Friday, February 25, 2011

Lyme Disease


This week I'll be describing Lyme disease, which is another vector-borne infection. The vector is once again an arthropod although this time it is a tick rather than a mosquito. The arthropod-borne pathogen for Lyme disease is a now bacterium, rather than a virus, as was the case for both of the two previous arthropod-borne infections we covered. This discussion will proceed a little differently than have the previous two arthropod-borne infections. First we'll cover the clinical disease itself, then we'll discuss the primary vector and it's ecology, then the bacterial organism, Borrelia burgdorferi, and finally the epidemiology. I think this discussion flow will feel more natural to the particular circumstances of Lyme disease.

Lyme disease can be a very debilitating disease, particularly if it is not identified and treated early. Lyme disease can be roughly categorized into three chronological stages, or manifestations, although all three stages do not necessarily manifest even in untreated individuals. In early Lyme disease, a red macule or papule will often appear on the skin followed later by a lesion with an erythematous border and clearing center. It looks like this:


This rash is very distinctive for Lyme disease and is very useful for diagnosis in the early stage, however the rash does not present in every person who becomes infected unfortunately. The lesion is not typically painful or itchy (pruritic), but can be warm to the touch. Early Lyme disease is also often accompanied by flu-like symptoms: headache, fever, chills, malaise, and body ache. Interestingly, it is only at this early stage that the bacterium causing infection, B. burgdorferi, can be isolated from blood and cultured, so unless the clinical symptoms are caught early the opportunity will be missed. Symptoms associated with the early stage will generally resolve in 3 to 4 weeks.

The second stage, known as disseminated Lyme disease, can occur 1 to 6 months after initial exposure. Disseminated Lyme disease can present with more generalized lesions (as opposed to the localized lesion of the early stage), myocarditis, and neurologic disease. More specifically, when disseminated Lyme disease is present, it will often occur with multiple lesions on the body, intense lethargy, encephalopathy, muscle pain, lymphadenopathy, and splenomegaly. Myocarditis will occur in approximately 5% of untreated persons who develop disseminated Lyme disease, while the neurologic complications will occur in about 15% of untreated persons that go on to develop disseminated disease. These neurologic complications can include meningitis, meningoencephalitis, cranial nerve neuropathies, radiculitis, and distal neuropathies. The symptoms of disseminated Lyme disease will typically resolve in about 6 weeks.

Finally the late stage of disease, if it occurs, can appear months to years after initial infection. The most common manifestation of late Lyme disease is arthritis in one or multiple joints. Approximately 60% of infections will develop Lyme disease-associated arthritis if the infection is untreated. Arthritic attacks can last from weeks to months and the episodes can recur over many years. This condition can cause long-term ongoing disability and diminished quality of life. Generalized encephalopathy and distal polyneuropathy can also accompany late Lyme disease, further contributing to dysfunction and disability.

Diagnosis of infection depends on when in the clinical course the disease is identified. Clinical presentation is very important in early stage Lyme disease. In particular, a thorough history that captures recent outdoor activity is absolutely critical and should be regular practice for physicians practicing in endemic areas. Identification of the erythematous (EM) rash is usually sufficient for diagnosis of infection in early Lyme disease, but this EM rash is not present in all persons infected and so, while it is quite specific it is not sensitive enough for consistent diagnosis. This is precisely why a detailed history of all outdoor activity is essential. Simply inquiring about tick bites is not enough because often the tick and it's bite are very small and go unnoticed. B. burgdorferi can be cultured, but only during this stage of early Lyme disease, so effective microbiology, in the absence of the EM rash, also depends on a thorough history. In disseminated and late Lyme disease the opportunity to identify the pathogen directly is lost. In secondary, or disseminated, Lyme disease clinical presentation is again very important. In particular the combination of meningitis and cranial or distal neuropathy are very informative and suggestive of Lyme disease. However, detailed history is again very important, though one must remember that the time point of exposure and initial infection will be further removed from clinical presentation of disseminated Lyme disease. Antibody response is measurable only several weeks after initial infection, as IgM is typically not detectable in early disease. On the other hand, IgG is often present (but not always) in disseminated disease so this can be a viable marker of infection in many (but not all) people.

The vector. So, we are switching from the mosquito vectors we have talked about in the last several weeks to a very different organism altogether: ticks. In particular we are talking about Ixodes scapularis, the deer tick, AKA blacklegged tick, in the northeastern United States, Ixodes pacificus in the western US, and Ixodes ricinus in Europe, the Mediterranean, the Middle East, and parts of Central Asia. These ticks are hard-bodied ticks of the family Ixodidae. Each of these three tick species can transmit Lyme disease. Additionally, I. scapularis is responsible for transmitting not only Lyme disease, which is caused by the bacterium B. burgdorferi, but also babesiosis and anaplasmosis. Because of the endemic nature of Lyme disease in parts of the northeastern and midwestern US, I. scapularis has been the most studied tick in relation to Lyme disease and so this discussion will focus on this species:

 Ixodes scapularis

An important characteristic of I. scapularis for infection transmission is that this tick is quite small. Moreover, while it is small in each of its developmental stages, it is barely visible in its nymphal stage until it reaches the point where it is completely engorged with blood. Here is a look at some scaled pictures of each of the developmental stages of this tick:


The top row of ticks represent I. scapularis and are scaled to a ruler and other ticks below.


The above picture compares engorged and non-engorged nymph and adult ticks. The two ticks on the left are both nymphs with the far left non-engorged and the one to its right an engorged nymph. The two ticks on the right are both adults with the one on the left a non-engorged adult and the one on the right an engorged adult.

The above picture shows just how difficult it can be to identify these ticks, particularly before they have become engorged with blood. If they are obscured by hair, one has little hope of identifying them to prevent infection without active tick inspection.

This tick has a complex life cycle that, unlike mosquitoes, is NOT completed with the passing of a single season (even though many mosquitoes are capable of overwintering). In fact, most mosquito species can complete several generations of life cycles within one season, depending on their local geography and climate. In contrast, Ixodes species require two years to complete their life cycle, with different developmental stages needing to transition through 8 distinct seasonal changes. This adds levels of complexity and layers of dependencies to the tick life cycle that we did not encounter with mosquito life cycles. Let's take a closer at this life cycle:



The life cycle proceeds as follows: First, the eggs hatch in the spring and the new larvae need to feed by taking a blood meal. The preferred host for this blood meal is the white-footed mouse. After this first, and single, blood meal, the larvae rest and overwinter. During this time they develop into dormant nymphs. Next, the nymphs emerge in the following spring, and they do so before the newly emerging larvae, which will be hatching from the eggs later in the spring. Are you still with me? Good, because the nymphs, now newly emerged, again require a blood meal to continue the life cycle of the tick. Once again the preferred host is the white-footed mouse. Following this blood meal and another period of rest, the adult ticks emerge in late summer or early fall and will require a second blood meal to reproduce, which is taken from a large mammal (typically the white-tailed deer, thus the common name, "deer tick"). The male and female ticks mate on the host mammal, the males dies and falls off, and the female overwinters for the second time in her life cycle. When the female emerges for the last time in the spring, she lays her eggs, which will hatch later that spring after the nymphs emerge. We can now appreciate the complex ecologically-driven evolution of these ticks, which pass through several levels of climate and weather variation, and multiple host population dynamics across two years of time. Impressive.

There are a some important features of this life cycle that are relevant to the transmission of the pathogen, B. burgdorferi. First, the staggered appearance of  the nymphs before the larvae each spring ensures the maintenance of the mouse reservoir for B. burgodorferi. Larvae that hatch in the spring are NOT infected with B. burgdorferi because this bacterium is not transmitted vertically from the adult female tick to her eggs. However, the larvae can become infected when they take their blood meal from an infected white-footed mouse, and they will remain infected as they develop into nymphs. When the nymphs emerge, if they became infected as larvae then they will now have the potential to infect any uninfected white-footed mouse if they happen to select such a mouse for their blood meal. Because the nymphs emerge in the spring before the larvae, and thus bite and infect mouse hosts before the larvae get to the mice, the nymphs replenish and maintain the mouse reservoir for B. burgdorferi, which can subsequently infect the pathogen-naive larvae emerging later that spring. This is a superb example of the co-evolution of this pathogen with it's vector and host species, and highlights the fine ecological balance required for its survival.

This brings us to the second important feature of the tick life cycle: human encroachment on this delicate ecology. Notice how humans are included as incidental hosts for both nymphal and adult ticks:



Humans are not natural hosts for either stage of the tick. Humans are also not the natural hosts for the bacterium. Humans are incidental hosts for both the vector and pathogen. Human contact with the tick results primarily from expanded land use development into areas that were previously undeveloped. For example, expansion of suburban residential communities and commercial zones into forest areas encroaches on the forest habitat. This encroachment brings humans into contact with the ticks in transition habitat areas (known as ecotones), which were previously comprised of the unmolested habitat of deer and mice. This is represented in the picture above by including humans in the host boxes along with the natural hosts at both the nymphal and adult stages of the tick life cycle.

Humans, like deer, are dead end hosts for B. burgdorferi, and so these large mammals cannot infect ticks with the bacterium. The mouse is the primary reservoir, therefore, while both the mouse and deer are necessary for the survival of I. scapularis, it is the mouse and the tick that are necessary for the survival of B. burgdorferi.

That brings us back to the agent of Lyme disease itself: the bacterium, Borrelia burgdorferi. Here's a look at it:



This is a gram negative spirochete bacterium. This motile organism's cellular structure is comprised of an inner and outer membrane and a flagellum. B. burdorferi's outer surface proteins are very important for the organism's infectivity and pathogenicity. There are two outer surface proteins that are of particular relevance: outer surface protein A (OspA) and outer surface protein C (OspC). While B. burgdorferi is in the tick gut, it expresses OspA, which allows the spirochete to attach to the wall of the tick gut. When the tick takes a blood meal, the host blood changes the environment inside the tick's gut. The spirochete senses this change in chemistry and temperature, which stimulates the bacterium to stop expressing OspA and to start expressing OspC. In the absence of OspA B. burgdorferi detaches from the stomach wall of the tick and is free moving. At this point the OspC expressing B. burgdorferi crosses the epithelium of the midgut and migrates to the salivary glands via the hemolymph. Here is a graphic depiction of the process:


This migration is a relatively SLOW process. It takes approximately 60 hours of this gradual accumulation of the organism in the salivary glands of the tick to produce sufficient numbers of the bacteria to infect a new host. This, of course, has very important implications for the prevention of Lyme disease in humans. Because infectivity requires a couple days of feeding, if you can identify a tick on the body early and remove it you can prevent it from transmitting the Borrelia pathogen.

The incidence of Lyme disease closely reflects the distribution of Ixodes ticks, as we would expect:




Lyme disease in the United States is most concentrated in the Northeast and upper Midwest where the deer tick is well-established, as can be seen in the two maps above. Incidence rates can be greater than 1 per 100 persons per year in some areas of New York and Connecticut. Here is the New York incidence depicted below:


Publications by the Morbidity and Mortality Weekly Report show that Lyme disease incidence rates vary greatly by state:


But there is also great variation within states by counties:


Control and prevention of Lyme disease must focus on the human point of contact with ticks. Attempts to intervene at the level of any of the other organisms is likely to consistently meet with failure because of the complex ecologies involved. For example, control of the favored host species of the tick (i.e. the white-footed mouse and the white-tailed deer) is extremely difficult as these animals are ubiquitous, highly adaptive, and can exploit a wide range of habitat. In addition, the wide variety of hosts available to the tick at the larval, nymphal, and adult stages make controlling Ixodes quite difficult. And finally, the complex life cycle of the tick, which maintains the reservoir status of the white-footed mouse, as well as the competency of this primary host to serve as a reservoir, ensure that B. burgdorferi will persist in concert with the mouse's persistence. Thus elimination of the bacterium is also highly unlikely. Therefore, control and prevention is best aimed at human points of contact. Use of long-sleeved shirts and long pants are very effective control measures as these eliminate tick access to human skin. However, this approach may not be realistic for those that live, or work outdoors, in endemic areas during the summer months. As such, individuals who do spend time outside during the summer months and are at risk of exposure to ticks, should practice regular body tick checks.

Here is a nice video on the proper way to remove ticks from the skin:





Next week I will begin an extended series on malaria, so be sure to follow the posts.

40 comments:

  1. Dear Dr. Walsh:

    Really interesting information on lyme disease and the almost "indestructible" ticks! I liked the insidious youtube video on the killer ticks.

    I just have some curious questions. Do different ticks from different environments exhibit differing types of lyme disease? Is lyme disease vector similar throughout every tick in the US? Has there been any resistant strains of lyme disease to current medical treatment? Any comments would be most appreciated.

    Thank you for the insight on ticks and I am looking forward to hearing your blogs and lectures again when I get a chance.

    -Lawrence

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  2. Hi Lawrence.
    These are excellent questions. Thanks for posting.

    The two main tick vectors in the US that transmit Lyme disease are Ixodes scapularis and Ixodes pacificus, corresponding to the Northeast and West, respectively. In Europe, the tick vector is Ixodes ricinus and in Asia the vector is Ixodes persulcatus. Moreover, the organism that causes Lyme disease, Borrelia burgdorferi, also varies by geographic region with certain strains being very prominent in the Northeastern US, and others dominating in Russia and China, for example. This variation in the Borrelia strains corresponds to the different tick distributions mentioned above. For example, in Europe the primary vector is Ixodes ricinus, and the Borrelia strains that are most prevalent are Borrelia burgdorferi sensu lato, Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. So in Europe, there is far greater variability of the organisms across geography than in the US, and this does indeed correspond to different tick species. Finally, the clinical manifestation can and does vary according to the different strains. However, all the clinical symptoms described in this post can and do occur in any geographic location where Lyme disease is endemic.

    Another important consideration for Lyme disease in any geographic location is the vectorial capacity of the tick in a particular environment. By vectorial capacity, I mean the rate of potential infectious contact between the host and the vector. The situation in the US demonstrates this concept well. In the northeastern US, for example, the tick comes into frequent contact with alternative human hosts because of human encroachment on the habitat of the tick's primary and natural hosts. Since humans provide a suitable alternative for this species of tick, the vectorial capacity of the tick for human transmission of Borrelia is heightened in this particular geographic region. On the other hand, in the southeastern US, Borrelia is maintained in the rodent reservoir by tick species that rarely bite humans (Ixodes spinipalpis, Ixodes affinis, and Ixodes minor). The bridge vector between rodents and humans, Ixodes scapularis, is also present here but it prefers lizards at key developmental stages. As such, there is far less contact between Ixodes scapularis and humans in the Southeast compared with the Northeast. So the vectorial capacity in the Southeast is low, while it can be quite high in the Northeast even though we are talking about the same vector and same Borrelia.

    There has been documented resistance to antibiotics in Borrelia burgdorferi, particularly to erythromycin. Doxycycline or amoxicillin are typically the first line drugs, for adults and children, respectively, and usually constitute effective therapy. Nevertheless, erythromycin resistance is important as this is the drug of choice for treatment in pregnant women. Another important issue in Lyme disease treatment is persistence of symptoms following treatment. This condition is not uncommon and is associated the syndrome known as "chronic Lyme disease". Whether this condition is due to a failure of the antibiotic therapy to clear the Borrelia or due to an autoimmune response induced by the organism, which remains even after the organism is eliminated, is not definitively known. However, most studies indicate that prolonged antibiotic treatment is not helpful in the alleviation of these symptoms.

    Thanks again for these insightful questions, Lawrence.

    Cheers,
    Michael

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    1. http://www.hindawi.com/journals/ipid/2010/876450/

      This article is discussing chronic lime disease (CLD)... This is actually a problem as there are at least 116 million people living with acute and chronic pain in the United States some of which may be attributed to persistent infection with the Lyme spirochete, Borrelia burgdorferi. CLD is beleived to cause pain and suffering equivalent to that of diabetes or congestive heart failure.

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  3. What does the incidence of Lyme disease look like in the exurbs and suburban areas that have no forest areas to speak of? I know that the deer thrive in the town my grandparents live in, but my guess would be that the mice would be actively exterminated as pests. In that case, perhaps the deer may act more as a sink in these areas for Borrelia infected ticks?

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  4. Robin,
    I found an article that talks about the rise of Lyme disease in suburban areas. It's interesting because the article addresses a rise in deer population in the area and also discusses how climate change has created a more habitable area for the tick. I also found a study from Westchester County that found the prevalence of Lyme disease for 114 persons entering the study to be 8.8%. It seems that as we alter the environment and change the habitat of animals we are mor prone to the diseases they carry.

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  5. Interesting article about the tick and the incidence of lyme disease. No comments on the article itslef but the video at the end looked scary enough that I don't think any body would try that on their own. It took a while for the tick to come out.

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  6. Tabraiz,

    As someone who lives near the woods I have had this done often, and have taken many off my dog. Sometimes they get as big as grapes before you find them in dense fur. I can attest that this video is no exaggeration, it really is this hard to get out a tick, the important thing is not to panic, you have plenty of time and pull all the tick out. The first time I found one I was so freaked out I just yanked on its body and half his head was still stuck in my leg, not fun.

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  7. It is interesting that even though there is a "classical" presentation of Lyme disease in the early stage, the later stages seem to have diffuse symptoms that can overlap with many other conditions (e.g. intense lethargy, muscle pain, arthritis). Because a tick bite can be so easily missed and exposure has become so easy as development begins to intrude on more forested areas, I wonder if there is a significant disease burden due to undiagnosed Lyme disease. It would be interesting to see if there is a correlation between the rates of individuals with those diffuse symptoms with other diagnoses (e.g. fibromyalgia, chronic fatigue syndrome, arthritis) and communities/towns in more forested areas.

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    1. In regards to the comment about the amount of Lyme disease that falls under the radar per say, the point is excellent and very plausible. Most likely however in areas with dense tick populations, people are vigilant of the clothing they wear outdoors and check their bodies for ticks. Obviously Lyme disease has a high disease burden, thus people are aware of the regular do’s and don’ts with ticks. Even in school systems I was taught from a young age how to check for ticks and of course how to remove them, thankfully however I have never been in the situation to remove one.

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    2. These are great points but it may still be plausible that people with Lyme Disease are still flying under the radar, if you will, and being misdiagnosed with other diagnoses with similar symptoms. This kind of misdiagnosis would most likely depend on the state you are in and the clinicians knowledge (and beliefs) of Lyme Disease. By this I mean, if you live in a state where Lyme Disease is less common (or the physician believes it is less common) then it is unlikely they will test you for Lyme Disease. A comment below talked about how in GA they knew someone who presented with all the common symptoms of Lyme Disease but was never tested and got increasingly sicker over an 18 month period. Thus it seems that depending on where you live and your exposure to information about Lyme Disease will determine how vigilant you and your physician are in the process of diagnosis.

      My point being I tend to agree about the vigilance in areas with a dense tick population. However, the issue is that we are continuously encroaching on the natural habitat and Lyme Disease is spreading (slowly) to places where they have little experience with it.

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  8. In response to Caleb:

    I can completely see your reasoning, however I would actually not be surprised if there was actually NOT a great burden of undiagnosed lyme disease for the reasons that you describe. The diseases whose symptoms overlap with those of Lyme disease are diseases of vague symptoms, which are hard to diagnose and which do not have a definitive cure or even especially effective treatment. In contrast, Lyme disease can be diagnosed with a blood test and treated. Especially in wooded areas, I would expect residents to be well aware of Lyme disease. Therefore, I would expect that anyone with symptoms at all similar to those of Lyme disease would be eager to get tested. If they had Lyme disease, this would be a relatively simple solution to their problems. For these reasons, I actually think Lyme disease would be diagnosed fairly frequently. I would be interested in seeing what percentage of people with the diseases that Caleb mentioned are tested for Lyme disease prior to their definitive diagnosis?

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    1. Regarding Caleb and Diana's discussion, I would second Caleb's concern: "I wonder if there is a significant disease burden due to undiagnosed Lyme disease". Making the diagnosis is not always so cut and dry even when there is a suspicion Lyme. I feel that clinically, it is so important to always consider Lyme’s disease. As it is nick-named, "the great imitator”, it can mimic virtually any disease, including multiple sclerosis, chronic fatigue syndrome, fibromyalgia, bipolar disorder, Alzheimer’s disease and ALS or Lou Gehrig’s disease. Testing is also not so cut and dry; according to the CDC the blood test for Lyme disease is correctly positive only 65% of the time or less. (http://www.cdc.gov/lyme/faq/) Ideally, early detection and removal of the tick is key but for non acute cases though, there may be more burden of disease than we are presently aware of. Worth looking into.

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  9. I agree with Diana Julie. I think that people who live in areas where Lyme disease is prevalent are aware of the symptoms and are constantly on the lookout for such symptoms. Another important factor is that even tough this disease has similar symptoms as many other illnesses - the initial stage lasts for several weeks. When most people fall ill - and it lasts a couple of weeks they will see their physician. At that juncture even if they were unaware of the specifics of Lyme disease - their physician would definitely be right on it.
    Also, the Lyme disease rash will appear within 60-80 percent of infected persons - and as the article states, it is a clear indication that you have been infected by the pathogen, B. burgdorferi.

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    1. (to Nachama's point):
      The potential symptoms of Lyme Disease vary pretty drastically. This is one of those diseases that may present early symptoms or late symptoms ("late" on the possible scale of years). We all know about the early symptoms, such as the infamous rash and the onset of flu-like symptoms. However, late symptoms include widespread joint pain and neurological issues. I have heard of the suggestion that Lyme Disease may, in fact, cause non-immuno-originating arthritis.

      A number of years ago, I found a tick on the inside of my shirt after a visit to Fire Island. Luckily, I was able to remove the tick without having it touch my skin. Because of this incident, I've always wondered how many people who live in deer-filled areas such as Fire Island have been bitten, surreptitiously, by a tick (not all tick bites produce that rash). It would be interesting to determine the potential outcomes from such unknown bites years down the line.

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  10. I was surprised at the long life cycle and developmental complexity of the deer tick. I also had not realized that New York and its neighboring states have among the highest prevalences in the US. (Lyme disease was apparently named for Lyme and Old Lyme, Connecticut, after several reported cases there in the 1970s.) Also, I was amazed at just how small the ticks are.
    I was not surprised to discover that human migration into previously uninhabited environments has significantly increased the rate of Lyme disease in certain areas.
    Interesting profile. -Nate

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  11. Nicole MastrogiovanniJuly 1, 2014 at 1:01 PM

    I find the distribution of Lyme disease map extremely interesting. I am from upstate and have thought once or twice in my life that I had Lyme disease after having to pull a tick out of my leg (I was never officially diagnosed but still think I had a close call and felt very tired) but there is a greater amount of Lyme disease downstate, where I live now, and I never would have thought that I needed to check myself for ticks after being out in the city as well. But then after thinking about it, it could be due to how much residential and commercial development has occurred down here, therefore bringing the animal life closer to humans on a daily basis than it would be upstate. I also never knew the life cycle of a tick and how the cycle of transferring B. burgdorferi actually occurs. I also learned how the tick primarily feeds on the white-footed mouse, I definitely would have said its primary food source was deer due to its common name of “deer tick”; perhaps a name change should happen.

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    1. Nicole,
      Interesting fact about Lyme disease, According to the CDC, 95% of the cases were from 13 states; Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, Pennsylvania, Vermont, Virginia, Wisconsin, New Jersey, and New York. According to the NYC Department of Health and Mental Hygiene, NYC patients were infected when traveling near NYC, Long Island, Westchester County, and the lower Hudson Valley region of upstate NY. It was also stated that ticks are moving near NYC such as Bronx near Westchester boarder, Long Island, and Staten Island, where the deers are present. Cases are increasing from 215 in the year of 2000 to 643 in the year 2009.

      EpiQuery is a great tool to see where certain health behaviors and Communicable Disease are most prevalent. It provides surveillance data which helps identify areas of interest.

      https://a816-healthpsi.nyc.gov/SASStoredProcess/guest?_PROGRAM=%2FEpiQuery%2FCDSS%2Fcdsstrend2&sort=no&year=2012&var=LYM&pop=sex&qtype=neighbor

      The link is to EpiQuery where it shows the cases among areas in NYC in the year 2012.

      Im curious to understand why only certain states are having cases of Lyme disease. And what caused the increase in prevalence and incidence of Lyme Disease.

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  12. Alexandr PinkhasovJuly 2, 2014 at 4:25 PM

    I must mention that the data is presented in a very clear concise and organized manner. It makes the material a lot easier to read for the lay person. The graphics neatly organize the data to display the incidence of Lyme disease, and show how this data is consistent with the distribution of ticks throughout the United States. I liked that the author presented data that showed variation in incidence between states, and even between counties within states. Another feature that I liked was the graphics that shows the rash that appears as a result of the disease and the pictures that show the ticks at different life stages and their relative sizes. I feel that this is important because many people who come from regions that don't have a high incidence of Lyme disease may not recognize the early symptoms which are clinically significant. Similarly, some people don't know what ticks look like and may not be aware of a bite that would require them to then monitor their bites for symptoms of Lyme disease.
    The CDC has data that indicates that incidence is greatest to people between the ages 5-15 and 45-55. I feel like this information is important because interventions should be modeled specifically towards each category. (i.e. kids should be taught what ticks look like, so they would be able to identify a bite if it occurs, and not just pull off the bug). This would allow for early detection, and ultimately result in more effective treatment and positive outcome.

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  13. I am from Connecticut (~1 hour from Lyme, CT) and I can personally attest that Lyme disease is a common reality for me. Lots of the people I went to high school with got Lyme, at some time or another. Even my sister got Lyme walking along a trail behind my house. It was mentioned that in diagnosing early stage Lyme, little more than very non-specific symptoms are often seen; if the characteristic "bulls-eye" rash is missing, or maybe a tick is not found burrowed into the skin, it can be quite challenging to diagnose clinically. For instance, my sister never had the “bulls-eye” rash; she just suddenly felt very tired and achy one day.

    Basically, the patients that walk in the clinic with the "bulls-eye" rash are considered lucky b/c their diagnosis is established quickly, and treatment is quickly started. Others are asked about symptoms, outdoor history, and often, lab tests are ordered. But, in places as endemic with Lyme as where I live, most folks (let alone doctors) have a keen eye toward anything that remotely looks like Lyme. The truth is many patients are treated empirically based on symptoms and history, with lab tests ordered to confirm the diagnosis (note: although cultures can be ordered, the most common laboratory test used identifies antibodies to B. burgdorferi, and is most reliable a few weeks after the initial infection). That is how my sister was treated; and indeed, when labs came back, she was confirmed to have Lyme.

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    1. I have a somewhat similar story with much more frustrating outcome. My friend's sister somewhat suddenly came down with what were classic lyme disease symptoms (severe fatigue, headaches, muscle and joint aches, swollen lymph nodes, etc), but since she didn't have the rash her diagnosis was drawn-out for about 18 months. Over that period she was worked up for chronic fatigue syndrome, endocarditis, fibromyalgia, even depression at one point because her doctor began to suspect it was psychosomatic. It was a grueling and intensely frustrating process for her. She became more debilitated as the months went on, and eventually had to quit her job (as a nurse!) because the fatigue and body aches rendered her unable to function normally. She did eventually become depressed because she felt that she would never recover. Finally, she went for an umteenth opinion and was finally diagnosed with Lyme and began treatment. Because she went undiagnosed for so long her recovery was slow-going. It was an unbelievably frustrating experience for her and her family, especially when she was finally diagnosed because she lived in Georgia and went hiking frequently. The physician who diagnosed her said that she should have been tested for Lyme from the beginning.

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  14. I'm curious to know whether the growing number of people moving from rural to urban areas contributed to any decreased incidence of lyme disease in the recent past here in the US.

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    1. If I have to guess, I will say that the incidence of lyme disease should decrease. based on what Dr. Walsh explained previously regarding the vertical capacity, "rate of potential infectious contact between the host and the vector", so if a growing number of people are moving from rural to urban areas and coming in less contact with the tick, the incidence of lyme disease should decrease.

      but looking at the CDC website, I found that the cases were gradually increasing from 1995 till 2009 and then plateaued in a way. http://www.cdc.gov/lyme/stats/chartstables/casesbyyear.html.
      Also in an interactive map on the same site, the incidence of cases gets more distributed over a bigger geographic area with time (from 1995 to 2013)
      http://www.cdc.gov/lyme/stats/maps/interactiveMaps.html

      If I have to guess again-:) as to what the reason is, I would say it could be that more cases are being picked up/diagnosed or reported through more awareness and better health care. another reason could be that people are doing more traveling, camping, or hiking in areas where they pick up the disease which explains the increase rate and then they go back to where they reside which explain the bigger geographical distribution.

      I am sure that Dr. Walsh will say that this sounds strong and reasonably convincing argument, but completely wrong:).

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  15. The life cycle of Borrelia burgdorferi and its path in transmission is truly impressive. The Ixodes tick has a complex 2 year life cycle, which consists of various stages of maturation, and a period of when the Borrelia burgdorferi bacterium is acquired. What is impressive is the ability for the Borrelia burgdorferi bacterium to migrate from the gut (post-ingestion of a blood meal) to the salivary gland using the lymphatic system of the Ixodes tick. The blood itself triggers a change in the expression of gut proteins within the Ixodes tick. When the tick is latched on to an individual, it ingest a blood meal and may maintain latched on for days. When the meal reaches the gut, area the where Borrelia burgdorferi bacterium reside, the blood itself causes a change in expression of the outer surface protein A to outer surface protein C which allows for the migration of Borrelia burgdorferi bacterium from the gut to the salivary gland. What’s important here, only after the trigger of the blood meal, does the Borrelia burgdorferi bacterium start to migrate. It takes approximately 60 hours for this gradual migration to take place. And therefore if a patient has a tick bite, the tick must have latched on for at least a 24 hour period before it is possible to transmit lime. Generally testing for Lyme disease is not done unless this criterion is met and if the patient shows any signs and symptoms. One of the early clinical manifestations is the ‘Bulls Eye” or “Target” appearance rash know as Erythema Migrans with fever. However, with a high prevalence of Lyme in the Northeast, and the severity of complications, patients in this region are often screened for Lyme Disease regardless of the latching period.

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    1. If someone takes their time in seeking medical attention,what forms of treatment or medication are made available to the ineffective?

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    2. What exactly do you mean by this question?

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  17. How is Lyme disease treated in the later stage of the infection? Is it possible to acquire Lyme disease by having sex with a partner? Are there any natural methods to remove a tick from the body?

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    1. B. burgdorferi has never been documented to transmit by way of sexual contact. Also, the only appropriate method for removing ticks is gently with a tweezers as described in the video.

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  18. I find it interesting that there is a clear distinction between the lifecycle of the hard bodied tick and other arthropod vectors, such as the mosquito. I would have assumed that they follow a similar sort of life cycle but it seems that this is not the case as I. scapularis must complete a full two years while mosquitoes complete several generations within a season. I wonder, do more arthropod vectors follow a course similar to the tick, the mosquito or do they all vary across many different species?

    -David

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  20. Humans are an incidental host for Lyme disease, and the incidence of Lyme disease is related to humans encroaching on and environment that heretofore was a deer/mouse/tick habitat.
    This is generally the same reason that humans are exposed to, or were at least initially exposed to, a number of other diseases. HIV is a mutated simian disease that crossed via an ecotone yes? So too ebola, which is found in communities where hunters are exposed to the putative natural host. The problem of exposure in new environments, it seems, is key to many emerging epidemics.
    I wonder what public health steps can, or should, be taken that might deal with the problem of our exposure to novel infectious agents as our habitat expands. Should we take this into consideration when we develop new lands for habitation?

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    1. I think I understand what you're saying Camilo. As the way in which humans interact with the environment changes, so will the dynamics of infectious diseases. I think what incredibly important public health tool in detecting new disease dynamics and emerging epidemics is surveillance. We will not know if the incidence and burden of a disease is changing unless we are reporting and recording it. It is already a given that most reportable diseases are underreported. One way to improve surveillance is to increase clinician awareness. Another way is to simplify the process by which diseases are reported

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  21. The complex life and infection cycle of the tick is enough to make my head spin. The resiliency of this tiny animal is remarkable. What is more remarkable however is the public health burden that comes out of encroachment onto forest lands for housing. One of the many selling points for Northeast real estate is often Greenbelts, where houses are built on tracts of land carved out of public forest space. Greenbelts mean that your house is adjacent to land that will not be developed and will remain pristine. This means that residential housing abuts wild forest and the possibility of interaction between humans and wild animals is exponentially increased. The adorable deer running through your back yard may be harbingers of disease spreading ticks. If humans go into the same space and are bitten, the disease spreads. Lyme disease has long lasting effects that can lead not only to debilitating symptoms but the need for expensive long term care. We may take this for granted here in the concrete jungle, but a quick look at the geography of the disease demonstrates that we are surrounded by it. Public Health efforts need to be centered around awareness and prevention in addition to treatment.

    If you live in a wooded area with deer, keep your lawn cut short, treat your clothes with Permetherin which kills the tick and is harmless to mammals, put clothes in a hot dryer right after coming into the house and always do a tick check after showering. These are a few simple and cheap ways to protect yourself.

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  22. I've seen public health messages on TV (issued by New York State DOH) about what to do if you've been bitten by a tick. According to the short ad, the next step is to gently remove the tick without breaking its mouthparts and leaving it in the skin. I've always wondered how it helps and why it's important to remove the tick ASAP-- doesn't infections occur as soon as one is bitten? After reading this article, it makes sense-- the migration of the bacteria from the tick's gut to the salivary glands to the human's skin is a very slowww process. Thus, one has a good chance of not getting a significant infection with the bacteria if one removes the tick ASAP!

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  23. Hi Dr. Walsh - Thank you for the interesting posting!

    You talked about how the characteristic "bulls eye" lesion or rash does not present in everyone who becomes infected. This seems to be pertinent information that should be distributed more widely both to the general public but also clinicians. Myself and two other family members had Lyme Disease a couple of years ago and I never had the rash that most people use to recognize Lyme Disease. From talking to a number of friends, many believe that you cannot have Lyme Disease without having that rash...which as you stated is not true. With regards to early (or earlier) intervention, it may be beneficial to disseminate more information on the both the rash and the other common symptoms so people know what to look for, especially in areas where Lyme Disease is endemic.

    One question: Is it only possible to diagnose Lyme Disease in the early stage but it is treatable in any of the three stages? Is that correct or did I misread that paragraph?

    - Lianna

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    1. Treating late Lyme disease depends on whether spirochetes are still present. If so, then these can be treated, but management of the complications is still required. There is also the question of what exactly is late or chronic Lyme disease, i.e. pathogenicity of the organism or autoimmune response.

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  24. Considering that immediate family members of mine have been diagnosed with Lyme Disease, as well as the fact that I am originally from "woody" upstate New York, I found this post particularly interesting.
    Looking at the complex lifecycle of I. scapularis, perhaps it is fathomable as to why an insecticide is not widely used to kill off the insects. Most insecticides target a very specific part of the lifecycle of the pest they are used to treat. Therefore, they are used when most of the pests present are assumed to be in that particular stage of the lifecycle when treatment is maximized. However, the deer tick does not have a point in time in which most of the insects are at the same point in their lifecycle therefore making it difficult to target.
    While explaining the life cycle you say several time "Once again the preferred host is the white-footed mouse". I winder if the tick has some sort of mechanism for recognizing a suitable host over a non-suitable host.

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  25. Ticks have a complicated lifecycle requiring hosts and transferring and continuing the lifecycle of bacteria. The challenge of the tick is that it can be difficult to diagnose. A person can have lyme disease and not know it because the tick is gone and there is no clear rash, furthermore the symptoms can be easily mistaken for other forms of sicknesses. As stated, it is therefore important for a physician to gain a thorough history of the persons activities. additionally, it is interesting that the system the tick goes through for the OspA to transition into the saliva containing OspC which takes approximately 60 hours, which gives time for the person to detect the tick and avoid infection.
    Lastly, what does one do there is no tweezers available? would using finger nails do the job. (I was once walking in a home in Virginia when someone grabbed my leg and casually removed a tick from my skin with his bare hands. Is that not a good idea?)

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    1. Removing ticks without tweezers used in the proper way is not recommended. The mouth parts often break off and are left in the skin and subsequent risk of infection is high.

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  26. The clinical diagnosis of Lyme disease is difficult because of the different manifestations of the disease, and the variability in onset of the stages. For pregnant women that are not diagnosed early, what is the transmission rate to the fetus?

    Also, I read an interesting article about Northeastern University researchers that have found that B. burgdorferi forms dormant persister cells, which are resistant to antibiotics. The research team also developed two methods of eradicating the bacteria in lab tests. One method is using Mitomycin C, an anti-cancer agent; it completely eradicated all cultures of B. burgdorferi in one round. However, it's not an treatment option because of its toxicity. The second method was pulse-dosing an antibiotic to eradicate the persisters. When the antibiotic was used the first time, the grow cells died, but not the persister cells. After the antibiotic washed away, the dormant persisters "woke up". The key is to deliver the antibiotic once dormant persister become activated so they don't restore their population. It took four rounds to eradicate the persisters completely in a test tube. Although, it would be difficult to identify the specific time when dormant persister cells become activated in humans, this research is promising!

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