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Joint Statement Before BPAC on Risk of Dengue Virus Infection in Blood Donors

 Joint Statement Before the Blood Products Advisory Committee

Risk of Dengue Virus Infection in Blood Donors

14 December 2010

Louis M. Katz, MD, Chair, AABB Transfusion Transmitted Diseases Committee

 Thank you for the opportunity to provide our thoughts about the issue of dengue and its relevance to transfusion medicine. This statement is presented on behalf of AABB, the American Red Cross and America’s Blood Centers.

There have been reports of transfusion-transmitted dengue from 3 donors to date (in Hong Kong, Singapore and Puerto Rico). This low number is reassuring given the fact that more than 50 million infections occur worldwide annually; however, it needs to be recognized that surveillance for these events has not been a priority in endemic areas, and transfusion transmission in such areas is difficult to differentiate from mosquito transmission. No dengue transfusion transmissions have been recognized in the continental US and Hawaii despite endemic dengue in the Rio Grande Valley, outbreaks in Hawaii, cases in the Florida Keys and among travelers returning from endemic/epidemic areas.

We believe that the cornerstone for mitigating the risk of transfusion-transmitted dengue viruses in the US is public health surveillance for autochthonous infection, with subsequent interventions scaled to estimates of risk. Dengue became nationally reportable in 2009, which should facilitate this activity. We, the blood community, have encouraged the potential manufacturers of dengue blood donation screening assays to develop prototype kits that could be available for use under investigational protocols should dengue more firmly establish itself in the continental US and Hawaii.

Although dengue has affected a substantial proportion of the population of Puerto Rico in outbreaks since 1963, travelers to the island or to other nonmalarious urban areas endemic for dengue appear to have a much lower quantitative risk of acquiring dengue infection than do residents due to their short length of time in Puerto Rico, and a likely higher standard of housing while in the endemic area. This very low risk does not justify deferring such travelers from blood donation. A risk model for travel to Singapore, a dengue-endemic area, published in 2009 (Massad et al. J Trav Med. 2009;(3)191-3) estimated a risk of 0.17% during a 1-week stay during the peak of a severe epidemic in 2005, vs. 0.004% during the low season of a nonepidemic year.  During 1996 through 2008, 1093 laboratory confirmed dengue cases were imported into the US (CDC. MMWR. 2010:59(23);715-19). If 67% of dengue infections are asymptomatic, then a 
minimum of approximately 3312 infected travelers entered the US over those 13 years. During the same interval there were 18,322 reported malaria cases (CDC. MMWR. 2010;59(SS-7).
Most rural areas affected by dengue have endemic malaria as well, and travelers to those areas are already deferred for this risk. In the absence of recognized transfusion-transmitted dengue in the US, we do not think a dengue-specific geographic deferral is appropriate at this time, and certainly not in the absence of a clear understanding of the impact of a putative deferral on the adequacy of the blood supply. 

Available data suggest that viremia is short lived in most if not all asymptomatic dengue infections. Based on extrapolation from WNV infection, it is likely that infectivity to a recipient would only be present prior to the development of IgG antibody. Thus, if a travel deferral were to be considered, it should be established separate from existing malaria policies and be confined to the interval of known asymptomatic viremia prior to the development of IgG. Based on available information, less than or equal to 28 days would appear to avoid viremic, infectious donors with a substantial margin of safety. This is consistent with evolving approaches of which we are aware in the EU and Asia-Pacific regions. The deferral period for healthy travelers to dengue endemic areas should not be of the same length as the currently proposed 120-day interval used to reinstate donors with documented asymptomatic (RNA or antigen positive) or symptomatic dengue virus infection, as in these latter cases it has been established that dengue infection has actually occurred.

Dengue is established in some areas of the US and its territories, with varying levels of transmission from year to year. Given the availability of dengue tests that could be developed for use under an IND, we think it is reasonable to recommend their use when a pre-agreed threshold of activity is reached in a region, unless blood centers voluntarily implement prior to an agreed level. During the interval before the implementation of such testing, it may be reasonable, after an assessment of the adequacy of the blood supply, to suspend collections in such a region during peak dengue incidence. Thresholds should also be established for discontinuation of such measures when appropriate.

We ask for an open dialogue with FDA and CDC on formulating definitions of the level of autochthonous infection that will define an outbreak in the US and an understanding of what, minimally, constitutes the establishment of endemicity in the US and its territories as well as who is responsible for determining and communicating that an agreed upon threshold for intervention has been reached.  Likewise, we believe that there is a need to establish in advance who would be responsible for collating worldwide data and designating areas or countries as epidemic or endemic as local epidemiology evolves over time. To date, the American Red Cross in Puerto Rico and an independent blood center in south Florida, in collaboration with the ARC, have voluntarily instituted blood donation screening with the best available assay under IND in response to epidemic dengue in Puerto Rico and a small number of cases that have occurred in the Florida Keys.

Retrospective studies performed by the American Red Cross in Puerto Rico clearly suggest that nucleic acid testing (NAT) would be preferable to NS1 antigen testing from the standpoint of sensitivity and specificity although antigen testing has interdicted high-titer viremic donations.  Antibody assays will not be useful for donor screening since a robust antibody response coincides with loss of infectivity.

Again, we support and encourage dialogue aimed at developing approaches to the prevention of dengue transmission in case the worldwide epidemic becomes established in the continental US and Hawaii.  We would like to see the successful cooperation between the blood community, diagnostic manufacturers, public health agencies and regulators similar to the process developed for the WNV epidemic replicated as we address the potential for a dengue epidemic in the US.

AABB is an international, not-for-profit association representing individuals and institutions involved in the field of transfusion medicine and cellular therapies. The association is committed to improving health by developing and delivering standards, accreditation and educational programs that focus on optimizing patient and donor care and safety. AABB membership consists of nearly 2,000 institutions and 8,000 individuals, including physicians, nurses, scientists, researchers, administrators, medical technologists and other health care providers. Members are located in more than 80 countries.

The American Red Cross, through its 35 Blood Services Regions and five National Testing Laboratories, supplies nearly half of the nation's blood supply.  Over six million units of Whole Blood were collected from more than four million Red Cross volunteer donors, separated into 12 million components, and supplied to 3000 hospitals to meet the transfusion needs of patients last year.

Founded in 1962, America’s Blood Centers is North America’s largest network of community-based blood programs.  Seventy-five blood centers operate more than 600 collection sites in 45 U.S. states and Canada, providing half of the United States, and all of Canada’s volunteer donor blood supply.  These blood centers serve more than 180 million people and provide blood products and services to more than 4,200 hospitals and health care facilities across North America.  ABC’s U.S. members are licensed and regulated by the U.S. Food & Drug Administration.  Canadian members are regulated by Health Canada.