Title: Emerging infections involving blood transfusion
1Emerging infections involving blood transfusion
- Roger Y. Dodd, PhD.
- GCP Region, MAC
- April 29th, 2009
2Blood 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
3Emerging 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)
4Some 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
5Why 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
6(No Transcript)
7Requirements 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)
8TTIs
- 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
9Can 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
10Why 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
11Elements of an Emerging Infections Program
- Surveillance/Intelligence
- Assessment for relevance
- Public health
- Public concern
- Measures of risk
- Investigation of intervention(s)
- Recommendations
- Implementation
- Evaluation
12vCJD
13vCJD 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
14vCJD 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
15National CJD surveillance unit (UK)
http//www.cjd.ed.ac.uk/cjdq56.pdf
16Number 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
17vCJD 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
18Comparison of transfusion transmission, CJD vs
vCJD
(P 0.0117)
19West Nile Virus Basic Transmission Cycle
Enzootic (Maintenance/Amplification)
Epidemic
Incidental hosts
Epizootic
Amplifying hosts
20West 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
21WNV Neuroinvasive Disease Incidence, by County,
US, 1999-2007
22Distribution of WNV-RNA-positive donations, 2007
23WNV
- 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
24Dengue
25Dengue
- 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.
26Dengue
- 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
27Dengue Eastern hemisphere
28Dengue Americas
29Issues
- 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
30Supplementary Testing of TMA-Positive Samples
LEGEND 1 Signal/Cut-Off positive, -
negative
(N 16,521)
31(No Transcript)
32(No Transcript)
33Chikungunya
34Chikungunya
- 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(No Transcript)
36Aedes albopictus Emergence
- Albania -- 1979
- United States 1985
- Brazil 1986
- Central America 1988
- Italy -- 1991
- Africa 1991
- France --1999
37(No Transcript)
38Reported distribution of Aedes albopictus in the
U.S., 2005
39HHV-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
40HHV-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
41HHV-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
42Uganda 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
43Malaria
44Malaria
- 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
45Malaria 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
4623,611,536 Presenting Donors
() 241,777 25,339
495 267,611 Deferred (90.3)
(9.5) (lt0.2)
Presenting Donors 1.0
0.11 0.002
47Chagas disease
48Chagas 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
49SARS
50Simian 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)
51Overview
- 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(No Transcript)