Page 2035 - Hematology_ Basic Principles and Practice ( PDFDrive )

1806 Part XI Transfusion Medicine

a smaller, blinded study in the United States, 7.7% of donors were group O infections have been detected in the United States among
anti-HEV positive and only two of approximately 19,000 were RNA patients who were born, lived, or had sexual contact in endemic
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positive: recipient follow-up was not possible. A current broader regions of West and Central Africa. HIV-2 infected persons in the
concern is the finding that highly immunosuppressed patients (such United States are rare (less than 1% of HIV cases diagnosed annually)
as solid-organ transplant recipients) do develop chronic HEV infec- and have, for the most part, been infected after heterosexual transmis-
tions with long-term clinical sequelae, although these have not been sion from West African emigrants or residents. HIV-2 disease requires
specifically linked to infection via transfusion. a longer time to evolve and is less severe than that from HIV-1 There
have been five confirmed cases of HIV-2 infection among blood
donors in the United States.
Non–A-E Hepatitis In 2010 CDC estimated a total of 1.2 million people in the
United States 13 years or older are living with HIV infection, or 1
Cases of posttransfusion hepatitis only rarely if ever occur but there per 300 Americans, with over 10% of those unaware of their infec-
remains speculation that undiscovered hepatitis agents exist. A small tion. The highest number of new infections occurs in those 25 to 34
but consistent percentage of community-acquired hepatitis cases years old with about 50,000 new infections per year and about half
test negative for known hepatitis viruses, some cirrhosis is classified of those in African-American males, most of whom are MSM. MSM
as “cryptogenic,” an etiologic agent for hepatitis-associated aplastic continue to bear the greatest burden of HIV infection among all race
anemia eludes description, and the cause of some cases of acute and ethnic groups. Although MSM represent 4% of the US popula-
liver failure remains elusive. Several candidate agents have been tion, in 2010 MSM accounted for nearly 80% of all new HIV
proposed as non–A-E hepatitis viruses. None of these agents have infections in males and over 60% of all new HIV infections. Anti-
been shown to be pathogenic and are instead likely commensal and retroviral therapy for HIV treatment has improved dramatically since
nonpathogenic. the advent of combination therapy in 1996, even against multidrug
GBV-C (initially called hepatitis G virus) is a flavivirus with no resistant viruses. HIV-associated morbidity and mortality have sig-
confirmed disease association that is transmitted parenterally, includ- nificantly been reduced so that HIV treatment has converted HIV
ing frequently from transfusion. Of interest, GBV-C infection may infection to a chronic, versus a fatal disease.
delay progression of disease in those co-infected with HIV, which has Antibody testing of blood donors detects both HIV-1 and its
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led to studies of the interactions of these viruses. 16 variants and HIV-2. Antibody testing for HIV-1 began in 1985,
From 1% to 4% of US blood donors are viremic compared with with the addition of HIV-2 in 1992 (although HIV-1 tests before
15% to 20% of injection drug users who have detectable GBV-C that time detected most HIV-2 infections arising from over 60%
RNA. Infection occurs frequently among those infected with HCV sequence homology between the two viruses) and for HIV-1 group
and HIV. More people have antibodies against the E2 envelope O in 2006.
protein, in the absence of RNA, suggesting viral clearance. GBV-C Both serologic testing and NAT are performed on every blood
has not been shown to cause liver disease or other morbidity, and donation. First-generation antibody tests had a window period (time
hence there is no consideration of donor screening at this time. between infection and detection) of 45 days on average, but has
GBV-C is now referred to as a human pegivirus. A second human decreased significantly as tests became more sensitive leading to less
pegivirus has recently been described associated with HCV likely as than a 20-day window period. HIV-1 NAT, implemented in 1999
a result of an acute parenteral co-infection event, but again, has not (in duplex tests with HCV performed in pools of 6–16 donations)
been associated with hepatitis or any pathology. This virus was identi- detects RNA at a minimum concentration of approximately 5 copies
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fied by next generation sequencing. Likely other such commensal per milliliter (50% lower limit of detection) leaving about a 9-day
agents will continue to be identified by use of sophisticated molecular window period of risk in which an infected donor could donate and
techniques. not be detected by any test in current use. Rare genetic variants of
The torque teno virus (TTV) complex is a genetically diverse HIV may escape NAT detection when nucleotide sequence changes
group of nonenveloped DNA viruses in the family Circoviridae, affect NAT primer or probe binding sites, but the vast majority of
which was discovered in 1997. They cause viremia, and they are these infections will be detected serologically. Further, tests are now
transmitted by transfusion, but they cause no recognized liver disease designed to detect two or more separate sequences representing dif-
or other clinical illness. ferent viral regions. Currently, the frequency of confirmed-positive
SEN virus (SENV), another member of the Circoviridae, was test results for antibodies to HIV is 0.26 per 10,000 donations.
described using degenerate polymerase chain reaction (PCR) primers Almost all of these are also RNA-positive as the finding of an infected
while working with TTV. After an initial report associating SENV donor with low-level RNA levels is very rare (on the order of 2%).
variants in two patients with transfusion-associated non–A-E hepati- One donation per 900,000 is confirmed positive for RNA in the
tis, subsequent epidemiologic studies have failed to link SENV with absence of antibody (NAT yield). 11
clinical hepatitis. To interdict donations in the window period between exposure
and test positivity, each blood donor is asked at each donation about
exposure risks using questions developed in the early to mid-1980s,
RETROVIRAL INFECTION subsequent to the first reports of AIDS in hemophiliacs and transfu-
sion recipients. These initial interventions targeted blood donations
Human Immunodeficiency Virus from homosexually active men and injection drug users, substantially
reducing the transmission risk between 1983 and 1985. Five clusters
The HIVs type 1 and type 2 (HIV-1 and HIV-2) are retroviruses of of transfusion transmissions have been documented subsequent to
the family Retroviridae, genus Lentivirus, and the etiologic agents of the introduction of NAT, three before 2002 and one in 2008. 8,19 It
the acquired immunodeficiency syndrome (AIDS). They are envel- is of interest to note that in two cases, although the transfused plasma
oped viruses with two linear, positive-sense RNA molecules, 9.2 kb component transmitted HIV, the corresponding red cell component
in length. The predominant transmission mechanisms are sexual, did not. Modeling suggests a residual risk for HIV transmission
perinatal, and parenteral. An acute retroviral syndrome may be seen persists at approximately one transmission per 1.5 million donations,
around 21 days after infection, although this period may range from because NAT cannot detect HIV infection during the immunosilent
5 to 70 days and may involve fever, lymphadenopathy, and rash. If 9-day eclipse phase between infection and test reactivity. Processing
untreated, the incubation period for full-blown AIDS is measured in and quarantine procedural errors do not now appear to be a risk for
years. Molecular characterization divides HIV-1 into three groups: transmission of HIV via transfusion. Fourth-generation tests combine
group M (main), group O (outliers), and group N (non-M/O). HIV-1/2 antibody and HIV antigen detection and detect almost 90%
Group M subtype B infections predominate in the United States; of infections detected by NAT. Their role is expanding worldwide
only 3% of HIV-positive blood donors have non-B strains. Very rare even in countries that use HIV-1 NAT. In 2014 the CDC published