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Prevalence of trachoma in the Republic of Chad: results of 41 population-based surveys

ABSTRACT Purpose: To estimate the prevalence of trachoma in suspected-endemic areas of Chad, and thereby determine whether trachoma is a public health problem requiring intervention. Methods: We divided the suspected-endemic population living in secure districts into 46 evaluation units (EUs), and used the standardized methodologies of the Global Trachoma Mapping Project. A two-stage cluster-sampling procedure was adopted. In each EU, the goal was to examine at least 1019 children aged 1–9 years by recruiting 649 households; all consenting residents aged ≥ 1 year living in those households were examined. Each participant was examined for trachomatous inflammation—follicular (TF), trachomatous inflammation—intense (TI), and trichiasis. Results: Two EUs had data that could not be validated, and were excluded from the analysis. GPS data for three other pairs of EUs suggested that EU divisions were inaccurate; data for each pair were combined within the pair. In the 41 resulting EUs, 29,924 households in 967 clusters were visited, and 104,584 people were examined. The age-adjusted EU-level prevalence of TF in 1–9-year-olds ranged from 0.0% to 23.3%, and the age- and gender-adjusted EU-level prevalence of trichiasis in ≥ 15-year-olds ranged from 0.02% to 1.3%. TF was above the WHO elimination threshold in 16 EUs (39%) and trichiasis was above the WHO elimination threshold in 29 EUs (71%). Women had a higher prevalence of trichiasis than did men in 31 EUs (76%). A higher ratio of trichiasis prevalence in women to trichiasis prevalence in men was associated (p = 0.03) with a higher prevalence of trichiasis at EU level. Conclusion: Public health-level interventions against trachoma are needed in Chad. Over 10,000 people need management of their trichiasis; women account for about two-thirds of this total. The association between a higher ratio of trichiasis prevalence in women to that in men with higher overall trichiasis prevalence needs further investigation.


Background
Trachoma, the leading infectious cause of blindness worldwide, 1 is a chronic kerato-conjunctivitis caused by the bacterium Chlamydia trachomatis. 2 Infections, most commonly occurring in children, 3 may lead to sub-epithelial follicles or more pronounced inflammation. 4 Repeated infection 5,6 can lead to scarring of the conjunctivae 7 which, when severe enough, can deform the eyelid and cause eyelashes to touch the globe (trichiasis). 4 Uncorrected trichiasis can result in corneal abrasion, ulceration, opacification, and potentially, vision loss and blindness.
Chad is a central African country of approximately 12 million people spread across three distinct ecologic zones: the Sahara Desert, the Sahel, and the Savanna. Currently the country has a total of 33 ophthalmic nurses; 35 ophthalmic technicians; and nine ophthalmologists (approximately one for every 1.5 million people) of whom 5 are in the capital N'Djamena. Though absolute numbers of eye-care personnel are low, Chad is fortunate that 90% of them work in the public sectorspecifically in five departments of ophthalmology (within two secondary and three tertiary hospitals) and 21 secondary eye care units.
A number of population-based trachoma prevalence surveys were undertaken in Chad in 1984, 12 1985, 13 2001 14 and 2004 15 (Table 1); however, due to financial constraints, SAFE strategy implementation was not commenced until 2015. The 1984-2004 surveys occurred prior to the recent growth in interest in trachoma elimination, 17 and were conducted at region level, covering large populations and wide geographical areas ( Table 1). Because of the age and relatively low resolution of existing data, in order to inform programmatic action, baseline mapping or re-mapping was felt to be required. 18 We set out to estimate the prevalence of TF in 1-9-year-olds and the prevalence of trichiasis in adults in population units of 100,000-250,000 people in suspected-trachoma-endemic areas of rural Chad.

Materials and methods
Administratively, Chad is divided into 23 regions. Each region (other than the capital, N'Djamena, which has a different internal administrative structure) is divided into two to six health districts, the level at which trachoma elimination activities are implemented. 19 There are 61 health districts in total, of which 45 were suspected to have trachoma as a public health problem and therefore to qualify for mapping, based on criteria published elsewhere. 20 Surveys were conducted in 2014 and 2015. Due to insecurity prevailing at that time, five suspected-trachoma-endemic health districts (Bol and Ngouri in Lac Region, Nokou in Kanem Region, Mandelia in Chari Baguirmi Region and Bardaï in Tibesti Region) could not be surveyed.
Survey design, field team training and certification, fieldwork, and data handling were conducted according to the systems and methodologies of the Global Trachoma Mapping Project (GTMP). [20][21][22][23] Each of the 40 secure health districts was generally surveyed as a single evaluation unit (EU), though six health districts with populations (estimated using 2009 population census data 24 and a mean annual population growth rate of 3.6%) significantly larger than the standard 100,000--250,000-person EU were divided into two EUs each, resulting in a total of 46 independent EUs.
Village-level population estimates were provided by the Division of Health & Information Systems. According to the 2009 census, 24 the proportion of the population aged 1-9 years was 36% and rural households had a mean of 5.3 residents. The estimated sample size requirement per EU was based on an expected TF prevalence of 10% in children aged 1-9 years, a design effect of 2.65, and a desire to be 95% confident of estimating the TF prevalence with ± 3% absolute precision. 22 The resulting sample size (n = 1019) was increased by 20% to account for non-response; this resulted in a total of 649 households being required per EU.
Using a two-stage cluster-sampling design, 22 clusters (villages or neighbourhoods) were systematically selected in each EU using probability-proportional-to-population -size sampling. In each cluster, compact segment sampling 25,26 was then used to select 30 households. All residents over the age of 12 months who had resided for at least six months in selected households were eligible for enrolment.
A survey team consisted of a grader (ophthalmic technician), a recorder (high school graduate at ease with Android smart phones and fluent in major local languages), a local facilitator and a driver. Members of the survey team underwent standardized GTMP training, using version 2 of the system. 27 Candidate graders were assessed after training, and only those obtaining a kappa of ≥ 0.7 for diagnosis of TF in an inter-grader agreement test with a GTMP-certified grader trainer were accepted as survey graders. Trachoma grading was done according to the WHO simplified grading system. 4 Graders used 2.5× magnifying binocular loupes and sunlight illumination to examine consenting residents. In eyes diagnosed as having trichiasis, the presence or absence of trachomatous conjunctival scarring 28,29 was not recorded, so we are unable to confirm that trichiasis cases detected were due to trachoma; consequently, we refer here to the prevalence of trichiasis instead of the prevalence of trachomatous trichiasis. Each survey team was trained to ask questions relating to access to water and sanitation at each selected household. 27 All data were captured electronically, through the Open Data Kit-based Android phone application purpose-built for the GTMP. Once saved, data were sent to and stored on the GTMP Cloud-based secure server, then cleaned and analyzed. 22 For each survey cluster, the proportion of 1-9-year-old children with TF was adjusted by age in one-year age bands, while the proportion of ≥ 15-year-olds with trichiasis was adjusted by age and gender in five-year age bands; age and gender data from the 2009 Chad census were used as the reference population for this purpose. 24 For each EU, the primary outcome of interest was the ageadjusted prevalence of TF in 1-9-year-olds; intended secondary outcomes were the age-and gender-adjusted prevalence of trichiasis in ≥ 15-year-olds, and household-level access to water and sanitation. Confidence intervals for TF and trichiasis prevalence estimates were calculated by bootstrapping sets of 22 adjusted clusterlevel proportions for each sign, with replacement, over 10,000 replicates, and taking the 2.5th and 97.5th centiles of the ordered results. Additional gender-specific age-adjusted estimates of trichiasis prevalence, with 95% confidence intervals, were calculated in analogous fashion. The ratio of trichiasis prevalence in females to that in males in each EU was also determined, and linear regression modelling (Stata 11, College Station TX, USA) used to generate an intra-class correlation coefficient, to assess the association between EU-level trichiasis prevalence and ratio of gender-specific prevalences.
Ethical clearance was obtained from the Chadian Ethical Committee for Applied Research, led by the Ministry of Higher Education; and from the London School of Hygiene & Tropical Medicine (6319). The examination procedure was explained to each eligible adult in the local language and verbal consent for enrolment and examination was obtained. For eligible children, verbal consent was obtained from a parent or guardian. Individuals with active trachoma were offered 1% tetracycline ointment for application into the conjunctival sac twice-daily for six weeks. Individuals with trichiasis were offered management by a surgeon.

Results
Fieldwork was undertaken from May 2014 to November 2015. At a subsequent field team meeting, it emerged that fieldworkers had considered their main task to be the acquisition of information on TF and trichiasis. Contrary to the survey protocol and the standard GTMP training package, in some villages, questions about access to water and sanitation had not been systematically asked in each selected household. Rather, information had been collected from the head of the village at the beginning of the day and those answers used for each household visited. Although this shortcut was not employed by all teams, it cast doubt on the accuracy of our water and sanitation data, and we do not include those data in this manuscript. Data cleaning revealed inconsistency in definitions of EU and district boundaries. In particular, in three health districts (Pala, Béré & Kélo, and Donomanga & Laï) that had each been split into two EUs, GPS data revealed considerable overlap between clusters that had ostensibly been drawn from separate EUs. Data from these pairs of within-health-district EUs were therefore combined to re-constitute health-districtlevel EUs; the numbers of clusters finally included in each EU are shown in Table 2. GPS data 30 were not received at all from a high proportion of households mapped in both of Moundou's two EUs; those that had GPS data were geolocated in a pattern inconsistent with known administrative divisions. For that reason, the data from Moundou did not pass GTMP quality control, and the outputs were, as expected, rejected by the health ministry. We therefore present data here from what became a total of 41 surveys.
In total, 104,705 people were enrolled and 104,584 (99%) examined in 29,239 households recruited from 967 clusters ( Table 2). There were almost equal numbers of 1-9-year-olds (n = 55,885) and ≥ 15-year-olds (n = 48,699) examined. While the sampling process was designed to facilitate examination of at least 1,019 children in each EU, the survey teams in five EUs did not reach this target, with the lowest number of 1-9-yearolds examined in an EU being 956; reports from the field indicated that in many locations, households had fewer resident children than expected.
In 12 EUs (29%), the age-and gender-adjusted trichiasis prevalence was below the WHO elimination threshold 31 of 0.2% in ≥ 15-year-olds (Table 3, Figure 2). In the remaining 29 EUs, trichiasis prevalence was ≥ 0.2%. Two EUs had trichiasis prevalence estimates of > 1%. The estimated number of trichiasis patients requiring management to achieve elimination of trichiasis as a public health problem at the time of conclusion of the surveys was 10,562 ( Table 3).
Analysis of gender-specific age-adjusted trichiasis prevalence estimates revealed mean EU-level prevalences of 0.55% in women and 0.28% in men; in 31 (76%) of the 41 EUs, the prevalence of trichiasis was higher in women than men (Table 4). There were five EUs in which none of the men examined had trichiasis. The mean ratio of prevalence in women to that in men (excluding the five EUs in which prevalence in men was 0) was 1.70 (SE = 0.53) in the EUs below the WHO elimination threshold, and 2.31 (SE = 0.48) in the EUs above the WHO elimination threshold. A higher prevalence of trichiasis was associated with a greater excess of disease in women (correlation coefficient = 250, SE = 114, p = 0.03).

Discussion
The results of these and previous surveys demonstrate that trachoma is a public health problem in Chad. To move towards elimination of trachoma as a public health problem, AFE interventions should be implemented for at least three years before re-survey for the approximately 887,000 people in the five EUs in which TF prevalence was ≥ 10%, and for at least one year before re-survey for the nearly 2.8 million people in the 11 EUs in which TF prevalence was 5-9.9%. Although we are unable to report our own data on access to water and sanitation, 2017 data released by the Chad Government and UNICEF suggest that region-level proportions of the population with access to potable water are as low as 12% (Ennedi-Est), and that outside N'Djamena, region-level rates of open defecation range from 61 to 93%. These conditions are associated with high risk of active trachoma, 32,33 highlighting the need for the F&E components of the SAFE strategy here.
The TF prevalence estimates from these GTMPsupported surveys are considerably lower than those of previous surveys completed in Chad. [13][14][15] There are a number of possible explanations for this. When surveys were first planned here, it would have been logical to choose to start in districts with higher expected burdens of trachomawhere, in other words, eye health professionals were already aware of cases. There may also, or alternatively, have been a temporal decline in the prevalence of active trachoma in the intervening period, 34-37 with older surveys reflecting C. trachomatis transmission intensities 38 occurring before more recent improvements in access to water, sanitation and health care. The GTMP's emphasis on standardization of trachoma grading (including grader training and qualification based on examination of real people, rather than projected images 20 ) may also have contributed.
Trichiasis is widespread in Chad (Figure 2), with more than two-thirds of EUs surveyed in 2014-2015 having trichiasis prevalence estimates above the WHO elimination threshold. Establishing a public health-level response to trichiasis throughout the widely dispersed communities in these EUs will require considerable capacity building for delivery of high-quality trichiasis surgery and programme management, as well as community-based efforts to generate awareness and encourage uptake of services. 39,40 The excess burden of trichiasis among females (Table 4), also noted elsewhere, 25,41,42 compels us to ensure that such efforts particularly serve women. Experience in other countries can inform strategies to improve use of eye care services by women. 43,44 The association noted here between higher prevalence of trichiasis and greater ratio of trichiasis prevalence in women to trichiasis prevalence in men cannot be explained from our data alone. We note that this was not a pre-specified hypothesis of the current work, and suggest only that further investigation is indicated.
Our work has a number of limitations. First, in five EUs, we did not quite reach the estimated sample size requirement. We report confidence intervals here, however, which facilitates objective assessment of the likely repeatability of our estimates. In future surveys in Chad, the sampling approach will be revised slightly to reflect the smaller-than-expected mean number of children encountered per household. Second, we recruited these marginally low numbers of examinees despite what was apparently an extraordinarily high enrolment rate: 99% of enumerated residents. We wonder whether field teams, fearing criticism for incomplete enrolment, may have failed to register absentees: anecdotally, this occurred in other constituent projects of the GTMP, but obtaining definitive proof was difficult. 20 Third, this survey work was commenced prior to the inclusion of examination for trachomatous conjunctival scarring (TS 4 ) in standard GTMP protocols, 45 as later recommended by a global scientific meeting. 29 It is therefore likely that some of the trichiasis cases included in our prevalence estimates were due to conditions other than trachoma 28,29 ; this may explain part of the association Table 3. Prevalence of trachomatous inflammation-follicular (TF) in 1-9-year-olds, prevalence of trichiasis in ≥ 15-year-olds, backlog of trichiasis cases and number of trichiasis cases needing management to reach the WHO elimination threshold, by evaluation unit, Global Trachoma Mapping Project, Chad, 2014-2015.

Region
Evaluation unit (label in Figures 1 and 2 Yao (    between the overall prevalence of trichiasis and the ratio of gender-specific prevalence estimates. We also did not ask about previous management of trichiasis, so the trichiasis prevalence estimates reported here include both cases known and unknown to the health system. 19 These refinements can be helpful in influencing whether or not public-health-level interventions are needed against trichiasis. 46 Fourth, as noted in the results section, three EU pairs were combined at the data cleaning stage; the main implication of this is that the resulting EU populations (like that for N'Djamena suburbs) are larger than the recommended 100,000-250,000 people. 19 Fifth, as also already noted, data from two EUs in Moundou, Logone Occidental Region, could not be approved due to missing GPS data; as a consequence, results from this EU are not included in the current report. Sixth, because household-level questions were not used as set out in the survey protocol, we are unable to report data on  (

Mayo Kebbi Ouest
Léré (16)  Adjusted for age in 5-year age bands (see text) CI, confidence interval; NA, not applicable access to water and sanitation. Though unfortunate, as much as this situation reveals a weakness in one part of fieldwork execution, it also demonstrates strength in fieldwork supervision.
Subsequent to completing these surveys, in addition to expanding SAFE interventions, the Ministry of Health commenced planning to re-map Moundou as well as to undertake mapping in some of, but not all, the EUs in which surveys were not attempted in 2014-2015.
Undertaking those surveys will contribute to the completion of nationwide mapping of suspected-trachomaendemic areas of Chad, and help chart a course towards national elimination of trachoma as a public health problem. 47

Disclosure Statement
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding
This study was funded by the Global Trachoma Mapping Project (GTMP) grant from the United Kingdom's Department for International Development (ARIES: 203145) to Sightsavers, which led a consortium of non-governmental organizations and academic institutions to support health ministries to complete baseline trachoma mapping worldwide, and by the United States Agency for International Development (USAID) through the ENVISION project implemented by RTI International under cooperative agreement number AID-OAA-A-11-00048. The GTMP was also funded by USAID through the END in Asia project implemented by FHI360 under cooperative agreement number OAA-A-10-00051. A committee established in March 2012 to examine issues surrounding completion of global trachoma mapping was initially funded by a grant from Pfizer to the International Trachoma Initiative. AWS was a Wellcome Trust Intermediate Clinical Fellow (098521) at the London School of Hygiene & Tropical Medicine, and is now a staff member of the World Health Organization. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated. None of the funders had any role in project design, in project implementation or analysis or interpretation of data, in the decisions on where, how or when to publish in the peer reviewed press, or in preparation of the manuscript.