BIRMINGHAM, Ala. – New research from the University of Alabama at Birmingham suggests that Fusobacterium necrophorum more often causes severe sore throats in young adults than Streptococcus pyogenes (Group A streptococcus)— the cause of the much better known strep throat. The findings, published February 17 in the Annals of Internal Medicine, suggest physicians should consider F. necrophorum when treating severe sore throat, known as pharyngitis, in young adults and adolescents that worsens.

In an analysis of 312 college students at UAB’s Student Health Clinic, investigators found that F. necrophorum was detected in more than 20 percent of patients with sore-throat symptoms, against only 10 percent for Group A strep and 9 percent for Group C or G strep.

“This is the first study in the United States that shows that F. necrophorum causes a significant number of cases of pharyngitis in this young adult population,” said Robert M. Centor, M.D., professor in the Division of General Internal Medicine in the UAB School of Medicine and the study’s lead author. “It is also the first to show that F. necrophorum pharyngitis and streptococcus pharyngitis share similar clinical signs. This study bolsters our understanding that this condition is common in the U.S. and very closely resembles strep throat.”

Centor says that F. necrophorum pharyngitis is the leading cause of a rare but potentially very dangerous condition known as the Lemierre’s syndrome. The syndrome affects mostly adolescents and young adults and is seen rarely in pre-adolescents. It often causes long, complex hospitalizations requiring intensive care, and about 6 percent of those contracting the Lemierre’s syndrome die.

Group A strep can also cause a serious disease, rheumatic fever, which remains common in many parts of the developing world, but is now rare in the U.S. The rapid test for strep and aggressive treatment with antibiotics have contributed to rheumatic fever’s decline in this country. Centor says F. necrophorum warrants the same consideration.

“It is not just about strep throat in this 15-30 age group,” said Centor. “Physicians have to consider F. necrophorum, which in our study caused more sore throats than streptococci. And F. necrophorum is itself associated with a potentially devastating complication, which while rare, is a more common side effect that acute rheumatic fever.”

The issue for physicians is that F. necrophorum pharyngitis is hard to recognize. Its signs and symptoms are very similar to those of strep throat. There is a rapid test for strep; but there is not a routine, commercially available rapid test for F. necrophorum. UAB investigators had to create their own research assay especially for this study — a real-time polymerase chain reaction or PCR test.

“We began work on the PCR test in 2009 in my research laboratory in the UAB Department of Pathology, and it was four years before we were confident that this test was accurate and sensitive enough to be able to begin data collection for this study,” said Ken Waites, M.D., a professor in the Division of Laboratory Medicine in the UAB Department of Pathology. “To our knowledge, ours is the first PCR test for F. necrophorum to be created in the United States.”

Li Xiao, Ph.D., an instructor in the Division of Clinical Immunology and Rheumatology, and a member of Dr. Waites’ research laboratory took the lead in the development of the PCR test. The UAB Department of Pathology is known for its work with Mycoplasma pneumoniae, a bacterium that causes walking pneumonia. Resources and methods originally developed by Dr. Xiao for the study of M. pneumoniae infections were integral to the development of the F. necrophorum test.

“We have a critical mass of knowledge, highly trained technical staff, and excellent facilities to do this kind of cutting-edge work,” said Waites. “And we are fortunate to have a blend of expertise from multiple disciplines such as pathology, microbiology, and immunology, along with clinical expertise from pediatrics and internal medicine.”

One of the time-consuming factors was the need to find a gene to use as a PCR target that was present in all F. necrophorum strains, but was not present in any other microorganisms likely to cause sore throats. Xiao and the team tested hundreds of strains of bacteria and viruses to be sure that the test was specific to detect F. necrophorum.

F. necrophorum is difficult to culture because it is an anaerobic bacterium requiring special methods to grow it in a lab, making it an expensive and labor-intensive process,” Waites said. “Therefore, culture is not widely used for its detection because turnaround time for results takes up to several days. We did not believe culture was a practical way to test for F. necrophorum, so we chose to develop the PCR method instead”.

While clinicians might like to have a rapid test for F. necrophorum, similar to the existing test for Group A streptococcus, Waites doesn’t anticipate that happening soon. Waites says the UAB PCR test could be adapted by a commercial company as a basis to create a viable product that could be employed in hospital laboratories, but it would not likely be suitable as a point-of-care test due to the inherent complexity of nucleic acid amplification tests. An antigen-based test similar to rapid tests for Group A streptococcus might be a better alternative for use in physician offices. The key would be convincing clinicians that such a test would be beneficial to their practices and to convince a diagnostics company to develop and sell such a test.

In the absence of a viable test for the presence of F. necrophorum, Centor suggests that treating with antibiotics empirically may be the best course of action. He says that those patients who have clinical symptoms, and score high on the Centor Score (a set of criteria used to identify the likelihood of a bacterial infection of adult patients with sore throat, named after Dr. Centor) should be considered for antibiotic treatment.

“This is the first step in a series of studies that need to be done to define the prevalence and extent of F. necrophorum and how it presents clinically,” Centor said.

The study was funded by UAB and the Justin E. Rodgers Foundation. In addition to Drs. Centor, Xiao and Waites, coauthors of the study published in Annals of Internal Medicine were T. Prescott Atkinson, M.D., Ph.D., Carlos Estrada, M.D., Michael Faircloth M.D., Walid Khalife, Ph.D., Jeremy Hatchett, M.D., Lisa Oestreich, D.O., Amy Ratliff and Donna Crabb.

About UAB

Known for its innovative and interdisciplinary approach to education at both the graduate and undergraduate levels, the University of Alabama at Birmingham is an internationally renowned research university and academic medical center and the state of Alabama’s largest employer, with some 23,000 employees and an economic impact exceeding $5 billion annually on the state. The five pillars of UAB’s mission deliver knowledge that will change your world: the education of students, who are exposed to multidisciplinary learning and a new world of diversity; research, the creation of new knowledge; patient care, the outcome of ‘bench-to-bedside’ translational knowledge; service to the community at home and around the globe, from free clinics in local neighborhoods to the transformational experience of the arts; and the economic development of Birmingham and Alabama. Learn more at www.uab.edu.

EDITOR’S NOTE: The University of Alabama at Birmingham is a separate, independent institution from the University of Alabama, which is located in Tuscaloosa. Please use University of Alabama at Birmingham on first reference and UAB on subsequent references.