Babesia in Florida: How Travel and Transfusion Facilitate Infection

1
Babesia in Florida How Travel and Transfusion
Facilitate Infection

• Amber Barnes, MPH
• FL-EIS Fellow, Epidemiology
• Duval County Health Department

2
Presentation Objectives

• To provide an overview of the current
  epizootiology of Babesia
• Describe routes of Babesia transmission
• Describe the potential impact of Babesia on
  Floridians

3
Background of Babesiosis

• Zoonotic infection of a protozoan parasite
  Babesia
• causes Babesiosis
• Transmitted through
• Ixodes scapularis deer ticks
• transfusion of infected blood products
• and congenitally
• Parasites invade the erythrocytes, or red blood
  cells
• causes asymptomatic, acute, and chronic infections

4
Epidemiology of Babesia

• There are over 100 known species of Babesia1
• The species known to parasitize in humans
  include2
• B. microti is the most common species to cause
  infection in humans in America
• B. divergens is the most common species infecting
  humans in Europe

• - B. microti - B.
  duncani
• - B. microti-like - B.
  duncani-like
• B. divergens - B.
  ovis-like
• B. divergens-like - B.
  bovis
• - B. canis

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Transmission

• Ixodes scapularis- black-legged deer tick
• Larval stage feeds on white-footed mouse
• Nymphal stage feeds on humans and white-tailed
  deer

DIME
From http//www.ent.iastate.edu/imagegal/ticks/isc
ap/
From http//fubyss.ento.vt.edu/vagm/enemies.html
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Transmission
B. microti transmission
Life Cycle of I. scapularis tick
RESEVOIR White footed mouse and other rodents
VECTOR/ PRIMARY HOST Black-legged deer tick
SECONDARY HOST mammals, i.e. humans
Courtesy of D.W. Miller within Vannier, et al.
Infectious Disease Clinics of N. America 22
(2008) 469488.
7
Life Cycle of Babesia
Some Babesia species are transmitted at every
stage of the ticks life
Reprinted with gracious permission from K.-P
Hunfeld et al. International Journal for
Parasitology 38 (2008) 1219-1237as modified from
Mehlhorn and Piekarski, 2002.
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Transmission

• Additional transmission routes
• congenital/perinatal infection to baby
• transfusion of blood from an infected donor
• donor may be asymptomatic
• currently no testing for Babesia in donated blood
  products or screening of blood product donors
• parasite can survive for 35 days in refrigerated
  blood bank conditions3
• patients receiving blood are immunocompromised or
  immunosuppressed

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Infection

• Asymptomatic infection
• majority of cases are unaware of infection
• parasitemia levels may be too low for detection
• Chronic infection
• can be infected for months, even years4
• infected blood donors can transmit disease
  unknowingly
• infected mothers have infected unborn babies and
  newborns
• Acute infection
• can cause severe illness and death
• primarily affects immunocompromised/suppressed
• especially asplenic and/or elderly patients5

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Clinical Symptoms

• Malaria-like infection6
• Common symptoms
• Additional symptoms may include

Fever Fatigue Chills
Hemolytic anemia Myalgia Jaundice
secondary to anemia
Headache Vomiting Anorexia Thr
ombocytopenia Nausea Normal or low WBC count
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Infection

• Most untreated infections will resolve but can
  take weeks to several months
• Incubation Period of Babesiosis
• ranges from 1 week to several months
• generally shorter for tick-borne transmission
• can be longer for transfusion transmission
• Period of Communicability
• very rare person-to-person transmission
• congenital/perinatal
• transfusions of infected blood

12
Diagnosing Babesiosis
CURRENTLY NOT REPORTABLE IN FLORIDA

• Can be difficult to diagnose
• Things to remember
• Babesia is not endemic to our area
• may not be considered in the differential
  diagnosis
• Babesia is often discovered by our state labs
  testing blood for malaria
• different Babesia species show up through
  different diagnostic methods

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Diagnosing Babesia

• Diagnosed through the identification of the
  intraerythrocitic parasites on Giemsa- or
  Wright-stained thick or thin blood smears7
• can be very difficult to distinguish from
  Plasmodium falciparum
• look for the disease-specific
• Maltese cross
• only visible during
• Merozoite stage

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Diagnosing Babesia

• Once identified, more serologic and molecular
  testing is performed by
• a reference laboratory
• confirms diagnosis
• CDCs parasitology lab
• confirm diagnosis
• and/or determine species
• animal innoculation
• can take up to two weeks for results8

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Guess That Parasite!
B. microti
B. microti
B. divergens
B. venatorum
B. venatorum
B. divergens
B. venatorum
P. vivax
P. falciparum
Images courtesy of the Liverpool School of
Tropical Medicine and arrow sources from
Häselbarth et al 2007 and Hildebrandt et al 2008.
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Treatment

• Asymptomatic infection is rarely treated
• General recommended treatment for immunocompetent
  individuals includes
• Clindamycin
• PLUS
• Quinine or Quinidine
• 7 to 10 day treatment
• can result in side effects that merit use of
  alternative drugs

17
Treatment

• Recommended treatment for individuals
  immunocompromised or those with very high
  parasitemia levels includes
• Azithromycin
• PLUS
• Atovaquone
• 7 to 10 day treatment
• some research indicates new resistance9
• In rare instances of severe infection, exchange
  transfusions are given10

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Wisconsin Case Definition Example

• Confirmed Babesiosis
• A clinically compatible illness that is
  laboratory confirmed. OR
• A patient who is lab-confirmed or who would meet
  the serology criteria of a probable case,
  regardless of symptomatology, who is
  epidemiologically linked to a confirmed case
  acquired via transfusion

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Wisconsin Case Definition Example

• Probable Babesiosis
• A clinically compatible illness with
  demonstration of a Babesia-specific antibody
  titer of at least 1256 with an indirect
  fluorescent antibody (IFA) test for total Ig or
  IgG. The titer should be at least 11024 for
  infection with WA1-type parasites.
• Comments Confirmation of the diagnosis of
  babesiosis by a reference laboratory is strongly
  encouraged. The validity of the diagnosis of
  babesiosis is highly dependent on the laboratory
  that does the testing. For example,
  differentiation between malaria and Babesia
  parasites on peripheral blood smears can be very
  difficult.
• From http//hanplus.wisc.edu/epinet/reports/C
  DES101_babesia.pdf

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Cases Examples

• Case 1 Wedding-acquired Babesiosis in NY
• 73 y/o female
• Arrived at ED after passing out in her doctors
  waiting room
• Had fever at night for last two weeks and anemia
• Exposure risk
• Previous month she had traveled to Connecticut
  for an outdoor wedding
• No memory of a tick bite
• RBC transfusion at hospital
• Peripheral smear showed parasites
• Considered malaria at first
• B. microti was confirmed instead
• Treated successfully with a 14 day course of
  Atovaquone and Azithromycin11

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Cases Examples

• Case 2 Probable congenital in NJ
• 26 day old infant
• Transferred to hospital for evaluation
• Complaints of fever, hyperbilirubinemia, not
  feeding well, irritable, and gagging
• Mother, a migrant crop worker, noticed the infant
  had yellow eyes
• Exposure risks
• No travel by mom or baby
• No tick exposure to child
• Mother had been bitten by two ticks while 8
  months pregnant
• RBC transfusion at hospital
• Peripheral blood smear discovered B. microti
• Treated successfully with Atovaquone and
  Azithromycin12

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Florida Cases

• Case 3 Probable transfusion transmitted
• 74 y/o male
• Arrived at ED on 4/11/2009
• Complaints of anemia and syncope
• Patient had a recent aneurysm repair
• Parasites present on peripheral smear
• malaria test was conducted on 4/12/2009
• Results were positive for Babesia, negative
  Malaria
• B. microti IgM level was lt110 with the range
  being Neg lt110
• B. microti IgG level was Neg. gt1320 with the
  range being Neg lt110
• Negative IgM and positive IgG serology may
  indicate a pervious or current babesiosis
  infection

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Florida Cases

• Case 3 Cont. Probable transfusion
• DSI Laboratory reviewed the specimen and
  confirmed it was Babesia
• Exposure risks
• No memory of tick bite
• No travel outside of the U.S. in gt50 years
• Transfusion history in past year
• Reported internally with the blood bank in April
  and to the FDOH in September

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Florida Cases

• Case 3 Cont. Probable transfusion
• Total of 27 different donors were used for
  patient
• 17 donors subsequently tested negative
• 10 were lost to follow up

RBC SDP Pooled Cryo FFP
2/6/09 7 donors 2 donors 1 donor 4 donors
2/7/09 2 donors
2/11/09 2 donors
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Florida Cases

• Case 4 Travel and transfusion exposures
• 60 y/o male
• Arrived at ED on 8/28/09
• Complaints of dizziness, intermittent fevers,
  fatigue, and several falls
• Once admitted, patient had severe anemia,
  thrombocytopenia, leukopenia and severe abdominal
  pain
• CT scan found patient had a lacerated spleen
• Patient underwent a splenectomy and transfusion
• 6 units of RBCs and 2 units of platelets
  administered 8/28/09 through 9/5/09

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Florida Cases

• Case 4 Cont. Travel/transfusion exposures
• Patient developed a post-op fever
• Blood smears interpreted as possible malaria
• State lab looked at smears at suspected
  babesiosis
• Specimens forwarded to CDCs Parasitology Lab
• Confirmed B. microti diagnosis
• Exposure risks
• Travel to Massachusetts for 5 weeks with a return
  date of 8/1/09
• No known tick bites
• No confirmed previous Babesia infection
• Transfusion history in past year
• Blood bank attempted to inform donors of
  potential infection
• Patient treated with Azithromycin and Atovaquone

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Florida Cases

• Case 5 Confirmed transfusion exposure
• 84 y/o male
• Admitted to hospital in February, 2008 with a GI
  bleed
• Given RBC and plasma transfusions due to surgical
  repair
• Patient returned to hospital 3/18/08
• Complained of fever, chills, diarrhea, sweats,
  back pain, and anorexia
• Peripheral blood smear at hospital was suspect
  for malaria
• State lab confirmed sample was negative for
  malaria but positive for B. microti
• Patient treated successfully and recovered

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Florida Cases

• Case 5 Cont. Confirmed transfusion exp.
• Blood banks did a trace back to find infected
  donor
• 3 units of blood and 2 units of plasma given 2/8
  and 2/11
• 3 separate RBC donors
• 2 Florida residents
• 1 vacationing Wisconsin resident
• FDOH developed questionnaire based on Babesia
  forms from endemic states for blood bank to use
• Found Wisconsin donor to be infected
• Donor was asymptomatic
• Owned a cabin in the woods of an endemic state
• Donated here and in home state of Wisconsin
• Wisconsin blood banks had to be notified of
  donors status
• Upon diagnosis, donor was reported in Wisconsin
  state data

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Expanding Babesia Range

• Residential development in tick-prone wooded
  areas
• More interaction with a growing population of
  deer11
• B. microti is already endemic and reportable in
• Northeastern United States
• Connecticut
• Massachusetts
• New Jersey
• New York
• Rhode Island
• Upper Midwestern United States
• Wisconsin
• Minnesota
• Prior travel history to these areas may indicate
  potential exposures in cases

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Expanding Babesia Range

• Prior to 2001, most NY cases were residents of
  Long Island or those with travel to endemic areas
  
• In 2001, there were 5 confirmed
  locally-acquired cases in
  residents
  of the Lower Hudson
  Valley, north of the endemic
  area with no travel or
  
  recognized risk factors
• NY Dept. of Health collected
  1,139 I. scapularis ticks from 5
  areas in the
  Lower Hudson
  Valley and found B. microti
• Babesia is moving up the state13

Reprinted with from Kogut et al. Emerging
Infectious Diseases 11, 3 (2005).
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Expanding Babesia Range
Table 1 Important Babesia spp. with zoonotic
potential including recently recognized defined
parasites
Species Vector Vertebrate host Geographical occurrence Reported human cases (N) Reported mortality
Species Stage
Large babesia
B. divergens and B. divergens-like
B. divergens s.s Ixodes ricinusa, Ixodes ventalloi (?) Larvae, nymphs, adults Cattle, wild ruminants Europe gt30 42
B. venatorum (EU1) Ixodes ricinusa Larvae, nymphs, adults Deer Europe 3 0
MO1 and related parasites Ixodes dentatus (?) ? Cottontail rabbits USA 3 33
B. ovis-like
KO1 Hemaphysalis longicornis (?) ? Sheep (?) Korea, Asia (?) 1 0
B. bovisb Boophilus spp., Ixodes spp. a, Rhipicephalus bursa Larvae Cattle, water buffalo, wild ruminants Southern Europe, Africa, USA, Asia, Australia 2 100
B. canisb Rhipicephalus sanguineusa, Hemaphysalis leachi, Dermacentor reticularisa Nymphs, adults dogs, Vulpes vulpes, wild canines Europe, Asia, Africa, USA, Australia 1 0
Small babesia
B. microti B. microti-like
B. microti complex Ixodes trianguliceps, Ixodes ricinusa, Ixodes ovatusa, Ixodes scapularisa, Ixodes spinipalpis, Ixodes angustus, Ixodes muris Nymphs, adults Rodents Europe, Asia, USA gt200 5
B. duncani B. duncani-like ? ? ? USA 9 (?) 11
a Known to regularly parasitize humans ?
unknown (?) questionable. b Unverified
infections with B. canis and B. bovis have been
reported (Gorenflot et al., 1998), though it is
likely that B. bovis infections are in fact B.
divergens. Reprinted with gracious permission
from K.-P Hunfeld et al. International Journal
for Parasitology 38 (2008) 1219-1237.
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Surveillance

• The FDA, CDC, CSTE, and other public health
  organizations have recently determined
  transfusion-transmitted Babesia to be a major
  public health concern
• Florida is currently discussing how best to
  investigate future Babesia cases, especially in
  regard to transfusion transmitted cases
• A draft of a Standard Operating Procedure for
  Babesia case follow up in Florida residents will
  be completed in the coming months

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Preventing Tick-borne Infection

• Use protective measures when outdoors
• avoid tick-prone areas May through October
• choose light colored clothing
• wear long sleeves and pants
• tuck pants into boots
• use tick and insect repellents that contain DEET
• inspect yourself for ticks
• if you find one, remove it with clean tweezers by
  gently pulling it straight away from the body,
  not twisting, and wash the area immediately14
• provide your pets monthly tick prevention
  medications

34

• Questions?

Courtesy of http//giveavoice.files.wordpress.com/
2009/06/questions.jpg
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References for Slide Material

• 1Gray, J.S., Weiss, L.M. 2008. Babesia microti.
  In Khan, N. (Ed.), Emerging Protozoan
  Pathogens. Taylor and Francis, Abingdon, UK, pp.
  303-349.
• 2Hunfeld, K.-P. et al., 2008. Babesiosis Recent
  Insights into an Ancient Disease. International
  Journal for Parasitology, 38, 1219-1237.
• 3Emerging Health Threats Forum. (2009).
  Babesiosis call for better blood screening.
  Retrieved on March 23rd, 2010 from
  http//www.eht-forum.org/news.html?targetPagenews
  /fulltext/news091023073616.htmlfromsearch.
• 4Dobroszycki, J. et al., 1999. A Cluster of
  Transfusion-Associated Babesiosis Cases Traced to
  a Single Asymptomatic Donor. JAMA, 281(10),
  927-930.
• 5Heymann, D.L. 2008. Babesiosis. In. Heymann,
  D.L. (Ed.), Control of Communicable Diseases
  Manual. American Public Health Association,
  Washington, D.C., USA, p.p.69-72.
• 6Weld, E.D., Eimer, K.M., Saharia, K., Orenstein,
  A., Hess, J.R. 2010. The expanding range and
  severity of babesiosis. Transfusion 50, 290-291.
• 7Pickering, L.K. 2009. Babesiosis. In. Pickering,
  L.K., Baker, C.J., Kimberlin, D.W., Long, S.S.,
  (Eds). Red Book 2009 Report of the Committee on
  Infectious Diseases. 28th ed. American Academy of
  Pediatrics, Elk Grove, IL, USA. p.p. 226-227.
• 8Asad, S., Sweeney, J., Mermel, L.A., 2009.
  Transfusion-transmitted babesiosis in Rhode
  Island. Transfusion, 49(12), 2564-2573.
• 9Wormser, G.P., et al. 2010. Emergence of
  Resistance to Azithromycin-Atovaquone in
  Immunocompromised Patients with Babesia microti
  Infection. Clinical Infectious Diseases 50,
  381-386.
• 10Leiby, D.A. 2006. Babesiosis and blood
  transfusion flying under the radar. Vox
  Sanguinis 90, 157-165.
• 11Rawling, R.A., et al. 2009. A Case of
  Wedding-Acquired Babesiosis. Clinical
  Microbiology Newsletter 31(15), 116-118.
• 12Sethi, S. et al., 2009. Probable Congenital
  Babesiosis in Infant, New Jersey, USA. Emerging
  Infectious Diseases, 15(5)
• 13Kogut, S.J. et al., 2005. Babesia microti,
  Upstate New York. Emerging Infectious Diseases,
  11(3).
• 14American Lyme Disease Foundation, Inc. (2010).
  Lyme Disease, How to Remove a Tick. Retrieved
  March 23rd, 2010 from http//www.aldf.com/lyme.sht
  mlremoval.

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References for Graphics and Table

• http//fubyss.ento.vt.edu/vagm/enemies.html
• http//www.ent.iastate.edu/imagegal/ticks/iscap/
• D.W. Miller within Vannier, E. et al., 2008.
  Human Babesiosis. Infectious Disease Clinics of
  N. America 22, 469- 488.
• K.-P Hunfeld et al., Babesiosis Recent Insights
  into an Ancient Disease. International Journal
  for Parasitology, 38, as modified from Mehlhorn,
  H. Piekarski, G., 2002. Grundriß der
  Parasitenkunde, 6th revised edition. Spektrum
  Akademischer Verlag GmbH, Heidelberg, Berlin,
  Germany, pp. 38-39.
• ASM http//www.MicrobeLibrary.org
• Liverpool School of Tropical Medicine and arrow
  sources from Häselbarth, K. et al., 2007, First
  Case of human babesiosis in Germany- Clinical
  presentation and molecular characterization of
  the pathogen. International Journal of Medical
  Microbiology 297, 197-204 and Hildebrandt, A. et
  al., 2008, Human babesiosis in Germany Just
  overlooked or truly new?. International Journal
  of Medical Microbiology 298, 336-346.
• http//hanplus.wisc.edu/epinet/reports/CDES101_bab
  esia.pdf
• Kogut, S.J. et al., 2005. Babesia microti,
  Upstate New York. Emerging Infectious Diseases,
  11(3).
• http//giveavoice.files.wordpress.com/2009/06/ques
  tions.jpg

37
Contact Information

• Amber Barnes, MPH
• EIS Fellow,
• FL DOH
• [phone]
• Amber_Barnes_at_doh.state.fl.us
• Robyn Kay, MPH
• Regional Epidemiologist,
• FL DOH
• [phone]
• Robyn_Kay_at_doh.state.fl.us

Danielle Stanek, DVM Medical Epidemiologist, FL
DOH [phone] Danielle_Stanek_at_doh.state.fl.u
s Beth Radke, MPH Arbovirus Surveillance
Coordinator, FL DOH [phone] ext.
2437 Elizabeth_Radke_at_doh.state.fl.us
Please visit the CDCs website on Babesiosis at
http//www.cdc.gov/babesiosis/ for more
information.