Health and economic impact of the pneumococcal conjugate vaccine in hindering antimicrobial resistance in China

Abstract

Antimicrobial resistance (AMR) poses a serious threat to global public health. However, vaccinations have been largely undervalued as a method to hinder AMR progression. This study examined the AMR impact of increasing pneumococcal conjugate vaccine (PCV) coverage in China. China has one of the world's highest rates of antibiotic use and low PCV coverage. We developed an agent-based DREAMR (Dynamic Representation of the Economics of AMR) model to examine the health and economic benefits of slowing AMR against commonly used antibiotics. We simulated PCV coverage, pneumococcal infections, antibiotic use, and AMR accumulation. Four antibiotics to treat pneumococcal diseases (penicillin, amoxicillin, third-generation cephalosporins, and meropenem) were modeled with antibiotic utilization, pharmacokinetics, and pharmacodynamics factored into predicting AMR accumulation. Three PCV coverage scenarios were simulated over 5 y: 1) status quo with no change in coverage, 2) scaled coverage increase to 99% in 5 y, and 3) accelerated coverage increase to 85% over 2 y followed by 3 y to reach 99% coverage. Compared to the status quo, we found that AMR against penicillin, amoxicillin, and third-generation cephalosporins was significantly reduced by 6.6%, 10.9%, and 9.8% in the scaled scenario and by 10.5%, 17.0%, and 15.4% in the accelerated scenario. Cumulative costs due to AMR, including direct and indirect costs to patients and caretakers, were reduced by $371 million in the scaled and $586 million in the accelerated scenarios compared to the status quo. AMR-reducing benefits of vaccines are essential to quantify in order to drive appropriate investment.

Keywords: China; antibiotic resistance; immunization; pneumonia; vaccine.

Fig. 1.

DREAMR model structure. Legend: Gen, generation. *Care seeking focuses on formal healthcare systems. ^†Pneumococcal meningitis patients are assumed not to self-medicate. ^‡Self-medication involves use of oral antibiotics.

Fig. 2.

AMR-related cost savings from increased PCV coverage in China. Legend: AMR, antimicrobial resistance; PCV, pneumococcal conjugate vaccine; USD, US dollars. *Scaled scenario linearly increased PCV coverage from 4.7 to 99% over 5 y. ^†Accelerated scenario increased PCV coverage linearly from 4.7 to 85% in the first 2 y, and to 99% over the next 3 y.

Fig. 3.

Sensitivity analysis: tornado diagram of select parameters. Legend: k, elimination rate constant; PKPD, pharmacokinetic–pharmacodynamic; Vd, volume of distribution. Note: Sensitivity analyses were conducted by adjusting each group of related input parameters together by ±15% to examine the impact on change in cumulative costs. *Incidence of pneumococcal pneumonia, pneumococcal meningitis, and AOM were concurrently ranged. ^†Care seeking at formal healthcare facilities was varied for all modeled diseases. ^‡All average unit costs of medical expenditures were ranged across health facilities. ^§PKPD parameters, k, Vd, and antibiotic utilization (%), were varied across all four modeled antibiotics. ^¶The proportion of individuals hospitalized was ranged for pneumococcal pneumonia. ^#Case fatality rates were ranged for pneumococcal pneumonia and pneumococcal meningitis.