cases due chlamydia infection in the control group from 13-53% using baseline values for all other parameters. The observed cumulative incidences of PID after one year (%) in the trial were: control group 1.9 (95% CI 1.2 to 2.9), intervention group 1.3 (95% CI 0.7 to 2.1).