ASSESSMENT

NURSING
DIAGNOSIS

PLANNING

OUTCOME
IDENTIFICATION

INTERVENTIONS

Subjective:
Musakit og ayo
ang ako bat-ang pag
mulihok ko, as
verbalize by the
patient.
Pain scale:10/10

Acute pain r/t

fracture and muscle
spasm

After 1hr. of
nursing
interventions,
the patient
will verbalize
absence or
controlled
pain.

The patient will be

able to:
1. Verbalize
decrease or
absence of
pain; from pain
scale of 10/10
to 0/10.
2. Verbalize
understanding
s about the
importance of
both
pharmacologic
and nonpharmacologic
therapies to
decrease pain.
3. Demonstrate
relaxation
techniques
and divertional
activities to
decrease pain.

Obtain patients
assessment of pain to
include location,
characteristics, and
intensity/quality,
frequency, and
aggrevating factors; use
pain scale of 0-10.

Objective:
Pain in the hip
bone
Cantt sit and
stand without
assistance
Altered ADL
Facial grimace
noted
Guarding
behavior noted
Pain upon
moving
Roentgenologic
report:
lumbosacral
APL
Moaning noted
Spinal
disproportion at
the lumbar
spine

SCIENTIFIC BASIS:
Osteoporosis is a
disease of bones
that leads to an
increased risk of
fracture.
Osteoporotic
fractures are those
that occur in
situations where
healthy people
would not normally
break a bone; they
are therefore
regarded as fragility
fractures. Typical
fragility fractures
occur in the
vertebral column,
rib, hip and wrist.
The symptoms of a
vertebral collapse
("compression
fracture") are
sudden back pain,
often with

Monitor skin color and

v/s.
Provide comfort
measures such as back
rubs, use of heat/cold
packs to the affected
area.

RATIONALE

EVALUATION

To obtain subjective
1. Goals are partially
met?
data about the pain
2.
The patient was
that the patient feels,
able to verbalize
and rule out underlying
decrease pain
condition/
sensation when
development of
taking
complications
medications?
3. The patient was
able to
These are usually
demonstrate
altered in acute pain;
nonpharmacologic
to obtain baseline data
techniques with
assistance of
To decrease pain
S.O?
sensation through
nonpharmacologic
approach.

Encourage patient to
have bed rest; provide a
comfortable linens and a
firm and non-sagging
mattress

To provide comfort and

decrease pain

Encourage patient to
perform relaxing
activities/exercise(deep
breathing exercises)

To distract attention
from pain and reduce
tension.

Advice patient (and

assist patient in turning

To minimize back pain

and prevent further

O- when performing
weight-bearing
exercises
L-lower back
(lumbar area)
D-5 minutes after
initiation of
movement
C-10/10
A- when sitting/
standing
R- lower extrimities
T- Tenoxicam 20mg
1 tab OD
Calcium carbonate
1 tab OD
Ketorolac
30mg
IVTT

radiculopathic pain
(shooting pain due
to nerve root
compression) and
rarely with spinal
cord compression or
cauda equina
syndrome. Multiple
vertebral fractures
lead to a stooped
posture, loss of
height, and chronic
pain with resultant
reduction in mobility.
(source:
http://en.wikipedia.or
g/wiki/Osteoporosis)

sides) to move the trunk

as a unit and avoid
twisting.

injury of the affected

back.

Encourage patient to
apply lumbosacral
corset/binder

To immobilize and
support the lumbar
area when moving.

Encourage patient to
take adequate balance
diet, rich in calcium,
phosphorus and vit. D.
(e.g. milk, salmon,
sardines, egg, liver)

Calcium, phosphorus
and vit. D are essential
for bone formation,
increase bone density
and mass

Assist patient to turn to

sides every 2hrs.

To prevent patient
from having pressure
ulcers.

Dependent:
Provide medication
To aide faster healing.
therapies as prescribed
by the physician such as
the ff.:
Tenoxicam 20mg 1 tab
OD
Calcium carbonate
1 tab OD
Ketorolac 30mg IVTT

ASSESSMENT

NURSING
DIAGNOSIS

PLANNING

OUTCOME
IDENTIFICATION

INTERVENTIONS

RATIONALE

EVALUATION

Subjective:
Musakit og ayo ang
ako bat-ang pag
mulihok ko, as
verbalize by the
patient.

Impaired physical
mobility r/t pain and
discomfort of the
lumbar area.

Within 8hrs.
of nursing
interventions,
the patient
will be able to
regain
mobility
without
hesitance.

The patient will be

able to:
1) Participate
ADLs and
desired
activities.
2) Demonstrate
willingness to
participate in
interventions
that will help
her improve
mobility
3) Verbalize
decrease or
absence of
back pain
upon moving.
4) Verbalize
understanding
s about the
importance of
both
pharmacologic
and nonpharmacologic
therapies to
decrease pain.
5) Maintain skin
integrity as
evidence by
absence of

Assess degree of pain in

accordance to patients
description.

To determine intensity
of pain perceived by
the patient and his/her
tolerance towards
pain.

Determine degree of
immobility in relation to
assessment for pain.

To assess functional
ability.

Note emotional/
behavioral response to
problem of immobility

Feelings of
frustration/powerlessn
ess may impede
attainment of goals

Provide comfort
measures such as use of
heat/ cold packs to the
affected body part.

To promote
nonpharmacologic
relief of pain.

Advice patient (and

assist patient in turning
sides) to move the trunk
as a unit and avoid
twisting.

To minimize back pain

and prevent further
injury of the back

1. Goals partially
met?
2. The patient was
able to perform
activities with
assistance and
when there is
absence of pain?
3. The patient was
able to verbalize
decrease pain
sensation when
taking
medications?
4. The patient was
able to
demonstrate
nonpharmacologic
techniques with
assistance of S.O?
5. The patient was
free from any
signs of pressure
ulcers; and free
from further injury?

Encourage patient to
perform relaxing
activities/exercise(deep
breathing exercises)

To distract attention
from pain and reduce
tension

Objective:
Pain in the hip
bone
Cantt sit and
stand without
assistance
Altered ADL
Facial grimace
noted
Guarding
behavior noted
Pain upon
moving
Roentgenologic
report:
lumbosacral
APL
Moaning noted
Spinal
disproportion at
the lumbar
spine
Altered mobility

SCIENTIFIC BASIS:
Osteoporosis is a
disease of bones
that leads to an
increased risk of
fracture.
Osteoporotic
fractures are those
that occur in
situations where
healthy people
would not normally
break a bone; they
are therefore
regarded as fragility
fractures. Typical
fragility fractures
occur in the
vertebral column,
rib, hip and wrist.
The symptoms of a
vertebral collapse
("compression
fracture") are
sudden back pain,
often with
radiculopathic pain

(shooting pain due

to nerve root
compression) and
rarely with spinal
cord compression or
cauda equina
syndrome. Multiple
vertebral fractures
lead to a stooped
posture, loss of
height, and chronic
pain with resultant
reduction in mobility.
(source:
http://en.wikipedia.or
g/wiki/Osteoporosis)

pressure ulcer
6) Be free from
any injury.

Encourage patient to
apply lumbosacral corset
or binder.

To support lumbar
area when moving

Assist patient to turn to

sides every 2hrs.

To prevent pressure
ulcers

Encourage increase fluid

intake 2000-3000ml/day
within cardiac tolerance.

To keep body well

hydrated and to
decrease risk for
constipation

Dependent:
To aide faster healing.
Provide medication
therapies as prescribed
by the physician such as
the ff.:
Tenoxicam 20mg 1 tab
OD
Calcium carbonate
1 tab OD
Ketorolac 30mg IVTT

ASSESSMENT

Subjective:
dili ko makatindog
og makalingkod kay
musakit ang ako
bat-ang. As
verbalized by the
patient.

NURSING
DIAGNOSIS

PLANNING

OUTCOME
IDENTIFICATION

Risk for injury:

fracture r/t effects
of change in bone
structure secondary
to osteoporosis.

After 8hrs. of
nursing
interventions
the patient will
maintain
absence of
additional
fracture.

The patient will be

able to:

SCIENTIFIC
BASIS:

Osteoporosis is a
disease of bones
Objective:
that leads to an
increased risk of
Spinal
fracture.
disproportion at
the lumbar spine. Osteoporotic
Pain at the hip
fractures are those
bone
that occur in
Cant stand and
situations where
sit
healthy people
Altered mobility
would not normally
Altered ADL
break a bone; they
Roentgenologic
are therefore
report:
lumbosacral APL regarded as
fragility fractures.

1. Report increase
comfort,
decrease pain.
2. Verbalize
importance of
health
teachings
imparted to
prevent
additional injury.
3. Report absence
of complications
due to lack of
mobility.

INTERVENTIONS

RATIONALE

Maintain bed rest as

indicated. Provide
support when
moving/turning.

Provides stability,
reducing possibility of
disturbing
alignment/muscle
spasms, which
enhances healing.

Advise the patient to

sleep on a soft mattress
and to avoid excessive
bed rest.

Excessive bed rest may

cause further
complications such as
pressure ulcers,
constipation and
contractures. Firm
mattress may increase
patients comfort.

Advice patient to apply

lumbosacral
corset/binder

.
To immobilize and
support the lumbar area
when moving.

Advice patient (and

To minimize back pain
assist patient in turning
and prevent further
sides) to move the trunk
injury of the affected
as a unit and avoid
back.
twisting.

EVALUATION

1. Goals are
partially met?
2. Patient does not
manifest any
signs of further
fractural injury?
3. The patient was
able to verbalize
decrease pain
sensation when
taking
medications?
4. The patient was
able to maintain
intact skin
integrity?

Typical fragility
fractures occur in
the vertebral
column, rib, hip and
wrist. The
symptoms of a
vertebral collapse
("compression
fracture") are
sudden back pain,
often with
radiculopathic pain
(shooting pain due
to nerve root
compression) and
rarely with spinal
cord compression
or cauda equina
syndrome. Multiple
vertebral fractures
lead to a stooped
posture, loss of
height, and chronic
pain with resultant
reduction in
mobility.
(source:
http://en.wikipedia.
org/wiki/Osteoporo
sis)

If the patient takes a

calcium supplement,
encourage liberal fluid
intake

To help maintain
adequate urine output
and thereby avoid renal
calculi, hypercalcemia,
and hypercalciuria.

Tell the patient to report

new pain sites
immediately, especially
after trauma.

To prevent patient from

having pressure ulcers.

Assist patient to turn to

sides every 2hrs.

To prevent pressure
ulcers

Encourage the patient

to install safety devices,
such as grab bars and
railings, at home.

To prevent additional
injury when at home.

Advice patient to use

support canes/walking
cane when walking or
standing.
Encourage patient to
take adequate balance
diet, rich in calcium,
phosphorus and vit. D.
(e.g. milk, salmon,
sardines, egg, liver)

To balance patient and

pevent additional injury.
Calcium, phosphorus
and vit. D are essential
for bone formation,
increase bone density
and mass

ASSESSMENT

NURSING
DIAGNOSIS

PLANNING

OUTCOME
IDENTIFICATION

INTERVENTIONS

Subjective:
Dili nako
makagam sa ako
kaugalingon as
verbalize by the
patient.

Self-care deficit:
Bathing and toileting
r/t pain & discomfort
upon moving.

Within 8 hrs. of
nursing
interventions,
the patient will
experience
increase
comfort &
decrease pain.

The patient will be

able to:
1. Perform self
care activities
within level of
own ability.
2. Express
positive
feelings about
her.

Tell the patient to report

new pain site
immediately, especially
after trauma.

These are usually altered

in acute pain; to obtain
baseline data

Advise to stay on a
non- sagging and firm
mattress and avoid
excess bed rest.

To decrease pain
sensation and to
provide comfort.

Encourage the patient

to perform knee flexion.

Increases comfort by
relaxing back muscles.

Encourage the patient

to move the trunk &
avoid twisting.

Moving the trunk as a

unit helps the pain
lesser and twisting can
promote pain sensation.

Apply intermittent local

heat and back rubs.

Promote muscle
relaxation.

Encourage good
posture and teach
proper body mechanics

To prevent back pain &

promote good posture.

Encourage use of
visualization, guided
imagery, & relaxation.

To promote positive
sense of self & distract
attention from pain and
reduce tension.

Objective:
Pain at the
hip bone
Cant stand
and sit
without
assistance
Altered
mobility
Altered ADL
Roentgenolog
ic report:
lumbosacral
APL
Pain upon
moving
Guarding
behavior

SCIENTIFIC BASIS:
Patient may be
immobilized by pain,
muscle weakness or
they may be
immobilized for
therapeutic reasons.
When mobility is
impaired, the wellknown
consequences may
include activity
intolerance, loss of
muscle mass,
strength and selfcare deficit.
Linton, A. et al,
(2007) Matteson and
McConnells
Gerontological
Nursing Concepts
and Practice 3
rd
ed. Pp. 284-285

RATIONALE

EVALUATION
1. Goals are
partially met?
2. The patient was
able to verbalize
decrease pain
sensation when
she feels
comfortable?
3. The patient able
to express
feelings without
hesitant?

 Provide for
communication among
those who are involved
in caring Instruct the
S.O. to provide privacy
and equipment of the
patient within easy
reach during personal
care activities for the
patient.

Enhances coordination
& continuity of care.

Dependent:
Provide medication
To minimize back pain
therapies as prescribed
and prevent further
by the physician such
injury of the affected
as the ff.:
back.
Tenoxicam 20mg 1 tab
OD
Calcium carbonate
.
1 tab OD
Ketorolac 30mg IVTT

ASSESSMENT
Subjective:
Wala na jud koy
gamit kay dili na
ako makalihok ug
ako ra usa as
verbalize by the
patient..

NURSING
DIAGNOSIS
Disturbed selfesteem r/t loss of
health status &
independent
functioning.
SCIENTIFIC BASIS:

Objective:
Perceived
herself as
unhealthy
(scale:1/10)
Pain upon
moving
Cant stand
and sit
without
assistance.
Altered
mobility
Altered ADL
Roentgenolog
ic report:
lumbosacral
APL
Guarding
behavior

Losing ones
dependent function
makes the patient
feels disable that
could probably affect
her/his self worth.
When a patient is
experiencing loss of
health status he/she
may feels also
losing ones hope
and faith.
Source:
www.google.com

PLANNING

OUTCOME
IDENTIFICATION

INTERVENTIONS

Within 8 hrs. of
nursing
interventions,
the patient will
verbalize
increase sense
of self worth in
relation to
current
situation.

The patient will be

able to:
1. Participate in
activities in a real
life situation to
enhance change.

Develop therapeutic
relationship:
Provide
encouragement
for efforts.
Maintain open
communication.

Promotes trusting
situation in which
patient is free to be
open and honest with
self.

Talk to patient with

positive outlook in life.

Addressing issues
openly provides
opportunity for change.

2. Demonstrate
behavior changes
to restore positive
self image.

RATIONALE

Advise to recall her past Can develop an

internal locus of
successes & strengths.
control by recognizing
these aspects of them.
Give reinforcement for
Positive word
progress noted.
encouragements
promote continuation
of efforts supporting
development of coping
behaviors.
Encourage expression
of feelings & anxieties.
Facilitates comfortable
feelings.
Encourage the patient
to involve in exercise
program & promote

Enhances sense of

EVALUATION
1. Goals are
partially met?
2. The patient was
able to verbalize
positive outlook
in current
situation?
3. The patient was
able to accept
her condition?

socialization.
Encourage use of
visualization, guided
imagery, & relaxation.
Emphasize importance
of grooming & personal
hygiene.
Involve the S.O. in
teaching to manage
current situation.
Assisting both the
patient & support
people to recognize
continued dependency.

well-being & can help

energize patient.
To promote sense of
self.
To make her feel better
when they present a
positive outer
appearance.
Increases likelihood
they will provide
appropriate support to
patient.
Helps patient identify 8
cope with the
underlying reason for
dependency.

Rizvan Ali

1004618A

Discuss the Potential for H5N1 influenza viruses to cause a human pandemic
Tutor Dr Benjamin Hale

Discuss the potential for H5N1 influenza viruses to cause a human pandemic
Influenza viruses have long been the cause of pandemics throughout human history, from the Middle Ages to the 21 st century, persisting due to its
constant genetic assortment and high mutation rate. Recent pandemics include the H1N1 Spanish flu of 1918 which claimed over 40 million lives,
the 1957 H2N2 Asian flu with a death toll of around 2 million and the 1968 H3N2 Hong Kong flu causing 1 million deaths worldwide. With all
previous pandemics having some segments of avian origins in combination with the resulting high mortality rate, fears have arisen that the HPAI
H5N1 avian influenza will have similar consequences (Horimoto and Kawaoka 2005) The WHO defines a pandemic as the worldwide spread of a
disease, with three conditions which must be met; 1) there must be a disease new to a population - or at least a disease that had not surfaced for a
long time. 2) This disease must be caused by disease-causing agents that infect humans, causing serious illness. 3) The agents must spread easily
and sustainably among humans. These conditions are met to some degree by HPAI H5N1 virus. It is a new influenza virus strain to humans and
has the potential to infect humans and cause serious illness. The main barrier presently which prevents a pandemic is that H5N1 is not easily
transmissible in humans. Here we will discuss the potential for H5N1 virus to become pandemic among humans by addressing host adaptation
factors, epidemiology, transmission, pathogenesis and molecular biology of this virus.
H5N1 Structure
Annual epidemics are a result of Influenza viruses A, B or C whereas large pandemics are usually associated with Influenza A. Influenza A viruses
are enveloped RNA viruses consisting of an eight-segmented, negative sense, single stranded genome. The genome encodes 10 proteins which are
the nucleocapsid, Neuraminidase (NA), Haemagglutinin (HA), Non Structural (NS) proteins NS1 and NS2, matrix proteins M1 and M2, three
polymerases, PB1, PB2 and PA (Figure 1). PB1-F2 protein present in some influenza viruses is a recent addition to the known encoded proteins
(Bruns et al 2006)

Figure 1. Structure of Influenza A virus Virion (Horimoto and Kawaoka 2005)

Influenza A viruses are identified by surface proteins HA and NA where a different iteration of the surface proteins is coded for by a number for
example H1N1. Genetic diversity in Influenza is generated through mutations and genetic re-assortment. Mutation in HA and NA genes lead to
antigenic drift over time which explains the recurrent influenza epidemics. The segmented genome allows genetic re-assortment of HA and NA
which leads to generation of novel viruses. These viruses will go on to cause a pandemic due to the fact that the population is immunologically
nave to the antigens. The 1918 H1N1 virus is thought to have arisen via direct adaptation of avian flu to humans through mutation. Whereas the
1957 strain was caused by H1N1 acquiring novel H2, N2 and PB1. Similarly the 1968 strain was a result of re-assortment of the previous strain
with H3 and a novel PB1 gene. (Horimoto and Kawaoka 2005)
Pathogenesis
H5N1 is a potentially fatal disease causing infection of the respiratory system. It may spread to other vital organs and causes dysregulation of
cytokines and chemokines. Symptoms include high fever, malaise, cough, sore throat, abdominal and chest pain, diarrhoea, ARDS and possible
neurologicalchanges. (WHO, 2013). Usually transmitted from animal to human, there are reports of human to human transmission. Lungs have
been observed with diffuse alveolar damage and positive stranded viral mRNA, a sign of viral replication, has been detected in the trachea and
lungs. Damage has been observed in other organs including the spleen, lymph nodes, intestinal tissues, brain and placenta. Positive stranded

mRNA has been detected in the brain and intestines although this may be attributed to viraemia. H5N1 has been shown to induce higher
expression of cytokines and chemokines than human influenza. (Korteweg and Gu 2008). Up regulation of TNF alpha and TRAIL, important
molecules involved in cell death signalling and apoptosis, has been shown in macrophages (Zhou et al 2006). HA of H5N1 has also been known to
suppress perforin expression in cytotoxic T cells. The pathogenesis of H5N1 is summarised in Figure 2.

Figure 2. Pathogenesis of H5N1 in Humans (Korteweg and Gu

2008)

H5N1 virus was first detected in Guangdong Province of China in

1996, it was found to be prevalent in geese. In the following year the first instance of a purely avian flu virus causing disease and death in humans
occurred, with 18 cases and 6 deaths. This 1997 strain of virus was a re-assortment of the previous 1996 strain with H9N2 and H6N1 genes. Due
to the crackdown on poultry farms and the slaughter of 1.5 million poultry in Hong Kong this strain has not returned. The 2005 outbreak of H5N1
in migratory waterfowl was a major factor in facilitating transmission across Asia (Peiris et al 2007). As a result, following this incident, the
geographic distribution widened, outbreaks occurred in Croatia, Turkey, Russia, Egypt and Nigeria (WHO 2013).
Since then various other H5N1 re-assort ants have been detected. Previously the strains were classified A, B, C, D, E, V, W, X0-3, Y, Z and Z+ 2
according to variability in re-assortments of the genotype (Figure 3) Around 2003 genotype Z began to emerge as the dominant genotype and from

this V, W and G genotypes also emerged. Genotype V became endemic in Japan and South Korea whereas in Vietnam, Cambodia, Indonesia,
Thailand and southern China genotype Z became dominant.

Figure 3. Evolution of
H5N1 from 1999 to 2005
(Peiris et al 2007)

With increasing variability and difference a new classification method was put forward by the WHO. This current phylogenetic classification
method consists of clades 0-9 with further sub clades (Appendix 1). Clades 2.2 and 2.3 have been the dominant circulating strains during 2011 and
2012 (FAO, 2013)
2003 brought the second incidence of H5N1 in humans. It presented in a father and son returning from holiday in Fujian province. Subsequently
further human cases have occurred across Asia and the Middle East with 615 cases in total, 364 of which have been fatal (WHO 2013).

The ability for H5N1 to cause a future human pandemic depends on several factors. Effective host adaptation is required for human infection.
Genetic reassortment and mutation of the virus has led to efficient transmission in avian sources however human to human transmission is still not
prevalent but recent studies have revealed the potential for it.

Transmission of H5N1 in Humans

Host Receptor Adaptation
For effective transmission from bird to humans, H5N1 requires affinity for human host receptors. Factors which determine viral tropism are not
very well understood and is thought to be mainly determined by HA and NA as well as other genes including PB2 (Neumann and Kawaoka, 2006).
Avian influenza viruses have an affinity for alpha 2-3 linkage sialic acid linked galactose. Human influenza viruses bind to alpha 2-6 sialic acid
linked galactose usually found in the upper respiratory tract (Rogers and Paulson, 1983). Considering this, the lower respiratory tract, namely the
terminal bronchioles and alveolar epithelial cells have been shown to possess the alpha 2-3 and alpha 2-6 receptors. (Kyoko et al 2006)
Other cells which have been shown to have alpha 2-3 receptors include pancreatic and bile duct epithelial cells, endothelial cells throughout body,
intestinal mucosa epithelia, T cells and Kupffer cells (Ulloa and Real, 2001, Yao et al, 2008). H5N1 was shown to infect and replicate in ex vivo
cultures of lung fragments (Nicholls et al, 2007). Additionally a small number of H5N1 strains have accumulated mutations in the HA gene at
positions 192 and 182 which allows them to bind to alpha 2-6 receptors. Although these mutations do not allow efficient human to human
transmission (Yamada et al 2006). Related to this is the fact that quails possess alpha 2-6 receptors which bind human influenza. This may be a
potential re-assort ant vessel for H5N1 in adapting to human receptors. (Wan and Perez, 2006). Surprisingly ex vivo cultures of the upper
respiratory tract also seem to be receptive to the virus although they seem to be lacking in alpha 2-3 receptors (Nicholls et al, 2007). This along
with the absence of infection of cells possessing alpha 2-3 receptors throws doubt on the validity of this receptor as the sole determinant in host
binding, therefore further study is required.

Haemagglutinin and Neuraminidase

H5N1 like most Influenza A viruses come in two formals which are Low Pathogenic Avian Influenza (LPAI) and Highly Pathogenic Avian
Influenza (HPAI) (http://www.cdc.gov/flu/avian/gen-info/flu-viruses.htm). LPAI strains have the ability to evolve into HPAI which is the source of
concern for the current H5N1 strains. The HPAI H5N1 strain is largely determined by mutations in the HA protein. Precursor HA (HA0) is
postranslationally cleaved into HA1 and HA2 by host proteases. These two subunits are connected by a peptide chain. The dual nature of HA
mediates the fusion of viral envelope and host membrane using trypsin like proteases which are restricted to the airways (Bottcher-Friebertshauser
et al, 2010). Mutations in the connecting peptide between HA1 and HA2 increase the sensitivity to proteolytic activity so that it has high
cleavability permitting greater virus replication and dissemination (Horimoto and Kawaoka, 2001).
NA stalk deletions correlate with expanded host range indicating that this mutation is associated with interspecies transmission (Wang et al, 2006).
NA sialidase activity is important for effective virus replication and must be balanced with HA activity. NA stalk deletion results in reduced
enzymatic activity which balances with the weaker H5 HA activity, hence restoring the functional balance. The NA stalk deletion has been shown
to contribute to increased virulence and pathogenicity. This mutation was found in all 173 human cases of H5N1 from 2004-2007 which may
indicate an association with gradual transmission to humans (Zhou et al 2009).
Two of eight Vietnamese patients died from H5N1 infection. Isolates of the virus were taken and a tyrosine to histidine substitution at position 274
in the H5N1 NA gene was found to confer resistance to the influenza drug oseltamivir. A major concern, this may lead to increased persistence of
H5N1 in humans therefore a greater risk of transmission (de Jong et al, 2005).
Polymerase and Matrix Proteins
PB1, PB2 and PA make up the polymerase proteins which are involved in influenza RNA synthesis. Several mutations have been shown to
increase pathogenicity in H5N1. A substitution at position 627 in the PB2 gene from glutamic acid to lysine was detected in human strains isolated
in Vietnam and Thailand. Strains containing this substitution replicated efficiently in the lungs and at a lower temperature of 33 degrees celcius,

facilitating greater dissemination and transmission of the virus. In the context of other mutations in receptor specificity it provides a platform for
efficient human to human transmission. (Hatta et al, 2007)
PB1-F2 and M2 genes were found to be the only genes under positive natural selection in human strains (Smith et al 2006). PB1-F2 is involved in
increased host sensitivity to apoptic stimuli (Conenello et al 2007). M2 has been shown to be involved in interspecies transmission. Also a
substitution at residue 31 of the M2 protein from serine to asparagine is associated with amantadine resistance. Although only a few clade 2
viruses possess this mutation, it may be possible that in future re-assortants it will become prevalent. (Smith et al, 2006).
Non-structural Proteins
Non-structural proteins are involved in viral replication of influenza. NS1 is vital in evading host immune system via inhibition of type I interferon
response. A glutamic acid present on NS1 at position 92 was found to confer resistance to TNF alpha. The resulting H5N1 virus was unaffected by
the antiviral effects of TNF alpha in porcine epithelial cells. (Seo et al, 2002). This may cause an increased risk of virus transmission, due to
the persistence of the virus, in the case of a human infection.
Airborne Transmission
Recently it was found that four amino acid substitutions in the HA gene and one in the polymerase complex protein
PB2 allowed H5N1 to become airborne transmitted it ferrets. These were consistently present throughout strains
which were airborne transmissible. The four mutations in HA were Q222L, G224S, H103Y and T156A. In PB1 the
mutation was E267K. The mutations in HA changed the binding preference of H5N1 from avian alpha 2-3 SA to
human alpha 2-6 SA receptors. Q222L and G224S are also associated with receptor binding specificity in H2 and H3
viruses which makes these the main suspects in H5N1 receptor specificity change. The role of the E267K mutation in
PB2 was unclear (Herfst et al, 2012).
Another study also identified a reassortant H5N1 which preferentially recognized human type receptors and spread
efficiently through respiratory droplets (Imai et al, 2012).

H5N1 Epidemiology in Humans

Bird to Human
The prevalence of H5N1 in avian sources and other animal sources creates a risk of re assortment and mutation to
occur within these species which will allow the virus to adapt to interspecies transmission especially humans.
Cracking down on avian and animal reservoirs of infection is a vital preventative measure in the introduction of a
possible human transmissible H5N1.
First detected in domestic geese in China there is reason to believe that a major method of transmission of H5N1 is
through the poultry trade. In Thailand and Vietnam human infection through direct contact with backyard flocks
and poultry have been In one study of human cases, 12 confirmed and 21 suspected cases were associated with
abnormal chicken deaths including direct contact and possession of backyard flocks have been reported
(Chotpitayasunondh et al, 2005 Dinh et al, 2006). Use of faeces as fertilizer is widespread and is another potential
risk factor (WHO Writing Committee, 2005). Waterfowl such as ducks have been widely investigated and shown to be
the Trojan Horse in H5N1 generation, maintenance and transmission (Li et al). H5N1 from infected ducks remain
asymptomatic with effective transmission and possess a long virus shedding period allowing the virus to persist.
Free-range ducks drink from common water sources, swim in them and mix with other species (Sturm-Ramirez et al,
2005). Humans which utilise this water source are put at a risk of acquiring infection (WHO Writing Committee,
2005). Mixed flocks can be implicated in the re-assortment of H5N1. Much of the Asian population keep backyard
flocks and some alongside pigs. (Ly et al, 2007)
The H5N1 outbreak in migratory waterfowl in Qinghai Lake, China highlighted the possibility of wild migratory birds
contributing to viral transmission (Liu et al, 2005). A study done comparing the phylogenetic relationships of virus
isolates with the migratory movements of wild birds proved that spread to most countries in Europe was likely

through migratory birds. H5N1 could transmit through wild birds migrating from Siberia to the USA across the Bering
Sea (Kilpatrick et al, 2006).
Human to Human
Cases of human to human transmission are few and far between as of yet. One case of possible person to person
transmission was described in Thailand and resulted in one death (Ungchusak et al 2005). Another group of cases in
Indonesia suggested that person to person contact may have been responsible for H5N1 transmission. The patients
were related and lived in small enclosed spaces with lots of close contact (Kandun et al 2006). Another person to
person case was reported in China where a father and son were infected. Isolates of the virus from each of the
patients were genetically identical apart from one nucleotide substitution (Wang et al 2008). These cases
demonstrate the ability of H5N1 to become transmissible in humans and although these events are relatively rare,
with the possibility of acquiring the mutations described above it could become more prevalent.

Prevention
For effective control procedures there must be a combination of several measures. An obvious factor is early
detection of the virus so that control measures can be taken and prevent further transmission of the virus.
Quarantine of infected patients would be vital to prevent further spread and vaccination of unaffected is required to
prevent potential infection. In preventing a H5N1 introduction in humans the primary options for control of avian
sources which have proved to work are stamping out, culling of poultry, movement controls, vaccination and
education (Sims et al, 2005). Predictive modelling and epidemic simulation have been shown to be effective tools in
the control of influenza. Situations can be predicted in advance and possible control strategies developed. From
using these tools strategies have been developed for the control of a pandemic. Treatment of cases with antivirals is
effective if they are given within a day of symptoms emerging. Drugs for at least 50% of the population combined

with school closures can reduce attack rates by 40-50%. Case isolation and household quarantine can also have a
significant impact (Ferguson et al 2006). The main lessons to be learnt from previous avian outbreaks are also
applicable to possible human pandemics, these are that; intensive surveillance should be implemented to allow for
early detection, to have contingency plans in the case a rapid response is required, preventative measures should
be taken.
Treatment
Antivirals provide another option to prevent further transmission. The main ones consist of amantadine,
rimantadine, oseltamivir and zanamivir. Adamantines were effacious on H5N1 strains in the 1997 Hong Kong
outbreak. H3N2 have now acquired resistance to these and they are no longer recommended (Bright et al, 2005).
This is a danger in that a reassortment could provide H5N1 with both oseltamivir and adamantine resistance.
Effective administration strategies must be developed such as combination therapy and intravenous dosing in
severely ill patients where the digestive system is compromised. Rising resistance calls for further research to be
done into novel antivirals. One potential target is the highly virulent polymerase complex genes (Salomon et al,
2006). In the meanwhile, one strategy which should be immediately implemented is to reduce the abuse of
antivirals. With reports of antiviral resistance in H5N1 viruses due to excessive administration, the use of such
antivirals should be limited to extreme cases and even then they should be administered with restraint. One point to
note is that the strains found to be effective in human to human airborne transmission remain susceptible to
oseltamivir (Herfst et al 2012).
Vaccination
Vaccines are the focus of investigation currently. Vaccines have been used as preventative measures in H5N1
outbreaks such as in Hong Kong (Ellis et al, 2004). Vaccination even if it is of low efficacy can significantly reduce
attack rates if stockpiled in advance (Ferguson et al 2006). A pandemic vaccine may be a useful tool in prophylaxis

as demonstrated by Lin et al in a phase I trial of a H5N1 inactivated whole virus vaccine (Lin et al, 2006). A cold
adapted, live attenuated vaccine has been shown to provide broad cross protection against antigenically diverse
H5N1 strains. Pre-emptive vaccination may be a risk due to the possibility of reassortment. This ceases to be an
issue in the case of a pandemic (Suguitan et al 2006). The Holy Grail lies in a universal influenza vaccine although
this is far from reality just yet. The M2 protein possesses antigenically conserved epitopes across different subtypes
and opens up the possibility of a universal vaccine (Neirynck et al 1999)
Conclusion
In conclusion the risks of H5N1 are clear and reason to believe that it has the ability to cause a pandemic is well
grounded. Although effective human to human transmission is not yet possible with H5N1, it possesses the capacity
for it. The main risk of infection currently is through direct contact with poultry which limits infection to a certain
portion of the world population. A pandemic of poultry to human infection is unlikely to occur. There is much to be
discovered regarding H5N1 receptor specificity. Current knowledge is restricted to what we know of sialic acid
receptors and studies have shown that it cannot be the determining factor in human infection. There may be other
host factors at play here. A Cambodian incident of H5N1 occurred in a village where many of the villagers were in
direct contact with infected poultry yet only a single person acquired infection (Vong et al, 2006). This calls for
further research to be done into the host factors which make a person susceptible to infection. Control measures
have been shown to be effective in reducing viral transmission. At present the antivirals are becoming obsolete as
H5N1 increasingly becomes resistant to them. Further targets have been identified and now it is a case of
developing the tools. Vaccination is still in preliminary stages but greater understanding of the flu virus should lead
to development of an effective pandemic vaccine. Currently there are many biological barriers in the way of H5N1
preventing it from becoming truly dangerous among humans, but the potential for it to overcome these through reassortment and mutation exists, and that creates a very real risk of a future H5N1 pandemic.

Appendiz 1

WHO | FAQs: H5N1 influenza. (n.d.).

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