Trachoma, Anti-Pgp3 Serology, and Ocular Chlamydia trachomatis Infection in Papua New Guinea.

BACKGROUND: In Melanesia, the prevalence of trachomatous inflammation-follicular (TF) suggests that public health-level interventions against active trachoma are needed. However, the prevalence of trachomatous trichiasis is below the threshold for elimination as a public health problem and evidence of conjunctival infection with trachoma's causative organism (Chlamydia trachomatis [CT]) is rare. Here, we examine the prevalence of ocular infection with CT and previous exposure to CT in three evaluation units (EUs) of Papua New Guinea. METHODS: All individuals aged 1-9 years who were examined for clinical signs of trachoma in 3 Global Trachoma Mapping Project EUs were eligible to take part in this study (N = 3181). Conjunctival swabs were collected from 349 children with TF and tested by polymerase chain reaction to assess for ocular CT infection. Dried blood spots were collected from 2572 children and tested for anti-Pgp3 antibodies using a multiplex assay. RESULTS: The proportion of children with TF who had CT infection was low across all 3 EUs (overall 2%). Anti-Pgp3 seroprevalence was 5.2% overall and there was no association between anti-Pgp3 antibody level and presence of TF. In 2 EUs, age-specific seroprevalence did not increase significantly with increasing age in the 1- to 9-year-old population. In the third EU, there was a statistically significant change with age but the overall seroprevalence and peak age-specific seroprevalence was very low. CONCLUSIONS: Based on these results, together with similar findings from the Solomon Islands and Vanuatu, the use of TF to guide antibiotic mass drug administration decisions in Melanesia should be reviewed.

Estimating the Intracluster Correlation Coefficient for the Clinical Sign "Trachomatous Inflammation-Follicular" in Population-Based Trachoma Prevalence Surveys: Results From a Meta-Regression Analysis of 261 Standardized Preintervention Surveys Carried Out in Ethiopia, Mozambique, and Nigeria.

Sample sizes in cluster surveys must be greater than those in surveys using simple random sampling in order to obtain similarly precise prevalence estimates, because results from subjects examined in the same cluster cannot be assumed to be independent. Therefore, a crucial aspect of cluster sampling is estimation of the intracluster correlation coefficient (ρ): the degree of relatedness of outcomes in a given cluster, defined as the proportion of total variance accounted for by between-cluster variation. In infectious disease epidemiology, this coefficient is related to transmission patterns and the natural history of infection; its value also depends on particulars of survey design. Estimation of ρ is often difficult due to the lack of comparable survey data with which to calculate summary estimates. Here we use a parametric bootstrap model to estimate ρ for the ocular clinical sign "trachomatous inflammation-follicular" (TF) among children aged 1-9 years within population-based trachoma prevalence surveys. We present results from a meta-regression analysis of data from 261 such surveys completed using standardized methods in Ethiopia, Mozambique, and Nigeria in 2012-2015. Consistent with the underlying theory, we found that ρ increased with increasing overall TF prevalence and smaller numbers of children examined per cluster. Estimates of ρ for TF were independently higher in Ethiopia than in the other countries.

Unimproved water sources and open defecation are associated with active trachoma in children in internally displaced persons camps in the Darfur States of Sudan.

PURPOSE: To estimate the proportion of children with trachomatous inflammation-follicular (TF) and adults with trachomatous trichiasis (TT) in internally displaced persons (IDP) camps in the Darfur States of Sudan and to evaluate associated risk factors. METHODS: IDP camps were identified from government census data. We conducted a subanalysis of data collected in these camps during 2014-2015 as part of surveys covering 37 districts of the Darfur States within the Global Trachoma Mapping Project. A random-effects hierarchical model was used to evaluate factors associated with TF in children or TT in adults. RESULTS: Thirty-six IDP camps were represented in the survey data, in which 1926 children aged 1-9 y were examined, of whom 38 (8%) had TF. Poor sanitation, younger age and living in a household that purchased water from a vendor were associated with TF in children aged 1-9 y. Of 2139 individuals examined aged ≥15 y, 16 (0.7%) had TT. TT was strongly independently associated with being older and living alone. CONCLUSION: Trachoma is found at low levels in these camps, but still at levels where intervention is needed. Disease elimination in conflict-related settings presents a unique challenge for the trachoma community, and may require an innovative approach. Understanding how best to undertake trachoma elimination interventions in these areas should be prioritized.

Neglecting the neglected: the objective evidence of underfunding in rheumatic heart disease.

BACKGROUND: Despite the substantial global burden of disease, rheumatic heart disease research receives little funding globally. METHODS: Using data from the Global Burden of Disease Study and funding from the G-FINDER database, we propose a novel logarithmic disability neglect index (DNI) to describe disease burden using disability-adjusted life years relative to funding for 16 major tropical diseases. RESULTS: Across a range of diseases, rheumatic heart disease received the least funding relative to disease burden (DNI=3.83). Other diseases facing similar underfunding include cysticercosis (DNI=2.71) and soil-transmitted helminths (DNI=2.41). CONCLUSIONS: Rheumatic heart disease remains severely underfunded relative to disease burden.

Optimising age adjustment of trichiasis prevalence estimates using data from 162 standardised surveys from seven regions of Ethiopia.

PURPOSE: The prevalence of trichiasis is higher in females and increases markedly with age. Surveys carried out in the daytime, particularly in developing countries, are prone to find older individuals and females at home at the time of the survey. Population-level trichiasis estimates should adjust sample proportions to reflect the demographic breakdown of the population, although the most accurate method of doing this is unclear. METHODS: Having obtained data from 162 surveys carried out in Ethiopia as part of the Global Trachoma Mapping Project from 2012 to 2015, we used internal validation with both Brier and Logarithmic forecast scoring to test stratification models to identify those models with the highest predictive accuracy. Selection of partitions was undertaken by both simple random sampling (SRS) and cluster sampling (CS) over 8192 selections. RESULTS: A total of 4529 (1.9%) cases of trichiasis were identified from 241,139 individuals aged ≥15 years from a total of 4210 kebeles and 122,090 households visited. Overall, the binning method using 5-year bands from age 15 to 69 years, with coarser binning in 20-year age-bands above this age, provided the best predictive accuracy, in both SRS and CS methodologies and for both the Brier and Logarithmic scoring rules. CONCLUSION: The greatest predictive accuracy for trichiasis estimates was found by adjusting for sex and in 5-year age-bands from the age of 15 to 69 years and in 20-year age-bands in those aged 70 years and greater. Trichiasis surveys attempting to make population-level inferences should use this method to optimise surgery backlog estimates.

Quality Assurance and Quality Control in the Global Trachoma Mapping Project.

In collaboration with the health ministries that we serve and other partners, we set out to complete the multiple-country Global Trachoma Mapping Project. To maximize the accuracy and reliability of its outputs, we needed in-built, practical mechanisms for quality assurance and quality control. This article describes how those mechanisms were created and deployed. Using expert opinion, computer simulation, working groups, field trials, progressively accumulated in-project experience, and external evaluations, we developed 1) criteria for where and where not to undertake population-based prevalence surveys for trachoma; 2) three iterations of a standardized training and certification system for field teams; 3) a customized Android phone-based data collection app; 4) comprehensive support systems; and 5) a secure end-to-end pipeline for data upload, storage, cleaning by objective data managers, analysis, health ministry review and approval, and online display. We are now supporting peer-reviewed publication. Our experience shows that it is possible to quality control and quality assure prevalence surveys in such a way as to maximize comparability of prevalence estimates between countries and permit high-speed, high-fidelity data processing and storage, while protecting the interests of health ministries.

Sanitation and water supply coverage thresholds associated with active trachoma: Modeling cross-sectional data from 13 countries.

BACKGROUND: Facial cleanliness and sanitation are postulated to reduce trachoma transmission, but there are no previous data on community-level herd protection thresholds. We characterize associations between active trachoma, access to improved sanitation facilities, and access to improved water sources for the purpose of face washing, with the aim of estimating community-level or herd protection thresholds. METHODS AND FINDINGS: We used cluster-sampled Global Trachoma Mapping Project data on 884,850 children aged 1-9 years from 354,990 households in 13 countries. We employed multivariable mixed-effects modified Poisson regression models to assess the relationships between water and sanitation coverage and trachomatous inflammation-follicular (TF). We observed lower TF prevalence among those with household-level access to improved sanitation (prevalence ratio, PR = 0.87; 95%CI: 0.83-0.91), and household-level access to an improved washing water source in the residence/yard (PR = 0.81; 95%CI: 0.75-0.88). Controlling for household-level water and latrine access, we found evidence of community-level protection against TF for children living in communities with high sanitation coverage (PR80-90% = 0.87; 95%CI: 0.73-1.02; PR90-100% = 0.76; 95%CI: 0.67-0.85). Community sanitation coverage levels greater than 80% were associated with herd protection against TF (PR = 0.77; 95%CI: 0.62-0.97)-that is, lower TF in individuals whose households lacked individual sanitation but who lived in communities with high sanitation coverage. For community-level water coverage, there was no apparent threshold, although we observed lower TF among several of the higher deciles of community-level water coverage. CONCLUSIONS: Our study provides insights into the community water and sanitation coverage levels that might be required to best control trachoma. Our results suggest access to adequate water and sanitation can be important components in working towards the 2020 target of eliminating trachoma as a public health problem.

Prevalence of trachoma in Yemen: results of population-based prevalence surveys of 42 evaluation units in nine governorates.

PURPOSE: In suspected trachoma-endemic areas of Yemen, we sought to determine the prevalence of the sign trachomatous inflammation-follicular (TF) in children aged 1-9 years, and the potential individual and household risk factors for TF in that age group. We also sought to determine the prevalence of trichiasis in adults aged ≥15 years. METHODS: We conducted a cluster-sampled survey in each of 42 evaluation units (EUs) comprising 166 rural districts of nine Governorates (Adh Dhale'a, Al Hodeihah, Al Jawf, Hadramoot, Hajjah, Ibb, Lahj, Ma'rib, Taiz) using the Global Trachoma Mapping Project systems and methodologies. Fieldwork was undertaken from September 2013 to March 2015. Risk factors for TF in children aged 1-9 years were evaluated using multilevel random effects logistic regression. RESULTS: The TF prevalence in children aged 1-9 years was ≥10% in two EUs (7 districts) and 5-9.9% in six EUs (24 districts). In adults aged ≥15 years, trichiasis prevalence was ≥0.2% in five EUs (19 districts). Being older (within the 1-9-year age bracket), being male, living in a household with higher numbers of children, and living in a household that reported the use of open defecation, were each independently associated with higher odds of TF. CONCLUSIONS: These surveys provided baseline data to enable planning for trachoma elimination. The World Health Organization Alliance for the Global Elimination of Trachoma by 2020 stands ready to assist Yemen once security considerations permit further surveys and implementation of control activities.

Epidemiology of trachoma and its implications for implementing the "SAFE" strategy in Somali Region, Ethiopia: results of 14 population-based prevalence surveys.

PURPOSE: Ethiopia is highly trachoma endemic. Baseline mapping was needed in Ethiopia's Somali Region to guide elimination efforts. METHODS: Cross-sectional community-based surveys were conducted in 34 suspected trachoma-endemic woredas, grouped as 14 evaluation units (EUs), using a standardised mapping methodology developed for the Global Trachoma Mapping Project. RESULTS: In total, 53,467 individuals were enumerated. A total of 48,058 (89.9%) were present at the time of survey teams' visits and consented to examination. The prevalence of trachomatous inflammation-follicular (TF) among children aged 1-9 years ranged from 4.1% in the EU covering Danot, Boh, and Geladin woredas in Doolo Subzone to 38.1% in the EU covering Kebribeyah and Hareshen woredas in Fafan Subzone (East). The trichiasis prevalence among adults aged over 15 years varied from 0.1% in the EU covering Afder, Bare, and Dolobay woredas in Afder Subzone (West) to 1.2% in the EU covering Awbere in Fafan Subzone (West). CONCLUSION: Mass drug administration (MDA) with azithromycin is needed in 13 EUs (population 2,845,818). Two EUs (population 667,599) had TF prevalences in 1-9-year-olds of ≥30% and will require at least 5 years of MDA; 5 EUs (population 1,1193,032) had TF prevalences of 10-29.9% and need at least three years of MDA; 6 EUs (population 985,187) had TF prevalences of 5-9.9% and need at least one round of azithromycin distribution before re-survey. In all 13 of these EUs, implementation of facial cleanliness and environmental improvement measures is also needed. Surveys are still needed in the remaining 34 unmapped woredas of Somali Region.

The Epidemiology of Trachoma in Mozambique: Results of 96 Population-Based Prevalence Surveys.

PURPOSE: Surveys are needed to guide trachoma control efforts in Mozambique, with WHO guidelines for intervention based on the prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years and the prevalence of trichiasis in adults aged 15 years and above. We conducted surveys to complete the map of trachoma prevalence in Mozambique. METHODS: Between July 2012 and May 2015, we carried out cross-sectional surveys in 96 evaluation units (EUs) covering 137 districts. RESULTS: A total of 269,217 individuals were enumerated and 249,318 people were examined using the WHO simplified trachoma grading system. Overall, 102,641 children aged 1-9 years, and 122,689 individuals aged 15 years and above were examined. The prevalence of TF in children aged 1-9 years was ≥10% in 12 EUs, composed of 20 districts, covering an estimated total population of 2,455,852. These districts require mass distribution of azithromycin for at least 3 years before re-survey. The TF prevalence in children was 5.0-9.9% in 17 EUs (28 districts, total population 3,753,039). 22 EUs (34 districts) had trichiasis prevalences ≥0.2% in adults 15 years and above, and will require public health action to provide surgical services addressing the backlog of trichiasis. Younger age, more children resident in the household, and living in a household that had an unimproved latrine or no latrine facility, were independently associated with an increased odds of TF in children aged 1-9 years. CONCLUSIONS: Trachoma represents a significant public health problem in many areas of Mozambique.

The Burden of and Risk Factors for Trachoma in Selected Districts of Zimbabwe: Results of 16 Population-Based Prevalence Surveys.

BACKGROUND: Trachoma, a leading cause of blindness, is targeted for global elimination as a public health problem by 2020. In order to contribute to this goal, countries should demonstrate reduction of disease prevalence below specified thresholds, after implementation of the SAFE strategy in areas with defined endemicity. Zimbabwe had not yet generated data on trachoma endemicity and no specific interventions against trachoma have yet been implemented. METHODS: Two trachoma mapping phases were successively implemented in Zimbabwe, with eight districts included in each phase, in September 2014 and October 2015. The methodology of the Global Trachoma Mapping Project was used. RESULTS: Our teams examined 53,211 people for trachoma in 385 sampled clusters. Of 18,196 children aged 1-9 years examined, 1526 (8.4%) had trachomatous inflammation-follicular (TF). Trichiasis was observed in 299 (1.0%) of 29,519 people aged ≥15 years. Of the 16 districts surveyed, 11 (69%) had TF prevalences ≥10% in 1-9-year-olds, indicative of active trachoma being a significant public health problem, requiring implementation of the A, F and E components of the SAFE strategy for at least 3 years. The total estimated trichiasis backlog across the 16 districts was 5506 people. The highest estimated trichiasis burdens were in Binga district (1211 people) and Gokwe North (854 people). CONCLUSION: Implementation of the SAFE strategy is needed in parts of Zimbabwe. In addition, Zimbabwe needs to conduct more baseline trachoma mapping in districts adjacent to those identified here as having a public health problem from the disease.

The cost of mapping trachoma: Data from the Global Trachoma Mapping Project.

BACKGROUND: The Global Trachoma Mapping Project (GTMP) was implemented with the aim of completing the baseline map of trachoma globally. Over 2.6 million people were examined in 1,546 districts across 29 countries between December 2012 and January 2016. The aim of the analysis was to estimate the unit cost and to identify the key cost drivers of trachoma prevalence surveys conducted as part of GTMP. METHODOLOGY AND PRINCIPAL FINDINGS: In-country and global support costs were obtained using GTMP financial records. In-country expenditure was analysed for 1,164 districts across 17 countries. The mean survey cost was $13,113 per district [median: $11,675; IQR = $8,365-$14,618], $17,566 per evaluation unit [median: $15,839; IQR = $10,773-$19,915], $692 per cluster [median: $625; IQR = $452-$847] and $6.0 per person screened [median: $4.9; IQR = $3.7-$7.9]. Survey unit costs varied substantially across settings, and were driven by parameters such as geographic location, demographic characteristics, seasonal effects, and local operational constraints. Analysis by activities showed that fieldwork constituted the largest share of in-country survey costs (74%), followed by training of survey teams (11%). The main drivers of in-country survey costs were personnel (49%) and transportation (44%). Global support expenditure for all surveyed districts amounted to $5.1m, which included grant management, epidemiological support, and data stewardship. CONCLUSION: This study provides the most extensive analysis of the cost of conducting trachoma prevalence surveys to date. The findings can aid planning and budgeting for future trachoma surveys required to measure the impact of trachoma elimination activities. Furthermore, the results of this study can also be used as a cost basis for other disease mapping programmes, where disease or context-specific survey cost data are not available.

Integrated Mapping of Yaws and Trachoma in the Five Northern-Most Provinces of Vanuatu.

Yaws and trachoma are targeted for eradication and elimination as public health problems. In trachoma-endemic populations mass administration of azithromycin can simultaneously treat yaws. We conducted a population-based prevalence survey in the five northernmost provinces of Vanuatu, where trachoma and yaws are suspected to be co-endemic. Clinical signs of trachoma were evaluated using the WHO simplified grading system, and skin examination with a serological rapid diagnostic test used to identify yaws. We enrolled 1004 households in 59 villages over 16 islands, and examined 3650 individuals of all ages for trachoma. The overall adjusted prevalence of trachomatous inflammation-follicular (TF) in 1-9 year-olds was 12.0% (95% Confidence Interval: 8.1-16.7%), and the overall adjusted prevalence of TT in those aged 15 years and greater was 0.04% (95% CI 0-0.14%). In multivariate analysis, the odds of children having TF was 2.6 (95% CI = 1.5-4.4) times higher in households with unimproved latrines, and independently associated with the number of children in the household (OR 1.3, 95% CI = 1.0-1.6 for each additional child). We examined the skin of 821 children aged 5-14 years. Two children had yaws, giving an estimated prevalence of active yaws in those aged 5-14 years of 0.2% (95% CI = 0.03-0.9%). Mass treatment with azithromycin is recommended in these provinces. Given the apparent low burden of yaws, integration of yaws and trachoma control programmes is likely to be useful and cost-effective to national programmes.

Correction: Low Prevalence of Conjunctival Infection with Chlamydia trachomatis in a Treatment-Naïve Trachoma-Endemic Region of the Solomon Islands.

[This corrects the article DOI: 10.1371/journal.pntd.0004863.].

Low Prevalence of Conjunctival Infection with Chlamydia trachomatis in a Treatment-Naïve Trachoma-Endemic Region of the Solomon Islands.

BACKGROUND: Trachoma is endemic in several Pacific Island states. Recent surveys across the Solomon Islands indicated that whilst trachomatous inflammation-follicular (TF) was present at levels warranting intervention, the prevalence of trachomatous trichiasis (TT) was low. We set out to determine the relationship between chlamydial infection and trachoma in this population. METHODS: We conducted a population-based trachoma prevalence survey of 3674 individuals from two Solomon Islands provinces. Participants were examined for clinical signs of trachoma. Conjunctival swabs were collected from all children aged 1-9 years. We tested swabs for Chlamydia trachomatis (Ct) DNA using droplet digital PCR. Chlamydial DNA from positive swabs was enriched and sequenced for use in phylogenetic analysis. RESULTS: We observed a moderate prevalence of TF in children aged 1-9 years (n = 296/1135, 26.1%) but low prevalence of trachomatous inflammation-intense (TI) (n = 2/1135, 0.2%) and current Ct infection (n = 13/1002, 1.3%) in children aged 1-9 years, and TT in those aged 15+ years (n = 2/2061, 0.1%). Ten of 13 (76.9%) cases of infection were in persons with TF or TI (p = 0.0005). Sequence analysis of the Ct-positive samples yielded 5/13 (38%) complete (>95% coverage of reference) genome sequences, and 8/13 complete plasmid sequences. Complete sequences all aligned most closely to ocular serovar reference strains. DISCUSSION: The low prevalence of TT, TI and Ct infection that we observed are incongruent with the high proportion of children exhibiting signs of TF. TF is present at levels that apparently warrant intervention, but the scarcity of other signs of trachoma indicates the phenotype is mild and may not pose a significant public health threat. Our data suggest that, whilst conjunctival Ct infection appears to be present in the region, it is present at levels that are unlikely to be the dominant driving force for TF in the population. This could be one reason for the low prevalence of TT observed during the study.

Low Prevalence of Ocular Chlamydia trachomatis Infection and Active Trachoma in the Western Division of Fiji.

BACKGROUND: Trachoma is the leading infectious cause of blindness and is caused by ocular infection with the bacterium Chlamydia trachomatis (Ct). While the majority of the global disease burden is found in sub-Saharan Africa, the Western Pacific Region has been identified as trachoma endemic. Population surveys carried out throughout Fiji have shown an abundance of both clinically active trachoma and trachomatous trichiasis in all divisions. This finding is at odds with the clinical experience of local healthcare workers who do not consider trachoma to be highly prevalent. We aimed to determine whether conjunctival infection with Ct could be detected in one administrative division of Fiji. METHODS: A population-based survey of 2306 individuals was conducted using the Global Trachoma Mapping Project methodology. Population prevalence of active trachoma in children and trichiasis in adults was estimated using the World Health Organization simplified grading system. Conjunctival swabs were collected from 1009 children aged 1-9 years. DNA from swabs was tested for the presence of the Ct plasmid and human endogenous control. RESULTS: The prevalence of active trachoma in 1-9 year olds was 3.4%. The age-adjusted prevalence was 2.8% (95% CI: 1.4-4.3%). The unadjusted prevalence of ocular Ct infection in 1-9 year-olds was 1.9% (19/1009), and the age-adjusted infection prevalence was 2.3% (95% CI: 0.4-2.5%). The median DNA load was 41 Ct plasmid copies per swab (min 20, first quartile 32, mean 6665, third quartile 161, max 86354). There was no association between current infection and follicular trachoma. No cases of trachomatous trichiasis were identified. DISCUSSION: The Western Division of Fiji has a low prevalence of clinical trachoma. Ocular Ct infections were observed, but they were predominantly low load infections and were not correlated with clinical signs. Our study data suggest that trachoma does not meet the WHO definition of a public health problem in this Division of Fiji, but the inconsistency with previous studies warrants further investigation.