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Trachoma: Prevention of Blindness

In the mid 1990s, WHO announced a program called Vision 2020, to tackle the world's major causes of blindness. Approximately 45 million people in the world are blind, with a further 135 million visually disabled. Some 90% of these people live in the developing world. Cataract, trachoma, childhood blindness and onchocerciasis account for roughly 70% of the global burden of blindness, much of it preventable [Thylefors, 1998]. Part of this program includes the Global Elimination of Trachoma by the year 2020, the acronym for which is GET 2020. Key to this has been the international trachoma initiative (ITI), a partnership between the pharmaceutical company Pfizer and the Edna MacConnell Clarke Foundation (EMCF), a philanthropic organisation founded on the Avon cosmetic empire. EMCF had already funded much valuable work on trachoma field studies and basic science including some key studies by West and her colleagues which indicated the efficacy of simple intervention measures, such as face washing, in the prevention of trachoma. Pfizer, commendably, provided their anti-chlamydial drug, azithromycin, free of charge for use in pilot studies in 5 countries of trachoma prevention by antibiotic treatment. These were key elements in the SAFE strategy for GET 2020.

Treatment

The SAFE strategy is: Surgery (to correct eyelid defects that lead to blindness), Antibiotic therapy (to eradicate active chlamydial infection), Facial cleanliness and Environmental improvement (particularly the provision of clean water supplies). So far, surgery and antibiotic therapy dominate most programmes that have been implemented [Emerson et al., 2000]. Surgery has a sustained effect in preventing an individual going blind, but it has no effect on trachoma transmission. Eyelid surgery is cheap, about US $20 per case, and can be completed within approximately 15 minutes. One study showed that surgery performed in a village setting was more acceptable to patients than surgery performed at a more distant health centre, even though the latter may have had better facilities [Bowman et al., 2000]. Prophylactic antibiotic reduces the transmission of infection but, unless frequently repeated, has no sustained effect on disease eradication [Emerson et al., 2000]. Of the antibiotics most commonly used, oral azithromycin has a similar order of efficiency to the traditional tetracycline eye ointment, but is far easier to administer and thus achieves better patient compliance [Bailey et al., 1993; Dawson & Schachter, 1999; Schachter et al., 1999]. In calculating the dosage of azithromycin, height may be used as a convenient surrogate for weight [Munoz et al., 2003]. The work of Solomon et al., 2003 suggests that antibiotic treatment might be successful if it was targeted at all children in an endemic area under 10 years of age.

Mathematical models suggest that antibiotic therapy should be given to communities twice a year in areas with hyperendemic trachoma (>30% of children infected) and once a year in communities where trachoma is only moderately prevalent (<30% of children infected) [Lietman et al., 1999]. A Cochrane Review meta-analysis of 15 studies that randomised a total of 8678 participants concluded that there was some evidence that antibiotics reduce active trachoma, but that the results were not consistent and could not be pooled. Oral treatment was neither more nor less effective than topical treatment [Mabey & Fraser-Hurt, 2002]. For patients with trichiasis , corrective eye lid surgery is essential to prevent the development of corneal opacities, as demonstrated in a 12 year longitudinal of the natural history of trachoma in The Gambia [Bowman et al., 2001].

A colateral effect of the widespread use of azithromycin for trachoma eradication might be the induction of azalide resistance in pneumococci, which are even more important pathogens in the developing world. While this situation clearly needs to be watched, Gaynor et al., 2003 working in Nepal were unable to identify enhanced resistance occurring in pneumococci.

Sustainable reductions in transmission are most likely through the F and E components of SAFE [Emerson et al., 2000]. Taken together, environmental improvement with improved hygiene, better access to water and better sanitation and education reduce trachoma transmission which must eventually lead to the disappearance of blinding sequelae. However, the transmission routes and factors that cause this reduction are not known. Consequently no single specific F and E tools are in place. Evidence from intervention studies indicates that the promotion of face-washing yields modest gains for intense educational effort, raising the question for how long the effect will be sustained once health educators have left a village.  Other studies have shown that latrines, improved access to water or reduction in eye-seeking flies are associated with a lower prevalence of active trachoma or with reduced transmission. This suggests that the beneficial effects of a combination of improved water supplies, provision of latrines [Courtright et al., 1991], facial hygiene promotion through established infrastructure and control of eye-seeking flies may be long term and sustainable. Each of these interventions offers other tangible public health benefits. However, Kuper et al., 2003 in a review of the SAFE strategy concluded that there was general acceptance of the efficacy of the antibiotics and surgery component but less clear evidence for a beneficial effect of the health education or environmental improvement components. While the main aim of the SAFE program is to reduce trachoma infection to a level where blindness would be minimal, Gaynor et al., 2003b report that multiple mass antibiotic treatments alone may be sufficient to eliminate infection in an area with modest disease.

Preliminary Results

The following information is abstracted from the review article for the International Chlamydia Conference  [see: Antalya conference report] in June 2002 [Knirsch et al., 2002].  

Approximately 4 million doses of Zithromax had been donated by Pfizer to support the ITI program from its start in 1998. By the end of 2002 it is expected that 10 million doses will have been donated. So far no evidence of azithromycin resistance in C. trachomatis has been observed as a result of the program [see: antibiotic resistance in Chlamydia]. However in Aboriginal communities with access to antibiotics and baseline pneumococcal resistance, a single dose of azithromycin, worryingly, lead to hugely increased colonisation with macrolide-resistant pneumococci [Leach et al., 1997] but beneficial effects on group A streptococci [Shelby-James et al., 2002].  The ITI-supported programming covers approximately 20% of the world's trachoma endemic regions. The five priority countries originally selected by WHO were Ghana, Mali, Morocco, Tanzania and Vietnam. These countries were considered to be relatively stable, with the necessary infrastructure to make a success of the SAFE strategy. 

Tanzania: Since 1999 Zithromax treatment reached more than 700,000 Tanzanians leading to an overall reduction in the prevalence of disease of 24.3% in program villages versus 12.1% in non program villages. Many of the program villages are remote, with many people living on less than USD $1 per day, but with the BBC World Service Trust providing radio health education messages. Initial efforts in Tanzania have been positive. Nevertheless it is clear that antibiotics alone in hyper-endemic regions are insufficient; it is necessary to implement the whole SAFE strategy. Lynch et al 2003 found it more effective to treat individuals with azithromycin using community volunteers rather than village government personnel.

Morocco: A major governmental control program decreased the prevalence of disease from 28 to 6.5% among the 1.5 million people living in program areas. Trachoma is now confined to the 5 southern provinces bordering on the Sahara. Indeed, Morocco may become the first country to eliminate trachoma using the SAFE strategy. More than 1 million doses of azithromycin have been donated, with about 90% of the eligible population receiving treatment. A major effort is now going into health education and into corrective eyelid surgery. This represents a huge achievement, though trachoma has been decreasing in N Africa for some time.

Ghana and Mali: SAFE programs launched in 2000 and 2001 respectively.

Vietnam: Trachoma control program launched, building on existing prevention of blindness program. Significant organizational capacity suggests that Vietnam may be the first country in Asia to eliminate blinding trachoma using the SAFE strategy.

Central Australia: Not part of the ITI programme. However evaluation of a SAFE-style trachoma control programme found a prevalence of trachoma among children of 40% (95% CI, 32%-46%) at baseline, 33% (95% CI, 26%-40%) at 7 months' follow-up and 37% (95% CI, 29%-46%) at 21 months. These proportions were neither clinically nor statistically significantly different. Efficacy of the SAFE programme was probably compromised by population mobility, with only 32% of residents appearing in all three censuses. Inadequate housing, crowding and concerns about antibiotic compliance were also problems [Ewald et al., 2003]. Johnson & Mak, 2003 considered that a SAFE type campaign was appropriate for endemic regions of Australia but questioned whether there was sufficient national coordination or willingness.

[MEW comment: The ITI program is an excellent example of a public - private initiative which has achieved major logistic success. However it is important to remember (i) that trachoma was and is a declining disease anyway and (ii) that the countries targeted by the program were those countries where success was most likely to be achieved. In countries like Ethiopia, where in many communities more than 70% of children have evidence of active trachoma and 7% of women over age 35 have trichiasis, the challenge is much greater. But as Chuck Knirsch points out, it would be a mistake not to take the opportunity to eliminate a significant cause of world blindness. However there are other problems. So far the strategy has heavily relied on antibiotic (azithromycin). The problem is: (i) antibiotics have a transient rather than sustained effect, so that treatment has to be repeated and the effort may ultimately not be sustainable; (ii) antibiotic use against chlamydiae may lead to collateral damage in the form of antibiotic resistance among important bacterial pathogens like pneumococci. Given that nearly 10 million doses of azithromycin have or are about to be dispensed in the developing world through the ITI program, it is alarming that we know so little about whether this is a real problem, or not. Further studies in other settings on the collateral impact of single dose azithromycin on antibiotic resistance in pneumococci & other bacterial pathogens are urgently required].

[MEW] September 2003

NEXT: Trachoma in history

References

Bailey, R. L., Arullendran, P., Whittle, H.C. & Mabey, D. C. (1993). Randomised controlled trial of single-dose azithromycin in treatment of trachoma. Lancet 342, 3453 - 3456.

Bowman, R. J., Soma, O. S., Alexander, N. et al., (2000). Should trichiasis surgery be offered in the village? A community randomised trial of village vs. health centre-based surgery. Tropical Medicine and International Health 5, 528 - 533. Full article. [Blackwell]

Bowman, R. J., Jatta, B., Cham, B., Bailey, R. L., Faal, H., Myatt, M., Foster, A. & Johnson, G. J. (2001). Natural history of trachomatous scarring in The Gambia: results of a 12-year longitudinal follow-up. Ophthalmology 108, 2219 - 2224.

Courtright, P., Sheppard, J., Lane, S., Sadek, A., Schachter, J. & Dawson, C. R. (1991). Latrine ownership as a protective factor in inflammatory trachoma in Egypt. British Journal of Ophthalmology 75, 322 - 825.

Dawson, C. & Schachter, J. (1999). Can blinding trachoma be eliminated world wide? Archives of  Ophthalmology 117, 974.

Emerson, P. M., Cairncross, S., Bailey R. L. & Mabey, D. C. (2000). Review of the evidence base for the 'F' and 'E' components of the SAFE strategy for trachoma control. Tropical Medicine and International Health 5, 515 - 527. Full article

Ewald, D. P., Hall, G. V. & Franks, C. C. (2003). An evaluation of a SAFE-style trachoma control program in Central Australia. Medical Journal of Australia 178, 65 - 68. Full article

Gaynor, B. D., Holbrook, K. A., Whitcher, J. P., Holm, S. O., Jha, H. C., Chaudhary, J. S., Bhatta, R. C. & Lietman, T. (2003). Community treatment with azithromycin for trachoma is not associated with antibiotic resistance in Streptococcus pneumoniae at 1 year. British Journal of Ophthalmology 87, 147 - 148.

Gaynor, B. D., Miao, Y., Cevallos, V., Jha, H., Chaudary, J. S., Bhatta, R. et al., (2003b). Eliminating trachoma in areas with limited disease. Emerging Infectious Diseases 9, 596 - 598. Full article (html)

Johnson, G. H. & Mak, D. B. (2003). An evaluation of a SAFE-style trachoma control program in central Australia. Medical Journal of Australia, 179, 116 - 118. Full article (html) [Commentary on Ewald et al., 2003].

Knirsch, C., MeCaskey, J., Chami-Khazraji, Y., Kilima, P., West, S. & Cook, J. (2002). Trachoma elimination and a public private partnership: the International Trachoma Initiative (ITI). In: Chlamydial Infections: Proceedings of the 10th international symposium on human chlamydial infections (Schachter J et al., eds)., pp 485 - 494, published by International Chlamydia Symposium San Francisco CA 94110. ISBN 0-9664383-1-0.

Kuper, H., Solomon, A. W., Buchan, J., Zondervan, M., Foster, A. & Mabey, D. (2003). A critical review of the SAFE strategy for the prevention of blinding trachoma. Lancet Infectious Diseases 3, 372 - 381.

Leach, A. J., Shelby-James, T. M., Mayo, M., Gratten, M., Laming, A. C., Currie, B. J. & Mathews, J. D. (1997). A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clinical Infectious Disease 24, 356 - 362.

Lietman, T., Porco, T., Dawson, C. & Blower, S. (1999). Global elimination of trachoma: how frequently should we administer mass chemotherapy? Nature Medicine 5, 572 - 576.

Lynch, M., West, S., Munoz, B., Frick, K. D. & Mkocha, H. A. (2003). Azithromycin treatment coverage in Tanzanian children using community volunteers. Ophthalmic Epidemiology 10, 167 - 175.

Mabey, D. & Fraser-Hurt, N. (2002). Antibiotics for trachoma (Cochrane Review). Cochrane Database Systematic Reviews 2002;(1) CD001860. [Interesting review and conclusion. Denise not David Mabey].

Mariotti, S. P. & Pruss, A. (1999). Preventing trachoma. A guide for environmental sanitation and improved hygiene. World Health Organisation Prevention of Blindness Program. Full article

Munoz, B., Solomon, A. W., Zingeser, J., Barwick, R., Burton, M., Bailey, R., Mabey, D., Foster, A. & West, S. K. (2003). Antibiotic dosage in trachoma control programs: height as a surrogate for weight in children. Invest Ophthalmol Vis Sci. 44, 1464 - 1469.

Negrel, A. D., Mariotti, S. P. (1998). WHO alliance for the global elimination of blinding trachoma and the potential use of azithromycin. International Journal of  Antimicrobial Agents. 10, 259 - 262.

Schachter, J., West, S. K., Mabey, D. et al., (1999). Azithromycin in control of trachoma. Lancet 354, 630 - 635.

Shelby-James, T.  M., Leach, A. J., Carapetis, J. R., Currie, B. J. & Mathews, J. D. (2002). Impact of single dose azithromycin on group A streptococci in the upper respiratory tract and skin of Aboriginal children. Paediatric Infectious Disease Journal 21, 375 - 380.

Solomon, A. W., Holland, M. J., Burton, M. J., West, S. K., Alexander, N. D., Aguirre, A., et al., (2003). Strategies for control of trachoma: observational study with quantitative PCR. Lancet 362, 198 - 204. Full article

Thylefors, B. (1998). A global initiative for the elimination of avoidable blindness. American Journal of Ophthalmology 125, 90 - 93.

Thylefors, B., Dawson, C. R., Jones, B. R. et al., (1987). A simple system for the assessment of trachoma and its complications. Bulletin of the World Health Organisation 65, 477 - 483.

Web resource

WHO Prevention of Blindness web site on the elimination of trachoma (GET 2020).

NEXT: Trachoma in history