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Emerging infections involving blood transfusion

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Title: Emerging infections involving blood transfusion


1
Emerging infections involving blood transfusion
  • Roger Y. Dodd, PhD.
  • GCP Region, MAC
  • April 29th, 2009

2
Blood safety 2009
  • Modern technologies have reduced the risk of
    classic TTIs to very low levels
  • Although still appreciable to chronically
    transfused patients
  • New infections continue to appear and old ones
    continue to spread
  • The horizons of blood safety have therefore
    expanded, rather than contracted

3
Emerging Infectious Diseases
those whose incidence in humans has increased
within the past two decades or threatens to
increase in the near future. Emergence may be due
to the spread of a new agent, to the recognition
of an infection that has been present in the
population but has gone undetected, or to the
realization that an established disease has an
infectious origin. Emergence may also be used to
describe the reappearance (or reemergence) of a
known infection after a decline in incidence.
(IOM)
4
Some EIDs
  • HIV/AIDS
  • Avian influenza
  • BSE/vCJD
  • Chagas Disease
  • Chikungunya (?)
  • Cryptosporidiosis
  • Dengue
  • Drug resistant Strep
  • Ebola
  • Ehrlichia
  • E. coli O157
  • Hantavirus
  • Hendra virus
  • HHV-8
  • Legionella
  • Lyme disease
  • Lyssa virus
  • Monkeypox
  • Mycobacteria
  • Nipah virus
  • SARS
  • Drug resistant Staph
  • WNV

5
Why do infections emerge?
  • New agent
  • vCJD
  • Species jump, possibly with mutation
  • HIV, SARS
  • Environmental change (eg global warming)
  • Dengue, malaria, babesia
  • Failure of control resistance and mutations
  • HBV mutants, malaria, drug resistance
  • Population movements migration, travel
  • T. cruzi, chikungunya
  • Transport of agents, reservoirs, vectors
  • WNV, monkeypox
  • Behavioral change among humans, including
    conflict
  • HIV, leishmania
  • In most cases (including those mentioned) there
    are multiple factors

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7
Requirements for transfusion-transmitted disease
  • Asymptomatic blood-borne phase
  • Chronic and/or acute
  • Survival of agent in donated blood
  • Infectious by IV route
  • Susceptibility of recipients
  • Recognized disease in recipients
  • Level of concern dependent on
  • Severity, incidence and/or prevalence, rate of
    emergence, (public/political perception)

8
TTIs
  • In the past, transfusion-transmissible infections
    were perceived to have common epidemiologic
    patterns
  • Thus, it was thought that behavioral risk
    questions could have utility in reducing the risk
    of transfusion-related infection from new or
    unrecognized infectious agents
  • Conversely, individuals with particular risk
    profiles might be sentinels for transfusion
    transmissibility
  • Example HBV as a model for HIV

9
Can we predict emerging TTIs?
  • EIDs do not appear to have any overall common
    characteristics with respect to class of agent,
    transmission route or pathogenesis. Consequently,
    they cannot be considered as a homogeneous group
  • All transfusion-transmitted infections must
    necessarily have a blood-borne phase
  • This does not however, assure transmissibility by
    sexual or low-volume non-parenteral routes
  • Consequently, risk behaviors associated with such
    transmission routes are not common to all TTIs

10
Why the disproportionate concern about TTIs?
  • Biological/medical
  • New portal for introduction of infections into
    human populations
  • Avoidance of adverse iatrogenic effects
  • Emotional/social
  • Imposed, not elective
  • Specific to given unit, therefore should be
    controllable
  • Dread outcome
  • History

11
Elements of an Emerging Infections Program
  • Surveillance/Intelligence
  • Assessment for relevance
  • Public health
  • Public concern
  • Measures of risk
  • Investigation of intervention(s)
  • Recommendations
  • Implementation
  • Evaluation

12
vCJD
13
vCJD and other TSEs
  • Agent prion disease presumed to be due to
    conformational variant of a normal protein
  • EID status New disease in domestic cattle (BSE)
    resulting from intensive agricultural
    technologies (MBM) and transmitted to humans via
    food-chain
  • Species issues Apparently unusual species jump
    (compare kuru and scrapie of sheep?)
  • Risk status Clearly transfusion transmissible,
    but future unclear, although food-chain exposure
    is largely controlled

14
vCJD general
  • Transmissible spongiform encephalopathy (prion
    disease)
  • Degenerative, fatal disease with lengthy
    incubation period
  • Results from consumption of tissue from
    BSE-infected cattle
  • Most cases in, or associated with UK (166),
    around 39 elsewhere
  • No endogenous case in US
  • 2 UK exposure, 1 Saudi Arabia

15
National CJD surveillance unit (UK)
http//www.cjd.ed.ac.uk/cjdq56.pdf
16
Number of infected persons
  • 12,674 tonsils and appendices examined
  • 3 were positive for vCJD prion
  • 237 (46-693) per million
  • Point estimate of gt4,000 infected?
  • 2 of the positives were VV homozygous at codon
    129
  • (All vCJD cases were MM homozygous)
  • Another tonsil study has much lower yield to date

17
vCJD and transfusion transmission
  • Initial concerns about vCJD justified
  • To date, four cases observed, three disease, one
    infection (MV)
  • 18/31 vCJD with donation history
  • 66 recipients, 3 of whom developed vCJD
  • 6.5 and 7.8 and 9 yrs post transfusion (2 from
    one donor)
  • Donors developed vCJD 40 and 21 months after
    donation
  • 29 recipients lived longer than 5 years
  • 3rd recipient had vCJD prion in spleen and
    cervical lymph node at autopsy (no vCJD symptoms)
  • 5 years post-transfusion from donation 18 months
    before vCJD
  • Additionally, vCJD prion found in one recipient
    of a pooled plasma product
  • Sheep model previously showed 17 transmission
    rate

18
Comparison of transfusion transmission, CJD vs
vCJD
(P 0.0117)
19
West Nile Virus Basic Transmission Cycle
Enzootic (Maintenance/Amplification)
Epidemic
Incidental hosts
Epizootic
Amplifying hosts
20
West Nile fever
  • Agent Flavivirus (RNA), transmitted by
    mosquitoes
  • S Europe, Africa, Middle East to India, arrived
    US 1999, endemic in essentially all of the
    continental US by 2004
  • EID status Explosive imported outbreak in
    Americas, but stable elsewhere
  • Up to 400,000 individuals infected in 2002, 2003
    in US
  • Species issues Infects many vertebrates, birds
    as amplifying hosts, not naturally transmitted
    between humans
  • Risk status TTI occurs as a result of high
    incidence of acute viremia, controlled via NAT in
    US

21
WNV Neuroinvasive Disease Incidence, by County,
US, 1999-2007
22
Distribution of WNV-RNA-positive donations, 2007
23
WNV
  • 23 cases or TTI reported in 2002
  • NAT implemented in 2003
  • 9 subsequent cases
  • Donors not detected by pooled NAT
  • IDT implemented in areas/times of high incidence

24
Dengue
25
Dengue
  • Over 2.5 billion people live in risk areas for
    dengue infection
  • WHO estimates that in 2004 there were 50-100
    million cases of DF, 500,000 of DHF, and 20,000
    consequent deaths
  • Epidemic is expanding due to global warming,
    expanding vectors and trafficking of subtypes.
  • Dengue is the most important arboviral disease of
    humans.

26
Dengue
  • Flavivirus, enveloped
  • 4 strains, no cross-protection
  • Dengue fever, dengue hemorrhagic fever
  • Transmitted by Aedes mosquitoes without need for
    animal reservoir
  • Known to cause very large epidemics
  • (Almost 800,000 cases in Brazil in 2002)
  • In many ways, similar to WNV
  • Known viremia
  • Two documented transfusion transmission clusters
    (Hong Kong, Singapore)
  • One possible BMT transmission
  • Needlestick transmissions known

27
Dengue Eastern hemisphere
28
Dengue Americas
29
Issues
  • Good example of an infection that is under study
    as a potential transfusion risk
  • Potential for infected travelers
  • Competent vector present in many areas
  • Donor viremia demonstrated during outbreaks in
    Puerto Rico (Caribbean), Brazil, Honduras

30
Supplementary Testing of TMA-Positive Samples
LEGEND 1 Signal/Cut-Off positive, -
negative
(N 16,521)
31
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33
Chikungunya
34
Chikungunya
  • Agent Alphavirus, transmitted by Aedes spp.
    mosquitoes recent mutation favors A. albopictus
  • EID status Appearing in new areas due to
    expansion of range of vector and travel
  • Species issues sylvatic and human-to-human
    cycles
  • Risk status Explosive epidemics, TTI presumed
    possible, future unclear but threatening
  • Blood safety interventions in la Rèunion, Italy

35
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36
Aedes albopictus Emergence
  • Albania -- 1979
  • United States 1985
  • Brazil 1986
  • Central America 1988
  • Italy -- 1991
  • Africa 1991
  • France --1999

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38
Reported distribution of Aedes albopictus in the
U.S., 2005
39
HHV-8
  • Agent Herpes virus, transmitted via saliva,
    sexual interactions
  • EID status Recently recognized, and emerging
    among MSM, etc.
  • Species issues Human infection of long standing,
    origin unclear
  • Risk status TTI demonstrated, some control by
    MSM travel restrictions, perhaps leukoreduction

40
HHV-8 background
  • Herpesvirus (enveloped, DNA)
  • Chronic, persistent infection, agent of Kaposis
    sarcoma (classic and HIV-associated)
  • Transmitted person-to-person (sexual, saliva,
    organ transplant)
  • Global distribution? Africa, s Europe? MSM
  • Seroprevalence is test-dependent, up to 2.4 in
    blood donors in US

41
HHV-8 and transfusion
  • Some indirect evidence of transfusion
    transmission
  • Transmission by organs, epidemiologic linkage of
    transfusion and elevated prevalence, IDUs
  • DNA identified in seropositive donation
  • Recipient susceptibility unknown
  • Risk profile unclear
  • No clear intervention, although 2 higher risk
    groups already excluded
  • Potential for Ab test, but no gold standard

42
Uganda Transfusion Study
  • HHV-8 seroprevalence in blood donors is 35-40
  • No leukoreduction
  • 1811 transfusion recipients with linked donors
  • 991 recipients HHV-8 seronegative prior to
    transfusion, followed gt 3 months
  • 41 patients seroconverted (2 or more consecutive
    HHV-8 positive follow-up visits)
  • No sero-reverters
  • More seroconversion with units lt 5 days old
  • Greatest risk _at_ 3-10 weeks (RR 4.73)
  • 2.3 of seropositive units led to infection

Hladik, Dollard et al, NEJM 20063551331-1338
43
Malaria
44
Malaria
  • Agent(s) Protozoan parasite(s) (5) of genus
    Plasmodium, transmitted by mosquitoes (Anopheles
    spp.)
  • EID status Expanding in range as a result of
    climate change, travel, change in interventions
  • Species issues Exclusively human (except P.
    knowlesi) presumed animal origin
  • Risk status TTI well-known, controlled by
    questions (non-endemic), donation/patient
    management, potential for failure in face of
    remergence

45
Malaria and transfusion
  • Globally, probably most frequent TTD
  • Survives in stored cellular products
  • Essentially all recipients susceptible
  • lt1 transfusion case annually in US
  • Risk stable, could increase with travel and
    potential reemergence
  • Travel history is current intervention
  • gt100,000 donors/year deferred

46
23,611,536 Presenting Donors

() 241,777 25,339
495 267,611 Deferred (90.3)
(9.5) (lt0.2)
Presenting Donors 1.0
0.11 0.002
47
Chagas disease
48
Chagas Disease
  • Agent Protozoan parasite, Trypanosoma cruzi,
    transmitted by hematophagous insects (reduvid
    bugs)
  • EID status Substantial vector control in
    endemic countries, emerging in US, W. Europe
    through population movement
  • Species issues Widespread among numerous
    mammalian species housing location and
    construction permit interaction of hosts, vectors
    and humans
  • Risk status TTI, transplant as major risk in
    non-endemic areas control by history, testing
  • 7 TT cases in US, Canada, 2-3 Spain, 3 transplant
    clusters in US
  • US testing program indicates 130,000 donors
    infected

49
SARS
50
Simian foamy virus
  • Infects various monkeys
  • Transmissible to humans
  • Appears to be apathogenic in humans
  • Exemplar of interspecies transmission
  • Concern about emergence of pathogenic
    characteristics
  • Canada Monkey handlers deferred from blood
    donation
  • USA discussed, but no action (to date)

51
Overview
  • Numerous emerging and newly recognized infections
    with potential for transfusion transmission
  • All classes of agents
  • Many zoonoses
  • No common pathogenesis, transmission route,
    infectious period or risk factor unpredictable
  • Absence of effective interventions

52
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