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Localized Aggressive Periodontitis: Pinning Down the Long Suspected Role of Aa

Media: The Inside Scoop

February 2008

Photo of Dr. Daniel FineFor dentists who treat an occasional child with localized aggressive periodontitis, or LAP, the research points to the likely culprit as a bacterium with a long name, Aggregatibacter actinomycetemcomitans (Aa).  But the case remains far from air tight.  Absent from the scientific literature are clinical studies that track the natural history of the disease in children and whether Aa indeed plays a role in its onset and progression.  In the December 2007 issue of the Journal of Clinical Microbiology, a team of NIDCR supported scientists offer the first results from a natural history study.  While a final verdict remains to be rendered, this study and a similar one in Morocco offer stronger evidence that Aa might just be a cause.  To learn more about this study, the Inside Scoop spoke with Dr. Daniel Fine, a scientist at the University of Medicine and Dentistry of New Jersey in Newark and the lead author on the JCM  paper. 


How rare is LAP? 

Localized aggressive periodontitis occurs in about 2 percent of African Americans, 1 percent of Hispanics, and .1 percent or less of Caucasians.  At our clinic here in New Jersey, we see maybe 10 patients per year with the condition.  So it’s relatively rare that dentists treat LAP, which typically involves the first molars.  That’s made it difficult to organize the needed clinical studies to pin down the long suspected role of the oral bacterium Aggregatibacter actinomycetemcomitans either in causing or contributing to the condition.

Let's use the acronym Aa.  How did this bacterium get stuck with such a long name? 

Well, its original name – Actinobacillus actinomycetemcomitans  - was coined by a German microbiologist named Klinger in 1912.  He isolated it from a person with a large jaw abscess.  The organism was found in conjunction with Actinomyces israelii, which is a gram-positive rod.  So, “commitans” means in common with actinomyces. 

He clearly wasn't in advertising. 

No, and the bacterium recently has been reclassified and placed into the Aggregatibacter genus.  So, Aa has picked up a few more syllables.

And why is it important to define the role of Aa in childhood periodontal disease? 

Well, number one, the disease tends to affect minority groups that often lack access to health care.  Therefore, it’s worth studying to help these kids keep their teeth.  Number two, the organism possesses several potentially dangerous pathogenic mechanisms. 

Do you mean its ability to stick to surfaces? 

That’s a big part of it.  Although LAP is relatively rare, Aa is a common member of the oral biofilm, the sticky, polymicrobial plaque that reforms on our teeth after brushing.  We estimate the bacterium is present in the mouths of about 20 percent of the people that we examine.

Twenty percent? 

Yes, that’s one of the big mysteries.  Why does Aa behave in most kids and adults but becomes an opportunistic oral pathogen in others?  As you mentioned, Aa sticks to everything.  So it tends to be an early colonizer of teeth and thus an initiator of the oral biofilm.  But Aa can slip into the bloodstream and, because it sticks to everything, contribute in some still undefined way to biofilms elsewhere in the body.  A recent study in Norway analyzed the aortic aneurysms from a large number of patients who had undergone aneurysm repair.  A surprisingly high percentage of the biopsied heart tissue contained Aa.  Moreover, several other studies have found Aa in atherosclerotic plaques or vessel walls.  Does this mean Aa can contribute to forming coronary blockages?  We have no idea.  But the finding suggests that this organism is one that we should take seriously. 

Can Aa also be virulent? 

Well, that’s another part of the equation.  Aa is endowed with genes to produce leukotoxin and cytolethal distending toxin. Every time these toxins have been found in other micro-organisms, they have been associated with an infectious disease.  So, turning back to the mouth, our work on LAP offers one of the best opportunities clinically to put this bug under the microscope, so to speak.     

Well, how did you pull together this study? 

We reached out to the local schools here in Newark.  The student population is predominantly African American and Hispanic, or those most at risk for LAP.  We’re in the process of providing baseline oral examinations to more than 3,000 school kids, ages 11 to 17. We’ve already done so for the first thousand, and that’s the data that we’ve just published. 

What did you find? 

In this first cohort, Aa was present in 147 kids.  That translates to 14.7 percent, which is about what we expected in this age group.  We divided our initial cohort of 1,075 students into two subgroups:  58 students who were healthy and Aa-negative, and 38 students who were in good oral health at baseline and Aa-positive.  Our group performed follow up oral examinations every six months to see which kids broke down over time and developed periodontal disease.

How did you define the "break down"?

Loss of tooth-supporting bone.  Obviously, this is not an ideal clinical endpoint.  We want to save every tooth.  But our examinations were performed biannually, and LAP can flare up and progress to bone loss within days or weeks.  That’s the nature of the disease.  In fact, according to its standard clinical criteria, LAP can only be definitively diagnosed after observing soft tissue changes and bone loss. 

So, what did you find in the study? 

We found eight of the kids with Aa broke down, and none without the bacterium broke down.  That reaffirmed that Aa could conceivably be a cause of the disease.  Now, we also did something else with the help of our friend and biostatistician Dr. Jack Gunsolley, whereby he looked at the progression of the disease from A to Z.  That would be health, inflammation, a periodontal pocket, loss of tooth attachment, and bone loss.  He found that at every level the individuals who stayed healthy were Aa negative.  Only the kids with Aa broke down.  That offered additional evidence that Aa might be the cause of disease. 

But you also got a surprise?

That’s right.  Unbeknownst to us, a group of Danish researchers had been conducting a similar study in Morocco.  Their data were just published in The Lancet with basically the same results, although they found that the Moroccan kids had an especially virulent form of Aa.  From my perspective, it was unbelievably exciting to see our data essentially confirmed almost immediately. 

Where does your study go from here? 

Well, we had eight kids who broke down in the Aa positive group.  But we had 30 who stayed healthy.  So, what’s different about the eight who progressed and the 30 kids who didn’t?  We banked saliva from seven of the kids, pre and post break down.  We also banked saliva from those who remained without disease.  We’re now using a very sensitive laboratory technique to evaluate the changes over time of 21 inflammatory molecules called cytokines suspended in the saliva.  We haven’t published the data yet.  But let’s just say that the research story continues to get better.

How so? 

Our primary goal from the start has been to find some way to prevent tooth loss for kids at risk of LAP.  The challenge has been to detect that risk before the disease flares up.  I think we’re moving in the right direction, and the next several months and years should be very interesting. 

I should add that we’re also collaborating with scientists at Forsyth Research Institute on a new protocol.  We’ll collect plaque from a first molar, looking at Aa and its relationship to 200 organisms in the oral biofilm.  What’s interesting is if this study involved adult periodontitis, you’d have to look at 28 teeth.  In this case, you pretty much know that LAP will affect the first molars.  So, that’s the beauty of this model.  We’re collecting plaque from those four teeth and banking it along with the saliva.  Then, retrospectively, if some of these kids develop LAP, we’ll analyze the plaque before, at the time of breakdown, and then perhaps after.  We’ll also look at this saliva before and after.  We’re hoping to put together a scenario that will tell us the organisms that associate with Aa and immune cells and other host factors that are associated with disease progression.  So, that’s where we’re hoping to go.

Thanks for the update.

My pleasure.




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This page last updated: February 26, 2014