Download Infection

ESTABLISHED AND EMERGING
BLOOD-BORNE VIRUSES
Juraj Petrik, PhD
Head, Microbiology R&D, Scottish National Blood
Transfusion Service &
Honorary Senior Lecturer, University of Edinburgh
Bratislava, 12 March 2008
OUTLINE
Human pathogens
Blood borne viruses (BBV)
Established and emerging BBV:
characterization, epidemiology,
pathogenicity, treatment
Highly pathogenic global BBV
Highly pathogenic endemic BBV
BBV pathogenic for certain patient groups
Pathogen detection, blood screening and residual risk of transfusion
Burden of BBV infections:
global
individual
Human pathogens
1, 407 → 58 % zoonotic; 177 emerging or reemerging
Most zoonotic pathogens not transmissible or minimally transmissible
between humans. 25 % some person-to-person transmission.
Number
Considered emerging
Bacteria:
538
54 (10 %)
Fungi:
317
22 (7 %)
Protozoa:
57
14 (25 %)
Helminths:
287
10 (3 %)
Viruses:
208
77 (37 %)
More than 20 families, but Bunyaviridae, Flaviviridae,
Togaviridae, Reoviridae accounting for > 50 %
[MEJ Woolhouse, S Gowtage-Sequeria, Emerging Infection Diseases (Dec 2005)11:1842]
Reasons for accelerated appearance of infectious diseases
1 Urbanisation → high density population areas → poor social & hygienic conditions
2 Increasing international travel (~ 2.1 billion airline passengers in 2006)
3 Increased migration: economy, result of conflict, forced displacement
4 Increasing international trade → unintentional spread of pathogens, vectors..
5 Changes in climate and habitat
6 Iatrogenic spread of unknown pathogens
7 Emergence of mutants, resistant strains to available drugs
8 Changes in intervention policies (e.g. widespread insecticide use)
9 Vaccination coverage (detrimental effect of conflicts, lack of funding,
unsubstantiated rumours etc.)
Blood-borne viruses (BBV)
BBV: can be transmitted via blood, blood products, body fluids, cells, tissues, organs.
Established and emerging BBV: Established: well understood pathogenesis, transmission; available
diagnostic tests; routinely tested for (at least on a proportion of donations).
Emerging: limited knowledge; regional, if any, routine testing.
Highly pathogenic global BBV:
HBV
HIV
HCV
[HTLV I, II]
Highly pathogenic endemic BBV:
WNV → WNV
Dengue
Chikungunya
[HAV, HEV]
BBV pathogenic for certain patient groups:
CMV
B19 → B19
LCMV
[HHV 6,8]
[Enterovirus ?]
BBV with non- established disease association:
[Anelloviruses, HGV]
HBV - hepatitis B virus; HIV - human immunodeficiency virus; HCV - hepatitis C virus; HTLV - human
T-cell lymphotropic virus; WNV - West Nile virus; HAV, HEV - Hepatitis A, E virus; CMV - Cytomegalovirus; B19 - Parvovirus B19; LCMV - Lymphocytic choriomeningitis virus; HHV 6, 8 - Human herpesvirus
6, 8
Highly pathogenic global BBV
HBV, HIV, HCV, [HTLV I, II]
Typical blood-borne viruses
Blood - related transmission: main transmission route
Often life-long infection
High morbidity and mortality
High global burden of infections worldwide
Routinely screened for in blood donations
Low residual risk of transfusion
Hepatitis B virus (HBV): Virion and Genome
Virion:
ø42 nm; enveloped (Dane particle)
Genome:
partially dS DNA (- strand complete);
3.2 kb; 5’cohesive ends
4 overlapping orfs coding for:
Surface S
Core C
Polymerase P (DNA poly, RT, RNase H)
Transactivating X
Genotypes:
A-F
Replication:
1
2
3
4
DNA repaired to fully complementary , closed circle
4 RNAs synthesized
3.5 kb RNA reverse transcribed
One DNA species for DNA amplification, another for virion
HBV: Transmission, Prevalence, Infection
Transmission:
vertical - most prevalent worldwide
transfusion and other medical procedures
intravenous drug use
sexual
Prevalence:
One of the most prevalent viruses
350 - 400 million chronic carriers worldwide
Sub-Saharan Africa, most of Asia, Western Pacific
Amazon, Central, Eastern, Southern Europe
India, Middle East
Australia, N.Zealand, Northern & Western Europe,
Northern America
Infection:
8 – 10 % chronic inf.
2–7%
5%
<2 %
10 % children & 30-50 % adults: symptomatic
2 - 10 % chronic infection
15 – 20 % cirrhosis/Hepatocellular
carcinoma (HCC)
1 million deaths worldwide (acute & chronic hepatitis, HCC)
HBV: Infection (cont.) and Pathogenesis
Infection - continued
HBsAg
used as a general marker of infection
anti-HBc IgM
marker of acute infection
anti-HBcIgG
past or chronic infection
HBeAg
indicates active replication of virus and therefore infectiveness.
Anti-HBe
virus no longer replicating. However, the patient can still be
positive for HBsAg which is made by integrated HBV.
HBV-DNA
indicates active replication of the virus, more accurate than
HBeAg especially in cases of escape mutants.
Used mainly for monitoring response to therapy.
Pathogenesis:
Noncythopatic virus.
Most liver damage through immune, especially CTL responses, with contribution
from antigen-nonspecific inflammatory cells
Occult hepatitis B (after resolved acute hepatitis B, or asymptomatic HBV exposure):
Presence of HBV DNA in:
serum
cells of the immune system and/or hepatic tissue
Absence of serum HBsAg
Accumulating data due to the NAT detecting low levels of HBV DNA
HBV: Prevention and Treatment
Vaccine:
Available since 1982- subunit; later recombinant (yeast)
95 % effective in preventing chronic infection development
116 countries - routine immunisation programme
Routine vaccination of 0-18 year olds
Vaccination of risk groups of all ages
Treatment:
six drugs used for the treatment of persons with
chronic hepatitis B:
Adefovir dipivoxil
interferon alfa-2b
pegylated interferon alfa-2a
lamivudine
entecavir
telbivudine
Human immunodeficiency virus (HIV): Virion and genome
Lentivirus, Retroviridae
Virion:
100 - 120 nm; enveloped
Genome:
2 copies of non-covalently linked 9.4 kb RNA+
Genotypes: HIV-1: M (99.6 %), N, O
M
A, B, C, D, F, G, K - subtypes
E, I - CFR (circulating recombinant forms)
predominant: C: 47.2 %)
A and CRF02_AG: 27 %
B: 12.3 %
HIV-2:
subtypes A - G;
A (0.11 %) and B most
prevalent
Proteins:
gag, pol, env
regulatory:
vif, vpr, tat, rev, nef, Vpx(HIV-2), Vpu (HIV-1)
HIV: Transmission and prevalence
Transmission:
unprotected sex
contaminated needles
breast milk
from an infected mother to her baby at birth (20 -30 %)
blood, blood products - almost eliminated in developed countries
Prevalence:
WHO 2007 estimates:
33.2 million people living with HIV
over 60 % in sub-Saharan Africa
~ 15 % South East Asia
2.5 million new infections
2.1 million deaths
HIV: Infection and pathogenesis
Infection:
CD4
CCR5 (almost all individuals initially infected with CCR5-trophic virus;
32 aminoacid deletion homozygots protected)
CXCR4
Mannose-specific C-type lectin receptors such as DC-SIGN
(dendritic cells)
Huge reservoir of replicating virus (1010 infected cells in an average
patient)
Pathogenesis:
Slow destruction of T-cells, in particular central memory cells,
necessary for lifelong protection against viruses
1 direct viral killing of infected cells
2 increased rates of apoptosis in infected cells
3 killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that
recognize infected cells
HIV: Prevention and Treatment
Preventative vaccine remains elusive
23 approved drugs (USA, 2007)
8 NRTI (nucleoside or nucleotide reverse transcriptase inhibitors): Zidovudine,
Didanosine, Zalcitabine, Stavudine, lamivudine, Abacavir, Tenofovir,
Emtricitabine
3 NNRTI (non-nucleoside reverse transcriptase inhibitors): Nevirapine, Efavirenz,
Delavirdine
10 PI (protease inhibitors): Saquinavir, Indinavir, Rotonavir, Nelfinavir, Amprenavir,
Lopinavir + Ritonavir, Atazanavir, Fosamprenavir, Tripanavir, Darunavir
2 E/F I (entry or fusion inhibitors): Enfuvirtide, Maraviroc
Need for new drugs:
resistant mutants
better tolerability
lower toxicity
co-formulations: better treatment adherence
Hepatitis C virus (HCV): Virus
Hepacivirus; Flaviviridae
Virion:
Enveloped, 55 - 65 nm
Genome:
9.6 kb sS RNA +
Coding for polyprotein,
subsequently cleaved:
Genotypes:
structural:
non-structural:
C, E1, E2,
p7, NS2, NS3, NS4A,
NS4B, NS5A, NS5B
1 -6 (> 100 subtypes)
Replication:
RNA poly error rate: 1 in 10,000 to
1 in 100,000
After: www.med.uni-heidelberg.de
HCV: Transmission and prevalence
Transmission:
injectable drug use
blood, blood products
vertical (3 - 15 % risk)
Prevalence:
~ 180 million people infected
worldwide:
USA
3 - 4 million
Europe
15 million
Asia
90 - 95 million
Africa
30 - 40 million
Americas
12 -15 million
It is estimated only about ½ diagnosed in developed countries
<1% Australia, Canada, Northern Europe
~1% USA, most of Europe
>2% Africa, Latin America, Central & South-Eastern Asia,
(some countries 5 - 10 %)
19 % (10 - 19 years old persons) - 60 % (30 years old persons) - Nile delta Egypt
HCV: Infection and pathogenesis
Infection:
CD81, SR-BI, [LDL rec, L/DC-SIGN]
60 - 70 % % asymptomatic
~50 - 80 % becomes chronic
Pathogenesis:
10 -20 % of chronically-infected individuals develop cirrhosis,
1 - 5 % HCC
HCV responsible for : 27 % cirrhosis
50 - 76 % of all liver cancers (25 % HCC)
2/3 of all liver transplants
Mechanism: both, the immune-system-mediated pathobiological changes
and direct viral cytopathic effects
HCV: Prevention and Treatment
Prevention:
no vaccine
In the absence of a vaccine, all precautions to prevent infection must be taken including:
 Screening and testing of blood and organ donors;
 Virus inactivation of plasma derived products;
 Implementation and maintenance of infection control practices in health care
settings, including appropriate sterilization of medical and dental equipment;
 Promotion of behaviour change among the general public and health care workers
to reduce overuse of injections and to use safe injection practices;
 Risk reduction counselling for persons with high-risk drug and sexual practices.
Treatment:
pegylated interferon and ribavirin:
success rate depends on
genotype: 1: up to 50 %
2&3: 50 - 80 %
Highly pathogenic endemic viruses
Mostly emerging:
WNV (→ WNV), Dengue, Chikungunya, [HAV, HEV]
Defined primarily as ‘arthropode-borne’ or mosquito-borne’ (WNV, Dengue,
Chikungunya) or ‘ food or water-borne’ (HAV, HEV)
But:
Emerging bloodborne pathogens include new and re-emerging agents that
can be transmitted through blood, blood products, body fluids, and biological
therapeutic products, including cells, tissues, and organs
Increasing territorial spread, following spread of suitable vectors, probably as
a consequence of the climate change
Significant morbidity and mortality
High global burden of infections
West Nile Virus (WNV)
Flavivirus, Flaviviridae
Virion:
~50 nm, enveloped
Genome:
sS RNA -; 11kb; coding for: structural C, E, M and
seven NS proteins
Lineages 1 and 2 (recently circulating in Central Europe)
Infection:
Majority asymptomatic
Minority:
Mild (fever)
Neuroinvasive - ~ 10 % deaths
In infected individuals the ratio between the three states is roughly
110:30:1.
Host range:
Mostly birds
Susceptible mammalian species: horse, dog, man
Transmission:
Mosquito - Culex and 16 other species
Blood, blood products
Prevalence:
Africa, Asia (India, Indonesia), Australia, Southern Europe,
Eastern Europe (co-circulation of 1 and 2)
1999 introduction to USA (lineage 1)
WNV US EPIDEMICS
1999
2002
2005
2000
2003
2006
2001
2004
2007
WNV: Statistics of US epidemics
Year
Overall
clinical cases
Viremic blood
donors
Fatalities
1999
62
nd
7
2000
21
nd
2
2001
66
nd
9
2002
4156
nd
284
2003
9861
818
264
2004
2539
224
100
2005
3000
417
119
2006
4269
361
177
2007
3576
332
115
nd not determined
Figures from CDC
Dengue virus
Flavivirus; Flaviviridae
Virion:
50 nm, enveloped
Genome:
sS RNA -
4 serotypes
DENV 1 - 4
Transmission:
most common mosquito-borne viral disease
Aedes aegypti (urban species);
Aedes albopictus
Prevalence:
2.5 billion people at risk of infection
>100 countries: Africa, Americas, Eastern
Mediterranean, South-east Asia, Western Pacific
Dengue virus - continued
Infection:
Mosquito bite; 2 - 7 day viraemia
Pathogenesis:
~50 - 100 million / year  Dengue fever (DF)  ~ 1% dengue
hemorragic fever (DHF) and Dengue shock syndrome (DSS) 
 ~ 2.5 % mortality (up to 20 % without treatment; ~ 1 % with
support treatment
Mechanism: 2 theories : 1) Antibody-dependent enhancement (ADE)
2) Inherent virulence
ADE: Second infection with a heterologous DENV serotype: significantly higher risk of
developing DHF and DSS. Pre-existing heterologous dengue antibody recognizes and binds,
but does not neutralize the infecting virus and facilitates its internalization via immunoglobulin
Fc receptors on the cell membrane of leukocytes, especially macrophages.
Prevention:
controlling vector mosquitoes - insecticides; water containers etc.
vaccine in development
Treatment:
No specific treatment; supportive therapy - most important is
maintaining the circulating fluid volume
Chikungunya virus
Alphavirus, Togaviridae
Virion:
70 nm; enveloped
Genome:
sS RNA +; 12 kb
Transmission:
mosquito (Aedes aegypti, albopictus)
Prevalence:
until recently tropical disease,
spreading with the spread of vector
Reunion: estimated 312,500 of 757,000 inhabitants infected (2005-07)
India:
ongoing; 1. 400,000 in 2006
Europe:
increasing risk
outbreak in Italy, 2007 (A.Albopictus since 1990;
scattered foci in almost all regions)
Chikungunya virus - continued
Infection:
self-limiting:
fever, headache, weakness, rash, arthralgia (some
up to several months even years)
6 - 7 day viraemia
Prevention & Treatment
No vaccine or preventative drug
Measures:
Insect repellent containing an DEET or another
EPA- registered active ingredient
Long sleeves and pants
Screens on windows and doors, mosquito net
Elimination of mosquito breeding sites (buckets,
barrels, tyres etc)
BBV pathogenic for certain patient groups
Immunocompromised
individuals:
~ 50 % transfusion recipients in UK have some
degree of immunosuppression
Pregnant
women:
Congenital infection or infection at/shortly after birth - risk of
miscarriage, developmental defects
CMV
Screened for in a proportion of donations. CMV-negative products
given to at risk patients
B19 → B19
Becoming established. However, ongoing discussion on the
introduction of PCR screening.
LCMV
Several episodes of fatal solid organ transplantations
[HHV 6, 8]
[Enterovirus ?]
Cytomegalovirus (CMV)
Cytomegalovirus, Herpesviridae
Virion:
120 -150 nm, enveloped
Genome:
dS DNA, 230 kbp → ~ 200 genes
Genotypes:
2 - 6 major subtypes when individual genes typed
Variants:
Complex population of virus strains (virtually infinite number if
sufficient number of genes analysed)
Transmission:
Person-to-person by direct contact; Minority - shedding in urine, saliva
Blood, blood products
Organ transplantations
Vertical
Prevalence:
Almost all people exposed to CMV when reaching adulthood
Seroprevalence 40 - 90 %
CMV - continued
Infection &
Pathogenesis:
Incubation period 3 -12 weeks
Lifetime infection; Mostly asymptomatic
Minority - infectious mononucleosis-like disease
~ 1 % of newly-born infected: 1 in 10 of these develops significant
illness involving nervous system damage or developmental
disabilities
Immunocompromised: significant morbidity and mortality
fever, leucopenia, pneumonia,
gastrointestinal problems, impaired graft function
Late -stage HIV: encephalitis, retinitis
Different strains may interact differently with host’s immune system
Co-infection with different strains frequent in immunocompromised,
new data suggest also in some 20 % of immunocompetent
Treatment:
Ganciclovir
Cidofovir, Foscarnate - alternatives as the resistant mutants appear
Parvovirus B19
Erythrovirus, Parvoviridae
Virion:
18 - 26 nm; non-enveloped
Genome:
sS DNA ~5.4 kb; + and - packaged; 115 nt at the ends → hairpin
Codes for VP 1 - 3, NS1, 11kDa protein, 7.5 kDa protein (?)
Genotypes:
1-3
Transmission:
Respiratory droplets
Blood, blood products
Prevalence:
Seroprevalence: children under 5: ~ 2%
15 year olds:
~ 50%
adult population: ~80 %
over 60 year olds: >90 %
B 19 (continued)
Infection:
“Fifth disease”
Seasonal character: maximum in spring in mild climate countries
108 - 1014 /ml
Until recently generally accepted view of self resolving infection
within 6 months.
New data (NAT) suggest persistence in immunocompromised
persons. Possibility of reactivation during other infections and drug
treatments
Pathogenesis:
Immunocompromised individuals: prolonged anaemia, aplastic crisis
in individuals with haemolytic anaemia
Vertical transmission:
Treatment:
anaemia, myocarditis → “hydrops fetalis”
Generally no treatment required
In cases of persistence, severe anaemia - intravenous IgGs
LCMV: Lymphocytic choriomeningitis virus
Arenavirus, Arenaviridae
Virion:
50 - 300 nm; enveloped
Genome:
sS RNA -; 2 segments:
L coding for:
polymerase
Z (zinc binding)
S coding for:
NP (nucleoprotein)
GPC (glycoprotein
precursor → GP1, 2
Strains: Armstrong immunostimulatory, clone 13 - immunosuppressive
WE , Pasteur, Traub, UBC
[Marseille, MX – Institute of Virology, Bratislava]
Transmission:
Exposure to rodent aerosolised excreta
Organ transplantation:
2 episodes 2003 and 2005 USA
1 episode 2007 Australia
10 out of 11 → deaths
[Blood, blood products?]
‘Rare’ person-to-person?
LCMV - continued
Infection &
Pathogenesis:
Prevalence:
Acute infection usually asymptomatic, self-limiting
‘Grippe-like’: fever, weakness, arthralgia, myalgia, headache, nausea
In some cases ‘acute aseptic meningitis’, meningoencephalitis
Pregnant women: may lead to abortion, congenital malformations
hydrocephalus, macro and microcephaly, chorioenitis
Acute infection:
NP, GPs well expressed
Persistent infection:
NP expressed normally, GPs very limited
expression
Seroprevalence: USA, Canada
Italy, Spain
Argentina
but:
Treatment:
Slovakia
Croatia
no specific treatment
4-5%
2-3%
1 - 3.6 %
37.5 % (anti - MX NP)
36 %
Pathogen detection
Antigen
Antibodies
(Glyco)protein
HBsAg
[HCV core]
Nucleic acid
TARGET
AMPLIFICATION
HCV RNA
HIV1 RNA
[HBV DNA]
[Bacteria]
ELISA, EIA
[Combi]
Anti-HIV 1,2
Anti-HCV
Anti-Treponema
Anti-HTLV
[Anti-HBc]
[Anti-malaria]
PCR
After J. Mullins (April 01) http://ubik.microbiol.washington.edu/Index.html
PCR vs. other amplification techniques
Method
Target
Signal
amplification amplification
PCR
Exponential
No
Yes
High
Dispersed
LCR
No
Exponential
Yes
High
Dispersed
No
High
Dispersed
NASBA
Branched
DNA
RCA
Exponential
Thermocycling
No
Sensitivity
Product
No
Exponential
No
Medium
Localised
No
No
Linear (1 primer)
Exponential (2 pr)
No
No
Medium
High
Localised
Dispersed
Serological Methods
After J. Mullins (April 01) http://ubik.microbiol.washington.edu/Index.html
Flat surface microarrays
Microparticle based microarrays
1 - 6 μm
Carboxylate
Avidin-modified
Hydrazide
Maleimide
75 – 900 μm
Solid, split pins
Particle encoding/decoding
Probes: Nucleic acids, proteins, carbohydrates, cells
Surfaces: Poly-L-lys, epoxy-silane, gold, amino-silane…
2-dye scale
100 combinations
100s to 100 000s of spots
In situ decoding
PCR and microarray
PCR
Standard
Sensitivity
Real time
High (~10 geq)
Multiplexing
Limited (30)
Confirmation
Gel, microarray
Protein assays
* not required
Microarray
Low - Medium
Very limited (5)
No
NR*
High
PCR (for expression
profiling)
Yes
Pathogen blood screening: Examples of assays used in SNBTS
Detected target
Detection
method
Instrumental
platform
HBsAg
Sandwich immunoassay
Abbott Prism
Chemiluminiscence
1-10 pg/ml a)
200/hr
Anti-HCV
Sandwich immunoassay
Abbott Prism
Chemiluminiscence
NA b)
200/hr
Anti-HIV1,2
Sandwich immunoassay
Abbott Prism
Chemiluminiscence
NA b)
200/hr
Anti-treponema
Agglutination
Olympus
CCD
NA b)
240/hr
HCV RNA
Real time PCR
In-house
Fluorescence
29 geq/ml c)
30 –50/6 hrs d)
HIV1 RNA
Real time PCR
In-house
Fluorescence
34 geq/ml c)
30 – 50/6 hrs
a)
b)
c)
d)
Signal
readout
Detection
limit
Throughput
(No of samples)
Estimate
Not applicable
geq: genome equivalent
minipools of 95 sample
Modified from: Petrik J, Robb JS: Microarrays and Blood Diagnostics. In:”BioArrays: From Basics to Diagnostics” (K.Appasani ed),
Humana Press Inc., Totowa, NJ, 2007; 215-230.
New Test Implementation and Declining
Risk of Viral Infections from Transfusion
Updated from AuBuchon, Birkmeyer, Busch. Ann Intern Med 1997;127:904-9.
Risk (per unit) of transmission of major viruses
pre-NAT
MP-NAT
ID-NAT
HIV
1 : 1,300,000
1 : 1,900,000
1 : 3,000,000
HCV
1 : 230,000
1 : 1,600,000
1 : 2,300,000
HBV
1 : 180,000
1 : 210,000
1 : 410,000
Summary of risks of transfusion
10
-8
10
-7
-6
10
10
-5
10
-4
10
-3
10
-2
10
General anesthesia
HIV
HCV
HBV
Bacteria
Mistransfusion
Lung injury
GVHD
Cardiac
After S. Dzik, MD Blood
Transfusion Service, MGH,
Boston
Metabolic risk in neonates
Under transfusion
-1
10
0
Global burden of BBV
Cumulative number of infections by HBV, HIV, HCV: 1/10th of world population
Mortality
related to
HIV
HBV
HCV
Chronic infections
Cost of HCV therapy
Cost of HAART
Cost of HBV therapy
2.1 million
1 - 1.2 million
~> 1 million
~£8,500 / year
$ 12,000 - 24,000 / year
( less in developing countries)
$3,500 (lamivudine)
$7,400 - 9,000 (adefovir, entecavir,
telbivudine)
$24,000 peginterferon
Liver transplant
$ 100,000 - 400,000 in developed countries
$ 18,500 in India
Testing
> $ 1.3 Billion
Individual burden of host - microbes interactions
Human cell
E coli
Vaccinia virus
ø 10 μm
0.8 x 2 μm
0.3 x 0.25 μm
1000 pg
0.665 pg
665 fg
0.095 pg
95 fg
1014
1015
Adenovirus
ø 0.075 - 0.09 μm
0.00029 pg
0.29 fg
>1012/day
What is the cumulative “metabolic burden” of simultaneously replicating microorganisms
in the host?
Levels of complexity of host - microbe interactions
1 Pathogen intraspecies variability
Quasispecies: heterogeneous, but closely related swarm of viruses within the same host
HCV example: error rate (1 in 10-4-5) and high turnover rate (1012 /day) →
→ every possible mutation in every position theoretically
generated in infected host every day
2 Pathogen - pathogen interactions: Co-infections:
HIV-infected individuals:
in Europe ~ 9 % co-infected with HBV, 30 % with HCV
generally accelerated diseases progress, worsened prognosis
HIV + TTV:
Increased titres of TTV with progression towards AIDS in
serum, bone marrow, spleen etc.
HIV + HGV:
There seem to be some slowing down effect of HGV coinfection
Complex populations of respiratory tract infections
3 Host genomic variability
Pharmacogenomics and individualised therapy
Prediction of response to particular drugs
Individualised dosing regimes
4 Drug interactions
Personalised medicine and infectious diseases
Concept of “clean” infection with one well-defined pathogen – very simplistic
Our data set prior to therapeutic intervention is currently extremely limited
Personalised infectious disease therapy will require:
Quick analysis of the pathogen populations present,
perhaps via coupled PCR - microarray approach:
Species identification
Genotyping
Characterised mutants
Quasispecies number estimate if relevant
Quantification
Host immune system components analysis
Host pharmacogenomics predicting drug responses
At the same time, continuous surveillance and monitoring of the emerging and
reemerging pathogens must take place, resulting in preventative measures and
development of vaccines and new therapeutic approaches
So there is a lot of work waiting
for you – good luck!
Thank you for your attention