The Vaccine Blog
youmevaccines@gmail.com
The Vaccine Blog
youmevaccines@gmail.com
Vaccines against antibiotic resistance
Please note that I am not a medical professional and this is not medical advice. It is for informational purposes only. For health advice, see your doctor.
Introduction - the impact of indisposition (illness) caused by antimicrobial resistance
Antimicrobial resistance (AMR)
It is one of the biggest causes of indisposition (illness) and death across the world
This is also projected to increase across the next several decades
In 2019, AMR was named by the World Health Organization as one of the most serious threats to global health, along with indisposition (illness) caused by ebola, dengue fever and climate change. In the same year, it was responsible for 1.27 million deaths globally, and contributed to a further 4.95 million additional deaths. Not only this, according to the Centre of Disease Control and Prevention, over 2.8 million antimicrobial resistant infections occur each year. It also costs over 4.6 billion USD annually to treat antimicrobial resistant infections caused by six antimicrobial resistant microbes. AMR is also projected to cause 5.2 million deaths in the Western Pacific by 2030.
Clearly this is anxiogenic (worrying)
Clearly, it poses a significant burden to global health and medical infrastructure.
Thankfully, the issue isn't irremediable. Combination therapies, that is, when 2 or more antibiotics are combined to treat patients in clinical settings, are frequently used to treat severe infections. Further, research looking for new antibiotics, and indeed altogether new approaches to antibiotic discovery are both very active areas.
However, what if we took a pre-emptive approach? What if we got ahead of antibiotic resistant infections, and resulting indispositions, before they happened? I`m sure the topic of my blog is a spoiler, but I am of course referring to vaccination against AMR pathogens and that's what I'll discuss in this post.
How does antibiotic resistance occur?
It's important to first ask the question; how does antibiotic resistance occur? According to the World Health Organisation, resistance evolves when “bacteria evolve or acquire genes that allow them to survive exposure to antibiotics, rendering the drugs ineffective.” According to a 2017 paper published by Nicholas Waglechner and Gerard D Wright, “the sources, distribution, and movement of resistance mechanisms in different microbes and bacterial populations are mosaic features.” That is, the specific resistance mechanisms used vary across different species and populations of bacteria. Further, new resistance mechanisms are consistently discovered; however, researchers are exploring methods to predict the evolution of such mechanisms.
And although I`ll mainly explore resistance in the context of indisposition (illness), it is important to note that microbes are everywhere and thus antibiotic resistance is not limited to the clinic - they are widely distributed across different bacterial species and strains. They are also present in almost all environments.
With that said, what are these mechanisms?
How does antibiotic resistance occur, specifically?
A detailed description of this is outside the scope of this article but broadly, bacteria may acquire a new genetic mutation that confers resistance to commonly prescribed antibiotics, exchange DNA with another bacterium of the same or a different species, or take up free DNA from the environment (this is known as transformation). Genetic material may also be packaged and transferred from one bacterium to another by a virus that specifically infects bacteria.
Vaccines and AMR
At this point, let's delve into the key focus of the article
Vaccines for AMR
According to a 2024 report from the World Health Organisation,
Although this accounts for only a small proportion of AMR-related infections and hospitalisations, significant advancements have been made in the area. I will give several examples of this here.
Tuberculosis
One couldn't discuss this topic with at least touching on tuberculosis.
Tuberculosis is the world's deadliest infection, causing over 1.4 million deaths annually. In 2023, 10.8 million people globally fell ill with tuberculosis, including 6 million men, 3.6 million women and 1.6 million children. Of these cases, it caused 1.25 million deaths. 161,000 of these had HIV, with tuberculosis being the leading cause of death in this population.
Further, certain regions are disproportionately impacted by tuberculosis. According to the European Centre of Disease Control and Prevention (eCDC), “Three countries (Poland, Romania and the United Kingdom) account for roughly 40% of all reported cases, with Romania alone accounting for approximately 20%.” Not only this, a 2022 study by Chuan de Foo and colleagues found that low and middle-income countries (LMICs) face a high prevalence of tuberculosis and noncommunicable diseases.
Are there vaccines to preemptively combat antibiotic-resistant tuberculosis?
Currently, the main vaccine available for tuberculosis prevention is the Bacillus Calmette-Guerin,which has been widely distributed for 140 years since its initial development. It is not routinely administered at birth; it is recommended only for children at high risk of tuberculosis. These include those with diabetes mellitus, HIV patients, household and other contacts of TB patients, socioeconomically disadvantaged individuals, prisoners, healthcare workers, those living in congregate settings, and those who have had certain medical procedures. Children are also at increased risk because their immune systems are developing.
There are a few important caveats to note here
Some people may fit one, more or all of these criteria
Others may have risk factors not even noted in research yet
Further, sometimes risk factors can interact in very complex ways and give unexpected and unpredictable outcomes
But does it work?
Does it actually combat indisposition caused by antibiotic-resistant microbes?
Broadly , the answer is yes.
However, it is not sufficient in certain groups in specific settings.
So, better vaccines are needed; however the beneficial effects of BCG vaccines must not be lost.
According to the World Health Organisation, it prevents indisposition (disease) caused by severe forms of tuberculosis in children, who are known to be particularly prone to disseminated tuberculosis. These include tuberculosis meningitis and miliary tuberculosis disease (a life-threatening, rare form of tuberculosis in which the bacteria spread through the blood and form lesions in different organs). In particular, it is effective in children under 5 years of age. Interestingly, it has also recently gained attention for its potential effectiveness in preventing COVID 19 (this also applies to other respiratory infections). Despite this, the official stance of the World Health Organisation (WHO) is that there is insufficient evidence to recommend BCG vaccination against COVID 19, and they do not recommend BCG vaccination to prevent contracting COVID-19.
In adults from developing countries and in certain other settings, however, it varies considerably in its effectiveness against tuberculosis. Its effectiveness in adolescents against pulmonary tuberculosis and adults varies greatly. Generally, effectiveness ranges from 0% to between 60% and 80% across studies. However it varies according to a number of factors. This effectiveness is also influenced by age (it is generally more effective in infants and children), socioeconomic status, previous exposure to environmental, nonpathogenic mycobacteria, and pre-existing conditions, particularly in patients who are immunosuppressed due to HIV infection.
Not only does baseline effectiveness vary, the duration of its effectiveness can also be different across populations. The majority of studies find that it is effective from 10-15 years following vaccination, and some up to 20 years.
Although severe or long term indisposition after BCG vaccination is rare, it is important to note that BCG vaccination is not recommended for some high-risk groups. A 2024 study of eleven children with severe combined immunodeficiency found high rates of severe complications post-vaccination. However, it is important to note here that eleven children is a small sample size, and larger studies are needed to make definitive conclusions. Further, according to the CDC website, people who are immunosuppressed, such as candidates for organ transplants or HIV-infected people, should not receive the BCG vaccine. It is also contraindicated (not recommended) for pregnant women as further research is needed to prove its effectiveness in this population.
Salmonella typhi
I can imagine most healthcare and scientific professionals, as well as the general public have at least heard of the indisposition caused by these bacteria.
According to the website of the Centre of Disease Control and Prevention (CDC),
Indisposition caused by these bacteria are rare in the European Union (EU) and European Economic Area (EEA) , with the majority of cases being acquired during travel to areas outside the EU and EEA. This is particularly true in areas with inadequate sanitation practices, and where water and food are not treated or screened properly for contamination with microbes. Such areas include Asia, Africa, and certain areas in Asia (eg. Pakistan, India, and Bangladesh).
In other words, it's unlikely that those in the West will contract these indispositions in everyday life.
Three vaccines are currently available to prevent typhoid fever. In no particular order, the first is an injectable typhoid conjugate vaccine , the second being an oral live attenuated (weakened) vaccine called Ty21a, and the third being an injectable unconjugated polysaccharide known as Vi-PS (short for polysaccharide).
The first, Typbar TCV, is a conjugate vaccine that was prequalified by the World Health Organisation in January 2018. It is recommended for use in individuals aged 6 months up to 45 years, and its administration is prioritised in countries with a high burden of typhoid disease or antimicrobial resistance. The CDC also notes that it is not 100% effective, and not a substitute for safe eating and drinking practices (ie. handwashing, safe food handling practices, and so on). Typbar TCV has had robust effectiveness across large-scale studies.ranging from 80% to 85% across different regions and populations.
Vi-PS is an injectable polysaccharide vaccine. It is recommended by the World Health Organisation for those aged 2 years or older. It should be administered as a single dose intramuscularly or subcutaneously. This single dose is found to provide more moderate (approximately 60%) protection in studies than is found with Typbar. Regardless, it is a crucial component of preventing typhoid fever in endemic regions, and so re-vaccination is recommended every 3 years. Finally, the Ty21a vaccine is an oral live attenuated vaccine. The World Health Organisation recommends a 3-dose oral immunisation schedule, administering the vaccine every second day. It is available in capsule formulation for those over 6 years of age
Conclusion
Indispositions related to antibiotic resistance are a global burden to health and healthcare infrastructure. This trend will escalate into the future. The research outlines the importance of underappreciated preventative strategies such as vaccination to address this and, in turn, save lives.
