New Steps toward Eliminating Blinding Trachoma
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《新英格兰医药杂志》
Despite long-standing efforts to control it, trachoma remains the leading cause of preventable blindness in the world. According to the most recent estimates, some 84 million people have active trachoma (the infectious stage) in 55 countries in which the disease is endemic (Figure 1), and 7.6 million people have trachomatous trichiasis, the blinding stage of this infectious disease. Trachoma is a chronic keratoconjunctivitis caused by repeated reinfection with the ocular serotypes A, B, Ba, and C of Chlamydia trachomatis, an obligate intracellular bacterium. The infection causes a mucopurulent conjunctivitis that is generally self-healing without sequelae.
Figure 1. Countries in Which Blinding Trachoma Is Endemic.
Data are from the World Health Organization.
Repeated episodes of chlamydial infection, sometimes in association with other types of epidemic bacterial conjunctivitis, can cause chronic inflammation. This is typically characterized by subepithelial follicles (Figure 2A) and papillary hypertrophy in the tarsal conjunctiva of the upper eyelid. Vascular infiltration of the upper cornea (pannus) is common but rarely causes visual loss. Such signs of active disease are mainly seen in young children. Chronic inflammation also leads to scarring of the upper tarsal conjunctiva (Figure 2B). The scarring can progress over many years, leading to distortion of the lid margin (entropion), which tends to cause the lashes to turn inward and rub against the cornea (trichiasis) (Figure 2C). The repeated trauma to the cornea with every blink eventually leads to corneal opacity and blindness. Secondary infection with other bacteria may also contribute to the opacification of the damaged cornea.
Figure 2. Trachoma.
Repeated infection with Chlamydia trachomatis causes chronic inflammation, resulting in follicles (Panel A) and scarring (Panel B), in the form of white lines, bands, or sheets, in the tarsal conjunctiva of the upper eyelid and causing eyelashes to turn inward and abrade the cornea (Panel C). Courtesy of the World Health Organization.
In 1998, the World Health Assembly, the governing body of the World Health Organization, adopted a resolution requesting that all countries where trachoma is endemic join the effort to eliminate blinding trachoma by the year 2020.1 The World Health Organization advocates the implementation of the SAFE strategy, an integrated intervention with four facets2: surgery, antibiotics, facial cleanliness, and environmental improvement. Surgery is indicated for advanced trichiasis. For those at imminent risk for blindness because of trichiasis, a surgical intervention can reduce or eliminate the risk of corneal damage and irreversible blindness. This procedure takes about 20 minutes and consists of correcting the inward deviation of the upper eyelid, which, in turn, prevents the eyelashes from rubbing against the cornea.
Three main techniques are used around the world to restore the anatomical structure of the lids: bilamellar tarsal rotation, the Trabut method, and the Cuenod–Nataf procedure. Surgery is performed at the level of the primary health care system, mainly by trained nurses, but general practitioners and ophthalmologists may be called in to operate on patients with complicated or recurrent cases.3 Antibiotic treatment is used to eliminate the chlamydial infection, to reduce transmission of the disease within the family and the community, and to avert progression of the disease to the blinding stage.
Facial cleanliness is an important part of the intervention strategy because it helps reduce transmission of the disease, and it can be particularly effective in children, who are taught to keep the area around their eyes clean and clear of secretions throughout the day. These secretions are the means of transmitting the infection, and therefore, keeping the face clean can reduce the risk of transmission through contact with fingers or fomites (especially tissues and flies).
Environmental improvement involves interventions to reduce the population of eye-seeking flies, which can be vectors for the transmission of chlamydia. Other environmental interventions are designed to increase access to clean water and reduce extreme crowding in living spaces, which promotes transmission of the active disease, mainly among children.
Trachoma disappeared from countries such as Italy, Spain, Portugal, Greece, and Poland in the 1940s and 1950s without the use of antibiotics for trachoma control. Rather, this was the result of socioeconomic progress, with improvements in personal hygiene, the availability of safe water and latrines, and the cleanliness of the environment and a decrease in the number of persons sharing the same bed.4 When efforts toward the global elimination of blinding trachoma were reorganized in 1997, it was mainly to implement an integrated, effective (SAFE) strategy that depended, in part, on the availability of a systemic antibiotic that was effective and safe for mass treatment (azithromycin). The chief problem with antibiotic treatment was its lack of availability to the poorer communities, owing to distribution problems and cost. The latter issue was addressed by the manufacturer, Pfizer, which set up a donation program that provided national control programs with the essential medication in accordance with certain guidelines.
Since efforts to control trachoma began, the possibility of mass antibiotic treatment has been considered a step forward. Systemic antibiotics were used before the introduction of azithromycin, but they were not suitable for mass treatment, since careful follow-up was required to monitor and manage possible side effects.5
As a result of the lessons learned decades ago in countries in which trachoma was once endemic, the effectiveness of the "FE" components of the SAFE strategy in helping to maintain infection at a low, nonblinding level is undisputed. Nor is there any controversy about the need for surgery in those with trichiasis who are at immediate risk for corneal opacity and irreversible blindness. Currently, the focus is on how to ensure the timely provision of good-quality surgery to prevent sight-threatening complications.
The role of and need for antibiotics have been endlessly debated and are a matter of controversy. Some see antibiotic intervention as the "silver bullet" for the elimination of trachoma. Others see less of a role for antibiotics and believe that socioeconomic development is the only way of solving the problem. It is true that development has proved to be the definitive solution for blinding trachoma. But can the international community afford to wait for promised economic development while millions more people needlessly become blind from trachoma? The answer is certainly no. The role of antibiotics is important in communities in which trachoma is endemic because they shorten the time needed to reduce the level of infection, and, hence, the use of antibiotics contributes effectively toward the SAFE strategy to avoid unnecessary blindness.
The findings presented by Solomon et al.6 in this issue of the Journal are important. If effective, broad antibiotic coverage can be achieved and if it can sufficiently lower the prevalence of chlamydia infection for an extended period of time, it could potentially lead to new intervention schemes for communities with characteristics similar to the ones studied by Solomon et al., even if the "F" and "E" components of the SAFE strategy do take longer to be implemented.
Caution must apply in analyzing the results of this study. We must take into account that the prevalence of infection at the beginning of the study was quite low (9.5 percent before treatment), whereas in many communities around the world it can be as high as 80 percent, and the same results have not yet been achieved in the latter. The unusually high coverage achieved (97.6 percent) is again an outstanding and encouraging result. However, in countrywide interventions, such a high rate of coverage is very rare in every community in need. Although the authors explain that no changes in personal hygiene or environmental cleanliness were made in the communities during the study, we have no information about the actual status of personal hygiene or the degree of cleanliness in the communities, nor do we know whether any educational efforts or interventions took place before the study began.
A number of operational questions remain, including the optimal candidates for and frequency of treatment, the geographic distribution needed for this intervention, the length of time during which reduction of infection must be sustained before antibiotic treatment can be suspended, and the appropriate community-level diagnostic tools to be used. Knowing that in some settings mass antibiotic treatment can be more effective than has previously been recognized may give renewed strength to the efforts of the ministries of health of countries in which trachoma is endemic, as well as local and international partners. Although the social-development components of the SAFE strategy must still be implemented in communities in which trachoma is endemic to ensure the continued elimination of blinding trachoma, the findings of Solomon et al. provide useful, new information on what antibiotic treatment can achieve. Increased knowledge of the effect of different components of the SAFE strategy can be of great help to poor communities that have already paid too high a toll in the form of preventable blindness.
Source Information
From Prevention of Blindness and Deafness, World Health Organization, Geneva.
References
Governance. Geneva: World Health Organization, 2004. (Accessed October 14, 2004, at http://www.who.int/governance/en/.)
Future approaches to trachoma control: report of a global scientific meeting, Geneva, June 17-20, 1996. Geneva: World Health Organization, 1996. (WHO/PBL/96.56.)
Reacher M, Foster A, Huber J. Trichiasis surgery for trachoma — the bilamellar tarsal rotation procedure. Geneva: World Health Organization, 1993. (WHO/PBL/93.29.)
Négrel AD. La nouvelle donne dans la lutte contre le trachome. Rev Int Trach 1999;1:25-32.
Resnikoff S. Chimiothérapie du trachome. Rev Int Trach 1998;1:29-44.
Solomon AW, Holland MJ, Alexander NDE, et al. Mass treatment with single-dose azithromycin for trachoma. N Engl J Med 2004;351:1962-1971.(Silvio P. Mariotti, M.D.)
Figure 1. Countries in Which Blinding Trachoma Is Endemic.
Data are from the World Health Organization.
Repeated episodes of chlamydial infection, sometimes in association with other types of epidemic bacterial conjunctivitis, can cause chronic inflammation. This is typically characterized by subepithelial follicles (Figure 2A) and papillary hypertrophy in the tarsal conjunctiva of the upper eyelid. Vascular infiltration of the upper cornea (pannus) is common but rarely causes visual loss. Such signs of active disease are mainly seen in young children. Chronic inflammation also leads to scarring of the upper tarsal conjunctiva (Figure 2B). The scarring can progress over many years, leading to distortion of the lid margin (entropion), which tends to cause the lashes to turn inward and rub against the cornea (trichiasis) (Figure 2C). The repeated trauma to the cornea with every blink eventually leads to corneal opacity and blindness. Secondary infection with other bacteria may also contribute to the opacification of the damaged cornea.
Figure 2. Trachoma.
Repeated infection with Chlamydia trachomatis causes chronic inflammation, resulting in follicles (Panel A) and scarring (Panel B), in the form of white lines, bands, or sheets, in the tarsal conjunctiva of the upper eyelid and causing eyelashes to turn inward and abrade the cornea (Panel C). Courtesy of the World Health Organization.
In 1998, the World Health Assembly, the governing body of the World Health Organization, adopted a resolution requesting that all countries where trachoma is endemic join the effort to eliminate blinding trachoma by the year 2020.1 The World Health Organization advocates the implementation of the SAFE strategy, an integrated intervention with four facets2: surgery, antibiotics, facial cleanliness, and environmental improvement. Surgery is indicated for advanced trichiasis. For those at imminent risk for blindness because of trichiasis, a surgical intervention can reduce or eliminate the risk of corneal damage and irreversible blindness. This procedure takes about 20 minutes and consists of correcting the inward deviation of the upper eyelid, which, in turn, prevents the eyelashes from rubbing against the cornea.
Three main techniques are used around the world to restore the anatomical structure of the lids: bilamellar tarsal rotation, the Trabut method, and the Cuenod–Nataf procedure. Surgery is performed at the level of the primary health care system, mainly by trained nurses, but general practitioners and ophthalmologists may be called in to operate on patients with complicated or recurrent cases.3 Antibiotic treatment is used to eliminate the chlamydial infection, to reduce transmission of the disease within the family and the community, and to avert progression of the disease to the blinding stage.
Facial cleanliness is an important part of the intervention strategy because it helps reduce transmission of the disease, and it can be particularly effective in children, who are taught to keep the area around their eyes clean and clear of secretions throughout the day. These secretions are the means of transmitting the infection, and therefore, keeping the face clean can reduce the risk of transmission through contact with fingers or fomites (especially tissues and flies).
Environmental improvement involves interventions to reduce the population of eye-seeking flies, which can be vectors for the transmission of chlamydia. Other environmental interventions are designed to increase access to clean water and reduce extreme crowding in living spaces, which promotes transmission of the active disease, mainly among children.
Trachoma disappeared from countries such as Italy, Spain, Portugal, Greece, and Poland in the 1940s and 1950s without the use of antibiotics for trachoma control. Rather, this was the result of socioeconomic progress, with improvements in personal hygiene, the availability of safe water and latrines, and the cleanliness of the environment and a decrease in the number of persons sharing the same bed.4 When efforts toward the global elimination of blinding trachoma were reorganized in 1997, it was mainly to implement an integrated, effective (SAFE) strategy that depended, in part, on the availability of a systemic antibiotic that was effective and safe for mass treatment (azithromycin). The chief problem with antibiotic treatment was its lack of availability to the poorer communities, owing to distribution problems and cost. The latter issue was addressed by the manufacturer, Pfizer, which set up a donation program that provided national control programs with the essential medication in accordance with certain guidelines.
Since efforts to control trachoma began, the possibility of mass antibiotic treatment has been considered a step forward. Systemic antibiotics were used before the introduction of azithromycin, but they were not suitable for mass treatment, since careful follow-up was required to monitor and manage possible side effects.5
As a result of the lessons learned decades ago in countries in which trachoma was once endemic, the effectiveness of the "FE" components of the SAFE strategy in helping to maintain infection at a low, nonblinding level is undisputed. Nor is there any controversy about the need for surgery in those with trichiasis who are at immediate risk for corneal opacity and irreversible blindness. Currently, the focus is on how to ensure the timely provision of good-quality surgery to prevent sight-threatening complications.
The role of and need for antibiotics have been endlessly debated and are a matter of controversy. Some see antibiotic intervention as the "silver bullet" for the elimination of trachoma. Others see less of a role for antibiotics and believe that socioeconomic development is the only way of solving the problem. It is true that development has proved to be the definitive solution for blinding trachoma. But can the international community afford to wait for promised economic development while millions more people needlessly become blind from trachoma? The answer is certainly no. The role of antibiotics is important in communities in which trachoma is endemic because they shorten the time needed to reduce the level of infection, and, hence, the use of antibiotics contributes effectively toward the SAFE strategy to avoid unnecessary blindness.
The findings presented by Solomon et al.6 in this issue of the Journal are important. If effective, broad antibiotic coverage can be achieved and if it can sufficiently lower the prevalence of chlamydia infection for an extended period of time, it could potentially lead to new intervention schemes for communities with characteristics similar to the ones studied by Solomon et al., even if the "F" and "E" components of the SAFE strategy do take longer to be implemented.
Caution must apply in analyzing the results of this study. We must take into account that the prevalence of infection at the beginning of the study was quite low (9.5 percent before treatment), whereas in many communities around the world it can be as high as 80 percent, and the same results have not yet been achieved in the latter. The unusually high coverage achieved (97.6 percent) is again an outstanding and encouraging result. However, in countrywide interventions, such a high rate of coverage is very rare in every community in need. Although the authors explain that no changes in personal hygiene or environmental cleanliness were made in the communities during the study, we have no information about the actual status of personal hygiene or the degree of cleanliness in the communities, nor do we know whether any educational efforts or interventions took place before the study began.
A number of operational questions remain, including the optimal candidates for and frequency of treatment, the geographic distribution needed for this intervention, the length of time during which reduction of infection must be sustained before antibiotic treatment can be suspended, and the appropriate community-level diagnostic tools to be used. Knowing that in some settings mass antibiotic treatment can be more effective than has previously been recognized may give renewed strength to the efforts of the ministries of health of countries in which trachoma is endemic, as well as local and international partners. Although the social-development components of the SAFE strategy must still be implemented in communities in which trachoma is endemic to ensure the continued elimination of blinding trachoma, the findings of Solomon et al. provide useful, new information on what antibiotic treatment can achieve. Increased knowledge of the effect of different components of the SAFE strategy can be of great help to poor communities that have already paid too high a toll in the form of preventable blindness.
Source Information
From Prevention of Blindness and Deafness, World Health Organization, Geneva.
References
Governance. Geneva: World Health Organization, 2004. (Accessed October 14, 2004, at http://www.who.int/governance/en/.)
Future approaches to trachoma control: report of a global scientific meeting, Geneva, June 17-20, 1996. Geneva: World Health Organization, 1996. (WHO/PBL/96.56.)
Reacher M, Foster A, Huber J. Trichiasis surgery for trachoma — the bilamellar tarsal rotation procedure. Geneva: World Health Organization, 1993. (WHO/PBL/93.29.)
Négrel AD. La nouvelle donne dans la lutte contre le trachome. Rev Int Trach 1999;1:25-32.
Resnikoff S. Chimiothérapie du trachome. Rev Int Trach 1998;1:29-44.
Solomon AW, Holland MJ, Alexander NDE, et al. Mass treatment with single-dose azithromycin for trachoma. N Engl J Med 2004;351:1962-1971.(Silvio P. Mariotti, M.D.)