TRACHOMA

INTRODUCTION

Trachoma is the leading infectious cause of ocular morbidity

• It ranks in the top three causes of blindness worldwide. Repeat infection with the organism Chlamydia

trachomatis leads to conjunctival inflammation and scarring, trichiasis, and ultimately blinding corneal opacification.

• Trachoma is an ancient disease, described clearly in the Ebers papyrus of 1500 BC, and well known to the ancient Greeks

• The name comes from the Greek word for rough ;a reference to the characteristic appearance of the subtarsal conjunctiva seen when the upper eyelid of an individual with active disease is everted.

EPIDEMIOLOGY

Trachoma is leading cause of preventable irreversible

blindness in the world The World Health Organization (WHO) reports trachoma

is endemic to more than 50 countries, with most blinding trachoma in Africa.

It is responsible for the visual impairment of about 2.2 million people, of whom 1.2 million are irreversibly blind*

*WHO Global Health Observatory (GHO) data http://www.who.int/gho/neglected_diseases/trachoma

• During the last two centuries, trachoma retreated from some formerly endemic regions, such as Europe and North America

• Today trachoma is prevalent in large parts of Africa, and in some regions of the Middle East, the Indian Subcontinent, South-east Asia and South America.1

• The highest prevalence of trachoma is reported from countries such as Ethiopia and Sudan where the prevalence of active trachoma in children is often greater than 50% and trichiasis is found in up to 5% of adults.2

1)Polack S, Brooker S, Kuper H et al. (2005) Mapping the global distribution of trachoma. BullWorld Health Organ, 83, 913–919.2) Berhane Y, Worku A, Bejiga A (2006) National Survey on Blindness, Low Vision andTrachoma in Ethiopia. Federal Ministry of Health of Ethiopia

Indian scenario

AGE• The prevalence of active disease peaks in pre-school

children and declines to low levels in adulthood• In contrast to the signs of active disease, the prevalence

of trachomatous conjunctival scarring increases with age,reflecting the cumulative nature of the damage

GENDER• Clinically active trachoma generally occurs with equal

prevalence in male and female children.• However, in most areas women are more frequently

affected by the blinding complications than men• About 75% of trichiasis and corneal blindness cases are

women, probably due to their greater lifetime exposure to C.trachomatis infection through contact with children

• FAMILY based disease • CLIMATE-More common in dry and dusty weather• SOCIOECONOMIC STATUS- More commmon in poor

classes due to overcrowding,poor hygiene,flies,paucity of water

PATHOGENESIS

• CAUSATIVE ORGANISM• Chlamydiae are obligate intracellular gram-negative

eubacteria that exhibit a highly specialized biphasic developmental cycle

• Genus is divided into four species: Chlamydia trachomatis, C. psittaci, C. pneumoniae, and C. pecorum.

• C. trachomatis and C. pneumoniae are important human pathogens, whereas C. Psittaci and C. pecorum are primarily pathogens of animals and birds, rarely infecting humans

Chlamydia trachomatis

• 19 different serovars based on immunological cross-reactivity of the major outer membrane protein (MOMP).

• These are sub-divided into two biovars; the trachoma biovar (serovars A–K) and the lymphogranuloma venereum biovar (serovars L1, L2, L2a and L3).

• Endemic trachoma is caused by serovars A, B, Ba and C.

• Genital chlamydial infection, which causes pelvic inflammatory disease and infertility, is associated with serovars D–K.

• The elementary body (EB) is a metabolically inert form of the organism that is responsible for infecting the host cell.

• Once host cells take up organisms, they are confined to a vacuole known as the inclusion.

• Within the inclusion, the bacteria are protected from lysosomal fusion and differentiate into the metabolically active reticulate body (RB) form.

• Reticulate bodies replicate within the inclusion, converting back into Elementary Bodies just before cell lysis.

• C. trachomatis infection mobilizes all arms of the adaptive immune system.

• Antibodies elicited against outer membrane proteins of C. trachomatis aid in blocking attachment and subsequent internalization of the bacteria by host cells

• Once organisms have entered host cells and begun developing, clearance of the bacteria requires the activity of T cells. In a number of studies, CD4+ T cells have been shown to play a crucial role in host defense against C. trachomatis.

• 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.

• The clinical changes are a delayed-type hypersensitivity reaction to the chlamydial antigens (thought to be HSP-60).

• C trachomatis has evolved various ways to evade the host immune response.

• First, its intracellular location protects it from attack by antibody and complement.

• Second,expression of MHC class I molecules at the surface of infected cells is downregulated, reducing the likelihood that the cells will be recognised and killed by class-I-restricted cytotoxic T cells.

• Last, fusion of the phagosome (containing the ingested organism) with host-cell lysosomes (containing microbicidal substances) is actively prevented.

EPITHELIOTROPIC

• Clinically, trachoma is sub-divided into active (early) and cicatricial (late-stage) disease -these phases are not stages along a linear pathway of disease pathogenesis; both phases may coexist in the same patient

SYMPTOMS• Many infections are asymptomatic. • In other cases, following an incubation period of 5 to

10 days, conjunctival infection produces an irritated, red eye and scanty mucopurulent discharge.

• Involvement of the cornea in the acute inflammatory process can cause pain and photophobia.

CLINICAL FEATURES

SIGNS

CONJUNCTIVA Follicular conjunctivitis Conjunctival scarring Limbal follicles Herberts pitsCORNEA Corneal ulcer Corneal opacityLIDS Entropion Trichiasis

• First sign of infection is a nonspecific vasodilation of conjunctival blood vessels

• Follicles develop subjacent to the conjunctivae of the fornices, the tarsal plates, and the limbus

• Papillae may also be noted at this stage: in mild cases, a few isolated, small red dots can be seen with the naked eye. When inflammation is severe, an intense papillary reaction on the tarsal conjunctiva is associated with a diffuse thickening of the conjunctiva, obscuration of the deep tarsal vessels, and, sometimes, eyelid edema.

• If the cornea is involved in the inflammatory process, a superficial punctate keratitis may be noted.

• Superficial infiltrates or pannus (subepithelial• infiltration of fibrovascular tissue into the peripheral

cornea), also indicate corneal inflammation. • Follicles, papillae, and these corneal signs are

features of active disease.

• Resolution of follicles may be accompanied by scarring of the subepithelial conjunctiva.

• Scar deposition is most prominent in the upper tarsal plate - Arlt's line (a horizontal line that results from conjunctival scarring at the junction of the anterior one third and posterior two thirds of the conjunctiva) is a characteristic finding on the superior pretarsal conjunctiva.

• At the limbus, replacement of follicles by scar results in the formation of translucent depressions in the corneoscleral junction called Herbert’s pits.

• If sufficient tarsoconjunctival scarring accumulates, contraction of it over the years will cause the upper eyelid to turn inward so that the lashes rub against the globe. This is known as trichiasis.

• When the whole lid margin is turned in, the condition is known as entropion.

• Secondary bacterial and fungal infections of the cornea and corneal drying due to scarring of forniceal-mucous, lacrimal, and meibomian glands accelerate epithelial damage.

GRADING SYSTEMS

FPC CLASSIFICATION

Dawson CR, Jones BR, Tarizzo ML. Guide to trachoma control inprogrammes for the prevention of blindness. Geneva: World HealthOrganization, 1981

WHO CLASSIFICATION

DIAGNOSIS

D/D

• Cicatricial conjunctivitis can be caused by mucus membrane pemphigoid, Stevens–Johnson syndrome, systemic sclerosis, chemical injuries and drugs.

• In nontrachomatous areas, most cases of entropion are due to involutional changes. Two rare congenital disorders result in lashes touching the eye: epiblepharon (upward riding of skin and orbicularis over the inferior tarsus) and distichiasis (additional row of lashes arising from the meibomian gland orifices).

MANAGEMENT

• The World Health Organization in the year 1997 formed an Alliance to work towards the Global Elimination of Trachoma by the year 2020 (GET 2020).

• The Alliance promotes the use of SAFE strategy for trachoma control.

• S = surgery • A = antibiotics • F = facial cleanliness • E = environmental improvement

SURGERY• Some advocate early surgery when one or more lashes

touch the eye, whereas others practice epilation until more severe TT develops.

• As the progression of TT can be quite swift in some people, where access to ophthalmic services is limited, surgery for mild disease is a logical approach.

• A major problem limiting the effectiveness of surgery is the recurrence of trichiasis following surgery, which can be as high as 40–60%.

• Bilamellar tarsal rotation (BLTR) was found to have the lowest TT recurrence rate and was therefore endorsed by the WHO

ANTIBIOTICS

• Currently two antibiotics are recommended for the control of trachoma: 1% tetracycline eye ointment and oral azithromycin.

• Tetracycline can clear the ocular infection if administered twice daily for 42 days but is ineffective in clearing extra ocular reservoirs. The compliance is poor for this drug.

• Oral azithromycin is well tolerated and has the advantage of good compliance. The dose is 20 mg/kg for children and 1 gm for adults (>18 years). The drug not only clears the ocular infection but also acts on the extra ocular reservoirs

• Azithromycin is not used in infants under the age of 6 months.

• The WHO currently recommends that a 6 week course of topical tetracycline be used for infants under 6 months.

• Currently 12 trachoma endemic countries are receiving azithromycin as part of a philanthropic donation from the manufacturer (Pfizer Inc.).

• There are no long-term data to guide programmes as to how long mass antibiotic treatment should be given and this remains a difficult area that requires further research.

• The current recommendation from the WHO is that three annual rounds of mass treatment should initially be given.

• After this, the community should then be re-assessed to see whether the prevalence of active disease has dropped sufficiently to discontinue treatment.

FACIAL CLEANLINESS AND ENVIRONMENTAL IMPROVEMENTS

• The F&E components of the SAFE strategy are primarily targeting the transmission of C. trachomatis between individuals

• By washing away potentially infected ocular secretions, the transmission of C. Trachomatis to others might be interrupted

• Controlling the fly population - (1) insecticide spray, (2) latrine provision

• General improvements in water supply (for face washing) and sanitation (to suppress fly populations).

• This drive has fortunately coincided with the setting of the United Nations’ Millennium Development Goals (MDG).

• The target for the seventh MDG is to halve the number of people without safe water and basic sanitation by 2015

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