Trachoma

INTRODUCTION — Trachoma is the leading infectious cause of blindness worldwide [1]. It is a chronic keratoconjunctivitis caused by recurrent infection with Chlamydia trachomatis (a small, gram-negative obligate intracellular bacterium); humans are the only hosts. Trachoma is caused almost exclusively by C. trachomatis serotypes A, B, Ba, and C; genital infection is caused by serotypes D through K. (See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections" and "Treatment of Chlamydia trachomatis infection".)

The Alliance for the Global Elimination of Blinding Trachoma by the year 2020 (GET 2020) was established by the World Health Organization in 1997 and has helped to coordinate trachoma elimination efforts. The Neglected Tropical Disease road map 2021-2030 has set 2030 as the new target year for global elimination of trachoma as a public health problem. The Global Trachoma Mapping Project and its successor, Tropical Data, have established where current elimination efforts need to be concentrated [2].

EPIDEMIOLOGY

Geography and prevalence — Trachoma is endemic in 40 countries [3] , largely in remote, resource-limited areas across Africa, Asia, Latin America, the Middle East, and the Pacific Rim (figure 1) [4].

The prevalence of active disease (characterized by follicles and/or severe inflammation of the upper tarsal conjunctiva) is highest in young children and declines to low levels in adulthood (figure 2). In endemic areas, it is common to be infected at least once (and often more than once) in childhood. In some studies, active disease has been observed in 60 percent of children <5 years of age, and half of the bacterial load of C. trachomatis in the community may be found in children <1 year of age [5-7]. A subgroup of children may have persistent, severe infection; these individuals are at risk for developing cicatricial (scarring) disease as older children and adults [8,9].

Trachoma may be associated with ocular pain and loss of vision, leading to loss of economic productivity and quality of life [10]. In 2023, an estimated 116 million people lived in districts in which the prevalence of active trachoma (trachomatous inflammation—follicular, TF) was ≥5 percent [11], and 1.5 million required surgery for trichiasis [11].

The number of individuals estimated to be affected by trachoma has declined in recent decades, likely due to trachoma elimination strategies as well as general improvements in hygiene standards. (See 'Prevention' below.)

Risk factors — A number of environmental, socioeconomic, and behavioral factors have been associated with trachoma [4,8,12].

Factors associated with increased risk of trachoma include poor access to water and overcrowding (facilitating transfer of infected secretions) [4,8,12]. Scarring complications occur approximately two times more frequently in women than in men [13], which may reflect frequent contact with children (the primary reservoir of infection).

Factors associated with decreased risk of trachoma include facial cleanliness and reducing fly contact (via insecticide spraying, building latrines) [8]. Issues related to prevention of trachoma are discussed below. (See 'Prevention' below.)

Transmission — C. trachomatis is highly infectious and transmitted directly or indirectly from eye to eye in areas of poor hygiene. C. trachomatis is thought to be transmitted between individuals via spread of ocular and nasal secretions on fingers and contaminated fomites [14]. Controlled laboratory experiments indicate that C. trachomatis remains viable for many hours on extraocular surfaces [15].  

In addition, transmission may occur via eye-seeking flies (such as Musca sorbens); in such cases, the flies serve as passive vectors but are not known to serve as reservoirs of infection [12,14].

CLINICAL MANIFESTATIONS

Disease phases — The clinical manifestations of trachoma include two phases: active trachoma (conjunctivitis) and cicatricial disease (conjunctival scarring). In general, active trachoma occurs largely in young children; cicatricial disease and blindness occur in adults (figure 2 and figure 3) [16].

The clinical manifestations are used to categorize the severity of the disease in the simplified World Health Organization (WHO) trachoma grading system (table 1), which was amended in 2020 to reflect changes in definitions and help users better understand and apply the definitions. The grading system can be used to guide management of individual patients and for screening programs. (See 'Physical exam and grading system' below.)

Active trachoma (conjunctivitis) — An initial isolated infection with C. trachomatis causes a mild, self-limited follicular conjunctivitis, best seen in the subtarsal conjunctiva of the everted upper eyelid (figure 4). Most patients with active trachoma are asymptomatic, even with marked signs of inflammation; for this reason, most cases of active trachoma are detected via screening programs (table 1) [17]. Symptoms, if present, are typical of chronic conjunctivitis; they include redness, discomfort, light sensitivity, and mucopurulent discharge.

Findings of active trachoma are largely observed in children. Older individuals with C. trachomatis infection often do not display a follicular response but may develop a papillary reaction, particularly if there is secondary bacterial infection [18].

Individuals with repeated episodes of infection are at risk of developing scarring complications.

Cicatricial disease (conjunctival scarring) — The greater the severity and duration of active trachoma infection, the greater the likelihood of progression to cicatricial disease in adulthood [19,20]. Results from a four year cohort study in Tanzania suggested that the effect of infection on scarring progression is mediated through intense papillary conjunctival inflammation and that other factors contributing to inflammation, including connective tissue changes [21], may be important in driving conjunctival scarring progression in children [22,23].

Repeated episodes of infection cause marked conjunctival inflammation, leading to eyelid scarring, as in panel A of the following picture (picture 1). A thick band near the lid margin (Arlt's line) may also be seen, as in panel B of the following picture (picture 1). These findings correspond with WHO grade trachomatous conjunctival scarring (TS) (table 1). It is estimated that over >100 conjunctival infections are needed during an individual's lifetime to develop conjunctival scarring [24].

Eyelid scar tissue eventually contracts and can distort the lid margin leading to entropion (inward rolling of the eyelid) and trichiasis (eyelashes rubbing against the eyeball), as in panel A of the following picture (picture 2). These findings in the upper eyelid correlate with WHO grade trachomatous trichiasis (TT) (table 1). An estimated 150 lifetime infections are thought to be required to lead to TT [24].

Individuals with TT have a greatly increased risk of blindness. TT is staged as minor (one to five eyelashes touching the eyeball) or major (six or more eyelashes touching the eyeball). Presence of TT should prompt surgical intervention. (See 'Surgery for trichiasis' below.)

Eyelash abrasion on the cornea leads to corneal edema, ulceration, and scarring. If untreated, corneal pannus (inflammatory vascular tissue) eventually develops, as in panel B in the following picture (picture 2), followed by corneal opacification, as in panel C in the following picture (picture 2), and loss of vision.

Physical exam and grading system — To grade the severity of disease, each eye should be examined with at least 2.5x loupe (magnifying lens) and a good flashlight with even illumination (figure 4 and picture 3). The conjunctiva should be evaluated for inflammation or discharge, and it should be noted whether eyelashes rub against the eyeball and whether eyelashes have been removed (epilated). The cornea should be examined for evidence of inflammation or opacification, and the upper eyelid should be everted to visualize the upper tarsal conjunctiva for evidence of follicles, inflammation, or scarring. Follicle size guides have been developed and are used in screening programs to help with the diagnosis of TF [25].

The WHO simplified grading system (amended in 2020) is summarized below and in the table (table 1) [26-28]:

●Trachomatous inflammation—follicular (TF) – Five or more follicles of ≥0.5 mm diameter in the central part of the upper tarsal conjunctiva, as in panel A in the following picture (picture 4)

●Trachomatous inflammation—intense (TI) – Papillary hypertrophy and inflammatory thickening of the upper tarsal conjunctiva obscuring more than half the deep tarsal vessels (picture 3)

●Trachomatous conjunctival scarring (TS) – Easily visible scars on the upper tarsal conjunctiva, as in panel A in the following picture (picture 1)

●Trachomatous trichiasis (TT) – At least one eyelash from the upper eyelid touching the eyeball or evidence of recent epilation (eyelash removal) of in-turned eyelashes from the upper eyelid, as in panel A in the following picture (picture 2)

●Corneal opacity (CO) – An easily visible corneal opacity that is so dense that at least part of the pupil margin is blurred when viewed through the opacity, as in panel C in the following picture (picture 2)

The major physical finding of active trachoma is the characteristic follicle on the superior tarsal conjunctiva (picture 4). The follicles are large, white or pale yellow foci of inflammatory material with a diameter of 0.5 to 2.0 mm, as in panel A in the following picture (picture 4). An individual with five or more follicles ≥0.5 mm in diameter in the central part of the upper tarsal conjunctiva should be categorized as WHO grade TF (table 1). Papillae may appear alongside the follicles as pinpoint red dots but can become much larger and can coalesce to give the conjunctiva a thickened and edematous appearance, as in panel B in the following picture (picture 3). If papillary hypertrophy and inflammatory thickening obscure more than half of the deep tarsal vessels, WHO grade TI is present. In later disease, the follicles may leave grossly visible shallow pits in the cornea (Herbert's pits) that are pathognomonic for trachoma, as in panel B in the following picture (picture 4).

The signs in the simplified trachoma grading system are useful for decisions regarding public health interventions, such as mass drug administration with antibiotics. The 2020 amendment aims to ensure this system continues to be useful in estimating the burden of trachoma in population-based surveys to determine the need for further elimination measures. (See 'Prevention' below and 'Mass antibiotic treatment' below.)

DIAGNOSIS — The diagnosis of trachoma should be suspected in patients with follicular conjunctivitis and/or conjunctival scarring in areas where trachoma is endemic or in areas with risk for trachoma. (See 'Epidemiology' above.)

The diagnosis of trachoma is established based on the clinical signs [26,28,29]. Physical examination findings are used to categorize the severity of disease using the simplified grading system (table 1) [26,28]. (See 'Clinical manifestations' above.)

As the prevalence of trachoma falls, the positive predictive value of clinical diagnosis decreases and the utility of microbiologic diagnosis increases [30,31]. In such settings, clinical signs of active trachoma are often present in the absence of active ocular C. trachomatis infection, particularly following mass drug administration [32]. Therefore, decisions to continue antibiotic distribution based solely on the prevalence of clinical signs may result in unnecessary antibiotic use, increasing the risk of macrolide resistance.

A 2021 World Health Organization (WHO) informal consultation on trachoma endgame challenges recommended that, in districts where TF prevalence has never fallen below the 5 percent elimination threshold ("persistent districts") or is not sustained below the 5 percent threshold at surveillance survey ("recrudescent districts"), tailored management be informed by C. trachomatis infection (diagnosed via nucleic acid amplification-based test [NAAT]) and/or anti-C. trachomatis antibody data [33].

NAATs are the most sensitive and specific diagnostic assays but are often prohibitively expensive and require expertise and resources that are not available in most endemic regions [4]. Novel isothermal NAATs requiring minimal technical expertise are being evaluated [34]. Other laboratory assays for diagnosis of C. trachomatis infection include direct immunofluorescent cytology, enzyme immunoassay, microscopy (Giemsa staining) of conjunctival samples, and tissue culture [8].

There is increasing interest in the use of serologic assays to measure antibody acquisition following exposure to C. trachomatis, which may be beneficial in identifying trends in population level transmission of public health significance. There would be potential application for this kind of diagnostic tool for programmatic surveillance, as trachoma-endemic areas near elimination targets [35,36]. Serologic data have been used to model seroconversion and seroreversion rates in trachoma-endemic settings to measure changes in transmission intensity [37]. Two antigens (pgp3 and CT694) have been proposed due to their correlation (at individual and population level) with clinical trachoma and ocular C. trachomatis infection [38].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of trachoma depends on the stage of disease.

The differential diagnosis of conjunctivitis includes:

●Viral conjunctivitis – Viral conjunctivitis causes red, irritated eyes with a gritty sensation. The tarsal conjunctiva may have a follicular appearance, and a tender, enlarged preauricular node may be present. Features that distinguish viral conjunctivitis from trachoma include a history of upper respiratory tract infection, rapid progression over several days, and the presence of a mucopurulent discharge. (See "Conjunctivitis", section on 'Viral conjunctivitis'.)

●Bacterial conjunctivitis – Patients with bacterial conjunctivitis present with redness and purulent discharge in one or both eyes. Discharge appears at the lid margins and corners of the eye, and more discharge appears within minutes of wiping the lids. Follicle formation is rare. (See "Conjunctivitis", section on 'Bacterial conjunctivitis'.)

●Allergic conjunctivitis – Allergic conjunctivitis is the most common cause of red, irritated, itchy eyes. Patients often have associated atopy and may suffer from eczema, hay fever, or asthma. A white, stringy discharge of mucus is common. Symptoms can be seasonal. The diagnosis is made clinically based on suggestive clinical history and consistent signs and symptoms. (See "Allergic conjunctivitis: Clinical manifestations and diagnosis".)

●Hypersensitivity conjunctivitis – Exposure to drugs, eye cosmetics, soaps, or other chemicals can lead to a hypersensitivity reaction that can appear follicular in nature. A detailed history is vital to identify and remove the causative agent. (See "Conjunctivitis", section on 'Noninfectious, noninflammatory conjunctivitis'.)

The differential diagnosis of cicatricial disease (conjunctival scarring) includes complications associated with bacterial conjunctivitis, trauma, or chalazion. (See "Eyelid lesions", section on 'Chalazion'.)

TREATMENT — Treatment of trachoma consists of mass drug administration (MDA) of antibiotics to entire districts, with the aim of treating infection, interrupting transmission, and reducing the risk of repeated ocular infection with C. trachomatis. Patients with TT warrant surgery tailored to individual physical findings.

Antibiotic therapy — Antibiotic therapy for trachoma is best managed as MDA to an entire evaluation unit (EU), defined on the basis of resident population rather than on an individual basis.

Antibiotic selection — Azithromycin (single dose 20 mg/kg orally, maximum 1 g) is given to all eligible members of an EU in MDA campaigns for trachoma elimination. Azithromycin is recommended since it is administered as a single oral dose; it is acceptable for use in children and for pregnant women [39]. Topical tetracycline (1% eye ointment twice daily for six weeks) can be used as an alternative, but adherence rates are likely to be very low. Our approach is consistent with the recommendations of the World Health Organization (WHO) [40].

The above approach is supported by randomized trials showing that a single dose of oral azithromycin is as effective as a long course of topical tetracycline for treatment of trachoma [41-43].

Development of antibiotic resistance is a major concern with MDA. Chlamydial resistance to azithromycin has not been documented, although this may be due to difficulties associated with culturing the bacterium [44].

However, development of resistance in the setting of widespread antibiotic use has been described with other organisms [44,45], including development of Streptococcus pneumoniae resistance to azithromycin [46-48]. However, resistance appears to disappear within 12 months of MDA cessation [44,48-50].

Approach to mass treatment — Antibiotic therapy for trachoma is best managed within an EU rather than on an individual basis, since C. trachomatis is highly infectious and transmitted rapidly in areas of poor hygiene [30,40,44,51-56]. Mass antibiotic treatment of a community reduces the reservoir of C. trachomatis infection [44].

We are in agreement with WHO guidelines, which recommend that an EU should undergo annual MDA for one year if the prevalence of TF among one to nine-year-old children (as assessed clinically) is 5 to 9.9 percent, for three years if the prevalence is 10 to 29.9 percent, and for five years if the prevalence is ≥30 percent [57,58]. (See 'Physical exam and grading system' above.)

For MDA, we favor oral azithromycin over topical tetracycline [54,55]. This approach is supported by a randomized trial including more than 1800 individuals in eight villages in The Gambia randomized to treatment with azithromycin (three doses at weekly intervals) or supervised topical tetracycline (daily for six weeks) [55]. Two months after treatment, the prevalence of trachoma was comparable (4.6 versus 5.1 percent, respectively); 12 months after treatment, the prevalence of trachoma was lower among those treated with azithromycin (7.7 versus 16 percent; adjusted odds ratio [OR] 0.52, 95% CI 0.34-0.80).

An impact survey should be conducted 6 to 12 months after the last planned round of MDA, to assess the TF prevalence in one to nine-year-olds; if ≥5 percent, additional MDA rounds are required [59]. Annual MDA should continue until the prevalence drops below 5 percent and this prevalence is sustained for at least two years measured by a surveillance survey; thereafter, MDA may be discontinued.

It is uncertain whether the strategy described above is always appropriate; in some reports, one or two treatments may be sufficient [60,61], and decline in the prevalence of clinical trachoma can lag behind the fall in the prevalence of infection detected by NAAT of conjunctival swabs [62]. In areas where the prevalence is greater than 50 percent, repeated MDA may be a viable tool for trachoma elimination [63-66]. However, in some settings, even many years of annual MDA appear insufficient to reduce the prevalence of TF to elimination levels [67]. As such, WHO has proposed tailored management strategies for persistent and recrudescent districts, including administration of mass treatment more frequently than annually [33].

In addition, it is uncertain whether there is benefit of biannual treatment over annual treatment. In one randomized trial including more than 14,000 individuals, biannual distribution was associated with lower trachoma prevalence than annual distribution (6.8 versus 0.9 percent) [66]. However, a subsequent randomized trial comparing annual with biannual azithromycin treatment noted comparable rates of infection at 18, 32, and 40 months following treatment [61]. Another trial observed that biannual treatment of children alone was comparable with annual treatment of the entire community [68].

Attempting to eliminate C. trachomatis infection with antibiotics alone (in the absence of addressing underlying hygiene issues) is likely to lead to recurrence once antibiotic distribution ceases. (See 'Environmental improvement' below.)

Wider impact of mass treatment — In addition to its benefit for trachoma, MDA with azithromycin has been associated with a reduction in childhood mortality in sub-Saharan Africa (in studies performed in Ethiopia, Niger, Malawi, and Tanzania) [39,60,69-71]. However, a study performed in Burkina Faso and Mali showed no benefit of adding azithromycin to seasonal malaria prophylaxis [72]. The trial data are discussed further below.

The significance of the findings, including longer-term effects and implications for health programs, requires clarification. Potential benefit of azithromycin may be attributable to the antimicrobial effect of azithromycin on gastrointestinal and respiratory pathogens and malaria infection; however, the mechanism is not fully understood. An important issue is the emergence of macrolide resistance with mass azithromycin administration, including in S. pneumoniae in the nasopharynx and Escherichia coli [44,45,73]. In a subsequent assessment of antibiotic resistance in communities that received azithromycin or placebo every 6 months for 4 years, determinants of macrolide resistance (based on stool metagenomic sequencing) were 7.5 times as high (95% CI 3.8-23.1) in the azithromycin group than the placebo group, suggesting that continued mass azithromycin distribution may propagate antibiotic resistance [74]. Further studies and careful consideration of the clinical impact of these findings need to be conducted to monitor the use of azithromycin in community MDA.

Notable trial data include:

●In a 2009 randomized trial in Ethiopia including 66,000 children aged one to nine years, mass administration of azithromycin (20 mg/kg single dose) was associated with a reduction in childhood mortality of 8.3 versus 4.1 per 1000 person years (OR 0.51, 95% CI 0.29-0.90) [60].

●In a 2018 randomized trial including more than 190,000 children in Malawi, Niger, and Tanzania, mass distribution of azithromycin (biannual [six monthly] 20 mg/kg single dose) was associated with a 13 percent reduction in mortality in children aged 1 to 59 months compared with placebo (annual all-cause mortality rate 14.6 versus 16.5 per 1000 person-years) [39]. The greatest reduction in mortality was observed in Niger (18.1 percent) and among children aged one to five months. Mortality reductions in Malawi and Tanzania were 5.7 and 3.4 percent, respectively.

In a longer term follow-up study by the same investigators, all communities received two additional open-label azithromycin distributions and no difference in mortality was observed between communities that received azithromycin for the first time and those that received it for a third year (24.0 versus 23.2 deaths per 1000 person-years), suggesting that the effect was not diminished by antimicrobial resistance [69].

In a further study of 700 Tanzanian children aged 1 to 36 months in thirty villages randomly assigned to biannual azithromycin (20 mg/kg single dose) or placebo followed for two years, no beneficial effect of azithromycin on diarrheal disease, acute respiratory illness, or anemia was observed [75].

●In contrast to the above studies, a randomized trial conducted in 2019 showed no benefit of adding azithromycin to seasonal malaria prophylaxis with respect to death or hospital admission; however, a lower disease burden was noted in the azithromycin arm [72]. The study included over 19,000 children in Burkina Faso and Mali; households were randomly assigned to receive azithromycin (three-day course) or placebo in addition to seasonal malaria prophylaxis (sulfadoxine-pyrimethamine and amodiaquine given at monthly intervals for four months of malaria transmission season for three years). There was no significant difference in the number of deaths or hospital admissions (24.8 versus 23.5 per 1000 person-years; incidence rate ratio 1.1, 95% CI 0.88-1.4). The effects of azithromycin alone, malaria prophylaxis alone, and placebo alone were not compared.

Surgery for trichiasis — The purpose of surgery is to stop the eyelashes from abrading the cornea, reduce ocular discharge, improve visual acuity, reduce progression to corneal opacity, and relieve discomfort.

For treatment of major trichiasis, we are in agreement with WHO recommends either bilamellar tarsal rotation (BLTR) or posterior lamellar tarsal rotation (PLTR). In one randomized trial including 1000 patients in Ethiopia who underwent PLTR or BLTR, one-year trichiasis recurrence rates were lower among those who underwent PLTR (22 versus 13 percent, respectively; adjusted OR 1.96, 95% CI 1.40-2.75) [76,77]. The patients enrolled in this trial were evaluated four years later; the PLTR surgical procedure had superior long-term outcomes in comparison to the BLTR, with significantly lower risk of postoperative recurrent TT [78]. Further operational study of PLTR would be beneficial.

For treatment of minor trichiasis, we favor surgery rather than epilation (eyelash removal) if an experienced surgeon is available. However, properly performed epilation with regular follow-up is a reasonable alternative to surgery for individuals who do not have access to surgery or who decline surgery [79]. In one randomized trial including patients with minor trichiasis in Oman randomized to treatment with BLTR, epilation via electrolysis or epilation via cryoablation, operative success was observed in 80, 29, and 18 percent of cases, respectively [80]. In a subsequent trial including 1300 patients with minor trichiasis in Ethiopia randomized to treatment with surgery or repeated epilation, vision and corneal opacity was comparable between the groups [81].

The role of antibiotics (azithromycin, doxycycline, or topical tetracycline) for prevention of recurrence following trichiasis surgery is uncertain [82]. The benefit of perioperative azithromycin may be greater in the setting of major trichiasis [83-87]. In one randomized trial including 451 patients in The Gambia with major or minor trichiasis who underwent surgery followed by randomization to azithromycin (single dose) or no treatment, there was no difference in the trichiasis recurrence rate (60 percent) between the azithromycin and control group at one year [86]. In a subsequent randomized trial including more than 1400 patients with trichiasis who underwent surgery followed by randomization to patient treatment with topical tetracycline (twice per day for six weeks), patient treatment with azithromycin (single dose), or patient and household treatment with azithromycin (single dose), the recurrence rate was lower among patients who received azithromycin than those who received topical tetracycline (7 versus 10 percent); there was no additional reduction in the arm that also treated household members [87]. Oral doxycycline (100 mg per day for four weeks) was not found to reduce recurrence in a randomized trial of 1000 people with trichiasis in Ethiopia [88].

The recurrence rate of trichiasis after surgery ranges from 5 to 60 percent in the first two to three years; the likelihood of recurrence increases with the severity of preoperative disease [86,89-93]. Recurrence may occur as part of the natural history of the initial disease or in association with repeat infection with further scarring. We favor repeat surgery for treatment of recurrent trichiasis, if feasible.

Challenges to successful implementation of a trichiasis surgery program include high rates of recurrent infection, limited resources for equipment, training and transportation, and patient barriers including limited understanding of the condition and potential benefits of surgery [12,94].

PREVENTION — The Neglected Tropical Diseases (NTD) Roadmap 2021-2030 targets trachoma for global elimination as a public health problem by 2030. The "SAFE" strategy is recommended to achieve this: Surgery for trichiasis, Antibiotics (mass treatment with azithromycin) to clear C. trachomatis infection, Facial cleanliness, and Environmental improvement to limit transmission [95]. Eighteen countries are validated by WHO as having met the elimination targets [96].

Because blindness is irreversible, the strategy focuses on prevention. Surgical correction of TT prevents development of corneal opacification. Antibiotics, facial cleanliness, and environmental improvements can disrupt the cycle of reinfection.

Surveillance — Trachoma is defined as a public health problem by WHO when the prevalence of TF among one- to nine-year-old children (as assessed clinically) is ≥5 percent and/or the prevalence of TT among those aged 15 years or older is ≥0.2 percent [12,97].

The Global Trachoma Mapping Project completed a comprehensive trachoma surveying program, which has helped guide national trachoma elimination programs (figure 1) [2,98]. Its successor, Tropical Data, has continued to support baseline mapping and impact surveys to assess whether the elimination thresholds have been reached and surveillance surveys to determine whether the elimination thresholds have been maintained [18].

Mass antibiotic treatment — Issues related to antibiotic therapy and mass treatment are discussed above. (See 'Antibiotic therapy' above.)

Facial cleanliness — Children with visible nasal discharge, ocular discharge, or flies on their faces are at least twice as likely to have active trachoma as children with clean faces [99-101]. However, it is unclear whether there is a causal relationship between dirty faces and trachoma, and facial cleanliness is difficult to measure in a standardized way [102]. Facial cleanliness is generally considered an important modifiable risk factor; water access and facial cleanliness are important factors in trachoma clustering in endemic regions [103]. Trachoma was once a major problem in Europe and North America; it disappeared from these areas as a result of improved living conditions rather than mass antibiotic distribution.

In one randomized trial including more than 1400 children in a trachoma-endemic area, villages were randomized to treatment with topical tetracycline ointment (30-day course) alone or in combination with an intensive community-based health education program to promote face washing [104]. The odds of developing severe active trachoma was lower in villages treated with received antibiotics and community-based health education than in villages treated with antibiotics alone (odds ratio 0.62, 95% CI 0.40-0.97).

In a study in Ethiopia, in the absence of antibiotic treatment, an integrated WASH (Water, Sanitation and Hygiene) intervention did not prevent resurgence of trachoma following cessation of antibiotics [105], suggesting that continued antibiotic treatment is required in settings with persistent trachoma, as part of the combined SAFE strategy. Further studies are required to improve the evidence base for WASH interventions for trachoma control.

Environmental improvement — C. trachomatis is highly infectious and transmitted rapidly in areas of poor hygiene. Within a family, spread of infection can recur up to six months after azithromycin treatment; among families, spread of infection can occur in 12 months after antibiotic treatment [51-53].

Environmental improvement, including water, sanitation, and hygiene (WASH) are necessary for trachoma prevention and elimination [106]. Modifications in the availability and use of water and latrines, fly control, health education, and proximity to domesticated animals have all been proposed to reduce transmission of C. trachomatis. However, resources for implementation of such interventions in trachoma elimination programs are often limited [12,107]. The WHO WASH-NTD toolkit aims to support NTD programs to improve WASH services [108].

Environmental factors likely affect C. trachomatis transmission as a function of their influence on facial cleanliness [109,110]. Availability of clean water is a critical resource for facial cleanliness. In one study from Tanzania, the risk of trachoma in a household increased with distance from a water source; however, there was no association between trachoma risk and quantity of water brought into the house [111]. It may be that the distance between a home and its water supply influences a family's prioritization of water use for hygienic purposes. Thus, modifying the perception of how water should be used in the home may be at least as important as making water more accessible.

Eye to eye transmission of C. trachomatis may be interrupted if faces are kept free of ocular and nasal discharge by washing hands and faces. In one study including 83 children from Ethiopia aged 1 to 9 years with active trachoma allocated to a face cleaning protocol (face washing with water, face washing with water and soap, or face wiping), faces were examined for ocular and nasal discharge and swabs were taken from faces and hands to test for C. trachomatis at baseline, immediately post protocol, and 1, 2, and 4 hours afterwards [112]. Washing with soap was more effective at removing ocular discharge than washing with water (89 vs 27 percent of discharge removed, respectively) or face wiping (42 percent).

In a population-based household survey investigating the presence of extraocular C. trachomatis DNA within households, C. trachomatis DNA was detected on hands, faces, and clothing of individuals in households where active trachoma was present; in addition, C. trachomatis DNA was detected on flies in households where trachoma was present as well as in households where trachoma was absent, suggesting that flies may be a vector for transmission within and between infected and uninfected households [14]. A study using viability polymerase chain reaction to detect C. trachomatis supports the hypothesis that nonocular surfaces may have a role in the transmission of infection in trachoma [15].

Household fly density is a potentially amenable risk factor [99]. However, it is uncertain whether insecticide spraying is effective for reducing trachoma prevalence [113,114].

SUMMARY AND RECOMMENDATIONS

●Trachoma is the leading infectious cause of blindness worldwide (figure 1). It is a chronic keratoconjunctivitis caused by recurrent infection with Chlamydia trachomatis; humans are the only hosts. C. trachomatis is transmitted in areas of poor hygiene, probably via spread of ocular and nasal secretions on fingers and use of contaminated fomites. In addition, transmission may occur via eye-seeking flies (which serve as passive vectors but do not serve as reservoirs of infection). (See 'Introduction' above and 'Epidemiology' above.)

●The clinical manifestations of trachoma include two phases: active trachoma (conjunctivitis) and cicatricial disease (conjunctival scarring). In general, active trachoma occurs largely in young children; cicatricial disease and blindness occur in adults (figure 2 and figure 3). (See 'Disease phases' above.)

•Initial C. trachomatis infection causes a mild, self-limited follicular conjunctivitis. Most patients with active trachoma are asymptomatic. For this reason, most cases of active trachoma are detected via screening programs. Symptoms, if present, are typical of chronic conjunctivitis; they include redness, discomfort, light sensitivity, and mucopurulent discharge. (See 'Active trachoma (conjunctivitis)' above.)

•Repeated episodes of infection cause marked conjunctival inflammation, leading to eyelid scarring. Eyelid scar tissue eventually contracts and can distort the lid margin leading to entropion (inward rolling of the eyelid) and trichiasis (eyelashes rubbing against the eyeball). Individuals with trichiasis have a greatly increased risk of blindness. (See 'Cicatricial disease (conjunctival scarring)' above.)

●The diagnosis of trachoma should be suspected in patients with follicular conjunctivitis and/or conjunctival scarring in areas where trachoma is endemic or in areas at risk for trachoma. The diagnosis is established based on the clinical manifestations. Physical examination findings are used to categorize the severity of disease using the World Health Organization (WHO) simplified grading system (table 1). This grading system can be used to guide management of individual patients and for screening programs. (See 'Physical exam and grading system' above.)

●Treatment of trachoma consists of antibiotic therapy; in addition, patients with trichiasis warrant surgery tailored to individual physical findings:

•For districts with prevalence of TF ≥5 percent among one- to nine-year-old children, we suggest mass treatment with azithromycin (Grade 2B). Antibiotic therapy for trachoma is best managed within an entire region rather than on an individual basis. If the prevalence is <5 percent, mass treatment is not needed. Azithromycin is preferred since it is administered as a single dose; topical tetracycline is an acceptable alternative. (See 'Antibiotic selection' above and 'Approach to mass treatment' above.)

•For surgical treatment of major trichiasis, procedures include bilamellar tarsal rotation or posterior lamellar tarsal rotation; the choice of approach depends on available expertise. For treatment of minor trichiasis, we suggest surgery over epilation (eyelash removal) (Grade 2C). (See 'Surgery for trichiasis' above.)

●We are in agreement with the World Health Organization, which advocates the "SAFE" strategy for trachoma elimination: Surgery for trichiasis, Antibiotics for C. trachomatis infection, Facial cleanliness, and Environmental improvement. Surgical correction of trichiasis prevents development of corneal opacification. Antibiotics, facial cleanliness, and environmental improvement can disrupt the cycle of reinfection. (See 'Prevention' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Heathcote Wright, PhD FRANZCO, Hugh Taylor, AC, MD, and Emily O'Kearney, MIPH, BPhty, who contributed to earlier versions of this topic review.