Basics

The bacterium Streptococcus pyogenes (group A Streptococcus or ‘Strep A’) can infect the upper respiratory system after a person inhales droplets containing the bacteria or gets the droplets in their mouth. People infected with the bacteria can pass it to others by coughing, sneezing, or sharing cups. Initially, strep infection will cause a sore throat and fever; it can also cause the skin rash known as scarlet fever. Children are most susceptible and often get strep throat; adults contract strep relatively rarely, although adults who are often in contact with children are at elevated risk. Strep infection is treatable with penicillin or amoxicillin. Left untreated, strep can worsen and cause kidney disease, rheumatic fever, and rheumatic heart disease, which elevate lifetime risk for heart attack and stroke. (Source: CDC)

Disease Burden

Children are most susceptible to strep A everywhere, but strep A is not usually a serious threat in wealthier countries. Rheumatic heart disease caused by strep A kills more than 300,000 people per year, primarily in low- and middle-income countries. Other conditions caused by strep A, such as necrotizing fasciitis, toxic shock syndrome, and sepsis, bring the total strep A death toll to more than half a million people per year. In addition, rheumatic heart disease caused by strep A is a chronic disease affecting more than 30 million people. In general, it is difficult to know how accurate our estimates of the strep A disease burden are, because of poor record-keeping in some of the hardest-hit places.

Treatment

Strep A is easily treated with a course of antibiotics, particularly penicillin and amoxicillin, which are well-studied, safe, and inexpensive. Other effective antibiotics such as cephalosporins are used as treatment for patients who are allergic to antibiotics in the penicillin family.

Why Are We Interested In Challenge Trials?

The lack of pharmaceutical interest in developing a Strep A vaccine can partly be explained by the cost; vaccine trials are risky and have a high failure rate. Challenge trials alleviate these problems by allowing researchers to use fewer participants, which are a large cost driver, and eliminate unsuccessful vaccine candidates earlier than otherwise. Strep A vaccines have had a “chicken and egg” problem–without proof that a vaccine works, funding is hard to find, and without funding, the trials to prove a vaccine works can’t be done. Strep A is a particularly good candidate disease for using challenge trials because it has well-known and successful rescue therapies. The success of these antibiotics makes the trials low-risk for the trial participants, and means that participants will not spread the infection to anyone else.

Current State Of The Art

The carefully screened healthy adult participants stay in the trials facility for up to five nights after having a specially chosen Strep A strain painted on the back of their throat. If they get strep throat (sore and red throat, big tonsils, sore neck glands, sometimes a fever) they are treated with antibiotics immediately. After four nights, if they still haven’t developed strep throat, they are treated with antibiotics to eradicate the strain. Either way, 24 hours after antibiotic treatment starts they are discharged home. During the stay, and at visits one week, one month, three months, and six months later, throat swabs and blood and saliva samples are collected. The first trial to prove the model was safe and reliable was funded by the Australian National Health and Medical Research Council. Upcoming challenge trials to test vaccines have been funded by the Australian Strep A Vaccine Initiative (ASAVI) and Australian Heart Foundation. (Source: All information provided directly by challenge trial principal investigator, Dr. Josh Osowicki.)