Abstract
Background: An emm-cluster based system was proposed as a standard typing scheme to facilitate and enhance future studies of Group A Streptococcus (Strep A) epidemiological surveillance, M protein function and vaccine development strategies. We provide an evidence-based distribution of Strep A emm clusters in Africa and assess the potential coverage of the new 30-valent vaccine in terms of an emm cluster-based approach.
Method: Two reviewers independently assessed studies retrieved from a comprehensive search and extracted relevant data. Meta-analyses were performed (random effects model) to aggregate emm cluster prevalence estimates.
Results: Eight studies (n=1,595 isolates) revealed the predominant emm clusters as E6 (18%, 95% confidence interval (CI), 12.6; 24.0%), followed by E3 (14%, 95%CI, 11.2; 17.4%) and E4 (13%, 95%CI, 9.5; 16.0%). There is negligible variation in emm clusters as regards regions, age and socio-economic status across the continent. Considering an emm cluster-based vaccine strategy, which assumes cross-protection within clusters, the 30-valent vaccine currently in clinical development, would provide hypothetical coverage to 80.3% of isolates in Africa.
Conclusion: This systematic review indicates the most predominant Strep A emm cluster in Africa is E6 followed by E3, E4 and D4. The current 30-valent vaccine would provide considerable coverage across the diversity of emm cluster types in Africa. Future efforts could be directed toward estimating the overall potential coverage of the new 30-valent vaccine based on cross-opsonization studies with representative panels of Strep A isolates from populations at highest risk for Strep A diseases.
Importance: Low vaccine coverage is of grave public health concern, particularly in developing countries where epidemiological data are often absent. To inform vaccine development for group A streptococcus (Strep A), we report on the epidemiology of the M Protein emm clusters from Strep A infections in Africa, where Strep A-related illnesses and their sequalae including rheumatic fever and rheumatic heart disease, are of a high burden. This first report of emm clusters across the continent indicate a high probably of coverage by the M Protein-based vaccine currently undergoing testing, were an emm-cluster based approach to be used.
Lay summary
Title
Researchers identify Africa’s Streptococcus types for better vaccines.
Brief summary of the what & so what (result and why it matters) [+- 20 words]
After looking at many studies on Streptococcus bacteria, researchers have identified the types that are common in Africa. Their findings will boost research into better vaccines against the specific types.
Why was this study done? (problem statement and background)
Infection with Group A Streptococcus bacteria, or ‘GAS’, can lead to a number of serious illnesses, including pneumonia and toxic shock syndrome, which can be fatal. In Africa, 1.78 million severe cases of GAS occur every year.
Over 200 varieties or ‘types’ of GAS have been identified, so scientists have developed a system for grouping the types, based on differences in a specific protein called the M protein. Using this approach, they developed a vaccine targeting groups of similar types, called emm clusters. The vaccine is based on data from studies in developed countries, but little information is available on how useful it would be in Africa.
What was the purpose of this study? (Aims and objectives)
In this study, researchers compared data from other GAS studies in African countries to determine which emm clusters are the most common across the continent. In particular, they wanted to understand how effective the current vaccine is likely to be in the region.
What did the researchers do (summary or overview of methods, the big picture)
The researchers started with a broad search of scientific articles about GAS in Africa, and then narrowed their findings down to the ones that specifically dealt with emm clusters. This left them with a total of eight studies, spread across five countries: South Africa, Mali, Kenya, Tanzania, and Tunisia.
By analysing those studies in more detail, the researchers were able to pin-point which emm clusters were most common, and how many individual types of GAS had been found. They then compared that information to the specific types of GAS targeted by the newly developed vaccine.
What were the results of the study?
They found four common clusters that appeared across the continent, but they didn’t see much variation in the age or socioeconomic status of people affected by them.
When they compared the types of GAS that occurred in Africa to types the vaccine protects against, they found that the vaccine was likely to be effective for around 60% of types. The researchers point out, however, that the vaccine might provide better protection against types that are part of the same emm clusters. In practice, that could mean the vaccine would protect people against 80% of GAS types found in Africa.
How do these findings add to what was already known? (impact on the current science)
The findings show that the new GAS vaccine is likely to be effective in Africa, but the researchers do note that the common African emm clusters are not the same as those seen in many other parts of the world. In the future, including under-represented types when developing vaccines could make it more effective in an African context.
What are the potential weaknesses/uncertainties/controversies of the study? (If the paper talks about them at all, but most important for where they mention where future research is needed, or where the data was lacking)
The researchers mentioned that there is also a lack of information about GAS in many low- and middle-income African countries. Adding data from these areas might therefore give scientists a more detailed picture of the problem.
In addition, there are some GAS types that aren’t part of the emm cluster system, possibly because they are new varieties. Future research focused on determining where these types fit in will contribute to better vaccine development, and better outcomes for patients in Africa.
“How will these findings help solve a challenge in Africa?” (question speaking to the impact of the research on society as a whole, outside of the scientific community).
The study highlights important areas for future work in an African context and is the first study of GAS emm clusters for the continent. The work was a collaboration between researchers from South Africa and the USA.
Number of words: 579
Glossary terms for translation and coining:
Streptococcus: A bacterium that can cause disease ranging from throat infections to skin disease, pneumonia and toxic shock.
Sequelae: Conditions that result from previous illness. For example, skin infection by Streptococcus can lead to more serious illnesses; like rheumatic fever.
Vaccine: A man-made substance designed to stimulate the body’s immune response and provide protection against disease.
Toxic Shock Syndrome: A potentially deadly outcome of bacterial infection that occurs in response to toxins released by the bacteria. Symptoms include fever and vomiting.
Other keywords for ease of understanding:
Emm-cluster: A grouping system for similar types of Group A Streptococcus bacteria. Groupings are based on changes to a protein on the bacteria surface called the M-protein.
Meta-analysis: A study of multiple other studies.
Epidemiological surveillance: Collecting and analysing data about a disease.
Cross protection: When the body is exposed to a certain disease-causing organism, like a bacterium, the immune system may be able to provide protection against other, similar bacteria. This is called cross-protection.
Phagocytes: Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells.
30-valant vaccine: Multivalent or polyvalent vaccines are designed to immunize against different strains of the same microorganism, or against multiple microorganisms. In this case, the number 30 indicates how many types of GAS the vaccine targets.
Final summary for translation
Researchers identify Africa’s Streptococcus types for better vaccines
After looking at many studies on Streptococcus bacteria, researchers have identified the types that are common in Africa. Their findings will boost research into better vaccines against the specific types.
Infection with Group A Streptococcus bacteria, or ‘GAS’, can lead to a number of serious illnesses, including pneumonia and toxic shock syndrome, which can be fatal. In Africa, 1.78 million severe cases of GAS occur every year.
Over 200 varieties or ‘types’ of GAS have been identified, so scientists have developed a system for grouping the types, based on differences in a specific protein called the M protein. Using this approach, they developed a vaccine targeting groups of similar types, called emm clusters. The vaccine is based on data from studies in developed countries, but little information is available on how useful it would be in Africa.
In this study, researchers compared data from other GAS studies in African countries to determine which emm clusters are the most common across the continent. In particular, they wanted to understand how effective the current vaccine is likely to be in the region.
The researchers started with a broad search of scientific articles about GAS in Africa, and then narrowed their findings down to the ones that specifically dealt with emm clusters. This left them with a total of eight studies, spread across five countries: South Africa, Mali, Kenya, Tanzania, and Tunisia.
By analysing those studies in more detail, the researchers were able to pin-point which emm clusters were most common, and how many individual types of GAS had been found. They then compared that information to the specific types of GAS targeted by the newly developed vaccine.
They found four common clusters that appeared across the continent, but they didn’t see much variation in the age or socioeconomic status of people affected by them.
When they compared the types of GAS that occurred in Africa to types the vaccine protects against, they found that the vaccine was likely to be effective for around 60% of types. The researchers point out, however, that the vaccine might provide better protection against types that are part of the same emm clusters. In practice, that could mean the vaccine would protect people against 80% of GAS types found in Africa.
The findings show that the new GAS vaccine is likely to be effective in Africa, but the researchers do note that the common African emm clusters are not the same as those seen in many other parts of the world. In the future, including under-represented types when developing vaccines could make it more effective in an African context.
The researchers mentioned that there is also a lack of information about GAS in many low- and middle-income African countries. Adding data from these areas might therefore give scientists a more detailed picture of the problem.
In addition, there are some GAS types that aren’t part of the emm cluster system, possibly because they are new varieties. Future research focused on determining where these types fit in will contribute to better vaccine development, and better outcomes for patients in Africa.
The study highlights important areas for future work in an African context and is the first study of GAS emm clusters for the continent. The work was a collaboration between researchers from South Africa and the USA.