Rebounding case notifications of chlamydia : an epidemiological game of 'Clue'?

Abstract

The genus Chlamydiae encompasses a unique class of obligate intracellular bacteria that can cause disease in a wide range of animals. In humans, Chlamydia trachomatis infections are common and are frequently observed in diseases of the eye, genital and respiratory tracts. Prevalent worldwide, Chlamydia infections can progress to chronic inflammatory sequellae and are the leading cause of curable sexually transmitted disease and preventable blindness. After falling in the face of intensified control efforts, case notifications of sexually transmitted Chlamydia in many countries are rising. In many jurisdictions, this unprecedented rise of Chlamydia case notifications has occurred after the introduction of wide spread control programs, and has been discussed to be a result of either increased testing volume, improvements to testing technologies, changes in sexual behaviour, or increased reinfection rates brought about by deleterious effects of treatment on acquired immunity. This thesis seeks to answer the question of why observed Chlamydia case notifications have rebounded? I have attempted to answer this question using simple dynamical models of Chlamydia transmission framed from immunological and epidemiological perspectives. Model structures are drawn from frameworks previously used for studying sexually transmitted infections, and represent a combination of theoretical and data-oriented formulations, as well as different (hierarchical) ecological scales. The results of this thesis highlight that increased testing volumes, rather than changes in the sensitivity and specificity of testing technologies, sexual behaviour, or truncated immunological responses brought about by treatment can explain the increase in observed chlamydia case notifications, and that simple explanations for these observed rates appear to have been dismissed in favor of an increase to the underlying prevalence. In addition to providing insights into current epidemiological trends, this thesis has also been able to produce significant insights into the natural history of chlamydial infection. In particular, the phenotype of an individual's immunobiology that results from multiple chlamydial infections suggests that longer periods between initial and repeat infection may increase an individual's chlamydial load, their duration of infection, as well as non-intuitively the formation of protective immunity, persistent infection, and the potential for immunopathogenesis. Additional population-scale analyses in this thesis also suggest the existence of a period of immunity that is, on average, much longer lasting than currently discussed in contemporary literature. The results of this research outline a potential way forward through filling several gaps in the immunological and epidemiological understanding of Chlamydia infections that involves both reviewing existing data as well as continued research using "systems science" approaches.