Planning for the FutureWhat’s coming for CBS?

Resident SeminarMay 29, 2009

Dr. Margaret FearonExecutive Medical Director, Medical Microbiology,

Canadian Blood Services

2

Risk Assessment – What Can Blood Supplier Do?

• Can high risk donors be excluded?

• Is there a screening test?

• Effect of leukoreduction (removal of white cells).

• Assess impact of measures on blood supply.

3

Current Pathogens of Concern for Blood Operators

• Chagas Disease - protozoan• Babesiosis - protozoan • vCJD (variant Creutzfeld Jacob Disease) – prion• Influenza - virus• Malaria - protozoan • Ehrlichiosis – bacteria• HHV8 - virus• Dengue - virus

4

Chagas DiseaseTrypanosoma cruzi

Protozoan flagellate Trypomastigotes (blood) Extracellular (not removed by

leucoreduction) Amastigotes multiply in smooth

muscle tissue – heart, gut

Amastigote in heart muscle

Trypomastigotes in blood

5

Where is Chagas Disease Found?

Most of South America Central America Parts of Mexico

18 million people infected 1-2 million in large, non-endemic areas (Sao Paulo, Rio, Buenos Aires)

100,000 in the U.S. (?)

6From CDC

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WHO/TDR

Reduvid Bug – aka ‘Kissing Bug’

8WHO/TDR

926

10

Stages of Chagas Disease• Acute stage: Immediate reaction to infection

– Only occurs in about 1% of people infected – Swelling of the eye, tiredness, fever, rash, loss of appetite– Can be fatal for infants and very young children– Severe in immunocompromised recipients (HIV/AIDS,

transplants)– Responds to Nifurtimox or Benzonidazole

• Chronic: 10 to 20 years after infection– Enlarged heart, arrythmias, cardiac failure (20-30%) or

digestive tract – megacolon, megaesophagus (9-14%) – Chronic encephalitis– 40-50% parasitemic with no symptomatic disease

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WHO/TDR

Cardiomegaly in Chronic Chagas Disease

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Reported cases of T. cruzitransmission via transfusion in the

U.S. and Canada

• 19871987 California via Mexican donor• 19891989 New York City via Bolivian donor• 19891989 Manitoba via Paraguayan donor• 19931993 Houston via unknown donor• 19991999 Miami via Chilean donor• 20002000 Manitoba via German/Paraguayan donor• 20022002 Rhode Island via Bolivian donor

– *5 cases – platelet transfusion, others unknown

Reference Source: Dr. D. Leiby, ARC

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Continental U.S. Map: Cumulative RIPA Positives (January 2007 to present) (updated 5/21/09)

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CBS Response To Chagas Disease Phase 1 - Risk Questions added to the Record of

Donation Feb.9, 2009

Questions:• 1. Were you born in Mexico, Central America, or South America?

• 2. Was your mother or grandmother born in Mexico, Central America, or South America? (If the answer is yes, the nurse would determine if it was the mother or maternal grandmother, leading to Chagas' risk, or the paternal grandmother, with no Chagas' risk)

• 3. Have you spent 6 months or more at any one time in Mexico, Central America, or South America?

Outcome for Donors • Platelets and transfusible plasma will not be made from donors who answer

‘yes’ to any of the risk questions.

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CBS Response to Chagas DiseasePhase 2 - Donor Testing - Spring 2010

• Implement donor testing as a mandatory screening test for those donors answering yes to risk questions.

• Testing performed in Toronto Donor Testing Lab – batched.• Repeat reactives (RR) will be tested by immunoblot (confirmatory assay)

at National Testing Lab in Ottawa.

• Donors permanently deferred based on a RR test.• All manufactured components destroyed based on RR result.• Lookback performed on all confirmed positive donors.• Risk questions retained on RD – platelets will not be made from donors

who answer yes to risk questions even if they test negative (issue with timing).

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Variant CJD (vCJD)

• Prion – transmissible protein – With aberrant folding– Transmitted by consumption of

BSE (bovine spongiform encephalopathy) contaminated beef

• Neurologic damage due to accumulation of abnormal protein

• Clinical – progressive, fatal neurodegenerative disease

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VARIANT CREUTZFELDT-JAKOB DISEASE CURRENT DATA (FEBRUARY 2009) European and Allied Countries Study Group of CJD (EUROCJD/NEUROCJD)

COUNTRY

TOTAL NUMBER OF PRIMARY CASES  (NUMBER ALIVE)

TOTAL NUMBER OF SECONDARY CASES: BLOOD TRANSFUSION  (NUMBER ALIVE)

CUMULATIVE RESIDENCE IN UK > 6 MONTHS DURING PERIOD 1980-

1996

UK 165 (4) 3 (0) 168

France 23 (0) - 1

Republic of Ireland

4 (0) - 2

Italy 1 (0) - 0

USA 3† (0) - 2

Canada 1 (0) - 1

Saudi Arabia 1 (1) - 0

Japan 1* (0) - 0

Netherlands 3 (0) - 0

Portugal 2 (0) - 0

Spain 5 (0) - 0

† the third US patient with vCJD was born and raised in Saudi Arabia and has lived permanently in the United States since late 2005.  According to the US case-report, the patient was most likely infected as a child when living in Saudi Arabia.*the case from Japan had resided in the UK for 24 days in the period 1980-1996.

*the case from Japan had resided in the UK for 24 days in the period 1980-1996.

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vCJD

• Four cases of probable transfusion transmission in U.K. All transfused non-leukoreduced RBCs 1996-1999 – Case 1 received blood in 1997, died 2003, vCJD (6 yrs post

transfusion). Donor symptomatic with vCJD 3 yrs after donation.– Case 2 received blood in 1999, died 2004, unrelated causes. Donor

developed symptoms 18 mo. post donation.– Case 3 developed vCJD 6 yrs post transfusion. Transfused 1998. Donor

symptomatic 20 mo. post donation. Reported 2006– Case 4 received blood 8 yrs prior to becoming symptomatic. Same

donor as case #3. Reported Jan.07.

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Case of vCJD in Plasma Product Recipient (UK)

• 70 yr. old male haemophiliac• Died early 2009 of unrelated condition, no symptoms of

vCJD• vCJD prion protein identified in spleen at autopsy• Treated with UK sourced clotting factors prior to 1999,

including one batch of Factor VIII manufactured using plasma from a donor who went on to

develop vCJD 6 months after donating.• Patient had other risk factors, including receipt of RBCs

and beef consumption.

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Current vCJD Donor Deferral Policy at CBS

• > 3 mo. (cumulatively) in UK (England, N. Ireland, Scotland, Wales, Isle of Man or Channel Is.) or France from Jan. 1, 1980-Dec.31, 1996.

• >5 yrs. (cumulatively) in Western Europe (Germany, Italy, Netherlands, Switzerland, Austria, Belgium, Spain, Republic of Ireland, Portugal, Denmark, Luxembourg, Liechtenstein) since Jan. 1, 1980.

• Received a blood transfusion or blood product in the UK, France or Western Europe since Jan. 1, 1980.

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Donor Testing

Donor Base of 3 M

True Positive300

False Negatives3

True Negatives2.97 M

False Positive30,000

Assuming that a donor screening test would have sensitivity and specificity characteristics of a typical donor screening test (99% specificity).

Several assays, including one from a Canadian company, Amorfix are urently under evaluation in the UK.

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Prion Removal from Blood• Two companies have prion reduction filters in the

marketplace.• Pall: Prion filter with CE mark

– underwent testing at NBS using a hamster-adapted scrapie strain inoculated into human blood and transfused to hamsters

– Of 418 animals receiving filtered prion infected blood, 3 developed symptoms – therefore filter failed this evaluation.

• MacoPharma and PRDT, Inc. – filter that has just received a CE mark. – Currently in safety trials Ireland

• At the present time, there are no data outside of company development work to indicate that a rigorous prion reduction filter is available.

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BabesiosisProtozoan parasites

Babesia microti, duncani,

http://www.ent.iastate.edu/imagegallery/ticks/deertick.html

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Epidemiology

• Sporadic cases in Europe and Asia• U.S. Cases reported in:

– Connecticut– Rhode Is.– New York State– California– Washington State– Mississippi– Kentucky– Minnesota– Wisconsin

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Clinical• Most infections asymptomatic or unrecognized• Incubation1-6wks.(9 post transfusion)

– Flu like symptoms– Severe: hemolytic anemia, thrombocytopenia, renal

failure, ARDS

• Overall mortality~5% (higher if at-risk)– i.e. immunocompromised, asplenics, v. young and

old, co-infection with other tick-borne diseases

• Treatment– Clindamycin + quinine x 7 d– Atovoquone + azithromycin

• Asymptomatic carrier state for months – years– up to 50% of seropositive cases may be parasitemic

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Transfusion Transmitted Babesiosis

• >70 cases reported since 1979, most US

• 1 Canadian report, 1999– 53 yr old female– intestinal tumour resected– Received 5 units RBC Nov 1998-Feb

1999– April 1999: fever, anemia, hepatitis– Smear initially interpreted as P.

falciparum– 1 donor reported camping in Cape Cod

prior summer• Smear and PCR positive for B. microti

Extracellular and intra-

erythrocytic forms,

one of which is vacuolated.

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Next Steps

• Better characterize donor risk of Babesiosis– Seroprevalence surveys– tick surveys (Ixodes species and Babesia prevalence)

• Assess donor risk of exposure– Specificity difficult because:

• Exposure common in endemic areas• Endemic areas are changing with climate and ecology change• Donors and blood move around

• Develop sensitive, specific laboratory donor screening assays – Selective vs universal donor screening?– Routine vs periodic or seasonal screening?– Serologic vs nucleic acid testing(NAT)?

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INFLUENZA A(H1N1) SWINE

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Source: Nature Medicine 1998; 4:1122-3.

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H1

H2

H3

H4

H5

H6

H7

H8

H9H10

H11

H12

H13

H14

H15

H16

N1

N2

N3

N4

N5

N6

N7

N8

N9

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Influenza A HA and NA Subtypes

Other Animals

Other Animals

Other Animals

Other Animals

Other Animals

Other Animals

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Seasonal Influenza Transmission Routes

• Transmission of influenza viruses– Direct contact with infected person (hand-

shake)– Droplets from coughing or sneezing– Transmission from objects (fomites)

possible– Infectious 1 day before and up to 7 days

after becoming sick

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U.S. Centers for Disease Control and Prevention

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Pandemic Influenza Phases

33

The World Health Organization

34

35

FluWatch April 26 – May 2

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FluWatch May 3 - 9

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Influenza strain characterization, Canada, cumulative, 2008-2009 influenza season by the Respiratory Viruses Section at the National Microbiology Laboratory

[N=1044]

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The Public Health Agency of CanadaInfluenza A(H1N1) Epidemic Curve May 25, 2009

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Pandemic PhasesCBS has identified 4 levels of alert escalation in line with the World Health Organization phases. The following chart shows the alignment.

CANADIAN BLOOD SERVICES WORLD HEALTH ORGANIZATION (WHO)

Pandemic Plan Activity Phases

Pandemic Escalation

Levels

Pandemic Escalation Categories

Colour Code

ActionWHO

Pandemic Alert Phase

Meaning

Interpandemic 1 Routine Green Business as usual 1 Low risk of human cases

Interpandemic 1 Routine Green Business as usual 2 Higher risk of human cases

Interpandemic 1 Routine Green Business as usual 3No or very limited human-

to-human transmission

Pandemic Alert 2 Stand by Amber

Risk of potential impact on CBS

increases. Escalate readiness.

4

Evidence of increased human-to-human

transmission in small, localized clusters

Pandemic Alert 2 Stand by Amber

Risk of potential impact on CBS

increases. Escalate readiness.

5

Evidence of significant human-to-human

transmission in larger but localized clusters

Pandemic 3 Active Red

National response to pandemic influenza is

required

6Efficient and sustained

human-to-human transmission

Post-Pandemic 4Transition to

Routine Operations

Black

CBS disengages from pandemic

state of emergency and resumes

business as usual

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CBS Influenza Pandemic Plan

Key Strategic Responses – department level (in order of preferred implementation):

1. Suspend non-critical business activities.

2. Re-assign departmental staff from performing non-critical business activities to more critical business activities, as required.

3. Where possible, offer surplus staff to other managers who might be experiencing more significant staffing difficulties.

4. Where possible, transfer work to another location that is not as

significantly impacted.

41

Maximizing Blood Inventories

It will be necessary and critical to implement temporary

changes to established policies and practices so as to:

1. Ensure most effective use of reduced staffing;

2. Maximize donor availability to fill collection capacity;

3. Maximize immediate access to and use of blood inventories.

Risk of the changes will need to be balanced against the

risk of depleted blood inventories.

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Modelled Pandemic Impacts on RBC Inventory Levels

Modelled RBC Inventory Levels Assuming 17,000 Jump-off

0

5,000

10,000

15,000

20,000

25,000

30,000

Wee

k -8

Wee

k -6

Wee

k -4

Wee

k -2

Wee

k 1

Wee

k 3

Wee

k 5

Wee

k 7

Wee

k 9

Wee

k 11

Wee

k 13

Wee

k 15

Wee

k 17

Wee

k 19

Wee

k 21

Wee

k 23

Wee

k 25

Wee

k 27

Wee

k 29

35% Model with 40% Offset 35% Model with no Offset

35% Model with 20% Deterioration Original 35% Model with 40% Offset

Ramp Up Outbreak Recovery

43

CBS Response to A(H1N1)• Convened regular meetings of the IBEPAG (International Blood

Emergency Planning Action Group) to discuss blood operators’ responses.• Developed key messages and Question & Answer material for:

– Internal staff communication; and– External messaging(Focus on hand hygiene, ‘cover your cough’, good infection control as well

as provision of up to date information on outbreak)• Provided EMT with status updates and convened National

Emergency Response Team (NERT) and Local teams (LERTs) to manage the CBS response.

• Assessed current donor screening criteria to conclude that sufficient criteria are in place to appropriately screen-out potentially infected donors

• Continue to monitor global outbreak information to guide CBS decision making.

• Will be reviewing and revising pandemic flu plans based on ‘lessons learned’.