Babesia in Florida: How Travel and Transfusion

Facilitate Infection

Amber Barnes, MPH

FL-EIS Fellow, Epidemiology

Duval County Health Department

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

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

Epidemiology of Babesia

• There are over 100 known species of Babesia1

• The species known to parasitize in humans include:2

• 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

Transmission

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

tailed deerDIME

From http://www.ent.iastate.edu/imagegal/ticks/iscap/From http://fubyss.ento.vt.edu/vagm/enemies.html

Transmission

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) 469–488.

Life Cycle of I. scapularis tick

B. microti transmission

RESEVOIR:

White footed mouse and

other rodents

Reprinted with gracious permission from K.-P Hunfeld et al. International Journal for Parasitology 38 (2008) 1219-1237as modified from Mehlhorn and Piekarski, 2002.

Life Cycle of Babesia

Some Babesia species are transmitted at every

stage of the tick’s life

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

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

Clinical Symptoms

• “Malaria-like” infection6

• Common symptoms:

• Additional symptoms may include:

Headache VomitingAnorexia ThrombocytopeniaNausea Normal or low WBC count

Fever FatigueChills Hemolytic anemiaMyalgia Jaundice secondary to anemia

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

Diagnosing Babesiosis

• 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

**CURRENTLY NOT REPORTABLE IN FLORIDA**

• 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

Diagnosing Babesia

tetrad

Diagnosing Babesia

• Once identified, more serologic and molecular testing is performed by:– a reference laboratory

• confirms diagnosis

– CDC’s parasitology lab • confirm diagnosis • and/or determine species

– animal innoculation • can take up to two weeks for results8

Guess That Parasite!

B. microti B. microti B. divergens

B. venatorumB. venatorumB. divergens

B. venatorum P. vivaxP. falciparum

Images courtesy of the Liverpool School of Tropical Medicine and arrow sources from Häselbarth et al 2007 and Hildebrandt et al 2008.

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

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

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

Wisconsin Case Definition Example

• Probable Babesiosis: • A clinically compatible illness with

demonstration of a Babesia-specific antibody titer of at least 1:256 with an indirect fluorescent antibody (IFA) test for total Ig or IgG. The titer should be at least 1:1024 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/CDES101_babesia.pdf

Cases Examples

• Case #1: Wedding-acquired Babesiosis in NY– 73 y/o female– Arrived at ED after passing out in her doctor’s 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

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

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 <1:10 with the range being Neg:

<1:10• B. microti IgG level was Neg. >1:320 with the range being

Neg: <1:10– Negative IgM and positive IgG serology may indicate a pervious

or current babesiosis infection

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 >50 years• Transfusion history in past year

– Reported internally with the blood bank in April and to the FDOH in September

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

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

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 CDC’s 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

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

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 donor’s status• Upon diagnosis, donor was reported in Wisconsin state data

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

Expanding Babesia Range

Reprinted with from Kogut et al. Emerging Infectious Diseases 11, 3 (2005).

• 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

Table 1: Important Babesia spp. with zoonotic potential including recently recognized defined parasites

Species Vector Vertebrate host Geographical occurrence

Reported human

cases (N)Reportedmortality

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 >30 ~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 >200 ~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.

Expanding Babesia Range

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

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

Questions?

Courtesy of http://giveavoice.files.wordpress.com/2009/06/questions.jpg

References for Slide Material1Gray, 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 23 rd, 2010

from http://www.eht-forum.org/news.html?targetPage=news/fulltext/news091023073616.html&from=search.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. 28 th 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 23 rd,

2010 from http://www.aldf.com/lyme.shtml#removal.

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_babesia.pdf• Kogut, S.J. et al., 2005. Babesia microti, Upstate New York. Emerging Infectious

Diseases, 11(3).• http://giveavoice.files.wordpress.com/2009/06/questions.jpg

Contact Information

Amber Barnes, MPHEIS Fellow, FL DOH(904) 253-1864Amber_Barnes@doh.state.fl.us

Robyn Kay, MPHRegional Epidemiologist, FL DOH(904) 791-1747 Robyn_Kay@doh.state.fl.us

Danielle Stanek, DVMMedical Epidemiologist,FL DOH (850) 294-1087Danielle_Stanek@doh.state.fl.us

Beth Radke, MPHArbovirus Surveillance Coordinator,FL DOH(850) 245-4444 ext. 2437Elizabeth_Radke@doh.state.fl.us

Please visit the CDC’s website on Babesiosis at http://www.cdc.gov/babesiosis/ for more information.