Transcript Hot Bugs’ What’s New in Emerging Pathogens CBS ORBCoN

Planning for the Future
What’s coming for CBS?
Resident Seminar
May 29, 2009
Dr. Margaret Fearon
Executive Medical Director, Medical Microbiology,
Canadian Blood Services
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.
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Current Pathogens of Concern
for Blood Operators
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Chagas Disease - protozoan
Babesiosis - protozoan
vCJD (variant Creutzfeld Jacob Disease) – prion
Influenza - virus
Malaria - protozoan
Ehrlichiosis – bacteria
HHV8 - virus
Dengue - virus
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Chagas Disease
Trypanosoma cruzi

Trypomastigotes in blood
Protozoan flagellate
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Trypomastigotes (blood)
Extracellular (not removed by
leucoreduction)
Amastigotes multiply in smooth
muscle tissue – heart, gut
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Amastigote in heart muscle
Where is Chagas Disease
Found?
Most of South America
 Central America
 Parts of Mexico

18 million people infected
 1-2 million in large, nonendemic areas (Sao Paulo,
Rio, Buenos Aires)
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
100,000 in the U.S. (?)
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From CDC
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Reduvid Bug – aka ‘Kissing Bug’
WHO/TDR
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WHO/TDR
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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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Cardiomegaly in Chronic Chagas Disease
WHO/TDR
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Reported cases of T. cruzi
transmission via transfusion in the
U.S. and Canada
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1987
1989
1989
1993
1999
2000
2002
California via Mexican donor
New York City via Bolivian donor
Manitoba via Paraguayan donor
Houston via unknown donor
Miami via Chilean donor
Manitoba via German/Paraguayan donor
Rhode Island via Bolivian donor
– *5 cases – platelet transfusion, others unknown
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Reference Source: Dr. D. Leiby, ARC
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:
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1. Were you born in Mexico, Central America, or South America?
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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
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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 Disease
Phase 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.
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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)
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
COUNTRY
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.
†
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*the case from Japan had resided
in the UK for 24 days in the period 1980-1996.
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
Assuming that a donor screening test would have sensitivity and specificity
characteristics of a typical donor screening test (99% specificity).
Donor Base of 3 M
True Positive
300
False Negatives
3
True Negatives
2.97 M
False Positive
30,000
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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Babesiosis
Protozoan parasites
Babesia microti, duncani,
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http://www.ent.iastate.edu/imagegallery/ticks/deertick.html
Epidemiology
• Sporadic cases in Europe and Asia
• U.S. Cases reported in:
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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
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Extracellular and intraerythrocytic forms,
one of which is vacuolated.
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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Influenza A HA and NA Subtypes
H1
H2
H3
H4
H5
H6
H7
H8
H9
H10
H11
H12
H13
H14
H15
H16
N1
N2
Other Animals
Other Animals
Other Animals
Other Animals
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N3
N4
N5
N6
N7
N8
N9
Other Animals
Other Animals
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Seasonal Influenza Transmission
Routes
• Transmission of influenza viruses
– Direct contact with infected person (handshake)
– Droplets from coughing or sneezing
– Transmission from objects (fomites)
possible
– Infectious 1 day before and up to 7 days
after becoming sick
U.S. Centers for Disease Control and Prevention
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Pandemic Influenza Phases
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The World Health Organization
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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 Canada
Influenza A(H1N1) Epidemic Curve May 25, 2009
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Pandemic Phases
CBS 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
Action
WHO
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
3
No or very limited humanto-human transmission
Amber
Risk of potential
impact on CBS
increases. Escalate
readiness.
4
Evidence of increased
human-to-human
transmission in small,
localized clusters
Amber
Risk of potential
impact on CBS
increases. Escalate
readiness.
5
Evidence of significant
human-to-human
transmission in larger but
localized clusters
Red
National response
to pandemic
influenza is
required
6
Efficient and sustained
human-to-human
transmission
Black
CBS disengages
from pandemic
state of emergency
and resumes
business as usual
Pandemic Alert
Pandemic Alert
Pandemic
Post-Pandemic
2
2
3
4
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Stand by
Stand by
Active
Transition to
Routine
Operations
CBS Influenza Pandemic Plan
Key Strategic Responses – department level (in order of
preferred implementation):
1.
2.
3.
4.
Suspend non-critical business activities.
Re-assign departmental staff from performing non-critical
business activities to more critical business activities, as
required.
Where possible, offer surplus staff to other managers who
might be experiencing more significant staffing difficulties.
Where possible, transfer work to another location that is not as
significantly impacted.
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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
30,000
Ramp Up
Outbreak
Recovery
25,000
20,000
15,000
10,000
5,000
W
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0
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35% Model with 40% Offset
35% Model with no Offset
35% Model with 20% Deterioration
Original 35% Model with 40% Offset
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’.
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