Modelling the value of vaccines in reducing the burden of antimicrobial resistance
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Antimicrobial resistance (AMR) is a global issue with increasingly severe consequences for the world economy and human health. The use of vaccines has been shown empirically to reduce AMR1, however, the benefits of vaccination campaigns in reducing AMR infections and improving health and economic outcomes have yet to be extensively quantified. Measuring these benefits is essential for public health planning, particularly as the costs associated with new vaccines increase, economic analysis is needed to justify the expenditure in different health contexts.
ARVac, a consortium including CDDEP, Yale, Berkeley, Imperial College London, and Princeton, is at the cutting edge of infectious disease modeling to assess the health and economic impact avertable by potential, new, or current vaccines targeting Typhoid, shigella, Streptococcus pneumoniae, rotavirus, respiratory syncytial virus, or tuberculosis (TB). Monoclonal antibodies that target Gram-negative organisms causing neonatal sepsis will also be included in the analysis. The project brings together a consortium of modelers who are experts in each of the disease areas from Yale, Berkeley, Imperial College London, Princeton, and CDDEP. The key outputs will be reductions in resistant infections, deaths, years of life lost and antibiotic consumption due to vaccination, and the associated economic outcomes.
This work is as part of a broader collaboration between CDDEP, World Health Organization (WHO), the Bill & Melinda Gates Foundation (BMGF), and the Wellcome Trust which aims to better define the role of vaccines against AMR and determine the priorities for strengthening the impact of vaccines against AMR.
Vaccines can reduce AMR via two mechanisms: (1) a lower overall burden of infection leads to a reduction in the transmission of resistant and susceptible pathogens; (2) fewer infections mean less need to consume antibiotics, thereby lessening the selection pressure for resistant pathogenic strains (Figure 1). Ultimately, this reduction in resistant cases will lead to fewer untreatable infections and more lives saved. These relationships are complex, however, and more in-depth analyses of the different contributing factors have been described elsewhere2.
In general, efforts to assess the benefits of vaccines in terms of deaths averted and reductions in medical impoverishment have not considered the effects on AMR3. Many vaccines, both those in current use and those in the pipeline, have the potential to help reduce the AMR disease burden and thereby save lives.
Pneumococcal disease is a cause of pneumonia, invasive disease, ear infections, and sinus infections and results in 1.6 million deaths annually 4. Treatment is becoming more complicated due to emerging resistance however there is extensive evidence that pneumococcal conjugate vaccine (PCV) has reduced resistant infections1,5,6. PCV has also been shown to reduce antibiotic consumption7,8. In the US alone it has been predicted that PCV-7 has the potential to prevent 1.4 million antibiotic prescriptions each year9. Other research suggests PCV could reduce the amount of antibiotics used to treat pneumonia by 47%, this is the equivalent of 11.4 million antibiotic days globally 10.
Seasonal influenza causes 1 billion cases of infection11and 650,000 deaths every year12. Influenza infections can lead to secondary bacterial infections requiring antibiotic 13however often antibiotic prescribing associated with influenza is inappropriate 6. 22% of influenza subjects in the US were prescribed antibiotics, despite the fact that 79% of them had no evidence of a secondary infection or comorbidity14. Evidence suggests vaccination reduces such usage15.
Tuberculosis (TB) claims more lives than any other pathogen worldwide16. The number of TB cases resistant to treatment is increasing and making treatment more difficult and prolonged16. Though bacillus Calmette–Guérin (BCG) vaccine was introduced in the 1920s new more effective vaccines are needed and there are multiple candidates in the pipeline16. Vaccines are likely to be a useful tool against drug resistant-TB, which can take up to two years to treat and have a high treatment cost relative to susceptible TB17.
21 million cases of typhoid and 222,000 typhoid-related deaths occur every year globally 18. Typhoid fever is caused by SalmonellaTyphi which is becoming increasingly difficult to treat due to emerging resistance19,20. Typhoid conjugate vaccine was prequalified by WHO in 2018 and is now being introduced across parts of the developing world21–23.
Shigella causes 165 million cases of dysentery annually worldwide, mainly in children under five living in developing countries24. Antibiotic resistance is increasingly prevalent, with deadly consequences25. Multiple vaccine candidates are currently undergoing evaluation though no approved vaccine yet exists26.
Rotaviruses are a common cause of severe diarrhea in young children27and associated with a large amount of antibiotic prescribing. Wider introduction of currently existing rotavirus vaccines has the potential to reduce antibiotic use and save lives 28.
Gram-negative Bacteria (monoclonal antibodies)
Drug-resistant Gram-negative bacteria, including Acinetobacter baumannii, Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae, are a rising threat. Monoclonal antibodies are highly specific, have a limited risk of resistance development, and may work synergistically with antibiotics by directly targeting resistant strains29. It has been suggested that this alternative to antibiotics has low risk and high potential30.
Lewnard, J.A., Lo, N.C., Arinaminpathy, N., Frost, I, Laxminarayan, R., Childhood vaccines and antibiotic use in low- and middle-income countries. Nature 581, 94–99 (2020). https://doi.org/10.1038/s41586-020-2238-4
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