The Path to Group A Streptococcus Vaccines: World Health Organization Research and Development Technology Roadmap and Preferred Product Characteristics

Vekemans, Johan; Gouvea-Reis, Fernando; Kim, Jerome H.; Excler, Jean Louis; Smeesters, Pierre; O’Brien, Katherine L.; Beneden, Chris C.A. Van; Steer, Andrew C.; Carapetis, Jonathan R.; Kaslow, David Dc

doi:10.1093/cid/ciy1143

Cited by 148 publications

(153 citation statements)

References 30 publications

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“…Table 1). Taken together, our findings stress the importance of renewed efforts to monitor antimicrobial susceptibility rates and values in this pathogen on an ongoing basis, formulating an efficacious human vaccine against S. pyogenes, and the need for expanded vaccine efforts, as noted by many (49)(50)(51). Importantly, these needs also were highlighted in the report of a symposium held more than two decades ago dedicated to the topic of lack of penicillin resistance in S. pyogenes (1).…”

Section: Identification Of Pbp2x Amino Acid Replacementsmentioning

confidence: 56%

Reduced In Vitro Susceptibility of Streptococcus pyogenes to β-Lactam Antibiotics Associated with Mutations in the pbp2x Gene Is Geographically Widespread

et al. 2020

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Recently, two related Streptococcus pyogenes strains with reduced susceptibility to ampicillin, amoxicillin, and cefotaxime, antibiotics commonly used to treat S. pyogenes infections, were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the pbp2x gene, encoding penicillin-binding protein 2X (PBP2X). This concerning report led us to investigate our library of 7,025 genome sequences of type emm1, emm28, and emm89 S. pyogenes clinical strains recovered from intercontinental sources for mutations in pbp2x. We identified 137 strains that, combined, had 37 nonsynonymous mutations in 36 codons in pbp2x. Although to a lesser magnitude than the two previously published isolates, many of our strains had decreased susceptibility in vitro to multiple beta-lactam antibiotics. Many pbp2x mutations were found only in single strains, but 16 groups of two or more isolates of the same emm type had an identical amino acid replacement. Phylogenetic analysis showed that, with one exception, strains of the same emm type with the same amino acid replacement were clonally related by descent. This finding indicates that strains with some amino acid changes in PBP2X can successfully spread to new human hosts and cause invasive infections. Mapping of the amino acid changes onto a three-dimensional structure of the related Streptococcus pneumoniae PBP2X suggests that some substitutions are located in regions functionally important in related pathogenic bacterial species. Decreased beta-lactam susceptibility is geographically widespread in strains of numerically common emm gene subtypes. Enhanced surveillance and further epidemiological and molecular genetic study of this potential emergent antimicrobial problem are warranted.

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Section: Identification Of Pbp2x Amino Acid Replacementsmentioning

confidence: 56%

Reduced In Vitro Susceptibility of Streptococcus pyogenes to β-Lactam Antibiotics Associated with Mutations in the pbp2x Gene Is Geographically Widespread

et al. 2020

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“…Biomedical research priorities include: ■ improving our understanding of how housing and environmental health contributes to ARF risk and how this can be mitigated; ■ exploring contributors to ARF susceptibility and opportunities for an improved ARF diagnostic test; ■ developing a new long acting prophylactic agent for secondary prophylaxis to reduce the need for frequent painful injections; ■ conducting a randomised trial to determine whether people with borderline RHD detected on echocardiography screening benefit from secondary prophylaxis; and ■ developing a Strep A vaccine, supported by funding to the Strep A Vaccine Global Consortium to coordinate international vaccine development, and $35 million of Commonwealth funding to establish the Australian Strep A Vaccine Initiative to take a leading vaccine candidate into an efficacy trial by 2024. 265,266 ARF = acute rheumatic fever. RHD = rheumatic heart disease.…”

Section: Outstanding Research Priorities To Accelerate Rhd Eliminationmentioning

confidence: 99%

Ending rheumatic heart disease in Australia: the evidence for a new approach

Wyber¹,

Noonan²,

Halkon³

et al. 2020

Medical Journal of Australia

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on behalf of the END RHD CRE Investigators Collaborators Acknowledgements: • Children, families and communities living with RHD-We thank the Aboriginal and Torres Strait Islander people for sharing their stories in the Endgame Strategy, and acknowledge that the research and data in this publication reflect the experiences of Aboriginal and Torres Strait Islander people and communities affected by the ongoing trauma of ARF and RHD. • END RHD Review Working Group-We thank the following members of the END RHD Alliance, who formed an expert working group to review content of the Endgame Strategy for feasibility and acceptability, including review from a cultural perspective:

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“…The streptococcus pyogenes live vaccines can inhibit the viruses by endonucleases. It could help develop an immune response for host surveillance through M-protein type vaccines (50).…”

Section: Streptococcus Pyogenesmentioning

confidence: 99%

Considering Interim Interventions to Control COVID-19 Associated Morbidity and Mortality—Perspectives

Arokiaraj

2020

Front. Public Health

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Aims and objectives: The pandemic of COVID-19 is evolving worldwide, and it is associated with high mortality and morbidity. There is a growing need to discuss the elements of a coordinated strategy to control the spread and mitigate the severity of COVID-19. H1N1 and Streptococcus pneumonia vaccines are available. The current analysis was performed to analyze the severity of COVID-19 and influenza (H1N1) vaccination in adults ≥ 65. Also, to correlate the lower respiratory tract infections (LRIs), and influenza attributable to the lower respiratory tract infections' incidence with Covid-19 mortality. Evolutionarily influenza is close in resemblance to SARS-CoV-2 viruses and shares some common epitopes and mechanisms. Methods: Recent influenza vaccination data of 34 countries from OECD and other publications were correlated with COVID-19 mortality from worldometer data. LRIs attributable to influenza and streptococcus pneumonia were correlated with COVID-19 mortality. Specifically, influenza-attributable LRI incidence data of various countries (n = 182) was correlated with COVID-19 death by linear regression and receiver operating characteristic (ROC) curve analyzes. In a logistic regression model, population density and influenza LRI incidence were correlated with COVID-19 mortality. Results: There is a correlation between COVID-19-related mortality, morbidity, and case incidence and the status of influenza vaccination, which appears protective. The tendency of correlation is increasingly highlighted as the pandemic is evolving. In countries where influenza immunization is less common, there is a correlation between LRIs and influenza attributable to LRI incidence and COVID-19 severity, which is beneficial. ROC curve showed an area under the curve of 0.86 (CI 0.78 to 0.944, P < 0.0001) to predict COVID-19 mortality >150/million and a decreasing trend of influenza LRI episodes. To predict COVID-19 mortality of >200/million population, the odds ratio for influenza incidence/100,000 was −1.86 (CI −2.75 to −0.96, P < 0.0001). To predict the parameter Covid-19 mortality/influenza LRI episodes * 1000>1000, the influenza parameter had an odd's ratio of −3.83 (CI −5.98 to −1.67), and an AUC of 0.94. Arokiaraj Influenza Reduces COVID-19 Severity Conclusion: Influenza (H1N1) vaccination can be used as an interim measure to mitigate the severity of COVID-19 in the general population. In appropriate highrisk circumstances, Streptococcus pneumonia vaccination would also be an adjunct strategy, especially in countries with a lower incidence of LRIs.

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The Path to Group A Streptococcus Vaccines: World Health Organization Research and Development Technology Roadmap and Preferred Product Characteristics

Cited by 148 publications

References 30 publications

Reduced In Vitro Susceptibility of Streptococcus pyogenes to β-Lactam Antibiotics Associated with Mutations in the pbp2x Gene Is Geographically Widespread

Reduced In Vitro Susceptibility of Streptococcus pyogenes to β-Lactam Antibiotics Associated with Mutations in the pbp2x Gene Is Geographically Widespread

Ending rheumatic heart disease in Australia: the evidence for a new approach

Considering Interim Interventions to Control COVID-19 Associated Morbidity and Mortality—Perspectives

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