Thinking outside the BOX? HCV Antibodies to test or not to
test??
–If we tets should it be routine or
selective screening?
Q. 1A:- (anti‐Hb) testing for all or only in high risk cases :-Many do it as a
routine basis. What is the reason? There is a
standard guideline for "universal screening for any diseases
globally". But those who doesn’t tets this as a routinely their argument
is “Does this disease (anti‐Hb)
testing (HCV infection) can fulfill
all the criteria-of universal screening?”..
HCV –is the Test worthy?? If no specific low cost drug is
available with high degree of efficacy-then guideline says that there is no
rationality of universal screening. But those who are in favour of routine testing of (anti‐Hb) testing their argument is it’s to take extra precautions for spillage
and transmission to self and theatre/ L room staff.
The nuntold story of HCV:--What
is the CV of HCV:- What is the similarity with
HBV?? Ans:-Similar to HBV, fulminant lethal acute HCV infection can occur
rarely. More typically, patients do not clear the virus on their own, so
HCV develops into a chronic hepatitis and the patients become chronic carriers
of the virus. Because many HCV infections are asymptomatic in the acute
setting, the diagnosis is often made during the chronic phase. After exposure
to HCV, usually parenteral, Hepatitis C antigen is present initially, and then
anti‐HCV
develops in the weeks following infection. The specific diagnosis of HCV
infection requires serological and/or molecular‐based (NAT) assays. In rare instances, anti‐HCV may not develop; in these cases, a definitive diagnosis of HCV
requires molecular‐based
(NAT) assays. Spontaneous recovery from HCV infection occurs in 15–45% of
infected individuals with recovery in the higher range occurring in women given
anti‐D
immunoglobulin contaminated
with HCV. NAT of plasma intended for fractionation and of blood donations for
HCV RNA began in the late 1990s when methodologies became available. NAT for
HCV is now required in many countries. As anti‐HCV testing is also generally performed in
addition to NAT, infected units from donors with spontaneous recovery from HCV would also be
eliminated from the blood supply.
Q.1B:-
(anti‐Hb)
testing: _ Issues that lurks in our mind: The issues on HCV: My task is to make you refresh
on the knowledge and initiating a debate. HCV: Universal screening in India?? Or
selective screening?-opinion of house??
Q.2:-When to implement
selective screening??? Ans:-It is
definitely indicated in women with H/o exposure to blood products & all blood products, needle pricks, , IV drug
abusers, H/O STD, Homosexuals, Such high risk women should always be screened
prior to preg or in preg and if +ve adequate counseling be done
Q.3: Why worried about Virus??
Ans:-Infants may be affected if born to HbsAg or HCV Ab +ve mothers,
, Q.4:- What
about preoperative testing?? Ans:-Prior to any planned surgery this is a
must irrespective risk categorization-, major or minor. Should be tested for
(anti‐Hb)
testing, But
unfortunately many avoids such useful trots in our country for reason best
known to you.
CV of
HCV(contd) ::_Q.5:-: Is a drug available for cure of the disease or prevention
of vertical transmission?? Ans:-No effective drug is available which is
safe in preg?
Q.6: Why this virus is a bit little different in contrast to
HbsAg?? Ans: - The good
side of HCV is that in contrast to HBV fortunately the quantum of transmission
by sexual route is less than that of HbsAg. Infectivity rate is less in than
HbsAg.
Q7:-Fight goes
on!!! Selective screening or Universal screening for HCV. Ans:-So far as I am
concerned I feel Universal is better. We don’t know who will end up in CS or vacuum
/ Operative vaginal delivery / amniocentesis or CVS!! So the old idea of
selective screening does not hold well, Screened primarily during
pregnancy for the benefit of healthcare professionals to prevent accidental
injuries.
Q.8:-No treatment available for this virus:-But dilemma prevails:-Many are of opinion that HCV
testing in ANC is just to add an extra cost burden on the family, more so as no
management options is available if virus is present (tets is +ve), Sadly, till date
no vaccination is available either in preg period if virus tets is -ve-in preg
or post delivery.
CV of
HCV(contd) Q.9: Then why
testing: Own protection
like HIV +ve, HbsAg ve cases?? But the fact remains there is a real threat of
transmission to health care personal, we're achieving near 100% Institutional delivery-Normal/
instrumental. If +ve:-then advised universal standard precautions like HIV +ve,
HbsAg +ve even if the patient is non infective. Infectivity rate is less in
than HbsAg. Yet many of us are not doing routine screening as we do in case of
Hep B. But there is strong demand and also all corporate hospitals are doing it
routinely in elective cases and in few places for all antenatal cases.
CV of HCV(contd) Transfusion‐transmitted virus (TTV): Role of nucleic acid technology (NAT) testing?? Sadly,
infections were not uncommon in the early days... Hepatitis
B, hepatitis C and HIV transfusion‐transmitted infections still do occur in the
21st century. In recent years with advanced technologies and
improved donor screening, the risk of viral transfusion transmission has been
markedly reduced but not Zero. . Hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency
virus (HIV) have all shown marked reduction in transmission rates. However, the
newer technologies, including nucleic acid technology (NAT) testing, have
affected the residual rates differently for these virally transmitted diseases.
Zero risk, which has been the goal, has yet to be achieved.
Q.14: Is it possible to have false –ve tets of such three
transfusion related virus. Ans:-False negatives still persist, and
transmissions of these viruses still occur, albeit rarely. It is known that HBV
serological testing misses some infected units; likewise,
The story of HCV:: Silent killer in the form
of poor quality of life (hepatic
subfuncion for decades): Etiology of
common cause of Cirrhosis of Liver in
2019::_Not the alcohol, neither HBV infection persistence but now HCV is coming fast as an imp cause of
Hepatic failure as no antiviral agent neither vaccine is available, HCV induced
cirrhosis:-Q.15: Surprisingly, HBV NAT–negative units of labeled blood or blood
products have also been known to transmit the virus. Similarly, HIV miniboom
NAT–negative units have transmitted HIV, as recently as 2007; likely, these
transmissions would have been prevented with single‐unit NAT testing.
CV of
HCV(contd) Q.17: Then what -: What is the full proof??
Ans:
Use more new technologies, such as pathogen
inactivation (PI), will (ideally) eliminate these falsely test negative components,
regardless of the original testing method used for detecting the viruses.
Q. 19:-What is new in (anti‐Hb) testing?
Nucleic acid technology (NAT) in 1999:-The
first cases of transmission of a viral illness through blood transfusion were
reported in 1943 .Laboratory testing for viral transfusion‐transmitted viruses began in 1969 with testing
for hepatitis B surface antigen (HbsAg).
To reduce the risks of transmission of other viral illnesses (e.g. non‐A, non‐B viral hepatitis-now termed as Hep C),
introduction of almandine aminotransferase (ALT) testing and antibody to
hepatitis B core antigen (anti‐Hb)
testing began in the 1980s .More
specific disease serological testing (anti‐Hepatitis C virus antibody and HIV antigen and
antibody testing) followed in the 1980s–1990s markedly reducing the risk of these transfusion‐transmitted viruses (TTV).
Days [ 000 with a ‘window period’ (time from
infection to first reactive test) of 30–38 000 to 1 in 357 .
What is NAT?? : -- Nucleic acid technology (NAT) was promulgated
in 1999, Later there was further reduction in viral infections transmitted by
blood transfusion. Using serological methods, the risk of Hepatitis B virus
(HBV) is currently estimated to be 1 in 2823units of blood products in highest quality of
blood banks...
Q.22 What about of the current risk of transfusion‐transmitted Hepatitis C virus (HCV) infection
with NAT testing in place along with serologic testing?? It is estimated to
be 0·03–0·5 in 11million transfusions. Earlier it was million to 1 in
4·3.
Q.23: What about HIV
transmission?? For human
immunodeficiency virus (HIV), transmission risk using NAT and serologic testing is currently estimated to be
1 in 154,. Although quite
small today, the risks for transfusion transmission of HBV, HCV and HIV
persist. So, efforts to reduce the risks to zero continue.
Hepatitis B
million carriers of
HBV worldwide, the infection, as measured by HBV surface antigen (HBsAg)
positivity, remains endemically high in Africa, parts of Asia, the Middle East
and parts of South America, ranging from 8% to 15% of those populations. In low
prevalence areas, such as the United States, western and northern Europe,
Canada and parts of South America, the prevalence is estimated to be after the
discovery of widespread HBV infection became evident in 1963 with the
introduction of HbsAg testing, HBV was noted to have a high prevalence in
multiply transfused patients. However, it is now known that HBV is a very
common infection in the general population and that transfusion transmission
accounts for a minority of those infections. The prevalence of HBV differs by
geography. With over 300 <2% [ 1]. Acute infection with HBV, whether transmitted via
transfusion, intravenous drug use, perinatally or via sexual contact, may be
asymptomatic or cause clinical viral hepatitis with nonspecific constitutional
symptoms, including jaundice. Rarely, acute infections, including acute
infections from transfusion‐transmitted
HBV, can cause culminant liver failure and death [6].
After transmission of HBV, HBV DNA is the first marker to be
present in the blood. After viral replication in the liver, HBV viral load can
attain 108–1010 viral particles per milliliters of
serum [1]. Vermeil during the window period, however, is
exponentially lower; infectivity, incidentally, in also lower in the WP, most
likely related to antibodies (anti‐Hb and
anti‐HBs) formed after acute infection [7]. Testing for those infected with HBV historically involves
detection of HbsAg. HbsAg is present in the serum of infected individuals from
weeks to months after onset of infection and before symptoms begin. Some infected
individuals never test positive for HbsAg, but generally will produce an
antibody response to Hepatitis B core antigen (HbsAg): anti‐HBc. The fact that there are some false‐negative tests for HBsAg is the reason
for testing for anti‐HBc in
some countries. However, determination of HBsAg‐negative/anti‐HBc‐positive
distant HBV infections in individuals, such as healthy blood donors without a
history of hepatitis, testing falsely positive for anti‐HBc has
been a persistent problem for blood donor collection facilities. Generally, two
positive anti‐HBc tests
will result in permanent deferral from donating blood in the United States.
Recently, however, an algorithm for re‐entry of
these donors has been approved by the
US Food and Drug Administration (F.D.A.) [8].
Q.25:-NAT HBV DNA testing how effective?? How specific?? Unlike HCV and HIV testing, NAT HBV DNA
testing has not eliminated the necessity for serological testing for HBV
carrier donors. Where instituted, it was hoped that NAT testing for HBV would
1) reduce the window period for HBV, 2) identify low‐level carriers of HBV, 3) provide another mechanism for re‐entry of HBsAg false‐positive
donors and 4) ultimately replace
serologic000 [ al testing. NAT testing for HBV DNA has been implemented to a
variable extent in industrialized countries in Europe, North America, Asia,
Australia and Africa. Occult HBV infections (HBsAg negative, HBV NAT positive)
have been identified in all studies, in the range of 1/2000–1/1079. Japan was in the higher part of the range with the
difference possibly being related to the use of larger pools for their NAT
testing .
It has been shown that occult HBV infections can transmit the virus via blood
transfusions, but the infectivity is not 100% [10], and the level of viremia needed to infect has not been
determined in humans. However, in chimpanzees, it may be related to HBV
genotype [11]. NAT testing for HBV varies by country and varies by blood
centre within countries. HBV NAT testing is mandated in some countries [12]. Single‐unit NAT
testing can detect very low levels of HBV DNA (<IU/ml). With the availability of multiplex testing of small
pools of donor sera, more blood centres are implementing HBV NAT, along with
HCV and HIV. However, without single‐unit NAT
HBV DNA testing, the window period may not be shortened that much, compared to
the sensitive tests available today for HBsAg (like PRISM/Abbott Park, IL,
USA). This can be explained by the relatively
slower doubling time of HBV in the window period, resulting in a lower viral
load. Thus far the consensus is that NAT should be used in conjunction with
serological testing to identify low‐level
infections as well as infections that are at the ends of the
window periods of detection. There is no consensus either on whether single‐donor NAT or what size pool NAT is optimal, and it may
depend on the prevalence of HBV in the country. Additionally, HBV infectivity
may depend upon the immunosuppressive state of
the recipient of the blood component. 100
Infectious disease testing on donated blood is of great
importance in the reduction in risk for TT HBV infection. Other processes may
also reduce the risk of HBV from blood components. For example, optimization of
donor screening pre‐donation
is where most of the potential infected donors can be eliminated from the donor
pool. This screening process could and should be individualized by country and
even community. On the other end of the process, post‐donation, pathogen inactivation (PI) may be almost 100%
effective in eliminating the risk of HBV TTD from platelets and plasma in
countries where it has been implemented. The role of effective testing remains
critical, at this time, because of the lack of availability of PI for
red blood cell components and whole blood. Finally, the role of vaccination for
HBV also has the potential of almost completely eliminating the potential risk
of HBV by blood transfusion; the reduction in risk that widespread vaccination
can provide would be large in countries where the virus is endemic and access
to vaccinations is currently limited.
Hepatitis
C
After the discovery of hepatitis A virus (HAV) and HBV, a
significant number of patients testing negative for HAV and HBV and with
clinical presentation or laboratory evidence of viral hepatitis were
identified; these patients were presumed infected with what was initially
termed non‐A, non‐B (NANB) viral hepatitis.
HCN:- Most
of these NANB viral hepatitis patients had a history of intravenous drug use. The majority of patients with NANB
hepatitis later tested positive for HCV after testing for anti‐HCV became widespread in the 1990s. After testing was
available, it was also verified that blood transfusion was another significant
mode of transmission of HCV. The
infection is present worldwide with lower incidence rates in North America,
Australia and Europe (approximately 2%) and a higher rate in Egypt (>5%).
Once infected with HCV, the virus travels via the blood to
the liver where it replicates. Viremia occurs usually with few symptoms.
Similar to HBV, fulminant lethal acute HCV
infection can occur rarely. More typically, patients
do not clear the virus on their own, so HCV develops into a chronic hepatitis
and the patients become chronic carriers of the virus.
Because many HCV infections are asymptomatic in the acute
setting, the diagnosis is often made during the chronic phase. After exposure
to HCV, usually parenterally, Hepatitis C antigen is present initially, then
anti‐HCV develops in the weeks following
infection. The specific diagnosis of HCV infection requires serological and/or
molecular‐based
(NAT) assays. In rare instances, anti‐HCV may
not develop; in these cases, a
definitive diagnosis of HCV requires molecular‐based
(NAT) assays. Spontaneous recovery from HCV infection occurs in 15–45% of
infected individuals with recovery in the higher range occurring in women given
anti‐D immunoglobulin contaminated with HCV. NAT of plasma intended for fractionation and
of blood donations for HCV RNA began in the late 1990s when methodologies
became available. NAT for HCV is now required in many countries. As anti‐HCV testing is also generally performed in addition to NAT,
infected units from donors with spontaneous recovery from
HCV would also be eliminated from the blood supply.
years of age [ 000 from 2005 to 2008. The increase has been
primarily in Caucasian donors, especially in those donors over 50 000 to
2·98/100 Further reduction in transfusion‐transmitted
HCV, as well as any TTV, begins with improved donor screening. Recent data from
the American Red Cross have shown that HCV positivity in blood donors has increased from a rate of 1·96/1004]. Donor screening, i.e. focusing donor questions on risk
factors and on certain racial/age populations may aid in eliminating
potentially infected donors prior to donation. A major risk factor identified
in population screening is sharing of needles, especially in use of drugs, as
well as reuse of non‐sterilized
needles. Having had surgery in a developing country (with unknown exposure to
one of the blood) may be a risk factor as noted in a study from Mexico where
risk factors to HCV infection
was noted to be having had surgery or a prior blood transfusion [15].
It is known that there are presumed false‐positive HCV donors (anti‐HCV positive, HCV NAT negative). With further complex
methods evaluating for immunological response to HCV (not ready for routine
screening testing) [16-18], it is known that some of these donors are truly negative,
some of those negative because of seasonal viral infections [19] and some of the donors being positive having recovered
from the infection. However, it is not believed that these positive donations
are capable of transmitting HCV. Unsafe endoscopy practices at a US endoscopic
clinic may have exposed patients to viral infections [20]. In the absence of other risk factors, these patients
would not have been identified as higher risk for HCV in donor screening.
days [ With the use of anti‐HCV
antibody testing only, before HCV NAT testing, the risk of transfusion
transmission of HCV was reduced considerably. The window period for HCV was
approximately 701days [ ]. With the introduction of NAT, the window period
has been reduced to approximately 121, 21]. NAT HCV testing is mandated in many industrialized
countries. Combined antibody/antigen testing is available, but this combination
still is not as sensitive as NAT [22]. Generally, pooled NAT testing identifies virtually all
HCV‐infected units because of the high
levels of HCV RNA [23, 24]. In a South African study, single‐unit testing was performed, and
only one window period HCV NAT–positive unit was identified. It should be noted
that South Africa has a low incidence of HCV. In a German study, multipool NAT
was used (10–96 donations per pool), and only one documented case of
transfusion‐transmitted
HCV was missed with multipool NAT over a 5‐year
period. All three main genotypes were detected. Individual NAT testing may not
improve upon the multipool testing; however, as noted in a case study, also
from Germany, HCV was transmitted from a red cell unit
that was negative by individual NAT HCV testing [21].
NAT testing has markedly improved the detection of HCV in
donor units, as well as dramatically reduced the window period. However, the
risk persists, albeit low. PI has been shown to virtually reduce the risk of
HCV transmission to zero in vitro. This has great potential,
especially in light of the fact that, unlike HBV, an effective vaccine against
HCV is not available. PI is not currently universally available. PI would be of
great benefit in developed countries where it could potentially reduce testing
and the costs associated with testing. PI would be of greater utility in
developing countries where universal testing is not available; testing for many
infections would not be needed. The major limitation is that PI is only
available for plasma and platelet products, and not for red blood cells. As
noted in the just‐mentioned
case study of individual NAT failure to identify a low‐level case of infectious HCV, the component transmitting the
HCV was a red blood cell unit.
HIV
In June 1981, the landmark report of five cases of
Pneumocystis jiroveci (then P. carini) Pneumonia in otherwise healthy young men
heralded a new disease eventually named acquired immune deficiency syndrome
(AIDS) [25]. Shortly thereafter, AIDS was also reported in IV drug
users and a few patients with Haemophilia. In December 1982, AIDS was diagnosed
in a San Francisco baby who had received a platelet transfusion from a gay man
who died of AIDS [26]. The realization that we had a new infectious agent
(possibly a retrovirus) that had started to infiltrate the blood supply
mobilized all blood collection agencies throughout the Western world to do
everything possible to prevent potentially infected individuals from donating blood.
The advent of AIDS also mobilized the research community to identify the
causative agent and develop a test for it.
In the United States, the first donor deferral guidelines
were put in effect in January 1983. Those early efforts to indefinitely defer
prospective blood donors at risk and their sexual partners helped decrease the
incidence of transfusion‐associated AIDS by an estimated 90% [27]. The human immunodeficiency virus (HIV) (originally named
HTLV‐III) was described by Gallo and
Montagnier [28] in 1984, and the first ELISA antibody test was available
to blood banks in April, 1985. It is estimated that in the early 80s, the risk
of being infected by a blood transfusion was in the order of 1:100 in some US
cities, like San Francisco [27]. The focus, as well as the public perception, of
transfusion medicine was changed forever.
days, respectively. The HIV P‐24 antigen
test was introduced in March, 1996 with the hope of further reducing the window
period. days. Second and
third generation anti‐HIV tests
reduced the window to 33 and 22 million people are
infected. The first generation ELISA tests for anti‐HIV were able to detect the great majority of asymptomatic
HIV carriers, but the window period (time to seroconversion) in newly infected
individuals was approximately 56 million had
died of AIDS. The vast majority of AIDS cases were not because of transfusions,
however. In sub‐Saharan Africa alone 24 million were newly infected and 2·8 million
people were living with HIV world wide, that 4·1 In 2005, it was estimated by
the WHO that 38
Transmission of HIV involving three different donors
negative for both anti‐HIV and P‐24 antigen testing was documented in 1986 [29], 1987 [30] and 2007 [31months earlier tested positive with individual NAT, but had
tested negative on a 96 sample minipool. Follo day one. The second one involved
transmission of HIV by both platelets and RBCs. NAT on the undiluted donor
plasma was positive, but detection was inconsistent in the 1:16 and 1:24
dilutions (the usual pool sizes in the USA). On the third case, a retained
sample from a donation 4 day donation, but negative for the −11 days (double
donation) prior to becoming HIV P24 antigen positive. Subsequent NAT testing
was positive on the −4 ]. The first one was a frequent platelet donor who
infected three recipients 11 and 4days. Minipool NAT testing had already been
implemented in some European Countries (like Germany). wing this case,
individual donation (ID) NAT testing for HIV, HCV and HBV was implemented in
Denmark. Minipool NAT testing for HIV and HCV was introduced in US blood
collection centres in 1999, reducing the HIV window of infectivity to 11
Five cases of HIV transmission by donations negative by NAT
minipool testing have been reported in the United States from four donors [32, 33], one in Germany [5] and one in France [34]. In working up these transmissions in detail, there are
several common findings: The viral load was too low to be detected by pooled
testing which generally requires >copies/ml. By look back, it was determined
that these donors’ seroconversions were recent, thus explaining the low viral
load. More important, further questioning of the involved donors revealed risk
factors, specifically recent male to male sexual contact, that were denied in
the original screening interview. Retesting of stored donor samples with ID NAT
was reactive in the cases where it was performed. 90
The importance of viral load is further illustrated by a
report by Ferreira and Nel [35copies/ml. days after collection; and fresh frozen plasma,
originally sent for fractionation but retrieved for further testing. The viral
load was estimated to be only 12 copies/ml. The sample tested negative for anti‐HIV and HIV p‐24
antigen. It tested positive, however, by NAT. The assay used has a sensitivity
between 16·7 and 25 days after
collection to a 20‐year‐old patient; platelets, transfused as part of a pool to a 12‐year old patient 5 ]. In January 2003,
a 52‐year‐old male tested HIV antibody positive on his 55th blood donation
to the South African National Blood Service. Look back on his earlier, HIV‐negative donation from October 2002 showed that three components
were made from it: RBCs, transfused 12
In January 2003, the recipient of the platelet pool tested
positive for HIV antibody and HIV p‐24
antigen. Phylogenetic analysis of donor and recipient samples confirms the
transmission from donor to recipient. The recipient of the red cells was tested
for HIV antibody in March 2003 and found to be negative. Again in July 2003, he
remained negative for HIV antibody, and NAT
for RNA, the same test found positive in the platelet recipient.
000. Further analysis of the data revealed some disturbing
trends: While in the years 2005/2006, 67 incident HIV positive tests (both NAT
and serology) were found, in the years 2007/2008 there were 92, with an
increase of 25 cases. The number of 16‐ to 19‐year‐old males
in both groups went from 6 to 21, a statistically significant increase ( 060 million donations tested, mostly pools of 16, there
were 32 positive HIV NAT yield samples with an incidence of 1:2 years
experience (1999–2008) after NAT minipool testing was implemented revealed the
following: Of 66 In the United States, American Red Cross’ 10P <0·01).
A preponderance of non‐Caucasian
donors was also noted [ 4]. These demographics parallel the incidence of HIV in the
community. While there was no suggestion of test seeking behaviour when
analysing the US data, a 2006 Brazilian study showed that donors still use the
blood donation process to obtain HIV testing [36]. These finding underscore the importance of the initial
donor history questionnaire, along with effective donor education, to ensure
its veracity.
ID NAT testing is out of reach, as is pooled NAT testing, in
many countries such as many in sub‐Saharan
Africa, where the incidence of HIV in the general population is
expressed in double % digits. To significantly improve the safety of transfused
blood, new technologies, such as PI, must be added to the already extensive
battery of strategies [37]. Such systems have proven successful in preventing viral
transmission when plasma and platelet components are treated [38]. They have been implemented in several European and Middle
East countries, and FDA approval is being sought in the United States. So far,
there is no available way to apply PI methods to red cells. The cost of such
intervention has yet to be determined, but it will be undoubtedly quite high
for the marginal increase in safety from HIV, HBV and HCV; but it may be
worthwhile for emerging transfusion transmissible infections, especially for
those agents for which we do not have effective tests or means to decrease
their risks.
Less common viruses
Rarely, other identified viral infections have caused
transfusion‐transmitted
infections. HAV is a food‐borne
illness that generally causes an acute clinical picture. As virtually all HAV
infections are symptomatic, potential
infectious donors would be eliminated by blood donor screening. There have been
documented cases of transfusion‐transmitted
HAV [1], including remote cases involving transmission via
contaminated factor VIII. HAV is not inactivated by solvent/detergent
treatment, but HAV vaccines are available. Hepatitis E virus (HEV) infection,
like HAV, is another enterovirus generally caused by fecally contaminated
water. The presentation of HEV infection is similar to HAV, but subclinical
infections are reported. Transfusion‐transmitted
HEV is rare, but has been reported. Antibody testing for HEV infection is
generally used to test for infection, but PCR testing is available.
A recent study from Japan showed the prevalence of anti‐HEV in qualified blood donors to be 3·4% [39], slightly higher than that reported in the United States
and Europe [1]. Like HAV, solvent‐detergent
treatment is not effective. Theoretically, PI would inactivate HEV as well as
HAV.
Conclusion
million for HIV. For maximum reduction in risk, testing of
units may not be able to reduce the rates of infection further. The best
opportunity for near zero risk is treatment of the blood components directly,
such as with PI. Although not approved worldwide, this technology has been
shown to reduce the rate to near zero with the potential of eliminating
extensive testing of all units [ 000 for HBV to 1 in 2 Careful donor screening
has been shown to eliminate the vast majority of HBV, HCV and HIV transfusion‐transmitted viral infections over the past four decades.
With viral specific antigen and antibody testing, viral‐transmitted infections have been reduced another log. With NAT testing over the past
decade, the risk of transmitting these infections through transfusion has been
reduced further in the range of 1 in 30040]. PI has not been fully adopted and needs further
investigation into the quantifying of pathogen reduction and toxicity. It has
been suggested that, in addition to infectious disease testing which has
reduced window period and established infections, PI could reduce transfusion‐transmitted viral infections by reducing pre‐NAT window period and occult
infections [41]. Clinical studies proving this have not yet been
performed.
As PI does not rely on specific disease testing, it allows
elimination of risk for yet unknown emerging infections. Furthermore, PI has
been shown not to affect protein composition or clotting capacity [42]. A major limitation on this technology, however, is that
is not available for use in red blood cells, although it has been suggested
that treatment of whole blood before fractionation could assist in resolving
this issue [43-45]. The challenge persists to develop a method capable of
achieving the near zero risk of TTV from red blood cells. Careful donor
selection remains the best way to prevent TTV before the unit is even collected
and tested.
References
The Society for Maternal-Fetal Medicine (SMFM) has issued
guidelines for screening and management of Hepatitis C infection in pregnancy.
Prevalence of HCV (Earlier teemed as NONE A, Non B
hepatitis):-:-It is estimated that on average nearly 1-2.5% of pregnant
women in US are infected with the virus and the risk of vertical transmission
is 5%.
The recommendations of “The Society for Maternal-Fetal
Medicine (SMFM”) are:
Why all of us need to brush
up our knowledge on Hepatitis C virus? Tips & Tricks on the virus:
Hepatitis C:-1) firstly It is a RNA virus, & surprisingly this virus is the
commonest cause of Post transfusion hepatitis!!! - . 2) set principles for
“population based screening”:-do not apply to this particular virus as such
screening tests are a) not cost effective b) serological tests are not highly
sensitive, & highly specific but HCV RNA PCR is considered as most
effective, c) no acceptable treatment course if diagnosed to be affected, though
for the rich men & women α-interferon, & Ribavirin is reasonably
effective for coupe of yrs (these are not possibly recommended in pregnancy
period). 3) No recognized drug protocol as to “how best to prevent transmission
to partner”., “partners treatment-though there is ongoing debate whether this
virus is at all transmitted by sexual intercourse or not.-most believe that the
rate of transmission is of little significance.
Then to summarize if one do
not follow routine screening then Who must be screened irrespective of her financial
constraints ? Who are at risk of acquiring
HCV infection?? It is indicated in women with H/o exposure to blood products
&all blood products should be tested for HCV. Only for I. V. Drug
abusers, patients &staff involved in dialysis programmers, pts with HIV
/HBV infection, partners of pts with HIV/HBV/HCV , with h/o body piercing
/tattooing, pts with unexplained elevated transaminases, in if from donors,
recipients of organ transplants. No intervention can be done to prevent mother
to child transmission. Hep Virus C: - The good news is that a) transmission to
partner is life long relationship is < 5%.-so why barriers?? It is expected
after one person is affected (mostly by transfusions) will live hopefully a
health life for about 20-30 yrs of symptom free active life.
Dr Nidhi Goel: Listen
to the bad news on HCV: - : - 1)
Significant risk of (60-70%) OF DEVELOPING Char infection-body therefore poorly
clear the virus and 20% of such Char carriers develop cirrhosis liver by 10-25
yrs time.2) the prevalence in India is about 1% (I am not very sure about current
statistics); COUPLE OF YEAR BACK the global burden was > 300 million!!
2) There is no proven
intervention to cut down vertical transmission-but the good news is that
“mother-to-child transmission” is only possible when viral load is > 104
copies per ml of serum!! This level is seldom achieved.
HCV prevalence slightly less than HbsAg. But much more than HIV in a study on blood donors in blood bank. he hepatitis C virus (HCV) infects some 170 million people worldwide--more than four times as many as HIV--and is causing rising rates of liver disease. Like HIV, it is a wily foe for researchers developing drugs and vaccines, because HCV also mutates rapidly, creating a swarm of different viruses in each infected person that can thwart antibodies easily. But progress is beginning to be made: Although to date no one has been able to grow HCV reliably in a laboratory culture of cells, on page 110, researchers describe a new system for culturing HCV's RNA. And a study on page107 offers one possible explanation for why some HCV strains are more resistant to interferon, the standard treatment for HCV, than others.
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Testing of individual blood donations for HCV RNA reduces
the residual risk of transfusion‐transmitted
HCV infection
First published: 24 April 2002
BACKGROUND: To allow cost‐effective RNA testing
with NAT techniques, the national authorities of several countries have planned
or already introduced tests of mixed specimens, that is, plasma pools.
STUDY DESIGN AND METHODS: High‐throughput extraction, amplification, and detection of HCV
RNA from individual blood donations were optimized and validated. The
feasibility of the method and the frequency of anti‐HCV‐negative, HCV
RNA‐positive donations were determined
in a prospective study of 27,745 allogeneic and 792 autologous individual
donations.
RESULTS: The 50‐ and 95‐percent detection limits of the method were determined at 44
IU per mL and 162 IU per mL, respectively (World Health Organization HCV
reference material).
When 201 HCV
RNA‐positive sera were taken as a
reference, the sensitivity was 97.5 percent. The assay specificity was
determined at 99.77 percent.
During a 20‐month period, two seronegative blood donors tested positive
in HCV PCR. The viral load of these donations was 6 × 106 and 3
× 107 copies per mL, respectively. Thus, the yield of HCV RNA
testing in this study was 7.63 per 100,000 screened donations (95% CI, 1.25‐22.07). In both PCR‐positive
donors, seroconversion was found in subsequent blood samples.
CONCLUSION: This study compares the feasibility of single‐donation HCV RNA screening, with the detection of a
relatively high percentage of window‐phase
donations, to data reported from groups using HCV RNA testing of plasma pools.
The relative yield of NAT of individual donations versus minipools should be
directly investigated in the near future.
...
The naked truth in
Blood Banks at night time in rural areas:-The virus is transmitted mostly by parenteral route
like HBV, less through sexual route.
Most infections, when probed revealed
in retrospect that infection was transmitted is by BLOD TR more so before 1995 & still
today in our country-.For instance in
Mouffasil (District level-Talks) Blood Banks where the screening of donated
blood is not rigorously screened for all the 6 common pathogens by Lab
personnel specially at night time..
We are undone at some emergent situations!! But what options
we have in cases of PPH?? We are undone. , But in myoma patients TAH we can
preoperatively improve Hob level née IV Fe therapy FCM etc thereby delaying
planned surgery. So far world prevalence is considered about 1% of world
population are affected by HCV. HBV is DNA but HCV is RNA virus, more vertical
transmission in HBV is not so much in HCV. Sexual TR of HCV is questionable,
but vertical transmission rate of HBV is more common in comparison to HCV Ab
titer is often remain unchanged after
the storm of HCV which is not so much with HBV. The prevalence of HBV infection
about 2-6% in adults as Char carriers where as in case of HCV is 1%only. For HCV it takes
about 10 yrs to have S/S of char hepatitis( anorexia, loss f wt diarrhea etc),
,it takes 20 yrs to develop cirrhosis as exemplified by USF and loss of venous
pulsation of Portal vein with dilated PV in spleen portal Doppler.
It takes about 30 yrs to develop
hepatocellar Ca. In those residual damages is much more with HCV than HBV. All
women who are at increased risk for Hepatitis C should get tested for anti-HCV
antibodies at their first prenatal visit. If the risk persists till later in
pregnancy or new risk factor arises, the screening should be repeated again.
Who are more prone to have infection?? According to American Liver
Foundation the risk of Hepatitis C is increased /may be: acquire
·
Shared needles to inject drugs or
straws to inhale them
·
Had tattoos or body piercings in an
unclean environment using unsterile equipment
·
Worked in a place where one can came in contact with infected blood or
needles, for example, healthcare workers
·
Received a blood transfusion or
organ transplant
·
Received a blood product for
clotting problems
·
Needed to have your blood filtered
by a machine (hem dialysis) for a long period of time because your kidneys
weren’t working
·
If someone is born to a mother with
HCV
·
Had unprotected sex with multiple
partners
·
Have or had a sexually transmitted
disease
·
Have HIV
What else to be screened?? A) ELISA test is
95% sensitive but HCV RNA virus is the most sensitive test and considered as
gold standard. All HCV positive pregnant women should be screened for other
sexually transmitted diseases (STDs) including HIV, syphilis, gonorrhea,
Chlamydia, and hepatitis B virus (HBV). In acute cases perinatal TR (vertical)
is 0-18%. . Immunoglobulin to neonate may be administered after birth 0.5 ml
and Rpt after 4weeks.After acute inn of HCV as high as 80% will develop Char
liver diseases. 35% will dev Cirrhosis & 5% will develop Hepatocellar Ca,
Transmission rate varies with HCV
RNA titers: - For instance if RNA titer is less than 104 copies per
ml3 then chance of transmission to foetus is almost Zero. By
contrast if titer is 106 than chance if vertical TR is about 36%!!!
) All patients with HCV, including pregnant women should be advised to refrain
from consuming alcohol-hepatotoxicity may be accelerated / augmented...
4) Is there any drug (effective
against HCV) antiviral agent available in India Direct-acting antiviral medications (DAA) like Ribavirin
& Interferon are contraindicated, therefore not to be used in pregnancy,
except in settings of clinical trials? The treatment should be initiated after
the delivery of the patient in the postpartum period.
5) If invasive prenatal testing is
requested than amniocentesis is preferred over chorionic villus sampling (CVS)
because of limited data on the risk of vertical transmission for CVS over
amniocentesis. Similarly scalp b monitoring in labour and prolonged labour is
avoided... Mode of delivery does not affect the risk of transmission to foetus.
6) HCV infection solely is not
an indication for Cesarean section in absence of other obstetric indication.
7) Internal fetal monitoring,
prolonged rupture of membranes, and episiotomy should be avoided during labor
in HCV+ women
8) Risk of transmission to foetus
depends on maternal HCV RNA titers , If titer load is < 10 4 copies
per ml3 then minimal risk, But
if such figure is > 106 copies
per ml then neonatal transmission rate will be somewhere 36%!!!!But those
mothers who have HIV as well in such cases the rich of transition will be as
highs 19% irrespective of maternal RNA leas,
8) Positive HCV status is not a
contraindication for breast feeding.
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