Lyme borreliosis. An emerging or re-emerging disease?

Table of Contents

Introduction

History of Lyme Disease

Characteristics of the Pathogen

Transmission

How Does Borrelia burgdorferi Causes Lyme Disease ?

Stages and Symptoms of Lyme Disease

Treatments

Statistics and Cases of Lyme Disease

Current Management of Lyme Disease

Modifications and Improvements to the Management

Conclusion

Reference

Source Analysis

Introduction

Diseases are lethal abnormal conditions of the body which stops it from functioning completely or partially (Centers for Disease Control and Prevention, NP). Diseases are separated into two different categories, infectious disease and non-infectious disease. Infectious diseases are diseases that can be transferred to another person through methods of direct or indirect contact. Non infectious diseases, on the other hand, cannot be transferred and can be due to lifestyle and environmental factors or genetics.

Emerging infectious diseases refers to a pathogenic disease that arose recently in a population for the first time (World Health Organization, NP). Re-emerging infectious diseases, however, are diseases that were once a major health problem but has declined due to reasons such as cures being developed. But the pathogen that caused the disease has rearose in a different form that is immune to its original cure (National Institutes of Health US, NP).

Pathogens are biological agents that infects its hosts and causes disruption of its normal physiology through diseases (Science Daily, NP). Pathogens are separated into different categories such as bacteria, viruses, fungi, protozoa, prions and macro parasites (Science Daily, NP). Each of these different types of pathogens have their own ways of transmission, infection, survival in the host and reproduce. In order for a pathogen to be successful, it needs to avoid the host’s immune system long enough to infect a new host (Biozone Learning Media Australia, 2014). There are many ways pathogens are transmitted amongst humans such as skin contact, contact of bodily fluids, airborne transmission and vector-borne transmission (Science Daily, NP). Pathogen transmission is efficient and successful in high density populated areas as the pathogens can be easily transmitted from person to person. After pathogens have entered the human body, they begin to multiply. The immune system of the host will respond to the foreign organism by sending out white blood cells and antibodies which functions to rid the pathogens either by directly attacking it or using other mechanisms such as raising the body temperatures which helps rid the viruses as the body becomes a less favorable host (Scientific American, 2005). However, some pathogens are able to evade the immune system and continue to cause diseases. The focus of this research, Lyme disease is an example of this.

History of Lyme Disease

Lyme disease has been around ever since ticks started feeding on human blood. However, the disease was not officially recognized until 1970s where a group of adults and children, from Lyme, Connecticut, started mysteriously suffering from symptoms such as paralysis, rashes and headaches (Bay Area Lyme Foundation, NP). These patients, who were left undiagnosed, started recording notes and researching about their own health problems (Bay Area Foundation, NP). Using the notes that were left by the patients, scientists were eventually able to discover the presence of the infectious bacterial disease that were causing the symptoms and later named it the Lyme disease.

Characteristics of the Pathogen

There is three different types of spiral shaped bacteria, or spirochete that causes Lyme disease (Encyclopedia Britannica, NP). Amongst them, Borrelia burgdorferi (Shown in Figure 1) is the most common cause of Lyme disease and it mostly affects the North America region. The other two pathogens, Borrelia afzelii and Borrelia garinnii mainly affects the Europe and Asia regions. Borrelia burgdorferi has a length of around 20 µm and a width of only around 1 µm, its growth is ideal in a micro-anaerobic environment at a temperature of 32°C (LymeNet Europe, NP). Borrelia burgdorferi is also known for having a flagella located in between the inner and outer membrane of the bacteria which helps it propel into tissues and heavy mucus (MicrobeWiki, 2013).

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Figure 1. Anatomy of Borrelia burgdorferi (Pearson Education Inc, 2006)

Transmission

Lyme disease is mainly transmitted by ticks of the genus Ixodes (Tilly K et al., NP). Ticks require blood meals to complete their life cycles. When a tick that is in its larvae stage has its first few blood meal on small mammals with one of them being the natural reservoir, the pathogen, Borrelia burgdorferi from the natural reservoir will then infect the tick and remain in the tick’s gut (Centers for Disease Control and Prevention, 2015). The tick will continue to have blood meals from small mammals and simultaneously infecting them with the bacteria, causing them to become natural reservoirs. Once the tick enters its nymph stage, the pathogen migrates to the salivary glands of the tick. These ticks then feeds on larger animals such as humans and will transmit the pathogen during a blood meal. (Bay Area Lyme Foundation, NP). These processes are shown in Figure 2.

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Figure 2. Life Cycle and Transmission of Borrelia burgdorferi in Ticks (Centers for Disease Control and Prevention, NP)

How Does Borrelia burgdorferi Causes Lyme Disease?

The immune system protects the body against pathogens and germs. It mainly consists of white blood cells that circulate through the blood stream to detect pathogens. However, Borrelia burgdorferi is able to not only evade the immune system's response but is also able to use the immune system against the host. When the pathogen enters the bloodstream, it encounters a dendritic cell which is responsible for alerting the immune system through the presence of a pathogen’s antigen (Envita Medical Center, 2008). The bacteria comes into contact of the dendritic cell and rubs its antigen on the cell intentionally. After the dendritic cell has processed the antigen, Helper T cells collects the antigen and passes it to another cell called the Killer T cell. This cell is responsible for directly killing any infected cells (T-cell Modulation Group, NP). The Killer T cells uses the antigen of Borrelia burgdorferi to track down the pathogen. Meanwhile, the pathogen spreads its antigen on the surface of a tissue or organ to attract the Killer T cells and the pathogen itself uses its flagella to propel into the tissue or organ (Envita Medical Center, 2008). The Killer T cells then follows the bacteria’s antigen to the tissue or organ that has been infected, however, the cell cannot identify and differentiate between the antigen of Borrelia burgdorferi and the tissue. Thus, the Killer T cells begins to attack the healthy tissue which causes inflammation in the tissue and destroys the tissue. This is shown in Figure 3. The pathogen is also capable of shifting its shape by altering the outer cell wall which "disguises" the pathogen against the immune system (Holtorf Medical Group, NP). As the pathogen spreads through the blood stream, heavy inflammatory responses occur throughout the body which potentially causes organ (including brain) and tissue damages (Holtorf Medical Group, NP).

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Figure 3. Killer T Cells Destroying the Healthy Tissues (Envita Medical Center, 2008)

Furthermore, the bacteria can also release a neurotoxin named Bacterial Lipoprotein (Envita Medical Center, 2008). This toxin can greatly weaken the immune system and can cause inflammation and damage to the nerve systems of the host which is shown in Figure 4. As a result, people who suffer from Lyme disease can have symptoms of memory loss and neurologic pain.

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Figure 4. Bacterial Lipoprotein Affecting the Nerves (Envita Medical Center, 2008)

Stages and Symptoms of Lyme Disease

In the first stage, the early localized stage of Lyme disease, the pathogen has just entered the human body. This stage has flu like symptoms and 70 to 80% of patients will also have a red, bull’s eye rash at the site of the tick bite (Centers for Disease Control and Prevention, NP). However, sometimes, there may also be no symptoms at all (WebMD, NP). In the second stage, the early disseminated infection, the pathogen has just started spreading around the body and the neurotoxin (Bacterial Lipoprotein) also starts to take effect (Envita Medical Center, 2008). Patients experience memory loss, fainting and rapid heartbeat (WebMD, NP). In the third stage, the late persistent Lyme disease, the bacteria has separated all over the body and affects the joints, nerves and the brain. This stage is the most lethal and symptoms of heart problems, sleep and speaking problems is present. At this stage, the pathogen may also hide in the body and reappear in months or years after the bite from the tick.

Treatments

The most effective treatments currently is the use of antibiotics. At the early stages, treatment is a 14 to 21 day course of either the doxycycline or the cefuroxime antibiotics (Centers for Disease Control and Prevention, NP). All signs and symptoms of infection is usually cleared after the course. However, the treatment has a chance of 14 to 39% failure rate and the symptoms will continue which causes the infection to enter second or third stage (LymeDisease.org, NP). The treatments become more complicated in later stages. At the second stage, depending on the seriousness of the symptoms, patients are either recommended to take oral or intravenous antibiotics and therapy (Hu L, NP). At the third stage of Lyme disease, the patients are recommended to take oral antibiotics for up to 28 days. If symptoms do not get better, it is recommended to take intravenous therapy which in most cases, symptoms will decrease (Hu L, NP).

Statistics and Cases of Lyme Disease

Lyme disease is the most common tick borne disease in the United States. In 2014, 25,359 confirmed cases of Lyme disease was reported (More detailed statistics, Figure 5) in the United States (Centers for Disease Control and Prevention, NP). However, the results of studies conducted claims that the actual number of people that are diagnosed with Lyme disease could be up to 300,000 each year (Stricker R, 2014). According to the Lyme Disease Association, a total of 36 deaths were reported from 2002 to 2007, with 2007 having the greatest number of deaths (Refer to Figure 6). Furthermore, reported cases of Lyme disease has tripled in 2009 since 1991. Nevertheless, Lyme disease is a continuous disease, it will infect people constantly and did not have any major epidemic or outbreaks.

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Figure 5. Detailed Statistics on Cases of Lyme Disease From 1995 – 2014 in the United States (Centers for Disease Control and Prevention, NP)

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Figure 6. Number of Deaths Due to Lyme Disease in the United States (Centers for Disease Control and Prevention, NP)

Current Management of Lyme Disease

Diagnosing, preventing and curing Lyme disease is difficult due to the mechanisms of the pathogen and its ways of transmission. Furthermore, it is impossible to eradicate the disease unless all of the pathogen’s wild reservoirs such as the white footed mouse are eliminated or the Ixodes ticks that transmit the pathogen are eradicated completely which is not achievable as it will have a heavy impact on the ecosystems. However, there has been many different approaches and steps taken into trying to prevent Lyme disease. One of the most notable achievement is the successful development of a vaccine to prevent Lyme disease, named LYMErix. The strategy of this vaccine is to vaccinate humans against the protein, Osp A, which is present on the outer membrane of Borrelia burgdorferi. This causes the immune system to develop bactericidal antibodies that circulate in the body’s blood (Oxford Journals, NP). When the tick ingests the blood during a blood meal, the antibodies enter the tick’s guts and effectively bind or neutralize the pathogen present in the tick (Oxford Journals, NP). This vaccine was extremely effective, with a prevention rate of 50 to 100% (Food and Drug Administration, NP). However, due to the public not knowing the dangers of this disease and health professional’s lack of knowledge about this disease and vaccine, the purchase of this vaccine was very low and the development was considered unprofitable. Furthermore, hypothesis was made by scientists which claimed that the Osp A protein contained in the vaccine may cause arthritis in people with certain genetic structures which caused continuing pressure placed on the developers of this vaccine by anti-Lyme vaccine groups, the developers soon withdrawn the vaccine from the market, leaving no vaccines available against Lyme disease (Oxford Journals, NP). However, the Food and Drug Administration later claimed that the vaccine was tested negative for the harm that this vaccine has been claimed to be causing (Centers for Disease Control and Prevention, 2015). Nevertheless, the only vaccine for Lyme disease was withdrawn.

Apart from developing vaccines to prevent Lyme disease, many local governments has also tried to warn the public with road signs of heavy tick infested areas. They have also urged the public to adopt tick prevention methods such as wearing long sleeves and using insect repellent when entering tick infested areas (Centers for Disease Control and Prevention, NP). However, this is not effective as some people do not understand the seriousness and the high chances of transmitting diseases like this one from ticks. Furthermore, even with long sleeve clothing, ticks are still able to potentially crawl into clothes through openings. Moreover, most commercial insect repellent uses diethyltoluamide as the main ingredient, but, these kind of insect repellent are not very effective towards ticks as they are against mosquitos (LymeNet Europe, NP). It is also practically impossible to accurately identify the geographical areas of tick infestation which causes many of the road signs to be inaccurate.

Many institutions currently have on going Lyme disease research and companies such as Baxter are developing new vaccines against the pathogen and may be released in the near future (National Institution of Health, NP).

Modifications and Improvements to the Management

Past vaccines has failed due to many factors such as having adverse effects and no market. However, these vaccines are, to some degree, successful in actually working as a prevention method towards Lyme disease. Developers require their vaccines to be profitable or it presents no value to the developers. Thus, to increase the market for Lyme disease vaccines, authorities should begin to firstly recommending this vaccine to people who lives or works in areas of tick infestation. Secondly, trying to raise awareness and educating the general public about the risks and dangers of Lyme disease through sources such as the media.

The next concern is the vaccine itself. Specific requirements must be met for the new vaccine to be successful in the prevention of Lyme disease. Firstly, the vaccine must provide protection for all Borrelia bacteria as Borrelia burgderforgi is not the only bacteria from that genus that causes Lyme disease. Secondly, the new vaccine must be also efficient and safe for the use of children as children between 5 and 10 years old has more reported cases then all other age groups which is shown by Figure 7. Thus, the use of this vaccine in children will be essential (Centers for Disease Control and Prevention, 2015). Thirdly, the vaccine would require at least an efficiency of 80% otherwise the vaccine would be insufficient in trying to protect the body against Lyme pathogens (Centers for Disease Control and Prevention, 2015). Fourthly, the vaccine needs to have prolonged efficiency or the vaccine will lose its effect after a short amount of time and the patients may need to revaccinate which could cause some patients to choose to not use a vaccine. Lastly, and most importantly, the vaccine must rid most after or side effects which was also one of the main reason that LYMErix was withdrawn.

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Figure 7. Cases of Lyme disease Based on Age and Sex in the United States (Centers for Disease Control and Prevention, NP)

Fundamentally, more research and development must be put into effectively preventing this disease from infecting more people. However, the research will require great amounts of money. Thus, governments should start considering increasing their funds towards Lyme disease research. The current yearly fund for tick borne diseases is only 74 million and Lyme disease research is only one part of it (National Academy Press, 2011). Yet the funding CDC received from the US government for the use of Ebola responses and prevention had a value of 1.771 billion dollars (Centers for Disease Control and Prevention, NP). However, Lyme disease had around 3,000 more confirmed cases than Ebola. Furthermore, the funding should not only be towards the research of Lyme disease but also contribute to educating the general public about the dangers of Lyme disease and the promotion of new vaccines.

One alternative method that is currently under consideration is to use the chemical named Permethrin which is a neurotoxin that is able to kill ticks when they come into contact (Leprince DJ, NP). This chemical is sprayed onto cotton balls and are distributed in different habitats. Small mammals (potential natural reservoirs) could collect these cotton balls and use it as nesting materials (Leprince DJ, NP). The chemical could then kill any ticks that tries to feed on the small mammals and systematically transmit pathogens to the small mammals (LymeNet Europe, NP). However, this method would be ineffective as the chances of these cotton balls being collected is very low unless a lot of it was distributed. The ticks would also be able to still reach the small mammals as this chemical must come into contact to take effect. Furthermore, the chemical only lasts up to a week and thus cotton balls would need to be continuously manufactured and distributed which makes this method inefficient.

A more feasible method could be to develop a vaccine for small mammals (potential natural reservoirs) (Kurtenbach K et al., NP). The strategy for this vaccine could be similar to LYMErix. This vaccine could be able to potentially deactivate or neutralize the pathogen whilst being transmitted from the ticks. The vaccine can be developed into a form of bait and placed around the habitats of small mammals. If this vaccine is successfully developed and distributed, this method could greatly decrease the population of natural reservoirs, infected ticks and Borrelia bacteria. And thus, reducing the number of people being infected. This vaccine must be able to firstly, deactivate or kill the bacteria whilst it is still in the tick's guts. Secondly, safe for the use of the small mammal with no significant adverse effects. Thirdly, this vaccine can be used for different species of small mammals and is effective towards different Borrelia bacteria.

On a smaller scale, an effective insect repellent that specifically targets ticks could also be developed and commercially sold. This could also reduce the chances of tick bites whilst in tick infested areas and potentially reduce the number of infections.

Conclusion

In conclusion, Lyme disease is a major emerging disease that is caused by Borrelia burgdorferi which is a bacteria that is transmitted from natural reservoirs to ticks and then to humans during tick blood meals. The bacteria is able to evade the immune system and cause this disease. This disease can be fatal if not treated during early stages with antibiotics and there is currently no vaccines to prevent this disease beforehand. This disease has not been viewed as seriously by the general public and has not attracted the pharmaceutical interest than other diseases such as HIV/AIDS and Tuberculosis but the consequences of this disease can be just as great (Daniel J C et al., 2014). Moreover, human’s knowledge on Lyme disease is also less compared to the other diseases which greatly prohibits humans to develop suitable prevention methods towards this disease.

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Source Analysis

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