Modalities of group A streptococcal prevention and treatment and their economic justification

Group A Streptococcus (Streptococcus pyogenes, ‘Strep A’) causes superficial infections (pharyngitis, impetigo) and invasive diseases (e.g., necrotising fasciitis, toxic shock, sepsis) and immune-mediated sequelae such as acute rheumatic fever (ARF) and acute post-streptococcal glomerulonephritis (APSGN), which can lead to chronic rheumatic heart disease (RHD) and chronic kidney disease. Globally, Strep A infections and complications cause over half a million deaths annually, with disproportionate burden in resource-limited settings, though morbidity from superficial infections and sepsis is also substantial in high-resource settings. Prevention of ARF and RHD is commonly framed as primordial (reduce exposure/transmission), primary (treat superficial infection), secondary (antibiotic prophylaxis after ARF/RHD), and tertiary prevention (manage severe disease). Despite long-standing technologies for these strategies, there is limited guidance on choosing between them across settings, and little on integrating transformative options such as vaccination. Economic modelling can support decision-making by clarifying costs, benefits, and uncertainties; however, clarity is easier for near-term clinical therapies than for long-term public health strategies, risking publication bias toward readily evaluated interventions. This scoping review compiles economic evaluations of Strep A treatment and prevention strategies, categorised within a prevention framework, to identify robust areas of evidence, gaps, and priorities to better inform policy makers, especially as interest in Strep A vaccination grows.

The review identified 839 records after removing 255 duplicates. After screening, 142 reports were sought for retrieval; 9 could not be retrieved. Of 133 full-text reports assessed, 41 were included; 3 additional studies were identified from reference lists, totalling 44 studies with economic evaluations of Strep A treatment or prevention strategies. By category: 1 study on primordial prevention, 34 on primary prevention, 8 on secondary prevention, and 1 on tertiary prevention; 6 studies compared strategies across multiple categories. Subtopics within primary prevention included: diagnostic/management strategies for pharyngitis (with and without accounting for prevention of sequelae), treatment strategies for skin and soft tissue infections (impetigo, cellulitis, general SSTIs), and studies combining primary with downstream strategies. Secondary/tertiary prevention studies included adherence interventions for secondary prophylaxis, echocardiographic screening for RHD, and surgical management for rheumatic mitral valve disease, as well as strategies to prevent recurrent disease (e.g., tonsillectomy, antibiotic prophylaxis for recurrent cellulitis). Evaluation quality was appraised against Drummond’s checklist.

Design: Scoping review conducted per PRISMA guidance (protocol developed but not registered). Inclusion criteria: Studies published 01/01/2000–10/12/2022 evaluating Strep A treatment or prevention strategies from an economic perspective, measuring and valuing resource use and comparing intervention costs to clinical/economic benefits. Included economic designs: cost-of-illness, cost-effectiveness, cost-utility, cost-benefit, budget impact, return on investment. Exclusions: Nosocomial infections; diseases caused by non–Strep A pathogens; studies not calculating intervention costs and comparing to benefits. No language or country restrictions (search terms in English).

Data sources and search: Web of Science (including WoS core and Medline) and Embase (Elsevier). Search strings provided in Supplemental Material 1. Titles/abstracts screened; full texts assessed for eligibility. Reference lists of eligible studies were hand-searched to identify additional studies.

Data extraction: First author and year; country; intervention target and strategies; target population and age; study design (trial- or model-based; CEA/CUA/CBA, etc.); evidence of effectiveness; benefits; costs; and evaluation outcomes.

Synthesis and analysis: Studies were categorised along an expanded prevention framework spanning primordial (prevent infection), primary (reduce duration/severity and/or prevent sequelae), secondary (prevent recurrence or worsening, including ARF/RHD and other Strep A diseases), and tertiary (prevent death in severe disease). Studies evaluating multiple categories were summarised under the most upstream category. Evaluation robustness was assessed using Drummond et al.’s checklist for economic evaluations.

• 44 studies included (41 from database screening plus 3 from references). Category distribution: primordial (n=1), primary (n=34), secondary (n=8), tertiary (n=1); 6 compared multiple categories.
• Primordial prevention: One Australian modelling study found potential value for a Strep A vaccine from a health sector perspective; acceptable incremental cost-effectiveness at annual vaccination costs < AU$260–289 per non-Indigenous child and < AU$897–920 per Indigenous child, with added value from reductions in superficial throat/skin disease and cellulitis.
• Primary prevention – reduced duration only (no sequelae): 16 studies (6 pharyngitis, 2 impetigo, 7 cellulitis, 1 general SSTI). For pharyngitis in upper-middle/high-income settings, 4/5 diagnostic strategy studies supported routine rapid antigen detection tests (RADTs) as lowest cost per accurate diagnosis/appropriate antibiotic; limited value for backup testing after negative RADTs.
• Primary prevention – reduce duration and prevent sequelae: 6 pharyngitis diagnostic strategy studies. Findings varied by assumptions (ARF risk, test costs, prevalence), but culture-all or RADT-based strategies were often cost-effective; pharmacy-based diagnosis/treatment found cost-effective in one study; one trial-based study measured QALYs for sore throat (no ARF observed); extended modelling including ARF prevention suggested RADT not cost-effective among high CDR score patients versus no testing.
• Primary prevention – prevent sequelae only (no acute duration benefit): 5 studies. Three CEAs in HICs found RADT for all or for high CDR patients cost-effective for preventing complications; one CUA on genetic testing for ARF susceptibility at birth; one CUA evaluating non-RADT diagnostic methods.
• Primary plus downstream strategies: Two Cuban program evaluations (1986–2002) concluded combined public health interventions were economically efficient versus prior care. Of four studies assessing strategies independently (three in Africa, one in India), findings varied: some favored primary prevention, others found secondary and tertiary prevention cost-effective or net beneficial; framework and inclusion of prevalent vs incident cases influenced conclusions.
• Secondary/tertiary prevention (ARF/RHD): Five studies among people with ARF/RHD history. One adherence intervention reported cost per additional benzathine penicillin G (BPG) injection (benefits not quantified beyond compliance). Three studies concluded echocardiographic screening for RHD was cost-effective versus usual care, with notable limitations in effectiveness evidence and identified conditions where screening may not be cost-effective. One Indian study: mitral valve repair for young adults with severe rheumatic disease was cost-effective versus usual care or replacement.
• Prevention of recurrent non-ARF disease: Two studies found tonsillectomy cost-effective for frequently recurrent pharyngitis; one study found a homeopathic adjuvant (SilAtro-5-90) cost-effective; one study showed antibiotic prophylaxis reduced recurrent cellulitis risk by ~one-third without significant cost increase.
• Evaluation quality (Drummond checklist): 27/44 scored ≥8/10; 35 scored ≥6/10. Common gaps: missing perspective (n=18); incomplete identification of relevant costs/consequences (n=18); lack of incremental analysis (n=15); limited discussion of implementation or similar evaluations (n=14); insufficient establishment of effectiveness (n=12).

The literature on economic evaluations of Strep A interventions is skewed toward clinical diagnostic and therapeutic strategies for acute disease, especially primary prevention of pharyngitis using RADT, with relatively little evaluation of population-level strategies to reduce ARF/RHD incidence or to manage established disease. While RADT-based strategies often appear cost-effective for managing pharyngitis and reducing inappropriate antibiotic use, the potential for detecting asymptomatic carriage and prompting unnecessary antibiotics is underexplored. Few studies inform system-level policies for reducing post-infection sequelae at the population level.

Decision-making is complicated by methodological inconsistencies and uncertainties: many evaluations use outdated or sparse data (e.g., wide ARF risk ranges after untreated infection), lack clear analysis perspective, and omit quality-of-life measurement/validation for post-infectious sequelae and the burden of long-term prophylaxis. Primary prevention studies often exclude the benefit of reduced acute illness duration despite its high frequency relative to ARF. Population-level analyses rarely stratify by risk, potentially obscuring impacts in high-burden groups (e.g., Indigenous and marginalized communities). Evidence for effectiveness is limited for certain strategies (e.g., echocardiographic screening outcomes), and impetigo as a contributor to ARF pathogenesis is largely omitted from prevention modelling.

Key gaps include economic evaluations of primordial prevention (environmental/social determinants, hygiene), tertiary prevention of invasive infection, and comprehensive assessments spanning the entire aetiological pathway. Broader public health strategies likely yield cross-disease and socioeconomic benefits inadequately captured by conventional methods; choice of productivity valuation (human capital vs friction cost) affects affordability interpretations, particularly in LMICs. Capacity and affordability analyses (e.g., budget impact, workforce requirements) are infrequently addressed, limiting practical guidance for implementation. Overall, economic evaluation has significant potential but currently provides limited, narrowly focused guidance for comprehensive Strep A control.

Economic evaluations of Strep A interventions predominantly address clinical diagnostics and treatment for acute pharyngitis, with limited attention to upstream (e.g., vaccination, social determinants) and system-level strategies to reduce ARF/RHD burden. Existing studies often rely on aging data and uncertain assumptions, lack clearly defined perspectives, and under-report quality-of-life impacts and implementation considerations. To inform comprehensive Strep A control—particularly amid progress toward Strep A vaccines—future research should: generate better primary data on effectiveness across a wider range of strategies; improve baseline epidemiology; validate QALY weights for Strep A sequelae; incorporate budget impact and affordability; consider heterogeneous risk groups; and evaluate broader public health approaches capturing cross-sector benefits. Enhanced transparency and robust uncertainty analyses in model-based studies, and inclusion of economic and social outcomes alongside clinical trials, are essential to strengthen the evidence base for decision-makers.

• Scoping review design; protocol not registered. A small number of relevant papers may have been missed despite broad searches; 9 identified reports were not retrieved.
• Search terms were in English, which may introduce bias despite no language restrictions on inclusion.
• Many included evaluations were model-based and relied on outdated or sparse parameters (e.g., highly variable ARF risk after untreated infection), limiting certainty and comparability.
• Limited or absent evidence of effectiveness for some strategies (e.g., outcomes among cases detected by routine echocardiographic screening vs usual care).
• Inconsistent or missing analysis perspectives and incomplete identification of relevant costs/consequences in numerous studies; limited incremental analyses and implementation discussions.
• Primary prevention studies often did not account for reduced duration of acute illness; few analyses considered detection of Strep A carriage leading to unnecessary antibiotics.
• Little consideration of health system capacity, workforce constraints, and budget impact, especially in LMICs.