Info / Q&A

Blood Safety and the Threat of Pandemic Influenza:
The Role of the INTERCEPT Blood System in Securing Platelet and
Plasma Components

Topics

• Challenges to the blood supply in a pandemic: availability as well as safety
• Pathogen inactivation (PI) provides immediate, prospective protection
• INTERCEPT Platelets: proven performance under epidemic conditions
• Broad-spectrum efficacy allows re-assessment of conventional safety measures
• Already protecting patients in 12 countries: >250,000 transfusions to date
• Q&A
• Additional Information & Resources

Challenges to the blood supply in a pandemic: availability as well as safety

Conventional blood safety techniques (donor screening questions, serological assays, nucleic acid tests) allow blood centers to identify and defer the small proportion of donors at greatest risk for a handful of bloodborne infections, including HIV, HBV, HCV, syphilis and others.  However, the threat of a pandemic challenges this model: the majority of the donor population may be at risk, screening questions may not be well defined, and reliable tests may not be available.  Blood suppliers may be forced to choose between halting collections entirely, or accepting local donors despite potential risks.

In addition, the number of available donors as well as blood center staff may be reduced due to illness, all putting pressure on the ability of blood centers to maintain an adequate supply of components.  Thus, those requiring blood transfusions during a pandemic may face a significant risk due to shortages of available blood components, independent of concerns regarding transfusion-transmitted influenza.

Pathogen inactivation (PI) provides immediate, prospective protection

As a pandemic threat is recognized, when does transfusion recipient risk begin?  Unlike reactive strategies such as donor screening or pathogen-specific tests, PI provides continuous, prospective protection from both known and as-yet-unrecognized threats. 

Adoption of universal PI in the plasma fractionation industry starting in the 1980s removed the risks of HIV and hepatitis, and also prevented any transmission of West Nile virus (WNV) by plasma products as this pathogen spread throughout the United States starting in 1999.  In contrast, 23 transfusion recipients were confirmed to be infected with WNV before effective safety measure were finally put in place for blood components in 2003 [1], and occasional infections still occur despite use of sensitive individual donor WNV nucleic acid tests. 

INTERCEPT Platelets: proven performance under epidemic conditions

In late 2005, the Indian Ocean island of La Réunion, a department of France, faced an unexpected challenge to maintaining the national blood supply when it became the epicenter of an explosive regional outbreak of Chikungunya virus. Spread by the bite of infected mosquitoes, the disease spread rapidly through the island, and by mid-2006 there were estimated to be over 250,000 infections out of a total population of approximately 750,000. With one in three inhabitants already infected, and the remaining two-thirds at risk, EFS officials concluded that local blood donors were not safe to use without significant changes to standard blood collection and processing.  

Local collections of plasma and red blood cells were halted, and units were temporarily imported from metropolitan France. Platelets, however, could not be imported because of the transportation time. 

The EFS made a rapid decision to implement INTERCEPT in La Réunion to avoid critical shortages of platelets. Installation and training required only a few weeks, and allowed La Réunion to treat thousands of platelet units that otherwise might not have been available to the island hospitals.  Use of INTERCEPT has already been extended to other French overseas departments at frequent risk of infectious diseases outbreaks such as dengue.

Broad-spectrum efficacy allows re-assessment of conventional safety measures

With efficacy against a broad range of viruses, bacteria, and protozoa, as well as leukocytes, INTERCEPT pathogen inactivation provides protection against a wider variety of infections than conventional safety techniques.  The product is CE marked as an alternative to gamma irradiation for prevention of transfusion-associated graft-vs-host disease, and customers have also replaced CMV testing and bacterial detection.  Thus INTERCEPT pathogen inactivation can streamline blood center operations and inventory management, in addition to providing prospective protection against emerging infections.

The added safety of pathogen inactivation might also allow re-assessment of additional conventional safety measures in the context of pandemic conditions and prevention of critical blood shortages.

Already protecting patients in 12 countries: >250,000 transfusions to date

The INTERCEPT Blood System was CE marked for use with platelets in 2002, and with plasma in 2006.  Since that time, the system has been used extensively in Europe, and more recently, in the Middle East.  Over 35,000 treated units have been studied in a post-marketing hemovigilance program, and demonstrate a safety profile comparable to conventional platelets and plasma.

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Q&A

1. How frequently is influenza transmitted by blood?
   
   Though blood and body fluids are not the primary mode of transmission for influenza, studies have detected the presence of the virus in blood, both in experimental models and in influenza patients [2,3].  The typical levels of infectious virus and frequency of transfusion transmission are not yet known, nor is it known whether pandemic strains may be more predisposed to viremia than seasonally circulating strains. [2]
   
   The AABB Interorganizational Task Force on Pandemic Influenza summarized the situation
   as follows:
   
   “Flu has never been recognized as a transfusion-transmissible infection.  However, asserting that influenza will not materially affect blood safety ignores the absence of systematic data establishing a lack of transfusion-transmission from asymptomatic blood donors incubating influenza, or during the recovery from active infection.  It also does not recognize the implications of the precautionary approach to blood safety that has dominated the past 20+ years.” [4]
   
   
2. Does the INTERCEPT treatment inactivate influenza, and H1N1 in particular?
   
   INTERCEPT inactivates high levels of influenza in platelets and plasma.  Inactivation of H5N1 is an approved product claim, and inactivation of H1N1 has also been confirmed in pilot studies. [5]
   
   The genetic sequences for influenza do vary between strains, but the overall structure and composition of the virus do not.  Therefore, the efficacy of INTERCEPT’s nucleic acid crosslinking is not expected to show substantial differences from strain to strain, in contrast to serological or nucleic acid test performance which can be sensitive to these variations.
   
   INTERCEPT viral inactivation claims:
   Platelets -- http://www.interceptbloodsystem.com/plt_viruses.html
   Plasma -- http://www.interceptbloodsystem.com/ffp_viruses.html
   
   
3. How does INTERCEPT help blood centers protect transfusion recipients?
   
   During the INTERCEPT treatment process, the compound amotosalen is added to platelets or plasma and then activated by UVA light to crosslink nucleic acid.  The nucleic acid crosslinks prevent replication, thereby preventing disease transmission to the transfusion recipient.
   
   INTERCEPT treatment is effective against a broad spectrum of viruses, bacteria and parasites, as well as white blood cells.  Susceptible organisms will be inactivated by the process, whether or not their potential threat has been recognized—so, use of INTERCEPT can provide patients with prospective protection against transfusion-transmitted influenza and other diseases, whether or not illness has been detected in the donor population.
   
   
4. How can use of INTERCEPT help to maintain availability of blood?
   
   Donor screening questions are often non-specific, leading to deferral of many healthy donors in addition to potentially infected ones.  Likewise, newly developed pathogen tests may lack specificity, generating false positives that lead to unnecessary loss.  INTERCEPT can help blood availability in two ways during an influenza pandemic: first, inactivation of influenza virus can obviate the need to use non-specific safety methods that disqualify healthy donors, and second, broad-spectrum pathogen inactivation may allow blood centers and health authorities the option to consider suspending other, non-influenza related deferrals in order to maximize access to their local pool of blood donors. 
   
   
5. Have INTERCEPT customers avoided additional tests or deferrals for H1N1 influenza?
   
   Information about the potential pandemic risk of swine influenza is evolving rapidly, and to our knowledge blood services and health policy makers are still evaluating the steps to be taken to ensure blood safety and availability in each country.  Cerus will stay in close contact with customers and share further information as it is received.
   
   
6. Can INTERCEPT protect units of red blood cells?
   
   Unfortunately, INTERCEPT is currently available only for treatment of platelets and plasma.  Red blood cell treatment is under development, and currently being evaluated in a Phase I trial in the United States.
   
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Additional Information & Resources

Cerus Corporate Site
http://www.cerus.com

World Health Organization – Global Outbreak Alert & Response Network
http://www.who.int/csr/outbreaknetwork/en/

European Union Public Health information, including links to member states:
http://ec.europa.eu/health/ph_threats/com/Influenza/swine_influenza_en.htm

European Center for Disease Prevention and Control (ECDC)
http://ecdc.europa.eu/en/

Eurosurveillance
http://www.eurosurveillance.org

United States Center for Disease Control (CDC) Swine Influenza Investigation
http://www.cdc.gov/swineflu/investigation.htm

ProMED (Program for Monitoring Emerging Diseases)
http://www.promedmail.org

HealthMap – Global Disease Alert Map
http://www.healthmap.org/en

HealthMap – Disease Updates on Twitter
http://twitter.com/healthmap

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References

1. LN Pealer, AA Marfin, et al., Transmission of West Nile virus through blood transfusion in the United States in 2002, New England Journal of Medicine 2003;349:1236-45.
2. AM Likos, DJ Kelvin et al., Influenza viremia and the potential for blood-borne transmission, Transfusion 2007;47:1080-1088.
3. MK Hourfar, A Themann, et al., Blood screening for influenza, Emerging Infectious Diseases 2007;13(7):1081-1083.
4. AABB Interorganizational Task Force on Pandemic Influenza and the Blood Supply, Pandemic influenza planning – efforts to ensure a safe, available blood supply, Planning Document Version 1.0, October 3, 2006, page 3.
5. Cerus Corporation, data on file.