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Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox's Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April-May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources.

Background: Following one to five years of antibiotic mass drug administration (MDA) for the elimination of trachoma as a public health problem, programmes must conduct impact surveys to inform decisions on whether MDA is still needed. These decisions are currently based on the prevalence of trachomatous inflammation-follicular (TF), which, after MDA, correlates poorly with prevalence of ocular Chlamydia trachomatis infection., Methodology/principal Findings: Impact surveys in six evaluation units (EUs) of Malawi were used as a platform to explore associations between the prevalence of TF, ocular C. trachomatis infection and anti-Pgp3 antibodies one year after the third annual round of MDA. Participants were examined for trachoma using the World Health Organization simplified grading system. Ocular swabs and dried blood spots (DBS) were collected from children aged 1-9 years. Swabs were tested for C. trachomatis DNA using GeneXpert. DBS were assayed for anti-Pgp3 antibodies using ELISA. EU-level prevalence of TF in children aged 1-9 years ranged from 4.7% (95% CI 3.4-6.3) to 7.2% (95% CI 5.8-8.9). Prevalence of C. trachomatis infection in children ranged from 0.1% (95% CI 0.0-0.6) to 0.7% (95% CI 0.3-1.3) while Pgp3 seroprevalence ranged from 6.9% (95% CI 5.4-8.6) to 12.0% (95% CI 10.1-14.0) and increased with age., Conclusions/significance: Based on current global policy, the prevalence of TF indicates that a further year of antibiotic MDA is warranted in four of six EUs yet the very low levels of infection cast doubt on the universal applicability of TF-based cut-offs for antibiotic MDA. Pgp3 seroprevalence was similar to that reported following MDA in other settings that have reached the elimination target however the predictive value of any particular level of seropositivity with respect to risk of subsequent infection recrudescence is, as yet, unknown., Competing Interests: The authors have declared that no competing interests exist.

Background: Program decision-making for trachoma elimination currently relies on conjunctival clinical signs. Antibody tests may provide additional information on the epidemiology of trachoma, particularly in regions where it is disappearing or elimination targets have been met., Methods: A cluster-randomized trial of mass azithromycin distribution strategies for trachoma elimination was conducted over three years in a mesoendemic region of Niger. Dried blood spots were collected from a random sample of children aged 1-5 years in each of 24 study communities at 36 months after initiation of the intervention. A multiplex bead assay was used to test for antibodies to two Chlamydia trachomatis antigens, Pgp3 and CT694. We compared seropositivity to either antigen to clinical signs of active trachoma (trachomatous inflammation-follicular [TF] and trachomatous inflammation-intense [TI]) at the individual and cluster level, and to ocular chlamydia prevalence at the community level., Results: Of 988 children with antibody data, TF prevalence was 7.8% (95% CI 6.1 to 9.5) and TI prevalence was 1.6% (95% CI 0.9 to 2.6). The overall prevalence of antibody positivity to Pgp3 was 27.2% (95% CI 24.5 to 30), and to CT694 was 23.7% (95% CI 21 to 26.2). Ocular chlamydia infection prevalence was 5.2% (95% CI 2.8 to 7.6). Seropositivity to Pgp3 and/or CT694 was significantly associated with TF at the individual and community level and with ocular chlamydia infection and TI at the community level. Older children were more likely to be seropositive than younger children., Conclusion: Seropositivity to Pgp3 and CT694 correlates with clinical signs and ocular chlamydia infection in a mesoendemic region of Niger., Trial Registration: ClinicalTrials.gov NCT00792922., Competing Interests: The authors have declared that no competing interests exist.

Trachoma is caused by Chlamydia trachomatis (Ct). It is targeted for global elimination as a public health problem. In 2014, a population-based cross-sectional study was performed in two previously trachoma-endemic areas of The Gambia. Participants of all ages from Lower River Region (LRR) (N = 1028) and Upper River Region (URR) (N = 840) underwent examination for trachoma and had blood collected for detection of antibodies against the Ct antigen Pgp3, by ELISA. Overall, 30 (1.6%) individuals had active trachoma; the prevalence in children aged 1-9 years was 3.4% (25/742) with no statistically significant difference in prevalence between the regions. There was a significant difference in overall seroprevalence by region: 26.2% in LRR and 17.1% in URR (p < 0.0001). In children 1-9 years old, seroprevalence was 4.4% in LRR and 3.9% in URR. Reversible catalytic models using information on age-specific seroprevalence demonstrated a decrease in the transmission of Ct infection in both regions, possibly reflecting the impact of improved access to water, health and sanitation as well as mass drug administration campaigns. Serological testing for antibodies to Ct antigens is potentially useful for trachoma programmes, but consideration should be given to the co-endemicity of sexually transmitted Ct infections.

Background: Efforts are underway to eliminate trachoma as a public health problem by 2020. Programmatic guidelines are based on clinical signs that correlate poorly with Chlamydia trachomatis (Ct) infection in post-treatment and low-endemicity settings. Age-specific seroprevalence of anti Ct Pgp3 antibodies has been proposed as an alternative indicator of the need for intervention. To standardise the use of these tools, it is necessary to develop an analytical approach that performs reproducibly both within and between studies., Methodology: Dried blood spots were collected in 2014 from children aged 1-9 years in Laos (n = 952) and Uganda (n = 2700) and from people aged 1-90 years in The Gambia (n = 1868). Anti-Pgp3 antibodies were detected by ELISA. A number of visual and statistical analytical approaches for defining serological status were compared., Principal Findings: Seroprevalence was estimated at 11.3% (Laos), 13.4% (Uganda) and 29.3% (The Gambia) by visual inspection of the inflection point. The expectation-maximisation algorithm estimated seroprevalence at 10.4% (Laos), 24.3% (Uganda) and 29.3% (The Gambia). Finite mixture model estimates were 15.6% (Laos), 17.1% (Uganda) and 26.2% (The Gambia). Receiver operating characteristic (ROC) curve analysis using a threshold calibrated against external reference specimens estimated the seroprevalence at 6.7% (Laos), 6.8% (Uganda) and 20.9% (The Gambia) when the threshold was set to optimise Youden's J index. The ROC curve analysis was found to estimate seroprevalence at lower levels than estimates based on thresholds established using internal reference data. Thresholds defined using internal reference threshold methods did not vary substantially between population samples., Conclusions: Internally calibrated approaches to threshold specification are reproducible and consistent and thus have advantages over methods that require external calibrators. We propose that future serological analyses in trachoma use a finite mixture model or expectation-maximisation algorithm as a means of setting the threshold for ELISA data. This will facilitate standardisation and harmonisation between studies and eliminate the need to establish and maintain a global calibration standard., Competing Interests: SG is employed by the commercial company IHRC, Inc. and is a contractor at the Centres for Disease Control and Prevention. The authors have declared that no competing interests exist.