Download West Nile virus vaccines and immunotherapy

West nile virus
Virology:
West Nile Virus (WNV) is a member of Flavivridae family" genus
Flavivirus"(Gubler DJ in Buane J,2007) and this virus was discovered in
Uganda in 1937 by taking a blood specimen from a febrile patient
(women)(Smithburn KC et al in Buane J,2007)
This virus which contain central of nucleocapside with about 50 nm-diameter
of single RNA which is surrounded by lipid membrane(Campbell et al,2002 in
Abigail E,Laura B,Robert E,2007).
The genomic RNA which contain two of untranstated regions(UTR) 3 and
5,also a single open reading frame (ORF) which is introduced as along
polyprotein that has a function of co-and post-translationally .In additionterminal protein in ORF have a great role to encode three structure and seven
non-structure of protein(Capasid C,membrane M and envelop
E),(NS1,NS2a,NS2b,NS3,NS4a,NS4b and NS5) respectively(Chambers et al
in Francesc et al,2009).
Epidemiology:
During the period of 1937 to 1999, this virus was rarely emerged in Europe
and it was particularly enzootic in Africa, west and East Asia and
Mediterranean(Hayes C in Buane J,2007) .In addition, WNV (Kunjin) is also
detected in Australia in that time and was identified as subtype of this virus.
So the percentage of cases of people who was infected with neuralgic
disease and death by this virus was very low. However, this infection had
reappeared in 1960s in region in France called Camargue when WNV was
associated with damage neurologic disease in humans (Joubert L et
al&Panthier R et al in Buane J, 2007), also, equines were presented infected
by virus during September to early of November in 2000.In contrast to 2003
when cases of human and equines reappeared in southern region in France
(A.Mailles et al in Gwena�lle D et al, 2004).
Similarty, in Italy 1998, where 14 horses had infected by this virus during
months of August and October and resulted six animals death because
mostly were associated with neurological signs thus, the virus disconnected
particularly from a brain biopsy (C.Cantile et al in Gwena�lle D et al, 2004).
Main outbreaks in Central Europe Countries:
Romania 1996, especially on July and October and return in appearance in
1997 and 1998(T.F.Tsai et al in Gwena�lle D et al, 2004).In Russia 1999,
during period of August and September when about 318 people have been
infected with virus which these has confirmed from serum samples testing
and statistics were reported 40 of fatal cases mostly in older patients
(A.E.Platonov et al in Gwena�lle D et al, 2004).
Main outbreaks in North African Countries:
In Algeria 1994, the virus was defected in regions in middle of Sahara where
50 conditions of virus presented with symptoms of fever and neurological
signs and this virus is also mentioned in children of ten months to nine years
old (B.Le Guenno in Gwena�lle D et al, 2004).Also, in Morocco between
1996 and 2003 in August and the middle of October, 94 cases were infected
mixing between human and equines. In addition, several fatal patients
observed there(A.Tber Abdeelhaq in Gwena�lle D et al,2004) whereas in
Tunisia 1997,particulary in Sfax and Mahdia where the number of patients
has increased dramatically in September and December to 173 cases, mostly
are tested and resulted with five fatal conditions(B.Murgue et al in Gwena�lle
D et al,2004).
Also, in Israel specifically in parts of northern and central areas in 1998 to
2000 when the percentage of older patients died because they suffered from
encephalomyelitis condition (M.Malkinson et al in Gwena�lle D et al, 2004).
Main outbreaks in Untied states:
Futherthemore, this infection had continued of occurrence .For example,
sixty-two cases and seven death were resulted from infection by WNV in
United states and particularly in New York in 1999 and also outbreak of this
virus was appeared into different animal(horses, crows and exotic birds) in a
zoo New York city.
So, after the wild spread appearance of this virus in united states, many
studies had discussed how this virus transmit to these areas and they had
concluded their reports by many finding which are similar to those cases that
occurred in Iraq and Israel between the period of 1980s to 2000s which
helped researchers to know the outbreak had accessible by international
transportation or trade.
Since 1999, the people who were infected and died by this virus increased
dramatically each year in united state and this is model below shows the
cases of condition and deaths between 1999 to 2006.
Transmission:
In general, mosquitoes have been found to transmit WNV.but because there
is more than one of variant species of mosquitoes (about 40 that have been
discovered) so it is difficult to know which one has a great role in natural
transmission to humans (Jeffrey R, Jan F,2008).
On the other hand, many reports have shown to the mostly of this infection is
transmitted by special mosquitoes related to Culex spp(Campbell et al,2002
in Abigail E,Laura B,Robert E,2007) that carries virus in their salivary glands
and then infect bird species during blood meal feeding (L.Gould and E.Flkrig
in G.Dauphin and S.Zietara,2006)
Moreover, birds can serve as transmissible of infection and this among using
their natural reservoir and this virus is able to replicate by itself to trillion
copies or more especially in birds bloodstream (Abigail E, Laura B, Robert E,
2007).
In schematic below shows transmission cycle of WNV which is transmitted by
mosquitoes to birds and many species such as human and horses are
incidental hosts.
In addition to mosquito bites the virus can transmit by transfusion and organ
transplant (Kurt link, 2007) and breastfeeding (Abigail E, Laura B, Robert E,
2007).All of these transmission methods of virus aid to infect directly human
by human (Daniel C, 2005).
In the temperate climate, people are mostly infected with WN virus in summer
or in the beginning of the autumn whereas in the tropics areas the infections
by this virus will increase dramatically in season of rain weather because
mosquitoes are plenty found in this weather (D Nash et al,AE Platonov&K
Marberg et al&TF Tsai et al&M Weinberger et al in Campbell et al,2002).
Interestingly, the strains of this virus can genetically divide into two lineages,
the first lineage that are considered in Africa in the Mediterranean basin,
Southern Europe, India, Australia and America, and the second lineage II are
specially enzootic in sub- Saharan Africa and Madagascan that are generally
not pathogenic (B.Murgue et al,F.X.Berthet et al,R.S.Lancroottiet al
,J.H.Scherrert,and R.S.Lanciotti et al in G.Dauphin and S.Zientara,2006).
Symptoms:
Most conditions of this virus are symptomatic and symptoms of WNV have
period of incubation about 3 to 14 days after the person has bitten from
mosquito and these symptoms are different and might not appear with person
who is infected by virus. About 80% of persons who carries virus has no
clearly symptoms and they are ignorant of have been infected and just 20%
have multitypes of symptoms including fever which usually more than
39c,headache,badily aches and pains,nausea,vomiting,swollen glands and
rush on the trunk. In addition to these symptoms there are other serious
symptoms are linked to elderly people for example, very high fever, stiff neck,
stupor, disorientation, convulsions, paralysis, visual loss and numbness (Kurt
link, 2007&Joyce E,Linda C,Pamela S,2007).
Moreover, recently when there has increased of infected population in many
states in the world ,outbreaks of WNV show develop cases with neurological
diseases in both humans and horses (this infection cause illness to human as
well as horses and birds)(L.R.Petersen and J.T.Roehig in G.Dauphin and
S.Zientara,2006).
So about 1% of patient who is infected has associated with disease of
nervous form of the disease: meningitis that refers to an inflammation of the
brain and the membrane around it while encephalitis refers only to an
inflammation of the brain (Glenda D et al, 2008) or melitis and this can be
harmful especially in old patients comparing to west Nile fever that can
recover during days and months.
As in a human, horses, donkeys and mules are also infected with virus and
about 10% of Equidae infection can develop with neurological disease and
there are major signs such as ataxia and hind limb paresis and properly
muscle tremors will appear with neurological illness(Mp.Ward et al&C.Cantile
et al in G.Dauphin and S.Zientara,2006).
It is important to know how this virus enters central nervous system and thus
crossing the blood-brain barrier (BBB) and the view point of entrance this
infection might start directly by infected micro vascular endothelial cells and
this in two ways endothelial cell junction or migrate within infected leukocytes
that penetrate the CNS (Dia mond et al,King et al&Samuel et al in Jianfeng
Dai et al, 2008).
In this case, the leukocyte infiltration will cause increasing the inflammation of
central nervous system thus, will contribute to encephalitis (King et al
&Samuel et al in Jianfeng Dai et al, 2008).
Adhesion molecules in which types of cell vascular endothelial and
leukocytes are responsible about leukocyte traffic into the brain. For example,
ICAM-1 (adhesion molecule) which is one of the most fundamental molecule
in this process (Dietrich, J.B &Lossinsky et al in Jianfeng Dai, 2008).Also, the
blocking of ICAM 1 will arrest the binding of lymphocytes to endothetrial cells,
as well as migration across the activated monolayer (Dejanan, E, Dietrich,
J.B& Gressnwood et al in Jianfeng Dai, 2008).
So the inflammation of brain is characterized by up-regulation of this type of
molecule in CNS vascular endothelium and leukocyte which cause trouble of
BBB and then in leukocyte recruitment into central nervous
system(Dietrich,J.B,Luster et al&Turowski et al in Jianfeng Dai, 2008).
In general, many of viral infection particularly in human can control in part by
early induction of type 1 interferon (IFN).So, researchers have attempted to
control WNV replication by discovered main type I IFN-regulated anti-viral
effectors pathways which include complex of two mechanisms, the double-
stranded RNA-dependent protein kinase (PKR) mechanism of protein
synthesis inhibition, and the 2'-5' oligoadenylate synthetase (OAS) pathway of
RNaseL-mediated RNA degradation(Samuel et al in Jean K,2009).
Many studies have introduced if the WNV of human has a genetic basis risk,
and they have discovered two human genes as susceptibility loci for WNF
infection. Chemokine receptor CCR5 that has a great function of regulation in
leukocytes trafficking in central nerve system, while in infected brain CNS
expression of the chemokine receptor CCR5 and its ligand CCL5 are clearly
up-regulated by WNV.In this case, all of these will cause infilratrain and
changes in function of different cells (Glass WG et al,2005) For
example,CD4+ and CD8+T cells (Sitati E, Diamond M,2006&Shrestha B,
Diamond M,2004).which play role in control of west Nile
infection.Also,NK1.1+ cells and macrophages expressing the receptor .
.OAS 1 gene is one of OAS cluster which contains in order of OASI,OAS3
and OAS2 on chromosome 12,and the structure of OAS 1 gene is different
between human and mice by scanning ,8 copies of OAS 1 have been
introduced in mice while only one copy in human genome(Justesen J et al in
Jean K,2009) .
In addition, OAS 1 is suggested one of genetic risk factor for primary WNV
infection not for disease.
Diagnosis
Laboratory diagnosis of this infection is essential a for human and horses as
well, and this due to subclinical or symptomatic of this virus in patient .For
example, if patient suffers from symptoms it becomes necessary testing WNV
because the clinical signs are not clear.
Generally, there are many difficulties related to diagnosis this type of WN
disease because it needs to using special requirement for level 3 safety
facilities and variant species testing that must be done due to complexes this
virus with other flaviviruses.In addition, methods that are used in diagnosis
are important to notice the short duration and low level viremia in humans and
horses and finally the clinical signs which appear lately in infected patient(G.
Dauphina and S. Zientara, 2006).
To diagnosis this infection it is important to detect antibodies of infection and
there are about six main types of assays which are characterized the
detection of WNV antibodies and this is an overview of these assays testing.
Complement fixation (CF) and Hemagglutination inhibition (HI) are played
role in early studies of clinical and seroprevalne of WNV infection but recently,
they rarely used(Harry E,Wayne R,2005).Also, plaque reduction
neutralization test(PRNT) which is still performed is some cases and this is
related to these a special factors which characterize it .For example, safety
issues that related to working with virus live and the time which is needed
perform the assay(D.A.Matin et al in Harry E,Wayne R,2005).
The forth assay testing is immunoflurescence assay (IFA) which has many
advantages compared to they are mentioned before, the volume of a sample
of this assay is lower than other.Also,it can be achieve in one day so the
result will be available in shortly time .In addition, main benefit is in their
ability to separate IgM and IgG antibodies(Shi and Wong in Harry E,Wayne
R,2005)
The next type is Enzyme-linked immunosorbent assay(ELISA) which is
particularly formet used to measure antibodies in the specific part of infection
disease serology(A.Voller and D.Bidwell in Harry E,Wayne R,2005) and the
latest assay is called Microsphere immunoassay(MIA) that has the best
advantages of system compared with others which is related to many factors
including available of antigen epitopes is resulted from increasing surface
area and the volume of specimen is smaller than in normal used assays(Shi
and Wong inHarry E,Wayne R,2005)
To diagnosis this virus which can be made by more one method.Intetialy,
culture of the virus from the blood and this by two way, finding of specific
antibodies to the virus and the RNA of the virus in tissue sample(David B.
Jacoby, M.D., R. M. Youngson,2004).
The main method that is used to diagnosis WNV infection is serological
testing which is basically based on ant-E Abs detection. Also, Enzyme-linked
immunosorbent Assay (ELISA) methods have been used and it has classified
into three types IgG, MAC-ELISA and epitope blocking ELISA. To add up,
other tests are used as confirmation tests such as cultivation of the virus and
plaque reduction neutralisation tests. And screening tests of blood and
plasma donor are necessary as a result of protective blood supply (G.
Dauphina and S. Zientara, 2006).
West Nile virus vaccines and immunotherapy:
There are several attempts by scientistics who using different strategies in
developing vaccines. For example, they used DNA vaccine, recombinant
antigen vaccine and attenuated or killed viral vaccines which applied many
experiments into animals particularly in mice thus, positive results that were
showed as well as other data demonstrating no effect (Tian W and Erol F,
2004)
Recently, they show to one type of immunotherapy for WNV by treated mice
with pooled plasma or intravenous immunoglobulin (IVIG) and then used as
an adjuvant therapy in patient with WN encephalitis(A.G
Agrawal&L.R.Petersen in Tian W and Erol F,2004).
Prevention of human WNF infection:
The large spread of WN across the untied states in 1999 lead whether it is
important to understanding the source of this infection, epidemiology,
transmission and everything concern to virus.
Also, the main risk factors that associated with WN virus and gives the
infection a big chance to infect human in shortly time which people have to
take into their account. For example, length of time that is spent outdoors
where is mosquitoes abundant, forgetting to use repellent, ignoring presence
mosquitoes at home and living in areas using flooded basemet(F Mostashari
et al&LL Han et al in Campbell at all,2002). In addition, wearing clothes that
are in light colour because dark clothes attract mosquitoes as well as growing
animals nearly living houses (J.Chin in Angella M.2004).
All of the recommendations in above are for all stages in age and particularly
in pregnancy because there are studies reported infected pregnant women
with disease by breastfeeding (D.L.Sudakin and W.R.Trevathan in Denise et
al, 2006).
Moreover, education of the public plays a great role to reduce the percentage
of infected cases which assist population to understand ways of transmission
and risk of this virus (CDC in Angella M.2004).
Treatment:
Although, ribavirin and interferon were used experimental in vitro to inhibit
WNV replication and cytopathogeinicity, there is no specific treatment is
developed in this infection (Jordan I et al& Anderson JF, Rahal JJ in Edward
B and Danied R, 2004)
In the one hand, in Israel during the outbreak of virus in 2002, there was a
child treated by ribavirin and the result was successful but there is no
evidence from specific report shows whether this patient is better than those
who did not receive ribavirin (Chowers MY et al&Spiegel R et al in Edward B
and Danied R, 2004).
So, the best way to arrange this virus is to take care health far away from
ways of transmission WNV.