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Human Borrelia miyamotoi Infection in Canada

Recently I was reading #WildMed topics on Twitter and saw @ExpeditionDocs tweet about an interesting article in NEJM: Human Borrelia miyamotoi Infection in the United States. I have previously written about Lyme Disease (Borrelia burgdorferi) in an article on this blog with my friend and amateur entomologist Scott Willis (The Low Down on Lyme Disease) as well as on the Family Medicine Reference blog (The Low down on Lyme Disease).

Krause et al. (NEJM Jan 27 2013) state:

Borrelia miyamotoi, a spirochete that is genetically related to the species of borrelia that cause relapsing fever, has been detected in all tick species that are vectors of Lyme disease.1,2 It was detected in Ixodes scapularis ticks from Connecticut in 2001 and subsequently has been detected in all areas of the United States where Lyme disease is endemic.

So this got me wondering about the prevalence of this spirochete in Canada given that we also have Ixodes scapularis. After a quick literature search I discovered an article titled, The prevalence of Borrelia miyamotoi infection, and co-infection with other Borrelia spp. in Ixodes scapularis ticks collected in Canada. Antonia Dibernardo et al. found that Borrelia miyamotoi infection (in ticks) was present in all provinces of Canad except Newfoundland. Thus Dibernardo et al. said,

Given the widespread distribution of B. miyamotoi, infection due to this agent should be considered in patients who have been exposed to blacklegged ticks in Canada.

What should be stressed is that there is a key methodological difference between these two studies. The first study in the US was looking at human serology tests to, “provide evidence of B. miyamotoi infection and the prevalence of this infection among people in the United States” (NEJM Jan 27 2013). While the latter study in Canada, was looking at specifically at infections in I. scapularis ticks (rather than humans).

Krause et al. conclude (NEJM Jan 27 2013) “The identification of B. miyamotoi antibody in 18 of our study patients, including seroconversion associated with symptoms in 3 patients, suggests that B. miyamotoi infection may [emphasis added] be prevalent in areas where Lyme disease is endemic in the United States”.

The Canadian study found on overall prevalence of less than 1 % for B. miyamotoi. They also noted:

Few ticks were co-infected, however a third of B. miyamotoi-infected ticks and a quarter of A. phagocytophilum-infected ticks were also infected with B. burgdorferi and co-infections of B. miyamotoi and B. burgdorferi occurred more frequently than would be expected by chance.

Overall these were two very interesting articles to read and further remind me of the importance of regular tick checks while working or playing in the outdoor environment. I particularly like the well summarized conclusion in the Canadian paper with the clinical so what statement:

The relatively limited (though expanding) distribution of blacklegged tick populations in Canada [22,28,29] and the lower prevalence of B. miyamotoi infection in these ticks means that at present the risk of infection of humans in Canada would be lower than in parts of the USA [6]. Nevertheless, our study indicated that B. miyamotoi is present across a wide geographic range in Canada, and clinicians should consider B. miyamotoi infection as a possible diagnosis, alongside Lyme disease, Anaplasmosis, Ehrlichiosis, Babesiosis and arboviral infections, in patients suffering from suspected infectious disease who have potentially been exposed to ticks in Canada.

Happy hiking! Comments or questions just drop me a line below.

References:

1.  Krause PJ, Narasimhan S, Wormser GP, Rollend L, Fikrig E, Lepore T, Barbour A, Fish D. Human Borrelia miyamotoi infection in the United States. New Engl J Med. 2013;368(3):291–293. doi: 10.1056/NEJMc1215469.

2.  Dibernardo A, Cote T, Ogden NH, Lindsay LR. The prevalence of Borrelia miyamotoi infection, and co-infections with other Borrelia spp. in Ixodes scapularis ticks collected in Canada. Parasites & Vectors. 2014;7:183. doi:10.1186/1756-3305-7-183.

Cyanide Antidotes

OLYMPUS DIGITAL CAMERA One of the interesting topics discussed today at PM Toxicology rounds was about the use of various antidotes for cyanide poisoning.

The discussion got me thinking about a presentation I put together on this topic a few years ago now, while in medical school on my Emergency Medicine clerkship block. The information is still relevant today and I draw the same conclusions from the literature as I did way back then.

To view my Cyanide Antidote  PowerPoint click here –> Cyanide Antidotes

Ibuprofen for Altitude?

Photo by Kerem Titiz http://www.flickr.com/photos/keremtitiz/
Photo by Kerem Titiz
http://www.flickr.com/photos/keremtitiz/

Acute Mountain Sickness (AMS) is a condition that affects many outdoor enthusiasts and tourists every year.

Diagnosis of AMS is based on:
1. A rise in altitude within the last 4 days
2. Presence of a headache
PLUS
3. Presence of at least one other symptom
4.  A total score of 3 or more from the questions below.
0-3 scale of symptoms related to: 1) Headache 2) Gastrointestinal symptoms 3) Severe nausea &/or vomiting 4) Fatigue &/or weakness 5) Dizziness/lightheadedness 6) Difficulty sleeping

See: Lake Louise Score for the diagnosis of AMS.

Study objective: Compare ibuprofen versus placebo in the prevention of acute mountain sickness incidence and severity on ascent from low to high altitude.

Methods: Healthy adult volunteers living at low altitude were randomized to ibuprofen 600 mg or placebo 3 times daily, starting 6 hours before ascent from 1,240 m (4,100 ft) to 3,810 m (12,570 ft) during July and August 2010 in the White Mountains of California. The main outcome measures were acute mountain sickness incidence and severity, measured by the Lake Louise Questionnaire acute mountain sickness score with a diagnosis of ≥ 3 with headache and 1 other symptom.

Authors conclusions: Compared with placebo, ibuprofen was effective in reducing the incidence of acute mountain sickness.

My conclusions: This small double blinded placebo controlled RCT was well designed and relevant to those who plan to travel from low to high altitude. Currently the only medications with indications for prevention of AMS are Acetazolamide and Dexamethasone both of which can be associated with potentially serious side effects and safety concerns.

The authors main conclusion supporting the use of Ibuprofen is based on Table 2.

Variables: Placebo, N42; Ibuprofen, N44

Difference in Estimates Between Treatment Groups, OR (95% CI)

AMS incidence (%)  Placebo 29 (69) Ibuprofen 19 (43)  OR 0.3 (0.1–0.8)
AMS severity: peak LLQ score, mean (SD) Placebo 4.4 (2.6) Ibuprofen 3.2 (2.4) OR 0.9 (0.3–3.0)*

LLQ = Lake Louise Questionnaire. *Reported as the mean difference in percentage.

My main concern is the relatively small overall sample size and wide confidence intervals for the difference in AMS severity and potential for overlap (meaning no true difference) between AMS severity in the placebo and ibuprofen groups. One surprising finding for me was that the Ibuprofen group had a similar incidence of headache (0.6 (0.2–1.6)) compared to the control group, but decreased incidence of GI complaints (OR 0.3 (0.1–0.8)) which is the opposite of what I would have expected. That said the difference in headache finding was not statistically significant.

My bottom line is that until I see further studies supporting the efficacy of Ibuprofen for the prevention of AMS, I will not be endorsing this prevention strategy. While the risk of adverse events is quite low, as would be the cost of treatment, I still remain skeptical.  What I would like to see in future research is further validation of this finding in a larger study. I would also like to see a well designed head-to-head non-inferiority double blinded RCT comparing Acetazolamide, Dexamethasone and Ibuprofen, although given the difficulties of recruiting adequate numbers of participants for altitude related research, I won’t be holding my breath.

Reference: Lipman et al. Ibuprofen prevents altitude illness: A randomized controlled trial for prevention of altitude illness with nonsteroidal anti-inflammatories. Ann Emerg Med. 2012;59:484-490 2011;39(7):1607-1612.

Simple ideas for preventing Acute Mountain Sickness: 1) Follow a strategy of staged ascent (Category 1A) 2) High carbohydrate diet (Category 2) 3) Until acclimatized moderate physical activity 4) Maintain adequate hydration.  (Wilderness Medical Society Practice Guidelines  5th Edition – High Altitude Illness)

Wilderness Rules of Engagement

Here are some humorous and easy to remember rules of thumb for Wilderness Medicine.

Ice fields of the Perito Moreno glacier, Argentina. License AttributionShare Alike Some rights reserved by MrHicks46 via Flickr
Ice fields of the Perito Moreno glacier, Argentina.
License
AttributionShare Alike Some rights reserved by MrHicks46 via Flickr

Rule 1: I am number one.

Rationale: You can be of no help to others, if you injure yourself. Be sure to use personal protective equipment and ensure your own safety and that of your team members when trying to provide patient care in a wilderness context.

Rule 2: Always use the other guys stuff first.

Rationale: If you need to make improvised litters or splints for evacuating a patient from a wilderness setting, use their gear if possible.

Rule 3: Replace your sweat, not your water.

Rationale: To avoid electrolyte derangement it is best to replace fluid with substances which contain electrolytes. If the patient has gastroenteritis consider the use of oral re-hydration solutions.

Rule 4: Hypothermia is a leadership issue.

Rationale: Hypothermia occurs when the exposure to cold overwhelms the body’s ability to produce and retain heat. Proper clothing for the environment, along with adequate nutritional intake can go a long what in preventing hypothermia.

Rule 5: If you don’t know a knot, tie a lot.

Rationale: While having proper knowledge of knot tying is critically important in mountaineering and sailing, if you lack the specific knowledge to tie sound knots, extra knots can provide redundancy against potential knot slippage.

Rule 6: Proper preparation prevents piss poor performance.

Rationale: Just like in a resuscitation, wilderness medicine scenarios can devolve into a scene of chaos. The person who is able to control that chaos is the person who is able to do what is needed for their patient and team. Maintaining composure and control will ensure your safety and your patients safety.

Rule 7: Three Bears, not too much, not too little, just enough.

The low down on Lyme disease

31530344-Lyme3Have you ever sat beneath a tree during the summer afternoon, and found yourself wondering if it might be raining? Saying “I just felt something land on me!” Only to realize it wasn’t rain, it was insects falling from the tree?
This actually happened as we were hosting our prestigious Wilderness Medicine Debate Society debates as part of a Wilderness Medicine Elective for medical students hosted by Wilderness Medical Associates International. Following the debate we informed students of the presence ticks and someone in the group let out a gasp, “Tick…OMG!” Apparently students had heard about tick borne illnesses.

Many participants were already aware of the connection between ticks and Lyme disease.  Thus we reminded participants about the importance of regular “Tick checks” after outdoor activities in tick endemic areas. A simple, yet effective way of reducing your risk of acquiring Lyme disease, this recommendation got a good giggle from the group, maybe because it was also noted to be “a great way to really get to know fellow travellers on a trip!”

This is the second in a series of collaborative blog posts related to insects and infectious disease with my good friend Scott Willis.

Ticks are small eight-legged arachnid parasites that need to feed on blood to grow and survive. They latch onto mammals, birds, reptiles, and humans by piercing the skin to get a blood meal. Usually people will find ticks attached to their body after walking through a forest, before the tick has started feeding. Once the tick has started feeding (sucking blood) it becomes engorged, meaning the abdomen becomes larger and turns greyish blue in colour. What makes ticks so medically relevant is that they can carry all sorts of diseases, such as Lyme disease, babesiosis, and anaplasmosis. Many species of ticks carry the Lyme disease causing spirochete bacterium Borrelia burgdorferi. Not all tick species carry Lyme disease however. The most common and widespread tick that can pass on Lyme disease in southern Ontario is the deer tick (Ixodes scapularis) – also known as the blacklegged tick.

Blacklegged ticks have a 2 year lifecycle, going from egg, larva, nymph, adult to egg. Each phase must get a blood meal and feed before maturing to the next stage. More often than not the nymph stage is the main source of transmitting Lyme disease, since they need the blood meals to grow and develop and are easily hidden on the body. They are most active during mid-May to August. The blacklegged tick’s range stretches from southern Ontario, Quebec and most of Eastern United States. They are most commonly found in deciduous forests, since this is where white-tailed deer are found- the tick’s animal host.

The risk of a patient contracting Lyme disease when bitten by a tick depends on many factors. First the longer the tick has been attached to the person, the greater a chance of transmission. People can feel the tick before it starts feeding and can easily get it off their body. Many however do not feel the tick bite and the tick can stay attached to the body and continue feeding for days. Studies suggest that it takes up to 36-48 hours for the bacteria to be transmitted when feeding. This can easily be prevented by tick checks at the end of the day. Not all blacklegged ticks contain the bacteria for Lyme disease, with an estimated 25% of nymph ticks having Lyme disease and 50% of adults.

One of the main tools in predicting whether or not someone has Lyme disease after a tick bite is to use entomological evidence. Identifying the species of tick that bites a patient as a blacklegged tick can help in diagnosing Lyme disease. After getting bitten, it is advisable to have your patient keep the tick and bring it in to be identified. It can be dead or alive and simply kept in a container, like a zip-lock bag. It is suggested though that when the patient is removing the tick, be as careful as possible to avoid damaging it and thus preventing proper identification. Also keep the tick in a container with damp wrapping to prevent dehydration of the sample. Dehydration of the tick makes identification extremely difficult.

The primary means by which Lyme disease is diagnosed based on physician-observed clinical manifestations and a convincing history of exposure to an infected tick.

Identifying ticks is done by process of elimination. The only other common tick that might be confused with a blacklegged tick is the dog tick, which is commonly found on pets. Dog ticks are not capable of transmitting Lyme disease since they are not very good hosts for the bacteria. You can identify blacklegged ticks from dog ticks by their size. Blacklegged ticks are very small, smaller than other ticks that they may be confused with. Usually the nymphs are only 1 to 2mm in diameter, compared to the dog tick, an equally common tick, which is 3mm. The size difference is very noticeable. Also dog ticks have very definitive white markings on their back that the blacklegged ticks lack. Examine the white markings in the picture below on the dog ticks.

31530335-Lyme2This picture is a good indicator of the size difference. On the top are unfed adult blacklegged ticks and on the bottom are adult dog ticks. You can also note the white pattern on the “back” of the dog tick.
If you are trying to identify a tick, the internet has many wonderful resources!

http://www.tickencounter.org/tick_identification

This is a wonderful place to start! There are pictures of all stages of ticks for different regions (Southern Ontario would be Northeast/Midwest). It evens offers the different tick’s abundance.

http://www.idph.state.il.us/envhealth/tickkey.htm

This site offers a dichotomy key of-sorts. A bit more entomology lingo is present though, so this is recommended for the more seasoned tick identifier.

It is important to note that if the tick is engorged, it makes the tick harder to identify, and you must focus on legs and upper part of the body. Identifying ticks can be challenging, if you are not comfortable with attempting to identify the tick then you can send it to an expert. Ticks that have been kept by the patient can be sent to a provincial laboratory for identification and Lyme disease testing. If the tick is identified as a blacklegged tick, it will be sent to the National Microbiology Laboratory (NML), where they will test it for Lyme disease using polymerase chain reaction along with any other potential pathogens. This service is provided by the Public Health Agency of Canada, and they use the data of Lyme disease positive ticks to monitor the tick’s spread. It is important to note that even if the tick tests positive for Lyme disease or that the tick that bit them was identified as a blacklegged tick, this is not a 100% guarantee that your patient has contracted Lyme disease. Additional blood tests should be ordered and symptoms must be considered.

31530328-Lyme_1
Blacklegged ticks becoming increasingly difficult to identify when they become engorged.
Generally IgM and IgG antibody blood tests are ordered for diagnosing Lyme disease in the patient, however it is often negative in the first weeks of the illness so if there is recent onset if symptoms or characteristic EM rash it may need repeating. Depending on lab resources, more sensitive PCR testing can also be done on the blood sample. If the patient is suspected of contracting Lyme Disease overseas its is important to test should using a C6 based assay as other serologic test may not detect infection with European species of Borrelia.

As always these tests are not 100% definitive and, as with all evidence-based medicine, everything must be considered before a diagnosis. Having entomological evidence as discussed in this blog can make ruling Lyme disease in or out much easier.

The concern is that Borrelia infection  (Lyme Disease) can result in dermatologic, rheumatologic, neurologic, or cardiac abnormalities. The typical incubation period is 3-32 days according to the CDC. It has been reported that anywhere from 70-80% of patients develop a rash, known as erythema migrans (EM) within 30 days of exposure to B. burgdorferi. EM is described as a red expanding rash (with or without central clearing) often accompanied by symptoms of fatigue, fever, headache, arthralgias or myalgias. Infection can also spread to causing more serious complications and conditions like meningitis or carditis with atrioventricular heart block. Untreated infection can progress to cause arthritis, peripheral neuropathy, or encephalopathy.

We must stress though that prevention is your most important tool in the fight against Lyme disease. If you are going into an area where blacklegged ticks are known to exist, stick to paths and wear long clothing. There are many commercial repellents available, but ones containing DEET or permethrin are your best bets. Perform tick checks at the end of the day. If you do find any ticks, use fine-tipped tweezers to remove it. Remember that the earlier you catch the tick, the less chance of Lyme disease transmission.

Knowledge is the best tool in the identification of blacklegged ticks and prevention of Lyme disease.

Sources:
http://www.cdc.gov/features/lymedisease/
http://www.phac-aspc.gc.ca/id-mi/tickinfo-eng.php
CDC Health information for International Travel 2010 – The Yellow Book

It wasn’t a Brown Recluse…

30669269-734px-Brown-recluse-2-editHave you ever heard some medicine or infectious disease keener throw out a “brown recluse bite” on their differential diagnosis for what looks like a simple insect bite? Have you seen a necrotic wound where a staff says it was likely due to a “spider bite”? Have you ever heard of Brown Recluse spiders? Do you live in Canada?
Below is an article about why it is exceedingly unlikely that your insect bite was a brown recluse, if you live in Canada. This is the first in a series of collaborative blog posts related to insects and infectious disease with my good friend Scott Willis.

To kick things off lets look at Table 1 from Swanson and Vetter, NEJM 2005 of conditions potentially misdiagnosed as bites from loxosceles spiders. This table always makes me smile.
30669276-Screen shot 2011-08-20 at 7.17.31 PM
David L. Swanson, M.D., and Richard S. Vetter, M.S. Bites of Brown Recluse Spiders and Suspected Necrotic Arachnidism. N Engl J Med 2005; 352:700-707. February 17, 2005.
Brown recluse spiders (Loxosceles reclusa) are small, brown spiders that have a potentially serious venomous bite that can cause skin necrosis (or at least that is what everyone is worried about). While this can be very startling, residents of Canada do not have to fear about being bitten by a brown recluse. The brown recluse spider can only be found in south Central/Midwest United States.

Wait, hold the press! What about a brown recluse which hitches a ride on a load of fruit shipped from the United States?

This question always gets raised and becomes a question of probabilities. I ask you to consider which is more likely…that a lone loxosceles spider hitch-hiked thousands of kilometers waiting stealthily to bite one unlucky soul…or that someone might not be using a suitably wide differential diagnosis (my money is on the later). Remember we should cast a wide net when formulating our diagnosis rather than settling on a diagnosis of convenience with little actual concrete evidence.

Brown recluse spider range
30669270-maps
http://dermatology.cdlib.org/DOJvol5num2/special/recluse.html

Despite this, many doctors in Canada still diagnose brown recluse bites. The belief that brown recluse spiders are in Canada is an urban legend; only 3 have been ever verified in Canada. Even having the spider accidentally transported from its natural habitat to Canada is extremely rare. The spiders themselves rarely bite, and are very shy in that they are only active at night. They prefer rocks and crevices, are not found in the open, and avoid human contact. They will only bite when trapped between you and a surface (putting on shoes with the spider inside for example).

Many times a patient will have their bite misdiagnosed as a brown recluse bite without anyone ever seeing a spider. Some states that do not have natural recluse populations have guidelines that state that if the spider is not seen in the act of biting then it should be treated accordingly and not as a necrotizing spider bite. Thus, it is important to have your patient bring in the offending spider if they are bitten, or at the very least they must report seeing the spider.

The diagnosis really comes down to whether the spider that bit the patient was a brown recluse or not. Brown recluse spiders are the most misidentified spider by amateurs and experts alike.

So you were bit by a spider, but was it a brown recluse?

Most people would consider the “violin head pattern” on the “middle” of the spider to be the most unique feature. Unfortunately most people identify the spider wrongly on this trait, as many other spiders have patterns that might resemble a violin head. The pattern itself on the recluse is not always vibrant or present, and can only be found on adult spiders. While brown recluse spiders are known for this pattern I would not recommend using it to identify the spider. If it is present, it can reinforce your identification, but it should not define it.

“Violin Pattern”
30669277-media_httpblogjimbail_vdrcp
The number of eyes and their arrangement on the spider is crucial to a proper identification. Most spiders have eight eyes. Brown recluse spiders only have six. This is rare, as there are few spiders that only have six eyes, none of which resemble the brown recluse. The arrangement of the eyes is also important.

Most other spiders have their eight eyes arranged in two rows of four like this:
30669273-Normal eyes

http://bugguide.net/node/view/84423

While the brown recluse has its six eyes arranged in pairs like this:

30669272-Recluse eyes

http://bugguide.net/node/view/84423
http://dermatology.cdlib.org/DOJvol5num2/special/recluse.html

One pair is in the middle, the other two are on each side. If you have a Web Frontal view Loxosspider with six eyes in this arrangement, you have a brown recluse.

There are a few other distinguishing characteristics that would help identify a brown recluse. Brown recluse spiders’ legs have a uniform light colour to them and there are no stripes or bands on the legs. Also, the legs have no spines, only fine hairs. The size of the spider is only about 6-20mm in size. If the spider meets all of these characteristics, it is a brown recluse spider. In a pinch though, the eyes are the key.

While the above information allows you to identify a brown recluse, we must stress that the bite isn’t a brown recluse bite. While the bites can be traumatizing, a diagnosis should only occur in regions and countries where Brown Recluses populate and live.

Consider other bugs as source of bite (unless presented otherwise); fleas, ticks, mites, bedbugs and assassin bugs. These bugs actually seek out humans, whereas spiders do not. If you can capture the spider, send it to an arachnologist for identification. Even if you get bit, a necrosis occurrence is very rare, occurring about 37% of the time. Most bites heal without any problems.

All of this, including the shyness and unwillingness of the spider to bite except in extreme circumstances makes a bite from a brown recluse in Canada – EXTREMELY UNLIKELY.

Wilderness Context

Forest

Wilderness medicine has been defined as any context that involves patient care in extreme environments, when resources may be limited or non-existent, and evacuation to greater medical care may be hours, days or longer. Applications of wilderness medicine may be in a remote corner of the planet, but also include environments such as urban disasters, severe weather conditions, multiple patients, police and military interventions or any situation that creates a context with minimal resources or extended scene patient management.

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