Evaluation of Pathogen Reduction Systems to Inactivate Dengue and Chikungunya Viruses in Apheresis Platelets Suspended in Plasma

Li Kiang Tan, Sally Lam, Swee Ling Low, Fang Hui Tan, Lee Ching Ng, Diana Teo

Blood Services Group, Health Sciences Authority, Singapore City, Singapore.
Environmental Health Institute, National Environment Agency, Singapore City, Singapore.

DOI: 10.4236/aid.2013.31001                

Abstract

The risk of blood-borne transmission of infectious diseases has led to an increasing awareness of the need for a safe and effective pathogen reduction technology. This study evaluated the efficacy of 2 pathogen reduction systems to inactivate dengue virus (DENV-2) and chikungunya virus (CHIKV) spiked into apheresis platelets (APLT) concentrates. Double-dose APLT collections (n = 3) were split evenly into two units and spiked with 107 infectious units of DENV-2 or CHIKV. APLTs samples were assayed for viral infectivity before and after Amotosalen photochemical treatment (PCT) or Riboflavin pathogen reduction treatment (PRT). Viral infectivity was determined by plaque assays. Platelet (PLT) count, pH and residual S-59 were measured during the storage of 5 days. Amotosalen PCT showed robust efficacy and complete inactivation of both viruses in APLTs, with up to 3.01 and 3.75 log reductions of DENV-2 and CHIKV respectively. At similar initial concentrations, Riboflavin PRT showed complete inactivation of CHIKV with up to 3.73 log reduction, much higher efficacy than against DENV-2 where a log reduction of up to 1.58 was observed. All post-treated APLTs maintained acceptable PLT yields and quality parameters. This parallel study of 2 pathogen reduction systems demonstrates their efficacy in inactivating or reducing DENV and CHIKV in APLTs and reaffirms the usefulness of pathogen inactivation systems to ensure the safety in PLTs transfusion.

Keywords

Pathogen Inactivation; Dengue; Chikungunya; Transfusion-Transmitted Disease; Platelets

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	S. P. Sharm, “Dengue Outbreak Affects More than 7000 People in Nepal,” BMJ, Vol. 341, 2010, pp. c5496. doi:10.1136/bmj.c5496
[2]	E. A. Gould, P. Gallian, X. De Lamballerie and R. N. Charrel, “First Cases of Autochthonous Dengue Fever and Chikungunya Fever in France: From Bad Dream to Reality!” Clin Microbiol Infect, Vol. 16, No. 12, 2010, pp. 1702-1704. doi:10.1111/j.1469-0691.2010.03386.x
[3]	G. Rezza, L. Nicoletti, R. Angelini, R. Romi, A.C. Finarelli, M. Panning, P. Cordioli, C. Fortuna, S. Boros and F. Magurano, “Infection with Chikungunya Virus in Italy: An Outbreak in a Temperate Region,” Lancet, Vol. 370, No. 9602, 2007, pp. 1840-1846. doi:10.1016/S0140-6736(07)61779-6
[4]	K. Zheng, J. Li, Q. Zhang, M. Liang, C. Li, M. Lin, J. Huang, H. Li, D. Xiang and N. Wang, “Genetic Analysis of Chikungunya Viruses Imported to Mainland China in 2008,” Virology Journal, Vol. 7, 2010, pp. 8. doi:10.1186/1743-422X-7-8
[5]	P. Renault, J. L. Solet, D. Sissoko,E. Balleydier, S. Larrieu, L. Filleul, C. Lassalle, J. Thiria, E. Rachou and H. de Valk, “A Major Epidemic of Chikungunya Virus Infection on Reunion Island, France, 2005-2006,” The American Journal of Tropical Medicine and Hygiene, Vol. 77, No. 4, 2008, pp. 727-731.
[6]	H. C. Hapuarachchi, K.B. Bandara, S. D. Sumanadasa, M. D. Hapugoda, Y. L. Lai, K. S. Lee, L. K. Tan, R. T. Lin, L. F. Ng and G. Bucht, “Re-Emergence of Chikungunya Virus in South-east Asia: Virological Evidence from Sri Lanka and Singapore,” Journal of General Virology, Vol. 91, No. 4, 2009, pp. 1067-1076. doi:10.1099/vir.0.015743-0
[7]	TDR/WHO, “Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control,” Geneva, 2009.
[8]	M. E. Beatty, A. Stone, D. W. Fitzsimons, J. N. Hanna, S. K. Lam, S. Vong, M. G. Guzman, J. F. Mendez-Galvan, S.B.Halstead and G. W. Letson, “Best Practices in Dengue Surveillance: A Report from the Asia-Pacific and Americas Dengue Prevention Boards,” PLOS Neglected Tropical Diseases, Vol. 4, No. 11, 2010, p. 890. doi:10.1371/journal.pntd.0000890
[9]	D. J. Gubler, “Dengue and Dengue Hemorrhagic Fever,” Clinical Microbiology Reviews, Vol. 11, No. 3, 1998, pp. 480-496.
[10]	S. B. Halstead, “Antibody, Macrophages, Dengue Virus Infection, Shock, and Hemorrhage: A Pathogenetic Cascade,” Clinical Infectious Diseases, Vol. 11, Suppl. 4, 1998, pp. S830-839. doi:10.1093/clinids/11.Supplement_4.S830
[11]	P. A. Tambyah, E. S. Koay, M. L. Poon, R. V. Lin and B. K. Ong, “Dengue Hemorrhagic Fever Transmitted by Blood Transfusion,” The New England Journal of Medicine, Vol. 359, No. 14, 2008, pp. 1526-1527. doi:10.1056/NEJMc0708673
[12]	V. W. Chuang, T. Y. Wong, Y. H. Leung, E. S. Ma, Y. L. Law, O. T. Tsang, K. M. Chan, I. H. Tsang, T. L. Que and R. W. Yung, “Review of Dengue Fever Cases in Hong Kong during 1998 to 2005,” Hong Kong Medical Journal, Vol. 14, No. 3, 2008, pp. 170-177.
[13]	S. L. Stramer, J. M. Linnen, J. M. Carrick, G. A. Foster, D. E. Krysztof, S. Zou, R. Y. Dodd, L. M. Tirado-Marrero, E. Hunsperger and G. A. Santiago, “Dengue Viremia in Blood Donors Identified by RNA and Detection of Dengue Transfusion Transmission during the 2007 Dengue Outbreak in Puerto Rico,” Transfusion, Vol. 52, No. 8, 2012, pp. 1657-1666. doi:10.1111/j.1537-2995.2012.03566.x
[14]	H. Mohammed, J. M. Linnen, J. L. Munoz-Jordan, K. Tomashek, G. Foster, A. S. Broulik, L. Petersen and S. L. Stramer, “Dengue Virus in Blood Donations, Puerto Rico, 2005,” Transfusion, Vol. 48, No. 7, 2008, pp. 1348-1354. doi:10.1111/j.1537-2995.2008.01771.x
[15]	J. M. Linnen, E. Vinelli, E. C. Sabino, L. H. Tobler, C. Hyland, T. H. Lee, D. P. Kolk, A. S. Broulik, C. S. Collins and R. S. Lanciotti, “Dengue Viremia in Blood Donors from Honduras, Brazil, and Australia,” Transfusion, Vol. 48, No. 7, 2008, pp. 1355-1362. doi:10.1111/j.1537-2995.2008.01772.x
[16]	D. S. Burke, A. Nisalak, D. E. Johnson and R. M. Scott, “A Prospective Study of Dengue Infections in Bangkok,” The American Journal of Tropical Medicine and Hygiene, Vol. 38, No. 1, 1988, pp. 172-180.
[17]	D. Teo, L. C. Ng and S. Lam, “Is Dengue a Threat to the Blood Supply?” Transfusion Medicine, Vol. 19, No. 2, 2009, pp. 66-77. doi:10.1111/j.1365-3148.2009.00916.x
[18]	A. Wilder-Smith, L. H. Chen, E. Massad and M. E. Wilson, “Threat of Dengue to Blood Safety in Dengue-Endemic Countries,” Emerging Infectious Diseases, Vol. 15, No. 1, 2009, pp. 8-11. doi:10.3201/eid1501.071097
[19]	L. C. Ng, L. K. Tan, C. H. Tan, S. S. Tan, H. C. Hapuarachchi, K. Y. Pok, Y. L. Lai, S. G. Lam-Phua, G. Bucht and R. T. Lin, “Entomologic and virologic investigation of Chikungunya, Singapore,” Emerging Infectious Diseases, Vol. 15, No. 8, 2009, pp. 1243-1249. doi:10.3201/eid1508.081486
[20]	Y. S. Leo, A. L. Chow, L. K. Tan, D. C. Lye, L. Lin and L. C. Ng, “Chikungunya Outbreak, Singapore, 2008,” Emerging Infectious Diseases, Vol. 15, No. 5, 2009, pp. 836-837. doi:10.3201/eid1505.081390
[21]	C. Brouard, P. Bernillon, I. Quatresous, J. Pillonel, A. Assal, H. De Valk and J. C. Desenclos, “Estimated Risk of Chikungunya Viremic Blood Donation during an Epidemic on Reunion Island in the Indian Ocean, 2005 to 2007,” Transfusion, Vol. 48, No. 7, 2008, pp.1333-1341. doi:10.1111/j.1537-2995.2008.01646.x
[22]	L. C. Ng, S. Lam and D. Teo, “Epidemiology of dengue and chikungunya viruses and their potential impact on the blood supply,” ISBT Science Series, Vol. 4, No. n2, 2009, pp. 357-367. doi:10.1111/j.1751-2824.2009.01274.x
[23]	P. Parola, X. de Lamballerie, J. Jourdan, C. Rovery, V. Vaillant, P. Minodier, P. Brouqui, A. Flahault, D. Raoult and R. N. Charrel, “Novel Chikungunya Virus Variant in Travelers Returning from Indian Ocean Islands,” Emerging Infectious Diseases, Vol. 12, No. 10, 2006, pp. 1493-1499. doi:10.3201/eid1210.060610
[24]	L. R. Petersen, S. L. Stramer and A. M. Powers, “Chikungunya Virus: Possible Impact on Transfusion Medicine,” Transfusion Medicine Reviews, Vol. 24, No. 1, 2010, pp. 15-21. doi:10.1016/j.tmrv.2009.09.002
[25]	L. Lin, C. V. Hanson, H. J. Alter, V. Jauvin, K. A. Bernard, K. K. Murthy, P. Metzel and L. Corash, “Inactivation of Viruses in Platelet Concentrates by Photochemical Treatment with Amotosalen and Long-Wavelength Ultraviolet Light,” Transfusion, Vol. 45, No. 4, 2005, pp. 580-590. doi:10.1111/j.0041-1132.2005.04316.x
[26]	C. H. Arturo and D. R. Smith, “Mammalian Dengue Virus Receptors,” Dengue Bulletin, Vol. 29, 2005, pp. 119-135.
[27]	Circular of Information for the Use of Human Blood and Blood Components. In.: AABB, 2011.
[28]	J. P. AuBuchon, L. Herschel, J. Roger, H. Taylor, P. Whitley, J. Li, R. Edrich and R. P. Goodrich, “Efficacy of Apheresis Platelets Treated with Riboflavin and Ultraviolet Light for Pathogen Reduction,” Transfusion, Vol. 45, No. 8, 2005, pp. 1335-1341. doi:10.1111/j.1537-2995.2005.00202.x
[29]	R. P. Goodrich, J. Li, H. Pieters, R. Crookes, J. Roodt and P. Heyns Adu, “Correlation of in Vitro Platelet Quality Measurements with in Vivo Platelet Viability in Human Subjects,” Vox Sang, Vol. 90, No. 4, 2006, pp. 279-285. doi:10.1111/j.1423-0410.2006.00761.x
[30]	S. L. Stramer, F. B. Hollinger, L. M. Katz, S. Kleinman, P. S. Metzel, K. R. Gregory and R. Y. Dodd, “Emerging Infectious Disease Agents and Their Potential Threat to Transfusion Safety,” Transfusion, Vol. 49, Suppl. 2, 2009, pp. 1S-29S. doi:10.1111/j.1537-2995.2009.02279.x
[31]	D. L. Vanlandingham, S. D. Keil, K. M. Horne, R. Pyles, R. P. Goodrich and S. Higgs, “Photochemical Inactivation of Chikungunya Virus in Plasma and Platelets Using the Mirasol Pathogen Reduction Technology System,” Transfusion, Vol. 53, No. 2, 2012, pp. 284-290.
[32]	Y. Singh, L. S. Sawyer, L. S. Pinkoski, K. W. Dupuis, J. C. Hsu, L. Lin and L. Corash, “Photochemical Treatment of Plasma with Amotosalen and Long-Wavelength Ultraviolet Light Inactivates Pathogens While Retaining Coagulation Function,” Transfusion, Vol. 46, No. 7, 2006, pp. 1168-1177. doi:10.1111/j.1537-2995.2006.00867.x
[33]	L. Kightlinger, “West Nile Virus Transmission through Blood Transfusion—South Dakota, 2006,” CDC—Morbidity and Mortality Weekly Report, Vol. 56, No. 4, 2006, pp. 76-79.
[34]	L. N. Pealer, A. A. Marfin, L. R. Petersen, R. S. Lanciotti, P. L. Page, S. L. Stramer, M. G. Stobierski, K. Signs, B. Newman and H. Kapoor, “Transmission of West Nile Virus through Blood Transfusion in the United States in 2002,” The New England Journal of Medicine, Vol. 349, No. 13, 2003, pp. 1236-1245. doi:10.1056/NEJMoa030969
[35]	H. Faddy, J. Fryk, P. Young, D. Watterson, R. Goodrich and D. Marks, “The Effect of Pathogen Reduction Technology (Mirasol) on the Infectivity of Dengue Viruses,” In: 32nd International Congress of the International Society of Blood Transfusion, Cancun, Vol. 103, 7-12 July 2012, p. 191.
[36]	S. P. Montgomery, J. A. Brown, M. Kuehnert, T. L. Smith, N. Crall, R. S. Lanciotti, A. Macedo de Oliveira, T. Boo and A. A. Marfin, “Transfusion-Associated Transmission of West Nile Virus, United States 2003 through 2005,” Transfusion, Vol. 46, No. 12, 2006, pp. 2038-2046. doi:10.1111/j.1537-2995.2006.01030.x
[37]	S. M. Picker, R. Speer and B. S. Gathof, “Evaluation of Processing Characteristics of Photochemically Treated Pooled Platelets: Target Requirements for the INTERCEPT Blood System Comply with Routine Use after Process Optimization,” Transfusion Medicine, Vol. 14, No. 3, 2004, pp. 217-223. doi:10.1111/j.0958-7578.2004.00503.x
[38]	M. A. Chernesky and R. P. Larke, “Contrasting Effects of Rabbit and Human Platelets on Chikungunya Virus Infectivity,” Canadian Journal of Microbiology, Vol. 23, No. 9, 1977, pp. 1237-1244. doi:10.1139/m77-185