Comparison of methods for assessing Chlamydia trachomatis transmission intensity: a systematic review

A systematic review was conducted. Five databases (MEDLINE, EMBASE, Global Health database, Scopus, and Global Index Medicus) were searched on October 19, 2022, and the e-Theses Online Service was searched on April 12, 2023. Studies from 1987 onward that reported primary data collection of field-graded TF in children and at least one other indicator were included. To compare field-graded vs. photo-graded TF, the mean difference in prevalence and 95% confidence intervals (CIs) were calculated. To compare field-graded TF against the other indicators, weighted correlation coefficients and p-values were calculated in pre-vs. post-antibiotic mass drug administration (MDA) settings. The review protocol was prospectively registered with PROSPERO (CRD42022356013).

A total of 35,764 studies were screened, yielding 235 included studies from 49 countries, spanning the years (of data collection) 1991–2021. For field-graded vs. photo-graded TF (n=10), the mean difference in prevalence was 0.7 percentage points, 95% CI (−15.2–16.7). The relationship between TF and other indicators was stronger pre-vs. post-MDA: TF vs infection (R2: 0.43, p=0.003 vs. R2: 0.002, p=0.788); TF vs seroprevalence (R2: 0.56, p<0.001 vs. R2: 0.03, p=0.353); and TF vs seroconversion rate (SCR) (R2: 0.52, p=0.012 vs. R2: 0.26, p=0.061). Post-MDA, infection and SCR were highly correlated (R2: 0.71, p=0.001). In studies reporting data used for programmatic decision-making, 48% of the areas warranting MDA based solely on TF had at least one other indicator categorized as indicating “low” or “medium” Ct transmission intensity.

The correlation between TF and measures of infection and serology weakens post-initiation of MDA, which is strongly suggestive of poor performance of TF prevalence for guiding programmatic decision-making post-MDA. Measures of infection and SCR are strongly correlated with each other post-MDA. Infection and/or serology should be considered to help guide programmatic decision-making post-MDA. Target Journal Ophthalmology Competing Interest Statement KKR and PJH are employees of the International Trachoma Initiative (ITI), a program of The Task Force for Global Health, which receives an operating budget and research funds from Pfizer Inc., the manufacturers of Zithromax (azithromycin). EMHE receives salary support from ITI, and CCL was an employee of ITI while assisting with this study. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated. Funding Statement RB's salary was funded by the Wellcome Trust (206275/Z/17/Z). AWS is a staff member of the World Health Organization. Funding organizations had no role in the design or conduct of this research. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Abbreviations and acronyms - CI - Confidence interval - Ct - Chlamydia trachomatous - FPC - follicles papillae cicatrices - IQR - Interquartile range - JBI - Joanna Briggs Institute - MDA - Mass Drug Administration - SCR - seroconversion rate - TF - trachomatous inflammation—follicular - TI - trachomatous inflammation—intense - WHO - World Health Organization