District-Level Forecast of Achieving Trachoma Elimination as a Public Health Problem By 2030: An Ensemble Modelling Approach.

Assessing the feasibility of 2030 as a target date for global elimination of trachoma, and identification of districts that may require enhanced treatment to meet World Health Organization (WHO) elimination criteria by this date are key challenges in operational planning for trachoma programmes. Here we address these challenges by prospectively evaluating forecasting models of trachomatous inflammation-follicular (TF) prevalence, leveraging ensemble-based approaches. Seven candidate probabilistic models were developed to forecast district-wise TF prevalence in 11 760 districts, trained using district-level data on the population prevalence of TF in children aged 1-9 years from 2004 to 2022. Geographical location, history of mass drug administration treatment, and previously measured prevalence data were included in these models as key predictors. The best-performing models were included in an ensemble, using weights derived from their relative likelihood scores. To incorporate the inherent stochasticity of disease transmission and challenges of population-level surveillance, we forecasted probability distributions for the TF prevalence in each geographic district, rather than predicting a single value. Based on our probabilistic forecasts, 1.46% (95% confidence interval [CI]: 1.43-1.48%) of all districts in trachoma-endemic countries, equivalent to 172 districts, will exceed the 5% TF control threshold in 2030 with the current interventions. Global elimination of trachoma as a public health problem by 2030 may require enhanced intervention and/or surveillance of high-risk districts.

When the Neighboring Village is Not Treated: Role of Geographic Proximity to Communities Not Receiving Mass Antibiotics for Trachoma.

BACKGROUND: Mass administration of azithromycin is an established strategy for decreasing the prevalence of trachoma in endemic areas. However, nearby untreated communities could serve as a reservoir that may increase the chances of chlamydia reinfection in treated communities. METHODS: As part of a cluster-randomized trial in Ethiopia, 60 communities were randomized to receive mass azithromycin distributions and 12 communities were randomized to no treatments until after the first year. Ocular chlamydia was assessed from a random sample of children per community at baseline and month 12. Distances between treated and untreated communities were assessed from global positioning system coordinates collected for the study. RESULTS: The pretreatment prevalence of ocular chlamydia among 0 to 9 year olds was 43% (95% confidence interval [CI], 39%-47%), which decreased to 11% (95% CI, 9%-14%) at the 12-month visit. The posttreatment prevalence of chlamydia was significantly higher in communities that were closer to an untreated community after adjusting for baseline prevalence and the number of mass treatments during the year (odds ratio, 1.12 [95% CI, 1.03-1.22] for each 1 km closer to an untreated community). CONCLUSIONS: Mass azithromycin distributions to wide, contiguous geographic areas may reduce the likelihood of continued ocular chlamydia infection in the setting of mass antibiotic treatments.

Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II).

BACKGROUND: Current guidelines recommend annual community-wide mass administration of azithromycin for trachoma. Targeting treatments to those most likely to be infected could reduce the amount of unnecessary antibiotics distributed. METHODS: In a cluster-randomized trial conducted from 1 November 2010 through 8 November 2013, 48 Ethiopian communities previously treated with annual mass azithromycin distributions for trachoma were randomized in equal numbers to (1) annual azithromycin distributions targeted to children aged 0-5 years, (2) annual azithromycin distributions targeted to households with a child aged 0-5 years found to have clinically active trachoma, (3) continued annual mass azithromycin distributions to the entire community, or (4) cessation of treatment. The primary outcome was the community prevalence of ocular chlamydia infection among children aged 0-9 years at month 36. Laboratory personnel were masked to treatment allocation. RESULTS: The prevalence of ocular chlamydia infection among children aged 0-9 years increased from 4.3% (95% confidence interval [CI], .9%-8.6%) at baseline to 8.7% (95% CI, 4.2%-13.9%) at month 36 in the age-targeted arm, and from 2.8% (95% CI, .8%-5.3%) at baseline to 6.3% (95% CI, 2.9%-10.6%) at month 36 in the household-targeted arm. After adjusting for baseline chlamydia prevalence, the 36-month prevalence of ocular chlamydia was 2.4 percentage points greater in the age-targeted group (95% CI, -4.8% to 9.6%; P = .50; prespecified primary analysis). No adverse events were reported. CONCLUSIONS: Targeting azithromycin treatment to preschool children was no different than targeting azithromycin to households with a child with clinically active trachoma. Neither approach reduced ocular chlamydia over the 3-year study. CLINICAL TRIALS REGISTRATION: NCT01202331.

Assessment of the status of improved F&E trachoma control practices among children of agro-pastoralists in Southern Ethiopia: a mixed design survey using theory of triadic influences.

BACKGROUND: Ethiopia is one of the countries with heavy trachoma burdens states globally. More than 75 million people in Ethiopia live in the trachoma endemic zones. Most populations with neglected tropical diseases (NTDs) live in hard-to-reach residences because of landscape and socio-cultural variances. This survey assessed the status of improved Face hygiene and Environmental cleanliness (F&E) trachoma control practices in children 1-9 years of age. METHODS: A mixed-method study design was applied concurrently. Enumeration was done through interviews using the standard tool and observational technique. Focus Group discussions (FGDs) and Key informant Interviews (KIIs) were used to conduct the qualitative arm. Confounders were controlled by modeling with multivariable logistic regression. RESULTS: For the Quantitative survey: The response rate was 99.8% of participants. The proportion with improved practice was 8%. About 13.9% of a child washed their faces and were visibly clean. About 15.2% of the households had an observable clean environment. High Wealth index, Perceived ability, knowledge about trachoma transmission from person to person, and stance toward preventive behavior were associated with improved practices. The odds of having improved F&E practice were 67% lower for those who reported positive normative preventive behavior than negatives. Qualitative arm: Some key informants reported village dwellers' shortage of basic knowledge; attitude and behavioral change for improved hygienic practices are the challenges. Inhabitants, including elder children, are aware of the hygiene issue though they do not practice it or have no intention to practice it. CONCLUSIONS: Improved F&E practices were much lower in the study region than the regional plan to achieve.

Genomics of Ocular Chlamydia trachomatis After 5 Years of SAFE Interventions for Trachoma in Amhara, Ethiopia.

BACKGROUND: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident. METHODS: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct. RESULTS: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence. CONCLUSIONS: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity.

Changing hygiene behaviours: a cluster-randomized trial, Ethiopia.

OBJECTIVE: To determine whether a water, sanitation and hygiene intervention could change hygiene behaviours thought to be important for trachoma control. METHODS: We conducted a cluster-randomized trial in rural Ethiopia from 9 November 2015 to 5 March 2019. We randomized 20 clusters to an intervention consisting of water and sanitation infrastructure and hygiene promotion and 20 clusters to no intervention. All intervention clusters received a primary-school hygiene curriculum, community water point, household wash station, household soap and home visits from hygiene promotion workers. We assessed intervention fidelity through annual household surveys. FINDINGS: Over the 3 years, more wash stations, soap and latrines were seen at households in the intervention clusters than the control clusters: risk difference 47 percentage points (95% confidence interval, CI: 41-53) for wash stations, 18 percentage points (95% CI: 12-24) for soap and 12 percentage points (95% CI: 5-19) for latrines. A greater proportion of people in intervention clusters reported washing their faces with soap (e.g. risk difference 21 percentage points; 95% CI: 15-27 for 0-5 year-old children) and using a latrine (e.g. risk difference 9 percentage points; 95% CI: 2-15 for 6-9 year-old children). Differences between the intervention and control arms were not statistically significant for many indicators until the programme had been implemented for at least a year; they did not decline during later study visits. CONCLUSION: The community- and school-based intervention was associated with improved hygiene access and behaviours, although changes in behaviour were slow and required several years of the intervention.

Azithromycin Reduction to Reach Elimination of Trachoma (ARRET): study protocol for a cluster randomized trial of stopping mass azithromycin distribution for trachoma.

BACKGROUND: The World Health Organization (WHO) recommends annual mass azithromycin distribution until districts drop below 5% prevalence of trachomatous inflammation-follicular (TF). Districts with very low TF prevalence may have little or no transmission of the ocular strains of Chlamydia trachomatis that cause trachoma, and additional rounds of mass azithromycin distribution may not be useful. Here, we describe the protocol for a randomized controlled trial designed to evaluate whether mass azithromycin distribution can be stopped prior to the current WHO guidelines. METHODS: The Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) study is a 1:1 community randomized non-inferiority trial designed to evaluate whether mass azithromycin distribution can be stopped in districts with baseline prevalence of TF under 20%. Communities in Maradi, Niger are randomized after baseline assessment either to continued annual mass azithromycin distribution or stopping annual azithromycin distribution over a 3-year period. We will compare the prevalence of ocular C. trachomatis (primary outcome), TF and other clinical signs of trachoma, and serologic markers of trachoma after 3 years. We hypothesize that stopping annual azithromycin distribution will be non-inferior to continued annual azithromycin distributions for all markers of trachoma prevalence and transmission. DISCUSSION: The results of this trial are anticipated to provide potentially guideline-changing evidence for when mass azithromycin distributions can be stopped in low TF prevalence areas. TRIAL REGISTRATION NUMBER: This study is registered at clinicaltrials.gov ( NCT04185402 ). Registered December 4, 2019; prospectively registered pre-results.

Understanding hard-to-reach communities: local perspectives and experiences of trachoma control among the pastoralist Maasai in northern Tanzania.

As progress to eliminate trachoma is made, addressing hard-to-reach communities becomes of greater significance. Areas in Tanzania, inhabited by the Maasai, remain endemic for trachoma. This study assessed the effectiveness of Mass Drug Administration (MDA) through an ethnographic study of trachoma amongst a Maasai community. The MDA experience in the context of the livelihoods of the Maasai in a changing political economy was explored using participant observation and household interviews. Factors influencing MDA effectiveness within five domains were analysed. 1) Terrain of intervention: Human movement hindered MDA, including seasonal migration, domestic chores, grazing and school. Encounters with wildlife were significant. 2) Socio-cultural factors and community agency: Norms around pregnancy led women to accept the drug but hide refusal to swallow the drug. Timing of Community Drug Distributor (CDD) visits conflicted with livestock grazing. Refusals occurred among the ilmurrani age group and older women. Mistrust significantly hindered uptake of drugs. 3) Strategies and motivation of drug distributors: Maa-speaking CDDs were critical to effective drug delivery. Maasai CDDs, whilst motivated, faced challenges of distances, encounters with wildlife and compensation. 4) Socio-materiality of technology: Decreases in side-effects over years have improved trust in the drug. Restrictions to swallowing drugs and/or water were relevant to post-partum women and the ilmurrani. 5) History and health governance: Whilst perceptions of the programme were positive, communities questioned government priorities for resources for hospitals, medicines, clean water and roads. They complained of a lack of information and involvement of community members in health care services. With elimination in sight, hard-to-reach communities are paramount as these are probably the last foci of infection. Effective delivery of MDA programmes in such communities requires a critical understanding of community experiences and responses that can inform tailored approaches to trachoma control. Application of a critical social science perspective should be embedded in planning and evaluation of all NTD programmes.

Trachoma Prevalence After Discontinuation of Mass Azithromycin Distribution.

BACKGROUND: As the World Health Organization seeks to eliminate trachoma by 2020, countries are beginning to control the transmission of trachomatous inflammation-follicular (TF) and discontinue mass drug administration (MDA) with oral azithromycin. We evaluated the effect of MDA discontinuation on TF1-9 prevalence at the district level. METHODS: We extracted from the available data districts with an impact survey at the end of their program cycle that initiated discontinuation of MDA (TF1-9 prevalence <5%), followed by a surveillance survey conducted to determine whether TF1-9 prevalence remained below the 5% threshold, warranting discontinuation of MDA. Two independent analyses were performed, 1 regression based and 1 simulation based, that assessed the change in TF1-9 from the impact survey to the surveillance survey. RESULTS: Of the 220 districts included, TF1-9 prevalence increased to >5% from impact to surveillance survey in 9% of districts. Regression analysis indicated that impact survey TF1-9 prevalence was a significant predictor of surveillance survey TF1-9 prevalence. The proportion of simulations with >5% TF1-9 prevalence in the surveillance survey was 2%, assuming the survey was conducted 4 years after MDA. CONCLUSION: An increase in TF1-9 prevalence may represent disease resurgence but could also be due to measurement error. Improved diagnostic tests are crucial to elimination of TF1-9 as a public health problem.

Interventions for preventing ophthalmia neonatorum.

BACKGROUND: Ophthalmia neonatorum is an infection of the eyes in newborns that can lead to blindness, particularly if the infection is caused by Neisseria gonorrhoeae. Antiseptic or antibiotic medication is dispensed into the eyes of newborns, or dispensed systemically, soon after delivery to prevent neonatal conjunctivitis and potential vision impairment. OBJECTIVES: 1. To determine if any type of systemic or topical eye medication is better than placebo or no prophylaxis in preventing ophthalmia neonatorum. 2. To determine if any one systemic or topical eye medication is better than any other medication in preventing ophthalmia neonatorum. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers, date of last search 4 October 2019. We also searched references of included studies and contacted pharmaceutical companies.  SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials of any topical, systemic, or combination medical interventions used to prevent ophthalmia neonatorum in newborns compared with placebo, no prophylaxis, or with each other. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Outcomes were: blindness or any adverse visual outcome at 12 months, conjunctivitis at 1 month (gonococcal (GC), chlamydial (CC), bacterial (BC), any aetiology (ACAE), or unknown aetiology (CUE)), and adverse effects.  MAIN RESULTS: We included 30 trials with a total of 79,198 neonates. Eighteen studies were conducted in high-income settings (the USA, Europe, Israel, Canada), and 12 were conducted in low- and middle-income settings (Africa, Iran, China, Indonesia, Mexico). Fifteen of the 30 studies were quasi-randomised. We judged every study to be at high risk of bias in at least one domain. Ten studies included a comparison arm with no prophylaxis. There were 14 different prophylactic regimens and 12 different medications in the 30 included studies. Any prophylaxis compared to no prophylaxis  Unless otherwise indicated, the following evidence comes from studies assessing one or more of the following interventions: tetracycline 1%, erythromycin 0.5%, povidone-iodine 2.5%, silver nitrate 1%. None of the studies reported data on the primary outcomes: blindness or any adverse visual outcome at any time point. There was only very low-certainty evidence on the risk of GC with prophylaxis (4/5340 newborns) compared to no prophylaxis (5/2889) at one month (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.24 to 2.65, 3 studies). Low-certainty evidence suggested there may be little or no difference in effect on CC (RR 0.96, 95% CI 0.57 to 1.61, 4874 newborns, 2 studies) and BC (RR 0.84, 95% CI 0.37 to 1.93, 3685 newborns, 2 studies). Moderate-certainty evidence suggested a probable reduction in risk of ACAE at one month (RR 0.65, 95% 0.54 to 0.78, 9666 newborns, 8 studies assessing tetracycline 1%, erythromycin 0.5%, povidone-iodine 2.5%, silver nitrate 1%, colostrum, bacitracin-phenacaine ointment). There was only very low-certainty evidence on CUE  (RR 1.75, 95% CI 0.37 to 8.28, 330 newborns, 1 study). Very low-certainty evidence on adverse effects suggested no increased nasolacrimal duct obstruction (RR 0.93, 95% CI 0.68 to 1.28, 404 newborns, 1 study of erythromycin 0.5% and silver nitrate 1%) and no increased keratitis (single study of 40 newborns assessing silver nitrate 1% with no events).    Any prophylaxis compared to another prophylaxis Overall, evidence comparing different interventions did not suggest any consistently superior intervention. However, most of this evidence was of low-certainty and was extremely limited. AUTHORS' CONCLUSIONS: There are no data on whether prophylaxis for ophthalmia neonatorum prevents serious outcomes such as blindness or any adverse visual outcome. Moderate-certainty evidence suggests that the use of prophylaxis may lead to a reduction in the incidence of ACAE in newborns but the evidence for effect on GC, CC or BC was less certain. Comparison of individual interventions did not suggest any consistently superior intervention, but data were limited. A trial comparing tetracycline, povidone-iodine (single administration), and chloramphenicol for GC and CC could potentially provide the community with an effective, universally applicable prophylaxis against ophthalmia neonatorum.

Impact of mass drug administration of azithromycin for trachoma elimination on prevalence and azithromycin resistance of genital Mycoplasma genitalium infection.

BACKGROUND: Mass drug administration (MDA) of 20 mg/kg (maximum 1 g in adults) azithromycin for ocular Chlamydia trachomatis (CT) infection is a key component of the WHO trachoma elimination strategy. However, this dose may be suboptimal in Mycoplasma genitalium infection and may encourage emergence of antimicrobial resistance (AMR) to azithromycin. OBJECTIVES: To determine the effect of MDA for trachoma elimination on M. genitalium prevalence, strain type and azithromycin resistance. METHODS: A secondary analysis of CT-negative vulvovaginal swabs from three outpatient antenatal clinics (Honiara, Solomon Islands) from patients recruited either pre-MDA, or 10 months post-MDA in two cross-sectional surveys was carried out. Swabs were tested for M. genitalium infection using Fast Track Diagnostics Urethritis Plus nucleic acid amplification assay. M. genitalium-positive samples were subsequently tested for azithromycin resistance by sequencing domain V of the 23S rRNA DNA region of M. genitalium and underwent phylogenetic analysis by dual locus sequence typing. RESULTS: M. genitalium prevalence was 11.9% (28/236) in women pre-MDA and 10.9% (28/256) 10 months post-MDA (p=0.7467). Self-reported receipt of azithromycin as part of MDA was 49.2% in women recruited post-MDA and 17.9% (5/28) in those who tested M. genitalium positive. Of samples sequenced (21/28 pre-MDA, 22/28 post-MDA), all showed a macrolide susceptible genotype. Strain typing showed that sequence types diverged into two lineages, with a suggestion of strain replacement post-MDA. CONCLUSION: A single round of azithromycin MDA in an island population with high baseline M. genitalium prevalence did not appear to impact on either prevalence or azithromycin resistance, in contrast to reported decreased genital CT prevalence in the same population. This may be due to limitations such as sample size, including CT-negative samples only, and low MDA coverage. Further investigation of the impact of multiple rounds of MDA on M. genitalium azithromycin AMR in antibiotic experienced and naïve populations is warranted.

Ocular Chlamydia trachomatis Infection Under the Surgery, Antibiotics, Facial Cleanliness, and Environmental Improvement Strategy in Amhara, Ethiopia, 2011-2015.

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.

Models of Trachoma Transmission and Their Policy Implications: From Control to Elimination.

Despite great progress in eliminating trachoma from the majority of worldwide districts, trachoma control seems to have stalled in some endemic districts. Can mathematical models help suggest the way forward? We review specific achievements of models in trachoma control in the past. Models showed that, even with incomplete coverage, mass drug administration could eliminate disease through a spillover effect, somewhat analogous to how incomplete vaccine campaigns can eliminate disease through herd protection. Models also suggest that elimination can always be achieved if enough people are treated often enough with an effective enough drug. Other models supported the idea that targeting ages at highest risk or continued improvements in hygiene and sanitation can contribute meaningfully to trachoma control. Models of intensive targeting of a core group may point the way to final eradication even in areas with substantial transmission and within-community heterogeneity.

Mass azithromycin distribution for hyperendemic trachoma following a cluster-randomized trial: A continuation study of randomly reassigned subclusters (TANA II).

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).

Enhanced antibiotic distribution strategies and the potential impact of facial cleanliness and environmental improvements for the sustained control of trachoma: a modelling study.

BACKGROUND: Despite some success in controlling trachoma with repeated mass drug administration (MDA), some hyperendemic regions are not responding as fast as anticipated. Available data suggests that individuals with higher bacterial infection loads are less likely to resolve infection following a single dose of treatment, and thus remain a source of re-emergent infection following treatment. We assessed the potential impact of a new double-dose antibiotic distribution strategy in addition to enhanced facial cleanliness (F) and environmental improvements (E). METHODS: Using a within-community mathematical model of trachoma transmission we assessed the impact of a new double-dose antibiotic distribution strategy given 2 weeks apart, with and without enhanced F&E. We compared the annual double-dose strategy to single-dose annual MDA treatment in hyper-, meso- and hypoendemic settings, and to biannual MDA at 6-monthly intervals in hyperendemic communities. RESULTS: The findings from our mathematical model suggest that implementing the new double-dose strategy for 5 years or less was predicted to control infection more successfully than annual or 6-monthly treatment. Infection was controlled more readily if treatment was combined with enhanced F&E. The results appeared robust to variation in a number of key epidemiological parameters. To have long-term impact on transmission, enhanced F&E is essential for high transmission settings. CONCLUSION: Our current findings are based on simualtion modelling only, due to lack of epidemilogical data, however they do suggest that the  annual double-dose treatment strategy is encouraging for trachoma control. In high transmission settings, both MDA and enhanced F&E are needed for sustained control.

CD8+ T cells define an unexpected role in live-attenuated vaccine protective immunity against Chlamydia trachomatis infection in macaques.

Trachoma, caused by the obligate intracellular organism Chlamydia trachomatis, is the world's leading cause of preventable blindness for which a vaccine is needed. We have previously shown that a plasmid-deficient live-attenuated trachoma vaccine delivered ocularly to macaques elicited either solid or partial protective immunity against a virulent ocular challenge. Solidly protected macaques shared the same MHC class II alleles implicating CD4(+) T cells in superior protective immunity. Understandably, we sought to define T cell immune correlates in these animals to potentially improve vaccine efficacy. In this study, following a 2-y resting period, these macaques were boosted i.m. with the live-attenuated trachoma vaccine and their peripheral T cell anamnestic responses studied. Both solidly and partially protected macaques exhibited a CD4(+) and CD8(+) T cell anamnestic response following booster immunization. CD8(+) but not CD4(+) T cells from solidly protected macaques proliferated against soluble chlamydial Ag. We observed a more rapid T cell inflammatory cytokine response in tears of solidly protected animals following ocular rechallenge. Most notably, depletion of CD8(+) T cells in solidly protected macaques completely abrogated protective immunity. Collectively, our findings support the conclusion that CD8(+) T cells play an important but unexpected role in live-attenuated trachoma vaccine-mediated protective immunity.

Australian trachoma surveillance annual report, 2013.

Australia remains the only developed country to have endemic levels of trachoma (a prevalence of 5% or greater among children) in some regions. Endemic trachoma in Australia is found predominantly in remote and very remote Aboriginal communities. The Australian Government funds the National Trachoma Surveillance and Reporting Unit to collate, analyse and report trachoma prevalence data and document trachoma control strategies in Australia through an annual surveillance report. This report presents data collected in 2013. Data are collected from Aboriginal and Torres Strait Island communities designated at-risk for endemic trachoma within New South Wales, the Northern Territory, South Australia and Western Australia. The World Health Organization grading criteria were used to diagnose cases of trachoma in Aboriginal children, with jurisdictions focusing screening activities on the 5-9 years age group; but some children in the 1-4 and 10-14 years age groups were also screened. The prevalence of trachoma within a community was used to guide treatment strategies as a public health response. Aboriginal adults aged 40 years or over were screened for trichiasis. Screening coverage for the estimated population of children aged 5-9 years and adults aged 40 years or over in at-risk communities required to be screened in 2013 was 84% and 30%, respectively. There was a 4% prevalence of trachoma among children aged 5-9 years who were screened. Of communities screened, 50% were found to have no cases of active trachoma and 33% were found to have endemic levels of trachoma. Treatment was required in 75 at-risk communities screened. Treatment coverage for active cases and their contacts varied between jurisdictions from 79% to 100%. Trichiasis prevalence was 1% within the screened communities.