Page 2045 - Hematology_ Basic Principles and Practice ( PDFDrive )

1816 Part XI Transfusion Medicine

elicitation of malaria risk history, residual risk remains because Babesiosis has been made a nationally notifiable infection in 2011
transfusion transmissions of P. falciparum, P. vivax, and P. ovale have and included in the nascent biovigilance network of the National
been reported 13, 27, and 7 years, respectively, after departure from Healthcare Safety Network, so more accurate measurements of
malarious areas. Because P. malariae infection can persist for more transfusion risk may become available in the future. In 2011–2013
than 70 years without symptoms, elimination of transfusion-induced up to 29 states reported a total of 3857 cases nationally of which 95%
malaria is a practical impossibility. At this time, licensed in vitro occurred in seven states in New England and the upper Midwest and
screening for at-risk donors using antibody tests, antigen detection, increased to 98.5% in nine states (adding New Hampshire and Maine)
or NAT are unavailable in the United States. It is not clear that the (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6127a2.htm).
limited commercial potential of assays to be used on a relatively small Transfusion-transmission risk estimates in endemic states have
fraction of donors will justify the investment required to pass the occurred with the advent of investigational testing and are about 1
stringent regulatory requirements of a blood donor screening assay. per 18,000 red cell units transfused in the highly endemic states of
Donor deferral guidelines have been modified in 2014 to reduce the New England to an overall risk of approximately 1 per 100,000 units
loss of more than 60,000 potential donors with travel to areas of throughout the all nine endemic states mentioned (including New
Mexico where the malaria risk is minimal. 67 Hampshire and Maine, where an increasing number of transfusion-
related cases have been reported).
Febrile patients must be queried for a transfusion history and
Babesiosis babesiosis considered when transfusion has occurred. Diagnostic
laboratory evaluation includes blood smear examination, which
Babesia species that infect humans include Babesia microti, Babesia requires differentiation of Babesia sp. from Plasmodium infections.
duncani (previously WA1 type), Babesia divergens (limited primarily Tetrad or “Maltese cross” forms are diagnostic for Babesia but occur
to Europe), B. divergens–like (MO1 and EU1), and Babesia venato- infrequently. Diagnostic testing most frequently involves indirect IFA
rum. B. microti, an intraerythrocytic protozoan, causes most human testing for identifying persons with low-level parasitemia such as
infections. The white-footed mouse, Peromyscus leucopus, serves as the patients with chronic infections but remains positive for up to 5 years
reservoir and the deer or black-legged tick, I. scapularis (also the after resolution or cure of babesiosis. PCR testing is more sensitive
vector of Lyme borreliosis and HGA), as the vector. Transmission for detecting acute infections before seroconversion.
follows bites from infected ticks, primarily nymphs, from May In the absence of an FDA-licensed test, mitigation of transfusion
through early September. The defined transmission period has less transmission involves deferral of potential donors with a history of
relevance for transfusion transmission because asymptomatic blood Babesia infection. Questioning donors about tick exposure or tick
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donors can be infected chronically. Most cases occur in Massachu- bite has no predictive value as a donor-screening question. Investiga-
setts and its coastal islands, Rhode Island, Connecticut, New York, tional testing most widely uses IFA and PCR to screen donations.
New Jersey, Wisconsin, and Minnesota; these states are considered One US blood center’s screening program screens red cell units
the seven endemic states. This geographic range has expanded intended for immunosuppressed patients considered at highest risk
recently, attributed to expansion of white-tailed deer, Odocoileus for Babesia infection complications such as neonates, pediatric
virginianus, populations. Although not a competent host, deer patients with sickle cell disease, and pediatric oncology patients.
provide a blood meal and transportation for adult ticks to new areas. However, when cases of transfusion-transmitted babesiosis are care-
The vast majority of both vectorial and transfusion-associated fully studied, such groups only represent about half of those who have
Babesia cases involve B. microti. B. duncani infections include those developed transfusion-transmitted babesiosis. The same investiga-
previously designated WA1. B. divergens cases occur predominantly tional assays (IFA and PCR) are being used together by another
in Europe. The incubation period varies from 1 to 9 weeks. The system in highly endemic regions for screening of red cells units.
severity of illness associated with Babesia infections relates more to Retrospective studies have demonstrated the feasibility and suitable
the infected individual’s immune status than the Babesia species. The performance characteristics of the combination of these tests, yielding
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very young, older adults, persons who have had a splenectomy, and a combined specificity of 99.8% and demonstrating an absence of
those with hereditary hemolytic disorders are at greatest risk for transfusion transmission by screened units. Donor prevalence in
morbidity and mortality. Approximately one-third of infected subjects endemic areas is 0.3%. Currently this program only screens enough
remain asymptomatic, and parasitemia may persist for more than 2 units to supply those hospitals requesting babesia-screened blood. An
years. Typical symptoms resemble malaria and include fever, head- attractive alternative to testing is the eventual development of red cell
ache, chills, sweats, and arthralgia, myalgia, malaise, nausea, diarrhea, or whole blood pathogen-reduction technologies.
and hemolytic anemia. Parasitemia levels vary from 1% to 2% in
otherwise healthy hosts to 85% in immunocompromised and asplenic
patients. Case fatality rates approximate 5%. Leishmaniasis
Case reports of transfusion-associated Babesia infections include
red cell units stored for up to 42 days. Babesia transmission has been Phlebotomine (Old World) and Lutzomyia (New World) sand-fly
reported following transfusion of cryopreserved red cells, and four bites transmit Leishmania infections to humans in most of the tropi-
cases involve whole blood–derived platelet transfusions presumably cal and subtropical world. Trypanosomatidae of various species cause
contaminated with red cells. At least 159 transfusion-associated B. visceral infection also known as kala-azar (L. donovani, L. infantum,
microti cases have occurred, primarily in endemic regions, but cases and others). Additional species are involved in cutaneous and muco-
in nonendemic states reflect the interstate movement of both blood cutaneous infections (L. tropica, L. major, L. mexicana, L. braziliensis,
components and blood donors and highlight the high index of sus- and others given a variety of local names). In addition, transplacental,
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picion required to recognize cases. More than three-quarters of the sexual, and transfusion transmissions occur. The promastigote form
reports occurred during the past decade. The all-cause mortality rate of the parasite resides in the gastrointestinal tract of sand flies and is
approaches 19%. Babesia represented the highest number of reported inoculated into humans through a skin bite. In humans, promasti-
transfusion-related fatalities to the FDA from any single microbial gotes are phagocytosed by monocytes, where they transform into
infection in the periods of 2008–2012 and again in 2010–2014 amastigotes that reproduce and reside in macrophages and the reticu-
including 8 of 21 (38%) and 4 of 15 (27%), respectively. The loendothelial system. Organisms in monocytes and free amastigotes
total number of transfusion-related fatalities in these periods was are released during refrigerated storage, transform back into extracel-
198 and 176, respectively (www.fda.gov/BiologicsBloodVaccines/ lular promastigotes, and mediate transfusion transmission. L. tropica
SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/). also survives in monocytes contained in frozen red cell preparations
There are three reports of transfusion-transmission involving B. and in platelet concentrates stored at room temperature. At least 10
duncani, and single cases have been reported from Japan (B. microti– cases of transfusion-associated leishmaniasis attributed to L donovani
like) and Germany. have been reported in endemic areas, mostly in young children or