Characterizing trachoma elimination using serology

Introduction

Trachoma, caused by repeated ocular infection with Chlamydia trachomatis, is targeted for global elimination as a public health problem (EPHP) by 2030^1,2. The World Health Organization (WHO) defined EPHP based on clinical signs of trachoma, and significant progress has been made globally, with 18 countries validated to have achieved EPHP as of July 2024³. As countries approach and achieve EPHP, programs are considering the use of complementary measures of C. trachomatis infection to monitor population-level transmission^{4, 5, 6, 7–8}. Potential approaches include nucleic acid amplification-based tests, such as polymerase chain reaction (PCR), and serologic assays that measure immunoglobulin G (IgG) antibody responses in young children. Unlike PCR-detectable infection, which is transient, IgG responses provide a measure of previous infection that is sensitive as populations approach trachoma elimination. Previous studies of IgG responses to C. trachomatis have characterized Pgp3 and CT694 antigens as highly immunogenic⁹. Consistent shifts in population-level age-specific seroprevalence and seroconversion rates (SCR) to these antigens among children correspond with changes in prevalence of trachoma^{6,10, 11–12}. Multiplex IgG assays lend themselves to inexpensive, concurrent surveillance of multiple diseases, including trachoma¹³. A key challenge remains: can surveys of serological responses reliably determine if C. trachomatis transmission falls below levels that require population-level trachoma interventions?

Deriving data-driven thresholds for intervention represents a generalizable problem for neglected tropical diseases and other infectious diseases, such as malaria. In the context of trachoma, some ocular C. trachomatis infections could still occur at very low levels of transmission, but cases of blindness from trachoma would be unlikely in the absence of repeated infections over many years¹⁴. Therefore, trachoma-specific population interventions in support of EPHP usually stop before interruption of ocular C. trachomatis transmission has been achieved. With this in mind, our focus was to characterize trachoma serology in relation to whether public health efforts were needed (or not).

Here, we combine data for IgG antibodies, PCR, and clinical observations from 63,911 children ages 1–9 years (41,168 ages 1–5 years) enrolled in 48 cross-sectional surveys across a gradient of trachoma prevalence settings to create a well-characterized trachoma serology dataset of unprecedented scale. Our objectives were to develop a serologic signature of trachoma elimination by examining...