Transfusion Transmissible Infection

Neil Allen Elquinto, RMT

College of Medical Technology
Center for Medical & Allied Health Sciences
New Era University
• Common TTI’s
• WHO recommendations and
technical considerations for SAFE
BLOOD

Outline
• The current risks of TTH, today, are extremely small,
but are still due, primarily, to the hepatitis B virus
(HBV) and the hepatitis C virus (HCV), the latter,
formerly being known as "non-A, non-B hepatitis.―
• The risk of HBV being transmitted by a transfusion
today is in the order of 1 per 63,000 units of blood.
• For transfusion-transmitted HCV, the risk is in the
order of 1 in 125,000 units
Post Transfusion Hepatitis Holland , Vox Sang 1998;74 Suppl 2:135-41.

Transfusion Transmitted Hepatitis

 SPECTRUM of disease
• Assymptomatic
• Silent carriers
• Chronic hepatitis
• Cirrhosis
• incubation period - 6 to 24 weeks
• Liver cancer
• nausea, vomiting, diarrhea,
anorexia and headaches • Fulminant hepatitis
• Jaundice

Hepatitis B
WHO data :
350 million – estimated to be persistently infected with HBV,
wherein, large fraction is eastern Asia & sub-Saharan Africa
• Diagnosis is confirmed by demonstration in sera of
specific antigens and/or antibodies.
• Three clinical useful antigen-antibody systems
have been identified for hepatitis B:
• hepatitis B surface antigen (HBsAg) and antibody to
HBsAg (anti-HBs)
• antibody (anti-HBc IgM and anti-HBc IgG) to hepatitis
B core antigen (HBcAg)
• hepatitis B e antigen (HBeAg) and antibody to HBeAg
(anti-HBe)

Laboratory diagnostic tools

Hepatitis B
• ACUTE infection
• usually asymptomatic
• very rarely associated with life-threatening disease
• About 15–45% of infected persons spontaneously clear the virus
within 6 months of infection without any treatment.

• CHRONIC infection
• The remaining 55–85% of persons will develop chronic HCV
infection.
• Of those with chronic HCV infection, the risk of cirrhosis of the
liver is 15–30% within 20 years
WHO data

Hepatitis C
HCV infection is diagnosed in 2 steps:
• Screening for anti-HCV antibodies.
• If the test is positive for anti-HCV
antibodies, a nucleic acid test for HCV RNA
is needed to confirm chronic HCV infection.
-----------------------------------------------
• Liver biopsy – fibrosis & cirrhosis

Laboratory diagnosis of
Hepatitis C
• The clinical manifestations of transfusion
transmitted HIV are similar to those of HIV
infection acquired through other routes.
• An acute viral syndrome occurs in about 60% of
cases.
• Untreated, asymptomatic infection persists for
about 10 years before acquired immunodeficiency
syndrome (AIDS)-defining illness occurs, although
progression tends to be more rapid in older
individuals
Henry’s 22nd ed Ch 36
 • Another type of test checks
• HIV is most commonly for HIV antigen p24
diagnosed by testing
your blood or saliva for
antibodies to the virus. • Nucleic-acid-based tests
• To develop the amplify and detect one or
antibodies — usually more of several target
up to 12 weeks. sequences located in
specific HIV genes, such as
• can take up to six HIV-I GAG, HIV-II GAG,
months for an HIV HIV-env, or the HIV-pol
antibody test to become
positive.

Tests & Diagnosis

 • Although the symptoms of
• PRIMARY acute primary HIV infection may
be mild enough to go
HIV infection unnoticed, the amount of
virus in the bloodstream
(viral load) is particularly
flu-like illness within a high at this time.
month or two after the virus
enters the body • As a result, HIV infection
spreads more efficiently
during primary infection
than during the next stage
of infection
Mayo Clinic
• persistent swelling of • Typically lasts eight to
lymph nodes 10 years.
• NO specific signs and
symptoms. • A few people stay in
• HIV remains in the this stage even longer,
body, however, and in but others progress to
infected white blood more severe disease
cells. much sooner.

Clinical LATENT
infection
• Early Symptomatic HIV infection

• Progression to AIDS
• HIV infection progresses to AIDS
when your CD4 count dips below 200
• Viral Load
• Drug Resistance
• Non-nucleoside reverse transcriptase inhibitors
(NNRTIs) - disable a protein needed by HIV to make copies
of itself
• Nucleoside reverse transcriptase inhibitors (NRTIs) - are
faulty versions of building blocks that HIV needs to make
copies of itself
• Protease inhibitors (PIs) - disable protease, another
protein that HIV needs to make copies of itself.
• Entry or fusion inhibitors - block HIV's entry into CD4 cells.
• Integrase inhibitors - works by disabling integrase, a protein
that HIV uses to insert its genetic material into CD4 cells.

Classes of anti HIV drugs

•

Syphilis : T. pallidum
 Muscle aches, fever,
sore throat, swollen
lymph nodes

Syphilis : Secondary to Latent Phase

 • Neurosyphilis :
• meningovascular syphilis
• tabes dorsalis
• general paresis

Tertiary syphilis
 Nontreponemal Treponemal

measure antibodies that

measure Ab to cardiolipin.
specifically react with T.
• rapid plasma reagin pallidum
(RPR)
• fluorescent treponemal
• Venereal Disease antibody absorption test
Research Laboratory
• T. pallidum enzyme
(VDRL) tests.
immunoassay test

Serologic Tests for Syphilis

Species :

• Plasmodium falciparum
• Plasmodium vivax
• Plasmodium ovale
• Plasmodium knowlesi
• Plasmodium malariae

Malaria
Intrinsic Acquired

• inherited alterations • following repeated or

that reduce the prolonged exposure
susceptibility of red which stimulates a
cells partially protective
immune response.

Host resistance to Malaria

Several types of mutations affecting red cells are highly
prevalent in parts of the world where malaria is endemic and
are absent in other parts of the world.

The mutations fall into four broad classes.

• Point mutations in globin genes—sickle cell disease (HbS),
HbC disease (hemoglobinopathies)
• Mutations leading to globin deficiencies—α- and β-
thalassemia
• Mutations affecting red cell enzymes—glucose-6-
phosphate dehydrogenase (G6PD) deficiency
• Mutations causing red cell membrane defects—absence of
DARC (Duffy surface blood group), band 3, spectrin
Robbins Pathologic Basis of Disease
P. vivax enters red cells by binding to the Duffy blood
group antigen, and most of the population of West Africa
is not susceptible to infection by P. vivax because they do
not have the Duffy antigen.

The mechanisms of the protective effects of the other

three types of mutations are less well understood, but
likely involve a favorable shift in the balance between
the growth of intraerythrocytic parasites and their
clearance by host phagocytes.

Individuals living where Plasmodium is endemic often

gain partial immune-mediated resistance to malaria,
evidenced by reduced illness despite infection.
Robbins Pathologic Basis of Disease
 • Rapid Diagnostic test
(RDTs) kits to detect
antigens derived from
• malaria parasites

• Giemsa stained blood • Parasite nucleic acids

film are detected using
• This technique remains polymerase chain
the gold standard for reaction (PCR).
laboratory confirmation
of malaria.
CDC USA

Lab Diagnosis of Malaria

Human T Cell Lymphotropic Virus
• Most carriers are assymptomatic

• HTLV-I is causally
• Blood donors who are HTLV-II
associated with adult T positive have a higher incidence
cell lymphoma/leukemia of acute bronchitis, pneumonia,
and HTLV-associated bladder or kidney infection, and
myelopathy (HAM) arthritis
Hall, 1996; Manns, 1999
• HTLV-I–positive donors have a
higher incidence of bladder or
kidney infection and arthritis
Murphy, 2004).

Other TTDs
 Cytomegalovirus

• Approximately 50% of • In patients with cellular

blood donors are CMV immunodeficiency, CMV can
seropositive, although the cause pneumonitis, hepatitis,
estimated risk of retinitis, and multisystem
organ failure
transmission by a
seropositive transfusion
• Leukocyte-reduced blood
is about 1% components are as effective
Preiksaitis,1988 as seronegative components
in reducing the risk of CMV
transmission
Bowden, 1995

Other TTDs
Parvovirus B19

• The incidence of viremia

among blood donors is • Transfusion-transmitted
variable, with episodic parvovirus infection has
peaks, but it averages been implicated in
around 1 : 5000 causing chronic anemia
Hitzler, 2002
after bone marrow
transplantation and in
thalassemia

Zanella, 1995; Cohen, 1997

Other TTDs
 West Nile Virus
• Most acute WNV infections are asymptomatic, with a febrile illness
occurring in about 1 in 5 infections and neuroinvasive disease in about
1 in 150 infections (Petersen, 2002).
• In 2002, 23 confirmed cases of transfusion-transmitted WNV were
reported by the Centers for Disease Control and Prevention (Pealer,
2003).
• In areas of peak WNV activity in 2002, the estimated rate of viremia
among blood donors was 1.5 in 1000 (Biggerstaff, 2002)
• Donor screening for WNV by nucleic acid testing (NAT) was
implemented in July of 2003 in North America. Subsequently, rare
cases of WNV transmission by blood transfusion have been reported,
most likely due to the low viral copy number that escaped detection
(Macedo de Oliveira, 2004)..

Other TTDS
 Babesiosis
• About 40 cases of • Transmitted by ticks of the
transfusion-transmitted genus Ixodes.
babesiosis have been
• Many cases are
reported in the United
States, although it is
asymptomatic or mild
possible that transmission in • may be more severe in the
endemic areas may be as asplenic or
high as 1 in 1800 red cell immunosuppressed patient
units • The parasite is capable of
Cable, 2001; Lux, 2003 survival in refrigerated red
cells.

Other TTDs
 Chagas disease
• Seropositivity rates among • Since the FDA approval of a
blood donors have been donor screening EIA test,
estimated to be 1 : 25,000 more than1000 confirmed
nationally and as high as 1 : positive donors have been
detected in the United States
2000 in Los Angeles
AABB Chagas
Leiby, 2002; Centers Biovigilance Network,
for Disease Control 2010
and Prevention, 2006–
2007

Other TTDs
• national policy on blood screening
• national programme for blood screening – strategy &
algorithm that define the actual tests to be used in each
screening facility
• All whole blood and apheresis donations should be
screened for evidence of infection prior to the release

WHO Key Recommendations

• Screening of all blood donations should be mandatory for the
following infections and using the following markers:

HIV-1 and HIV-2: screening for either a combination of HIV

antigen-antibody or HIV antibodies
Hepatitis B: screening for hepatitis B surface antigen (HBsAg)
Hepatitis C: screening for either a combination of HCV
antigen antibody or HCV antibodies
Syphilis (Treponema pallidum): screening for specific
treponemal antibodies.

WHO Key Recommendations

• Screening of donations for other infections, such as those
causing malaria, Chagas disease or HTLV, should be
based on local epidemiological evidence

• Where feasible, blood screening should be consolidated

in strategically located facilities at national and/or
regional levels to achieve uniformity of standards,
increased safety and economies of scale

WHO Key Recommendations

• Adequate resources should be made available for the
consistent and reliable screening of blood donations for
transfusion-transmissible infections.
• There should be a national system for the evaluation,
selection and validation of all assays used for blood
screening.
• The minimum evaluated sensitivity and specificity levels of
all assays used for blood screening should be as high as
possible and preferably not less than 99.5%.

WHO Key Recommendations

• Quality-assured screening of all donations using serology
should be in place before screening strategies utilizing
nucleic acid testing are considered.
• There should be a national procurement policy and supply
system to ensure the quality and continuity of test kits,
reagents and other consumables required for the screening of
all donated blood.

WHO Key Recommendations

• Quality systems should be in place for all elements of the
blood screening programme, including standards,
training, documentation and assessment.
• There should be regulatory mechanisms for oversight of
the activities of blood transfusion services, including
blood screening.
• A sufficient number of qualified and trained staff should
be available for the blood screening programme.

WHO Key Recommendations

• Every facility in which screening is performed should have a
suitable infrastructure and quality system to perform effective
blood screening for transfusion-transmissible infections.
• All staff involved in blood screening should be trained to
perform their functions to nationally required standards.
• Specific indicators of performance of all assays should be
designated and monitored continuously to assure the
reliability of results.

WHO technical recommendations

• All test kits and reagents should be stored and transported
under appropriate controlled conditions.
• All blood screening tests should be performed in a quality-
assured manner following standardized procedures.
• A quarantine system should be in place for the physical
segregation of all unscreened donations and their blood
components until all required tests have been completed and
the suitability of donations for therapeutic use has been
determined.

WHO technical recommendations

• Only blood and blood components from donations that
are nonreactive in all screening tests for all defined
markers should be released for clinical or manufacturing
use.

• All reactive units should be removed from the

quarantined stock and stored separately and securely until
they are disposed of safely or kept for quality assurance
or research purposes, in accordance with national
policies.

WHO technical recommendations

 • Systems should be put in place to maintain the
confidentiality of test results.

• Confirmatory testing of reactive donations should be

undertaken for donor notification, counselling and
referral for treatment, deferral or recall for future
donation, and look-back on previous donations.

WHO technical recommendations