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Molecular Testing Shows Bacterial Cause of Sore Throat as Common as Strep

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NEW YORK(GenomeWeb) – Molecular testing has revealed that an anaerobic bacterium called Fusobacterium necrophorum, also referred to as fuso, may be present as often as group A and group C/G Streptococci in pharyngeal swabs from young adult patients with sore throat.

In a study published this week in Annals of Internal Medicine, researchers at the University of Alabama Huntsville Regional Medical Campus evaluated throat swabs from 312 students, ages 15 to 30, who sought treatment for sore throats at a student health clinic. They also examined swabs from 180 healthy controls.

Samples were evaluated for the presence of group A and group C/G Streptococci, and Mycoplasma pneumoniae using PCR assays. The research group also modified previously-developed PCR assays for F. necrophorum, and showed that the new test had enough analytical sensitivity to detect a single bacterium.

In the study, group A strep was detected in about 10 percent of pharyngitis cases and 1 percent of asymptomatic individuals, while group C/G strep was present in 9 percent of cases and about 4 percent of the control group. The pneumonia bacterium was discovered in almost 2 percent of patients but was not present in the asymptomatic students.

Fuso, meanwhile, was detected in more than 20 percent of patients, but also in more than 9 percent of the asymptomatic individuals.

An accompanying editorial in the journal emphasized that detection of a pathogen by PCR is "not definitive evidence of infection," and, since a viral infection may have altered the microbiome of the throat and disinhibited fuso growth, more research is called for.

Fuso can cause a severe septicemic bacterial infection called Lemierre's syndrome, sometimes referred to as "the forgotten disease," in which a bad sore throat becomes metastatic and leads to clumps of infection clogging the jugular vein.

With the advent of penicillin, mortality from Lemierre's syndrome declined and reports of the disease became rare. However, a 2009 systematic review of 84 studies suggested it may now be increasingly common.

While fuso has been known to cause Lemierre's syndrome, its relationship to pharyngitis and tonsillitis was not reported until about fifteen years ago, Robert Centor, an author on the study and a professor of internal medicine at the University of Alabama at Birmingham, told GenomeWeb.

"When penicillin first came out, everybody with sore throat got penicillin," Centor explained. Antibiotic resistance led to a focus on strep, and recommendations became, "Do rapid tests for strep, but that's the only thing we cared about," he said. "We had totally forgotten about [F. necrophorum], and its complications."

Sore throat is much more common in children, and rapid tests for strep were developed, in part, because it can cause rheumatic fever in pediatric populations, Centor said.

Fuso, meanwhile, appears to rarely affect pre-adolescents, whose sore throats are more often studied, which may explain why it has remained off the radar for so long. Clinicians also more routinely do aerobic throat cultures, so fuso may have gone under-detected.

"What we're suggesting is that, for teenagers and college students, this bacteria is at least as important, if not more important" as strep, he said. In a population of adolescents and young adults under 30 years old, Centor said he believes that fuso also causes more deaths and more complications than strep.

Centor is the eponymous author of a commonly-used assessment tool for bacterial causes of sore throat, called the Centor criteria, which was developed in the early 1980s to triage young adults in an emergency room in Richmond, Va..

These criteria are also recommended by the US Centers for Disease Control and Prevention to guide appropriate antibiotic use in acute pharyngitis.

Investigators in Europe have recently revealed that fuso may be an important cause of tonsillitis and peritonsillar abscess in teens and young adults. But this is the first US study of fuso, and the first to collect significant clinical information, Centor said.

"If we can work with somebody in industry and develop a rapid test and we can collect more data from more patients at more sites, I would bet a lot of money that we'd continue getting the same results," Centor said.

While there are no commercially available assays for fuso, strep is a very common infectious disease menu option on nucleic acid amplification testing platforms, and a number of tests are already approved as in vitro diagnostics by the US Food and Drug Administration.

Examples of companies offering nucleic acid amplification tests for strep include Becton Dickinson, Cepheid, Quidel and Roche.  Firms currently developing assays include Great Basin, Alere, and Hibergene.

Centor explained that his group's Fuso PCR assay was developed for research purposes to begin to understand the epidemiology of these infections, but added that his lab would "love to find someone to partner with to create a point-of-care or rapid test of some kind. I hope this study makes people think, maybe we ought to be looking for this."

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