At the first classification of Lyme disease in 1981, its symptoms had already been well known all around the world. Among the characteristic “Bull’s-eye” rash called erythema migrans at the site of the tick bite, the fever, and fatigue, its symptoms were and still are continuously misdiagnosed, due to how easily they can be associated with other diseases (CDC, 2022). Within the last two decades, the number of Lyme disease cases reported in the United States has doubled, and the number of counties considered high-risk for Lyme disease has tripled (CDC, 2022). Because this is a tick borne disease, and people are often at risk simply by spending time outdoor, this drastic increase is largely due to the rise in global temperatures affecting both habitat and ecosystems of both the black-legged ticks that transmit the disease and the host mammals they subsist on such as deer and mice. Presently, there is only one way to treat Lyme disease, through the use of antibiotics such as doxycycline and amoxicillin. While these antibiotics can effectively treat Lyme disease if caught early enough, the overuse of antibiotics can lead to the emergence of antibiotic-resistant bacterial strains, making prevention critical in reducing the burden of the disease. Due to the continuous increase of the global climate, predicted to affect Lyme disease, and the overall prospect of declining anti-infectives, I propose a new standard preventative treatment using the VLA15 vaccine to both maximize individual health outcomes and improve the overall preservation of antibiotics for critical infections. This preventative treatment will counter the continuous rise in healthcare costs associated with Lyme disease, cut the total number of people catching the disease, and lower the overall use of antibiotics, reducing the risk of the emergence of new antibiotic-resistant bacteria.
Introduction to Lyme:
Directly after being infected with the borrelia burgdorferi bacterium, the symptoms start at the early localized stage, which is typically seen within 1 to 28 days after the infection. Generally, symptoms at this stage only include the characteristic circular skin rash and flu-like symptoms. The type of tick and the length of time it was attached to its host can influence when the symptoms set in, and their strength. Approximately 20-30% of those infected can be asymptomatic until the disease has progressed into its later stages. Stage 2, the early disseminated stage, typically develops 3-12 weeks after the initial infection. At this point, the bacteria has spread through the body and multiple symptoms may occur, the most common of which include neurological problems such as facial paralysis and cardiac symptoms such as heart palpitations. These symptoms may last up to 12-20 weeks. Late disseminated stage Lyme disease can occur months or even years after the initial infection. Typical symptoms at this stage include neurological and rheumatological involvement with its “key feature” being painful arthritis in the knee’s (Simonsen, K, 2023).For early cases, a 2-4 week supply of oral-antibiotics is usually curative. However, in early and late disseminated stage Lyme, treatment may become complicated due to antibiotic treatment failure and the further health complications caused by the disease. Furthermore, approximately 5% of all patients that contract Lyme disease incur lingering symptoms of fatigue, pain, or joint and muscle aches after their treatment (Simonsen, K, 2023). This condition is often called post-treatment Lyme disease syndrome (PTLDS) and can last at least 6 months after the final administered treatment. The reason some patients experience PTLDS and others don't is still not fully known. Many experts believe it is due to the presence of “persisters cells'' that resist the effects of antibiotics by entering into a dormant state (CDC, 2021).
Currently, based on state and local health department passive reporting systems, approximately 35,000 people are reportedly affected by the Lyme borrelia burgdorferi bacterium every single year (CDC, 2021). However, cases can often go unnoticed because this disease is very geographically and seasonally oriented and its symptoms often overlap with other diseases. In addition, the passive reporting system relies on the providers submitting their records, resulting in a massive underreporting of the true prevalence of the disease. As a result, this value is only a fraction of the systematically estimated value calculated through insurance claims data. The CDC recently released an estimate of approximately 476,000 Americans being diagnosed and treated for Lyme disease each year (CDC, 2021).
Effects of climate change on Lyme:
Not only does Lyme disease have the potential to cause long-term harm to its victims, but recent reports suggest that global rates are on the rise. A 2022 report from the FAIR health nonprofit group used its database of over 36 billion privately billed healthcare claims to estimate that Lyme disease diagnoses rose 357 percent in rural areas around the US since 2007 (FAIR Health, 2022). A large reason for this massive growth of Lyme disease can be attributed to the increase in global warming. Borrelia burgdorferi is primarily transmitted to humans through the bite of an infected black-legged tick. Ticks thrive in warmer temperatures since they themselves are exotherms, their bodies don't maintain consistent internal temperatures like mammals and birds (Chrobak. U, 2022). Coincidentally, the changes in global temperatures and precipitation patterns have led to a geographical expansion of these ticks. Statistics from the Environmental Protection Agency (EPA) have shown a rise in transmission of Lyme disease from 3.74 per 100,000 people in 1991 to 7.21 per 100,000 people in 2018. Many factors, including global warming, have nearly doubled the number of people transmitting Lyme disease (EPA, 2021). As the climate warms, tick populations have been able to thrive in areas where they were previously unable to and longer than they've previously been able to. Increasing the likelihood of contact with humans. Furthermore, climate change already has impacted the behavior and range of multiple mammals that act as hosts for the ticks. As the habitat and ecosystem of these mammals continues to shift due to global warming, the tick population will follow (EPA, 2021). This growth in cases has shown researchers that the market for a new and improved method to treat Lyme exists and this market will continue to expand. When asked in August 2022 about the use of a new vaccine, VLA15, Annaliesa Anderson, Senior Vice President and Head of Vaccine Research & Development at Pfizer claimed, “With increasing global rates of Lyme disease, providing a new option for people to help protect themselves from the disease is more important than ever.” As the threat for any infectious disease increases due to an unavoidable external factor, the need for an effective and affordable preventative treatment becomes increasingly urgent. The development and widespread use of the VLA15 vaccine could provide this treatment for Lyme disease.
Treatment or Prevention:
With the current reliance on successful antibiotic therapies for Lyme disease, the development of a vaccine may seem unnecessary. Antibiotics have long been considered one of the most significant discoveries in 20th century medicine; however, the constant heavy usage and misuse has led to a new and growing global concern: antibiotic-resistant bacteria. These new bacterial strains, often called superbugs, have developed resistance to the effects of some or, in few cases, all antibiotics. This makes infection much more difficult to treat. Antimicrobial resistance mechanisms develop when a bacteria or fungi mutates to develop resistance naturally. These mechanisms include the development of new cell processes or the modifying of the antibiotic’s target protein. A bacteria might even find a way to destroy the antibiotic directly with its own enzymes or proteins (CDC, 2021) As a result, antibiotic-resistant bacteria are a growing concern in various professional industries, especially in the field of medicine. Infections caused by these bacteria almost always lead to prolonged illness and increased hospital costs, often even causing death. Presently, antibiotics are among the most commonly prescribed drugs for people. When used properly, an antibiotic does what it's meant to, destroy the disease causing bacteria in the host. But antibiotics also often end up destroying a wide variety of good bacteria that are used to fight other infections and help keep you healthy. When an antibiotic is overused, the bacteria that are strong enough to survive the drug will continue to have a chance to grow and multiply, creating the superbug. “We need to make the best use of the drugs we have, as there aren’t many in the antibiotic development pipeline,” says Dr. Jane Knisely, who oversees studies of drug-resistant bacteria at the National Institute of Health (NIH). “It’s important to understand the best way to use these drugs to increase their effectiveness and decrease the chances of resistance to emerge.” (NIH, 2014). To combat the increase in drug-resistant bacteria, we must use antibiotics judiciously and only when necessary. In the case of Lyme disease, a vaccine such as VLA15 could provide an alternative treatment, reducing the overall reliance of antibiotics for its treatment. This, in turn, can help preserve the effectiveness of antibiotics for critical infections, providing a longer solution to this growing problem of antibiotic resistance.In addition to preserving antibiotics, a vaccine would also help shift the approach to Lyme disease from treatment to prevention. The latter is preferred since simply getting infected can lead to increased healthcare costs and potential long term health complications. Currently, there are multiple ways one can prevent Lyme disease, including both personal protective measures and environmental control measures (CDC, 2022). Personal protection consists of: knowing when and where to expect ticks; wearing protective clothing and insect repellent in these areas; conducting tick checks on your body, clothing and pets; and removing any attached ticks. For environmental control measures, keeping your lawn and surrounding areas well-groomed and managed with repellents such a DEET or acaricides (tick pesticides) may help reduce the number of ticks (Clark, R. N. et al, 2008). A study using 2727 households in 3 northeastern states tested the effectiveness of these acaricides and concluded that acaricide barrier sprays do reduce the total abundance of ticks by 63% but did not significantly reduce the household risk of tick exposure or incidence of tick-borne disease (Hinckley, A. F. et al, 2016). By combining both of these measures you can still largely reduce the possibility of getting bit, but they won't be able to provide complete protection against the disease. There is still a risk of exposure and infection, and in cases where these preventative measures fail, treatment becomes necessary. In contrast, the new VLA15 vaccine can provide a more reliable and long term solution to prevention.
VLA15 Vaccine:
The VLA15 vaccine is the only Lyme disease vaccine candidate currently in clinical development. This multivalent protein subunit vaccine works by triggering the immune response and stimulating the production of antibodies. VLA15 antibodies specifically target a protein on the Borrelia bacteria called the Outer Surface Protein A (OspA). This protein is essential for the bacteria's survival in the gut of the tick, which is then transmitted to humans through the tick's bite. The vaccine's resulting antibodies prevent this protein from attaching to human cells after its migration into the human host where it would then cause infection (Comstedt, 2017). So far, VLA15 has demonstrated a strong immune response and has entered phase 3 of clinical studies as of March 2022. In Phase 2 of the VLA15 study, 294 healthy adult and children participants received either 2 or 3 shots spaced out at about 3 months apart. The results showed highest immunogenicity in adults receiving the triple-dose schedule. The safety and tolerability profile levels observed for the children, ages 5-17, was still very similar to the adult participants but not as effective (Valneva 2022). Further testing is planned to study this variability in greater detail. The randomized phase 3 study called VALOR is planned to enroll 6000 participants aged 5 years and older. All participants will be receiving 3 doses over 9 months at the most effective dosage level, followed by a booster dose (Valneva and Pfizer 2022).One potential benefit to VLA15 is its cost. The cost of any vaccine can vary, and largely depends on multiple factors, such as the type of vaccine, its production costs, research and development costs and where it's being administered. In the case of VLA15, it is challenging to estimate the potential cost, considering it is still under development and has not yet been approved for use by any public agencies. I was able to calculate a potential price for a single VLA15 dose by using the data of a previously discontinued lyme vaccine called LYMErix. This discontinued vaccine was approved into the market for $50 a shot and was also a recombinant protein-based vaccine that targeted the outer surface protein A. While LYMErix and VLA15 are biologically similar, VLA15 is designed to address some of the limitations of the previously discontinued lyme vaccine (NIH, 2021). Knowing they both had similar biological frameworks, the VLA15 shot can be estimated to be priced around $50. With the understanding that a full VLA15 vaccination might require three shots, the total cost is around $150. However, this value of $150 is significantly less than the average costs of typical treatment for the disease. According to a study done by researchers at Tufts Medical Center in collaboration with the Centers for Disease Control (CDC), the average cost of treatment per patient for Lyme disease was estimated to range from $3000 to $5000, including medical costs such as doctor visits, tests, medications, as well as indirect costs associated with lost productivity due to illness (Mac, S. et al, 2019). This estimate does not include the potential addition of one or multiple acaricide treatments, which would add an extra $100-$200 per acre of land. (Jordan, R. A. et al, 2019). Therefore, investing in the development of the VLA15 vaccine would not only help prevent Lyme disease but also be a more cost-effective solution for patients and the healthcare system.
Public perception on a Lyme Vaccines:
In 1998, the FDA approved the recombinant Lyme disease vaccine called LYMErix, which was able to reduce the amount of infections in vaccinated adults by nearly 80% (Nigrovic et al, 2006). The vaccine was unfortunately discontinued in 2002 due to insufficient sales and the unfounded belief that it further caused arthritis in Lyme disease. LYMErix was just one of many vaccines whose sales were affected by the anti-vaccine movement. Starting the same year, Andrew J. Wakefield led a public outcry against vaccinations, stating they caused autism, intussusception and many other problems. Because of this, the public climate was disquieted around any new shot, especially an optional one such as LYMErix. Since then, no one has tried to replicate anything similar. This public perception has thankfully changed since then. In 2010, Wakefield's research was retracted and considered fraudulent (Sathyanarayana et al, 2011). Over time, this public perception has improved. Recent surveys done by the National Institute of Health after the Covid-19 pandemic showed that 60-70 percent of the general population is now willing to accept and use vaccines (Fisher et al, 2020). The discontinuation of LYMErix and the anti-vaccine movement serves as a poignant reminder of the effects that misinformation and fear can have on public health. Fortunately, this perception has changed for the better, and hopefully will continue to grow.The comparatively low cost of the VLA15 vaccine would also allow for wide distribution in high-incidence areas. Those who live in warmer climates and are at higher risk could be targeted to receive the vaccine, as data suggests populations in these areas may be receptive to a new preventative approach. Cases in high incidence states in the northeast, mid-atlantic and upper midwest have been rising relatively consistently while cases in states neighboring the high incidence states have been increasing at a rate faster than ever seen before in the U.S, proving the geographic distribution of this disease is quickly expanding into new states. Among the most high incidence states, Maine, Vermont and New Hampshire, there's been an increase in about nearly 100 cases per 100,000 people since 1991 (EPA, 2021). In these states, a preventative treatment such as this vaccine can be more useful than simply relying on antibiotics after becoming infected. A quantitative research questionnaire was conducted among 357 private woodland owners in southern Maine to test their perceptions of psychological constructs related to Lyme disease. The results showed that 80% of the respondents agreed that there is a high risk of being bitten by ticks if they spend time in their own wooded land. 82% of the respondents showed emotional discomfort in avoiding those same areas in fear of developing Lyme disease. Some more interesting results from the data showed that 72% of the woodland owners believed that contracting Lyme disease would have a significant impact on their life and 46% showed emotional discomfort at the fact that their communities don't take preventable measures towards managing tick populations (Olechnowicz, 2023). These correlations show an advertently large number of individuals that have high susceptibility truly concerned about Lyme disease, with over 75% of the woodland owners intentionally not spending time in certain areas of their property due to these concerns and potential health problems after infection. In a survey, where 3313 respondents from high incident states were asked if they would be willing to receive a Lyme disease vaccine specifically, 64% reported they were willing, with 29% saying they were undecided (Hook, 2022). By raising awareness and promoting education about the importance of immunizations and vaccinations, the potential number of individuals supporting the idea of any vaccine can increase, ultimately leading to a higher percentage of individuals willing to get a Lyme Vaccine.
PrEP or VLA15:
A different approach to preventing Lyme Disease is being developed by the University of Massachusetts Medical School using Pre-exposure prophylaxis (PrEP). Unlike the vaccine, this specific PreP treatment uses a laboratory-made monoclonal antibody that, when administered, binds to and neutralizes a specifically chosen pathogen, preventing it from attaching to the host and causing harm. In the case of Lyme disease, the monoclonal antibody attaches to the outer surface protein A (Wang, Y. et al, 2016). This is the same protein that is being targeted in the VLA15 vaccine. The Lyme PrEP treatment has already entered Phase 1 of human trials as of February 2021 with the intention of learning how long it remains in the bloodstream (Jim Fessenden, 2021). A potential benefit from the PrEP approach is that it greatly reduces the likelihood of side effects since it’s a singular dose and makes the recipient immune to the disease the same day they receive the shot, unlike most vaccines where one would have to wait a few weeks before the antibodies are made. While the development of the Lyme PrEP treatment is an interesting alternative to preventing Lyme, it’s important to weigh the potential benefits versus the financial costs of a PrEP treatment.Presently, there are two monoclonal antibody PrEP treatments available on the market, one is being used for HIV and the other for Covid-19. The Covid-19 treatment, Evusheld, was bought by the U.S government in December 2021 and supplied at no cost to the public due to the pandemic (HHS, 2021). The cost of Cabenuva, the HIV treatment, typically ranges from $1200 - $2500 per month, covering only the cost of the medication. The high cost for this treatment is due to multiple factors. A significant one is that this type of treatment is still relatively new. PrEP was only first approved by the FDA in 2012 (CDC, 2021). The development of new drugs is a long and complex process that involves years of research, clinical trials and then regulatory approval. These research and development costs are then often passed onto the consumer. The Lyme monoclonal antibody PrEP treatment just recently entered its phase 1 clinical trials, with the intention of finding out how often a shot would be necessary (Jim Fessenden, 2021). Although it is incredibly promising in preventing the infectious disease, its high cost still poses a challenge for widespread use. On the other hand, the VLA15 vaccine, estimated to cost only $150 for full vaccination, presents a more accessible and cost-effective option for everyone. The success of previous, more affordable, vaccines highlights the importance of investing and developing in new cost-effective preventative measurements such as VLA15 to fight against infectious diseases.
Conclusion:
The development of the VLA15 multivalent protein subunit vaccine is a promising solution in the fight against Lyme disease. The need for a new and more effective form of preventing this disease is now eminent. Vaccines have been tested and used as preventative treatments for over a century now. This new vaccine would greatly benefit the world, and especially the communities most burdened by Lyme disease. Not only would the introduction of this vaccine reduce healthcare associated costs but it would also greatly help decrease the risk of the emergence of new antibiotic-resistant bacteria. This vaccine would benefit the country both medically and financially. By contributing to the development and distribution of the VLA15 vaccine, we can take a step towards the elimination of Lyme disease as a public health concern, and provide a better future for the millions of people affected by this debilitating disease.
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