Vaccine Development Nears Warp Speed as SAVAC Doubles Down on Strep A Seven

Strep A Seven Status Quo, SAVAC

Since the recent publication of best practice monitoring methods for seven diseases caused by group A Streptococcus (strep A), public health researchers have been working hard to pinpoint a number of crucial sentinel sites where they might be put into effect. According to Chris Van Beneden, M.D., MPH, co-chair of the Strep A Vaccine Global Consortium (SAVAC) Burden of Disease Working Group in charge of developing the protocols, harmonizing case definitions and the surveillance methodologies is a crucial step in accelerating the development of a secure, reliable, and cost-effective strep A vaccine to prevent these illnesses.

Being able to produce a wide range of illnesses, from minor infections to ones that can be fatal, makes streptococcus A bacterium both interesting and problematic. The seven diseases for which protocols have been devised are the most important, either because they are widespread (such as pharyngitis or impetigo) or because they constitute a route for more serious outcomes (such as acute rheumatic fever and rheumatic heart disease) by immunological sequelae.

Van Beneden, who will retire in 2020 and currently works as a consultant, has a long history of working on both domestic and international surveillance for bacterial infections. For the Centers for Disease Control and Prevention, she directed epidemiologic research, public policy development, and public health response for group A strep infections.

Surveillance Protocols and the Strategic Seven Sentinels

The protocol development effort was coordinated by an international group of researchers and physicians that included a 13-person Burden of Disease Working Group from seven strategically different nations. The group collaborated with other international experts on certain diseases on the project. This was a crucial component of SAVAC’s epidemiology workstream, which was situated in South Korea at the International Vaccine Institute.

According to Van Beneden, once a vaccine is approved, it is anticipated that it will lessen the financial and social burden brought on by the strep A illness syndromes. These comprise common illnesses like cellulitis that are also brought on by etiologies other than strep A, such as group B streptococci and animal bites, as well as infectious disease syndromes, such as bacterial pharyngitis and acute rheumatic fever, that are primarily caused by strep A.

The surveillance guidelines were just released by the Infectious Diseases Society of America in Open Forum Infectious Diseases (DOI: 10.1093/ofid/ofac210) , making them generally accessible for deployment. The project aims to standardize epidemiological surveillance of pharyngitis (DOI:  10.1093/ofid/ofac251), impetigo (DOI: 10.1093/ofid/ofac249), cellulitis (DOI: 10.1093/ofid/ofac267), invasive group A streptococcal infections (DOI: 10.1093/ofid/ofac281), acute rheumatic fever (DOI: 10.1093/ofid/ofac252), rheumatic heart disease (DOI: 10.1093/ofid/ofac250), and acute poststreptococcal glomerulonephritis (DOI: 10.1093/ofid/ofac346).

To track the effects of strep A vaccines across populations in diverse geographical areas, SAVAC hopes to build a number of sentinel surveillance stations. There are currently a number of strep A vaccines being developed, the most of which are still in phase 1 clinical trials.

The Need for Precision, Accuracy and Specificity

An estimation of the burden of each of the significant endpoints is necessary to provide an accurate estimation of the overall illness burden caused by strep A infections. However, the perception of such endpoints as serious public health issues differs by nation and location, as does the ability to identify and monitor them.

In comparison to nations like Australia, New Zealand, and Uganda, the United States has low rates of acute rheumatic fever and rheumatic heart disease. As a result, these nations have considerably stricter surveillance for rheumatic heart disease and acute rheumatic fever. Furthermore, some nations do not keep track of pharyngitis, the primary antecedent to acute rheumatic fever, in contrast to the United States and several European nations since it is merely seen as a mild infection that will go away on its own.

A benefit of having accurate disease burden estimates broken down by region is that it helps public health organizations in the affected areas assist the development and evaluation of the strep A vaccination as well as the value of prevention.

The authors of the summary paper on the standardized strep A protocols stress the significance of precise case definitions, thorough case classifications, and well-defined case ascertainment methodologies, particularly for general clinical syndromes. Stronger disease burden estimates are made possible by these essential surveillance components. When compared to active surveillance from a prospective birth cohort that included more in-depth training on case ascertainment and categorization, the incidence of all-cause pneumonia was found to be 30% lower in South Africa, for instance.

Harmonization, Estimation and Endpoint Dependence

The inclusion of the same elements as the World Health Organization’s published monitoring requirements for diseases that are preventable by vaccination is one way in which the protocols are harmonized. Every one of them functions as a blueprint for how to establish surveillance for a distinct result, and they all attempt to use the same procedures so that the results may be compared to those of other infectious diseases and nations.

Calculating the “attributable fraction” of cases that are attributable to group A strep is necessary to estimate the burden of prevalent diseases like cellulitis and pharyngitis that are brought on by several bacteria. One important part of the published protocols is the various methods for using microbiological tests to identify strep A as the cause of these illnesses.

Another aspect of the protocols, surveillance systems’ characteristics, also vary depending on the strep A endpoints. For instance, passive surveillance for severe disease outcomes like invasive strep A infections (e.g., meningitis, necrotizing fasciitis), where infected people typically seek medical attention, may entail routinely reviewing hospital discharge records, while passive monitoring for milder disease with a higher community-level burden of disease (e.g., pharyngitis) may involve continuous checks.

Discrepancies and Differences, The Need for Standardization

For several of the seven diseases with strep A etiology, surveillance studies are already under progress in numerous nations, states, and municipalities. However, it is frequently challenging to draw accurate and convincing comparisons between different jurisdictions due to discrepancies in case definitions and case identification procedures.

Researchers recently performed a systematic review on worldwide pharyngitis and came to the conclusion that different incidence estimates are caused by various surveillance strategies. No two of the 26 studies analyzed in an eClinicalMedicine published study by Miller et al. used similar case ascertainment and surveillance methods.

Van Beneden believes that the standardized methodology indicated in the recently published protocols will be adopted by public health organizations who have not yet begun surveillance in their investigations. The guidelines provided by the standards should make it simpler for authorities to start monitoring. In a press release describing the universal protocols, one of which is already being used by the Telethon Kids Institute in Perth, Western Australia, their simplicity of usage is emphasized.

The True Value of Good Surveillance and Better Estimates

According to current estimates, strep A is widely known for having a significant negative impact on public health, causing over 600,000 annual deaths and 600 million new infections, Van Beneden notes. She stated that while accurate illness estimations are not required in order to produce a vaccine, they are required in order to assess the vaccine’s effectiveness.

As was the case with the rollout of the COVID vaccines, accurate disease forecasts can indicate trends and determine groups at highest risk based on factors like their age and underlying medical conditions. This information can then be used to focus prevention efforts and inform decisions about who to target for initial vaccination. When creating sentinel sites to test potential strep A vaccines, information gathered from effective surveillance systems will eventually be helpful.

In order to address the inconsistent quality and quantity of disease burden estimates worldwide, the surveillance methods were developed with this goal in mind. Better estimates are required in low- and middle-income countries, where the potential benefits of introducing a vaccine may not be realized if the burden of some common strep A illnesses, such as pharyngitis or rheumatic fever, is poorly captured and consequently underappreciated.

According to Van Beneden, surveillance that significantly underestimates the prevalence of a particular group A infection will not only deceive public health organizations about the true burden of disease. If surveillance procedures improve as a result of a public health initiative, they can conclude incorrectly that the endeavor was ineffective. This was observed with the previous approaches to other bacteria.

Engr. Dex Marco Tiu Guibelondo, BS Pharm, RPh, BS CpE

Editor-in-Chief, PharmaFEATURES

The mission of SAVAC (Strep A Vaccine Global Consortium) is to ensure that safe, effective and affordable Strep A vaccines are available and implemented to decrease the burden of Strep A disease in the most in need. Visit savac.ivi.int and linkedin.com/company/idsociety to learn more about SAVAC and the latest published articles and supplements of the Infectious Diseases Society of America (IDSA).