Page 2041 - Hematology_ Basic Principles and Practice ( PDFDrive )

1812 Part XI Transfusion Medicine

many areas visited by US travelers. It has spread rapidly in Latin Emerging Infections
America and the Caribbean since the 1980s. Dengue is endemic in
Puerto Rico, the US Virgin Islands, and American Samoa, and there The experiences with human immunodeficiency virus (HIV), new
have been outbreaks in Hawaii, Texas, and Florida during the last 10 variant Creutzfeldt-Jakob disease (vCJD), and West Nile virus (WNV)
years. Dengue is caused by four related flaviviruses spread person to have made it clear that planning for the emergence of new pathogens
person by Aedes aegypti and Aedes albopictus, which are present in 16 that may threaten the blood supply is critical in order to shorten the
and 35 US states, respectively. Over 2.3 million dengue clinical cases interval from emergence to mitigation. To that end, the characteristics
occurred in the Americas during 2015. of pathogens likely to enter the blood supply must be understood.
Most infections are asymptomatic, but illness ranges from undif- These include the ability of the agent to establish an asymptomatic
ferentiated fever to classic break-bone fever and severe dengue (dengue blood-borne phase, to survive under contemporary processing and
hemorrhagic fever and dengue shock syndrome). An approximately storage conditions, to establish infection by the intravenous route, and
to cause significant morbidity in a transfusion recipient.
7-day viremia is a feature of both asymptomatic and symptomatic Using these characteristics and a review of contemporary literature,
infection, and asymptomatic blood donors from Hong Kong, Singa- the Transfusion Transmitted Diseases Committee of the American
pore, Brazil, and Puerto Rico have transmitted dengue to blood Association of Blood Banks (AABB), from 2005 to 2009 produced
recipients in seven clusters. Although such reports are limited, com- a compendium of infectious agents that might become relevant to
pared with the high rates of vector-borne infection, there is no sys- transfusion medicine and attempted to prioritize those that were identi-
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tematic surveillance for transfusion-transmitted dengue and its fied. A series of 68 fact sheets was developed. The fact sheets provide
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recognition in the face of widespread outbreaks is problematic. transfusion medicine professionals and clinicians with an overview of
RNA-positive, asymptomatic donors have been identified in Brazil, the agents’ phylogeny, epidemiology, clinical characteristics, and inter-
Central America, and Puerto Rico using NAT and antigen detection ventions that might be useful to protect the safety of the blood supply.
Three agents were included in the highest priority stratum: Babesia sp.,
tests. Rates of donor RNA positivity in Puerto Rico are comparable dengue viruses, and the vCJD prion; a section on each is included in
to those found in US donors during the most active WNV seasons. 43,44 this chapter. The fact sheets are freely available online, cover many of
A recent study in Brazil documented transfusion transmission; the agents discussed in this chapter, and have been updated when
however, when patient charts of those donors who received an RNA- required (www.aabb.org/tm/eid/Pages/eidpostpub.aspx).
positive unit and were shown to be infected were compared with Since the original publication, several new monographs have been
control recipients who did not receive an RNA-positive unit, there added, reflecting an ongoing “horizon-scanning” initiative designed
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was no reported increase in clinical illness. This further illustrates to alert the medical community to potential threats. These include
the difficulty in identifying transfusion-transmitted dengue among yellow fever and the yellow fever vaccine viruses after the latter was
severely ill patients who are frequently transfused. 44 transmitted to blood recipients when recent vaccine recipients failed
to divulge that information during blood donation. Other fact sheets
In the absence of significant outbreaks of locally-transmitted have been updated and rereleased to capture relevant new information
dengue in the continental United States, transfusion risk relates (see box on Xenotropic Murine Leukemia Virus-Related Virus). The
mainly to return of infected, asymptomatic or presymptomatic travel- availability of these materials to the transfusion medicine and general
ers to the United States from endemic areas A 3- to 14-day incubation medical communities is meant to increase awareness that unexpected
period precedes symptom onset. Deferral for travel to malarious areas infections in transfusion recipients should trigger consideration of that
(1 year for a US resident) offers some protection, but a large propor- source and to provide background allowing the rational consideration
tion of dengue-affected areas frequently visited from the United States of approaches to avert and minimize their spread. 47
are malaria-free and donor-travelers to those areas could potentially
introduce the virus into the community and the blood supply. Careful
surveillance and a high index of suspicion when sustained febrile Xenotropic Murine Leukemia Virus–Related Virus
illness occurs following transfusion are required to recognize transfu-
sion-related dengue. Preliminary data on travelers from the United The alleged association of the gammaretrovirus xenotropic murine
States to dengue-endemic destinations that are malaria-free suggest leukemia virus–related virus (XMRV) with chronic fatigue syndrome/
that 2- to 4-week deferral for travel to dengue-affected areas may have myalgic encephalomyelitis (CFS/ME) is paradigmatic of the difficul-
a greater adverse impact on blood donation than current malaria ties inherent in the real-time assessment of potential and emerging
deferrals. To date, however, there are no instances of transfusion- transfusion-transmissible infections. A group of CFS/ME patients and
transmitted dengue in the continental United States that are attribut- controls were evaluated using polymerase chain reaction (PCR), virus
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isolation, serology, and immunohistochemistry. Evidence of the virus’s
able to donor exposure through travel. The conditions for sustained presence was strongly associated with the clinical diagnosis, culturable
spread of dengue exist in large areas of the United States: a source of virus was found in plasma, and the issue of transfusion transmission
infection from travelers and immigrants; a susceptible population; was appropriately raised.
and competent vectors. Whether the recently identified outbreaks in Multiple subsequent studies from other groups over the ensuing 2
the United States will continue or increase, and whether sustained years failed to confirm the presence of XMRV in a variety of popula-
transmission will begin is unknown. Transfusion-transmitted dengue tions. Several publications suggested that PCR contamination underlies
has been identified by one group as one of the three highest-priority some positive results; however, data now indicate that XMRV arose
emerging infections posing a potential threat to transfusion recipients as a recombinant of two murine leukemia viruses during passages in
in the United States and Canada and has been the subject of discus- nude mice, leading to the conclusion that the initial findings were an
artifact. With these findings, the original publication was retracted.
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sions at the FDA’s Blood Products Advisory Committee (see box on The absence of transfusion transmission and of the agent were also
Emerging Infections). demonstrated in studies on the donor pool. The amount of research
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and resulting publications on this recombinant laboratory-generated
virus were simply another lesson in caution that is required prior to
CHIKUNGUNYA VIRUS claims of a viral agent being a human pathogen, or in this case, being
the result of recombinant contamination.
Chikungunya virus is another tropical arbovirus transmitted by Aedes
spp. mosquitoes. It is a togavirus of the alphavirus group and,
although first recognized in Africa has been notably responsible for Notably, French authorities responded to the outbreak in La Réunion
explosive outbreaks in the islands of the Indian Ocean and has most by halting local collection of red cells (providing for the island’s needs
recently spread to the Caribbean, where more than 1.7 million clini- by supplying blood from the French mainland) and by implementa-
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cal cases were reported from the end of 2013 to the middle of 2015, tion of limited NAT and the use of pathogen reduction for platelets.
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including RNA positivity in blood donors. Although there have Other precautions that have been used have been to strengthen
been no reported cases of transmission by transfusion, the similarity requirements of postdonation information from donors (a process
of early infection to that of dengue has resulted in significant concern. that is enhanced by the high [50%–80%] frequency of symptoms