20 Trachoma

Background

Definition

Active trachoma is chronic inflammation of the conjunctiva caused by infection with Chlamydia trachomatis. The World Health Organization classification for active trachoma defines mild trachoma (grade TF) and severe trachoma (grade TI). Scarring trachoma is caused by repeated active infection by C. trachomatis in which the upper eyelid is shortened and distorted (entropion) and the lashes abrade the eye (trichiasis). Blindness results from corneal opacification, which is related to the degree of entropion/trichiasis.

Incidence/prevalence

Trachoma is the world’s leading cause of preventable blindness and is second only to cataract as an overall cause of blindness.1 Globally, active trachoma affects an estimated 150 million people, most of them children. About 5·5 million people are blind or at risk of blindness as a consequence of trachoma. Trachoma is a disease of poverty regardless of geographical region. Scarring trachoma is prevalent in large regions of Africa, the Middle East, southwest Asia, the Indian subcontinent, and Aboriginal communities in Australia, and there are also small foci in Central and South America.1 In areas where trachoma is constantly present at high prevalence, active disease is found in more than 50% of preschool children and may have a prevalence of 60–90%.2 The prevalence of active trachoma decreases with increasing age, with less than 5% of adults showing signs of active disease.2 Although similar rates of active disease are observed in male and female children, the later sequelae of trichiasis, entropion and corneal opacification are more common in women than men and as many as 75% of women and 50% of men over the age of 45 years who had trachoma as children may show signs of scarring disease.3

Aetiology/risk factors

Active trachoma is associated with young age and with situations in which there is close contact between people. Discharge from the eyes and nose may be a source of further re-infection.4 Sharing a bedroom with someone who has

active trachoma is a risk factor for infection.5 Facial contact with flies is held to be associated with active trachoma, but studies reporting this relationship employed weak methods.6

Prognosis

Corneal damage from trachoma is caused by multiple processes. Scarring may cause an inadequate tear film and a dry eye may be more susceptible to damage from inturned lashes, leading to corneal opacification. The prevalence of scarring and consequent blindness increases with age and, therefore, is most commonly seen in older adults.7

Treatement options

The WHO-led campaign for elimination of blinding trachoma uses the SAFE strategy of Surgery, Antibiotics, Facial cleanliness and Environmental improvement.

Question

What are the effects of public health interventions in reducing active trachoma?

The evidence

Two systematic reviews6,8 and one additional RCT9 were identified. The first systematic review6 identified one RCT and one pilot study for an RCT, the second systematic review9 identified the same RCT and pilot study as the first review plus two subsequent RCTs (see comment below).

Promotion of face washing

Both reviews identified one RCT10 that compared promotion of face washing plus 30 days of daily topical tetracycline (ointment) versus 30 days of daily topical tetracycline alone in 1417 Tanzanian children aged one to seven years. The trial found that promotion of face washing plus topical tetracycline increased the likelihood of children having a clean face on at least two of three follow up visits, although the result was not significant (odds ratio for having

a clean face with face washing plus topical tetracycline versus topical tetracycline alone 1·6, 95% CI 0·94–2·74). The RCT also found that promotion of face washing plus topical tetracycline versus topical tetracycline alone significantly reduced the risk of severe trachoma after one year (OR for severe trachoma 0·62, 95% CI 0·40–0·97), but found that this reduction was not significant for all grades of trachoma combined (OR for mild and severe trachoma 0·81, 95% CI 0·42–1·59). The RCT found that when all participants from intervention and control villages were pooled, children who had a sustained clean face were significantly less likely to have active trachoma than those who had ever had a dirty face (OR 0·58, 95% CI 0·47–0·72). The additional RCT9 recruited 1143 children in 36 communities in Australia and compared three groups: daily face washing (performed by a teacher); daily face washing (performed by a teacher) plus daily topical tetracycline (as drops for one week each month); and no intervention. Trachoma was defined as the presence of at least one follicle or some papillae on the upper tarsal plate (this study pre-dated the present World Health Organization definition of trachoma). Losses to follow up were treated as being trachoma positive. The RCT found no significant difference between face washing alone versus no intervention in the number of children with trachoma after three months (191/246 (78%) with face washing alone versus 160/211 (76%) with no intervention; relative risk 1·0; CI not provided). It also found that face washing plus tetracycline drops versus no intervention significantly reduced the number of children with trachoma after three months (215/312 (69%) with face washing plus topical tetracycline versus 160/211 (78%) with no intervention; RR 0·9; CI not provided).

Fly control using insecticide

The reviews identified one pilot study for an RCT (414 children younger than 10 years) that compared spraying of deltamethrin for three months versus no intervention in two pairs of villages.11 One pair received the intervention or none in the wet season and one pair received the intervention or none in the dry season. There were a total of 191 children under 10 years of age in the control villages and 223 children in the intervention villages. The pilot study found that spraying of deltamethrin significantly reduced the number of new cases of trachoma (World Health Organization classification) after three months (RR 0·25, 95% CI 0·09–0·64).

Comment

Cluster randomisation used in the RCTs and the pilot study limits the power to detect differences between

groups, and makes interpretation of the results for individual children difficult.9–11 The RCT comparing promotion of face washing plus topical tetracycline versus topical tetracycline alone was too small to rule out a clinically important effect.10 The two subsequent RCTs identified by the second systematic review compared antibiotics versus health education plus face washing, and it was not possible to extract data relating to the health education and face washing interventions separately.8 The additional RCT pre-dates the simplified World Health Organization classification of trachoma, limiting the applicability of the results.9

Question

What are the effects of antibiotics in reducing active trachoma?

The evidence

There has been a Cochrane review that identified 12 antibiotic treatment trials for active trachoma.12 The comparisons were of any antibiotic treatment against placebo/no treatment and of oral antibiotic treatment against topical antibiotic treatment. A further RCT, not included in the review, has compared topical plus oral treatment with the oral antibiotic azithromycin13 and found no significant difference between treatments.

Antibiotic treatment versus placebo or no treatment

The Cochrane review of antibiotics for trachoma considered topical treatment, oral treatment or any combination compared with placebo/no treatment.12 The results of the trials that compare an oral antibiotic to placebo/no treatment and the trials that compare a topical antibiotic to placebo/no treatment show high degrees of heterogeneity in their outcomes. A synthesis of the results to give a summary statistic was therefore not performed but point estimates of relative risk were given. For the outcome of active trachoma, the trials did not show a significant effect of antibiotics but suggested a lowering of risk at three and 12 months after treatment. This was similarly the case for the outcome of laboratory evidence of trachoma.

Oral versus topical antibiotics

The Cochrane review of antibiotics for trachoma cites the results of four trials that compared an oral with a topical treatment for active trachoma.12 The results showed highly significant degrees of heterogeneity for both the outcome

measures of active trachoma and the laboratory evidence of infection. Point estimates of relative risk were given but no summary statistic was calculated because of the heterogeneity. Three of the trials were small and low powered. The fourth trial compared mass treatment in which people were treated irrespective of disease status and were randomly allocated by village (cluster randomisation). The results suggest that oral treatment is neither more nor less effective than topical treatment for the outcomes of active trachoma at three and 12 months. Azithromycin was significantly better than topical treatment at reducing laboratory evidence of infection with heterogeneity showing a P value of 0·036.

Comment

No harms were reported but adverse reactions to systemic antibiotics were not recorded in the trial protocols.

Question

What are the effects of surgical treatments for scarring trachoma (entropion and trichiasis)?

The evidence

Three RCTs were identified, two of which compared surgical interventions versus each other for entropion/ trichiasis14,15 and the third compared village-based versus health centre-based tarsal rotation surgery for major trichiasis.16

Surgical technique

The two RCTs that compared surgical interventions versus each other defined operative success as no lashes in contact with the globe in primary position of gaze and complete lid closure with gentle voluntary effort. The first RCT14 compared five surgical techniques in Omani villagers. Analysis was not by intention to treat and the power of the trial was low. The second RCT of 200 eyelids in Oman compared bilamellar tarsal rotation versus tarsal advance and rotation.15 It found that tarsal rotation significantly increased operative success after 25 months (relative risk (RR) for failure, tarsal advance and rotation v tarsal rotation 3·1, 95% CI 1·9–5·2).

Location of surgery

One RCT compared village-based versus health centrebased tarsal rotation surgery for major trichiasis.16 It found that attendance rates were not significantly different

between interventions (57/86 (66%) v 32/72 (44%); RR 1·5, 95% CI not provided). The RCT also found that there was no significant difference between interventions in operative success rate (defined as no evidence of trichiasis) after three months.

Harms

Adverse outcomes of interventions were corneal exposure, ulceration, phthisis bulbi and severe recurrent trichiasis.14 In the two RCTs that compared different surgical techniques versus each other, major trichiasis and defective closure after surgical procedures for scarring trachoma were more common after eversion splinting, tarsal advance, and tarsal grooving than after bilamellar tarsal rotation and tarsal advance and rotation.14,15 Cryoablation of the eyelashes can cause necrosis of the lid margin, corneal ulcers, and in the RCT in which cryoablation was used it was the only procedure associated with onset of phthisis bulbi (two cases out of 57).

Implications for practice

Face washing is beneficial for intense trachoma if used in conjunction with topical antibiotics. Fly spraying reduces the incidence of active trachoma. No conclusions can be drawn on the effectiveness of antibiotic treatment for active trachoma, although there is a suggestion of a reduction in the point prevalence of the relative risk for those treated with antibiotics. The bilamellar tarsal rotation procedure is the surgical procedure least associated with recurrence.

Implications for research

The WHO Global Elimination of Blinding Trachoma programme has endorsed the donation of azithromycin for the treatment of trachoma in selected countries. This provides the setting for determining whether antibiotics are an effective treatment and whether they have a place in the surgical treatment of entropion/trichiasis.

References

1.Thylefors B, Negrel AD, Pararajasegaram R et al. Global data on blindness. Bull World Health Organ 1995;73:115–21.

2.West SK, Munoz B, Turner VM, Mmbaga BB, Taylor HR. The epidemiology of trachoma in central Tanzania. Int J Epidemiol 1991;20:1088–92.

3.Courtright P, Sheppard J, Schachter J, Said ME, Dawson CR. Trachoma and blindness in the Nile Delta: current patterns and projections for the future in the rural Egyptian population. Br J Ophthalmol 1989;73: 536–40.

4.Bobo L, Munoz B, Viscidi R, Quinn T, Mkocha H, West S. Diagnosis of Chlamydia trachomatis eye infection in Tanzania by polymerase chain reaction/enzyme immunoassay. Lancet 1991;338:847–50.

5.Bailey R, Osmond C, Mabey DC, Whittle HC, Ward ME. Analysis of the household pattern of trachoma in a Gambian village using a Monte Carlo simulation procedure. Int J Epidemiol 1989;18:944–51.

6.Emerson PM, Cairncross S, Bailey RL, Mabey DC. Review of the evidence base for the “F” and “E” components of the SAFE strategy for trachoma control. Trop Med Int Health 2000;5:515–27.

7.Munoz B, West SK. The forgotten cause of blindness. Epidemiol Rev 1997;19:205–17.

8.Pruss A, Mariotti SP. Preventing trachoma through environmental sanitation: a review of the evidence base. Bull World Health Organ 2000;78:258–66.

9.Peach H, Piper S, Devanesen D et al. Trial of antibiotic drops for the prevention of trachoma in school-age Aboriginal children. Annu Rep Menzies Sch Health Res 1986:74–6.

10.West S, Munoz B, Lynch M et al. Impact of face washing on trachoma in Kongwa, Tanzania. Lancet 1995;345:155–8.

11.Emerson PM, Lindsay SW, Walraven GE et al. Effect of fly control on trachoma and diarrhoea. Lancet 1999;353:1401–3.

12.Mabey D, Fraser-Hurt N. Antibiotics for trachoma (Cochrane Review). In : The Cochrane Collaboration: Cochrane Library. Issue 1. Oxford: Update Software, 2002.

13.Bailey RL, Arullendran P, Whittle HC, Mabey DC. Randomised controlled trial of single-dose azithromycin in treatment of trachoma. Lancet 1993;342:453–6.

14.Reacher MH, Huber MJ, Canagaratnam R, Alghassany A. A trial of surgery for trichiasis of the upper lid from trachoma. Br J Ophthalmol 1990;74:109–13.

15.Reacher MH, Munoz B, Alghassany A et al. A controlled trial of surgery for trachomatous trichiasis of the upper lid. Arch Ophthalmol 1992;110:667–74.

16.Bowman RJ, Soma OS, Alexander N et al. Should trichiasis surgery be offered in the village? A community randomised trial of village v. health centre-based surgery. Trop Med Int Health 2000;5:528–33.