The basis of blood product safety Donor selection Testing Elimination/removal Have you, your sexual partner any member of your household, or any other close contact ever received human body fluids, cells, tissues or organs that came into contact outside of the body with live cells, tissues or organs from an animal? The foregoing is an example of: A) A provision in a prenuptial agreement. B) A reading comprehension test. C) A proposed donor screening question. D) A question from Ken Starr to Bill Clinton.
Current screening for:
Proven route for plasma products
Technologies available for fresh products
Safety/quality issues still unresolved
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
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
83% of global population has access to only 40% of world’s blood
Donations/1000 is 41-50 in High HDI, but 1/20th that rate in Low HDI
High HDI 98% voluntary, Low HDI 31% voluntary
Paid donations often masquerade as “replacement/family”
Up to 13 of the 75 million donations were not fully tested (1998-99), mostly in low or medium HDI countries.
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
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)
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
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
WNV is a virus which is transmitted through mosquito bites and is endemic in certain parts of Africa and the Middle East. As a result of international travel and commerce, this is one of many pathogens which has started to cause disease outside its original area of endemicity. WNV has caused small epidemics in Europe but has become a serious public health problem in North America where the infection has affected thousands of individuals and caused hundreds of deaths. This virus is now known to be transfusion transmissible and people infected with the virus through transfusion have suffered serious illnesses and a number have died. The TGA has therefore instituted measures to ensure the minimisation of risk from WNV in travellers to North America. These individuals' donated blood will not be used to manufacture blood components such as red cells and platelets, which are known to transmit WNV when this is present in the donor. Plasma from these donors will be fractionated as this is known to inactivate the virus. The TGA will also mandate a test for WNV for these donors who will be deferred according to their travel history, once such a test is available.
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.
World Distribution of Dengue 1999 Areas infested with Aedes aegypti Areas with Aedes aegypti and recent epidemic dengue
Like WNV, DFV was thought not to be a risk as far as blood transfusion is concerned. However, the virus is transmitted through mosquitos and has been shown to be transmitted through needle stick injury. The TGA therefore considers that it is a potential hazard of blood transfusion in areas where the disease is prevalent. One such area currently is North Queensland, where outbreaks of Dengue fever have been occurring over the past thirty years. An epidemic of Dengue fever is currently causing illnesses in Cairns. The TGA has therefore directed the blood service to not use fresh blood components from people resident or visiting Cairns for a certain time period, although the plasma can still be used to manufacture derivatives. This measure will allow risk to be minimised while maintaining the blood bank in the Cairns community. The TGA will review its current requirements once evidence accrues regarding the current Dengue epidemic in North Queensland.
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.
Degenerative, fatal disease with lengthy incubation period
Results from consumption of tissue from BSE-infected cattle
Most cases in, or associated with UK (152), 6-10 others in Europe
No endogenous case in Australia
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)
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
Transmission of BSE by blood transfusion in sheep Houston et al 2000 UK Cheviot sheep fed BSE-affected cattle brain Transfused into NZ (scrapie-free Sheep) (Positive control transfused with BSE brain)
1/19 transfusion transmitted BSE in sheep
Tx given 310 days after oral challenge (donor asymptomatic)
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
Infections with very long incubation periods in the modern era of trade and travel (Kimball et al Globalization and Health 2005:1:3)
Global forces eg market demand, GATT provisions:
may set the stage for streamlining processing of product
2) Streamlining of production
drives efficiency and cost savings
may contribute to emergence of new infections
when biological materials are used
3) Emerging new pathogens are disseminated through trade and travel
creates a "science gap"
where rapid research is imperative to find and implement remedies
before extensive infection occurs
4) Once clinical disease is manifest widespread dissemination of infection has occurred and risk can be mapped using product specific trade data. This mapping may allow timely institution of surveillance.