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Ophthalmology > INFECTIOUS DISEASE
Trachoma
Article Last Updated: Sep 5, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 12
Author: Anthony W Solomon, MBBS, DTM&H, PhD, MRCP, Specialist Registrar in Infectious Diseases, Lister Unit, Northwick Park Hospital, London; Honorary Lecturer, International Centre for Eye Health, Clinical Research Unit, London School of Hygiene and Tropical Medicine, London
Anthony W Solomon is a member of the following medical societies: Royal College of Physicians of the United Kingdom
Coauthor(s):
Hugh Ringland Taylor AC, MD, MBBS, BmedSc (Melb), DO (Melb), FRACO, FRACS, FAAO, FACS, FAICD, Harold Mitchell Professor of Indigenous Eye Health, School of Population Health, University of Melbourne
Editors: Anastasios J Kanellopoulos, MD, Assistant Program Director, Clinical Associate Professor, Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, New York University; Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles; Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Hospital; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Author and Editor Disclosure
Synonyms and related keywords:
Chlamydia trachomatis, C trachomatis, chronic keratoconjunctivitis, SAFE strategy for trachoma, trichiasis, simplified trachoma grading scheme, trachomatous scarring, corneal opacity
Background
Trachoma is the leading infectious cause of ocular morbidity. This disease is a chronic keratoconjunctivitis caused by the obligate intracellular bacterium Chlamydia trachomatis. Disease transmission occurs primarily between children and the women who care for them. Some have characterized this transmission cycle by describing trachoma as a disease of the crèche (day nursery). Repeated episodes of reinfection within the family cause chronic follicular or intense conjunctival inflammation (active trachoma), which leads to tarsal conjunctival scarring. The scarring distorts the upper tarsal plate and, in some individuals, leads to entropion and trichiasis (cicatricial trachoma). The end result includes corneal abrasions; corneal scarring and opacification; and, ultimately, blindness. Prevention of trachoma-related blindness requires a number of interventions. The World Health Organization (WHO) and their partners endorse the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy for trachoma control. The interventions are discussed in greater detail in Treatment.
Pathophysiology
Trachoma is caused by serovars A, B, Ba, and C of C trachomatis. Different serovars predominate in different families and in different communities. Chlamydiae are gram-negative, obligate intracellular bacteria. The species C trachomatis causes trachoma and also genital infections (serovars D-K) and lymphogranuloma venereum (serovars L1-L3). Serovars D-K occasionally cause a chronic follicular conjunctivitis that is clinically indistinguishable from trachoma, including follicular conjunctivitis with pannus and, at times, conjunctival scarring. However, these genital serovars do not typically enter stable transmission cycles within communities. Therefore, they are not involved in the genesis of trachoma blindness. Regardless of the serovar (which is determined by polymorphisms in a surface-exposed protein), isolates of C trachomatis obtained from the eye have mutations that inactivate the genes coding for tryptophan synthase, whereas genital isolates have a functional enzyme.
Infection causes inflammation, that is, a predominantly lymphocytic and monocytic infiltrate with plasma cells and macrophages in follicles. The follicles are typical germinal centers with islands of intense B-cell proliferation surrounded by seas of T cells. Recurrent conjunctival reinfection causes the prolonged inflammation that leads to conjunctival scarring. Scarring is associated with atrophy of the conjunctival epithelium, loss of goblet cells, and replacement of the normal, loose, vascular subepithelial stroma with thick compact bands of type IV and type V collagen.
Frequency
United States
Trachoma was once endemic in North America and Europe, but it has disappeared in these locations with the improvement of living standards.
International
Trachoma is endemic in parts of Africa, Asia, the Middle East, Latin America, the Pacific Islands, and aboriginal communities in Australia. Worldwide, an estimated 84 million people in 55 endemic countries have active trachoma. In hyperendemic areas, most members of nearly all families may have active disease. When the overall community prevalence decreases to around 20%, active disease is clearly seen to cluster in families. In 1 of 5 families, most children have active trachoma (as opposed to 1 in 5 children in most families). This clustering becomes more apparent in communities as the prevalence decreases.
Mortality/Morbidity
Blindness from any cause is associated with increased risk of mortality in endemic communities. Approximately 1.3 million people are blind because of trachoma.
Race
- A disease of poverty and poor hygiene, trachoma has no racial preponderance.
- Trachoma persists in areas with poor personal and community hygiene, for example, communities with inadequate access to water and sanitation in hot, dry, dusty climates.
- Trachoma typically affects the most marginalized, deprived members of a community.
Sex
- Active disease most commonly occurs in preschool children of both sexes and their (usually female) care providers.
- Trichiasis and blindness may be 2-4 times more common in women than men.
Age
- Active disease most commonly occurs in preschool children, with the highest prevalence in children aged 3-5 years.
- Cicatricial disease is most common in middle-aged adults. The age group in which cicatricial disease begins to appear depends on the intensity of transmission in the community. In areas of extremely high endemicity, rare cases of trichiasis occur in children younger than 10 years.
- Because of repeat infection, aging may be accompanied by sequential worsening of disease. Young children have follicular trachoma with intense conjunctival inflammation; young adults, especially mothers, have trachomatous scarring; and middle-aged patients or grandparents have trichiasis and corneal opacity. However, these signs are not mutually exclusive. Individuals may have episodes of follicular trachoma with intense conjunctival inflammation even after cicatricial complications develop; therefore, follicles, scarring, and trichiasis may all be present in the same patient.
History
Two phases of the disease process exist: the active phase and the scarring (cicatricial) phase. As implied above, though, these phases are not stages along a linear pathway of disease pathogenesis; both phases may coexist in the same patient.
- The active phase resembles many other diseases in which follicular conjunctivitis is a feature. Without laboratory facilities, the diagnosis is solely based on the clinical appearance of active trachoma in someone living in a community where trachoma is endemic or suspected to be endemic.
- Most patients with active trachoma are relatively asymptomatic.
- The cicatricial phase has unique clinical features, which lead to definitive diagnosis in most cases.
- Determine the amount of time that the patient has spent in a trachoma-endemic community and/or near a pool of infection.
- Conjunctival scarring alone tends to be asymptomatic, though the associated disturbance of the architecture of the tear film (due to scarring and destruction of mucous and serous glands) often leads to dry eye.
- Trichiasis causes an intensely irritating foreign body sensation, as well as blepharospasm. Ultimately, it leads to corneal scarring.
- Many patients self-epilate before their presentation.
- Corneal opacities or scars that cover any part of the pupil impair the patient's vision.
Physical
Active trachoma is characterized by a mucopurulent keratoconjunctivitis. The conjunctival surface of the upper eyelid shows a follicular and inflammatory response. The cornea may have limbal follicles, superior neovascularization (pannus), and punctate keratitis. Infection with C trachomatis concurrently occurs in other extraocular mucous membranes, commonly the nasopharynx, leading to a nasal discharge.
- Follicular trachoma (designated TF in the WHO simplified trachoma grading scheme)
- Follicular trachoma is defined as the presence of 5 or more follicles at least 0.5 mm in diameter in the central part of the upper tarsal conjunctiva.
- Follicular trachoma indicates active disease.
- This form is most commonly found in children, with a peak prevalence in those aged 3-5 years. The prevalence rapidly decreases in school-aged children as they leave the pool of re-infection (ie, their family childcare group).
- Follicles are germinal centers that primarily consist of lymphocytes and monocytes.
- The presence and involution of follicles at the limbus (corneoscleral border) give rise to the pathognomonic lesion of past active trachoma, Herbert pits.
- Intense inflammatory trachoma (designated TI in the WHO simplified trachoma grading scheme)
- Intense inflammatory trachoma is defined as pronounced inflammatory thickening of the upper tarsal conjunctiva that obscures more than one half of the normal deep tarsal vessels.
- The cause is an intense inflammatory response.
- The normally thin tarsal conjunctiva develops a velvety thickening.
- Papillae are visible under slit lamp examination.
- Intense inflammatory trachoma indicates an increased potential for significant conjunctival scarring and, hence, a higher ultimate risk of blinding disease.
- Surveying the prevalence of intense inflammatory trachoma in children can help in predicting the risk of future blinding trachoma in that cohort of children.
- Trachomatous scarring (designated TS in the WHO simplified trachoma grading scheme)
- Trachomatous scarring is defined as the presence of easily visible scars in the tarsal conjunctiva.
- Trachomatous scarring indicates past inflammatory disease and a risk of future trichiasis. The more severe the scarring, the higher the risk of subsequent trichiasis.
- This form may be associated with the development of dry eye syndrome, but chronic, low-grade bacterial conjunctivitis and dacryocystitis may also lead to a weeping eye.
- Trichiasis (designated TT in the WHO simplified trachoma grading scheme)
- Trichiasis is defined as at least 1 eyelash rubs on the eyeball or evidence of recent removal of in-turned eyelashes.
- This is a potentially blinding lesion that can lead to corneal opacification.
- Trichiasis is due to subconjunctival fibrosis over the tarsal plate that leads to lid distortion.
- Some vision can be restored with the successful correction of trichiasis.
- Corneal opacity (designated CO in the WHO simplified trachoma grading scheme)
- Corneal opacity is defined as easily visible corneal opacity over the pupil that is so dense that it blurs at least part of the pupillary margin when it is viewed through the opacity.
- Corneal opacity or scarring reflects the prevalence of vision loss and blindness resulting from trachoma.
- This condition includes pannus, epithelial vascularization, and infiltration only if it involves the central cornea.
Causes
Trachoma is caused by repeated conjunctival infection with C trachomatis. The greatest individual-level risk factor for active trachoma appears to be having a family member with active disease. At the community level, adequate water access for personal hygiene, sanitation, and fly control determine the risk of endemic trachoma.
Conjunctivitis, Allergic
Conjunctivitis, Bacterial
Conjunctivitis, Neonatal
Conjunctivitis, Viral
Trichiasis
Other Problems to be Considered
Acute chlamydial infection (inclusion conjunctivitis)
Toxic follicular conjunctivitis (secondary to topical medications or other compounds)
Lab Studies
- In endemic areas, the diagnosis is almost always based on the clinical appearance.
- Laboratory assays are principally used in research.
- To confirm that the clinical diagnosis of active trachoma is the result of ocular C trachomatis infection, the best laboratory techniques are the nucleic acid amplification tests (NAATs), of which the polymerase chain reaction (PCR) is one example.
- The NAATs have high sensitivity and specificity but are too expensive and too technically complex to be widely available in most settings where trachoma is endemic.
- On any assay, apparent false-positive and false-negative results (compared with the clinical signs of active trachoma) may be related to the natural history of infection and disease.
- Individuals become infected several weeks before specific clinical signs appear, and evidence of conjunctival inflammation persists for weeks to months after the infection resolves.
- Other useful techniques are direct fluorescein-labeled monoclonal antibody (direct fluorescent antibody [DFA]) assay and enzyme immunoassay (EIA) of conjunctival smears. These tests are less sensitive than the NAATs. However, to determine whether antibiotics are needed by a community, the prevalence of infection may be an important parameter, so a test with high specificity may be useful even if it has lower sensitivity. A dipstick-based EIA for infection that can be deployed in remote trachoma-endemic villages has now been developed and has shown good performance characteristics in early trials.
- Newer diagnostic methods have superseded cell culture, which was the criterion standard for laboratory diagnosis. Cell culture requires a highly specialized laboratory and is expensive and technically demanding. Cell culture has virtually 100% specificity but only moderate sensitivity.
- Giemsa cytology is microscopic examination of stained conjunctival scrapings for intracytoplasmic inclusions. Giemsa cytology is technically demanding. This test has high specificity but low sensitivity.
Medical Care
The key to the treatment of trachoma is the SAFE strategy developed by the WHO. The surgical ("S") component of this strategy is described in Surgical Care below. - Antibiotic therapy
- The WHO recommends 2 antibiotics for trachoma control: oral azithromycin and tetracycline eye ointment.
- Azithromycin is better than tetracycline, but it is more expensive.
- National trachoma control programs in a number of countries are fortunate to be beneficiaries of a philanthropic donation of azithromycin.
- Azithromycin is the drug of choice because it is easy to administer as a single oral dose. Its administration can be directly observed. Therefore, compliance is higher than with tetracycline and can actually be measured, whereas, with the home administration of tetracycline, the level of compliance is unknown.
- Azithromycin has high efficacy and a low incidence of adverse effects. When adverse effects occur, they are usually mild; gastrointestinal upset and rash are the most common adverse events.
- Infection with C trachomatis occurs in the nasopharynx; therefore, patients may reinfect themselves if only topical antibiotics are used.
- Beneficial secondary effects of azithromycin include its treatment of genital, respiratory, and skin infections.
- Current WHO recommendations for antibiotic treatment of trachoma are as follows:
- Determine the district-level prevalence of follicular trachoma in 1- to 9-year-old children. If the prevalence is 10% or higher, conduct mass treatment with antibiotic of all people throughout the district. If the prevalence is less than 10%, conduct assessment at the community level in areas of known disease.
- If assessment at the community level is undertaken in communities where the prevalence of follicular trachoma in 1- to 9-year-old children is 10% or more, conduct mass treatment of all people with antibiotics.
- If assessment at the community level is undertaken in communities where the prevalence of follicular trachoma in 1- to 9-year-old children is 5% or more but less than 10%, targeted treatment should be considered. Targeted treatment should involve the identification and treatment of all members of any family in whom one or more members have follicular trachoma.
- If assessment at the community level is undertaken in communities where the prevalence of follicular trachoma in 1- to 9-year-old children is less than 5%, antibiotic distribution may not be necessary, though targeted treatment can be considered.
- Development of significant resistance to either azithromycin or tetracycline has not yet been demonstrated in C trachomatis.
- Macrolide resistance may be induced in Streptococcus pneumoniae by the mass distribution of azithromycin for trachoma, but multiple rounds of treatment and/or the presence of macrolide resistant isolates at baseline may be necessary for epidemiologically-significant resistance to emerge.
- Facial cleanliness
- Epidemiologic studies and community-randomized trials have shown that facial cleanliness in children reduces both the risk and the severity of active trachoma.
- To be successful, health education and promotion activities must be community based and require considerable effort.
- Environmental change
- Environmental change activities are the promotion of improved water supplies and improved household sanitation, particularly methods for safe disposal of human feces.
- These activities should be prioritized.
- The flies that transmit trachoma preferentially lay their eggs on human feces lying exposed on the soil. Controlling fly populations by spraying insecticide is difficult. Studies on the impact of fly control on trachoma have had variable results. Trials undertaken to evaluate the installation of pit latrines suggested that the prevalence of trachoma was reduced but failed to demonstrate a statistically significant effect.
- General improvements in personal and community hygiene are almost universally associated with a reduction in the prevalence—and eventually the disappearance—of trachoma. This is true not only in Europe, the Americas, and Australia but also in Africa and Asia.
Surgical Care
The key to the treatment of trachoma is the SAFE strategy. “S” stands for trichiasis surgery. The antibiotics (“A”), facial cleanliness (“F”), and environmental improvement (“E”) components of this strategy are described in Medical Care.
- Eyelid surgery to correct trichiasis is important in people with trichiasis, who are at high-risk for trachomatous visual impairment and blindness. Eyelid surgery to correct entropion and/or trichiasis may prevent blindness in individuals at immediate risk.
- Eyelid rotation limits the progression of corneal scarring. In some cases, it can result in a slight improvement in visual acuity, probably due to restoration of the visual surface and reductions in ocular secretions and blepharospasm.
- The WHO has produced a training manual on the bilamellar tarsal rotation procedure.
- This procedure involves a full-thickness incision of the scarred lid and external rotation of the distal margin by using 3 sutures.
- In regions where access to ophthalmologists is limited, well-trained and well-supported health workers can perform bilamellar tarsal rotation.
- Results of randomized clinical trials have confirmed the superiority of this method over other techniques.
- Even after successful surgery, patients remain at risk for recurrence. Therefore, long-term follow-up care and intermittent screening are important after surgery.
- Recurrence rates vary greatly between surgeons. Ongoing audit is an essential element of trichiasis surgery programs.
- Evidence supports the adjuvant use of single-dose azithromycin to patients at the time of surgery.
The aim in treatment is to reduce the amount C trachomatis in the infection reservoir in the family. Treating an individual and not treating infected family members leaves the individual at risk for repeat infection. All family members, including infants, should be treated. The antibiotic of choice for treating active trachoma is azithromycin. The dose for children is 20 mg/kg in a single dose; adults receive a single dose of 1 g. The second-line treatment is topical tetracycline eye ointment 1%. Topical tetracycline is applied to both eyes twice a day for 6 weeks. If the patient lives in a hyperendemic area, the whole district (or whole community) is eligible for antibiotic treatment.
Drug Category: Antibiotics
Antibiotic therapy is part of the WHO SAFE strategy for trachoma.
| Drug Name | Azithromycin (Zithromax) |
| Description | Macrolide antibiotic; DOC for trachoma. Plasma concentrations are low, but tissue concentrations are higher, giving it value in treating intracellular organisms. Long tissue half-life. Single dose recommended. |
| Adult Dose | 1 g PO once |
| Pediatric Dose | 20 mg/kg PO once Many trachoma control programs now use height-based dosing in mass azithromycin distribution campaigns.
|
| Contraindications | Documented hypersensitivity; hepatic impairment; do not administer with pimozide |
| Interactions | May increase toxicity of theophylline, warfarin, and digoxin; effects reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity possible with coadministered cyclosporine |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
| Precautions | IV site reactions possible; bacterial or fungal overgrowth possible with prolonged antibiotic use; may increase hepatic enzyme levels and cholestatic jaundice; caution in impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients |
| Drug Name | 1% Tetracycline ointment (Achromycin) |
| Description | Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit. Use if azithromycin is unavailable. Minimal systemic adverse effects. |
| Adult Dose | 0.5-inch ribbon in both eyes bid for 6 wk |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
| Precautions | Local irritation and temporary blurring of vision possible |
Further Outpatient Care
- Long-term, intermittent follow-up care is required for patients with active or cicatricial disease.
- One episode of infection may be treated adequately, but reinfection from the community pool of infection is likely unless an effective mass treatment campaign is implemented. When mass treatment is undertaken, antibiotic coverage should be as high as possible, with 80% being an absolute minimal target. It is important to treat all family members, especially the younger children.
- Some studies suggest a great benefit if coverage in excess of 95% can be achieved.
- Surgical patients require annual follow-up care because of the potential for recurrence.
Deterrence/Prevention
- Facial cleanliness and environmental improvement are major components of the SAFE strategy.
- Many regard the lack of facial cleanliness in children as the key factor for the persistence of trachoma.
Prognosis
- The prognosis depends on the severity of the disease at the time of treatment, the appropriateness of the treatment, and the risk of reinfection.
- Patients in whom early disease is treated appropriately have an excellent prognosis.
- Severe disease may be stabilized, but the patient's vision may not improve once corneal scarring has developed.
- Reinfection worsens the prognosis.
Medical/Legal Pitfalls
- Emphasize to patients that their entire families require assessment and treatment.
- Although appropriate treatment is curative, aggressive steps may be required to prevent reinfection.
The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor, Denise Mabey, FRCOphth, MBBS, to the development and writing of this article.
| Media file 1:
Trachomatous inflammation, follicular (TF), is the presence of 5 or more follicles (each at least 0.5 mm in diameter) on the central part of the upper tarsal conjunctiva. Images from the Slides/Text Teaching Series, No. 7, Trachoma, published by The International Centre for Eye Health, Institute of Ophthalmology, 11-43 Bath St, London EC1V 9EL, United Kingdom. Photograph courtesy of John D. C. Anderson, MD. |
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| Media file 2:
Trachomatous inflammation, intense (TI) is pronounced inflammatory thickening of the upper tarsal conjunctiva that obscures more than one half the normal deep tarsal vessels. Photograph courtesy of Allen Foster, MD. |
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| Media file 3:
Trachomatous conjunctival scarring (TS) is the presence of easily visible scars in the tarsal conjunctiva. Photograph courtesy of John D. C. Anderson, MD. |
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| Media file 4:
Trachomatous trichiasis (TT) is defined as the presence of at least 1 eyelash rubbing on the eyeball or evidence of recent removal of in-turned lashes. Photograph courtesy of John D. C. Anderson, MD. |
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| Media file 5:
Easily visible corneal opacity over the pupil; it is so dense that at least part of the pupil margin is blurred when viewed through the opacity. Photograph courtesy of John D. C. Anderson, MD. |
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| Media file 6:
The image on the left shows intense inflammatory trachoma, and the image on the right shows allergic conjunctivitis with the typical cobblestone papillae. Courtesy of John D. C. Anderson, MD, and Murray McGavin, MD. |
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Trachoma excerpt Article Last Updated: Sep 5, 2007
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