Episode 6: Tick Borne Illness Part 2 – Anaplasmosis

Episode 6: Tick Borne Illness Part 2 – Anaplasmosis

EMOttawa Podcast Episode 6
Tick Borne Illness Part 2 – Anaplasmosis

Click here for Part 1, focusing on Lyme disease.

In part 2 of our 2-part series on tick-borne diseases, Dr. Rajiv Thavanathan interviews Dr. Mikkey McGuinty, an infectious disease clinician-scientist on the topic of anaplasmosis. For a basic review of the disease and pathophysiology, we suggest our previous posts on lyme disease, vector borne illnesses part I and part II. 

Introduction

Anaplasmosis is the broad name for diseases cause by the Gram-negative bacterium Anaplasma phagocytophilumIt is a tick-borne illness, carried by the same Ixodes Scapularis tick that can cause Lyme disease. In humans, it’s called HumanGranulocytic Anaplasmosis (HGA). 

Why are we hearing about Anaplasmosis only recently?

Increased prevalence of ticks with climate change and the evolution of their habitat.

Up until 2020, many physicians had never seen HGA in Ottawa. There were 2 documented cases in Ontario over the last 5-years, both of which were in the Toronto region, which made sense given it’s proximity to the southernmost part of Ontario. Until recently clinicians were not routinely testing for it, and it’s likely that this represents an underestimation of the true prevalence. To date in 2021, there have been 5 documented hospital cases in the Ottawa region 

Epidemiology

  • In Ontario and most of Canada, the same as Lyme disease. That is, tick endemic regions.
    • Ticks in these regions are often found in areas with long grass and low brush. 
    • HGA is more common in Europe. It infects a different tick species (not Ixodes Scapularis), hence the difference in prevalence. 

Classic Presentation

  • Febrile, summer illness.
  • No erythema migrans.
  • Delayed presentation. On-average, illness occurs 1-2 weeks from exposure.
  • Symptoms are general and can include fever, fatigue, myalgias, headache, and less commonly, GI symptoms of nausea, vomiting or diarrhea.

Populations at Risk

  • Elderly (age >60), advanced HIV disease, or impaired T-cell immunity such as organ transplant recipients.
  • Unlike Lyme disease, most people will have a self-limited illness. It doesn’t have as delayed a presentation.
    • However, It can cause severe illness, including syndromes that look like septic shock because of cytokine response to the infection. You can have multi-organ system failure as a result, including brain disease, myocardial involvement, respiratory failure, severe hepatitis, renal failure.
  • 3-5% morbidity, with a case fatality rate of ~1%.

Diagnostic Clues

  • Cytopenia – particularly thrombocytopenia and leukopenia (less commonly anemia)
  • Mild biochemical hepatitis

 Advanced Testing

Bottom line: A challenging diagnosis to make in the ED. Needs to be a clinical diagnosis and confirmatory tests take a while to come back. 

  • Typically, morulae are found in the 1st 3-5 days of the infection, as opposed to later in the course.
  • Serology can be ordered but is only diagnostic when paired. You need an acute sample while sick, and a paired convalescent sample to determine the antigen titre delta.
  • PCR is the gold standard test, and the test of choice in regions with high prevalence.
    • In the ED, this could be helpful for high-suspicion presentations that will be treated empirically or referred to infectious disease.
      • A convincing clinical history, including tick exposure within the last 2-weeks now presenting with fever, myalgias and headache, with thrombocytopenia and biochemical hepatitis.

Prophylaxis & Treatment

  • Does doxycycline prophylaxis change the likelihood of developing HGA?
    • No, at least we don’t have data for it.
    • However, if they have risk factors (RF) for HGA, they have RF for Lyme disease, so if they meet tick criteria for doxycycline prophylaxis this should be given.
  • Treatment is Doxycycline 100mg PO BID x 10-14 days.
    • HGA is incredibly doxycycline sensitive, and the duration could be as short as 7-days, but we’re also concerned about treating Lyme disease.
  • The ID physician’s joke: No one should die without a trial of doxycycline.

Ottawa Specific Testing

At TOH

  • Epic doesn’t have HGA set up as a specific test for blood films
  • If you’re planning to order microscopy and asking to look for morulae, call the hematopathology team to inform them that HGA is on your differential.
    • Simply commenting on this in the EPIC comment section if often missed.

Take-Home Points

  • Anaplasmosis, also known as HGA, is a tick-borne illness carried by the same tick that can cause Lyme disease.
  • The classic presentation is a febrile summer illness, typically 7-days post tick exposure. Symptoms include fever, myalgias, headache, and less commonly, GI symptoms.
  • While typically self-limited, populations at risk of complications are the elderly (age >60), advanced HIV disease, or those with impaired T-cell immunity such as organ transplant recipients.
  • Suggestive lab abnormalities include thrombocytopenia, leukopenia, and mild biochemical hepatitis.
  • Testing in the ED can include ordering microscopy by hematopathology to look for morulae, which are intraneutrophilic bacterial bodies, with peak sensitivity on days 3-5.
  • PCR is the gold-standard test. For patients being treated empirically or referred to infectious disease, this can be considered.
  • Treatment: Doxycycline 100mg PO BID 10-14 days.
  • It’s never the wrong time to offer preventative care for tick-bites.

 

 

Episode 5: Tick Borne Illness Part 1 – Lyme Disease

Episode 5: Tick Borne Illness Part 1 – Lyme Disease

EMOttawa Podcast Episode 5
Tick Borne Illness Part I – Lyme Disease

In part 1 of our 2-part series on Tick-borne diseases, Dr. Rajiv Thavanathan interviews Dr. Mikki McGuinty, an infectious disease clinician-scientist. This episode covers nuances of lyme disease with relevance to the front line provider. For a basic review of the disease and pathophysiology, we suggest our previous posts on lyme disease, vector borne illnesses part I and part II. 

Local Prevalence of Lyme Disease 

Common. Five years ago, it would be incredibly rare to see a case of locally acquired Lyme disease in Ottawa. They were seen in Kingston often, but now we’re seeing more and more cases in Ottawa. In the province of Ontario in 2017, we documented over 1000 cases, and numbers have been rising since. However, four years prior, we were roughly seeing 300-cases per year. This isn’t just due to under recognition, there’s more Lyme carrying ticks. Reasons for this include complex dynamics of climate change, as well as habitat change for typical reservoir animals of these diseases. Overall, the IDSA threshold for an endemic area is 20% or more of ticks infected with Borrelia Burgdorferi.

Do we need to identify the tick?

The bottom line: no. In Dr. McGuinty’s experience, a patient bringing in a suspected tick in Ottawa hasn’t helped. Most tick-borne illnesses diagnosed do not have a tick identified. Physicians are generally not any more skilled than the public in comparing the identified tick to those found in a textbook or on the internet.

However, if you live in a region that has multiple infectious ticks (i.e. lone star ticks or dog ticks) that can carry different diseases than in our local Ontario region, there’s more value to identification to target treatment. In Ontario, we assume it’s an Ixodes tick.

Exposure Duration 

In determining prophylaxis treatment, does the duration of tick attachment matter? There’s a good science answer for this, and a practical real-life answer for this:

There are lots of good studies showing that borrelia burgdorferi is NOT transmitted during the first 24-hours of attachment. However, the vast majority of those who have a tic-borne illness don’t recall having a Tic attached. And just because you’re seeing a patient with a tick attached doesn’t mean that same patient didn’t have three ticks on them earlier and this is the only one left. Therefore, our local practice is treating regardless of the presumed attachment duration.

Tick engorgement is also notoriously unreliable to the untrained eye. Albeit if you’re an ER or family physician living in New York State, you might have more experience with this.

Erythema Migrans 

A common clinical miss for Lyme disease is failing to recognize disseminated (or secondary) Lyme. Often called about a patient febrile with a weird rash. And at this point it’s disseminated with different stages of bullseye rashes. It’s not just a simple or single lesion.

Regarding the timing of erythema migrans, its variable, with some lesions showing within 2-3 days of exposure, and some as late as 30-days after. The appearance can also vary amongst patients significantly. While many patients get the classic targetoid lesion with the central bite, some get erythema throughout. Therefore, if a patient has a tick exposure, and you think it’s a possibility the rash could be migrans, it’s best to err on the side of caution.

Clinical pearl: it should never be painful. (It should also never be pruritic, but Dr. Mcguinty has seen a few cases with associated pruritus).

Prophylaxis 

IDSA Guidelines: 200mg of doxycycline x 1 dose (or 4.4mg/kg in pediatrics), beginning within 72-hours of tick removal, for an Ixodes tick, in an edemic area, where the Tick was on for 36-hours or more.

However, regarding the timing, you should use your clinical judgement.

I.e., a patient presenting at the 84-hour mark post-tick removal might still benefit from prophylaxis, whereas a patient with a tick removed one week ago will not. There’s good evidence that delayed prophylaxis doesn’t mitigate the presence of Lyme disease.

Lyme Serology 

In acute Lyme disease with erythema migrans, there’s typically no utility in sending serology for Lyme. It takes at least 3-weeks, and up to 6-weeks, to develop antibodies to Borrelia. And depending on your institution’s lab, it takes an average of 1-week for serology to come back.

ID Referrals  

Should you refer every patient treated for Lyme disease to ID?

Bottom line: No. Unless you feel uncomfortable or have questions regarding the case. Almost everyone with acute Lyme disease will improve, with outpatient wait times to see an ID specialist are typically ≥ 2-months.

Facial Nerve Palsy 

Steroids in the setting of a facial nerve palsy with suspected Lyme disease:

  • If you’re confident it’s Lyme, and you’re treating a Bell’s palsy, it’s an appropriate indication for an earlier resolution of symptoms.
  • IDSA says there’s no added benefit from adjunctive steroids in the general for Lyme neuropathy, but it’s worth starting early in the <72-hour window for cranial neuropathies.
  • There’s neither good evidence for benefit or harm.

Duration of Doxycycline 

  • 10-days? 14-days? 21-days?
  • It’s not black and white. In Dr. McGuinty’s practice, generally will give 14-day courses.
  • More likely to give 21-days if there’s features that suggest dissemination, if it’s been at least 2-3 weeks since possible exposure, presenting with delayed onset of rash or recurrence of fever. As it’s hard to say whether it’s primary or early secondary disease.

Headaches 

  • A common symptom of Lyme disease, and Dr. McGuinty notes clinician’s often inappropriately treat these patients for meningitis with IV antibiotics.
  • If they have no physical exam findings of meningitis, it’s likely not meningitis.
  • Headache, even severe headache, is quite common in the early stages of these diseases. i.e., Covid patients get bad headaches, but it’s often not meningitis, rather it’s related to the underlying infectious process with a significant cytokine release.

Take-Home Points 

  • Lyme disease is becoming increasingly prevalent in Ontario and across Canada, and this isn’t just due to increased disease recognition.
  • Tick identification seldom changes clinical management, and most tick-borne illnesses diagnosed never have a tick identified.
  • IDSA Prophylaxis recommendations: 200mg of doxycycline x 1 dose (or 4.4mg/kg pediatrics), within 72-hours of tick removal, for an Ixodes tick, in an endemic area, where the tick was attached for >36-hours.
  • In clinical practice, the duration of tick-attachment is notoriously unreliable, and this should not be used to preclude prophylaxis.
  • Erythema migrans has a variable appearance. However, it should never be painful.
  • Lyme serology lacks utility in the ED and should not typically be sent. In addition to the results taking 1+ weeks to result, it takes an average of 3-6 weeks to develop antibodies to borrelia burgdorferi
  • A headache with Lyme disease is common and does not typically indicate meningitis.

 

 

References 

  1. Ottawa Prevalence. https://med.uottawa.ca/en/news/tiny-predators-park-1-out-3-ticks-tested-new-ottawa-study-carry-lyme-disease
  2. IDSA Guidelines. https://www.idsociety.org/practice-guideline/lyme-disease/

 

 

EMOttawa Podcast Episode 4: Reflections with Ian Stiell

EMOttawa Podcast Episode 4: Reflections with Ian Stiell

Podcast Episode #4 – Dr. Tiffany Lam & Dr. Ian Stiell

(Click here to access Podcast Main menu)

For our fourth episode of the Ottawa EM Podcast, Dr. Tiffany Lam makes her much anticipated Podcast debut! She sits down to talk to Dr. Ian Stiell, a world-renowned clinician and researcher best known for his development of the Ottawa EM decision rules.

How did you get involved in research?

It was ultimately unexpected, as I was not involved in research as a medical student or clinician. It began with leading journal club as a junior staff, learning how studies should be designed, and then going on to pursue a master’s in epidemiology.

Sometimes you need to go with your gut and follow any opportunities that arise, you can’t pre-ordain what’s going to happen.

Who were your mentors growing up?

My father was a forestry researcher, and although not a clinical researcher, I suppose this rubbed off. There was not a lot of emergency medicine research happening early-on in my career, so I relied on a multidisciplinary team of other clinicians early-on.

Advice for students or residents interested in emergency medicine research?

Reach out to known researchers as early as you can. If you’re a medical student, ask for opportunities in your 1st or 2ndyear volunteering or potentially working as a summer student. In Ottawa, there are multiple new EM projects happening each year, including opportunities to get involved helping with the resident research projects.

How does your clinical work influence your research?

After working in the ED for 40-years, it’s really a never-ending opportunity of ideas. Residents are always asking “why do you do it that way?” and you’re expected to know the answer. If you don’t, potentially there’s a new research idea. EM is unique in that we see the early stages of the undifferentiated patient. Whether in identification of disease, risk stratification or prognostication, there are always new opportunities for research in the ED.

What is the most meaningful change you’ve seen regarding the use of evidence in EM?

The shift away from eminence-based medicine, that is, away from old professors telling you what’s right just because it’s always been that way. Now we look at the studies first, and trainees are being taught earlier-on to critically appraise the literature.

How do you maintain a balanced schedule?

Part of it comes with learning how to be more efficient. Working hard, but also being proficient with your time. As an editor-and-chief for CJEM, this includes appraising articles quickly.

How does Ian Stiell prevent burnout?

Right now, it’s through having lots of hobbies outside of medicine and exercising. My hobbies have included skiing, mountain biking, playing golf, tennis and travelling when it’s not a global pandemic. Currently, I’ve been spending a lot of time with my family and grandchildren.

What are some of the greatest life lessons you’ve learned during your career?

You can’t totally preplan your life. In medical school I wanted to be a neurologist, then surgeon, then family doctor, and all of that seemingly went by the wayside as I grew up. You need to be open to new opportunities. Allow yourself to change course if you find something you like better. And don’t be afraid to admit you don’t like the path you’re on and change course.

What’s next for Dr. Ian Stiell?

I’m still actively involved in research, but part of my role has shifted more towards mentoring residents and new researchers. I’m also involved in working as the editor-and-chief of the Canadian Journal of Emergency Medicine (CJEM).

Any final parting words of advice?

While it depends on your personality, emergency medicine is an amazing career to pursue, particularly if you have a short-attention span. It’s exciting, fast paced, a team sport, and there are countless opportunities for clinical research—whether in quality improvement, simulation, or point-of-care ultrasound (POCUS) to name a few.

 

EMOttawa Podcast: CaRMS Gone Wild!

EMOttawa Podcast: CaRMS Gone Wild!

So what if we’ve only had one ‘real episode’, it’s time for a bonus one! Dr. Rajiv Thavanathan sits down with FRCPC Program Director Dr. Lisa Thurgur, and Assistant PD Dr. Michael Ho to talk about the CaRMS process, and what they’re looking for in applicants. 

(Podcast Main Menu) 

CaRMS

 

 

 

 

 

 

 

 

 

 

 

What happens during the CaRMS file review process?

  • A deep dive into better understanding the applying medical students, applicants, and potential future residents.
  • Different programs use different scoring systems and data points.
  • For Ottawa, like many sites, reference letters make up a significant component of this score. That being said, given the Covid pandemic, there was no preference given to the writing physician’s specialty or home site. Rather, referees were asked to comment on whether a potential applicant would make an excellent emergency medicine resident and physician.

What about students who feel they decided late on emergency medicine as a career?

  • Not a red-flag, and not uncommon.
  • Can be addressed honestly in one’s personal letter and if it comes up during interviews.

How well should applicants know the specific details and nuances of each program?

  • Applicants will not be quizzed on the nuances on each program (i.e., how many weeks is our EMS block). They should have a general understanding, and perhaps even more importantly, know the city well as it’s where they’ll be living for the next five years.

How does a student decide which program is the best fit for them if they’re unable to visit?

  • Firstly: the good news for applicants is that you will get a great emergency medicine education in Canada no matter which city you match to.
  • Despite Covid-19, programs have been trying to give students a feel for what their program is like through virtual Q&A nights, 1-on-1 sessions, social media platform posts, and teaching days.

Remember: programs are interviewing you, but you’re also interviewing programs!

Think about what’s important to you: this can be program specific, i.e. what the teaching and half-day curriculum is like, or city specific, i.e. what do the residents like to do for fun.

Thoughts on residency programs use of social media?

  • Love it! In Ottawa we try our best to highlight our city and EM program.
  • Applicants should be aware that like all forms of social media, not all the challenging or difficulty times are reflected (i.e. long-call hours).

How can applicants come across genuine, enthusiastic about themselves and their accomplishments without coming across arrogant?

  • Consider practicing talking about yourself. It’s not something that comes naturally to most people. There’s nothing wrong with practicing questions and thinking about answers to common questions ahead of time.

Is there anything residents say they wish they knew before CaRMS?

  • Residency is a lot of work. Just as a lot of rewarding things in life are! You want a program that’s supportive, with a resident group, faculty and staff that has your back. Most of the things in your life that you don’t choose is what shapes you, and five years is a building block for the kind of future doctor you can be, but sometimes hard to realize when you’re in the thick of it.

To all of the medical students going through the CaRMS process this year:

You’re nearing the finish-line, try to enjoy the process, and best of luck!

 

Episode One Shownotes: GI Bleeds & TTM

Episode One Shownotes: GI Bleeds & TTM

Dr. Rajiv Thavanathan sits down with Dr. Jim Yang to talk about some of the best high impact trials in the last year in Emergency Medicine. Which patients with a GI bleed need urgent endoscopy, and which patients ACTUALLY need targeted temperature management (TTM) after cardiac arrest.

Acute Upper GI Bleeds– Does timing matter?

Timing of Endoscopy for Acute Upper Gastrointestinal Bleeding

Design

  • Single centre, RCT performed in Hong Kong
  • 516 patients
  • Patients with overt UGIB, specifically with hematemesis or melena, with a Glasgow Blatchford Score (GBS) of >12

Rapid GBS Review

  • GBS > 1 suggests at risk for needing intervention
  • GBS > 6 traditionally predicted the need for intervention
  • GBS > 12 associated with increased mortality

Intervention

Compared urgent endoscopy (endoscopy performed within 6-hours of GI consult) to early endoscopy (endoscopy performed within 6-24 hours of GI consult). Practically, speaking this means that people in the urgent endoscopy group were scoped overnight if they came in the evening.

All patients received standardized care, consisting of a high-dose PPI, and if concerns for variceal bleeding, vasoactive medications (i.e. octreotide) and antibiotics for spontaneous bacterial peritonitis (SBP) prophylaxis.  

Exclusion Criteria

  • Patients with hypotensive stock who failed to stabilize after initial resuscitation or patients moribund from terminal illness. 

Endoscopic Findings

  • Peptic ulcer disease (PUD) ~60% 
  • Variceal bleeding (7-9% of study)

Note: Epidemiologically, PUD is seen at much higher rates in Asian populations, so this prevalence was expected.  

Outcomes

No difference in all-cause mortality at thirty-days.
No difference in further bleeding, the amount of blood transfusions, the rates of surgery or embolization, or hospital or ICU length of stay. 

Urgent endoscopy is more technically challenging. Waiting gives the medications more times to act, which improves visibility, resulting in less and more-targeted interventions. 

Limitations

Given the study’s low prevalence of variceal bleeds, we can’t apply this to variceal bleeds, a known higher-risk population. This study also excluded patients in shock, so clinical judgement and early involvement of endoscopists is still warranted in these very sick patients. 

Additionally, this only applies to larger centers where you have quick access to endoscopists. Particularly in the community, it’s prudent to still discuss these cases with gastroenterology early, as we know these patients can quickly decompensate.

Case application

60 y/o M, known PUD, CC’ melena & presyncope.
Vitals: HR = 115, BP = 90/60 mmHg
Labs: Hgb = 52 g/L

As per our trial, this is indeed a patient who could be delayed until the next morning for early endoscopy. However, if that patients develops any hemodynamic instability, or signs of ongoing bleeding, Dr. Jim Yang would advocate for an earlier endoscopy.

Therapeutic Hypothermia after ROSC

Is therapeutic hypothermia post ROSC always a good thing?
Or does this depend on the underlying etiology (cardiac vs non-cardiac) and the pre-post ECG rhythm? What temperature should we aim for? 

Pathophysiology Summary:

Anoxic brain injury is associated with increased mortality and morbidity. Fevers are bad and can worsen ischemic brain injury. The theory behind therapeutic hypothermia is that it reduces free radicals, cerebral oxygen consumption, and ultimately reduces ischemic injury.

The initial trials (early 2000s) were small RCTs showing a huge difference in favorable neurologic outcomes for hypothermia post shockable rhythms (post VF and pVT arrest).  

But in 2013 the TTM trial was published: Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

The TTM Trial by Nielsen et al. (2013) was a large RCT of 939 patients. It showed that unconscious survivors of out-of-hospital (OOH) cardiac arrest, of presumed cardiac cause (but of all rhythms, shockable and non-shockable) there were no difference in outcomes between a temperature target of 33° C vs. 36° C. 

Flash-forward to the HYPERION Trial this past year: Therapeutic Hypothermia After Cardiac Arrest With Non-Shockable Rhythm

Design

  • Multi-center, RCT performed in 25 ICUs in France
  • 581 adult patients

Included

  • ROSC following in hospital (IH) or out of hospital (OOH) cardiac arrest with non-shockable rhythm due to any cause
  • Patients had to be comatose post (GCS <8)

Excluded

  • Patients with poor prognostic indicators. 
    • More than 10-minutes from collapse to initiation of CPR.
    • More than 60-minutes from initiation of CPR to ROSC
    • Those in refractory shock despite vasopressors

Intervention

  • Randomized to either period of hypothermia (targeted temp 33°) vs normothermia (targeted temp 37°)
  • Hypothermia group was cooled after randomization and maintained at 33° for 24-hours, then slowly rewarmed with fever avoided over the subsequent 24-hours.
  • Normothermia group cooled if need (avoidance of fever) for up to 48-hours

 Outcomes

  • Primary outcome: Survival with favorable neurologic outcome
  • Secondary outcomes: mortality, length of mechanical ventilation, length of ICU stay, adverse events

Results

Hypothermia was associated with improved survival with favourable neurologic outcome. 10% in hypothermia group vs. 6% in normothermia group. However: No difference in overall mortality, no difference in duration of mechanical ventilation, ICU length of stay, or adverse events. 

Note: hypothermia group had TTM for a longer duration than the normothermia group. 

The normothermia had avoidance of fever for 48-hours, whereas the hypothermia group had induction of hypothermia & maintenance for 24 hours, a period of rewarming, and then maintenance of rewarming for an additional 24 hours. In total, between 56-64 hours of TTM. 

Also, a substantial number of patients in the normothermic group were not normothermic! Although target was 37° C, Patients randomized to this group developed fevers > 38° C throughout the TTM period. 

Bottom Line

  1. Fever is bad.
  2. All patients who are comatose following ROSC should be cooled to prevent fever. 
  3. Temperature you end up at isn’t as important as long as you avoid fever. 

For Dr. Jim Yang, the next patient he sees post ROSC, regardless of shockable vs non-shockable rhythm, he’ll be targeting a temperature of 32-36^C, keeping with the American Heart Association and European Resuscitation Counsel.

We should be initiating cooling for all ROSC patients in the ED.

This can be as simply as

  • Inserting a bladder temperature probe
  • Placing ice packs on the patients groin and axilla

 Any regarding rates of adverse events?  

There has never been any document increase in rates of adverse events between hypothermia and normothermia in ANY of published RCT to-date. 

Show notes compiled by Dr. James Gilbertson

Original music by Eusang