Lecture to the University of Canberra April 2007

1. Emerging (and re-emerging) infectious risks to the global (and Australian) blood supply Albert Farrugia University of Canberra Faculty of Applied Science April 2007

4. Risk of HIV per Unit (%) Year of Transfusion First AIDS cases reported First TA-AIDS cases reported; High-risk donor deferral / self-exclusion initiated. HIV discovered; Progressive impact of high-risk donor education. Anti-HIV screening impmented Risk of HIV Transmission by Blood Transfusions Before the Implementation of HIV-1 Antibody Screening Busch et al. Transfusion 1991; 3: 4-11 2.0 1.5 1 0.5 0 1978 1979 1980 1981 1982 1985 1983 1984 1990

6. Testing for Hepatitis C HCV RNA 0 10 20 30 40 50 60 70 80 90 100 - HCV MP-NAT - HCV ID-NAT Pre- MP NAT WP = 60 days ID-NAT WP = 3 days MP-NAT WP = 10 days Anti-HCV (3.0 EIA)

7. Safety Concerns The things we know and love

8. Geographic Distribution of Chronic HBV Infection HBsAg Prevalence  8% - High 2-7% - Intermediate <2% - Low

9. GLOBAL PREVALENCE OF HEPATITIS C

10. Adults and children estimated to be living with HIV/AIDS as of end 2002 Total: 42 million Western Europe 570 000 North Africa & Middle East 550 000 Sub-Saharan Africa 29.4 million Eastern Europe & Central Asia 1.2 million South & South-East Asia 6 million Australia & New Zealand 15 000 North America 980 000 Caribbean 440 000 Latin America 1.5 million East Asia & Pacific 1.2 million

12. Risk/million repeat donations (with NAT) – High HDI * NAT not included (From: Glynn et al, Transfusion 2001) HIV HBV* HCV Australia 0.2 1.9 0.9 France 0.4 NA 0.1 Italy 1.1 2.1 6.6 Spain 1.0 13.5 6.0 US 0.5 4.9 0.5

13. HIV incidence, prevalence and risk PHT donations (RSA) Includes impact of HIV p24 antigen testing Prevalence Incidence Residual Risk High Prevalence 4850 512 14 (1:7100) Low Prevalence 99 12.9 0.7 (1:143000) Overall (NA) 62.8 3.4 (1:29400)

14. Range of coverage, prevalence and risk, Latin America, 2001-2 HIV HBV HCV T. cruzi Cov High Low 100% 86% 100% 93.4% 100% 49% 100% 25.1% Prev High Low 5.0/1k GUT 0.3 CHI 11.3 GUT 0.7 CHI 11.0 COL 1.3 CHI 99.1 BOL 1.5 ECU Risk High Low 11/10k 0 8.0 0 14.0 0 28.0 0

15. HIV HBV HCV 1996 1994 1992 1990 1988 1986 1984 1:100 1:1000 1:10 000 1:100 000 1:1 000 000 1998 2000 Risk, per unit 2002 Bacterial Contamination (platelets) Septic Fatalities (platelets) TRALI Fatalities 1:2,000 1:140,000 1:100,000 Evolution of Transfusion Risks Mistransfusion Fatalities 1:600,000

16. Risks in repeat donors HIV, HCV & HBV

19. Residual risk of TTI’s per 10 6 repeat donations Glynn et al (2002) Transfusion 42:966-972 HIV HCV HBV

20. Emerging infectious agents West Nile Virus, 1999 Hantavirus, 1993 Nipah, 1998 Diphtheria, 1993 Variant CJ Disease, 1996 E. coli O 157 H7, 1998 V. cholerae O 139, 1992 Dengue, 1992 Morbillivirus, 1994 Plague, 1994 Rift Valley fever, 1993 Yellow fever, 1993 Bolivian hemorrhagic fever, 1994 HIV-1 subtype O, 1994 Lassa fever, 1992 Dengue, 1994 Anthrax, 1993 Cholera, 1991 Yellow fever/VEE, 1995 Leptospirosis, 1995 Dengue, 1993 Adenovirus type 7, 1995 Arenavirus, 2000 Ebola 2000 Ebola, 1995

24. Concern high, Action favored Benefit High Action favored vCJD CJD Lyme HGV, etc RMSF CTF HAV Ehrlichia B19 Babesia T.cruzi Bacteria HHV 8 HHV 6 (HIV) idprio2001 Chlamydia, WNV , JC, Leptospira Bartonella etc Ebola etc Leishmania Malaria

25. Concern high, Action favored Benefit High Action favored vCJD CJD Lyme HGV, etc RMSF CTF HAV Ehrlichia B19 Babesia T.cruzi Bacteria HHV 8 HHV 6 (HIV) idprio2001 Chlamydia, JC, Leptospira Bartonella etc Ebola etc Leishmania Malaria WNV

26. Malaria

29. Proposed reinstatement protocol for donors traveling to malarious areas Seed et al 2005

30. Babesia

33. Chagas’ disease

35. LA Seroprevalence: 1996-98 % Donors Positive 0.000 0.002 0.004 0.006 0.008 0.010 0.012 0.014 0.016 0.018 1996 1997 1998 1/9,900 1/7,200 1/5,400

43. LAC SLE WN DEN2 WEE (VEE) CTF LAC SLE POW WN DEN2 EEE HJ EVE (VEE) EEE WEE VEE MAY WN DEN2 EEE WEE VEE MAY SLE WN YF DEN2 SIN CHIK WN YF DEN2 TAH SIN POW(TBE) WN (TAH,INK) CHIK SIN POW(TBE) JE WN SSH RR BF SIN MVE DEN2 Global Distribution of Major Human Flaviviruses

45. West Nile Virus Transmission Cycle West Nile virus West Nile virus Mosquito vector Incidental infections Bird reservoir hosts Incidental infections

46. ~80 % Asymptomatic ~ 20% “ West Nile Fever” <1% CNS disease WNV Human Infection “Iceberg” in 2002 284 fatalities ~ 3300 severe disease ~ 400,000 asymptomatic ~100,000 mild illness

47. Human WNV infections WNV activity West Nile Virus Activity: 1999-2002 1999 2000 2001 2002

49. WN virus infection in organ donor and four organ recipients, August 2002 WNV PCR-neg WNV IgM-neg Organ Donor Blood components 63 donors Organ Donor 36 hours WNV PCR-pos WNV culture-pos WNV IgM-neg F/U: 1 seroconverting donor; Retrieved, stored plasma – WNV PCR-positive Kidney recipient WNME (fatal) Kidney recipient WNME Liver recipient WNF Heart recipient WNME

50. Model for Relative Duration of Stages of WNV Infection 10 1 10 2 10 3 10 4 10 5 WNV RNA (gEq per mL) Days post infectious mosquito bite 2 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+/- MP-NAT ID-NAT Stage-V IDNAT +/- MPNAT- IgM+ IgG+ Stage-I IDNAT+/-MPNAT- IgM- Stage-III MPNAT+ IgM-

52. MJA 6 January 2003

55. Murray Valley encephalitis (MVE) and Kunjin virus disease are endemic in the tropical parts of the Northern Territory and Western Australia, but have been absent from Central Australia since 1974. In 2000, 5 laboratory-confirmed cases of encephalitis occurred over a short period in the normally dry inland region of Central Australia. The sudden occurrence of cases in March and April 2000 followed unusually high rainfall in the preceding months and evidence of flavivirus activity in the endemic areas in the Kimberley region of Western Australia . Further cases were reported in the following wet season, without preceding human cases in known endemic areas. These findings indicate the reintroduction of these viruses into Central Australia and establishment of local cycles of infection with an ongoing risk to the local population. This area may also act as a potential source for reintroduction of MVE into south-eastern Australia. Commun Dis Intell 2002;26:39-44.

56. World Distribution of Dengue 1999 Areas infested with Aedes aegypti Areas with Aedes aegypti and recent epidemic dengue

59. Temperature, Virus Positivity and Anti-Dengue IgM , by Fever Day Dengue IgM Mean Max. Temperature Virus Adapted from Figure 1 in Vaughn et al., J Infect Dis , 1997; 176:322-30. Fever Day Percent Virus Positive -4 -3 -2 -1 0 1 2 3 4 5 6 39.5 39.0 38.5 38.0 37.5 37.0 Temperature (degrees Celsius) Dengue IgM (EIA units) 0 20 40 60 80 100 300 150 0 75 225

67. SARS

75. Wei-Kung Wang, Chi-Tai Fang, Hui-Ling Chen et al. Detection of severe acute respiratory syndrome coronavirus RNA in plasma during the course of infection. J Clinical Microbiology. 2005;43(2):962-965.

79. Total Exports of MBM 1988 - 1993 No data 0 - < 5 5 - < 10 10 - < 20 20 - < 100 100 - < 1.000 1.000 - < 10.000 > 10.000 Legend: (in tonnes)

80. Transmission of TSE by blood transfusion in hamsters Rohwer 2000 263 K scapie adapted hamster Exchange transfusion 2 ml blood (total blood volume = 7 ml) Normal hamster 2 ml blood removed 3 out of 100 transfusions resulted in transmission

83. Lancet 2004; 363: 51–61

85. Recipients surviving >5 yr post transfusion of blood components from vCJD/CJD Donors (using data from UK TMER and US ARC look-back studies [S Anderson, FDA; P Page, R Dodd ARC at FDA TSEAC 14 Oct 2004]) Fisher's Exact Test comparing rates of infection after transfusions from vCJD and CJD donors suggests a statistically significant difference between the two groups (  1% likelihood that the difference occurred by chance). [Conclusion: Risk of TT CJD is much less than TT vCJD.] Infection No Infection vCJD 4 14 CJD 0 >116

98. Total Exports of MBM 1988 - 1993 No data 0 - < 5 5 - < 10 10 - < 20 20 - < 100 100 - < 1.000 1.000 - < 10.000 > 10.000 Legend: (in tonnes)

99. UK Beef Exports, in 1,000 U.S. Dollars, 1970 – 1999. FAO