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Moving Science Forward
New JAMA Study by CHORI Scientist Suggests Antibiotics Can Interfere with Protective Immunity

For the last 10 years, the World Health Organization (WHO) has been heading an ambitious project to eliminate blinding trachoma by the year 2020. No simple task, as trachoma is the second leading cause of preventable blindness in the world and already infects over 600 million people across the globe, with nearly 146 million people at risk for blindness. However, a new study just published in the Journal of the American Medical Association (JAMA) by CHORI scientist Deborah Dean, MD, MPH, has unearthed some stunning results about the WHO strategy.

“WHO’s strategy has four components called SAFE,” explains Dr. Dean. “S for surgery, A for antibiotics, F for facial cleanliness, and E for environmental improvement.”

Surgery is used to treat the in-turned eyelashes, called trichiasis, that can result from scarring due to Chlamydia trachomatis infection. The eyelashes scrape the eyeball, causing scarring over the cornea and blindness, while antibiotics are used to treat the infection itself. The other elements are geared toward decreasing the transmission of the infection.

There have been no studies, however, that assessed the efficacy of antibiotic treatment beyond 1 year in populations receiving various components of the SAFE strategy - until now.

“We were very interested in determining both the risk factors for, and the rates of occurrence of, active trachoma and chlamydial infections 3 years after the first treatment,” Dr. Dean says.

The results were not what Dr. Dean expected: the unintended consequences of the SAFE strategy, at least in its current implementation, are that those treated with antibiotics are at a far greater risk for re-infection than those who have not been treated at all.

“There was a significant increase in the rates of re-infection with chlamydiae in those populations that received targeted azithromycin compared with those that did not,” Dr. Dean says of the results, which are similar to those in a study conducted in Vancouver, British Columbia, in which the risk of re-infection increased yearly (after an initial decrease) following the introduction of a control program aimed at treating chlamydial sexually active diseases with azithromycin.

While in the short term, antibiotics might clear an infection faster, in the long term, the body isn’t allowed to build up its own immunity through the full course of the infection, which significantly increases the risks of re-infection.

“What we’ve learned from this,” explains Dr. Dean, “is that we really do need to look evaluating at all four prongs of the SAFE program, especially the F and the E because as long there is chlamydiae in the environment, these individuals will always be at risk for re-infection.”

Dr. Dean is hopeful that as a result of the study WHO will place more emphasis on the F and E components. Improved implementation of facial cleanliness and environmental improvement alone are not likely to be enough, however.

“It’s unlikely that the F and E components will make it to every corner of the globe where trachoma is endemic or that the socioeconomic status will change in these developing countries,” points out Dr. Dean.

As a result, Dr. Dean’s study also emphasizes the potential need for an element of prevention not currently available to the SAFE strategists - a vaccine.

"There's no other example in the world of an infectious disease that was eradicated by antibiotics alone, and it would be impossible to treat all 600 million people,” says Dr. Dean. “Treating everyone with antibiotics wouldn’t be ethical either, given the potential for azithromycin resistance in both chlamydiae and other pathogens."

Ultimately, Dr. Dean’s ground-breaking study raises more questions, both in terms of how to best implement the SAFE program, and in terms of understanding what the increased rates of re-infection mean for disease progression. “We have to look at the repercussions of treatment and re-infection,” explains Dr. Dean. “When people do become re-infected after antibiotic treatment, is the scarring worse or is it milder? Is the final outcome better or worse? What happens at all levels of the immune response? We don’t yet know.”

As Dr. Dean is quick to note, however, that is the very point of research. “That’s why you conduct research – to discover important findings that then lead to more questions, and more research. That’s what’s exciting about making discoveries that can move science forward - and improve people's lives.”

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Monday, May 16, 2011 11:33 PM

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