Vaccines as key players in mitigating AMR (Part-III).
-Vaccines against Viral pathogens: an oft-neglected strategy to reduce Antibiotic usage
Prescription of antibiotics during a viral infection due to misdiagnosis or as prophylactics is observed commonly. This is an effective strategy from the standpoint of acute patient care but can be detrimental in case of excessive use in the long run as it can lead to the development of resistance to antibiotics. The Indian medical community and policy eco-system are aware of this challenge, but the issue needs more awareness and action. Sporadic advisories or news reports mentioned below show the reactionary measures currently in place.
The relaxation of precautions post-COVID led to increased viral infections manifesting as flu-like symptoms. Hyderabad was one of the cities witnessing a spike in viral infections in January 2023. A general physician in the city catering to many such patients made the following observation “Due to the easy availability of drugs after COVID-19, everybody has stocked up on antibiotics like Azithromycin and Amoxiclav and is popping them without any prescription.” (1).
A recent outbreak of H3N2 influenza cases in Karnataka also did not warrant an unadvised use of antibiotics, as cautioned by the then health minister. However, vaccination of healthcare workers and the vulnerable were emphasized (2).
The above instances from the media ignite a correlation between vaccination and antibiotic use in the general public, but systematic awareness amongst the citizenry on this issue is need of the hour.
Connecting the dots: the link between viral and secondary bacterial infections
Viral infections can predispose individuals to secondary bacterial infections, thus requiring the use of antibiotics. For example, post-influenza bacterial infections are often caused by S. pneumoniae, S. aureus, S. pyogenes, or H. influenzae.
Influenza virus predisposes individuals to bacterial colonization by depleting immune cells from the upper airway (5). Vaccination against such viral infections (influenza, measles, and respiratory syncytial virus) reduces the viral load and infection length minimizing the chance of bacterial invasion.
A universal influenza immunization program in Ontario region, Canada, witnessed a concomitant 64% decrease in antibiotic prescriptions (6). Similar studies in Italy, Japan, and Pakistan reported a significant reduction in antibiotic prescriptions; in fact, in some pediatric cohorts, as high as 88% (7).
Mild pediatric chickenpox skin infection, too, is associated with antibiotic use against Staphylococci or Streptococci secondary bacterial infections. A modeling study published last year estimated that broader vaccination coverage could reduce the annual expenditure for antibiotics from $82 million to $17 million (8).
Another study set out to predict the effect of flu vaccination on antibiotic use. It indicates that a 50% efficacious influenza vaccine at 30% coverage can avert 390 prescriptions per 100, 000 population per year in countries like Senegal and South Africa (10).
Global Policy Push for Viral Vaccines
Both data and the biology of pathogens indicate secondary infection or co-infection to be the drivers of antibiotic prescription. Vaccination and its awareness can be vital in dissuading the empirical resort to antibiotics. While incidental advice on vaccination is helpful, it is crucial to incorporate systemic solutions to discourage antibiotic use.
The immunization agenda by the World Health Organization aims to leverage vaccines to battle antimicrobial resistance (9). The WHO agenda additionally suggests combination vaccines to counter the need for antibiotics. Since clinical presentations of viral and bacterial infections overlap, prescribing antibiotics is empirical and routine. However, a combination of viral and bacterial vaccines can lead to a synergistic effect in decreasing the use of antimicrobials.
Need for the Expansion of India’s Universal Immunization Program
The Indian Council of Medical Research (ICMR) in 2019 issued guidelines on managing common syndromes and the prescription of antibiotics (3). It suggested curbing the use of antibiotics, especially for low-grade fever and upper respiratory infections, and suggested popularizing annual vaccines for flu.
Organizations such as the Centre for Disease Control (CDC) have generated awareness campaigns on the cause of common respiratory infections caused by viral pathogens and advised when not to take antibiotics (4).
A step towards a systemic solution could include a wider gamut of viral vaccines in universal immunization programs (UIP). As per experts involved in the Indian national vaccine policy 2011, a major hurdle to introducing new vaccines was the lack of indigenous surveillance data to assess the disease burden (11). Since then, due to increasing surveillance, there has been a push to include more vaccines in addition to the ones against the 12 diseases in the current UIP. In December 2022, the Indian Association of Pediatrics recommended the inclusion of vaccines against typhoid, chicken pox, Hepatitis A, influenza, and Japanese Encephalitis (12).
In 2017, the Indian National Technical Advisory Group for Immunization (NTAGI) recommended the introduction of the human papillomavirus (HPV) vaccine in the UIP for 9-year-old girl children (13). As of 2023, tenders for procurement are being floated ton integrate this systematically in the immunization program (14).
Meanwhile, approximately 125,000 Indian women are diagnosed with cervical cancer annually. Until it is included in UIP, the vaccine shot will continue to be an out-of-pocket expense by INR 2,000–11,000 per shot (15).
Flu vaccines are often called upon by government authorities to minimize viral outbreak breakouts (16). However, their cost has been a deterrent. In 2023, flu shots (against the influenza virus) cost up to INR 2000 per shot. Even among healthcare workers, where influenza vaccination is strongly recommended, the number of takers could be higher if the cost per shot is brought down.
Conclusion
The evidence linking correlation between viral vaccines and reduction in antibiotic usage is increasing. A few countries and the WHO are focusing on expanding the ambit of immunization programs to include common as well as rare viral diseases. The Indian government and innovation eco-system can adopt best practices by expanding UIP with available vaccines as well as promoting R&D of new vaccines.
Disclaimer: The blog is a compilation of information on a given topic that is drawn from credible sources; however, this does not claim to be an exhaustive document on the subject. It is not intended to be prescriptive, nor does it represent the opinion of C-CAMP or its partners. The blog is intended to encourage discussion on an important topic that may be of interest to the larger community and stakeholders in associated domains
REFERENCES:
3. https://main.icmr.nic.in/sites/default/files/guidelines/Treatment_Guidelines_2019_Final.pdf
5. Ghoneim HE, Thomas PG, McCullers JA. Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J Immunol. 2013;191(3):1250–1259. doi:10.4049/jimmunol.1300014
6. Kwong JC, Maaten S, Upshur RE, Patrick DM, Marra F. The effect of universal influenza immunization on antibiotic prescriptions: an ecological study. Clin Infect Dis. 2009;49(5):750–756. doi:10.1086/605087
7. Doherty TM, Hausdorff WP, Kristinsson KG. Effect of vaccination on the use of antimicrobial agents: a systematic literature review. Ann Med. 2020;52(6):283–299. doi:10.1080/07853890.2020.1782460
8. Pawaskar M, Fergie J, Harley C, et al. Impact of universal varicella vaccination on the use and cost of antibiotics and antivirals for varicella management in the United States. PLoS One. 2022;17(6):e0269916. Published 2022 Jun 10. doi:10.1371/journal.pone.0269916
9. Immunization Agenda 2030 Leveraging Vaccines to Reduce Antibiotic Use and Prevent Antimicrobial Resistance: An Action Framework. https://cdn.who.int/media/docs/default-source/immunization/product-and-delivery-research/action-framework-final.pdf?sfvrsn=13c119f3_5&download=true
10. Knight GM, Clarkson M, de Silva TI. Potential impact of influenza vaccine roll-out on antibiotic use in Africa. J Antimicrob Chemother. 2018;73(8):2197–2200. doi:10.1093/jac/dky172
11. National Vaccine Policy, Ministry of Health and Family Welfare, 2011, url: https://main.mohfw.gov.in/sites/default/files/108481119000.pdf
13. 17th National Technical Advisory Group on Immunization (NTAGI)Meeting
