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Safety of Blood (from an infectious disease standpoint)

Safety of Blood (from an infectious disease standpoint). David M. Smith, M.D. Medical Director. History of CBC/CTS. CBC Founded in 1964; Serves 27 hospitals in 15 counties in Southwestern Ohio and Eastern Indiana

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Safety of Blood (from an infectious disease standpoint)

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  1. Safety of Blood(from an infectious disease standpoint) David M. Smith, M.D. Medical Director Professionals for Infection Control March 14, 2006

  2. 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. Professionals for Infection Control March 14, 2006

  3. 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 Professionals for Infection Control March 14, 2006

  4. 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) Professionals for Infection Control March 14, 2006

  5. 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 Professionals for Infection Control March 14, 2006

  6. 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) Professionals for Infection Control March 14, 2006

  7. 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 Professionals for Infection Control March 14, 2006

  8. Major Infectious Diseases(not currently screening blood) • HIV type O • Malaria • Chagas Disease • vCJD Professionals for Infection Control March 14, 2006

  9. 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 Professionals for Infection Control March 14, 2006

  10. Viral Disease Screening in Blood Banking 1993-Present Updated from AuBuchon, Birkmeyer, Busch. Ann Intern Med 1997;127:904-9. Professionals for Infection Control March 14, 2006

  11. 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 Professionals for Infection Control March 14, 2006

  12. What Tests are Available to Detect Viral Infectious Diseases? • Tests that look for antibody produced by the body against viral antigens • Window phase forcurrentantibody tests is22 days for HIV, 59 days for HBV, and 70 days for HCV Professionals for Infection Control March 14, 2006

  13. 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 Professionals for Infection Control March 14, 2006

  14. Methods of Nucleic Acid Testing • Polymerase chain reaction (PCR) • RocheAmplicor, AmpliScreen, TaqMan • Transcription-mediated amplification (TMA) • Gen-Probe/ChironProcleix, Procleix Tigris • Others • Nucleic acid sequence-based amplification (NASBA), ligase chain reaction (LCR), branched DNA signal amplification (bDNA) Professionals for Infection Control March 14, 2006

  15. 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 Professionals for Infection Control March 14, 2006

  16. 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 Professionals for Infection Control March 14, 2006

  17. 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.) Professionals for Infection Control March 14, 2006

  18. 0 10 20 30 40 50 60 70 80 90 100 HIV Viremia During Early Infection Peak viremia HIV RNA (plasma) Ramp-up viremia HIV Antibody EIA HIV p24 Ag p24 Ag EIA ------ 1st gen Pooled NAT - 2nd gen Individual NAT - 3rd gen 11 16 22 Professionals for Infection Control March 14, 2006

  19. HCV Markers During Early Infection Plateau phase viremia HCV RNA Anti-HCV EIAs 1st gen 150 d 2nd gen 80 d 3rd gen 70 d Ramp-up phase Pre-ramp-up blip viremia ALT 0 10 20 30 40 50 60 70 80 90 100 Professionals for Infection Control March 14, 2006

  20. HBV Viremia in Early Infection Professionals for Infection Control March 14, 2006

  21. 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 Professionals for Infection Control March 14, 2006

  22. 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 Professionals for Infection Control March 14, 2006

  23. Modes of Transmission • Mosquito Bite • Transplantation • Transfusion • Breastfeeding • Transplacental Exposure • Occupational Exposure Professionals for Infection Control March 14, 2006

  24. A Culex quinquefasciatus Mosquito on a Human Finger Professionals for Infection Control March 14, 2006

  25. 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 Professionals for Infection Control March 14, 2006

  26. 8 cases WNV Professionals for Infection Control March 14, 2006

  27. 21 cases, 2 deaths Professionals for Infection Control March 14, 2006

  28. 66 cases, 9 deaths Professionals for Infection Control March 14, 2006

  29. 4161 cases, 277 deaths Professionals for Infection Control March 14, 2006

  30. 9862 cases, 264 deaths Professionals for Infection Control March 14, 2006

  31. Human WNV Infections 2004 2470 cases, 88 deaths Professionals for Infection Control March 14, 2006

  32. WNV Activity 2005 2949 cases, 116 fatalities Professionals for Infection Control March 14, 2006

  33. Human WNV Viremic Blood Donors 2005 399 presumptive viremic blood donors Professionals for Infection Control March 14, 2006

  34. Kidney recipientWNME (fatal) Kidney recipientWNME Liver recipientWNF Heart recipientWNME West Nile Virus Infection in an Organ Donor and Four Transplant RecipientsAugust 2002 Blood components from 63 donors Organ Donor Organ Donor WNV PCR +Culture +IgM – WNV PCR –IgM – Professionals for Infection Control March 14, 2006

  35. 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 Professionals for Infection Control March 14, 2006

  36. 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 Professionals for Infection Control March 14, 2006

  37. 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 Professionals for Infection Control March 14, 2006

  38. Stage-I IDNAT+/-MPNAT- IgM- Stage-II IDNAT+ MPNAT- IgM- Stage-III MPNAT+ IgM- Stage-IV IDNAT+ MPNAT- IgM+ IgG+/- Stage-V IDNAT +/- MPNAT- IgM+ IgG+ West Nile Virus 6-7 days IgM RNA 105 WNV RNA (gEq per mL) IgG 104 103 102 ID-NAT 101 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Days post infectious mosquito bite Professionals for Infection Control March 14, 2006

  39. 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 Professionals for Infection Control March 14, 2006

  40. 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 Professionals for Infection Control March 14, 2006

  41. 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 Professionals for Infection Control March 14, 2006

  42. 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 Professionals for Infection Control March 14, 2006

  43. 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 Professionals for Infection Control March 14, 2006

  44. 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 Professionals for Infection Control March 14, 2006

  45. 1/5,400 0.018 0.016 1/7,200 0.014 0.012 1/9,900 0.010 % Donors Positive 0.008 0.006 0.004 0.002 0.000 1996 1997 1998 LA Seroprevalence: 1996-98 Leiby, D. et al. Transfusion. 2002 Professionals for Infection Control March 14, 2006

  46. 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 Nationwide risk of Chagas Professionals for Infection Control March 14, 2006 Leiby, D. Pers. Comm.

  47. 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 Professionals for Infection Control March 14, 2006

  48. 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 Professionals for Infection Control March 14, 2006

  49. 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 Professionals for Infection Control March 14, 2006

  50. 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 Professionals for Infection Control March 14, 2006

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