Serology for trachoma surveillance after cessation of mass drug administration.

BACKGROUND: Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious cause of blindness worldwide. Yearly azithromycin mass drug administration (MDA) plays a central role in efforts to eliminate blinding trachoma as a public health problem. Programmatic decision-making is currently based on the prevalence of the clinical sign "trachomatous inflammation-follicular" (TF) in children. We sought to test alternative tools for trachoma surveillance based on serology in the 12-year cohort of Kahe Mpya, Rombo District, Tanzania, where ocular chlamydial infection was eliminated with azithromycin MDA by 2005. METHODOLOGY AND PRINCIPAL FINDINGS: The present study was a community-based cross-sectional survey in Kahe Mpya. Of 989 residents, 571 people aged 6 months to 87 years were enrolled: 58% of the total population and 73% of 1-9 year olds, the key WHO indicator age group. Participants were examined for TF, had conjunctival swabs collected for nucleic acid amplification test (NAAT)-based detection of Ct, and blood collected for analysis of antibodies to the Ct antigens pgp3 and CT694 by multiplex bead-based immunoassay. Seroconversion rate was used to estimate changes in the force of infection in a reversible catalytic model. No conjunctival swabs tested positive for Ct infection by NAAT. Among 1-9 year olds, TF prevalence was 6.5%, whereas only 3.5% were seropositive. Force of infection modelling indicated a 10-fold decrease in seroconversion rate at a time corresponding to MDA commencement. Without baseline serological data, the inferences we can make about antibody status before MDA and the longevity of the antibody response are limited, though our use of catalytic modelling overcomes some of these limitations. CONCLUSIONS/SIGNIFICANCE: Serologic tests support NAAT findings of very low to zero prevalence of ocular Ct in this community and have potential to provide objective measures of transmission and useful surveillance tools for trachoma elimination programs

The utility of serology for elimination surveillance of trachoma

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, Pinsent et al. analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low transmission and post-elimination settings

The utility of serology for elimination surveillance of trachoma.

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, we analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low-transmission and post-elimination settings. Analyses with sero-catalytic and antibody acquisition models provide insights into transmission history within each population. To accurately estimate sero-conversion rates (SCR) for trachoma in populations with high-seroprevalence in adults, the model accounts for secondary exposure to Chlamydia trachomatis due to urogenital infection. We estimate the population half-life of sero-reversion for anti-Pgp3 antibodies to be 26 (95% credible interval (CrI): 21-34) years. We show SCRs below 0.015 (95% confidence interval (CI): 0.0-0.049) per year correspond to a prevalence of trachomatous inflammation-follicular below 5%, the current threshold for elimination of active trachoma as a public health problem. As global trachoma prevalence declines, we may need cross-sectional serological survey data to inform programmatic decisions

Force of infection modelling of seroconversion rates before and after MDA.

<p>A. Maximum likelihood fits from reversible catalytic equilibrium model for antibody responses either pgp3 or CT694 is shown. X-axis represents the time in years that each model has a change point. The y-axis is the log-likelihoods from each model where log-likelihoods are rescaled against a maximum of 0 and a log-likelihood above -2 is an approximate 95% confidence interval when the change occurred. B. A model in which SCR changed 10 years previously, to represent the time at which MDA ceased, had a better fit than the model that assumed the SCR had remained constant (likelihood ratio test X² = 45.4 p,0.0001). The triangles represent deciles of observed seroprevalence; the solid blue line represents the predicted values based on the model with dotted lines and the 95% CI.</p

Population structure of Kahe-Mpya and the study population.

<p>Population structure of Kahe-Mpya and the study population.</p

Antibody responses to <i>Ct</i> antigens 10 years after MDA cessation.

<p>A. Age-prevalence curves for antibody responses grouped by decade. Black squares represent individuals with any antibody-positive test (to pgp3 alone, CT694 alone, or both antigens), and red squares represent responses positive to both pgp3 and CT694. B. Plots show box-and-whiskers graph (min-max) of MFI-BG against age ranges grouped by decade for antibodies against pgp3 (left) and CT694 (right). C. Plots show age against MFI-BG for children aged 1–9. Each dot represents a single individual. Note the differences in the y-axis scales for pgp3 (left) and CT694 (right). Indeterminate range is shaded. Horizontal lines indicate cutoffs for antibody positivity. Ag = antigen.</p