Created: Thursday, 04 February 2016 20:40
Recent scientific and public press reports have heightened awareness of the Zika virus and its emergence in the Americas (1). The temporal link between the emergence of the virus in Brazil and the birth of babies with microcephaly (2) is most alarming. PPTA is aware that persons who rely on plasma protein therapies are understandably concerned whether these therapies are safe with respect to the Zika virus.
Zika virus is a Flavivirus that is primarily transmitted by the Aedes mosquitos (3), however it has been reported that it may be transmitted, even if rarely, from mother to child and also by transfusion of infected blood or by sexual contact (4). PPTA member companies have considerable experience with the capacity of their production processes to effectively eliminate Flaviviruses, in case they were present in the plasma. Based on these experiences, Zika virus is not a concern for the safety of plasma protein therapies.
Practically all Zika infection cases detected in Europe and the USA so far acquired the disease outside of these geographical areas. While the number of cases of travelers to the risk areas showing Zika infection at return may increase, the current situation indicates an almost total absence of Zika infection in the European or USA plasma donor population. In addition, donor screening procedures make it highly unlikely that any person showing disease symptoms typical of Zika would be accepted for donation.
Zika virus is of intermediate size (approximately 40 nm in diameter) and is similar to other Flaviviruses like the West Nile (WNV), Dengue, Yellow Fever and Japanese Encephalitis viruses, as it has a lipid envelope. The relatively large size and lipid envelope makes it highly susceptible to steps with virus inactivation and removal capacity used during the manufacturing processes, such as solvent-detergent (S/D), low pH incubation, caprylate, pasteurization or dry-heat treatments, nanofiltration or fractionation processes. The effectiveness of these processes has been demonstrated on other lipid-enveloped model viruses which are quite similar to Zika virus, e.g. Bovine viral diarrhea virus (BVDV) or Tick-borne encephalitis virus (TBEV), and most importantly the WNV, another Flavivirus which is even more closely related to the Zika virus (5-10). Based on these data, PPTA is assured that existing manufacturing methods will also be effective against the Zika virus.
PPTA is aware that there are recommendations by agencies and blood collection organizations to defer potential donors of blood components (2,11,12) who have traveled to areas considered at risk for Zika virus (i.e., Mexico, the Caribbean, and Central and South America) (1, 13). However, based on the practical absence of the virus in areas used for plasma sourcing such as the US (1) and Europe (1, 13), the low-levels and short-lived viraemia in the blood of infected individuals (14, 15), as well as the established and very substantial processes with virus inactivation and removal capacity during manufacturing of plasma-derived products, PPTA does not consider that deferral of donors is warranted for donation of plasma for manufacturing use.
- European Centre For Disease Prevention and Control. Rapid Risk Assessment: Zika virus epidemic in the Americas: association with microcephaly and Guillain–Barré syndrome [Internet]. ECDC; 10 December 2015 http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf
- European Centre for Disease Prevention and Control. Zika virus infection (factsheet for health professionals) [Internet]. Stockholm: ECDC; 2015 [cited 18 May 2015]. Available online: http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/factsheet-health-professionals/Pages/factsheet_health_professionals.aspx.
- Dichtelmüller HO, Biesert L, Fabbrizzi F, Gajardo R, Gröner A, von Hoegen I, Jorquera JI, Kempf C, Kreil TR, Pifat D, Osheroff W, Poelsler G. Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies. Transfusion. 2009 Sep;49(9):1931-43
- Caballero S, Diez JM, Belda FJ, Otegui M, Herring S, Roth NJ, Lee D, Gajardo R, Jorquera JI. Robustness of nanofiltration for increasing the viral safety margin of biological products. Biologicals. 2014 Mar;42(2):79-85
- Remington KM, Trejo SR, Buczynski G, Li H, Osheroff WP, Brown JP, Renfrow H, Reynolds R, Pifat DY. Inactivation of West Nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma-derived products. Vox Sang. 2004 Jul;87(1):10-8
- Kreil TR, Berting A, Kistner O, Kindermann J. West Nile virus and the safety of plasma derivatives: verification of high safety margins, and the validity of predictions based on model virus data. Transfusion. 2003 Aug;43(8):1023-8
- Stucki M, Boschetti N, Schäfer W, Hostettler T, Käsermann F, Nowak T, Gröner A, Kempf C. Investigations of prion and virus safety of a new liquid IVIG product. Biologicals, 2008, 36(4):239-47. doi: 10.1016/j.biologicals.2008.01.004. Epub 2008 Mar 12.
- Dichtelmüller HO, Biesert L, Fabbrizzi F, Falbo A, Flechsig E, Gröner A, von Hoegen I, Kempf C, Kreil TR, Lee DC, Pölsler G, Roth NJ. Contribution to safety of immunoglobulin and albumin from virus partitioning and inactivation by cold ethanol fractionation: a data collection from Plasma Protein Therapeutics Association member companies. Transfusion. 2011 Jul;51(7):1412-30).
- European Centre for Disease Prevention and Control: RAPID RISK ASSESSMENT: Zika virus disease epidemic: potential association with microcephaly and Guillain-Barré syndrome (first update), 21 January 2016; Available online: http://ecdc.europa.eu/en/publications/Publications/rapid-risk-assessment-zika-virus-first-update-jan-2016.pdf
- Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, Stanfield SM, Duffy MR. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 2008; 17:1232-1239
- Musso D Nhan T, Robin E, Roche C, Bierlaire D, Zisou K, Shan Yan A, Cao-Lormeau VM and Broult J. Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014. Euro Surveill. 2014;19(14):pii=20761. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20761