community blood center community tissue services professionals for infection control march 14, 2006...

Professionals for Infection Control

March 14, 2006

Community Blood CenterCommunity Tissue Services

Safety of Blood(from an infectious disease standpoint)

David M. Smith, M.D.

Medical Director


March 14, 2006


History of CBC/CTS

• CBC Founded in 1964; Serves 27 hospitals in 15 counties in Southwestern Ohio and Eastern Indiana

• Full service blood center that collects, processes and distributes blood components, provides red cell and platelets reference laboratory, HLA typing, stem cell collection and processing, therapeutic phlebotomy and therapeutic apheresis, and transfusion medicine expertise.


March 14, 2006


History of CBC/CTS

• CTS developed in 1985; since 1994 has expanded to seven branches in six states with recovery partners throughout the US

• Collects, processes and distributes musculoskeletal tissue and skin

• Distributes tissue first to local communities, then nationally and internationally


March 14, 2006


Community Blood Center

• Not-for-profit 501 (c)(3) company established in 1964 to provide blood products to the Dayton community – independent blood center member of America’s Blood Centers (ABC)

• Dayton Regional Tissue Bank established as a Division of CBC in 1986 in response to the needs of local surgeons for allograft tissue

• Name changed to Community Tissue Services in 1995 to reflect growth into communities across the nation (and currently internationally)


March 14, 2006


Community Blood Center • Two operational units

• Community Blood Center• Local/regional service• Supporting multiple local hospitals• Distribution of approximately 130K blood products• Other internal and external services

• Reference Laboratory• HLA/Molecular• Testing Laboratory• Microbiology• Therapeutic Apheresis

• Community Tissue Services• National and international service• Multiple branches nationwide• Supporting health care facilities and workers nationwide and internationally• Distribution of over 80K tissue products


March 14, 2006


Strategies for Minimizing Risks

• Volunteer donor base – no financial incentive to donate blood products

• Donor screening – least effective• Directed donation – no safer than allogeneic• Autologous donation - safe• Testing of blood – largest effect on safety• Processing of blood (including leukoreduction,

pathogen inactivation)


March 14, 2006


Major Infectious Diseases(screening blood tests)

• HBV – HBsAg, HBcAb, HBV NAT*• HCV – antibody to HCV, HCV NAT• HIV 1, 2 – antibody to HIV, HIV NAT• Syphilis – RPR• HTLV I &II – antibody to HTLV• WNV – WNV NAT• CMV –antibody to CMV

* Currently available but not required


March 14, 2006


Major Infectious Diseases(not currently screening blood)

• HIV type O

• Malaria

• Chagas Disease

• vCJD


March 14, 2006


Donor Screening

• Screening is least effective tool to prevent transmission of infectious diseases

• FDA regulates screening requirements and defines permanently deferred categories as well as temporary deferrals

• There are some inconsistencies between deferrals for blood donation and tissue donation


March 14, 2006


Viral Disease Screening in Blood Banking 1993-Present

Updated from AuBuchon, Birkmeyer, Busch. Ann Intern Med 1997;127:904-9.


March 14, 2006


Reaction to Viral Infections

• Virus enters host (infection)• Virus enters target organ and begins replicating, no

virus in blood (eclipse phase)• Virus in blood (viremic phase)• Immune reaction to virus • Antibody production (days to weeks); antibodies can

be protective or non-protective• The window phase is the time interval between

infection and presence of detectable viral NA, viral antigens, or antibody to viral antigens


March 14, 2006


What Tests are Available to Detect Viral Infectious Diseases?

• Tests that look for antibody produced by the body against viral antigens• Window phase for current antibody tests is 22

days for HIV, 59 days for HBV, and 70 days for HCV


March 14, 2006


What Tests are Available to Detect Viral Infectious Diseases?

• Tests that look for virus specific antigens (HIV p24Ag, HBsAg)

• Tests that look for viral DNA or RNA (NAT)• Become positive more quickly• Remain positive as long as virus is present • Window period for HIV is 11 days, HBV 20-30

days, and HCV 10-12 days

• Virus can be transmitted in the window period


March 14, 2006


Methods of Nucleic Acid Testing• Polymerase chain reaction (PCR)

• Roche Amplicor, AmpliScreen, TaqMan

• Transcription-mediated amplification (TMA)• Gen-Probe/Chiron Procleix, Procleix Tigris

• Others• Nucleic acid sequence-based amplification

(NASBA), ligase chain reaction (LCR), branched DNA signal amplification (bDNA)


March 14, 2006


Nucleic Acid Tests (NAT)General Characteristics

• Sample preparation, including viral concentration and extraction of DNA or RNA

• Amplification of the target viral DNA or RNA

• Detection of the amplified product


March 14, 2006


What NAT means to the Window Period (Blood)

EIA Window Post-NAT Window

• HCV 70-80 days 10 days

• HIV 16 days 10 days

• HBV 56 days 20-30 days


March 14, 2006


Viral Characteristics

• HBV-DNA harder to detect by virtue of the slower reproductive cycle of the virus

• Virus Doubling Times• HCV--17.7 hrs.• HIV-- 21.5 hrs.• HBV--2.8 days (67.2 hrs.)


March 14, 2006


HIV Viremia During Early Infection

HIV RNA (plasma)HIV Antibody EIA

11

0 10 20 30 40 50 60 70 80 90 100

HIV p24 Ag

16 22

Ramp-up viremia

1st gen

2nd gen3rd gen

p24 Ag EIA ------

Pooled NAT -

Individual NAT -

Peak viremia


March 14, 2006


HCV Markers During Early Infection

HCV RNAAnti-HCV EIAs

1st gen 150 d 2nd gen 80 d 3rd gen 70 d

0 10 20 30 40 50 60 70 80 90 100

Ramp-up phase

Plateau phase viremia

Pre-ramp-up blip viremia

ALT


March 14, 2006


HBV Viremia in Early Infection


March 14, 2006


Advantages of NAT testing in Blood

• Test manufacturers have incentive to develop and market tests • 14 million donor units per year in the United

States alone• Uniform test samples are available because donors

are alive

• Required for HIV, HCV, and WNV; currently optional for HBV


March 14, 2006


West Nile VirusBackground Information

• WNV is a mosquito-borne flavivirus

• WNV has a positive strand RNA genome of about 11 kb that encodes several proteins

• Primarily infects birds, occasionally also infects humans and horses

• About 80% of infected persons remain asymptomatic, rest 20% develop mild febrile illness (flu-like illness)

• Meningitis or encephalitis develops in ~1 in 150 infected persons

• Viremic period can occur up to 2 weeks prior to symptoms and last up to several months from the initiation of the infection


March 14, 2006


Modes of Transmission

• Mosquito Bite• Transplantation• Transfusion• Breastfeeding• Transplacental Exposure• Occupational Exposure


March 14, 2006


A Culex quinquefasciatus Mosquito on a Human Finger


March 14, 2006


West Nile Fever: Classic Clinical Description

• Mild illness of sudden onset• Duration 3-6 days• Fever, lymphadenopathy, headache, abdominal pain,

vomiting, rash, conjunctivitis, eye pain, loss of appetite


March 14, 2006


8 cases WNV


March 14, 2006


21 cases, 2 deaths


March 14, 2006


66 cases, 9 deaths


March 14, 2006


4161 cases, 277 deaths


March 14, 2006




March 14, 2006


Human WNV Infections 2004



March 14, 2006


WNV Activity 2005

2949 cases, 116 fatalities


March 14, 2006


Human WNV Viremic Blood Donors 2005

399 presumptive viremic blood donors


March 14, 2006


West Nile Virus Infection in an Organ Donor West Nile Virus Infection in an Organ Donor and Four Transplant Recipientsand Four Transplant Recipients

August 2002August 2002

Organ Donor

WNV PCR –IgM –

Organ Donor

WNV PCR +

Culture +IgM –

Kidney recipientWNME (fatal)

Kidney recipientWNME

Liver recipientWNF

Heart recipientWNME

Blood Blood components components

from 63 donorsfrom 63 donors


March 14, 2006


Infectivity of WNV and Laboratory Testing

• The infectious dose is low compared with many other viruses

• NAT tests are very sensitive• It was recognized that pooled testing was missing

WNV due to dilution (low level viremia in one sample was diluted leading to negative pool results)

• Blood Centers instituted policies to switch to single donor testing from pooled testing when prevalence of disease increases


March 14, 2006


Serologic and NAT Testing

• It was initially felt that once donors developed antibodies that they would be non-infectious, even though there is some overlap with viremia

• It was later recognized that viremia can persist for several months, even in the presence of antibodies, leading to increased deferral period for blood to 120 days

• Most recently, evidence suggests that the virus can be transmissible when antibodies are present but virus is undetectable by NAT


March 14, 2006


Serologic and NAT Testing

• Within the last approximate year, it is now recognized that you can have initially reactive WNV NAT, but when multiple additional aliquots from the same sample are tested, they can be negative (up to 10 replicates before another positive)

• Not false positive or negative, but samples tested may not contain enough virus particles to get a positive reaction


March 14, 2006


101

102

103

104

105

WN

V R

NA

(gE

q pe

r m

L)

Days post infectious mosquito bite2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

RNA

IgM

IgG

6-7 days

Stage-II

IDNAT+ MPNAT- IgM-

Stage-IV

IDNAT+ MPNAT-

IgM+IgG+/-

ID-NAT

Stage-V

IDNAT +/- MPNAT- IgM+

IgG+

Stage-I

IDNAT+/-MPNAT- IgM-

Stage-III

MPNAT+ IgM-

West Nile Virus


March 14, 2006


vCJD• vCJD is caused by an abnormal prion protein that causes

normal prion proteins to change into abnormal proteins• It was initially unclear whether vCJD could be

transmissible by blood transfusion• Recently, the third case of presumptive transmission was

announced; statistically almost impossible to be chance occurrence

• The “epidemic”, 172 cases worldwide, is declining but may be a second wave due to longer incubation in persons heterozygous for certain normal prion proteins who may incubate vCJD for longer periods of time


March 14, 2006


vCJD• Current strategy is to defer blood donors

who have spent significant time in Europe

• Development of prion filters with some success

• Recently a cow in the Southern US was discovered to have BSE


March 14, 2006


Malaria• Approximately 120 cases are diagnosed in

US every year; almost all “imported” from endemic areas

• Anopheles mosquitoes are found in Southern US so there is still risk of malaria re-establishment in US


March 14, 2006


Chagas Disease(American Trypanosomiasis)

• Caused by Trypanosoma cruzi and spread by the Triatomine “kissing bug”

• Disease of poverty; bugs live in cracks and holes of substandard housing in Central and South America and Mexico


March 14, 2006


Chagas Disease(American Trypanosomiasis)

• Infection from exposure to insect feces (oral, mucosal, non-intact skin)

• Vertical transmission from mother to fetus

• Blood or organ transmission


March 14, 2006


Chagas Disease(American Trypanosomiasis

• Most asymptomatic acute infection

• Chronic infection common leading to heart failure or dilatation of gastroenteric tract

• Very long incubation; decades before chronic symptoms


March 14, 2006


LA Seroprevalence: 1996-98

0.000

0.002

0.004

0.006

0.008

0.010

0.012

0.014

0.016

0.018

1996 1997 1998

% D

onor

s P

ositi

ve

1/9,900

1/7,200

1/5,400Leiby, D. et al. Transfusion. 2002


March 14, 2006


Nationwide risk of Chagas

13.2 million donations 100%

330,000 at risk donations 2.5%

528 seropositive donations 0.16%

845 seropositive donations/year

989 potentially infectious components

Leiby, D. Pers. Comm.


March 14, 2006


Transfusion Chagas:

1987: California - Mexican donor

1989: New York City - Bolivian donor

Manitoba - Paraguayan donor

1993: Houston - unknown donor

1999: Miami - Chilean donor

2000: Manitoba - German/Paraguayan donor


March 14, 2006


Why so few cases if there are 1000 infected donors/yr?

• Reported cases are “sentinels”

• Immunosuppressed

• Fulminant disease

• Easily detected/diagnosed

• Many cases missed

• Immunocompetent

• Misdiagnosed

• Not recognized


March 14, 2006


What Will We Do?

• Donor history screening

• To identify at-risk donors for deferral or testing

• Lack sensitivity & specificity

• Donor testing

• Lack of licensed tests: Will be implemented when available

• Potential strategies

• One-time testing of new donors?

• Universal testing?

• Added value of NAT testing minimal


March 14, 2006


Bacterial Contamination of Platelets

• Incidence of bacterial contamination and consequent patient infections have remained stable for years

• As risks of viral transmissions have declined dramatically, bacterial issues have come to the forefront again


March 14, 2006


Bacterial Contamination of Blood and Blood Products (Review)

• Discussions of bacterial contamination as early as 1939 in JAMA

• In the 1950’s, bacterial contamination of blood was identified in up to 2.2% of bottles

• In the late 1960’s and early 1970’s, concerns about bacterial contamination were raised because of RT storage; one study found 1.6% contamination rate

• 16% of transfusion fatalities reported to FDA (1986 - 1991)


March 14, 2006


Selected History

• 1981 - 2nd generation of platelet containers providing prolonged platelet viability

• 1982 - Platelet storage extended to 5 days• 1983 - Platelet storage extended to 7 days• 1986 - In response to an increase in the number

of reports of platelet-transfusion associated sepsis, the BPAC recommended reverting to a five day old platelet storage interval


March 14, 2006


Why is this a platelet recipient issue?

• The numbers of bacteria that circulate in the donor are usually small, and cleared by the normal immune system.

• Only a few bacteria are required from donor• Venipuncture site• Asymptomatic transient bacteremia • Bacteria grow in the blood bag

• Increased risk with room temperature storage and nutrients in plasma

• Many blood recipients are immunocompromised


March 14, 2006


HIVHIV

HBVHBVHCVHCV

19961996199419941992199219901990198819881986198619841984

1:1001:100

1:10001:1000

1:10 0001:10 000

1:100 0001:100 000

1:1 000 0001:1 000 000

19981998 20002000

Transmission risk, Transmission risk, per unitper unit

Updated from: Goodnough LT Updated from: Goodnough LT e t al. NEJMe t al. NEJM 1999;341:126-7 1999;341:126-7

20022002

BacterialBacterialContaminationContamination

(platelets)(platelets)

MistransfusionMistransfusionFatalitiesFatalities(red cells)(red cells)

SepticSepticFatalitiesFatalities(platelets)(platelets)

Comparison of Residual Risks


March 14, 2006


Bacterial Contamination of Blood Products: The BaCon Study

Between Jan. 1998-Dec. 2000, there were 34 confirmed cases of

transfusion transmitted bacteremia or infection (TTI) in the U.S.

Breakdown of Implicated Components

Confirmed TTI (34)

TTI Fatalities (9)

18SDP

11Pooled RDP

Red Blood Cells 5

4

23

Kuehnert MJ, Roth VR, Haley NR, Gregory KR, Elder KV, Schrieber GB, Arduino MJ, Holt SC, Carson LA, Banerjee SN, Jarvis WR. Transfusion-transmitted bacterial infection in the United States, 1998 through 2000. Transfusion 2001 Dec;41(12):1493-1499.


March 14, 2006


Bacterial Contamination/100,000 Platelet Transfusions

BaCon UHC

TT Bacterial Disease 1 200

TT Bacterial Death 0.2 10

R. Yomtovian in Engelfriet et al: International Forum. Bacterial Contamination of Blood Components. Vox Sang 2000; 78:59-67; Kuehnert MJ et al. Transf 2001 Dec;41(12):1493-1499.


March 14, 2006


BACTERIAL CONTAMINATION OF PLATELETS

BaCon Study

UHC Prospective Surveillance


March 14, 2006


Clinical Significance of Platelet Bacterial Contamination

- 1:2000 units (RD and SD) are contaminated - 1:500 pooled unit transfusions are associated with septic transfusion reactions - 1:10,000 pooled unit transfusions are associated with a fatality

R. Yomtovian in Engelfriet et al: International Forum. Bacterial Contamination of Blood Components. Vox Sanguinis 2000; 78:59-67


March 14, 2006


What are We Doing?• Single donor platelets are being tested on the

BacTAlert system• Unit sits for 24 hours• Sample drawn and inoculated into bottle• Continuous monitoring in instrument• Product released on day 3• Bottled incubated for 5 days

• Sensitivity fairly high and can subculture for identification of organisms


March 14, 2006


What are We Doing?• Random donor platelets

• Urine dipstick for glucose and pH• Testing occurs as close to transfusion as

possible• Sensitivity not high with significant false

positive results


March 14, 2006


Influenza Virus

• Influenza A viruses infect birds, swine, horses, humans et al

• Antigenic “drift”• Accumulated point mutations and annual epidemics

• Antigenic “shift”• Appearance of new subtype of influenza A virus

with novel hemagglutinin (H) and/or neuraminidase (N) glycoproteins


March 14, 2006


Clinical Influenza

• Influenza A among humans: H1N1; H1N2; H3N2

• Clinical virology:

• Incubation period ~ 2 days (1-4 days)

• Fever, myalgias, headache, chills, cough, complicated by pneumonia

• Viral shedding: 3-5 d. with onset 1 d. before symptoms

• Viremia – rare, but how hard have we looked?

• Prevention: Immunization and antiviral medications

• Treatment: Supportive and antiviral medications


March 14, 2006


Pandemic influenza impact in US (CDC)

• Mortality:

• 89,000 - 207,000 in U.S. (ann. average 36,000)

• Medical infrastructure:

• 314,000 - 734,000 hospitalizations in U.S. (average yearly 114,000)

• Community impact:

• 20 - 47 million additional not seeking care• 20 - 30% “attack rate” in general population• 40 - 50% “attack rate” for school-age children


March 14, 2006


Planning activities

• International• National• State/local health authorities• Blood organizations

• Interagency task force


March 14, 2006


Avian Influenza A (H5N1) Virus and the blood supply?

• Is it transfusable?

• Impact on donor base?

• Impact on blood center

operations

Probably not

Could be awful

Could be awful


March 14, 2006


H5N1 + strand RNA in lung and gut only(human autopsy x 1)

Uiprasertkul, M et al. EID July 2005


March 14, 2006


Our major concerns• Donor loss due to flu or fear

• Donor deferrals

• Staff protection and absence

• Blood needs

community blood center community tissue services professionals for infection control march 14, 2006...

Documents

service blood center

safety of blood

blood components

tissue products

safety processing of

infection control

musculoskeletal tissue

allograft tissue