Determinants of active trachoma among rural children aged 1-9 years old in Aw-Bare Wereda, Somali Region of Ethiopia: a cross-sectional study.

INTRODUCTION: Chronic and highly contagious, trachoma is a condition characterized by recurrent bacterial infection with ocular strains of Mycoplasma trachoma. It spreads through fingers, flies, and fomites, especially in situations where there is overcrowding. If untreated, the illness may result in blindness. Trachoma is an ancient disease and has previously been a significant public health problem in many areas of the world, including parts of Europe and North America. There are at least 400 million cases of active trachoma in the world, 8 million of which have resulted in blindness. Trachoma is a serious public health issue that is very common in Ethiopia. Therefore, the objective of this study is to identify the determinants of active trachoma among rural children aged 1-9 years old in Aw-bare woreda, Somali region of Ethiopia. METHOD: A cross-sectional community-based study involving children aged 1-9 who lived in six selected rural kebeles in the Awbare woreda Somali region and carried out using an ordinal logistic regression model. The study comprised 377 children in total. Our sample youngsters were chosen through a two-stage cluster sampling procedure. Then also chose our sample kebeles by simple random sampling. The main environmental, personal, and demographic factors that influenced the outcomes of active trachoma status were modeled using partial proportional odds modeling and descriptive statistics. RESULT: The study showed that the prevalence of active trachoma was found to be 47.7%. The covariate secondary level of education of mother OR = 1.357; 95% CI (1.051, 1.75), P-value = 0.0192, Inside house cooking place of children family OR = 0.789:95% CI (0.687, 0.927), P-value = 0.0031, children stay at home OR = 2.203:95%CI (1.526, 3.473), P-value = 0.0057,rich income family OR = 1.335:95%CI(1.166,1.528),P-value = 0.0001,Amount of water fetched per day OR = 2.129,95%CI(1.780,2.547),P-Vaue = 0.0001 were significant effect on active trachoma. PPOM represents the best fit as it has the smallest AIC and BIC. It is also more parsimonious. CONCLUSION: The mother's educational level, the location where the children spent the majority of their time indoors cooking, the fly density during the interview, the family's income, the child's age in years, the distance to the water source, the quantity of water fetched daily, and the number of people sharing a room have all been found to be significant predictors of the child's active trachoma status. Thus, increasing maternal education, access to clean water, and socioeconomic position are all crucial measures in preventing trachoma. Preventing trachoma also involves reducing the number of kids in a room and enhancing activities linked to personal cleanliness, such as giving kids a thorough facial wash to remove debris and discharge from their eyes.

Multimodal mucosal and systemic immune characterization of a non-human primate trachoma model highlights the critical role of local immunity during acute phase disease.

BACKGROUND: Trachoma is a leading cause of infection-related blindness worldwide. This disease is caused by recurrent Chlamydia trachomatis (Ct) infections of the conjunctiva and develops in two phases: i) active (acute trachoma, characterized by follicular conjunctivitis), then long-term: ii) scarring (chronic trachoma, characterized by conjunctival fibrosis, corneal opacification and eyelid malposition). Scarring trachoma is driven by the number and severity of reinfections. The immune system plays a pivotal role in trachoma including exacerbation of the disease. Hence the immune system may also be key to developing a trachoma vaccine. Therefore, we characterized clinical and local immune response kinetics in a non-human primate model of acute conjunctival Ct infection and disease. METHODOLOGY/PRINCIPAL FINDINGS: The conjunctiva of non-human primate (NHP, Cynomolgus monkeys-Macaca fascicularis-) were inoculated with Ct (B/Tunis-864 strain, B serovar). Clinical ocular monitoring was performed using a standardized photographic grading system, and local immune responses were assessed using multi-parameter flow cytometry of conjunctival cells, tear fluid cytokines, immunoglobulins, and Ct quantification. Clinical findings were similar to those observed during acute trachoma in humans, with the development of typical follicular conjunctivitis from the 4th week post-exposure to the 11th week. Immunologic analysis indicated an early phase influx of T cells in the conjunctiva and elevated interleukins 4, 8, and 5, followed by a late phase monocytic influx accompanied with a decrease in other immune cells, and tear fluid cytokines returning to initial levels. CONCLUSION/SIGNIFICANCE: Our NHP model accurately reproduces the clinical signs of acute trachoma, allowing for an accurate assessment of the local immune responses in infected eyes. A progressive immune response occurred for weeks after exposure to Ct, which subsided into a persistent innate immune response. An understanding of these local responses is the first step towards using the model to assess new vaccine and therapeutic strategies for disease prevention.

Comparison of metrics for assessing face washing behaviour for trachoma control.

There is currently no single, easy-to-use, reliable indicator to assess whether a face has been washed with soap in the context of trachoma elimination. This study aimed to compare survey report, script-based pictorial recall and facial cleanliness indicators as alternatives to structured observation for measuring face washing behaviour. This method validation study was nested in the Stronger-SAFE trial, Oromia Region, Ethiopia. Structured observation was conducted in randomly selected households for three hours from dawn. The primary caregiver in each household participated in a survey to capture (self)-reported behaviour and/or script-based pictorial recall, a routine-based diary activity to covertly capture information on face washing behaviour of themself and any children aged 1-12. Children 4-12 years old directly participated in the survey and pictorial recall in a subset of households. The facial cleanliness of children aged 1-12 was assessed qualitatively and using the quantitative Personal Hygiene Assessment Tool (qPHAT). Prevalence estimates, sensitivity, specificity and predictive values were computed for each behavioural indicator with observation data as the gold standard. The appropriateness of script-based pictorial recall was assessed using baseline and 3-month follow-up data. Baseline data were collected from 204 households in 68 clusters. Survey estimates of face washing and face washing with soap among caregivers and children were 32% to 60% and 5% to 31% higher than observed behaviour, respectively. Face washing prevalence estimates from pictorial recall were lower than survey estimates and comparable with observations for some face washing with soap indicators (0.3% to 13% higher than observations). Specificity of pictorial recall indicators was high (85% to 99%), but the sensitivity was low (0% to 67%), resulting in a low positive predictive value for all indicators. Both qualitative facial cleanliness indicators and qPHAT scores were poorly correlated with observed face washing earlier that morning. Pictorial recall overestimated face washing with soap among both caregivers and children following intervention delivery but not at baseline. Survey (self)-reported data on face washing is highly inaccurate. Script-based pictorial recall does not correctly classify those who wash their face with soap, and is subject to differential bias following intervention exposure, and facial cleanliness is a poor indicator of recent face washing in settings where faces become rapidly dirty again after washing. Alternatives to structured observation cannot be recommended to monitor the effectiveness of face washing interventions in community settings. Trial Registration ISRCTN registry ISRCTN40760473, https://doi.org/10.1186/ISRCTN40760473.

Cirugía de la triquiasis tracomatosa. Tercera edición

En esta tercera edición se actualiza la definición de la triquiasis tracomatosa según lo acordado en la cuarta Reunión Científica Mundial sobre el Tracoma (Ginebra, del 27 al 29 de noviembre del 2018), se agrega una descripción sobre cómo examinar el entropión, se mejoran las listas de instrumentos y material fungible necesarios para la cirugía, se amplía y se mejora la orientación sobre los cuidados posoperatorios, se incluyen ilustraciones actualizadas, se mejora la presentación en todo el libro, y se elimina el contenido redundante.

Photographic grading to evaluate facial cleanliness and trachoma among children in Amhara region, Ethiopia.

BACKGROUND: Promotion of facial cleanliness is recommended for the elimination of blinding trachoma, largely because of observational studies that have found an association between various measures of facial uncleanliness and trachoma. However, when a field grader assesses both facial cleanliness and trachoma, associations may be biased. Assessment of photographs of the face and conjunctiva by masked graders may provide a less biased estimate of the relationship between facial cleanliness and trachoma. METHODS: Face photographs, conjunctival photographs, and conjunctival swabs were obtained on a random sample of 0-9-year-old children from each of 40 communities in Amhara region, Ethiopia. Face photographs were assessed for the presence of seven measures of an unclean face (i.e., wet nasal discharge, dry nasal discharge, wet ocular discharge, dry ocular discharge, food, dust/dirt, and flies) by three independent masked photo-graders. Conjunctival photographs were similarly graded in a masked fashion for signs of clinically active trachoma. Conjunctival swabs were processed for Chlamydia trachomatis DNA. RESULTS: Of 2073 children with complete data, 808 (39%) had evidence of clinically active trachoma, 150 (7%) had evidence of ocular chlamydia infection, and 2524 (91%) had at least one measure of an unclean face. Dry ocular discharge had the strongest association with clinically active trachoma (age- and sex-adjusted prevalence ratio [PR] 1.4, 95% CI 1.2-1.6) and ocular chlamydia infection (PR 1.9, 95%CI 1.3-2.9), although significant associations were observed between each of the measures of facial uncleanliness and trachoma. CONCLUSIONS: Masked assessment of face and conjunctival photographs confirmed prior observational studies that have noted associations between various measures of facial uncleanliness and trachoma. The causal relationship between facial uncleanliness and trachoma is unclear since many features used to measure facial cleanliness (e.g., ocular discharge, nasal discharge, and flies) could be consequences of antecedent ocular chlamydia infection. TRIAL REGISTRATION: NCT02754583, clinicaltrials.gov.

Model of yearly transition to severe trachomatous scarring and trichiasis in a cohort of women in Kongwa Tanzania.

One criterion for validation of trachoma elimination is the management of Trachomatous Trichiasis (TT) after Trachoma inflammation-follicular (TF) is eliminated in children ages 1-9 years at district level. No data exist on how long countries must have dedicated TT programs, as the timeline for progression to TT from trachomatous scarring is unknown. We used eight years of longitudinal data in women in Kongwa Tanzania to model progression from no scarring (S0) through grades of scarring severity (S1-S4) to TT. Markov models were used, with age, community prevalence of TF (CPTF), and household characteristics as co-variates. Adjusted for covariates, the incidence of S1 was estimated at 4∙7% per year, and the risk increased by 26% if the CPTF was between 5-10% and by 48% if greater than 10%. The transition from S4 to TT was estimated at 2∙6% per year. Districts, even after elimination of TF, may have some communities with TF ≥ 5% and increased risk of incident scarring. Once scarring progresses to S2, further progression is not dependent on CPTF. These data suggest that, depending on the district level of scarring and degree of heterogeneity in CPTF at the time of elimination, incident TT will still be an issue for decades.

Field- and laboratory-based studies on correlates of Chlamydia trachomatis transmission by Musca sorbens: Determinants of fly-eye contact and investigations into fly carriage of elementary bodies.

Musca sorbens (Diptera: Muscidae) flies are thought to be vectors of the blinding eye disease trachoma, carrying the bacterium Chlamydia trachomatis (Ct) between the eyes of individuals. While their role as vectors has been convincingly demonstrated via randomised controlled trials in The Gambia, studies of fly-borne trachoma transmission remain scant and as such our understanding of their ability to transmit Ct remains poor. We examined fly-eye contact and caught eye-seeking flies from 494 individuals (79% aged ≤9 years) in Oromia, Ethiopia. Ct-carrying flies (harbouring Ct DNA) were found to cluster spatially in and nearby to households in which at least one resident had Ct infection. Fly-eye contact was positively associated with the presence of trachoma (disease), lower human body weight and increased human body temperature. Studies of laboratory-reared M. sorbens indicated that Ct is found both externally and internally following feeds on Ct culture, with scanning electron microscopy revealing how Ct bodies can cling to fly hairs (setae). Testing for Ct on field-caught M. sorbens found fly 'bodies' (thorax, wings and abdomen) to consistently test positive for Ct while legs and heads were infrequently Ct-positive. These studies strongly support the role of M. sorbens as vectors of trachoma and highlight the need for improved understanding of fly-borne trachoma transmission dynamics and vector competence.

Active trachoma and associated factors in children aged 1 to 9 years living in Sasiga rural districts, East Wallaga Zone, Ethiopia, in 2022: a community- based cross-sectional study.

BACKGROUND: Trachoma, caused by the bacteria Chlamydia trachomatous, is a contagious eye condition that frequently affects children and quickly spreads from child to child and from child to caregiver. The study aimed to assess the distribution of active trachoma and its associated risk factors among children 1-9 years aged in Households of Sasiga Rural District, Western Ethiopia, in 2022. METHODS: A community-based cross-sectional study was conducted among 577 randomly selected children from March to May 2022. A multistage sampling technique was used. Data was collected through an interviewer-based questionnaire, physical observation, and clinical eye examinations. Epi Data 3.1 was used for data entry. The data were analyzed with SPSS version 24. Bivariate and multivariate binary logistic regressions were performed. In multivariable logistic regression analysis, the adjusted odds ratio with a 95% confidence interval was used to identify factors associated with active trachoma. A P-value of 0.05 was considered statistically significant. RESULTS: The distribution of Active Trachoma among children 1-9 years aged in Households of the study area was 9.5%(95%CI:7.11,11.89). Being from a low-income household with a monthly income of less than 1500 ETB [AOR = 3.49, 95% CI: 1.39, 8.75], Households where the nearest water supply is more than 30 min away [AOR = 8.34, 95%CI: 1.89, 36.73], households with only one room [AOR = 2.98, 95%CI: 1.027, 8.68], and presence of feces in the compound of the households [AOR = 3.08, 95%CI: 1.41, 6.75] were associated with active trachoma in 1-9 years aged children living in the study setting. CONCLUSION: The distribution of Active Trachoma among children 1-9 years aged in Households of the study area was found to be high. Monthly income, the time it took to get water for home use, and the presence of feces in household compounds were all linked to active trachoma in children living in the study area. As a result, continuous sanitary education on trachoma transmission and prevention should be strengthened in the district.

Prevalence of active trachoma among 1-9 years of age children in Ethiopia: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study is to determine the pooled prevalence of active trachoma among 1-9 years old children in Ethiopia. DESIGN: A systematic review and meta-analysis were employed in accordance with the Preferred Reporting Items for Systematic Reviews. DATA SOURCES: Medline/PubMed, Scopus, Web of Science, African Journal of Online and Google scholar databases were systematically explored to find studies published in English until July 2023. ELIGIBILITY CRITERIA: The following criteria apply: (1) condition (Co): studies examined the prevalence of trachoma among children (1-9) years old; (2) context (Co): studies conducted in Ethiopia; (3) population (Pop): studies that were done among children (1-9) years old; (4) study type: observational studies and (5) language: studies published in English. DATA EXTRACTION AND SYNTHESIS: The data were extracted using a Microsoft Excel spreadsheet. DerSimonian-Laird random effect model was used to estimate the pooled prevalence of active trachoma among 1-9 years old children. Cochrane Q-tests and I2 statistics were used across studies to assess heterogeneity. To identify possible publication bias, Egger's test was performed. PRIMARY OUTCOME: Prevalence of active trachoma among children aged (1-9 years old)". RESULTS: Overall, a total of 42 articles with 235 005 study participants were included in the final analysis. The estimated pooled prevalence of active trachoma using random effect model was 24% (95% CI 20% to 27%). The subgroup analysis by region revealed that the highest prevalence of trachoma was 36% (95% CI 13% to 58%) in the Tigray region, and publication year revealed the prevalence of trachoma was decreasing from 32% to 19% after 2015. CONCLUSION: In this review, the pooled prevalence of active trachoma was found to be high in Ethiopia compared with WHO threshold level. This underscores the need for increased focus on high-risk age groups to decrease trachoma and to achieve the elimination of trachoma from the country by 2030.

Association of polymorphisms of HSD11B1 and ACE genes with trachoma disease.

Trachoma, caused by Chlamydia trachomatis, is the most common infectious blindness in the world and is present in indigenous Mayan from Chiapas (Mexico). Inflammatory genes are activated when suffering from trachoma, thus some polymorphisms could increase the susceptibility to develop irreversible blindness. This study aimed to evaluate the genetic risk of developing late-stage trachoma in Mayan ethnic groups. In a case-control study (n = 51 vs n = 102, respectively), the following single-nucleotide polymorphisms (SNPs) in genes related to inflammation were analysed: HSD11B1 (rs11807619), HSD11B1 (rs932335), ABCG2 (rs2231142), SLCO1B1 (rs4149056), IL-10 (rs1800890), TNF (rs1800629), MMP2 (rs243865) and ACE. Three SNPs were associated with late-stage trachoma risk: (i) the T allele of rs11807619, (ii) the C allele of rs932335, which are linked to the HSD11B1 gene (OR = 22.5-27.3), particularly in men when adjusts for gender (OR = 16-16.7); and (iii) D allele of rs4340 in the ACE gene (OR = 5.2-5.3). In fact, significant linkage disequilibrium demonstrated association between ACE gene and HSD11B1 SNPs (r = 0.17-0.179; P = 0.0048-0.0073). Two SNPs HSD11B1 gene (P = 0.013 vs 0.0039) and HSD11B1-ACE haplotypes showed association with late-stage trachoma in Mayan ethnic groups.

Acceptability and feasibility of tests for infection, serological testing, and photography to define need for interventions against trachoma.

BACKGROUND: Trachoma causes blindness due to repeated conjunctival infection by Chlamydia trachomatis (Ct). Transmission intensity is estimated, for programmatic decision-making, by prevalence of the clinical sign trachomatous inflammation-follicular (TF) in children aged 1-9 years. Research into complementary indicators to field-graded TF includes work on conjunctival photography, tests for ocular Ct infection, and serology. The perceived acceptability and feasibility of these indicators among a variety of stakeholders is unknown. METHODOLOGY: Focus group discussions (FGDs) with community members and in-depth interviews (IDIs) with public health practitioners in Tanzania were conducted. FGDs explored themes including participants' experience with, and thoughts about, different diagnostic approaches. The framework method for content analysis was used. IDIs yielded lists of perceived strengths of, and barriers to, implementation for programmatic use of each indicator. These were used to form an online quantitative survey on complementary indicators distributed to global stakeholders via meetings, mailing lists, and social media posts. RESULTS: Sixteen FGDs and 11 IDIs were conducted in October-November 2022. In general, all proposed sample methods were deemed acceptable by community members. Common themes included not wanting undue discomfort and a preference for tests perceived as accurate. Health workers noted the importance of community education for some sample types. The online survey was conducted in April-May 2023 with 98 starting the questionnaire and 81 completing it. Regarding barriers to implementing diagnostics, the highest agreement items related to feasibility, rather than acceptability. No evidence of significant differences was found in responses pertaining to community acceptability based on participant characteristics. CONCLUSIONS: All of the indicators included were generally deemed acceptable by all stakeholders in Tanzania, although community education around the benefits and risks of different sample types, as well as addressing issues around feasibility, will be key to successful, sustainable integration of these indicators into trachoma programs.

Postoperative trachomatous trichiasis and associated factors among adults who underwent trachomatous trichiasis surgery in Ambassel District, North-East Ethiopia.

BACKGROUND: In Trachoma endemic countries, many people who underwent Trichiasis surgery faced a recurrence of the disease. Postoperative Trichiasis is a significant problem for patients and health care providers because it puts the eye at renewed risk of sight loss. Despite the low utilization of Trachomatous Trichiasis surgery and the high recurrence rate, evidence that elucidate why it recurs after surgery is limited. This study was aimed to assess the magnitude and associated factors of postoperative Trichiasis among 18 years and above individuals who underwent Trachomatous Trichiasis surgery between 2013 and 2019 in Ambassel District, Northeast Ethiopia, 2020. METHODS: The community-based cross-sectional study design was conducted from March 10 to March 23/2020 in selected kebeles of Ambassel District. The required sample size (506) was calculated using EPI-INFO Version 7. A multi-stage sampling technique was used to employ study participants. Data were collected through the interviewer-administered structured pre-tested questionnaire and entered into EpiData version 3.1 and then exported to SPSS version 23.0 for analysis. Bi-variable and multivariable logistic regression models were fitted to identify associated factors of Postoperative Trachomatous Trichiasis. RESULTS: Four hundred ninety two individuals participated in this study with a response rate of 97.2%. In Ambassel district, the prevalence of postoperative Trichiasis was 23.8% (95% CI = 19.9-27.8). Among associated factors of postoperative Trachomatous Trichiasis: age 50-59 (AOR = 3.34, CI = 1.38-8.1), 60-69 (AOR = 3.24, CI = 1.38-7.61), ≥70 years (AOR = 6.04, CI = 2.23-16.41), duration since surgery (AOR = 1.7, CI = 1.35-2.14), complication (AOR = 2.98, CI = 1.24-7.2), washing the face two times (AOR = 0.25, CI = 0.13-0.47), washing the face three and more times (AOR = 0.1, CI = 0.41-0.25), taking Azithromycin following surgery (AOR = 0.19, CI = 0.09-0.41), pre-operative epilation history (AOR = 2.11, CI = 1.14, 3.9) and having a knowledge about TrachomaTtrichiasis (AOR = 0.21, CI = 0.08-0.58) showed a statistical significant association. CONCLUSIONS: The prevalence of postoperative Trichiasis in Ambassel District was higher than most Ethiopian studies. Age, frequency of face washing, medication following surgery, duration since the last surgery, knowledge about trachoma, pre-operative epilation history, and complication after surgery were identified to be independent factors. To minimize postoperative Trachomatous Trichiasis stakeholders need to consider health education for patients, provision of Azithromycin after surgery, and proper training for integrated eye care workers.

An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial.

BACKGROUND: There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a clinical trial administering CTH522, a recombinant version of the C trachomatis major outer membrane molecule, in different dose concentrations with and without adjuvant, to establish its safety and immunogenicity when administered intramuscularly, intradermally, and topically into the eye, in prime-boost regimens. METHODS: CHLM-02 was a phase 1, double-blind, randomised, placebo-controlled trial at the National Institute for Health Research Imperial Clinical Research Facility, London, UK. Participants were healthy men and non-pregnant women aged 18-45 years, without pre-existing C trachomatis genital infection. Participants were assigned into six groups by the electronic database in a pre-prepared randomisation list (A-F). Participants were randomly assigned (1:1:1:1:1) to each of the groups A-E (12 participants each) and 6 were randomly assigned to group F. Investigators were masked to treatment allocation. Groups A-E received investigational medicinal product and group F received placebo only. Two liposomal adjuvants were compared, CAF01 and CAF09b. The groups were intramuscular 85 µg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 µg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 µg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 µg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 µg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F). The primary outcome was safety; the secondary outcome (humoral immunogenicity) was the percentage of trial participants achieving anti-CTH522 IgG seroconversion, defined as four-fold and ten-fold increase over baseline concentrations. Analyses were done as intention to treat and as per protocol. The trial is registered with ClinicalTrials.gov, NCT03926728, and is complete. FINDINGS: Between Feb 17, 2020 and Feb 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 years). No serious adverse events occurred but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal product doses. Study procedures were otherwise well tolerated; the majority of adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (severe). There was 100% four-fold seroconversion rate by day 42 in the active groups (A-E) and no seroconversion in the placebo group. Serum IgG anti-CTH522 titres were higher after 85 µg CTH522-CAF01 than 15 µg, although not significantly (intention-to-treat median IgG titre ratio groups A-C:D=5·6; p=0·062), with no difference after three injections of 85 µg CTH522-CAF01 compared with CTH522-CAF09b (group E). Intradermal CTH522 (group C) induced high titres of serum IgG anti-CTH522 neutralising antibodies against serovars B (trachoma) and D (urogenital). Topical ocular CTH522 (group B) at day 28 and 112 induced higher total ocular IgA compared with baseline (p<0·001). Participants in all active vaccine groups, particularly groups B and E, developed cell mediated immune responses against CTH522. INTERPRETATION: CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 µg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials. FUNDING: The EU Horizon Program TRACVAC.

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.

Comparison of two approaches to measuring clean faces as part of the facial cleanliness component of the SAFE trachoma elimination strategy.

BACKGROUND: The Alliance for the Global Elimination of Trachoma (GET) endorses the full SAFE strategy to eliminate trachoma; Surgery (for trichiasis), Antibiotics (to reduce the community pool of infection, Facial cleanliness, and Environmental improvement (to decrease transmission). There is no accepted measure of facial cleanliness. This study compared two possible metrics for facial cleanliness. METHOD/FINDINGS: Metric one: Clean face was defined as observed absence of ocular and nasal discharge on the face. Metric two: observing a grade of dirtiness (scale 10 = lightest to 0 = darkest) on a standard facial wipe. The reliability of grading a child's face or grading a facial wipe was determined in children in Kongwa Tanzania. We also observed both measurements in a cohort of 202 children ages 1 to <7years prior to face cleaning, immediately afterwards, and 4 hours afterwards. Fifty of the children did not have face cleaning and were controls. Intra-and interobserver reliability was similar for both measures, the latter = 0.53 for observing a clean face and 0.52 for grading a facial wipe. There was no correlation between the two. Both measures detected facial cleaning, compared to control children who were not cleaned, immediately after cleaning; control children with 53% clean faces and wipe score of 6.7 compared to cleaned children with 88% clean faces and wipe score of 8 (p = .0001, p = < .0001, respectively). Both measures also detected face washing 4 hours previously compared to controls. CONCLUSIONS: The two metrics were equally reliable, and both measured the behavior of face washing. They measure different aspects of a clean face; one measures the amount of dirt on wiped area and the other measures ocular and nasal discharge. Both measurements appear to capture the behavior of facial cleaning, and the choice of metric would appear to rest on the measurement that captures the stated objective of the behavior, consideration of costs, training, logistics, and implementation.

Unravelling Chlamydia trachomatis diversity in Amhara, Ethiopia: MLVA-ompA sequencing as a molecular typing tool for trachoma.

Trachoma is the leading infectious cause of blindness worldwide and is now largely confined to around 40 low- and middle-income countries. It is caused by Chlamydia trachomatis (Ct), a contagious intracellular bacterium. The World Health Organization recommends mass drug administration (MDA) with azithromycin for treatment and control of ocular Ct infections, alongside improving facial cleanliness and environmental conditions to reduce transmission. To understand the molecular epidemiology of trachoma, especially in the context of MDA and transmission dynamics, the identification of Ct genotypes could be useful. While many studies have used the Ct major outer membrane protein gene (ompA) for genotyping, it has limitations. Our study applies a typing system novel to trachoma, Multiple Loci Variable Number Tandem Repeat Analysis combined with ompA (MLVA-ompA). Ocular swabs were collected post-MDA from four trachoma-endemic zones in Ethiopia between 2011-2017. DNA from 300 children with high Ct polymerase chain reaction (PCR) loads was typed using MLVA-ompA, utilizing 3 variable number tandem repeat (VNTR) loci within the Ct genome. Results show that MLVA-ompA exhibited high discriminatory power (0.981) surpassing the recommended threshold for epidemiological studies. We identified 87 MLVA-ompA variants across 26 districts. No significant associations were found between variants and clinical signs or chlamydial load. Notably, overall Ct diversity significantly decreased after additional MDA rounds, with a higher proportion of serovar A post-MDA. Despite challenges in sequencing one VNTR locus (CT1299), MLVA-ompA demonstrated cost-effectiveness and efficiency relative to whole genome sequencing, providing valuable information for trachoma control programs on local epidemiology. The findings suggest the potential of MLVA-ompA as a reliable tool for typing ocular Ct and understanding transmission dynamics, aiding in the development of targeted interventions for trachoma control.

Navigating diagnostic and therapeutic challenges in ocular manifestations of Hansen's disease and trachoma: A narrative review.

Neglected tropical diseases (NTDs) encompass a group of approximately 20 diseases prevalent in tropical and subtropical regions, closely associated with poverty, affecting over a billion people in low-income countries. This manuscript aims to explore the ocular manifestations and burden of two significant NTDs, namely Hansen's disease and trachoma while addressing gaps in understanding and management. Hansen's disease, caused by Mycobacterium leprae , has a long history and presents with diverse neurological and ocular manifestations. Despite the availability of treatment, ocular complications persist, leading to significant visual impairment in some cases. The manuscript emphasizes the importance of early diagnosis, regular ophthalmic examinations, and follow-ups to prevent and control ocular complications, reducing the burden of visual impairment and blindness. Trachoma, caused by Chlamydia trachomatis , remains the leading infectious cause of blindness in underdeveloped and remote areas. The manuscript highlights the clinical diagnosis and implementation of the World Health Organization's (WHO's) SAFE (surgery, antibiotics, facial hygiene, and environmental sanitation) strategy to prevent transmission and associated blindness. However, challenges in health surveillance tools and underreporting of trachoma cases are addressed, emphasizing the need for improved strategies to combat the disease effectively. Through a comprehensive review of the ocular manifestations and management of Hansen's disease and trachoma, this manuscript contributes to the existing knowledge base and enhances a deeper understanding of these NTDs. Addressing gaps in understanding and management emphasizes the importance of implementing WHO's strategies and collaborative efforts to achieve the global goal of reducing the burden of NTDs and improving community health and well-being. The manuscript underscores the significance of early intervention, preventive measures, and technological advancements, providing valuable insights for policymakers, healthcare professionals, and researchers working in the field of NTDs.