Phage therapy, which is using bacteriophage viruses to treat bacterial infections , could be acceptable to the public if they were "primed" to regard it as an appropriate alternative to antibiotics, according to a new study from the University of Exeter.
Researchers said that the "crisis" in antimicrobial resistance was shaping a world in which previously treatable infections could be lethal.
"This has revitalised the development of antibiotic alternatives," they said.
The therapeutic use of bacteriophages was first explored over a century ago. "However, most of the Western world abandoned phage therapy in favour of antibiotics," researchers noted.
Unlike antibiotics, phages are biological entities that can only replicate within their specific target bacteria.
"This high specificity and self-limiting ability means the commensal microbiome of the patient remains intact," the authors explained. This results in minimal side effects compared with antibiotics. Moreover, phages are cheaper to produce as they are naturally abundant in the environment.
Interest in phage therapy has recently revived; an editorial in Nature Biotechnology earlier this month described it as "an exciting alternative to antibiotics", noting particularly that "it can take months to years to recover a more normal microbiome following antibiotic treatments".
However, the study authors said, there had been "minimal effort to understand and tackle the social challenges that may hinder its development and implementation".
For their research, published in PLoS ONE, they set out to assess the UK public’s awareness, acceptance, preferences, and opinions on phage therapy using an online survey with embedded experiments distributed in mid-December 2021.
The survey included a conjoint (discrete choice) experiment, a framing experiment (testing responses to different descriptions of phage therapy), and responses to an open-ended question. The included sample size was 787 respondents, 51.6% women, mean age 47.2 years (standard deviation 15.5 years), with an average survey completion time of 10.5 minutes.
High Public Awareness of Antibiotic Resistance
The researchers reported "a high awareness of antibiotic resistance", with 92% of those who took part in the survey having heard of it. However only 13% had heard about phage therapy prior to the survey.
On a scale of 1 (not at all likely) to 7 (very likely), respondents' mean score for acceptance of phage therapy was 4.71, suggesting that "acceptance of phage therapy among the lay public is already moderate", the team said.
The survey ranked factors influencing acceptance in two scenarios: a minor infection, or an infection that had not responded to antibiotics for 3 months. Success and side effect rates, treatment duration, and countries where the medicine had been approved for use all had statistically significant effects on participants' treatment preferences.
Respondents who had recent exposure to information about antibiotic resistance and alternative treatments were more accepting of phage therapy. "Priming participants to think about novel medicines and antibiotic resistance" significantly increased the likelihood of approving the use of phage therapy, the team said.
Additionally, when participants were randomly assigned, 1 of 4 descriptions of phage therapy, their acceptance levels were lower when perceived 'harsh' words, such as "kill" and "virus", were used rather than alternative descriptions, such as "natural bacterial predator".
Of the 213 participants who responded to the open-ended question, 38% were interested in phage therapy, while a further 17% supported developing antibiotic alternatives generally.
The authors commented: "The antimicrobial resistance crisis is a global scientific and societal challenge. Antibiotics are becoming increasingly ineffective against previously susceptible bacteria, which will likely force the world into a post-antibiotic era where common infections and minor injuries could kill.
They noted that in 2019, an estimated 1.27 million deaths were attributable directly to bacterial antimicrobial resistance, and that it has been predicted that as many as 10 million people could die annually from antimicrobial resistance by 2050.
Importance of Maximising Public Acceptance
Their study provided an initial insight into how phage therapy could be developed and introduced in the UK to maximise acceptance rate.
"The public are in favour of the development of bacteria-killing viruses as an alternative to antibiotics", they said, and "more efforts to educate will make them significantly more likely to use the treatment".
Team leader Professor Susan Banducci, a political analyst and director of research at Exeter, said: "While phage therapy remains poorly understood by the UK public, our research suggests there is extensive acceptance and support for its development. Exposure to only very limited information about antibiotic resistance and alternative treatments to antibiotics greatly increases the public acceptance of phage therapy."
Nature Biotechnology observed: "Right now, we can still treat the majority of these resistant bacteria, but this will not always be the case, so other approaches are needed." While finding a new antibiotic candidate and bringing it to market can take anywhere from 8-20 years, machine learning algorithms now hold the promise of identifying potential bacteriophages from existing databases of viral sequences.
Currently bacteriophages are unapproved in the UK, but biotech companies are reportedly "racing" to test them , sometimes with their "exquisitely specific killing prowess" enhanced by equipping them with "CRISPR-based targeted payloads". In future, using phages to destroy drug-resistant bacteria selectively while keeping the microbiome intact could become "a much needed complement to the antibiotic armamentarium".
Sophie McCammon, a graduate research assistant at Exeter and co-author of the new study said: "An advantage of phage therapy is often the minimal side effects. Emphasising this through education and marketing may increase public acceptance of phage therapy.
"Even though phage therapy may be some years away from routine clinical use in the UK, increasing pressures from the AMR crisis require evaluation of the UK public’s acceptance of alternative treatments."
This study was funded by the University of Exeter, through hybrid funding from the Living Systems Institute (Catalyst Fund), Department of Biosciences (College of Life and Environmental Sciences) and the College of Social Sciences and International Studies (Associate Dean of Research Fund). The authors have declared no competing interests.
