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Tip of the Iceberg
CHORI Scientist Provides Dramatic First-Time Evidence of Multiple Chlamydiaceae Species infection in Trachoma Patients

"Animals can get infected with the animal agents and develop ocular findings that are very similar to those present in humans who have trachoma - so it's not a leap to think that animal pathogens could be involved in trachoma."

An obligate intracellular organism, Chlamydia trachomatis has long been implicated in the pathogenesis of trachoma, the leading cause of preventable blindness in the world, and in sexually transmitted bacterial diseases as well. Now, however, CHORI’s Deborah Dean, MD, MPH, for the Center of Immunobiology and Infectious Diseases, reports in the January 3rd issue of PLoS Medicine, the first significant evidence that additional species of the family Chlamydiaceae may be involved.

“We randomly selected 9 households in a trachoma-endemic region in Nepal for screening, and found Chlamydia psittaci and Clamydia pneumoniae in addition to C. trachomatis in 8 of the 9 households. We were just shocked,” says Dr. Dean.

In retrospect, the results aren't that surprising, especially in countries where trachoma is endemic, which tends to be agrarian communities in which people live side by side with their animals, and in many cases, use mud made from animal feces as both fuel and housing material.

"It makes sense that these people would be much more susceptible to the same diseases that animals are susceptible to, such as C. psittaci, which is commonly found in the feces of large mammals such as ox and cattle as well as pigeons that are kept near their dwellings," explains Dr. Dean.

That said, while Dr. Dean's curiosity was piqued enough to do the radical, and test for additional species, she had no idea what she was going to find.

"It's always hindsight. Some famous people have said that you always have to be conscious of things that are obvious and keep an open mind because in science you learn the dogma, which almost teaches you not to think creatively," Dr. Dean say. "Our study could not have panned out, but it did, and now of course we wonder why didn't we think of this sooner."

"Not only are there other viable Chlamydiaceae species in the eye, but now we have inflammatory responses that correlate with the individual organisms. That's pretty strong evidence,"
Saying the study panned out is nearly an understatement, with results as dramatic as these: 50 percent of the trachoma infections were associated with strains other than ocular C. trachomatis (urogenital C. trachomatis strains as well as C. pneumoniae and C. psittaci), while 35 percent of the infections were mixed strains.

While additional studies need to be duplicated in other trachoma-endemic regions in Asia, Africa and South America in order to confirm Dr. Dean's data, the evidence is particularly conclusive when combined with the additional analyses Dr. Dean undertook on antibody responses to chlamydial heat shock protein 60 (Hsp60).

"We've previously established very strong correlations between inflammation and scarring and the presence of antibodies to C. trachomatis Hsp60 in trachoma patients," explains Dr. Dean. "We found the same thing here, only we also found that the associations with inflammation and scarring were species-specific."
This is critically important, as it suggests that these other species with which the Nepali villagers were infected are eliciting the same detrimental host-antibody response that is part of what results in disease.

"It's the heat shock component of the study that really starts to tell us that these other pathogens are important. Not only are there other viable Chlamydiaceae species in the eye, but now we have inflammatory responses that correlate with the individual organisms. That's pretty strong evidence," says Dr. Dean.
Not only that, but the results take the first steps toward solving some significant mysteries regarding the pathogenesis of trachoma infections.

"Historically we've only tested for C. trachomatis. You could have a population of 1000, with 200 of them showing clinical evidence of trachoma, but only 50 percent of those 200 showing positive PCR results for C. trachomatis," Dr. Dean says. "The theory was always that individuals resolved the infection but still had common signs of disease, or that it was just too early in the infection to detect the organism. But now it appears that there are actually other species involved that we just weren't testing for."

In addition, multiple species could also explain the many, many cases of infection and trachoma recurrence, and potentially even some of the treatment failures, if the anti-microbial treatment isn't specific, or given for long enough, for a particular species.

"I think that our findings will revolutionize the field," says Dr. Dean. "I've been working on Chlamydia for a couple of decades now, and it's a whole new arena of research that has just opened up. This is just the tip of the iceberg."

FOR COMPLETE ACCESS TO THE PLOS PUBLICATION, CLICK HERE

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Monday, May 16, 2011 11:33 PM

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