Table 2.

Priorities for Data Requirements Describing Burden of Disease Across Vaccine Development and Evaluation Objectives for Acute Group A Streptococcus Diseases

Clinical Endpoint	Vaccine Objective
	Advocacy	Regulatory/Licensure	Policy and Post-Licensure Evaluation	Financing
Pharyngitis (children)	Passive or active surveillance data measuring age-specific disease incidence and strain (eg, emm type) distribution Data on population transmission Vaccine acceptance HICs: Markers of immune response to differentiate asymptomatic carriage vs acute infection LMICs: Syndromic surveillance data to establish need for subnational vs regional estimates for countries lacking capacity; Strep A–specific pharyngitis data where feasible	Prospective, active surveillance with laboratory-confirmed clinical endpoints Strain-specific disease incidence where possible HICs: Establish infrastructure and data mechanisms for phase II/III vaccine clinical trials Monitor adverse events/safety from vaccine candidates Markers of immune response to assess asymptomatic carriage vs acute infection LMICs: Correlate with pre-existing syndromic surveillance sites	Prospective and retrospective data measuring age-specific (or reporting age-standardized) incidence rates (pre- and post-vaccine introduction) Trends in antibiotic use (and AMR in Strep A and bystander pathogens) over time HICs: Economic value of vaccine Estimates of herd immunity LMICs: Correlate with pre-existing syndromic surveillance sites Strep A–specific in limited sentinel sites	Retrospective economic (cost of illness) data from all available levels of health service indicators, but primarily general practice HICs: Level and cost of antibiotic use plus trends in AMR Economic value of vaccine
Impetigo (children)	Passive or active surveillance data measuring age-specific disease incidence and prevalence Vaccine acceptance HICs: Strep A–specific (laboratory-confirmed) where possible Data from a limited number of sentinel settings are adequate (as impetigo unlikely to be major driver in HICs) LMICs: Syndromic surveillance data with laboratory confirmation from selected high-performing sites	Prospective active surveillance with laboratory-confirmed clinical endpoints HICs: Only required in a small number of sentinel sites Phase II/III vaccine clinical trials unlikely to be feasible (given low disease prevalence) LMICs: Measure disease incidence/prevalence from selected regional sites Identify sites with adequate resources for future vaccine trials	Prospective and retrospective data measuring age-specific or age-standardized incidence/prevalence rates (pre- and post-vaccine introduction) Does not need to be Strep A–specific HICs: Potential basis for later vaccine effectiveness evaluation LMICs: Strep A–specific in a subset of sentinel sites	Retrospective economic (cost of illness) data from all available levels of health service indicators
Cellulitis	Prospective and retrospective passive and active surveillance data measuring age-specific disease incidence and prevalence HICs: Measure disease outcomes Strep A–specific data from limited sites if feasible	Not critical as initial efficacy needs to be demonstrated for pharyngitis and impetigo HICs: Consider phase III trials in targeted populations (eg, recurrent cellulitis in diabetics or elderly)	Incidence/prevalence rates, focusing on adults Does not need to be Strep A–specific LMICs: Syndromic surveillance data may be useful to monitor temporal trends	Retrospective economic (cost of illness) data from all available levels of health service indicators HICs: Lost productivity data Measure severe disease outcomes LMICs: Unlikely to be a priority
Invasive Strep A	Prospective and retrospective passive and active surveillance data measuring age-specific disease incidence and outcomes, including mortality Societal/economic burden HICs: Serotype (eg, emm type) data important High-risk populations (eg, First Nations) as likely to influence decision making LMICs: Establish sentinel site surveillance in geographically representative areas	Not critical as initial efficacy needs to be demonstrated for pharyngitis and impetigo but need to plan for post-licensure evaluation HICs: Strain-specific endpoints useful for post-licensure evaluations in some countries	Prospective and retrospective data measuring age-specific or age-standardized incidence/prevalence rates (age group will depend on clinical focus) HICs: Laboratory-confirmed infections Assess some key foci separately (eg, puerperal sepsis) Impact on AMR of group A strep LMICs: Strain-specific data from several select, high-performing sites	Retrospective economic (cost of illness) data focusing on hospitalizations and mortality Data on imputations and other sequelae, including DALYs where possible
Scarlet fever	Prospective and retrospective passive and active surveillance data measuring age-specific disease incidence	Not critical as initial efficacy needs to be demonstrated for pharyngitis and impetigo but may be observable in some settings	Prospective and retrospective data measuring age-specific or age-standardized incidence rates HIC: Serotype data important Trends in antibiotic use (and AMR) over time	Retrospective economic (cost of illness) data from, primarily, general practice HICs: Level and cost of antibiotic use plus trends in AMR

Abbreviations: AMR, antimicrobial resistance; DALY, disability-adjusted life-year; HIC, high-income country; LMIC, low- and middle-income country; Strep A, group A Streptococcus.