A recent article by House et al. in The Lancet* described a study of mass distribution of antibiotics to prevent trachoma. Trachoma is a debilitating disease that results in blindness, is one of the “neglected tropical diseases, and is more prevalent in children under age 10. The goal of the mass distribution approach is to disrupt the transmission cycle enough to eliminate infection and promote “herd protection” in the community. This strategy is promising as a means of preventing trachoma in developing country communities and mass treatment distribution has been used with several parasitic diseases.
Caused by the same bacterium that causes sexually transmitted Chlamydia (Chlamydia trachomatis), trachoma is commonly treated with antibiotics azithromycin and tetracycline. The strategy of mass distribution of these antibiotics, successful in preventing trachoma in this study, has also shown promising results in other studies. For those at risk of trachoma and other disabling diseases, mass treatment distribution is a viable strategy to fight disease. If the disease can be eliminated via transmission interruption, the benefit of mass treatment would be apparent. However, unlike vaccine distribution campaigns, immunity is not conferred with widespread distribution of drugs; distribution efforts would need to continue until transmission can be sufficiently interrupted to result in local elimination of the disease.
So far, C. trachomatis has not developed significant resistance to the antibiotics used in the mass treatment campaigns. However, a concern is that other bacteria living in the region will develop resistance to the drugs, which are used to treat other infections. Viral and bacterial resistance to drugs is becoming more common, reducing the effectiveness of these treatments and requiring the use of more expensive second- or third-line drugs to treat infections.
Although drug resistance is already problematic for some diseases, such as tuberculosis, widespread resistance to antibiotics and antivirals would have a devastating impact on the ability to treat disease. Using drugs needed for treatment as part of a large-scale prophylactic strategy may accelerate the development of drug resistance. Given the long timeline for producing new antibiotics and antivirals, the difficulty of developing new and effective strategies, and the added costs of having to switch to more expensive second-line drugs to treat patients, it is worth considering whether the short-term gain is worth the long-term problems. In the case of trachoma, it may be worth it if the disease can be eliminated locally. We understand the probable benefits, but are we prepared for the potential consequences of this type of intervention?
*House JI, Ayele B, Porco TC, Zhou Z, Hong KC, Gebre T, Ray KJ, Keenan JD, Stoller NE, Whitcher JP, Gaynor BD, Emerson PM, Lietman TM. 2009 Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomized trial. Lancet 373 (9669): 1111-1118.
Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection. Theoretically, elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities, which is similar to herd protection in vaccine programmes. We assessed indirect protection against trachoma with mass azithromycin distributions.
In a cluster randomised trial, 24 subkebeles (government-defined units) in Amhara, Ethiopia, were randomised, with use of a simple random sample, to distribution four times per year of single-dose oral azithromycin to children aged 1—10 years (12 subkebeles, 4764 children), or to delayed treatment until after the study (control; 12 subkebeles, 6014 children). We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles, and at 12 months between the treated and control subkebeles. Health-care and laboratory personnel were blinded to study group. Analysis was intention to treat. The study is registered with clinicaltrials.gov, number NCT00322972.
At 12 months, 637 children aged 1—10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48·4% (95% CI 42·9—53·9) to 3·6% (0·8—6·4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (≥11 years) was 47% (95% CI 33—57) less than baseline (p=0·002), and 35% (95% CI 1—57) less than that in untreated communities (p=0·04).
Frequent treatment of children, who are a core group for transmission of trachoma, could eventually eliminate infection from the entire community. Herd protection is offered by repeated mass antibiotic treatments, providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable.
National Institutes of Health.