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[This corrects the article DOI: 10.1371/journal.pntd.0007130.].

Trachoma, the leading infectious cause of blindness worldwide, is one of several neglected tropical diseases targeted by WHO for elimination by 2030. The disease starts in childhood with repeated episodes of conjunctival Chlamydia trachomatis infection. This infection is associated with recurrent conjunctivitis (active trachoma), which, if left untreated, leads to cicatricial trachoma characterised by scarring of the conjunctiva, and potentially in-turned eyelashes (trachomatous trichiasis) in later life. Trachoma mainly affects the poorest and most rural communities; these populations typically have limited access to water and hygiene facilities. Blinding complications are most common in women who, in many cultures, act as caregivers from a young age for infected children. To eliminate trachoma as a public health problem, programmes implement a package of interventions known as SAFE; namely, surgery to treat trachomatous trichiasis, antibiotic mass drug administration to treat infection, facial cleanliness, and environmental improvement to limit transmission. The SAFE strategy has brought considerable success in the last two decades. As of December, 2024, 21 countries have eliminated the disease, and several others are on track to eliminate it soon. However, persistent and recrudescent active trachoma in some populations might challenge the success of the 2030 global elimination target. In such settings, novel, or more intensive, approaches must be promptly developed, tested, and scaled up to accelerate elimination.

Trachoma is targeted for global elimination as a public health problem by 2030. Measurement of IgG antibodies in children is being considered for surveillance and programmatic decision-making. There are currently no programmatic guidelines based on serology, which represents a generalizable problem in seroepidemiology and disease elimination. Here, we collate Chlamydia trachomatis Pgp3 and CT694 IgG measurements from 48 serosurveys across Africa, Latin America, and the Pacific Islands (41,168 children ages 1–5 years) and propose a novel approach to estimate the probability that population C. trachomatis transmission is below or above levels requiring ongoing programmatic action. We determine that trachoma programs could halt control measures with >90% certainty when seroconversion rates (SCRs) are ≤2.2 per 100 person-years. Conversely, SCRs ≥4.5 per 100 person-years correspond with >90% certainty that further control interventions are needed. More extreme SCR thresholds correspond with higher levels of confidence of elimination (lower SCR) or ongoing action needed (higher SCR). This study demonstrates a robust approach for using trachoma serosurveys to guide elimination program decisions. The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

The World Health Organization recommends annual mass azithromycin administration in communities with at least 10% prevalence of trachomatous inflammation-follicular (TF) in children, with further treatment depending on reassessment after 3-5 years. However, the effect of stopping mass azithromycin distribution after multiple rounds of treatment is not well understood. Here, we report the results of a cluster-randomized trial where communities that had received 4 years of treatments were then randomized to continuation or discontinuation of treatment. In all, 48 communities with 3,938 children aged 0-9 years at baseline in northern Ethiopia had received 4 years of annual or twice yearly mass azithromycin distribution as part of the TANA I trial. We randomized these communities to either continuation or discontinuation of treatment. Individuals in the communities in the continuation arm were offered either annual or twice yearly distribution of a single directly observed dose of oral azithromycin. The primary outcome was community prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years, 36 months after baseline. We also assessed the change from baseline to 36 months in ocular chlamydia prevalence within each arm. We compared 36-month ocular chlamydia prevalence in communities randomized to continuation versus discontinuation in a model adjusting for baseline ocular chlamydia prevalence. A secondary prespecified analysis assessed the rate of change over time in ocular chlamydia prevalence between arms. In the continuation arm, mean antibiotic coverage was greater than 90% at all time points. In the discontinuation arm, the mean prevalence of infection in children aged 0-9 years increased from 8.3% (95% CI 4.2% to 12.4%) at 0 months to 14.7% (95% CI 8.7% to 20.8%, P = 0.04) at 36 months. Ocular chlamydia prevalence in communities where mass azithromycin distribution was continued was 7.2% (95% CI 3.3% to 11.0%) at baseline and 6.6% (95% CI 1.1% to 12.0%, P = 0.64) at 36 months. The 36-month prevalence of ocular chlamydia was significantly lower in communities continuing treatment compared with those discontinuing treatment (P = 0.03). Limitations of the study include uncertain generalizability outside of trachoma hyperendemic regions. In this study, ocular chlamydia infection rebounded after 4 years of periodic mass azithromycin distribution. Continued distributions did not completely eliminate infection in all communities or meet WHO control goals, although they did prevent resurgence. This study was prospectively registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).

Background. The World Health Organization recommends annual treatment of entire trachoma-endemic communities, although children typically have a higher load, longer duration, and greater likelihood of infection. Methods. Forty-eight communities in Matameye, Niger, were randomized to annual oral azithromycin treatment of the entire community or biannual treatment of children aged 0–12 years only. Both children and adults were monitored for ocular chlamydial infection by polymerase chain reaction. Results. The prevalence of childhood infection was reduced in the annually treated arm from 21.2% (95% confidence interval [CI], 15.2%–28.0%) at baseline to 5.8% (95% CI, 3.2%–9.0%) at 36 months (P < .001) and in the biannual arm from 20.2% (95% CI, 15.5%–25.3%) to 3.8% (95% CI, 2.2%–6.0%; P < .001). Adult infection in the annual arm was reduced from 1.7% (95% CI, .9%–2.7%) to 0.3% (95% CI, .0%–.7%) and in the biannual arm from 1.2% (95% CI, .5%–2.2%) to 0.0% (95% CI, .0%–.7%; P = .005). The effect of biannual treatment of children compared with annual treatment of the entire community in both children (95% CI, −.04% to .02%) and adults (95% CI, .9%–2.7%) excluded the prespecified noninferiority threshold of 6% (P = .003 and P < .001, respectively). Conclusions. Periodic distribution of antibiotics to children in trachoma-endemic communities reduces chlamydial infection in both children and untreated adults, suggesting a form of herd protection. Biannual treatment of children was comparable to (specifically, noninferior to) annual treatment of the entire community, and may offer lower antibiotic use and other logistical advantages. Clinical Trials Registration. NCT00792922.

Genital Chlamydia trachomatis infection is the most commonly diagnosed sexually transmitted infection. Trachoma is caused by ocular infection with C trachomatis and is the leading infectious cause of blindness worldwide. New serological assays for C trachomatis could facilitate improved understanding of C trachomatis epidemiology and prevention. C trachomatis serology offers a means of investigating the incidence of chlamydia infection and might be developed as a biomarker of scarring sequelae, such as pelvic inflammatory disease. Therefore, serological assays have potential as epidemiological tools to quantify unmet need, inform service planning, evaluate interventions including screening and treatment, and to assess new vaccine candidates. However, questions about the performance characteristics and interpretation of C trachomatis serological assays remain, which must be addressed to advance development within this field. In this Personal View, we explore the available information about C trachomatis serology and propose several priority actions. These actions involve development of target product profiles to guide assay selection and assessment across multiple applications and populations, establishment of a serum bank to facilitate assay development and evaluation, and development of technical and statistical methods for assay evaluation and analysis of serological findings. The field of C trachomatis serology will benefit from collaboration across the public health community to align technological developments with their potential applications.

IntroductionTrachoma is caused by the bacterium Chlamydia trachomatis (Ct). The WHO recommends the SAFE strategy for trachoma elimination: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Multiple rounds of SAFE implementation have proven insufficient to eliminate trachoma in Ethiopia, where over 50% of the global trachoma burden remains. More effective antibiotic treatment schedules and transmission-suppressing approaches are needed. The aim of stronger SAFE is to evaluate the impact of a novel package of interventions to strengthen the A, F and E of SAFE on the prevalence of ocular Ct and trachoma in Oromia, Ethiopia.Methods and analysis68 clusters were randomised in a 1:1:1:1 ratio to one of (1) standard A/standard F&E (standard SAFE), (2) standard A/enhanced F&E, (3) enhanced A/standard F&E or (4) enhanced A/enhanced F&E (stronger SAFE). Enhanced A includes two height-based doses of oral azithromycin (equivalent to 20 mg/kg) given as single doses 2 weeks apart, as mass drug administration, annually. Enhanced F&E includes fly control measures (permethrin-treated headwear and odour-baited traps) and face-washing hygiene behaviour change implemented at household level in selected communities. The interventions will be implemented and reinforced over 3 years.The primary outcome is the prevalence of ocular Ct by quantitative PCR in children aged 1–9 years at 36 months. A key secondary outcome is the prevalence of active (inflammatory) trachoma in the same children, assessed by validated trachoma graders and conjunctival photography. Laboratory technicians and photo-graders are masked to treatment allocation. Other important secondary analyses include process evaluations, assessment of behaviour change, fly indicators, adherence and coverage of interventions and a cost analysis.Ethics and disseminationStudy protocols have been approved by the National Research Ethics Review Committee of the Ethiopian Ministry of Science and Higher Education and the London School of Hygiene & Tropical Medicine Ethics Committee. An independent data safety and monitoring board oversees the trial. Results will be disseminated through peer-reviewed publications, presentations and reports.Trial registration number ISRCTN40760473.

Neglected Tropical Diseases amenable to Preventive Chemotherapy (PC-NTDs) affect the poorest populations around the world, especially in Africa. Scientific information on the distribution and level of endemicity of these diseases in the Republic of the Congo (RoC) is scarce in the published literature. We sought to collect all available epidemiological data on PC-NTDs in the RoC to document the historical and current situation and identify challenges in reaching the elimination of NTDs. We searched Medline and Horizon databases for studies published until to July 4th, 2019, on onchocerciasis, lymphatic filariasis, soil-transmitted helminth infections, schistosomiasis, and trachoma in the RoC. Unpublished reports were also reviewed. We included all epidemiological studies containing community data and excluded case reports. Location, prevalence data, and dates of the studies were extracted. We identified 933 records, of which 56 met the inclusion criteria. The articles published before 1960 mainly concerned onchocerciasis and schistosomiasis. Despite a low number over the studied period, since 2005 there has been a steady increase in the number of publications. Most of the studies were cross-sectional and conducted in the general population. Trachoma is endemic in the Sangha and Likouala departments (prevalence of trachomatous inflammation-follicular > 5% in some villages), and further mapping is essential to properly assess the burden of this disease in the country. While the prevalence of soil-transmitted helminths is still high (over 20%) in a large part of Congo, cases of lymphatic filariasis (based on Wuchereria bancrofti antigenaemia and/or microfilaraemia) and onchocerciasis are becoming rare and very focused. To achieve the elimination of PC-NTDs, further intervention is required. Except for trachoma, whose epidemiological situation should be better evaluated, PC-NTDs are endemic in the RoC, and actions to control them have been taken by health authorities. To eliminate PC-NTDs, which are still present in some locations, new mapping surveys are needed, and increased investment in scientific research should be encouraged in the country.

Abstract Background World Health Organization (WHO) recommendations for starting and stopping mass antibiotic distributions are based on a clinical sign of trachoma, which is indirectly related to actual infection with the causative agent, Chlamydia trachomatis. Methods This study aimed to understand the effect of SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) interventions on ocular chlamydia in Amhara, Ethiopia, by describing the infection prevalence in a population-based sample of children aged 1-5 years. Trachoma surveys were conducted in all districts of Amhara, from 2011 to 2015 following approximately 5 years of SAFE. Ocular swabs were collected from randomly selected children to estimate the zonal prevalence of chlamydial infection. The Abbott RealTime polymerase chain reaction assay was used to detect C. trachomatis DNA. Results A total of 15632 samples were collected across 10 zones of Amhara. The prevalence of chlamydial infection in children aged 1-5 years was 5.7% (95% confidence interval, 4.2%-7.3%; zonal range, 1.0%-18.5%). Chlamydial infection and trachomatous inflammation-intense (TI) among children aged 1-9 years were highly correlated at the zonal level (Spearman correlation [r] = 0.93; P < .001), while chlamydial infection and trachomatous inflammation-follicular were moderately correlated (r = 0.57; P = .084). Conclusions After 5 years of SAFE, there is appreciable chlamydial infection in children aged 1-5 years, indicating that transmission has not been interrupted and that interventions should continue. The sign TI was highly correlated with chlamydial infection and can be used as a proxy indicator of infection. Appreciable ocular chlamydial infection remains in Amhara, Ethiopia, after 5 years of SAFE, indicating that transmission has not been interrupted. The sign trachomatous inflammation-intense was highly correlated with chlamydial infection and can be used as a proxy indicator of infection.