Page 2040 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 120 Transfusion-Transmitted Diseases 1811

mL. Patients at risk for persistent infection include those receiving 2002, a model suggesting a significant risk for WNV infection in
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chemotherapy and immunosuppression, organ transplant recipients, blood donors was published, and then four recipients of organ
and those with HIV. Infection in these groups tends to respond allografts from a single donor developed neuroinvasive WNV infec-
favorably to intravenous immunoglobulin infusions. tion. Infection of the organ donor was traced to donor blood trans-
B19 virus–impaired erythropoiesis appears to be multifactorial. fused before death from trauma. Transfusion transmission was
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B19 viral nonstructural protein 1 (NS1) mediates apoptosis via an documented in 23 recipients in 2002 against a background of 2946
11-kDa protein that perturbs signal transduction and induces apop- cases of WNV-meningoencephalitis (WNME). These events pro-
tosis. B19 viral DNA activates Toll-like receptor 9 inhibiting cell voked a multidisciplinary effort, successfully engaging the blood
growth and is toxic for infected cells. community, the manufacturers of blood donor–screening NAT
Blood and plasma-derivative transmission involves donations platforms, and public health officials and regulators to develop and
during the transient 1- to 2-week high-titer viremic period. The deploy, under an investigational new drug (IND) exemption, high-
prevalence of B19 viremia has been reported as 0.003% to 0.84% in throughput screening tests in the 10 months before the 2003 trans-
blood and plasma donors. In a study involving more than 12,100 mission season began. WNV test implementation represents the
B19 DNA–tested blood donations, given to surgical patients with a benchmark for responsiveness to a serious emerging transfusion-
78% pretransfusion B19 IgG seroprevalence, no B19 transmissions transmitted infection in the United States. 37,38
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occurred from transfusions containing less than 10 IU per mL. In 2003 2946 WNME were reported and 714 healthy blood
Hence most blood transfusion recipients are believed to be at low risk donors tested WNV RNA positive. In 2004 case reports declined in
for an infectious exposure. However, careful studies in Japan have the Northeast but extended westward into Arizona and Southern
demonstrated some transmissions from components with compara- California. In 2005 more than 1300 WNME cases were reported,
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tively low viral loads of around 10 IU per mL). 32,33 with approximately 25% occurring in California, relatively high
By contrast, recipients of plasma-derived products made from activity in South Dakota, Nebraska, Louisiana, and Illinois, and low
manufacturing pools of thousands of donations have a significant risk activity in the Northeast. In 2006 over 400 WNV RNA-positive
because the virus survives partitioning, ethanol fractionation, and blood donors were identified. Subsequently WNV activity was
other antiinfective measures applied to derivatives, and a single high- reported in Washington State for the first time, and high rates of
titer viremic donation can overcome the neutralizing activity of infection were noted in Idaho, California, Nebraska, Illinois, Louisi-
antibody in the pool. Recipients of coagulation concentrates are at ana, and the Dakotas. By 2011 fewer than 150 blood donors tested
highest risk, whereas those of intravenous immunoglobulin and positive with the highest frequencies in New York, Texas, Arizona,
albumin are less so based on cohort studies of prevalence. In one and California. The frequency of both WNME cases and RNA-
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report, 14% of viremic plasma donors had titers between 10 and 10 positive blood donors continues to vary by year and remain unpre-
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IU per mL, and one in 13,000 had titers greater than 10 . In obser- dictable. In total from 2002–2014, nearly 19,000 cases of WNME
vational studies, seroconversion occurred among recipients of plasma have been recorded with 4355 RNA-positive blood donors identified,
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derivatives with high titers, 10 to 10 IU per mL, treated with the which are related in magnitude by year. 39
solvent/detergent pathogen-reduction technique, suggesting that the WNV RNA is believed to appear 1 to 3 days after a bite of an
protective effect of neutralizing anti-B19 antibodies is exceeded in infected mosquito. In contrast to HIV and HCV, peak WNV levels
the presence of high viral loads (see box on Pathogen Reduction). are low (maximum observed 720,000 copies/mL, median 3500
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Since B19 is a nonenveloped virus, solvent/detergent pathogen- copies/mL compared with 10 to 10 copies for HIV and HCV). In
reduction treatment is ineffective in preventing B19 transmission in cohort studies of blood donors with positive WNV RNA tests, only
hemophilia patients receiving factor concentrates. Freeze-drying and 29% to 61% (retrospectively) describe any symptoms before or after
dry-heat treatment (80°C [176°F] for 72 hours) inactivate more than donation consistent with WNV infection, compared with 3% to 20%
4.7 logs B19, but this is not always sufficient to prevent transmission. of those not infected, demonstrating that the donor history is neither
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Currently, plasma derivative manufacturers use “in-process” NAT to sensitive nor specific enough to prevent transfusion transmission.
identify and remove source (from paid and volunteer donors) and Testing for antibodies also will not prevent transmission because IgM
recovered (from volunteer whole blood donors) plasma units with the antibodies appear a median of 14 days and IgG antibodies a median
objective to assure that manufacturing pools have parvovirus B19 of 17 days after infection and infectivity disappears rapidly with the
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DNA titers no greater than 10 IU per mL. Approximately 1 per development of antibody. These data explain the selection of WNV
10,000 plasma units is withheld from further processing. For volun- NAT for the testing strategy. To maximize efficiency, donation
teer whole blood donors, 1 per 6000 to 1 per 16,000 have titers samples are tested in minipools containing aliquots from 6 to 16
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greater than 10 IU per mL. Because individual whole-blood dona- donors, as is done for HCV, HBV, and HIV.
tions rarely cause recognized parvovirus infection, testing of single Despite minipool NAT, six transfusion-associated WNV cases
red cell units, platelets, or plasma for transfusion for B19 DNA is occurred during 2003. The implicated donors were antibody-negative
not currently required, although some advocate use of B19-tested and had low-level RNA that escaped detection in the minipool (i.e.,
blood components for those potentially at risk, including pregnant diluted) samples. At the end of 2003 an observation was made, even
women, neonates, those with reduced RBC survival, and immuno- before the documentation of these transfusion transmissions, that the
compromised patients. viral load in some donor samples is too low for detection by minipool
Of note, PARV4 and PARV5 have been detected in pooled plasma NAT. Consequently, strategies have been developed to switch from
derivative samples, but the clinical significance is not known; limited minipool-NAT to NAT on individual donation aliquots in areas
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clinical disease associations have been described. 34 experiencing high WNV activity. In total, following the 23 cases of
transfusion-transmitted WNV documented before the initiation of
donation NAT screening, an additional 14 have been reported, most
WEST NILE VIRUS related to donations having only low-levels of RNA; the last was in
2016. All implicated donations, except one in 2002, have been IgM
WNV is a mosquito-borne lipid-enveloped RNA virus in the Japanese negative. Blood centers must remain vigilant for appropriate conver-
encephalitis complex of the family Flaviviridae. Transmitted bird-to- sion to individual donation-NAT for this strategy to be effective.
bird primarily by culicine mosquito vectors, human infections occur
incidentally. The first cases were identified in the West Nile district
of Uganda in 1937. Subsequently, outbreaks occurred in the Middle DENGUE VIRUSES
East, South Africa, and Europe. The first North American cases
appeared in New York City in 1999. Starting in July 2000, WNV This mosquito-borne infection is of great interest as an emerging
cases spread to the Mid-Atlantic States. This was followed in the next pathogen with the potential to spread by transfusion. Forty percent
3 years by transcontinental dissemination. During the summer of of the world’s population lives in areas with risk for dengue, including