A Leading Cause of Blindness May Be Controlled by Simple Course of Oral Antibiotic
A study published in the Aug. 21 issue of The Lancet provides evidence that treating entire communities with a short course of the oral antibiotic azithromycin is more effective than the standard six-week course of daily tetracycline ointment in controlling development of trachoma. Children are particularly vulnerable to infection by the bacterium Chlamydia trachomatis, which results in trachoma, a leading cause of preventable blindness in the world.
"We have known for decades that we had the antibiotics to successfully treat this disease when cases developed, but we didn’t seem to have the right drug delivery method to control the infection over time. Now we know that we do, and we are very excited at the promise of these results," says Julius Schachter, Ph.D., professor of laboratory medicine at the University of California at San Francisco (UCSF) and lead investigator of the study.
Trachoma affects the inner eyelid. Of the nearly 600 million people living in trachoma endemic areas, 150 million have active disease as conjunctivitis. After repeated episodes, which begin in childhood, scarring occurs, and the eyelids turn inward causing damage to the cornea. Total blindness occurs in middle to late life. In endemic communities, 25 percent of individuals age 50 to 60 may become blind. Blind adults may not be able to earn a living and can be an economic burden to families and communities.
"Six million people around the world are blind or severely disabled due to this disease," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). "Treatment of trachoma with azithromycin provides long-term benefits not usually available for people in developing countries." Thomas C. Quinn, M.D., of NIAID and Johns Hopkins University is a co-author of the study. NIAID, the Edna McConnell Clark Foundation, Abbott Laboratories and Pfizer Inc supported the study.
Since the 1950s, the standard treatment for trachoma has been daily application of tetracycline ointment in the inflamed eye for six weeks. In the UCSF study, researchers compared the effect of the two antibiotic regimens on infection rates in villages located in trachoma endemic areas where transmission of infection is high. The villages were in the African countries of Egypt, The Gambia and Tanzania. Village-by-village comparison of treatments showed that three doses of oral azithromycin at one-week intervals reduced levels of chlamydial infection significantly more than the standard tetracycline regimen delivered by health providers. Furthermore, village-wide treatment with azithromycin resulted in a 60 to 90 percent decrease in infection rates a year later.
The authors conclude that the effective reduction of chlamydial infection, coupled with the ease of administration, make azithromycin an important component of trachoma control programs. Although azithromycin costs more than tetracycline ointment, the expense may be offset by the higher costs of distributing and administering multiple doses of the ointment.
Treatment with antibiotics is one of several steps in a comprehensive trachoma control strategy called SAFE: Surgery for advanced disease; Antibiotics to treat and prevent infections; Face washing and good personal hygiene; and Environmental improvements, such as better access to clean water and sanitation and health education. The strategies of SAFE, including treatment with azithromycin, may provide substantial benefit to people in endemic areas by reducing both individual infections and persistence of infection in low-prevalence areas.
"Last November, as a result of these research findings, Pfizer and the Edna McConnell Clark Foundation pledged $66 million to eliminate blinding trachoma. A key component is Pfizer’s donation of Zithromax,® their trade name for azithromycin, which the World Health Organization (WHO) now recommends for the treatment of trachoma," says Penny Hitchcock, D.V.M., chief of the sexually transmitted diseases branch of the NIAID. Pfizer and the Edna McConnell Clark Foundation founded the International Trachoma Initiative, an independent agency using azithromycin in the SAFE strategy to control trachoma in Tanzania, Morocco, Mali, Ghana and Vietnam.
C. trachomatis infects not only the eyes, but the nose, throat, genital tract and rectum as well. The eye infection is transmitted easily from person to person by hand-to-eye contact, possibly aided by flies attracted to the sticky discharge from the eyes. In earlier studies in Tanzania and The Gambia, many children who had been treated with topical tetracycline showed evidence of recurring infection within weeks of treatment. The ointment treats only eye infections and is very short-acting. Oral antibiotics that work throughout the body are more effective for treating trachoma than antibiotic ointment. Although short-acting oral antibiotics also can be used to treat the infection, the need for repeated doses makes them less effective compared with fewer doses of a longer-acting oral antibiotic.
According to the Lancet report, short-course azithromycin proved to be an efficient and effective way to treat many people. "In our study, the advantage of oral azithromycin will be even greater because of the good compliance that can be achieved," says Dr. Schachter. "In these studies, health care workers made extraordinary efforts to administer topical tetracycline. In most treatment programs for endemic trachoma, eye ointment is provided to families for treatment, so topical drug delivery is probably lower than in this study."
As the study designers expected, at all sites the prevalence of trachoma was highest in children—greater than 30 percent in children younger than 10 years old. Traditionally, children have been targeted for intervention, but an appreciable number of older individuals also tested positive for the bacterium.
"A goal for this study was to assess control of trachoma through treatment of entire communities," Dr. Schachter explains. "This study not only shows that a short course of oral antibiotic achieves greater patient compliance than the longer term traditional treatment, but that control of this disease can be achieved through treatment of all individuals within a community. The results indicate that with azithromycin, trachoma control is an attainable goal."
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Reference: J. Schachter, et al. Azithromycin in control of trachoma. Lancet 354(9180):630-35 (1999).
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