Babesia from a donor perspective American Red Cross, Massachusetts Region Bryan Spencer, MPH Research Scientist American Society for Apheresis Annual Meeting May 8, 2015 San Antonio, TX The need is constant. The gratification is instant. Give blood. TM
2 TTD charge: monitor and prioritize EID agents Transfusion Supplement, Aug 2009
Public Perception CWD Chikungunya virus HHV-8 B. burgdorferi SLE virus HIV variants Influenza virus subtype H5N1 HAV Dengue viruses Babesia Leishmania T. cruzi vcjd high EID Agent Priority Matrix Range reflects subjectivity/uncertainty geographic variability 3 Plasmodia moderate low B19 virus very low absent SFV theoretical very low low moderate high Science/Epidemiology
4 How does risk from babesiosis compare to other transfusion risks in the United States? Agent HIV HBV HCV Population prevalence 0.45% (Lansky, ACBSA, May 2010) 0.27% (Ioannou, Ann Int Med, 2011) 1.3% (Armstrong, Ann Int Med, 2006) Estimated Residual Risk 1:1.5M* (Zou, et al. Transfusion 2010) 1:300k (Zou, et al. Transfusion 2009) 1:1M (w/ NAT) (BPAC, Apr 2009) 1:1M (Zou, et al. Transfusion 2010) Annual transfusions: 14M RBC, 2M plt, 4M plasma
5 How does risk from babesiosis compare to other transfusion risks in the United States? Agent Population prevalence Historical / recent risk Chagas* ~ 100,000 prevalent infections 1:30,000 in blood donors < 12 transfusion cases N. Am. 5 solid organ transplant cases Malaria Unknown ½ case TTM per year Babesia 1-2% seroprevalence in endemic areas 162 cases over 30 years; recently 1:10 6 transfusions HBV: Annual transfusions: 14M RBC, 2M plt, 4M plasma *transmissibility ~ 1% in U.S.
6 Babesia spp. agents of human babesiosis: B. microti: U.S. B. divergens: Europe infects red blood cells transmitted by Ixodes ticks Infection often silent or associated with flu-like illness that is normally self- limited, but can be severe or fatal in: elderly infants immunocompromised asplenic Persistent parasitemia not uncommon
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Babesia species in North America 8 B. microti accounts for most reported disease Expanding endemic range Made nationally notifiable disease by CSTE in 2011 Sporadic distribution of other Babesia organisms B.duncani, CA-type1-4, MO1, TN isolate B. microti B. duncani, CA-type MO1 isolate
Babesia surveillance, 2013 9 95% of cases in 7 states: NY, NY, CT, MA, RI in Northeast WI, MN in Upper Midwest
Babesiosis an emerging disease 10 1966-2010 2011 2012 2013 2014 States reporting 7 18 22 27 31 States w/ cases Varies 15 14 22 20 Cases reported < 2000 1124 911 1762 1571 Transfusion cases 159 10 7 14 Not available 1 per 200,000 national rate
Common signs and symptoms 11 Case Fatality Rate 6.5% White et al. Arch Int Med, 1998;158:2149-54.
Babesiosis characteristics, 2013 12 Median age 62 65% male 44% hospitalized (median stay 4d) Signs & Symptoms Fever 83% Thrombocytopenia 69% Anemia 64%
Frequency of undetected infection? 13 presence and severity of symptoms brought to medical attention clinical suspicion / ability to detect Krause (NEJM 2012) suggests ½ of children and ¼ of healthy adults have no symptoms
Distribution by age compared to Lyme 14 Courtesy Al de Maria, MA State Epidemiologist
15 Active vs. passive surveillance: seroprevalence by CT county per 10,000 donations vs. CT-DPH case reports County Seroprevalence in donors, 2007-2008 Reported case rates per 10k population, 2002 Hartford 39 0.06 New Haven 43 0.02 Fairfield 49 0.15 New London 198 1.5 Middlesex 242 0.2 Windham 51 0.4 Tolland 82 0.2 Litchfield 17 0 Statewide 70 0.15
Persistent asymptomatic infection 16 NEJM 1998;339:160-5
17 3 donor patterns for infection / clearance transient elevation of IFA titer with/without parasitemia clearance of measurable parasitemia serologic status returns to baseline long-term elevation of IFA titer with/without parasitemia infection/clearance/re-infection (intermittent parasitemia) residence in endemic area no knowledge of tick re-exposure All donors seropositive deferred indefinitely
B. microti: Survival In Blood Products 18 survives in red cells maintained at 4 o C 21 days experimentally 42 days in association with a transfusion case survives indefinitely in cryopreserved red cells parasite killed in frozen plasma contaminating red cells pose potential issues for platelet apheresis & fresh plasma products
19 ; ; ; ; ; and Herwaldt et al., Ann Intern Med 2011;155:509-519
162 Cases 20 162 cases in 30 years (1979 2009) 159 cases attributed to B. microti 3 cases attributed to B. duncani median patient age - 65 years primarily associated with red cells (4 platelets) fatalities (n=12) increasingly reported likely undercounts cases lack of physician recognition case selection criteria 87% of cases in 7 endemic states
TTB Cases on the Rise 21 Herwaldt et al., Ann Intern Med 2011;155:509-519
Year-Round Risk of TTB? 22 Herwaldt et al., Ann Intern Med 2011;155:509-519
23 Risk Mitigation for Babesia Transmission Donor Questions History of babesiosis most donors unaware of history 1 per 20k donors CT and 1 per 80k MA) History of tick bite predictive value limited to none Travel deferral possible but logistically challenging, low specificity Geographic Deferral (seasonal or otherwise) practice used in some areas but of unproven effect Donor Testing Serology vs. NAT serology good to determine exposure, NAT is good tool but might miss low level parasitemia
24 Diagnosis of Babesiosis No licensed diagnostic test in U.S. Direct testing peripheral blood smear PCR hamster inoculation Indirect testing IFA Automated immunoassays under development
Progress towards a test... 25 IND protocols Rhode Island Blood Center with Imugen CMV model New York Blood Center with Immunetics American Red Cross with Imugen (+) good performance characteristics (+) high throughput
ARC IND - 1 26
ARC IND - 2 27
ARC IND - 3 28
Updated AABB Bulletin 29
Implementation Questions 30 serology and/or NAT? seasonal or year-round? universal vs. regional screening? 7 vs 20 states? selective CMV model? role for pathogen reduction? blood importation? donor re-entry? does licensure = mandate?
What level of intervention can we afford? 31 - IFA, ELISA, PCR, combinations thereof - 4, 7, 20, or all-state strategy - estimated $ 5-6M / QALY under 4- or 7-state ELISA+PCR strategy Transfusion, Sept 2014
Cautionary lesson from Chagas testing 32 Chagas RIPA-Positives through 10/25/11
Summary Babesia risk 33 Donor exposure to B. microti is many times higher than passive surveillance data suggest Babesia spp. pose a significant blood safety risk Known geographic range continues to expand, and blood products travel, so risk in areas not known to be endemic might have greater than appreciated risk from both locally-collected and imported blood Licensed diagnostic test not available, and is sorely needed Significant challenges will follow test licensure: whom to test, and which patients should get tested blood?