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Episode #18 – Tick Talk

18 Cover Art OPT

Summary

Dr. Peter Krause helps us through a case of summertime fever and approaching tick-borne illnesses.

Credits

Host: Sara Dong

Guest: Peter Krause

Writing/Producing/Editing/Cover Art/Infographics: Sara Dong

Our Guest

Peter Krause, MD

Peter is a Senior Research Scientist in the Department of Epidemiology and Public Health at Yale School of Public Health and Yale School of Medicine in New Haven, CT.  He completed his pediatric internship and residency training at Yale-New Haven Hospital and Stanford University Medical Center, followed by his Pediatric Infectious Disease fellowship at UCLA.  He carries out translational, epidemiological, and clinical research in the study of vector-borne disease.  He has focused on human babesiosis, Lyme disease, and relapsing fever caused by Borrelia miyamotoi.  He is the author of many peer reviewed publications and book chapters, and he recently served as the Chair of the Clinical Practice Guidelines for the IDSA’s 2020 Guideline on Diagnosis and Management of Babesiosis.

Culture

Peter’s family is #1!  His hobbies outside of work include walking, classical music, and reading novels when he can.

Consult Notes

Consult Q

65 yo F with fatigue and fever

One-liner

65 yo F with history of pancreatic cancer s/p partial pancreatectomy and splenectomy 5 years ago who presented with profound fatigue, fever, and headache, and was found to have babesiosis.

Key Points

Jump to these Babesia topics:

Resources
Epi/Micro basics
Clinical
diagnostics
babesia vs malaria
Abx management
Other management
Monitoring
Future questions and take-homes

Peter discussed his general approach to fever in the summertime and emphasized the importance of epidemiological history.  This episode focused on babesiosis, but the differential diagnosis for Babesia often includes the following illnesses.  We’ll have some compare/contrast charts in the infographics to follow!

  • Babesiosis
  • Malaria (if the right exposure!)
  • Other infections via Ixodes ticks: Anasplasma phagocytophilum, B.burgdorferi and B.mayonii (Lyme disease), B.miyamotoi, Ehrlichia muris, Powassan
  • Ricketssioses
  • Leptospirosis
  • Viral hepatitis, bacteremia, or a noninfectious cause of hemolytic anemia

Babesiosis!

Resources:

Babesia basics

Clinical manifestations of babesiosis can range from asymptomatic disease to severe or fatal infection → severity of infection depends on the Babesia species and the immune status of the host

  • Asymptomatic infection 
  • Mild to moderate disease (generally <4% parasitemia): fatigue, fever, chills, sweats, myalgias, headaches.  Sometimes can have anorexia, nausea, or dry cough
  • Severe disease can often be seen in older patients, immunocompromised hosts, and those with parasitemia >=4%
      • Risk factors for severe babesiosis: 
          • Extremes of age (>50 years old, <2 months old)
          • Neonatal prematurity
          • Asplenia
          • Malignancy
          • HIV/AIDS
          • Immunosuppressive drugs (such as TNFa blockers, anti-CD20 agents like rituximab)
      • Complications of babesiosis with end-organ disease include:
          • ARDS
          • Severe anemia
          • Congestive heart failure
          • Renal failure
          • DIC
          • Shock
          • Splenic rupture
          • Warm autoimmune hemolytic anemia (late complication)
          • Relapsing disease in immunocompromised patients
  • A few notes on clinical manifestations
      • Rash is rarely noted and should raise concern for possible concurrent co-infection such as Lyme disease

We mentioned a way to remember Babesia is to think of it like a North American malaria

  • Both infections invade RBCs and have some similarities in clinical characteristics — but very different epidemiologic exposures
  • Differences between the two:
      • Plasmodium spp: 
          • Transmitted by mosquitoes from person to person, using humans as reservoir hosts
          • Have exoerythrocytic (hepatic) stage
          • Leave hemozoin deposits in RBCs
      • Babesia spp:
          • Transmitted by ticks; not transmitted person to person but rather use mammals as reservoir hosts
          • Lack exoerythrocytic stage
  • When looking at thin smear, the two have similar appearing intraerythrocytic ring forms but…
      • Plasmodium leave hemozoin deposits in RBCs (more brown pigment than Babesia) and have banana-shaped gametocytes
      • Babesia can have presence of extracellular forms and maltese cross

Diagnosis of babesiosis

  • Once you have a clinical syndrome with likely epidemiologic exposure, you’ll likely be sending baseline labs as well as specific diagnostics for the tick-borne illnesses on the differential.  There is no pathognomonic signal from history and physical exam that can tell you that a case if babesia
  • Baseline labs:
      • CBC: Expect anemia and thrombocytopenia.    Leukopenia might make you think more about Anaplasma (organism invades WBCs, specifically neutrophils)
      • Chemistry: elevated LFTs can be seen with Babesia (and Anaplasma). In severe disease, may see elevated BUN/Cr
      • Elevated LDH
  • Initial test/screen is a parasite blood smear!!
      • Looking for intraerythrocytic ring forms (might look similar to Plasmodium falciparum) – these trophozoites are round, oval, or pear-shaped with blue cytoplasm and reddish chromatin
      • Maltese cross (presence of merozoites arranged in tetrads) is pathognomonic for Babesia if you see it
      • Extracellular forms also indicate Babesia (rather than malaria)
      • Peter also discussed items you might see that indicate a different infection: 
          • Morulae (characteristic of Anasplasma), which occur once organism is ingested by neutrophils and multiples in phagolysosome
          • In B.miyamotoi (relapsing fever), you might see spirochetes in the blood during a febrile illness
  • Babesia PCR is available as an alternate test, although in many settings a smear is likely a little more rapid and generally sensitive
  • Babesia serology
      • We need to remember that antibody usually do not generally appear until ~2 wks into acute illness
      • You can have residual positive Ab testing for years after an illness, so this doesn’t prove a current infection.  As Peter discussed, treatment of patients with just a positive Babesia Ab in setting of fever is not recommended → if you are concerned, should be getting parasite smear and/or PCRTreatment of babesiosis
      • Can be used as adjunct though

Management of babesiosis

  • We discussed how patients are often placed on empiric Doxycycline when there is concern for possible tick-borne infection.  It’s important to remember that Doxy treats B.burgdorferi, B.miyamotoi, Anasplama — but not babesiosis.  So if a patient is not responding to empiric doxycycline, might be a clue that you are dealing with babesiosis.
    •  
  • Clinda/quinine is still an alternative in back pocket, especially if not responding to first line

Duration of therapy:

  • Ultimately duration of therapy is guided by parasite clearance and clinical improvement
  • **Patients with positive serology but in whom no parasites can be detected by smear or PCR or asymptomatic patients should NOT be treated**
  • A brief 7-10 day course is likely ok for most immunocompetent patients with low grade parasitemia and uncomplicated disease.  In fact, many of these might be treated as outpatient is doing reasonably well and no obvious risk factors
  • Immunocompromised hosts may require upwards of 6 weeks of therapy.  Those with evidence of impaired antibody production in particular (B cell lymphoma, rituximab, asplenia), may have fulminant or protracted disease.  It is very difficult to eradicate infection completely and patients may have relapsing disease if not treated for long enough

Other babesiosis management notes

RBC exchange transfusion (remove patient rbc and replace with allogeneic rbcs; either partially or completely) may be warranted in some pts

Patient counseling

  • Symptoms should improve within ~48h of starting antibiotics
  • It is important to counsel patients that fatigue may persist for months though and doesn’t necessarily warrant extension of therapy
  • Discuss tick bite prevention
        • Avoidance of areas where ticks, deer, and mice are common if able, particularly those who are asplenic or otherwise immunocompromised
        • If live or travel to endemic area, avoid tall grass, brush, forested areas (or stay in middle of path/trail)
        • Use protective clothing sprayed or impregnanted with DEET or permethrin
        • Wear long sleeved shirts and long pants, lightly colored (so can see the ticks and hopefully less likely to attach)
        • Have a tick search upon return home and check in hidden areas where ticks may have hidden!  (such as behind the knees/ears, etc)
        • Environmental measures might include keeping mown lawns, placing stone barriers between lawn and woods, etc

How do you monitor these patients after diagnosis?

  • Immunocompetent pts: 
      • Monitor parasitemia during treatment of acute illness with peripheral smears
      • Once there is evidence of downtrending parasitemia and clinical improvement,  recommend against further testing for parasitemia once symptoms have resolved
      • Patients do not have to remain in the hospital until parasitemia is gone if they are otherwise doing well
  • Immunocompromised hosts are in a different boat though: 
      • Would monitor parasitemia with peripheral blood smears even after asymptomatic and until blood smears are negative
      • PCR testing should be considered if blood smears negative but symptoms persist
      • That being said, its important to remember that PCR can remain positive for a very long time (years!) in both immunocompetent or immunocompromised patients — so it is not necessary to monitor PCRs for clearance (even in ICH) if patient is clinically improving and blood smears are negative.  As Peter mentioned, maybe we’ll be able to use quantitative PCR in the future when it has been studied more

Peter also discussed future areas to consider in babesiosis and what we still need to learn more about:

Some of Peter’s take-homes

  • Consider Babesia in the differential diagnosis of febrile patients living in or recently traveled to endemic areas as well as those with blood transfusion in past 6 months.  The biggest challenge is thinking about it!
  • Immunocompromised patients, particularly those with risk factors such as asplenia, require close monitoring!
  • The good news is that in majority of cases, patients do well!

Other miscellaneous mentions and notes:

Episode Art & Infographics

Goal

Listeners will be able to describe the clinical presentation, diagnosis, and management of human babesiosis

Learning Objectives

After listening to this episode, listeners will be able to:

  • Identify the primary vector of B.microti and other co-infections that are transmitted by the same vector
  • List the routes of transmission of babesiosis
  • Compare and contrast the features of Babesia on blood smear to anaplasma and malaria
  • Describe the first-line antimicrobials for babesiosis as well as other management considerations (such as exchange transfusion)

Disclosures

Our guest (Peter Krause) as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Krause, P., Dong, S. “#18: Tick Talk”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/ae181a08-25ff-4d4a-b06c-c293d6d6cd97

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