Why your child's strep throat keeps coming back

Every year, some 600 million people worldwide contract strep throat. But for some children (and their parents), it's more than an occasional misery. It's a recurring nightmare. However, it was difficult to understand why some children are prone to repeated episodes of strep throat while others seem more or less immune. The latest study by researchers at the La Jolla Institute of Immunology (LJI) provides early clues as to why some children are more likely than others to contract streptococcal tonsillitis. recurrent group A, better known as strep throat.

Their conclusions, published in the February 6, 2019 issue Translational medicine science, suggest that recurrent tonsillitis is a multifactorial disease in which immunological factors combined with underlying genetic susceptibility allow Group A streptococci to invade the throat of some individuals again and again. Better understanding why some children do not develop protective immunity also opens the door to developing a vaccine against strep throat, according to the researchers.

"We have more than 100 years of experience in treating this disease, but nothing really helps to explain why some children suffer from strep throat recurrence," said the author Lead of the study, Shane Crotty, Ph.D., professor at the Vaccine Division. Discovery. "We believe that it is the first strong evidence that there is an important immunologic component as well as a genetic component that together contribute to recurrence of angina." streptococcal, let's try to use it. "

"Repeated angina pectoris is the second most common indication for the removal of tonsils in children, and, like every surgical operation, carries some risk, but recent evidence suggests that tonsillectomy may increase the number of tonsillitis." risk of diseases of the upper respiratory tract in the long term, "says the pediatrician. Otorhinolaryngologist and Lead Co-Author Matthew Brigger, MD, MPH, Head of Division of Otolaryngology at Rady's Hospital Children's Hospital San Diego. "I hope that as we learn more about the causes of repetitive streptococcal infections, we will be able to intervene before they happen."

Strep throat is one of many conditions caused by the bacteria. Streptococcus pyogenes, better known as Group A Streptococcus (GAS). It can cause pneumonia, scarlet fever, impetigo, which causes extremely infectious skin lesions and necrotizing fasciitis, the dreaded disease that nourishes the flesh. Unlike necrotizing fasciitis, strep throat is easily treated with antibiotics. But if you do not diagnose it, it can also lead to serious complications.

"Here in the US, we rarely see the consequences of untreated GAS infections," says physician and infectious disease specialist Jennifer Dan, MD, Ph.D. Dan holds an badociate position Clinic at LJI, which allows him to split his time between visiting patients at UC San Diego and advanced research in the Crotty lab. "However, strep throat recurrences are a major concern in developing countries, as children not treated with antibiotics run a real risk of contracting rheumatic fever or acute rheumatic heart disease, major cause of acquired heart disease." among young adults around the world. "

In trying to understand the long-standing mystery of why some children are prone to frequent tonsillitis attacks and what their immune response looks like, the researchers turned to the tonsils. The tonsils are structures resembling lymph nodes located on each side of the back of the throat. Small pockets, or crypts, on their surface, collect and sample microbes and can become fertile ground for GAS.

Dan took tonsil tissue from a cohort of children aged 5 to 18 who had a tonsil removed either because they had multiple episodes of strep throat or when they had underwent tonsillectomy for unrelated reasons, such as sleep apnea. She was particularly interested in germinal centers, the central centers where B cells must team up with helper follicular T cells (Tfh cells) to start producing antibodies.

In addition to a significant decrease in the frequency of helper B cells and follicular helper T lymphocytes, the tonsils of children with recurrent tonsillitis generally exhibited ever smaller areas of germinal centers. "These kids have a bad germ-center response," says Dan. "Interestingly, it is badociated with a particularly weak antibody response to SpeA, which is an important aspect of protective immunity."

Abbreviation for streptococcal pyrogenic exotoxin, SpeA is not an essential component of the GAS genome. However, a particularly potent version of the toxin appeared in the bacteria in the 1980s and these strains quickly swept the world to become the most common cause of strep throat. Children in the control group had high titers of anti-SpeA antibodies, which indicated that they had been exposed to the bacteria but had not become ill.

In children with recurrent GAS tonsillitis, the disease was likely to affect the family, suggesting a genetic component. Genetic testing revealed two specific genetic variants in the HLA region, which determine how pathogens interact with the immune system, which were badociated with increased susceptibility to recurrent tonsillitis and one that protected against the disease.

"Since the immunological link as well as the genetic link are all related to an insufficient antibody response against SpeA, this suggests that recognition of this factor is actually a key issue for these children," says Crotty. "Having a vaccine that drives the immune system in advance may be able to stimulate a protective immune response that can prevent recurring access to tonsillitis."

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Institute of Immunology La Jolla