“With the new Zika virus infections, are doctors worried about giving virally infected plasma products to HAE patients?”
Jun 13, 2016
Dr. C: This is a timely topic to discuss. Why are we worried about Zika virus (ZIKV)? ZIKV is a mosquito borne flavivirus, a member of the Flaviviridae family, which includes dengue, yellow fever, and West Nile among others. It was originally isolated from a sentinel primate in Uganda in 1947. Until recently ZIKV was believed to cause only mild disease with fever and rash, which is still true in the majority of cases. Emerging evidence however has now linked ZIKV with severe neurologic complications including Guillanin-Barre syndrome and microcephaly in unborn babies. The World Health Organization has declared the ZIKV epidemic a public health emergency of international concern.
As our reader is aware risk of transmission is not limited to mosquitoes but also includes blood products and sexual contact from an infected individual. This is where “the rubber hits the road” for HAE patients. Many of you receive plasma derived C1 inhibitor for either acute or prophylactic care of your disease. FFP is also an option used in some cases. The good news is that we have lots of reassuring information to share. Marc could you explain to our reader the protections in place for ZIKV?
Certainly a good question given the emerging health concerns associated with Zika virus. Zika belongs to a family of viruses known as Flaviviruses and appears to be spread primarily via the Aedes mosquito, but can less commonly be transmitted from person to person through blood or sexual contact. So what’s the risk that a person could get Zika from blood plasma product such as C1INH concentrate? Bruce will walk us through the blood product processing procedures in greater detail, but there are a number of steps which prevent Zika from being a problem in plasma products. First, donors are screened for signs and symptoms of illness, so this might prevent individuals infected with Zika from donating blood or plasma. But because not every Zika infection causes symptoms, let’s suppose that doesn’t catch everyone and some Zika infected blood or plasma is donated. The Zika virus is of a relatively large size (as viruses go) and has a lipid envelope or cover. This makes it susceptible to a number of steps used to inactivate and remove viruses from plasma during the manufacturing process. These include solvent-detergent (S/D) treatment, low pH incubation, pasteurization, and nano filtration steps. This multi-staged processing has been repeatedly shown to be reliably effective at eliminating numerous Flaviviruses of similar size and composition, most importantly Hepatitis C and West Nile Virus, which are closely related to Zika virus. Since the implementation of these multiple viral inactivation and removal steps, there have been NO confirmed cases of any Flavivirus transmission in plasma products using these processes. So we’re quite confident that Zika virus transmission isn’t a risk of using plasma C1INH-concentrates and other plasma products when these manufacturing procedures are used as required by the FDA.
Thank you Marc. Bruce, you have been working with C1 inhibitor for many years. Could you comment for our reader on the various steps that have been taken to ensure safety and any pitfalls along the way? I would also be interested in your thoughts on FFP. This is being used less and less in the US but at times is the only available acute treatment in other parts of the world.
At the recent HAEi summit in Madrid, Mark Skinner talked about the heart-breaking consequences that the hemophilia patient community experienced from receiving unscreened and untreated plasma products in the 1970s and early 1980s. Never again! It’s crucial to recognize how far we’ve come since those days. Plasma-derived C1INH concentrates undergo a series of steps during manufacturing that are designed to protect patients from transmission of infectious agents from the donor plasma to the HAE recipient. These processes are both comprehensive and redundant.
This process starts with screening of all plasma donors to eliminate any plasma that may contain viral agents, including HIV and hepatitis A, B, and C, as well as parvovirus B19 before the plasma goes into the pool of plasma used for production. The screening includes both detecting antibodies as well as PCR tests to detect viral genomic material. Plasmas that show no evidence of infection, then enter the production process and go through a variety of steps to inactivate any infectious agents that somehow might not have been detected. These steps include chromatography to separate the plasma components based on physicochemical properties, pasteurization to inactivate any infectious agents, and nanofiltration to remove virus particles based on size differences. Taken together, we have a high degree of confidence that C1INH concentrates do not contain known viral pathogens. That said, these processes are being performed by human beings and it’s never possible to know with complete certainty that there’s zero risk.
The question that we’re focusing on deals with Zika virus. As pointed out, Zika is a flavivirus and should be successfully inactivated by pasteurization and nanofiltration. The situation for plasma is a little less clear. Solvent/detergent treated plasma is likely safe even if contaminated with Zika virus; however the more common form of plasma used to treat HAE is FFP. In this case, we have to rely on guidelines to prevent collection of plasma from potentially infected donors. I anticipate that screening of plasmas for Zika virus may be added to the process of making FFP.
Thank you Bruce and Marc. I hope that this discussion was reassuring for our reader and followers with HAE. Dr Z: and I will be off to Macedonia next week to participate in a HAEi conference. We will send you the news and look forward to our next QOTW when we return.