Life After Lyme Disease

White footed mouse - Peromyscus leucopus

The Borrelia burgdorferi bacterium responsible for Lyme disease can infect humans, birds and mammals, and is transmitted to different hosts by tick bites. There are a number of animals that can carry the Borrelia burgdorferi bacterium and they can pass this on to uninfected ticks, but in many cases of zoonotic diseases (those transmitted from wild animals to domestic animals and humans) there is one natural animal host in particular responsible for incubating the bacterium. In the case of Lyme Disease researchers had historically considered mice (in particular white-footed mice) to be the main animal reservoir for this disease in North America, as past studies have shown that almost 90% of all ticks feeding on infected mice pick up the Borrelia burgdorferi bacterium, which is an infection rate almost double of any other species. Also mice are very common animals that occupy diverse habitats from woodland to residential districts, which would increase the spread of this disease across a larger area and this combined with the high infection rate would support the assumption that mice were the primary reservoir of Lyme disease.  Current vaccination strategies aimed at bringing Lyme disease under control throughout northern America have been based on the assumption that white footed mice are the main source of the Borrelia burgdorferi infection cycle.

New Studies

However new evidence from studies undertaken by biologists from the University of Pennsylvania have revealed that Lyme disease may have a much more complicated host pattern than first thought, and that there are actually a wide number of vertebrate species that contribute to transmitting the Borrelia burgdorferi bacterium. In a recent in-depth study carried out in the high risk tick infection area of the Hudson Valley, researchers discovered that both mice and deer (another species that is commonly linked to Lyme disease), did not actually factor very highly in the cycle of transmitting the Borrelia burgdorferi bacterium infection. The research revealed that just 25% of infected ticks were fed by mice, much less than the 55% of infected ticks discovered to have been fed by shrews in the same area. This evidence indicates that other factors such as animal population density had a huge influence on the spread of the Borrelia burgdorferi bacterium, and that focusing on just one species such as the white-footed mouse was not an effective way to combat the spread of this disease.

Combating Lyme Disease

Zoonotic pathogens (such as the Borrelia burgdorferi bacterium that causes Lyme disease) that can cross easily between human and animal species are a major threat to ecological systems all around the world, and areas where residential and wild land converge such as at forest and woodland boundaries are particular high risk zones. It is very important that researchers understand exactly how the diseases spread to

Woodland edges are high risk areas for Lyme Disease

different species and across to humans, so that they can work with governments and health authorities in finding new strategies to help protect the public and minimize the spread of infection both in wild and domestic animals. Identifying the main animal host or hosts of pathogens such as Lyme disease can be a key weapon in combating the impact of zoonotic emergences, as strategies can be implemented that interrupt the transmission of infection such as between the ticks and the primary animal hosts, thereby breaking the infection cycle and preventing the disease from spreading to new areas.

Lyme disease is a condition transmitted by the saliva of ticks when they feed on a host (human or animal), and is caused by the Borrelia burgdorferi bacteria.  It is thought that the Western blacklegged tick and the deer tick are the primary carriers of the Borrelia burgdorferi, and these are common throughout northern America and southern Canada, and high risk areas of infection for humans include forest and woodland edges and open grassy areas.

Diagnosing Lyme Disease

Testing for the Borrelia burgdorferi infection

Lyme disease typically manifests in the early stages as a skin rash, often with a characteristic ‘bulls eye’ inflammation pattern, which can take between 3 to 30 days to develop.  However it has been estimated that in as many as 30-50% of cases no rash will develop at all, and this can make diagnosis in the early stages very difficult.  If left untreated Lyme Disease can develop into more serious symptoms, which can include meningitis, heart problems, arthritis, nerve damage (peripheral neuropathy) and inflammation of the spinal cord and brain (encephalomyelitis).  Lyme disease can be challenging to diagnose, as many of the symptoms are common across a wide range of other conditions, and there are as yet no conclusive tests for identifying the disease in its early stages (serological testing is only useful when the disease has progressed further). Many patients with Lyme disease are not correctly diagnosed in the early stages, and this can lead to months and even years of unnecessary suffering.  Lyme disease can actually be treated very successfully with either oral or injected antibiotics if caught in the early stages, but if left untreated the condition can become very serious and then it can be much more difficult to combat the disease and its symptoms once it has turned chronic.  Many physicians are still relying on serological testing to identify the condition, but this is simply not reliable enough and has been shown to fail to detect the Borrelia burgdorferi infection in as much as 20% of clinical tests.  One of the reasons current tests are ineffective in the early stages of the condition is that it can take as much as six weeks after the initial infection for the Borrelia burgdorferi bactera in the blood to reach large enough levels to show up in testing.  Also this bacteria can sometimes lie dormant for long periods of time, and this can make a diagnosis difficult if it emerges later on, as the patient may not connect the condition with any exposure to ticks that occurred in the past.

Blood test for Lyme Disease

This is why it is so important that physicians are educated in the process of identifying and diagnosing Lyme disease in its early stages, and the key to this is not clinical tests but possessing a good epidemiological understanding about the risks of patient exposure to infected ticks.

Surveillance

Physicians also play a vital role in the surveillance of ticks and can help to identify new endemic areas quickly by being able to diagnose the disease effectively, and also by reporting all suspected and confirmed cases to the local Health Authority.  This process has helped researchers to pinpoint infected tick emergence in Canada, and has shown tick populations spreading in Ontario, Nova Scotia, Manitoba, Quebec and British Columbia. Through enhanced surveillance and increased awareness of symptoms and treatments, physician can play a crucial role in minimizing the impact of Lyme disease as it spreads to new areas.

Not all ticks carry the Borrelia burgdorferi bacterium responsible for Lyme disease, and if you live in, or intend to travel through an area with a risk of Lyme disease it is important you understand which species of ticks are potentially harmful so that if you do get bitten you can take the appropriate action. 

Ixodes scapularis - The Deer Tick

Deer Ticks

Those ticks that primarily carry the Borrelia burgdorferi bacterium are blacklegged ticks (Ixodes scapularis), also known as deer or bear ticks, and these are very small when they are not engorged (around the size of a pinhead), and when they have fed they swell to around the size of the tip of a pen.  The female is slightly larger and reddish brown and the male darker brown in color, and they are very difficult to spot on household pets.  Deer ticks live in the woodland and forest in dense, cool underground, leaf litter and brush and feed mainly on mammals such as rodents and deer, and because they predominantly live on the woodland edges and in densely landscaped residential areas they can regularly come into contact with humans.  Deer ticks wait near ground level for passing prey, and can latch onto your feet, legs and ankles as you brush past, crawling upwards until they find a spot to bite you.  Lyme disease can be treated with oral or injected antibiotics, and early diagnosis and treatment is essential as this disease can cause serious complications such as Lyme arthritis and problems with the heart and nervous system.

Western blacklegged Ticks

Western blacklegged ticks (Ixodes Pacificus) are physically very similar to the blacklegged deer tick, and are also known to carry the Borrelia burgdorferi bacterium that causes Lyme disease and are found in the same kinds of habitats and also throughout more open grasslands.

Rhipicephalus Sanguineus - The Brown Dog Tick

Brown Dog Ticks

Brown Dog ticks (Rhipicephalus Sanguineus) are a slightly larger species and are much easier to spot, and when they are engorged they form a visible, grey/green color blob, about the size of a fingernail.  They are not known for carrying the Borrelia burgdorferi bacterium, but they can transmit Ehrlichiosis to both pets and humans, which can cause fever, fatigue and lameness. Ehrlichiosis can be treated with antibiotics, and it is important to diagnose the condition early as it can cause serious blood related problems in vulnerable people such as young children and older adults.  Brown dog ticks can be found in grassy and wooded areas and anywhere dogs are kept including kennels and barns.

Dermacentor variabilis - The American Dog Tick

American Dog Ticks

American Dog ticks (Dermacentor variabilis) do not carry the Borrelia burgdorferi bacterium, but they can transmit other diseases to both pets and humans such as Rocky Mountain Spotted Fever (RMSF), which is caused by the Rickettsia rickettsii bacterium, and symptoms include fever, nausea, vomiting, and severe headaches, and this can be treated effectively with antibiotics. American dog ticks can be found in grassy areas, meadows and woodland.

Amblyomma Americanum - The Lone Star Tick

Lone Star Ticks

Lone Star ticks (Amblyomma Americanum)  are also known as seed ticks, and are similar in size to dog ticks but they have a distinctive white blob on their backs.  There is some debate over whether or not Lone star ticks carry the Borrelia burgdorferi bacterium, but they have been confirmed as carriers for Ehrlichiosis and RMSF.  Lone star ticks live mostly in wooded areas with ground cover and brush, and are also found along creeks and rivers

Image of adult blacklegged tick

Lyme disease is a tick-borne infection, and is primarily spread to humans through bites from deer ticks, Western blacklegged ticks and possibly lone star ticks.  These tick species carry the Borrelia burgdorferi bacterium which causes Lyme disease, and feed on a number of small to medium size mammals and birds including small rodents, deer and household pets.

Birds

Birds play a major role in the spread of Lyme disease as they can pick up a tick carrying the Borrelia burgdorferi bacterium in one location, and because it takes a long time for ticks to feed they could be hundreds or even thousands of miles away before the tick finally drops off.  The seasonal migration of birds in Northern America is key to the spread of Lyme disease and over 650 species of bird migrate to different parts of the world annually, either taking part in long distance migration to places such as Africa, Eastern Europe and South America, or short distance migration of just a few hundred miles.  Many birds such as White-throated Sparrows and robins spend the winter in Northern America before moving on to summer feeding grounds in Canada, and there are also a number of transitory birds that pass through Canada as a stop over on the way to other feeding grounds, and many of these could potentially be carrying infected ticks or the Borrelia burgdorferi bacterium itself, which they could pass on to uninfected ticks in the areas they feed in.

The spread of ticks carrying Borrelia burgdorferi bacterium into Southern Canada

Reforestation

A number of factors can influence the spread of any insect species, but the main culprit for the spread of ticks is thought to be reforestation.  Ticks are hardy creatures, but they do require the right habitats to live in. For example the blacklegged tick thrives in cool, moist conditions and the majority can be found in forested areas with dense shrub layers to provide shade and moisture, and tend to condense along the forest and woodland edges, where food is most abundant.  They can also survive in denser underground planting in some landscaped residential areas.

In recent years many areas that were previous cleared for farmland in northern America have been reverted back to small patches of woodland and forest, creating ideal environments not just for ticks, but for the animals they feed on such as deer and small rodents.  This increase in wild tick populations would not normally be a major problem but as urbanization is also increasing, with residential developments encroaching on wild areas, more and more infected ticks are coming into contact with humans, and these woodland border areas in which ticks are prevalent are now coexisting alongside residential areas, creating high risk zones for Lyme disease crossing to humans.

Reforestation is thought to be having a significant impact on the increasing spread of Lyme disease from North America into Canada, and studies by the Public Health Agency of Canada have so far tracked new infected tick emergence in Ontario, Nova Scotia, New Brunswick, Quebec and Manitoba. 

Steps to Prevent the Spread

The Public Health Agency of Canada and other organizations are calling for national surveillance to be put in place to monitor the changing patterns of tick behavior, to identify new endemic areas quickly and effectively in order to notify the public and local health authorities and ensure education is put in place to minimize the impact of Lyme disease.  Doctors are now required to report any suspected and confirmed cases of Lyme disease to the Public Health Agency, and this enhanced surveillance combined with greater physician and public awareness are crucial steps to help mimize the impact of the disease as it spreads into Canada.

Microscopic Image of a Tick

Bacteria are some of the oldest forms of life on earth, and all life is thought to have developed from these simple but highly effective organisms.  During Earth’s turbulent history bacteria and other basic life forms have survived many natural disasters from devastating global forest fires to volcanic eruptions, glacial ages and meteor strikes, of all which saw billions of other species become extinct, and one of the greatest mass extinctions in history during the Permian Period 248 million years ago saw so many animal species wiped out (including 90-95% of all marine life) that Earth very nearly returned to a similar state as the Precambrian eon 3–4 billion years ago, where the only life on earth were microorganisms.

Pre-Ice Age Europe

It is not surprising to learn then that researchers have now discovered that the bacterium responsible for Lyme disease (Borrelia burgdorferi) is incredibly old and could actually predate the Ice Age, and was also thought to have originated in the continent we now know as Europe, rather than North America.

Previously experts had believed that the Borrelia burgdorferi bacterium originated in North America, but new studies from researchers at the University of Bath, which combined findings from both the UK and USA, have revealed a fascinating evolutionary history to this bacterium that charts its emergence and spread all the way back to pre-Ice Age Europe.  This research was gathered by extracting samples from infected ticks and humans and studying the sequence of a number of ‘housekeeping genes’ (a code for proteins which are essential for basic cell functions and present under any conditions), which evolve very slowly over a long period of time.  Because these housekeeping genes are so fundamental to the survival of the cell they are passed down through history largely unchanged, and contain valuable information dating back to the origins of the cell, and from this scientists can track the evolutionary path of the bacterium.

Results from Studies

From the results of the study carried out by the University of Bath’s Department of Biology & Biochemistry, researchers found 33 different combinations of these housekeeping genes in just 64 samples, and from this they were able to construct a ‘family tree’ based on actual molecular information, which is the first time this technology has been applied to tick-borne disease.  This family tree revealed that the oldest molecular information charted the origins of the Borrelia burgdorferi bacterium back to pre-Ice Age Europe, but did also show that it has been present in North American for a very long time as well.  The research also suggested that the geographic territory of the tick species that carry the Borrelia burgdorferi bacterium spread in the 1970’s, which can explain the re-emergence of Lyme disease during this time, and this may have been linked to efforts to restore woodland in North America that created new sustainable habitats for insects such as ticks to breed and spread.

The importance of this research cannot be underestimated as by understanding more about how this bacterium has spread throughout history, experts can predict more accurately just how it will develop into the future, and find more effective ways in which to combat and contain it.

New studies published in the November 2009 issue of Cell Host & Microbe (a leading scientific journal published by Cell Press) have shown some possible ways forward for scientists who are working hard to develop an effective vaccine for Lyme disease, which is caused by the bacterium Borrelia burgdorferi and transmitted through tick bites.  Researchers at the Yale School of Medicine and the Howard Hughes Medical Institute have discovered evidence that suggests a vaccine could be developed from a protein in the tick’s salvia (the pathogen’s transmitting agent), which could confer immunity to those people living in areas affected by this disease.

Developing the Vaccine

The interaction between the Borrelia burgdorferi bacterium and ticks is highly complex, and lead author Erol Fikrig, M.D. of Yale University stated that the recent studies have shown that the bacterium actually uses a protein in the tick’s saliva to ‘facilitate infection of the mammalian host’.  This means that the bacteria effectively ‘wraps’ itself in a coating of these proteins (which it stimulates the tick into producing in excess quantities), which masks its presence from the host’s immune system and allows it to pass into the system unnoticed.  Researcher believe that this interaction between the protein in the tick’s salvia and the bacterium is absolutely key to the infection process, and by interfering with this process an effective protective vaccine could be developed against Lyme disease.

Previous vaccines have been developed against Lyme disease but these have subsequently been removed from the market following unsuccessful field trials, and as yet no other antigens have been released for testing in phase III clinical trials.  These previous vaccinations targeted just the outer surface proteins of the pathogen itself, but the new research suggests that by adopting a different strategy and targeting the transmitting agent (in this case the tick’s salvia) instead of the pathogen a much more effective form of defense could be developed, which could have far reaching effects in the fight against not just Lyme disease, but other harmful insect-borne pathogens that as yet we are unable to vaccinate against such as dengue fever, West Nile virus and even one of the most deadly killers in the world, malaria.

As yet the research on tick’s saliva is still only in the laboratory stages, but the initial studies on animals at the Howard Hughes Medical Institute have shown that mice test subjects responded well to a basic antiserum produced to interfere with the protein in the tick saliva identified as being essential to the Borrelia burgdorferi bacterium infection of the host, which significantly reduced the risks of the mice becoming infected with Lyme disease after being exposed to this tick-borne pathogen.

Hope for the Future

These results are encouraging for the future of vaccination against not just Lyme disease but other insect-borne diseases, and can certainly bring a measure of hope for all those living in areas affected by the Borrelia burgdorferi bacterium.  Ticks produce anesthetics in their salvia that stop the bite from stinging, so in many cases the host does not even realize they have been attacked by the insect, and Lyme disease is an insidious condition and can be difficult to diagnose in the early stages as symptoms are wide ranging and include rashes (that can go unnoticed), fever and chills, tiredness, weakness and joint pain, and if left untreated can result in serious conditions such as heart problems and chronic fatigue.

If you know anything about Lyme disease, it is that there are conflicting opinions on how to treat the problem. In fact, this has been a sticking point for many years and it does not seem that things are going to calm down anytime in the near future. Many doctors, scientists and Lyme disease sufferers feel that long term antibiotics are the best way currently available to treat Lyme disease.

On Wednesday, February 17, 2010, New Hampshire House lawmakers approved a bill that would make it easier for doctors in the state to treat Lyme disease through the use of long term, prescribed antibiotics.

Why is this such a big deal, you may ask? In the past, doctors have been reluctant to prescribe long term antibiotics because many were skeptical of the existence of a chronic form of Lyme disease, primarily because of the flawed guidelines issued by the Infectious Disease Society of America (IDSA) who has consistently ignored scientific evidence that does not agree with their position. In addition many doctors are afraid that the IDSA will go after them and try to revoke their license to practice medicine, as has happened in several cases. With the passage of this bill, New Hampshire doctors will be able to treat their patients as they and their patients feel is best, without any intrusion by the IDSA.

Rep. Jen Coffee (R) of Andover had this to say about passing the bill: “Any medication has the potential to have a problem, but we allow long-term antibiotic use for treatment of acne — acne of all things.” She added, “Why wouldn’t we allow it for Lyme disease?”

Many people don’t think Lyme disease is a big problem, but once they take a closer look at the statistics they find out differently. Believe it or not, more than 25,000 new cases of Lyme disease are diagnosed across the country every year, and since Lyme disease is so frequently misdiagnosed, the true number of cases is most likely much higher. This has led to New Hampshire, as well as several other states, passing legislation to protect doctors who actually try to treat this debilitating disease. The states that have yet to have done so are holding back because they feel that long term treatments need to be studied in more depth, no doubt the result of the confusion caused by the controversy with the IDSA guidelines.

Lawmakers and doctors are not the only ones supporting the bill. Many Lyme disease sufferers have been actively lobbying for such bills to be passed in their state. They are tiered of being told by doctors who follow the IDSA guidelines that it’s all in their heads and they should just go home and suffer. Furthermore, because of these guidelines many insurance companies have began to refuse to pay for antibiotic treatments for chronic Lyme disease, adding more problems to the lives of those who suffer from this disease.

Kathy Kettmann a Lyme disease sufferer and supporter of the New Hampshire bill said: “I couldn’t walk. I couldn’t talk,”… “I was very sick, and to be put in a car for five hours to go to the doctor because we couldn’t get treated in New Hampshire was hard.”

It yet remains to see if the New Hampshire State Senate will pass the bill. It will also be interesting to see if more states follow suit with similar legislation.

Parker Posey is questioning conventional medicine after the pills she was prescribed failed to cure her of Lyme disease.

The Best In Show star was forced to pull out of an off-Broadway play earlier this year (2009) to focus on battling her tick-borne illness.

Doctors had put Posey on a course of antibiotics but after that treatment failed to restore her health, she decided to try a holistic approach and treat her Lyme disease with supplements and a complete change in her diet. She felt so much better after her holistic treatment that she decided to lend her backing to a new documentary, Rethinking Cancer, about patients who seek out alternative methods of treatment.

She says, “As someone who dealt with Lyme disease recently, I had the opportunity to approach it both with conventional medicine (antibiotics) and homoeopathic remedies and supplements. The first round of antibiotics did not destroy all the bacteria and I made a decision not to take them anymore and instead approach it purely holistically – through the help of my homoeopathic doctor, who guided me with my diet and gave me the natural supplements to bring my body back to its vitality.
“It raises the questions: How can a natural approach to healing oneself be considered so unconventional? Why do we think we can’t play an active role in getting healthy? Why do we give ourselves away so easily to pharmaceuticals that deplete our system and confuse the natural healing process?”

New Haven, Conn. — Yale researchers have discovered that a protein found in the saliva of ticks helps protect mice from developing Lyme disease. The findings, published in the November 19th issue of Cell Host & Microbe, may spur the development of a new vaccine against infection from Lyme disease, which is spread through tick bites .

Traditionally, vaccines have directly targeted specific pathogens. This is the first time that antibodies against a protein in the saliva of a pathogen’s transmitting agent (in this case, the tick) have been shown to confer immunity when administered protectively as a vaccine.

The Lyme bacterium known as Borrelia burgdorferi is transmitted by ticks. When it moves through the tick, it is coated with a tick salivary protein known as Salp15. The Yale research team injected Salp15 into healthy mice and found that it significantly protected them from getting Lyme disease. When combined with outer surface proteins of B. burgdorferi , the protection was even greater.

Lead author Erol Fikrig, M.D. of Yale School of Medicine and Howard Hughes Medical Institute said, “The interaction between the Lyme disease agent and ticks is very complex, and the bacteria uses a tick salivary protein to facilitate infection of the mammalian host. By interfering with this important interaction, we can influence infection by the Lyme disease agent.”

Several years ago there was a Lyme vaccine on the market that utilized just the outer surface proteins of the bacteria. It was taken off the market in 2002, and to date no other antigen has been tested in phase III clinical trials.

The authors believe this new strategy of targeting the saliva – the “vector molecule” that a microbe requires to infect a host – may be applicable not just to Lyme disease but to other insect-borne pathogens that cause other human illnesses.

“We believe that it is likely that many arthropod-borne infection agents of medical importance use vector proteins as they move to the mammalian host,” Fikrig explained. “If so, then this paradigm, described with the Lyme disease agent, is likely to be applicable to these illnesses. Currently, we are working to determine if this strategy is likely to be important for West Nile virus infection, dengue fever, and malaria, among other diseases.”

Other researchers were Jianfeng Dai, Penghua Wang, Sarojini Adusumilli, Carmen J. Booth and Sukanya Narasimhan of Yale School of Medicine, and Juan Anguita of the University of Massachusetts. This work was support by grants from the National Institutes of Health.

Contact: Helen Dodson , 203-436-3984

Source: Yale University

Using a powerful microscopic live imaging technique, a research team led by Dr. Justin Radolf, professor in the Departments of Medicine and Genetics and Developmental Biology at the University of Connecticut Health Center, has discovered that how ticks transmit Lyme disease to humans is different than was previously thought. His research is published online in the Journal of Clinical Investigation .

It has been known for some time now that Lyme disease is caused by the transmission of the spirochete bacterium Borrelia burgdorferi from ticks to humans, but the transmission process has been difficult to study for a number of technical reasons.

Dr. Radolf and researchers Star Dunham-Ems and Melissa Caimano tried a novel approach at solving this mystery. They genetically modified a virulent strain of B. burgdorferi with a green fluorescent protein (GFP). “This bacterium glows and can be followed in the living state as it migrates through the tick to the mouse during feeding,” explains Radolf. “Then using a powerful microscopic technique called confocal microscopy, we discovered that the transmission process unfolds quite differently than previously believed.”

Spirochetes in culture are highly motile, and it is widely believed that during feeding, the spirochetes in the mid-gut rapidly move through the wall of the mid-gut. But Radolf and his team discovered that during much of the feeding period, the spirochetes do not move. They actually divide and surround the cells of the mid-gut lining or epithelium, forming tight networks. “We also found that the reason they don’t move is that the tick mid-gut secretes molecules that actually inhibit the motility of the spirochetes,” explains Radolf.

Eventually, spirochetes in the networks reach the base of the epithelium by completely surrounding the epithelial cells. At this point, they become motile, detach, and completely penetrate the mid-gut, although in very small numbers. These bacteria then swim to the salivary glands, which they penetrate en route to the mouse. “So rather than being entirely motility-driven, dissemination of spirochetes within ticks actually happens in two phases,” says Radolf, “which is something we didn’t know before.”

Lyme disease is the most prevalent vector-borne infection in the United States with more than 25,000 new cases reported annually. “The improved understanding of the transmission process revealed by our study could lead to novel strategies for controlling the spread of Lyme disease,” says Radolf.