Transusion Transmitted Infections Flashcards
When did we introduce hepatitis E testing?
Testing introduced in January 2016
What is Hepatitis E
A small, nonenveloped, single-stranded RNA virus of the family Hepeviridae, a Hepevirus
There are 4 main strains HEV1-4
Talk about the four different strains of hepatitis E virus
HEV1 and HEV 2 infections in developing countries -> waterborn infection
HEV3 and 4 infections endemic in the developing world - zoonotic infections, under reported, many cases subclinical
Talk about the prevalence of HEV
Prevalence of 1:5000 donors approximately
HEV1 and 2 causes 3.4 million sympotomatic cases nicluding 70,000 deaths and 3, 000 stillbirths
Significant proportion of symptomatic cases are misdiagnosed or unrecognised especially with HEV3 and HEV4
What was originally thought about hep e
it was thought to originally be due to alcoholism i.e. alcoholic cirhhosis
What is the main zoonotic source of Hepatitis E
Pigs
What are some HEV1 and 2 endemic areas
China
India
Rural Malasia
What are the main sources of hepatitis E
Human hosts, certain animal species including pigs and wild boar
There is evidence of zoonotic transmission via the food-borne route
Consumption of uncooked meat including pig, wild-boar, deer etc
Elevated seroprevalence in pig farmers, abattoir workers and veterinarians
Who do we see chronic hepatitis E infections in?
Immuno-compromised patients
Solid-organ transplant recipients
Patients with haematological disease
HIV infection with low CD4 cell counts <100/mm^3
How does hepatitis E manifest in the immuno-compromised?
Rapid progression of liver fibrosis, chronic hepatitis after 15 months, cirrhosis E after 3 years
Extra-hepatic manifestations including neurological complications
When did we become concerned with hepatitis E
We didnt think it was an infectious virus so we didnt really bother with it
We only started after two studies carried out in the UK and US revealed that between 3 and 13% of suspected drug-induced liver injury was in fact HEV3 infection
After this Ireland was quick to develop an assay for HEV -> we have a large pork industry and large prevalence so we didnt want to be cought with this as we had been HCV
What is HTLV 1 and 2
Oncogenic viruses causative of adult T-Cell leukaemia and lymphoma (in chronic)
They may also cause a tropical spastic paraparesis
What is tropical spastic paraparesis?
A progressive degeneration of spinal cord neurones
How is HTLV transmissed
HTLV1 is transmitted by cellular blood components but not by cell free
Both 1 and 2 are transmitted by sexual contact, needles and breast milk
NB: blood storage decreases risk
What is the incubation period and seroprevalence of HTLV 1 and 2
30-90 days incubation
Seroconversion and possible disease up to 40 years after infection
IgM first produced then IgG
20 million people are infected worldwide, 3-8 million are in Africa
In the US prevalence of 0.016 percent of donors have it
Remains in the body for life, once in your system it can reactivate whenever immunosuppressed etc
When did we start screening for HTLV
Screening donors since 1996
But weve only had 4 HTLV donors in 22 years
What is cytomegalovirus
Herpes virus 5
It usually causes an asymptomatic infection which resolves on its own and is replaced by anti-CMV antibody
thus the Ab is a marker for infection
Many donors and patients are therefore exposed to the virus and only the immunosuppressed are of concern
Talk about the seroprevalence of CMV
26% of Irish donors - low compared to other -> can be up to 90% in certain countries
-> 29% in females, 24% in males
Seroconversion rate was 1.55% -> i.e. donors tat were previously neg that are now pos
Prevalence is highest in over 60s
Talk abou CMV in the immunocompromised
Immunosuppressed or neonates get CMV- blood
Its a common cause of fatality in HIV
-> causes hepatitis like infection
-> terrible encephalitis and eventually death
-> historic cause of death though
antiviral medications may stop the replication of the virus but will not destroy it
What problems are associated with CMV
Virus can remain latent in healthy donors - donors arent excluded from donating
reactivation of virus upon transfusion in immunocompromised
Cellular blood components are the potential transmitters
Window period of 6-8 weeks
CMV DNA is present weeks to months before the antibody appears
Why do we still use CMV+ units?
This is because immunecompetent people cannot get CMV from LD blood -> it is considered CMV safe to give to healthy people
Who should be given CMV negative blood?
Intra-uterine foetuses
Exchange transfusion infants
Neonates up to 1 year
Bone marrow recipients
PBSC recipients
Other organ transplants
Seronegative pregnant mothers
HIV patients, not yet infected
Patients immunosuppressed in general
What is West Nile Virus, how is it transmitted
A mosqiuto botn virus carried by birds
Lipid enveloped RNA virus
Its not that dangerous but 1% of people get encephalitis
Transmitted from humans then to birds and from birds to other parts of america etc
Talk about the initial outbreak of WNV
Initial outbreak in USA in 1999
It used to be unheard of until the early 2000s where we had our first cases
There was first an outbreak in a NY blood bank
Transplanted organs gave 4 recipients WNV
>30 cases of transplant/transfusion cases
Incidence of 1.5 cases per 10000 donors are positive
Talk about the European outbreak of west nile virus
Outbreak occureed in Denmark
Associated with imported tires
Mosquitos on old tires were infected with virus
How do we test for WNV
Tested using PCR
How do we test for WNV?
tested using PCR
We used to just defer people from america but one it became a european disease we had to start testiing
What is the incubation period of WNV?
2-21 days post transfusion
How do we test for WNV?
Tested using PCR
What encephalitis viruses are we concerned with?
Concerned wiith flaviviruses such as:
- West Nile Virus
- Japanese Encephalitis
- St. Louis Encephalitis
- Murray Valley Encephalitis
What is significant about japanese encephalitis
It has a 33% fatality rate
How did we deal with the WNV outbreak
The WNV outbreak is a great example of a rapidly emergent agent but a succefful intervention
We were able to get WNV out of the blood bank system very quickly - we were on top of it very quickly
In 2002 USA had 23 transfused cases but in recent years we have had o
What kind of disease does WNV cause, comment on its mortality
80% of cases are asymptomatic
18-20% cause mild illness, fever, headache, malaise
1-2% cause encephalitis
In 2003 the CDC recorded 9862 cases in 46 states and 264 deaths
How do you remove WNV from a pack?
Low pH, high temperature and SD treatment
Hence why we use SD treated plasma and we test for WNV in summer moths so it wont be present in plasma or red cells
We dont do pathogen inactivation of platelets though
When do we test for WNV?
May to December testing
What three viruses are the future threat to TTI
St. Louis Encephalitis
Japanese Encephalitis
Dengue virus
Talk about Dengue virus
The most common insect spread virus in the world
Used to be killed by DTT pesticides in the 1950s however these caused a lot of childhood deformities so their use was stopped
Were now seeing a resergence in numbers -> 50x more cases in US from 1980 to 1999
Migration from south america into southern states has resulted in more serious infections etc
Comment on the prevalence and mortality of JEV
33% mortality
20-50,000 cases per year in china
Talk about SARS in transfusion
Both SARS and Covid arent transfusion related
Would have been a problem as we found covid in packs
Why are we concerned with flaviviruses
As their vectors, mosquitos are starting to move into Europe
Now were wondering if we need to srart viral inctivation
Talk about Ebstein Barr Virus
EB virus also known as HHV 4 is a herpes like C<V virus endemic
It causes infectious mononucleosis/glandular fever
90% of donors have antibodies against it which can coesxist with latent virus -> you can have it but never have an infection -> can become dormant and can flare up
Transfusion transmission is rare -> usually very sick if you have it
Questionnarie deferral
Talk about parvo virus
Small single stranded DNA non enveloped virus
It doesnt cause chronic infection and is resolved in 1-2 weeks
It dosnt cause serious infection, most people have had it and cleared it, most have antibodies against it
Causes fifth disease in children
One of the most commom reasons for IUT can cause aplasia and anaemia in unborn babies
Talk about Parvo virus in blood products
Rarely transmitted in blood products as donor or recipient will usually have antibodies against it
Since its a non-envloped virus its not affected by SD treatment
if you pool plasma and on unit is positive then the antibodies in al 999 others will subdue the singular positive
When was parvo virus first detected in blood products?
First detected while testing for HBsAg in Australia
-> P antigen receptor in cells
Talk about parvo in children
Causes fifth disease in children
Red rashed cheeks
Usually cleared in a couple of weeks
Talk about Parvo in pregnancy
In pregnancy it can effect erythrocyte progenitor cells and cause aplasia in the unborn
This causes a problematic anaemia
One of the most common causes of IUT
Risk of foetal loss is about 10% if infection occurs before week 20 of gestation
Talk about parvovirus B19
Non-envelope viruses
Resistant to chemical and physical inactivation
Targets red cell progenitors, replicates within them, causing a variety of haemolytic crises, especailly in the young
Talk about the prevalence of Parvo B19
High prevalence - up to 90% have had it, anti-B19
Many never know thy have it
Most of us clear it without any problems
How do we prevent parvo B19 being transmissed?
We rely on the fact that your not sick when you donate
But we dont test for it or do viral inactivation of plate;et etc
Assumption that antibodies in pooled plasma overpower etc
How does prion disease occur
Human tissue contains prion protein PrP
Natural cellular form PrPc or as a variant pathological form PrPsc (scrapie isoforms)
Both forms have identical amino acid sequence but differ in secondary structure
The pathological form is able to change other normal proteins to the abnormal aggregates that cause spongiform degeneration in the brain
When was prion disease first noted
discoved in tribes in papa new guinea
Cooru disease - Males would drink the ashes of those whove died -> caused similar disease to VcJD
This caused initial confusion as whatever was causing the disease wasnt destroyed through cremation
What are prions, how do they become diseased
Background/filler proteins in cells
They normally form globular structures -> which stuff can move around normally
They can develop into abnormal structure, beta sheets which form filaments
Thes filaments damage the cells
The cells then atrophy and die
Where did vcjd originate
Variant form of pions fund in sheep and deer -> known as scrapey as it caused these animals to start scraping the group before going mad
sprad to humans when cattle were fed sheep meat - mad cow disease -> disease didnt occur when humans ate the affected sheep but only when affected cow was eaten -> prions werent close enough to our prions
Takes like 2 years to develop symptoms
Evidence of familial spead - eating same food but not transfused
What does cjd stand for
Creutzfeldt-Jakob disease
How was CJD spread, how long to develop symptoms etc
Sporadic
Familial
Not transmitted by blood transfusion
Acquired:
- growth hormones, dura mater graphs, corneal grafts
- can take 60 years to develop symptoms
- can cause memory loss and confusion
Talk about vCJD in humans
Started with Bovine spongeform E
It then crossed the species barrier to cause vCJD in humans
It affects younger people
Peaked in 1996 last case reported in 2004 - releastically anyone living in UK during this time who had eaten beef will have prions
PrPsc has been found in tonsils, spleen, lymph nodes and appendix
Not everyone will develop the disease - certain muatations are more likely to develop cjD -> certain types tend to lend to switching
Mutation at 129
How do we test for vCJD?
There is no blood test available
We use a sickical amplification assay but this requires a tissue
No test in BT for it
Talk about the first transmissed vCJD case in the UK
1st patient was 62 years old -> he recieved 5 units in 2000
6.5 years later he became irritable and depressed
13 months later he died
One of his initial donors was aged 24 died 3 years 4months later of vCJD
There has been 4 cases in the UK of suspected transfusion related vCJD
How have we prevented vCJD
We initially thought it was in leucocytes but we were wrong -> it is only in 3%
Hence why we introduced LD
But now we know 68% of CJD is found in plasma
NB:Hence we introduced ligand filtered plasma which binds any prions
What has recent research on VJCD revealed?
New research looked at tonsils of people who had died and found that there was actally a high prevalence of the disease
However some people were more susceptible than others ie. wasnt the cause of death
=> its present in the community but its not causing infections - indicating vCJD carrier status
Only recently we allowed people who lived in the UK to donate again
What is the vjd filter called?
P-Capt filter
How does the P-Capt filter work
Use of affinity resin
Resin coated in ligands for prions
Red cells wont bind but prions will
This removes all detectable infectivity from plasma products
What technolog is incorporated into P-Capt filter
PRDT
Pathogen Removal and Diagnostic Technologies
Talk about bacterial contamination of products
Bacteria are usually prevented from growing due to antibacterial properties of blood
Complement attaches to bacteria and are phagocytosed by white cells during storage
However platelet contamination is common -> way more common then red cells
Autologous blood contamination can also occur
Can be endogenous or exogenous
What is one way of preventing bacterial contamination thats suggested but not recommended?
Adding antibiotics to blood
Currently how do we prevent bacterial contamintion
Clean the site of donation thoroughly
Divert first few mls of blood
Store blood at room temperature for 24 hours after donation as this allows wbcs to be active at 22 degrees and kill any bacteria that may be present
Store blood at 4 degrees to prevent growth
How frequent is bacterial transfusion transmitted infections?
There was 97 suspected bacterial TTI investigations reported to SHOT in 2018
Only one was a probable S. epidermidis
what is the rate of SAR to bacterial contamination of red cells?
1:500,000
What bacteria are most likely to contaminate products
Red cells: P. fluorescens (26.5%), Psuedomonas putida (4.1%), Yersinia enterocolitica (51%), treponema pallidum (4.1%)
Yersinia contaminated 51% -> grows well at 4 degrees, uses citrate as a source of energy and requires iron -> thus red cells are ideal growth medium
Psuedomonas is also capable of growing in cold temperatures
How would a contaminated blood pack look?
RC looks unhealthy very quickly
Blood will congeal
White spots in back etc
Talk about yersinia infected blood packs
Yersinia has caused fatal reactions
Live beacteria can survive in leucocytes
What bacteria most commonly infect platelets
Staphylococcus epidermidis (25%)
Salmonella cholerasuis (13.5%)
Serratia marescens (9.6%)
Stapylococcus aureus (5.8%)
Bacillus cereus (5.8%)
Streptococcus viridans group (3.5%)
Other species (36.5)
NB: staph, strep, serratia, flavobacteria
Talk about platelet contamination rates
Rate of SAR to bacterial contamination of platelets 1:5000
Due to storage at 22 degrees
How do we prevent platelet contamination
BacT for all platelets
Talk about malaria contamination of products
Any product that contains red cells can transmit malaria
Malaria can survive in stored blood 1 week and longer but then it dies in the pack
Talk abou the prevalence of malaria
300 million cases of infection per year
More than 1 million fatalities per year
Frequency of transmission of 0.2 per million in the US -> 3 cases per year -> especially in southern states
How do we test for malaria
ELISA testing as microscopy sens is poor
we also defer
What is chagas disease
Trypanosoma Cruzi
Endemic to Latin America
Used to be associated with mud huts but now endemic to urban areas
50-90% recover on their own with no sequelae -> no condition associated
Once infected an individual generaly remains infected for life
Talk about the prevalence of chagas disease
8 to 11 million people in Mexico, Central America and South America have Chagas disease, most of whom do not know they are infeced
its not an uncommon disease
Seen in USA an spain
Just hasnt been a problem yet in Ireland
Only transmissed in America
How do we avoid transmission of Chagas disease
We defer -> any one from south America
Never take blood from those from Bolivia where 68% of people are ELISA positive
125mls of Gentian/crystal vioelt can be added to packs
What are some examples of emerging infections?
HIV and vCJD -> previously unknown diseases that emerged
Inluenza - change in microorganism
WNV, Chik V, malaia, Q fever, Dengue fever -> change in habitat with organism spreading to new area
XMRV -> identification that disease is caused by infection
Mycobacterium TB -> an old infection thats re-emerging
Chronic fatigue syndrome -> ME -> lasts for years -> thought to be caused b certain viruses but we dont knoww which ones -> will probably have a test for this in the future
What are the two methods of heat inactivation of pathogens?
Dry heat at 80 degrees for 72 hours destroys HIV and hep
Pasteurisation also destroys these organisms
Give an example of a virus not destroyed by heat treatment
Non enveloped viruses arent destroyed such as Parvovirus B19
What does solvent detergent treatment involve?
Solvent = tri-(n-butyl) phosphate TNBP
Detergent = Triton X
What is the issue with SD treatment
Non-enveloped viruses are not inactivated
Its currently used on plasma and coagulation factors and fibrinogen but theres still problems
What is an alernative to SD treatment with TNBP?
Heating with n-heptane at 60 degrees for 20 hours
But this is also not effective on non-enveloped viruses
What is an alternaive to SD treatmenet?
Methylene Blue treatment
How does methylene blue treatment work?
MB is a virucidal agent with high affinity for viruses and nucleic acids
On exposure to light adjacent molecules are destroyed
Give two examples of MB treatment
Intercept or mirosol (vitamin B6)
What pathogen inactivation is being developed for rbcs?
s59 -> amotosalen
?????
Intercept is available for what two products
Platelets and plasma but we dont do this
How does Intercept work?
Works via covalent bond crosslinking
S-59 targets helican region of single-or double-stranded DNA or RNA
Intercalation
Crosslinking
Multiple crosslinks block strand separation and replication
What protozoa are potentially transmissible through blood?
Plasmodium species (malaria)
Trypanosoma cruzi (Chagas disease)
Toxoplasma gondii (toxoplasmosis)
Babesia (microti/divergens) (babesiosis)
Leishmania species (Leishmaniasis)
How do we prevent protozoal contamination of blood?
Mostly done by deferal -> no testing for these other than malaria
What test could potentially be included in he IBTS in the next few years
Lyme disease screnning especially in those from the west of Ireland
What are some issues with introducing a test in the IBTS
Screening test - sensitivity versus specificity
Confirmatory Tests
Mandatory testing or not
Donor counselling -> what do you do if positive
Acquisition of anti-viral Ig
Viral inactivation procedures
Surveillance
Donor look backs -> when you introduce a test are you going to go back and re test old samples etc
