THE
HISTRIOGRAPHY,PHYSIOGRAPHIC
RANGES AND MOLECULAR
GENETIC EPIDEMIOLOGIC
CONSIDERATIONS FOR THE
AVIAN(BIRD) FLU AND ITS
MULTIMODAL AMELIORATION AND
DETERRENT OPTIONS.
P R O F. D O T T. E M M A N U E L U D E M E Z U E O N Y E K W E L U .
CSci,CSciTeach,ChirB(Hons),MB(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon)
C L A S S I C S A N D R E V I S I T S I N S C I E N T I F I C M E D I C I N E U P D AT E D 2 0 2 4 .
THE HISTRIOGRAPHIC,GEOGRAPHIC AND
MOLECULAR GENETIC EPIDEMIOLOGIC
CONSIDERATIONS FOR THE AVIAN(BIRD) FLU .
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Most infectious disease outbreaks in Homo sapiens commence with zoonotic transmission.
However, the mandate on how to address zoonotic epidemics is not stringent rigorous or robust,
unless it involves edible proteinogenic and economic livestocks or there is crossover and spillover to
Homo sapiens.
Today, the world is currently facing the largest outbreak of H5N1 avian influenza virus, which is
alarming because, although it is not easily transmitted to and between Homo sapiens, of almost about
one thousand (1000) cases of H5N1 in the past three decades, the case fatality was more than fifty
percent(50%) or (0.5) in Homo sapiens.
The scale of this epidemic is unprecedented as many mammals are dying from the disease, tasking
equally a lot more, the climate change instigated demands for wildlife conservation and preservation
efforts.
However, in itself, ongoing approaches and strategies on public health promotions and interventions
do not specifically address how climate change is driving several outbreaks of zoonotic pathologies.
Avian influenza has always been associated with migratory birds that would intermingle and
crossbreed with domesticated poultry birds.
However, the rising sea levels, tides and temperature changes due to the unprecedented impact of
climate change are also affecting the migration patterns of many migratory birds, potentially causing
them to integrate with other species with impacts of wider consequences and connotations on our
world today.
Although, overall ,on the average the global impact of the other given mammalian viruses implicating
the equine,canine,feline,swine and porcine species as proffered in the link presenting this question on
the science subject aspect of this questions-set are equally, however given the gross and rapid
borderless transmigratory pathway for these migratory birds, they have the greatest potential to fly
around the whole world in a very short like the airplane which was designed and modeled along the
birds themselves.
Although equally, massive transport of the given domesticated, feral or wild mammalian species,
including the avian species in themselves could equally hasten their spread through the land, sea, rail
or flights, in addition to the very motion abled wild life species physical efforts. However overall the
air where the avian species moves have no clearly demarcations, so it will be very much easier and
rapid for the Avian species Influenza virus outbreaks to turn into a global pandemic
This is exactly what inspired me to take AIV as my topic of discussion and interest in this context.
(Onyekwelu.E, Monographs in Press)
THE GENOME AND PROTEINOGENIC ORGANIZATION OF THE AVIAN VIRUS IN CONTEXT.
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Nosologically, the HPAI H5N1 virus is scientifically categorized as a
subtypology of the influenza A virus, which is a member of the
Orthomyxoviridae ancestral phylogeny.
HPAI H5N1 virus genome comprises of a negative single-stranded RNA
molecule, spanning approximately thirteen and half (13.5kb) kilobases in
length.
The genome is segmented into eight distinct segments, each encoding
specific proteins that play critical roles in the viral lifecycle.
These proteins include, but not confined to:
[I]-Haemagglutinin (HA, 568 amino acids)
[II]-Matrix protein 1 (M1, 252 amino acids)
[III]-Matrix protein 2 (M2, 97 amino acids)
[V]-Neuraminidase (NA, 499 amino acids)
[IV]-Nucleoprotein (NP, 498 amino acids)
[IVa]-Polymerase basic 1 (PB1, 757 amino acids)
[IVb]-Polymerase basic 2 (PB2, 759 amino acids)
[IVc]-Polymerase acidic (PA, 716 amino acids)
In addition to other nonstructural proteins NS1 (225 amino acids) and NS2
(121 amino acids).
The HA and NA glycoproteins are the predominant glycoproteins on the AIV
surface and exist in several different forms and have high mutation tendency
and rate.
THE GENOME AND PROTEINOGENIC ORGANIZATION OF THE HIGHLY INVASIVE
PATHOGENIC AVIAN INFLUENZA (HPAI) H5N1 VIRUS; ESPOUSES THE MOLECULAR
PATHOBIOLOGICAL MECHANISMS OF GENOMIC PROTEINOGENIC
REASSORTMENT,MUTATIONS ,POLY- BASAL CLEAVAGING AND VIRAL REPLICATIONS.
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This brief, concise and precise scientific narrative proffers a lucid overview of the intricate genomic
architecture and proteinogenic biology of the HPAI H5N1 virus.
The genomic proteinogenic biology of HPA H5N1 elucidates and matches the pathobiological and
pathophysiological mechanisms of the key viral components such as Hemagglutinin (HA) and
Neuraminidase (NA) Glycoproteins, Matrix proteins (M1, M2) etc, and non-structural proteins (NS1,
NS2) etc, with each committed to a designated functional role crucial for viral survival and virulence.
For a fairly long time, there has been a growing interest and attention on the heteromeric polymerase
complex, showcasing its implication and central role in the AIV viral replication.
The heteromeric polymerase complex is composed of the PA, PB1, and PB2 subunits, this complex
diligently chaperones and facilitates the committed and programmed phases in the AIV’s transcription
and replication, espousing and directing the virus's sustenance and progression.
Also through the fulcrum and pivot of the heteromeric polymerase complex the intricate, invasive and
intriguing phenomenon of encapsidation resulting in the formation of Viral Ribonucleoprotein (vRNP)
capsid is achieved.
The Hameagglutinin (HA) undertakes the role of the principal glycoprotein on the surface of the H5N1
virus and is implicated as a major participant in the initial stages of AIV viral infection.
The Hameagglutinin (HA) is committed and designated to undertake the role of AIV viral binding to
specific receptors on the surface of host cells, espousing and facilitating viral entry.
Additionally, the HA protein undertakes a committed, crucial and determinant participant function in
the release and integration of the viral genome into the host cell's cytoplasm by inducing membrane
fusion.
On the other hand, the Neuraminidase (NA) protein is involved in the final stages of AIV viral infection
and invasion by the cleavages of the sialic acid-containing receptors and glycoproteins on the surface
of newly formed virus particles through an enzymic lytic activity of the Neuraminidase (NA) protein,
which assists and facilitates the release of the AIV from the already infected cells, while facilitating
and permitting its dissemination to other index host’s cells, as well as offering a facilitated
opportunity for its transmission to new mammalian and Homo sapiens host cells.
This highly complementary, organised and synergistic actions of the HA and NA proteins are central
and pivotal for the uneventful, unhindered and accomplished duplication and multiplication of the
H5N1 virus.
THE GENOME AND PROTEINOGENIC ORGANIZATION OF THE HIGHLY
INVASIVE PATHOGENIC AVIAN INFLUENZA (HPAI) H5N1 VIRUS;
ESPOUSES THE MOLECULAR PATHOBIOLOGICAL MECHANISMS OF
GENOMIC PROTEINOGENIC REASSORTMENT,MUTATIONS ,POLYBASAL CLEAVAGING AND VIRAL REPLICATIONS.
The nucleoprotein (NP) undertakes the determinant and critical role of encapsidation of the
genome of HPAI H5N1 virus.
The NP synergistically with the three polymerase subunits—PA, PB1, and PB2—forms a viral
ribonucleoprotein (vRNP).
This RNP complex plays a crucial and pivotal role in several phases of the AIV viral life
cycle, such as, but not confined to its RNA transcription, replication, resistance, packaging
and protection.
The Matrix protein 1(M1) is an indispensable and committed component of the HPAI H5N1
virus particle and has been elucidated to play a central and very contributory part in the
process of viral budding from the plasma membrane of infected cells and it also interacts
with vRNP to regulate the vRNP transport between the cytoplasm and the nucleus of its
mammalian and Homosapiens host cells.
The M2 protein of the HPAI H5N1 virus, also referred to as the M2 proton channel, sustains
the acid base pH equilibration that transcends across various phases of the AIV viral life
cycle.
The HPAI H5N1 virus RNA polymerase consists of three subunits: PB1, PB2, and PA which
constitutes into a heteromeric protein complex.
RNA polymerase undertakes the transcription of the viral genes and replication of the viral
RNA.
The NS1 protein of the virus assumes a stringent pivotal role of inhibiting mammalian and
Homo sapiens host interferon elaboration and the circumventing and undermining the
function and prowess of the interferon-proactivating proteins that limits and prevents the
replication of the HPAI H5N1.
Employing its polyactive defensive characteristics, endowments and features, NS1 aids in
evading the host immune responses and espousing very rapid viral replication in the
mammalian or Homo sapiens host cells.
Analogously, on the other hand, the NS2 protein has been elucidated to fast track the
nuclear emigration of viral ribonucleoprotein complexes (vRNPs) by acting as an anchor,
facilitator and chaperone between the viral RNPs and the cellular mechanisms dedicated
for nuclear emigration.
REASSORTMENT,PHYLOGENIC EVOLUTION AND MUTATIONS ARE SOME INHERENT ,INNATE AND ADAPTIVE MECHANISMS
THROUGH WHICH THE AIV PERSISTS IN HOST CELLS,ACQUIRE TOLERANCE TO HOST CELLS IMMUNE RESPONSES AND
PERPETUATES THEIR SPECIFIC RECALCITRANT AND RECIVIDIST CYTOPATHIC AND CYTOPATHOGENIC EFFECT AND IMPACT
ON MAMMALIAN AND HOMO SAPIENS HOST CELLS ACROSS THE WHOLE WORLD OF TODAY.
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The HPAI H5N1 virus has been categorized into ten principal monophyletic natural
group (primary clades) with a common phylogenic ancestry (denoted as 0–9),
complemented by numerous subordinate (secondary clades) and monophyletic natural
groups and diverse subsidiary monophyletic natural groups (minor clades).
To date, HPAI H5N1 viruses have undergone several physiographic domiciliary, regional
and international spontaneous, episodic and impulsive variations in its evolutionary
histriographic phylogeny with some consequential divergence, including but not
confined to H5Ny principal monophylegenic natural group 2.3.4.4b between(2016–2017);
H5N1 principal monophylegenic natural group 2.3.2.1c and H5N8 principal
monophylegenic natural group 2.3.4.4a from (2014 to 2015); H5N1 principal
monophylegenic natural group 2.3.2.1c within (2009 and 2010) in addition to H5N1
principal monophylegenic natural group 2.2 between (2005 and 2006).
From 2020 to 2021, an exotic new onset spontaneous, episodic and impulsive variations
in its evolutionary histriographic phylogeny with some consequential divergence of the
Highly Pathogenic Avian Influenza Virus (HPAIV) H5N1 principal monophylegenic natural
group 2.3.4.4b evolved within the widely ranged physiographic regions of continental
Europe, Asia, and Africa, affecting, invading and impacting an extensively distributed
miscellenous subsets of feral, wild and domesticated birds, in addition to the Avian
species held in captivity in domiciliary abodes, zoos and wildlife parks etc.
Towards the penultimate physiographic seasons of 2021, in China, in East Asia two
exotic new onset reassortants of HPAIV (H5N1) principal monophylegenic natural group
2.3.4.4b.2 were identified in demised exotic cross border intercontinental Avian species
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The attenuated, diminutive and compromised antigenic immunological response of this
new onset reassortants to vaccine antiserum demonstrates its enormous potential
deleterious negative impact, in addition to the attributive and relative risks posed to the
preventive and public health coverage in a global epidemiological context.
REASSORTMENT,PHYLOGENIC EVOLUTION AND MUTATIONS ARE SOME INHERENT ,INNATE AND
ADAPTIVE MECHANISMS THROUGH WHICH THE AIV PERSISTS IN HOST CELLS,ACQUIRE
TOLERANCE TO HOST CELLS IMMUNE RESPONSES AND PERPETUATES THEIR SPECIFIC
RECALCITRANT AND RECIVIDIST CYTOPATHIC AND CYTOPATHOGENIC EFFECT AND IMPACT ON
MAMMALIAN AND HOMO SAPIENS HOST CELLS ACROSS THE WHOLE WORLD OF TODAY.
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In one of the most recent reports of HPAIV (H5N1) principal monophylegenic natural group
2.3.4.4b outbreak reported by Centre for Disease Control (CDC) in New England North Eastern
USA, HPAI infections were observed among gray seals and harbor, leading to an inordinate
and unprecedented mortality of seals which was instantaneous and contemporaneous with a
spontaneous, episodic and impulsive variations of avian infections.
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In this context, the investigators inferred the occurrence of more than two cross species viral
transmission phenomnena, from the avian to the seal population with a spontaneous, episodic
and impulsive variations of avian infections.
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This multiple viral externalisms from the avian species to the seal species were ascertained
and elucidated, through phylogenetic analysis of Sanger sequenced genomic data obtained
from avian- and seal-derived virus genomes, in addition to other available data of the most
proximate sequence.
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In this context, evidential and scientific proof of positive adjustments, adaptations and
tolerance were demonstrated in a limited number of seals, it is possible that Homo sapiens
comparable immunology may equally proffer a committed channel for adaptation, adjustments
and tolerance to the AIV like the seals.
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The principal findings from the derived dataset infers the importance and relevance of
assessments, evaluations,monitoring and observations of both the aquatic and mammalian
species and the wild inshore and maritime avian species, which would be contributory in the
definition, description, qualification and quantification of the distinctive features and nature of
the AIV disease affecting Homo sapiens cohabiting through vast physiographic areas and
ranges and ,in this way to determine the extensively huge epidemic capability, capacity and
prowess of H5N1 .
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Previous reports from Indonesia in Southeast Asia and Oceania between the Indian and Pacific
oceans sent in alerts and notifications of the invasion of the HPAI H5N1 principal
monophylegenic natural group 2.3.2.1c virus in South Sulawesi, Indonesia, duck poultry farms.
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There were initial hypothetical postulations that the principal monophylegenic natural group
2.3.2 AIVs had reassorted with H9 viruses and that principal monophylegenic natural groups
2.3.2.1c, 2.3.2.1b, and 2.3.2.1a viruses had reassorted as well.
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In a related but distinctive study, for the very first time, previous Ecuadorian reports
announced the identification and isolation of the highly cytopathogenic H5N1 principal
REASSORTMENT,PHYLOGENIC EVOLUTION AND MUTATIONS ARE SOME INHERENT ,INNATE AND ADAPTIVE MECHANISMS
THROUGH WHICH THE AIV PERSISTS IN HOST CELLS,ACQUIRE TOLERANCE TO HOST CELLS IMMUNE RESPONSES AND
PERPETUATES THEIR SPECIFIC RECALCITRANT AND RECIVIDIST CYTOPATHIC AND CYTOPATHOGENIC EFFECT AND IMPACT
ON MAMMALIAN AND HOMO SAPIENS HOST CELLS ACROSS THE WHOLE WORLD OF TODAY.
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This principal monophylegenic natural group was stringently linked to the H5N1
principal monophylegenic natural group 2.3.4.4b viruses obtained from a North
American red fox and a South American Avian prey falcon, indicating a potential
transmission pathway from North America to South America and across host species.
The H5N1 principal monophylegenic natural group 2.3.4.4b virus strains discovered in
the Ecuadorian series have been categorized collectively with those identified in
pelicans from Peru and wild birds from Chile.
These strains were also phylogenically proximate to those elucidated in the Venezuela
pelicans, demonstrating that the HPAIV H5N1 principal monophylegenic natural group
2.3.4.4b viruses is preponderance and cross migrating in multiple countries in South
America.
In South America, domestic poultry birds are frequently present in the hinterlands
especially the provincial, rural, underdeveloped areas of Ecuador, especially in the AIV
sporadically affected regions, which later became known as epidemic hot spots for AIV.
This ecosystem could untowardly support and facilitate Homo sapiens-infectedmammalian close but non-symbiotic association and co-habitation, which unfavourably
fortifies the avian influenza zoonotic transmission in a compromised and less endowed
preventive public health operational mechanisms.
Previous investigations have demonstrated that maximum likelihood (ML) phylogenetic
analysis suggests two distinct HA H5N1 principal monophylegenic natural groups,
which are one (1 and two (2) 2.3.4, as well as two distinct NA groups within the
corresponding H5N1 principal monophylegenic natural group one (1) virus through
indepth investigations on the genetic evolution of the HA and NA genes of HPA1 H5N1.
REASSORTMENT,PHYLOGENIC EVOLUTION AND MUTATIONS ARE SOME INHERENT ,INNATE AND ADAPTIVE
MECHANISMS THROUGH WHICH THE AIV PERSISTS IN HOST CELLS,ACQUIRE TOLERANCE TO HOST CELLS IMMUNE
RESPONSES AND PERPETUATES THEIR SPECIFIC RECALCITRANT AND RECIVIDIST CYTOPATHIC AND CYTOPATHOGENIC
EFFECT AND IMPACT ON MAMMALIAN AND HOMO SAPIENS HOST CELLS ACROSS THE WHOLE WORLD OF TODAY.
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Employing the Bayesian evolutionary reconstruction for molecular clocks models other
investigators proposed that chronologically, the H5N1 HA and NA emerged in Thailand
in 2001.(95% HPD: 2001.34–2002.49) and 2002.38 (95% HPD: 2001.99–2002.82),
respectively .
This presupposition implies that the AIV virus would have been existing prior to its
identification, isolation and proclamation about two decades ago.
The AIV identified in Thailand of the H5N1 HA principal monophylegenic natural group
2.3.4 was grouped into subordinate monophylegenic natural group 2.3.4, 2.3.4.1, 2.3.4.2,
and 2.3.4.3, and its nucleotide comparabilities to the reassortant H5Nx subordinate
monophylegenic natural group 2.3.4.4 ranged from 92.4 to 96.8%.
The phylogenetic study demonstrated that the H5N1 subordinate monophylegenic
natural group 2.3.4 gave rise to the single-branched H5Nx subordinate monophylegenic
natural groups 2.3.4.4 .
Previous seminal studies have characterised and reported the alterations at positions
129 and 134 in a virus taken from a person who died because of the viral infection.
Further investigations on this theme asserted that these alterations could equally
modify the pattern of HA binding to the receptors from SA_2,3Gal to SA_2,3Gal and
SA_2,6Gal.
Complementary investigations on this theme through molecular modeling demonstrated
that this molecular divergence could probably confine SA_2,6Gal in its most structurally
favourable- cis form at the receptors binding point or site.
In this contexual study, the investigators demonstrated that about one-half of the viral
sequences which were instantaneously magnified from a respiratory sample of the
demised index case with AIV infection mentioned above carried the mutation
REASSORTMENT,PHYLOGENIC EVOLUTION AND MUTATIONS ARE SOME INHERENT ,INNATE AND ADAPTIVE
MECHANISMS THROUGH WHICH THE AIV PERSISTS IN HOST CELLS,ACQUIRE TOLERANCE TO HOST CELLS IMMUNE
RESPONSES AND PERPETUATES THEIR SPECIFIC RECALCITRANT AND RECIVIDIST CYTOPATHIC AND CYTOPATHOGENIC
EFFECT AND IMPACT ON MAMMALIAN AND HOMO SAPIENS HOST CELLS ACROSS THE WHOLE WORLD OF TODAY.
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In this patient, the investigators demonstrated and confirmed the H5N1 virus
binding to a Homo sapiens prototype receptor, which was interpreted as
evidence for the selection and expansion of the mutant with Homo sapiens
prototype receptor specificity in the Homo sapiens host internal milieu.
To expedite, hasten and incite pandemics and viral transmissions in Homo
sapiens, a mutation in the HA gene at the receptor binding site(RBS) could
drift and translocate the receptor binding choices and options from the
avian SA-2,3-Gal to the Homo sapiens SA-2,6-Gal.
Several workers on this theme have confirmed that all the Sulawesi isolates
in Indonesia, have maintained the same receptor binding site (RBS) amino
acid constitution, since they were initially demonstrated, elucidated,
isolated and discerned.
Previous Indonesian studies on ducks in have equally demonstrated Q222
(glutamine) and G224 (glycine) receptor binding site which are members of
the subordinate monophylegenic natural group 2.3.2.1c.
Permutation of Q222L and G224S in the HA sequence may diminish binding
to 2.3 receptors and augment binding to Homo sapiens 2.6 receptors.
When the Homo sapiens H5N1 influenza A virus neuraminidase mutations
were evaluated for their phenotypic attributes and characteristic features in
an eminent research on this theme, the investigators deciphered that when
compared invitro in avian cells and Homo sapiens cells, the replication
capacity, capability, rapidity, magnitude and quality of H5N1 AIV with avianor Homo sapiens-cellular analogues of NAs were comparable or equivalent.
On further investigations, it was demonstrated that however, the Homo
sapiens-cellular analogues of NA espoused and supported viral replication in
human airway epithelia.
REASSORTMENT,PHYLOGENIC EVOLUTION AND MUTATIONS ARE SOME INHERENT ,INNATE AND ADAPTIVE MECHANISMS
THROUGH WHICH THE AIV PERSISTS IN HOST CELLS,ACQUIRE TOLERANCE TO HOST CELLS IMMUNE RESPONSES AND
PERPETUATES THEIR SPECIFIC RECALCITRANT AND RECIVIDIST CYTOPATHIC AND CYTOPATHOGENIC EFFECT AND IMPACT
ON MAMMALIAN AND HOMO SAPIENS HOST CELLS ACROSS THE WHOLE WORLD OF TODAY.
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Across ten (10) divergent influenza viruses harboring NA from the subsidiary monophylegenic natural
groups 1 and 2, the (L204 M) mutation was demonstrated to have a universally restrictive and
undermining influence effect on NA activity.
It was equally elucidated that the Homo sapiens cellular analogues of H5N1 virus does not replicate
as much viral NA RNA or elaborate as much NA protein as its avian ancestry did.
The Homo sapiens equally demonstrated diminished viral export and enhanced transcellular
translocation and in addition to an augmented accumulation of NA at the plasma membrane.
Furthermore, it was equally elucidated that AIV virus binding to Homo sapiens receptors was equally
augmented by NA mutations.
Although the evaluated NA mutations had no direct influence on the highly pathogenic nature of H5N1
in chickens, they did alter the virulence and replication of H5N1 AIV in the experimental mice rodent
test system models, to a lesser consequence, in ferrets.
Categorically, alterations to the NA of Homo sapiens H5N1 viruses have characteristically peculiar
impacts during infections in mammals but have no discernible effect on the virus cytopathogenicity or
ability to spread among chickens.
It is presumed that these findings should aid in the prediction of AIV with zoonotic potential and
further the more lucid comprehension of the genetic instigators and facilitators for AIV replication in
mammals.
In another contexual study, peramivir-resistant H5N1 strains with a dual H274Y–I222K mutation was
demonstrated as the culprit pathogen.
Additionally, it was deciphered that mutations within the PB1, PB2, and PA subunits could proffer
consequential implications for the virulence, transmission, cytopathogenicity, biological behaviour and
drug resistance of the H5N1 virus.
The PB1 subunit, serving as the catalytic core of the polymerase complex, is amenable, vulnerable and
susceptible to mutations that carry the potential to influence a spectrum of viral fitness attributes and
pathogenic characteristics.
Of much interest and especially of consequence is the H99Y mutation, which has demonstrated a correlation with
heightened polymerase activity and enhanced replication efficiency within mammalian cell contexts.
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Mutations occurring within the PB2 subunit, constituting the principal component of the polymerase complex, have
demonstrated significant implications, including elevated replication efficiency and adaptability to mammalian hosts.
Remarkably, the E627K permutation eloquently presents a characteristically peculiar mutation, consequent on the swapping of
glutamic acid with lysine at position 627.
REASSORTMENT,PHYLOGENIC EVOLUTION AND MUTATIONS ARE SOME INHERENT ,INNATE AND ADAPTIVE MECHANISMS
THROUGH WHICH THE AIV PERSISTS IN HOST CELLS,ACQUIRE TOLERANCE TO HOST CELLS IMMUNE RESPONSES AND
PERPETUATES THEIR SPECIFIC RECALCITRANT AND RECIVIDIST CYTOPATHIC AND CYTOPATHOGENIC EFFECT AND IMPACT
ON MAMMALIAN AND HOMO SAPIENS HOST CELLS ACROSS THE WHOLE WORLD OF TODAY.
• This genetic alteration plays a pivotal role in facilitating
proficient replication within the human host.
• Another consequential genetic mutation, D701 N, also
situated within the PB2 subunit, entails the substitution of
aspartic acid with asparagine at position 701.
• This mutation has been correlated with intensified
polymerase activity and heightened virulence within
mammalian environments.
• PA, serving as the third subunit within the polymerase
complex, undertakes the role of an essential and pivotal
endonuclease engaged in the synthesis of viral mRNA.
Analogous to the PB2 and PB1 subunits, thorough
investigations have pinpointed specific amino acid positions
within the PA protein—namely PA-573, PA-383, PA-353, PA347, PA-343, PA-241, PA-237, PA-224, PA-185, PA-127, PA-101,
and PA-44—that play a discernible role in influencing both the
replication process and the virulence characteristics of the
virus .
MOLECULAR GENOMIC MARKERS FOR AIV ADAPTATION:
IN MAMMALIAN CELLS,TISSUE AND ORGAN SYTEMS
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The molecular marker 627K, or its equivalents such as 701N, in the
PB2 gene have been detected in some but not all sequences of
viruses obtained from mammalian infections.
• It has been detected in very few sporadic wild bird and poultry
cases.
• These markers are known to increase viral replication in mammalian
cells.
• In studies on viruses from the wild avian species and poultry, there
is no indication that the viruses have changed their preference for
binding to avian-like receptors as such.
• Although, none of the viruses from infected mammals, including
Homo sapiens, have alterations indicating an enhanced specificity
of binding to Homo sapiens-like receptors.
• However, some genetic mutations are present which have been
demonstrated to augment the capability and flair to bind to Homo
sapiens-like receptors.
• The AIV virus isolated from the infected minks has a genetic
mutation that might make the virus replicate more efficiently in
mammal cells.
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The viruses from mink, and some viruses from the avian species, had
additional mutations more commonly seen in Homo sapiens viruses.
THE ANTIVIRAL SUSCEPTIBILITY OF THE
NAÏVE NATIVE AIV AND THE MUTATED AIV:
• Virus sequences from Homo sapiens cases,
where available, did not demonstrate
markers for resistance to neuraminidase
inhibitors (such as oseltamivir) or
endonuclease inhibitors (such as baloxavir).
• Sequences analyzed from circulating
viruses in animal species contained only
sporadic mutations which are associated
with resistance to antiviral
pharmacotherapies.
• On the basis of the evidential reports and
the available information on the human
population, immunity against the influenza
A (H5) clade 2.3.4.4b virus haemagglutinin
is expected to be minimal.
THE EPIDEMIOLOGY ,VIRULENCE AND HOST DYNAMICS OF HPAI H5N1.
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It has been demonstrated that Type A AIVs pose considerable disease burden to the preventive and
public health systems of any contexual population, given their inherent capacity and capability to
incite excessive epidemics.
Several previous studies on this theme, indicates that AIVs, most especially subtypes H1 to H16, are
naturally prevalent in aquatic avian species, which serve as their primary reservoir.
Chronologically, several years before 2005, a consequential transmission of HPAI H5N1 from poultry to
wild avian species was relatively uncommon.
Thereafter however, a drift happened causing a novel phase in the epidemiological dynamics of HPAI
H5N1 in exotic wild Avian species populations.
The most consequential wave in the HPAI H5N1 virus among poultry and wild Avian species
populations occurred during the period of 2004–2006.
As an aftermath, HPAI H5N1 is inciting an extensive fatality that cuts across both the wild avian
species and mammalian populations that transcends several physiographic and epidemiologic regions
globally.
This highly adapted virus is projected to persist in its dissemination, thus perpetuating adverse
consequences on conservation and preservation endevours.
Commencing from 2020, a significant global exponential increase has been noted in the notification
trends of HPAI H5N1 outbreaks impacting both domestic and wild avian species.
In the years 2021 and 2022, a total of fifty four (54) countries documented an exponential increase in
the impact of H5N1 avian influenza in the Avian populations.
It has been reported that from January 2022 and June 27, 2023, the HPAI H5N1 virus was identified in
over seven thousand (7,000) wild birds across fifty(50)states and in more than eight
hundred(800)commercial and backyard flocks in forty seven(47)states within the United States,
marking the initial occurrences of such detections since 2016 .
The rapid and concerning spread of HPAI H5N1 among both domestic and wild bird populations is a
phenomenon that transcends continental boundaries.
It’s highly intricate, sophisticated and specialised genomic and proteinogenic molecular virulent
factors in addition to its immense capacity and capability which facilitates its permeation of the
widely ranged avian ecological and physiographic habitats across very extensive regions, impacting
on miscellenous wide range of bird species.
The virus has demonstrated its capacity, capability and prowess to impact domestic poultry farms of
all sizes, as well as wild bird populations that transcends the continents of the Americas, Asia, Europe
and Africa.
HPAI H5N1 has been naturally isolated from an extensive range of other mammalian al species,
including the canindes and the feline species, in addition to their hybrids,
such as coyotes, lions,Tilions,leopards, cats, dogs, foxes, seals, , mustelidae (minks and otters),
skunks, tigers, lions, ligers, pikas, otters, polecats, porpoises, raccoons, raccoon dogs, pigs, Virginia
opossums, civets, badgers, bears, dolphins, stone/beech martens, and even the pisces species, etc.
Normally AIVs, invades the gastrointestinal systems of the wild Avian species and are usually released
into the environment by these Avian species through various means, such as saliva, feces, and nasal
THE EPIDEMIOLOGY ,VIRULENCE AND HOST DYNAMICS OF HPAI H5N1.
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The transfer of HPAI H5N1 infection to Homo sapiens principally occur through direct contact with
infected avian species.
The migration of infectious HAPI H5N1 within airborne particles encompasses distances of less than
ten (10) metres.
However, within macroscopic particles containing viral RNA, the potential for translocation extends
remarkably to approximately eighty (80) metres.
On the basis of evaluation reports on this theme, the probability of inter-premises airborne
translocation of the subsidiary monophylegenic natural groups 2.3.4.4b HAPI H5N1 is considered to be
inconsequential.
In addition, other factors, such as the covert interaction of the AIV with the wild avian species and the
strengths and vigour of the biosecurity measures in place, play a more pivotal role in influencing
disease introduction dynamics.
Furthermore, viral RNA from HPAI H5N1 was detected in environmental specimens such as dust
swabs, thus raising concerns about the potential for airborne transmission through inhaling suspended
infectious particles.
While the H5 subtypes of AIVs are generally not efficient in infecting humans, as they do not replicate
effectively in the upper respiratory tract of humans, they typically do not facilitate human-to-human
transmission.
However, certain strains have demonstrated the ability to permeate the species barrier and infect
Homo sapiens, leading to a spectrum of infections ranging from mild flu-like symptomatologies to
severe cases resulting in demise and uniform fatality.
Interestingly, it is disheartening that HPAI H5N1 has the ability, capacity and capability to migrate
through the placental barrier, resulting in the infection of the fetus.
Overall, on the average, H5 subtype of AIVs pose a challenge and concern primarily to Homo sapiens
who have direct contact with infected avian species.
However, the probability of these viruses inciting a huge-scale human outbreaks is considered to be
more or less negligible.
Chronologically for a fairly longtime, the H5 viruses have been subject to some genetic heterogeneity,
amounting to the emanation of several principal, subordinate and subsidiary monophylegenic natural
groups.
Among these monophylegenic natural groups, a subordinate monophylegenic natural group’s referred
to as 2.3.4.4b has demonstrated extensive spread across Eurasia and Africa since 2020.
THE EPIDEMIOLOGY ,VIRULENCE AND HOST DYNAMICS OF HPAI H5N1.
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In early 2022, this subordinate monophylegenic natural group was detected in North America (new
world), likely introduced by transatlantic migratory birds from the European continent (the old world)
into the new world.
Thereafter, it rapidly disseminated throughout the American continent.
It is already given and well known that HPAI H5N1, has the ability, capability, capacity, propensity,
prowess and virulence, in addition to other primary and acquired adaptive attributes such as but not
confined to segmentation, reassortment and mutations etc, to infect both Homo sapiens and their
domestic animals.in addition to several wild animals.
Although, it has been believed that the transmission of HPAI H5N1 from the avian species to the Homo
sapiens is thought to be infrequent, and Homo sapiens -to-Homo sapiens transmission is seldom, a
restricted number of Homo sapiens cases have been documented in several epidemiological and
physiographic regions globally since 2003 with relatively high fatality rates.
Given the demonstrated drifts in the HPAI H5N1 epidemiological dynamics during 2022–23 in the
European continent, it is prudent to scale up the surveillance of zoonotic transmission events between
animals and Homo sapiens.
Transmission of Highly Pathogenic Avian Influenza (HPAI) H5N1 to Homo sapiens, the avian species,
and the other animals which triggers on the hosts actions of adaptive and innate immune responses
against HPAI H5N1, which includes the activation of the innate immune response of the host cells
upon detection of HPAI H5N1 viral immunogenic components.
This response includes, but not confined to the elaboration of pro-inflammatory cytokines, such as
Interferons (IFNs), and the co-option and recruitment of innate immune cells.
Overall, on the average, the adaptive immune responses, implicates both the humoral and cellular
immune responses, triggered on by the HPAI H5N1 infection.
Technically, this response implies the activation and proliferation of antigen-specific B cells, leading
to the production of virus-neutralizing antibodies and the activation of T cells, including both cytotoxic
T lymphocytes (CTLs) and helper T cells.
Principally, this process, involves very synergistic and complementary interactions between adaptive
and innate immune cells, such as the presentation of viral antigens by antigen-presenting cells (APCs)
a form of dendritic cells to activate T cells and the cooperation between B cells and T cells for the
production of specific antibodies and humoral factors.
In summary, to recapitulate, although the transmission of avian influenza from the avian species to
Homo sapiens is relatively rare, it is crucial to pay attention to the specific and overall impacts of this
infection due to several significant reasons.
These reasons could be summarized as follows:
[I]-THE OVERALL IMPACTS OF THE UNANTICIPATED AND UNPRECEDENTED OUTBREAKS:
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The recent outbreak of AIVs represents the largest bird outbreak ever recorded histriographically.
The magnitude of this infection evokes some challenges with utmost considerations about the
futuristic and prospective potential for the virus to disseminate rapidly and have a significant impact
on avian populations, the ecosystems and naturally on Homo sapiens and other mammals for obvious
reasons.
• [II]-THE ECONOMIC IMPACT OF THE AIV:
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It has been given that the invasion of even minimal co-habitats of a poultry flock could result in a rapid
dissemination of the AIV amongst other members of the index flocks result in the loss of the entire
flock and beyond.
Of course, naturally this would be expected to have very severe economic consequences for the entire
poultry farm industry as a group, including financial losses and disruptions in the supply chain.etc.
[III]-THE UNTOWARD IMPACT FOLLOWING THE INVOLVEMENT OF AN
EXTENSIVE RANGE AND MISCELLENOUS SPECIES OF HOSTS:
The current outbreak has seen a higher number of the avian species and mammalian species being
infected in comparison to previous outbreaks.
This expanded range of hosts increases the potential for the virus to persist, evolve, and potentially
cross species barriers, posing a threat to both mammalian species and Homo sapiens health.
• [IV]-THE COMMERCIAL IMPACT OF THE AIV INVASIONS.
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It would not be illogical to speculate and accept that the anecdotal propositions that the avian
influenza outbreaks has led to an exponential and erratic augmentation in the price of poultry
products, chicken and eggs in the North America and beyond.
This reiterates and pinpoints the untoward impact and economic the negative financial implications
and challenges encountered by the private and public agroentreprenurial enterprise, the consumers,
the end users and the wider society at large.
[V]-THE GRIEVOUS IMPACT OF THE EMANATION OF PROBABLY
EXOTIC,NOVEL,FLORID AND DELETERIOUS BIOLOGICAL VIRAL CLADES:
The wider physiographic ranges of the new onset viral infections and the involvement of newly evolved
species proffer springboards for the emanation of novel and potentially more deleterious clades of the
virus.
The diligent and utmost epidemiological and ecological evaluations, observations and lucid
comprehension of these clades are seminal to appraise their probability, prowess and flair for an
enhanced virulence, mutagenicity, transmissibility pathogenicity and pharmacotherapeutic
susceptibility and resistance.
[X]-THE INORDINATE AND UNUSUAL PREPONDERANCE OF NEW CASES
STAPHYLOCCOCAL,HAEMOPHILUS INFLUENZAE AND STREPTOCOCCAL PNEUMONIAS AND
RESPIRATORY SYSTEM INFECTIONS WHICH ARE FREQUENT
EPIPHENOMENAL,POSTPHENOMENAL AND PARAINFECTIOUS CO-PATHOGENS OF
INFLUNZAE PNEUMONIA AND RESPIRATORY SYSTEM INFECTIONS.
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Almost all we know today on this theme, have been derived from experimental test system animal
models which have demonstrated that complex and intricate molecular mechanisms underlie the
ability of viruses to predispose to bacterial superinfection following primary AIV infection of the
respiratory system and its adnexal organ systems.
In essence, it is already well known that, viral infection could incite decimation of the airway both
histologically and physiologically, encouraging secondary bacterial co-pathogen invasion.
As has been analogously previously demonstrated X-ray reotenogenographically by the
author(PROFESSOR GLADSTONE) and other scholars on this theme,in essence,primary influenzael
pneumonia like measles viral pneumonia are viral interstitial pneumonia, whereas bacterial
pneumonia are epiphenomenal or post measles or influenzael viral phenomena.
And these X-ray retongenographic features could be employed to achieve a therapeutically useful
antimicrobial guide at the first instance when blood cultures may not be rapidly achievable as is the
case in most industrialised regions globally.(Onyekwelu.E. 2009)
On the basis of the implicated primary viral pathogen, the histopathology induced could be relatively
mild, moderate, severe or profound and cellular atrophy and aplasia, goblet cell hypertrophy and
hyperplasia, altered mucus secretion and/or biochemistry, disruption of surfactant, reduced ciliary
oscillatory frequency, dis-coordinated mucociliary clearance function and reduced oxygen exchange
etc.
For a long time, it is already well known that in themselves, all of these invasive pathological impacts
have been associated with potential mechanisms by which viruses could predispose the respiratory
tract to bacterial superinfection.
In addendum, other specific mechanisms associated with viral-bacterial co-infection include, but not
confined to; dysregulated activation, migration and function of antigen presenting cells (T-cells
alveolar macrophages, antigen presenting dendritic cells, native naïve tissue and macrophages);
disruption of opsonisation and phagocyte function; abnormal expression of antimicrobial/host defense
peptides.
Other mechanisms by which viruses predispose to secondary bacterial infection includes, but not
confined to generalized immunosuppression which incites immune-incompetence and immuneparalysis; destruction of the airway epithelium/induction of hyperplasia/cell loss/exposure of basement
membrane;increased receptor availability on epithelial cells promotes augmented bacterial
adherence; virus induced alteration of the microbiome with increase in pathogens associated with
secondary infections.
[VII]. THE PREVAILING PATHOBIOLOGICAL TRANS-SPECIES
AND INTERSPECIES TRANSLOCATIONAL MECHANISMS.
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The rapid and facilitated translocational mechanisms noted and demonstrated amongst
several miscellenous subsets of mammalian species, such as Spanish minks and
southern American marine felines, evokes immense considerations about the capability
and capacity for the virus to create niches and reservoirs in several divergent animal
populations and present imminent, instantaneous and prospective ongoing risks to both
animal and Homo sapiens health.
• [VIII]-IMPACT OF THE AIV IN ANIMAL ETHOLOGY AND
HOMOSAPIENS BEHAVIOUR AND PSYCHOLOGY.
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Besides its direct impact on the health of Homo sapiens and animals as will be discussed
prospectively, it is speculated and known that the unbalanced ecosystem brought in by the AIV
epidemic has negatively influenced the already known and predictive mammalian ethology and Homo
sapiens behaviorism and psychology.
While the animal species got more unpredictably, paradoxically aggressive and violent in some
instances, in other circumstances they became unexpectedly too docile, lazy and lethargic.
As for Homo sapiens, especially those working in the poultry industry and the veterinary and health
sectors, the fear, trepidation and apprehension of getting infected or affected by the AIV has brought
in lots of anxiety,depression,and in some instances neurosis etc in addition to low productivity at work
with its consequential untoward financial implications.
[IX]-THE NEGATIVE IMPACT OF THE IMPLIED WORK PRESSURE ON THE
MULTIDISCIPLINARY, INTERDISCIPLINARY AND TRANSDISCIPLINARY
PERSONNEL ,LOGISTICSAND RESOURCES AT LARGE AND BEYOND.
It is given that previous histriographic retrospective scientific research, the ongoing
research and the prospective research and the application of its resulting prophylactic,
diagnostic, therapeutic, prognostic and integrative interventions will have immense
logistics, resource and personnel implications that cuts across several health and its
allied scientific disciplines and much more.
The ecological, physiographic, biological and epidemiological research on AIV
outbreaks will involve ornithologists, research scientists, biologists,animal
scientists,immunologist,pathologists,ecologists,epidemiologists,ethologists,geogrphers
,virologists ,animal scientists, veterinary doctors,project managers, scientific quality
assurance auditors etc.
[X]-THE INORDINATE AND UNUSUAL PREPONDERANCE OF NEW CASES
STAPHYLOCCOCAL,HAEMOPHILUS INFLUENZAE AND STREPTOCOCCAL PNEUMONIAS AND
RESPIRATORY SYSTEM INFECTIONS WHICH ARE FREQUENT
EPIPHENOMENAL,POSTPHENOMENAL AND PARAINFECTIOUS CO-PATHOGENS OF
INFLUNZAE PNEUMONIA AND RESPIRATORY SYSTEM INFECTIONS.
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Other additional host compromising defense mechanisms that
encourage secondary bacterial co-pathogen invasion in influenza
RTI includes, virus-induced type I interferons alteration of the
phenotype of the immune response, augmented production of
inflammatory mediators (cytokines, chemokines, acute phase
reactants with other humoral factors)etc.
Additional mechanisms encouraging secondary bacterial invasion
includes virus-facilitated and mediated release of bacteria from
biofilms and viral dysregulation of nutritional immunity, in addition
to diminished ciliary oscillatory frequency/disruption of mucociliary
clearance/altered mucus rheology and other non-specific immune
compromising mechanisms etc.
The ultimate goal of research in the field of viral–bacterial coinfections of both the upper and lower respiratory tract is to
translate our improved understanding of the molecular mechanisms
that underlie these superinfections into development of better
diagnostics, treatment modalities and prevention strategies.
This is particularly consequential as the potential for prospective
pandemics and emergence of novel viruses, the expansion of
antimicrobial resistance by bacterial co-pathogens is anticipated, in
addition to due considerations for the impact of the ubiquitous
globally migratory birds and very frequent travel and expedition on
the facilitation of the relatively rapid trend of transmission.
UNDERSTANDING THE IMMUNOPATHOLOGICAL IMPACT OF THE AIV
ON HOMO SAPIENS THROUGH INDEPTH INSIGHTS AND ELUCIDATION
OF THE IMMUNE MODULATION,REACTIVITY,REGULATION AND
RESPONSIVENESS AGAINST HPAI H5N1 VIRAL EVASION.
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The immune response is known to play a significant role in the infectivity and virulence of the HPAI
H5N1 virus.
The current and ongoing elucidation and comprehension of the immune responsiveness to the HPAI
H5N1 virus is based on these primary sources:
[I]- In vitro studies and experimental animal test system models.
[II]- The assessment and evaluation of the immunological behaviour in index cases and other patients
infected and afflicted with HPAI H5N1as research candidates.
[III]-The appraisal, examination and evaluation of the invitro, preclinical and clinical immunological
behaviour to investigational vaccines targeting HPAI H5N1.
[IV]-Critical studies,metanalysis,systematic reviews,extrapolations and scientific inferences using the
Bayesian statistical models, machine learning and other artificial intelligence prototype’s inferences
and extrapolations from existing body of knowledge base regarding the already known and partly
studied seasonal influenza viruses.
The innate immune system serves as the initial defense mechanism against viral infections.
It detects viral infections by recognizing pathogen-associated molecular patterns through specific
receptors known as pattern recognition receptors (PRRs).
With regards to the influenza virus, at least three different classes of PRRs contribute to its
recognition: retinoic acid–induced gene I (RIG-I)–like receptors, Toll-like receptors (TLRs), and
nucleotide oligomerization domain (NOD)–like receptors.
The complex and intricate interactions between the influenza-associated molecular patterns and PRRs
in cells of the upper and lower respiratory systems is essential for the induction of innate immune
responses against the virus in the host.
Influenza viruses primarily infect lung epithelial cells, which express TLR3 and RIG-I.
It has been established that TLR3 and RIG-I have significant roles in the induction of type I interferon
(IFN) production upon detection of influenza virus replicative and genomic RNA.
Macrophages and dendritic cells (DCs) are also present and active participate in the immune
modulation and responsiveness in the respiratory system, of Homo sapiens and they are crucial
elements of the innate immune responsiveness to pathogens. Since the DCs are dedicated and
specialised antigen-presenting cells (APCs), therefore, they link innate and adaptive immune
responses.
Indeed, it is daunting to note that the HPAI H5N1 virus has demonstrated some tendency towards nonsusceptibility and resistance to the antiviral effects of IFNs and TNF-α.
UNDERSTANDING THE IMMUNOPATHOLOGICAL IMPACT OF THE AIV ON HOMO SAPIENS THROUGH INDEPTH INSIGHTS AND ELUCIDATION
OF THE IMMUNE MODULATION,REACTIVITY,REGULATION AND RESPONSIVENESS AGAINST HPAI H5N1 VIRAL EVASION.
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It is already known that adaptive immunity undertakes a crucial and pivotal role following an infection
with the H5N1 virus.
The assessment of antibody responses against H5N1 virus demonstrates that HA-specific antibodies
that recognize epitopes on the globular head of HA could neutralize virus infectivity by hindering
cellular adherence of the virus to sialic acid.
The dynamics and kinetics of the antibody responsiveness to the H5N1 virus are analogous to primary
responses observed in seasonal H3N2 and H1N1pdm09 viruses.
Multiple studies have demonstrated the protective efficacy of antibodies targeting the HA in
experimental animal test system models.
Furthermore, studies have demonstrated that the passive transfer of anti-NA antibodies effectively
protected an experimental rodent test system models from the deleterious impact and lethality
associated with HPAI H5N1 viral invasion.
Following infection with the HPAI H5N1 virus, specific CD4+ and CD8+ T cell responses against the
virus are elicited.
Although the exact and precise role of cell-mediated immune responses in combating H5N1 infection
remains incompletely understood, studies have proposed that prominent influenza-reactive CD4+ T
cells recognize conserved peptides derived from internal viral proteins, including the M1 protein and
NP of this contexual virus.
Furthermore, some studies have demonstrated the presence of CD4+ T cell responses directed against
the polymerase proteins PB1, PB2, and PA of influenza A virus.
It is noteworthy to acknowledge that the HA and NA were targeted by CD4+ T cells only.
The function of influenza A virus-specific CD8+ T cells includes several crucial and pivotal roles, such
as but not confined to protection against severe influenza, facilitation of rapid host recovery, and
acceleration of viral clearance.etc.
Previous studies on the immunopathology and fate of the committed participants in the cellular
immune responses in this context, infers that a given population of influenza A virus-specific CD8+ T
cells attains a high nadir within one week following infection and subsequently wanes and undergoes
a rapid attenuation.
Additionally, therefore, a comprehensive assessment of viral adaptation to infect and propagate within
cells of Homo sapiens through specific genetic mutations is imperative.
Significant mutations in the HA of the HPAI H5N1 virus have been observed to aid in its evasion from
the clearance impact of the immune system.
Furthermore, re-assortment events, also known as antigenic shift, can further contribute to the virus'
ability to evade immune detection.
Consequently, the immune system may struggle to recognize the newly formed virus variants, leading
to a compromised functionality in the antigen-antibody interaction pattern.
UNDERSTANDING THE IMMUNOPATHOLOGICAL IMPACT OF THE AIV ON
HOMO SAPIENS THROUGH INDEPTH INSIGHTS AND ELUCIDATION OF
THE IMMUNE MODULATION,REACTIVITY,REGULATION AND
RESPONSIVENESS AGAINST HPAI H5N1 VIRAL EVASION.
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The HA gene mutations, for instance, exerts significant influence over the virus's
binding affinity to the cells of Homo sapiens. Intriguingly, the initial H5 HA
demonstrated restricted binding to human tracheal epithelium; however, strategic
introduction of selected mutations facilitated a transition to a binding profile akin to
that of contemporary Homo sapiens influenza HA strains. Noteworthy differences
emerge between HA proteins from Homo sapiens influenza A and avian isolates in their
binding preferences for sialic acid residues.
While the Homo sapiens strains prefer α2-6 conformers, avian variants exhibit an
affinity for α2-3 linkages.
Consequently, avian isolates necessitate adaptive mutations to effectively engage
human-type receptors.
The receptor binding site (RBS) of the HA is endowed with an important seminal and
central role ,given that amino acid mutations within it undertakes crucial roles in
determining the virus's ability to adapt, invade, and replicate within Homo sapiens
cellular milieu which transcends through the pathological pathway of the influenza A
virus evolution, development and cytopathogenicty.
Beyond the HA gene, multiple H5N1 isolates have undergone mutations in critical viral
genes, particularly the PB2 component of the polymerase complex, augmenting their
replicative efficiency within the cells of Homo sapiens.
Notably, the amino acid at position 627 of PB2 emerges as a focal point, exerting major
influence over the host range of influenza A virus.
Moreover, amino acids at positions 591 and 701 of PB2 contribute to the replication
dynamics of avian influenza viruses in mammalian hosts.
Finally, immune escape mechanisms could be achieved through mutations occurring in
the NA protein of the HPAI H5N1 virus.
ELUCIDATING THE IMPACT OF THE AIV (HPAI H5N1) IN ON THE WORLD TODAY THROUGH ADDRESSING THE
KNOWLEDGE GAPS IN ITS PATHOGENESIS AND CLINICAL MANIFESTATIONS IN HOMO SAPIENS.
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The pathogenesis of a viral infection could be categorized into distinct phases on the basis of the
specific route undertaken by the virus within the host organism.
The molecular pathobiological mechanisms driving the pathogenesis of the HPAI H5N1 is
multifactorial, with viral replication and dysregulation of cytokines, chemokines and other non-specific
humoral factors being determinant and principal contributors. and active participants in its
pathogenesis.
The dysregulation of immune factors, including the upregulation of TNF-related apoptosis-inducing
ligand (TRAIL) and diminished cytotoxicity of CD8+ cells, have been implicated in the progression of
this invasive pathology, in addition to being associated and linked with the peculiar pathological
behaviour and patterns of the features in affected Homo sapiens cases.
It has been demonstrated that the HPAI H5N1 virus induces a substantial upregulation of numerous
cytokines, chemokines and other active participant humoural factors in the macrophages of Homo
sapiens and respiratory syncytial epithelial cells.
The induction of functional TRAIL, a cell apoptosis inducer, in macrophages affected by the HPAI
H5N1 virus may have a determinant role in the pathogenesis of this invasive viral pathobiology.
Apoptosis, triggered by the direct viral replication and/or the overdrive of unregulated over production
of deleterious cytokines chemokines and other invivo qualitative and quantitative dependent humoural
factors, can be considered a major determinant pathogenic pathway contributing to the multi-organ
involvement observed in HPAI H5N1 infection.
Additionally, influenza-related lymphopenia has been observed as another mechanism of HPAI H5N1
pathogenesis, particularly in severe cases affecting Homo sapiens.
Another pathogenic mechanism of HPAI H5N1 invasion involves the reduction of perforin activity in
cytotoxic T cells by HAs.
This could lead to a decrease in cytotoxic function, impairing the clearance of infected cells, including
APCs carrying the HPAI H5N1 virus.
The incubation period of HPAI H5N1 infection is typically short, lasting for approximately one week or
less, with an average duration of two (2) to five (5) days.
In addition to respiratory symptomatologies and feature, Homo sapiens infected with HPAI H5N1 may
experience accompanying symptomatologies such as cephalgia, myalgia, pharyngo-tonsillitis, acute
rhinitis and occasionally, conjunctivitis or bleeding gums.
HPAI H5N1 has an immense capacity, capability and potential to affect several cells, tissues and
organ-systems in Homo sapiens, including the lungs, central nervous system (CNS), and the
gastrointestinal systems and its adnexae.
Histopathologically, more often than not, the lungs is demonstrated and observed to have commonly
undergone diffuse alveolar destruction, haemmorrhagic epiphenomenon, formation of hyaline
membrane, lymphocytic infiltration, and excessive fibroblasts elaboration, especially in the Homo
sapiens cases, where the HPAI H5N1 have been implicated as the viral culprit.
ELUCIDATING THE IMPACT OF THE AIV (HPAI H5N1) IN ON THE WORLD TODAY THROUGH ADDRESSING THE
KNOWLEDGE GAPS IN ITS PATHOGENESIS AND CLINICAL MANIFESTATIONS IN HOMO SAPIENS.
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The observed lung damage in HPAI H5N1 cases may be partially explained by the unmodulated
sensitization and up-regulation of TRAIL.
In cases of influenza A virus infections in Homo sapiens, CNS involvement emerges as the
predominant extra-respiratory tract complication.
Notably, it has been demonstrated that HPAI H5N1 virus infections are characterized by a heightened
inclination toward CNS disease manifestation when contrasted with infections stemming from
seasonal influenza viruses.
In ferrets, a recognized animal model for influenza pathogenesis research, the HPAI H5N1 virus has
demonstrated the ability to access the CNS via the olfactory nerve, consequently giving rise to severe
meningoencephalitis.
Intriguingly, intranasal inoculation of ferrets with HPAI H5N1 viruses commonly leads to infection of
the olfactory mucosa, facilitating subsequent infiltration into the CNS. This infiltration predominantly
occurs through the olfactory nerve pathway, with the trigeminal nerve pathway also serving as an
additional conduit for virus transmission.
Hepatic complications of influenza, while infrequent, have been associated with elevated
transaminase levels, particularly pronounced in severe cases and among Homo sapiens infected with
HPAI H5N1.
Very challenging and difficult circumstances arise, when avian influenza viruses become highly
pathogenic for Avian poultry.
This typically happens when the haemagglutinin (HA), one of the two proteins on the surface of the
virus (with neuraminidase (NA) being the second protein), acquires a polybasic cleavage site.
This permits and facilitates the HA to be activated not just by selected proteases, which confines the
localization of the virus to specified and committed tissues, but also equally there will be activation
by furin-like proteases found in almost all tissues, allowing wider dissemination and tropism of the
virus throughout the host.
This polybasic cleavage site is the same element that is found in some coronaviruses, including SARSCoV-2 and some Homo sapiens seasonal coronaviruses.
Acquisition of a polybasic cleavage site could happen spontaneously, often when an avian influenza
virus enters a poultry farm and replicates extensively in large concentrations of susceptible
mammalian cells.
ELUCIDATING THE IMPACT OF THE AIV (HPAI H5N1) IN ON THE WORLD TODAY THROUGH ADDRESSING THE
KNOWLEDGE GAPS IN ITS PATHOGENESIS AND CLINICAL MANIFESTATIONS IN HOMO SAPIENS.
Extensive replication augments the probability of insertions occurring in the viral genome, which could
lead to the emanation of a polybasic cleavage site.
In some cases, the source material of the insertion seems to be fragments of chicken ribosomal RNA1.
This acquisition of a polybasic cleavage site by avian influenza viruses has been well documented and
reported across poultry farms in North America and beyond.
It has equally been documented and reported for H5 subtype HA.
Avian H5 and H7 subtype influenza viruses with polybasic cleavage sites cause severe invasive disease in
poultry, result in massive economic losses including augmented poultry and egg prices, whilst
endangering the wild avian species as well.
These viruses could equally cause severe invasive disease in Homo sapiens as well, if significant amounts
are inhaled quite well into the lungs, in which case, the fatality rates could be quite high.
Typically, these Avian viruses are problematic most for individuals in direct contact with infected birds.
However, there are two other major concerns for the avian influenza viruses that could occur even in the
absence of acquisition of a polybasic cleavage site.
At the first instance, an avian influenza virus may co-infect an individual, who is at the same time infected
with a human influenza virus.
In that case, the two viruses may infect the same cell and re-assort their genomic segments, which could
result in a virus that replicates well in the cells of Homo sapiens, but has HA and NA glycoproteins to
which humans are naive.
An analogous genomic segment assortment could equally occur in other mammals including the domestic
porcine species.
This mechanism was likely involved in the emanation of up to seventy five percent, if not all, of the
historiographic influenza pandemics.
Also it has been speculated and demonstrated that, an avian influenza virus may grow in a mammal and
start to mutate in a way that would allow it to spread efficiently from mammal to mammal and
potentially to Homo sapiens.
Such as is the case fairly recently following an outbreak of H10N7 infections in seals in Northern Europe,
in which case, the virus mutated thereafter to become transmissible to Homo sapiens .
This virus did not have a polybasic cleavage site but still led to mass mortality among seals.
All of the current highly pathogenic avian H5N1 viruses that are endemic in many parts of the world trace
back to A/goose/Guangdong/1/96.
ELUCIDATING THE IMPACT OF THE AIV (HPAI H5N1) IN ON THE WORLD TODAY THROUGH ADDRESSING THE
KNOWLEDGE GAPS IN ITS PATHOGENESIS AND CLINICAL MANIFESTATIONS IN HOMO SAPIENS.
This virus lineage caused its first zoonotic outbreak in 1997 in Hong Kong.
Histriographically, following a short break, zoonotic infections were recorded again in 2003
which has lingered on till date , with the virus spreading across Eurasia and Africa in
the migratory avian species.
According to the World Health Organization, almost nine hundred cases in Homo sapiens of
H5N1 infection with about five hundred fatalities were recorded between January 2003
and 23 January 2023 , with most of the cases occurring before 2016.
This suggests a very high case fatality rate of more than one half.
However, many cases of asymptomatic or abortive infection may not have been recorded in
areas where there is increased Homo sapiens contact with the virus.
Equally, these infections in mammals have caused severe disease, including neurological
complications and high fatality rates.
The virus has also infected several mammals that may feed on carcasses of dead birds,
including foxes, raccoons and bears.
Most have been one way tracked infections, implying that the virus spread from the Avian
species to mammals but did not spread among mammals.
Very few Homo sapiens cases have been reported, and only after close contact with
infected Avian species.
Similar to the situation in Eurasia and Africa, the H5N1 virus is causing much damage to
the poultry industry in North America and has devastated several Avian bird
populations.
A subclade of clade 2.3.4.4, namely 2.3.4.4b, now having an N1 NA again, commenced to
spread extensively across Eurasia and Africa in 2020.
Whereas, Clade 2.3.4.4b viruses were then detected in North America early in 2022, where
they arrived via migratory birds from Europe ; they have now spread across the
Americas.
AN OVERVIEW OF THE PATHOGENICITY OF THE HIGHLY PATHOGENIC
AVIAN INFLUENZA (HPAI) H5N1 AND ITS CHARACTERIZATION.
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Severe cases of HPAI H5N1 infection have been associated with hospitalization due to the
development of complications such as acute respiratory distress syndrome (ARDS) and multi-organ
failure, such as respiratory and renal failure, pulmonary hemorrhage, pneumothorax, and pancytopenia
etc.
Fatal outcomes in HPAI H5N1-infected individuals have been associated with high viral loads,
lymphopenia, and elevated levels of inflammatory cytokines and chemokines.
• IMPACT OF THE VIRUS IN THE WORLD TODAY
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Avian influenza viruses (AIVs) are globally challenging due to their extensive dissemination and high
fatality rates.
Highly pathogenic avian influenza (HPAI) strains like H5N1 have caused significant outbreaks in the
avian species.
It is given that since 2003 to 14 July 2023, the World Health Organization (WHO) has documented 878
cases of HPAI H5N1 infection in humans and 458 (52.16%) fatalities in 23 countries.
Recent outbreaks in wild avian species, domestic avian species, marine feline species, minks, and
etc., and the occurrence of genetic variations among HPAI H5N1 strains evokes concerns about their
potential transmission and untoward public health implications.
• IMPACT OF THE VIRUS IN THE WORLD TODAY
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AIVs are categorized into two groups based on their pathogenicity to chickens as determined by the
intravenous pathogenicity index (IVPI) test: highly pathogenic avian influenza viruses (HPAIV) and
minimal or low pathogenic avian influenza viruses (MPAIV/LPAIV) Fairly recently, the transmission of
HPAIV strains such as H5N1, H5N8, and H7N9 has presented real significant threats to public health
Among the various HPAIV strains, the H5N1 virus is regarded as the most pathogenic, with a high
mortality rate impact in chickens and Homo sapiens.
Following the initial outbreak of the highly pathogenic avian influenza (HPAI) H5N1 virus in 1959
among poultry in Scotland and its subsequent transmission to humans in 1997 in Hong Kong,
numerous outbreaks among birds have been documented and reported .
Fairly recently, several regions globally have encountered an infection of the HPAI H5N1 virus, evoking
great concerns among domicilliary,regional and international global health authorities .
Accounting for the global epidemiology of its impact from 2022–2023,this outbreak proffered a
notification trend and endemic channels of HPAI H5N1 virus identifications across a diverse spectrum
of hosts, including but not confine to the wild avain species , poultry, and domestic avian species,
distributed across about thirty countries in the European continent.
IMPACT OF THE VIRUS IN THE WORLD TODAY
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Notably, the impact of this outbreak extended beyond avian
populations, leading to the unfortunate demise of
about three
thousand five hundred marine feline species within the Peruvian
region.
This event in itself highlights the intricate dynamics of viral
transmission among these divergent mammalian species.
Such a widespread infection among bird populations could
contribute to the persistence of the virus within avian species and
increase the risk of transmission to other species, including those of
economic importance or even Homo sapiens.
The current global outbreak of HPAI H5N1 among animals has
brought urgent attention to the need for a comprehensive
understanding of this virus and its implications for public health.
With increasing reports of Homo sapiens infections and the potential
for devastating consequences, it is imperative to tackle the
intricacies of HPAI H5N1 in order to effectively respond to the
ongoing outbreak among animals, mitigate its impacts, and prevent
future outbreaks and transmission to Homo sapiens.
THE IMPACT OF THE ORIGIN AND EVOLUTION OF HPAI H5N1 VIRUS IN THE WORLD TODAY.
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HPAI H5N1 virus has shown significant advancements in its evolution over the past six decades with
considerable impacts on Homo sapiens, the fauna and flora in addition to the environment supporting
these lives.
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As given previously, following the initial outbreak of HPAI H5N1 virus in 1959 among poultry in
Scotland, United Kingdom a notable incident occurred in Hong Kong, whereby the HPAI H5N1 virus
claimed the lives of about half a dozen Homo sapiens out of about a score who contracted the
infection in 1997.
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This histriographic devastating occurrence denoted the foundational identification of a HPAI H5N1
virus strain in Homo sapiens, attracting global attention and wider connotation to its potential
untoward impact to public health.
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Following a temporary hiatus, HPAI H5N1 resurged in 2003 and have persisted since then, with the
virus disseminating among wild avian populations across the three continents of Europe, Asia, Africa
and beyond.
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Between 2003 and 2008, the geographic expansion of HPAI H5N1 virus escalated, encompassing not
only East Asia but also Southeast Asia, West Asia, North Africa, and various other regions perceived
its untoward impact.
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Consequently, a growing number of nations found themselves afflicted or affected by the impact of the
virus
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Subsequently, thereafter several cases are consistently reported in China, Vietnam, Cambodia,
Indonesia, and Egypt on an annual basis.
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Although the incidence of cases in Asia remained relatively low between 2013 and 2015, Egypt in
North Africa experienced a significant surge in 2014 and 2015.
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In 2020, HPAI H5N1 was initially identified in both wild and domestic avian populations within the
continent of Europe.
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This pathogen subsequently spread across the continents of Africa, the Middle East, and Asia in a
pattern similar to the 2003 epidemic wave.
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Global notification trends indicated that during May 2021, the HPAI H5N1 virus was detected in wild
foxes in the Netherlands in the European continent.
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Thereafter, in late 2021, there were also reports of HPAI H5N1 virus cases among wild foxes in
Estonia.
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Reviews of global endemic channels infers that between late 2021 to 2022, the HPAI H5 virus caused
significant poultry outbreaks across the globe, untowardly impacting various regions globally.
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Further international notification trends indicated that from 2022 till date, the occurrence of animal
infections caused by HPAI H5N1 was notably frequent and alarming.
THE IMPACT OF THE ORIGIN AND EVOLUTION OF
HPAI H5N1 VIRUS IN THE WORLD TODAY.
• Notably, the majority of fatalities in Homo sapiens occurred
prior to 2016 .
• According to the mortality and morbidity reports, between
2022 and July 2023, a total of fourteen cases of HPAI H5N1
were confirmed in Homo sapiens in accordance with the WHO
report, resulting in two fatalities.
• It was anecdotally speculated and evidentially demonstrated
that there are subtle and marked genetic variabilities, lack of
concordance and divergence among various HPAI H5N1
strains in various physiographic regions globally.
• A further case of HPAI H5N1 was reported to WHO on March
29, 2023, by the Chilean Ministry of Health.
• On April 7, 2023, the National Institute of Communicable
Diseases (NIC) announced the results of its genome
sequencing, concluding that the most implicated virus was
HPAI H5N1, phylogenetic clade 2.3.4.4b .
THE HISTRIOGRAPHIC,PHYSIOGRAPHIC RANGES AND MOLECULAR GENETIC
EPIDEMIOLOGIC CONSIDERATIONS OF THE GLOBAL IMPACT OF THE AVIAN(BIRD) FLU
In 1918, a strain of influenza A virus caused a human pandemic resulting in the deaths of
about fifty(50) million people globally.
A century later, with the advent of sequencing technology and corresponding phylogenetic
methods, we know much more about the origins, evolution and epidemiology of
influenza epidemics.
Here we review the history of avian influenza viruses through the lens of their genetic
makeup: from their relationship to human pandemic viruses, starting with the 1918
H1N1 strain, through to the highly pathogenic epidemics in birds and zoonoses up to
2018.
As given to the index link complementing this question that I am responding to the
Influenza virus mammalian invasion cuts across several mammalian species.
Although major lineages for avian, swine, human, equine and canine hosts could be
demonstrated and observed, however cross-species transmissions are quite common.
HISTRIOGRAPHIC NOTES ON NOMENCLATURE AND AVIAN MODELS FROM FOWL PLAGUE TO AVIAN INFLUENZA.
Histriographically several centuries ago, severe non-bacterial pathogenic outbreaks with high mortality
rates in domesticated Avians have been on records since the late 1800s .
In the nineteenth and early twentieth centuries, these outbreaks were termed ‘fowl plague’, and it was not
until 1955 that (Schafer, 1955)determined that ‘fowl plague virus’ (FPV) was indeed a type of AIV, with
similar internal antigens to human and swine influenza viruses. [Schafer W. 1955).
Sequencing studies performed many years later resulted in the identification of the highly pathogenic
avian influenza (HPAI) virus strains responsible for these outbreaks as H7 subtype IAVs.
In 1959, an antigenically divergent HPAI H5 subtype was found in a chicken farm in Scotland, while in 1961
an H5N3 strain was isolated from a wild common tern (Sterna hirundo) in South Africa.
Because of the highly pathogenic phenotype of these first H5 and H7 isolates, it was prudent to consider
all H5 and H7 viruses to have very closely related biological virulence behaviour.
However, this stance was reexamined after the isolation of low pathogenic avian influenza (LPAI) H5 and
H7 strains from ducks in the 1950/1960s and from turkeys in the 1960s/early 1970s
THE HISTRIOGRAPHIC,PHYSIOGRAPHIC RANGES AND MOLECULAR GENETIC
EPIDEMIOLOGIC CONSIDERATIONS OF THE GLOBAL IMPACT OF THE AVIAN(BIRD) FLU
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Since then, an enormous variety of LPAI and HPAI H5 and H7 subtypes have been isolated from
domestic and wild avian species, as well as the viruses bearing the majority of all other possible
combinations of H1–H16 and N1–N9 surface glycoproteins- etc.
As previously given, one hundred years ago, in 1918, the ‘Spanish flu’ pandemic, caused by an H1N1
influenza virus is estimated to have contributed to the deaths of around fifty (50) million Homo sapiens
species.
Since then, thereafter, three other Homo sapiens AIV pandemics have occurred: H2N2 in 1957 (Asian
flu), H3N2 in 1968 (Hong Kong flu), and H1N1 again in 2009 (swine flu) etc.
Typically in each given event,AIV strains bearing segments coding for antigenically novel NA and/or
HA surface protein(s) rapidly spread through a Homo sapiens population with no or little prior
immunity.
The relationship between fowl plague, avian influenza and human influenza was not apparent before
the 1950s, but by 1967 Pereira, Tumova & Webster suggested that the human H2N2 and H3N2
pandemic viruses might have had an avian origin on the basis of antigenic cross-reactivity. (Pereira H
G, Tumova B, Webster R G., 1967 pp982-3)(Pereira HG.1969, pp46-79) (Tůmová B, Pereira H. G.1968;
pp415–420).(Webster R.G., Campbell, C.H. Granoff A. 1971,pp317-328)
As soon as IAVs were sequenced, phylogenetic analyses commenced to demonstrate how avian and
human viruses were related, and how this relationship could vary according to the segments involved.
This contexual studies lucidly reaffirmed the veracity of the avian virus origin of the Homo sapiens
1957 and 1969 pandemic glycoprotein genes.
The complete sequences of 1918 human H1N1 viruses are also available (e.g. A/Brevig Mission/1/18
(H1N1)) despite this pandemic preceding the identification of IAV as the causative agent, since
samples have been obtained direct from tissue samples of the afflicted Homo sapiens
However, it has been quite challenging and difficult to infer the host species of the ancestor(s) of the
1918 pandemic virus, since there are only three partial sequences of HA or NP from contemporary
avian isolates (obtained from museum samples collected between 1915 and 1919) , and most of the
earliest other avian and swine virus sequences are from samples from the 1930s .
Although the Homo sapiens 1918 H1N1 sequences form a group with the contemporaneous classical
swine H1N1 lineage, analysis of the polymerase gene sequences and time-scaled phylogenetic studies
indicate that these 1918 Homo sapiens IAV segments probably do have an avian ancestral origin [39,
40].
The subsequent two Homo sapiens pandemics (1957 and 1968) were not caused by completely avianorigin viruses, but were rather reassortant viruses with avian-origin HA, PB1 polymerase and (for the
1957 pandemic) NA segments .
The N2 neuraminidase in the 1968 strain, however, was a continuation of the avian N2 previously
introduced in the Homo sapiens population in 1957.
THE HISTRIOGRAPHIC,PHYSIOGRAPHIC RANGES AND MOLECULAR GENETIC
EPIDEMIOLOGIC CONSIDERATIONS OF THE GLOBAL IMPACT OF THE AVIAN(BIRD) FLU
The 2009 H1N1 ‘swine flu’ pandemic was a
result of reassortment between different
strains of AIV that had been circulating in
swine for at least a decade, but these
precursor swine strains all had segments
tracing back to avian origins some three
decades previously.
Sporadic infections of Homo sapiens with a
restricted number of avian virus subtypes (H5, H6,
H7, H9, H10) have also been demonstrated to
impact directly from avian sources, but without as
yet leading to sustained Homo sapiens to Homo
sapiens transmission.
Typically, these infections impacts severely on Homo
sapiens globally, often inciting demise, and
imminent zoonotic epidemics are equally
challenges worthy of utmost considerations.
THE MOLECULAR BASIS FOR THE STRIKINGLY DIFFERENT VIRULENCE
PHENOTYPES SEEN WITH H5 AND H7 VIRUSES HAS ALSO BEEN ELUCIDATED .
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THE MOLECULAR BASIS FOR THE HIGH AND LOW PATHOGENIC PHENOTYPES OF H5 AND H7 STRAINS OF IAV.
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Histochemically,it has been elucidated that HA is synthesized on the
endoplasmic reticulum as a precursor HA0 polypeptide, assembled into a
trimer, glycosylated and transported intracellularly through the Golgi
apparatus to the cell surface.
At this point, it has the potential to be incorporated into budding virus and
thereafter would be active as a receptor binding molecule.
However, it is quite inert and incapable of promoting membrane fusion and
thus virus entry into the next cell, until a post-translational cleavage event
has taken place to activate it by separating the HA1 and HA2 domains and
liberate a fusion peptide at the new N-terminus of HA2.
In LPAI strains of virus, cleavage is performed extracellularly by host
proteases present on mucosal surfaces, after a single basic residue.
By contrast, as previously intimated, the HPAI strains have an expanded
multi-basic sequence that allows intracellular processing via ubiquitous
furin-like proteases; this has the consequence of expanding the tissue
tropism of the virus and facilitating systemic invasive disease.
This phenomenon is well established for H5 and H7 HAs, but for reasons that
are still enigmatic and unclear, not been seen outside of the laboratory for
other HA subtypes.
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GLOBAL PATTERNS OF AVIAN INFLUENZA PHYSIOGRTAPHIC RANGES S AND ITS CIRCULATION.
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Anecdotally and evidentially, the water fowl, especially Anseriformes (ducks,
geese and swans) and Charadriiformes (gulls, terns and sandpipers), are
thought to be the natural reservoir of IAV , and infection in these host
species is not only typically low pathogenic but more often than not could be
asymptomatic .
It has also been demonstrated that migratory birds may carry HPAI as well
as LPAI viruses asymptomatically over very long distances, and that avian
AIV lineages can spread along migratory fly pathways.
Employing geographic information systems (GIS) and high definition
performace and resolution phylogenetic analysis of remote sensing and
phylogenetic analyses it has been demonstrated that the distribution of
H5N1 viruses in Eastern Asia followed wild avian species migratory flyways
in the time period 2003–2012.
Also, transmission between places and host species can be inferred by
phylodynamic and phylogeographical analyses, and these techniques are
particularly suitable for the utmost comprehension of the avian influenza
systems since they make use of the fast-evolving viral sequence data to
reveal dispersion patterns etc.
Phylogeographic analyses have revealed the role of migratory avian species in the intracontinental circulation of LPAI in North America, and have implicated wild avian
following North American flyways in the introduction of H7N3 strains into Mexico in
2012–2013 .
Similarly phylogeographic techniques have equally been employed to demonstrate the
effects of HPAI H5N1 transportation by different avian species across Asia and that the
spread of LPAI H9N2 strains in Asia was a combination of long-range distribution by
wild avian species coupled with more localized spread via the domestic avain species
trade.
INFERENCE OF TRANSMISSION ROUTES USING PHYLODYNAMICS AND PHYLOGEOGRAPHY.
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The spatial and temporal distribution data of the AIV viral sequence data sampled over a specified
period of time, AIVs spatial locations and different host species could be used to infer transmission
patterns.
Typically for AIVs, time-scaled phylogeny reconstruction is often performed using the programme
BEAST (Bayesian Evolutionary Analysis Sampling Trees) in which trees and relaxed molecular clock
models are colorates of the relationship between genetic distance and time, and other parameters,
which are collectively derived and inferred.
To infer transmission rates between discrete localizations or hosts, or to model subtype alterations,
phylogenetic analysis with discrete traits could be employed, where transitions from one state to
another are inferred along the phylogeny as a continuous time Markov chain model such as H5N1 in
Asia and H7N3 in North America etc.
Discrete trait analyses can be extended by parameterizing the transition rate matrix as a log–linear
function of various potential covariates in a generalized linear modeling framework, to identify the
host species or environmental factors associated with the observed spatial spread.
When the additional feature of interest is continuously distributed, e.g. location as latitude and
longitude, Brownian random motion walks can be used to model the diffusion of the trait along the tree
corresponding to the dispersal history of the pathogen.
The impact of environmental factors on virus dispersal could be estimated by correlating the
distances along branches of the trees with the resistances resulting from the diffusion path through
landscapes of environmental variables using R package SERAPHIM.
In addition to trait-based approaches, BASTA and MASCOT make use of structural coalescent
approximations to reconstruct evolutionary trees while considering the size of the different subpopulations involved in the meta-population, improving inference of the migration rates between subpopulations.
Finally, by combining epidemiological data and recent phylogenetic inference techniques, several
methodologies such as SCOTTI, Outbreaker and Beastlier are now able to reconstruct, with some
success, the transmission tree of only partially observed epidemics.
The effect and impact that bird migratory flyways have on the global circulation of IAV could be
appreciated in the phylogeny of all segments, where two very distinct major clades corresponding
either to the Americas or to Asia, Europe, Africa and Australasia could be discernibly observed.
\
INFERENCE OF TRANSMISSION ROUTES USING PHYLODYNAMICS AND PHYLOGEOGRAPHY.
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Estimates of the time to most recent common ancestor (TMRCA) of these clades varies by segment
and methodology, but appears to be in the region of about a century, a value close to the root of the
major contemporary human, swine and avian lineages, etc and as such represents a categorically
deep divide.
Although viral dissemination via wild birds could be thought of as occurring along fly pathways,
divergent species have different migratory patterns, and these general fly pathways could
considerably overlap. Consequently, cross-fly pathways, and the intercontinental transmission of
avian IAV by wild birds does occur.
There is a robust evidence for transfer of AIV genes from the Americas to Eurasia.
Flyways of migratory water fowl run approximates from north–south, and also overlap in northern
regions, including in Greenland, Alaska Siberia, and across the Bering straits etc , which allows
occasional transmission of influenza viruses between North America and Eurasia as well.
However, even if migratory birds might be good vectors of AIV, transmission patterns indicate that
circulation is partially maintained through trade of infected domestic birds.
Therefore, it is given that the global spread of avian IAV results from an intricate synergy between
trade of infected domestic avian species and wild avian species motions through migratory fly
pathways.
New HPAI strains are thought to emerge from an LPAI ancestral progenitor as a result of their
introduction into domestic avian populations.
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Anecdotally, it has been speculated that since domestic ducks could share the same habitat, water
and food as wild waterfowl, their presence and concentration are thought to make them key
intermediate hosts between wild avian species and poultry, and consequently they play an
important role in the emergence and circulation of HPAI strains, especially in Asia.
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The bridging role of domestic ducks between wild birds and domestic Galliformes has been
particularly reiterated in the H7N9 IAV outbreaks in China, most notably in areas where high
concentrations of free-grazing ducks live in close contact with potentially infected wild avian
species, such as the Poyang and Dongting Lakes.
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Agricultural practices, such as the emancipation of a huge quantities of juvenile ducks in paddy
fields before the arrival of the wild avain species, might further augment the spread, transmission
and circulation of the AIV virus between wild and domestic animals.
EXPONENTIAL ESCALATION OF THE HIGHLY PATHOGENIC AVIAN INFLUENZA
It has been given that the H5 and H7 avian strains of AIV are further classified as highly pathogenic on the
basis of their ability to cause invasive disease and mortality in chickens .
For well over two decades now, phylogenetic analysis of HA sequences indicated that HPAI strains had
independently evolved on separate occasions from ancestral LPAI viruses.
This has since been demonstrated and confirmed by several extensive and rigorous sequencing analyses
of outbreaks where direct LPAI precursors have been identified, even up to individual poultry farms.
Previous meta-analysis of H5 and H7 outbreaks from 1959 to 2015 and found about ninety five percent
(95%) independent LPAI to HPAI transition events, and the majority of these were associated with
commercial entrepreneurial poultry farming.
As HPAI in poultry has a rapid onset and high mortality rate, farm outbreaks can be short lived, partly
because a large percentage of the birds die in a few days, but also because HPAI is a notifiable
disease with mandatory control measures, including culling remaining birds and movement bans to
limit the contagious spread to neighbouring areas.
However, on some very remarkable and notable occasions HPAI outbreaks have impacted untowardly by
causing major losses in the domestic avian specie.
Apart from the widespread HPAI H5s originating in Asia from 1996 onwards, and the associated H7s which
have been mentioned in this text, other outbreaks resulting in huge impacts globally such as the
demise or destruction of more than one million birds have occurred chronologically in the America
,Europe and beyond.
H5N1 was first reported in Africa in Nigerian poultry in February 2006 , closely followed by reports of
poultry outbreaks in Egypt .
The virus continued to spread in Africa, west and northwards in Europe and through the Middle East and
South Asian subcontinent in 2006 and 2007.
It had also caused several Homo sapiens demise with estimated case-fatality ratios of around twenty five
percent to eighty five percent on the basis of the ecological, physiographic and epidemiological region
or country country in question, however, the probit case-fatality ratio estimate could be different due
to case definitions, survey methodologies, endemic channels and notification trends reporting
patterns etc.
In 209, the impact of the AIV outbreak was compounded, when the world was overwhelmed by the
trepidation of the much milder 2009 H1N1 ‘swine flu’ pandemic.
EXPONENTIAL ESCALATION OF THE HIGHLY PATHOGENIC AVIAN INFLUENZA
Despite mostly inconsequential and covert symptoms
in Homo sapiens, the lack of immunity to this quite
divergent strain from the previously circulating
H1N1 seasonal virus implied that a significant
fraction of the population of Homo sapiens could
probably been infected.
After aggregating data from serology studies from about a score
of different countries globally in other to compute the
proximate evidential global impact of AIV, an age-adjusted
cumulative incidence estimate of just under a quarter (25%)
of the population was derived, and the excess mortality in
the first year was estimated as between one hundred and
fifty thousand and six hundred thousand people.
The pandemic H1N1 strain went on to replace the previous
H1N1 Homo sapiens seasonal AIV, and now co-circulates
alongside seasonal H3N2 IAV and influenza B viruses in the
Homo sapiens population globally.
THE GLOBAL IMPACT OF THE EMERGENCE OF H7N9 IN THE POULTRY AND HUMANS
• Whilst the world is being overwhelmed by the
HPAI H5N1 IAV and the new pandemic H1N1 virus
in Homo sapiens, transmission of LPAI wild avian
species viruses to domestic ducks, reassortment
with co-circulating domestic viruses, and onwards
transmission to poultry populations resulted in
circulating lineages of H7N9 and H7N7 viruses in
several regions impacting globally.
• It was demonstrated that the internal gene
segments were from an amalgamation of the H9N2
virus lineages circulating in poultry, one of which
probably also donated internal segments to the
HPAI H5N1 viruses.
• IMPART NOF THE AIV ON THE WORLD TODAY
• Around fifty (50) million birds were infected and/or
destroyed as part of control measures, and with a
cost of at least 1 billion US$ to the industry, this is
the most expensive recorded North American avian
influenza epidemic to date.
CONCLUSIVE REMARKS.
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It is clear that H5 and H7 viruses have the capacity to evolve (on multiple occasions) an HPAI
phenotype, probably as result of transmission in high avian species density settings and the
susceptibility of chicken and other domestic Galliformes species.
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In recent years, one such H5 lineage has become extensively inbreed and have found a niche in the
Asian domestic avian populations.
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Both H5 and H7 HPAI viruses have been sporadically transmitted to Homo sapiens from domestic
poultry, and for H5 at least been transmitted back into wild avian and mammalian populations.
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However, because HPAI does not necessarily kill its anseriform hosts, reassortment with cocirculating LPAI viruses can occur, advancing the sophistication and evolution of the virus, while the
minimally expressed symptomatologiess allow the long-range and intercontinental conveyance of this
invasive disease.
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In a way, the dynamics of the epidemiology and pathogenesis of the Homo sapiens avian influenza and
the avian influenza in the avain species are analogous motion wise, since both species move and
migrate alot.
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However, unlike human IAV, where reassortment between the few dominant subtypes is rare,
reassortment is a common feature for avian IAVs, especially in wild bird populations, consequently,
avian IAVs are far more diverse and more easily generate novel pathogenic strains than the more
specialized Homo sapiens viruses.
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It would not be pessimistic to anticipate that in future, the emergence of more HPAI strains, should be
expected.
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Experientially it is well known that this has occurred previously in several settings globally
approximately once or twice per decade; and the fundamental lassitude of leaving H5 and H7 LPAI
viruses uncontrolled in a host-dense environment until de novo mutation into HPAI occurs has not
been addressed.
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Also, it seems quite possible that HPAI H5 will continue to circulate and diversify, especially for clade
2.3.4.4 because it does not necessarily cause intensely overt clinical features in its wild hosts and is
therefore capable of covert distribution.
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Hence increasing biosecurity and vaccination in domestic poultry are likely to be important strategies
to minimise outbreaks in these populations.
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Ongoing avian influenza virus spill-overs into Homo sapiens cases suggest that zoonotic avian flu is a
continued threat to Homo sapiens health; however, the apparent success of the H7N9 vaccination
programme in China suggests that it is possible to control virus circulation in domestic avian species
and thus vastly reduce the number of Homo sapiens infections and the risk of ongoing Homo sapiens
to Homo sapiens spread.
Therefore, as we aim to continue the active disease surveillance programmes in avian, Homo sapiens and
other domestic animal populations, and control avian influenza in domestic avian populations, then it is
certain that we could surely reduce the risks of a new Homo sapiens avian influenza pandemic.
IMPACT OF AVIAN FLU IN THE WORLD TODAY
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The current outbreaks of avian influenza (also called “bird flu”) have caused devastation
in animal populations, including poultry, wild birds, and some mammals, and harmed
farmers’ livelihoods and the food trade.
Although largely affecting animals, these outbreaks pose ongoing risks to Homo
sapiens.
The Food and Agriculture Organization of the United Nations (FAO), the World Health
Organization (WHO), and the World Organisation for Animal Health (WOAH) are urging all
countries globally to work collectively across sectors to save as many animals as
possible and to protect Homo sapiens as well.
Avian influenza viruses normally spread among the avain species, but the increasing
number of H5N1 avian influenza detections among mammals, which are biologically
closer to Homo sapiens than birds evokes a lot of concern that the virus might adapt to
infect humans more easily.
Furthermore, some mammals may act as mingling reservoirs for influenza viruses,
leading to the emergence of new viruses that could be more harmful to animals and
Homo sapiens
As from 2020, a variant of these viruses belonging to the H5 clade 2.3.4.4b has led to
an unprecedented number of deaths in wild birds and poultry in many countries in
Africa, Asia and Europe.
In 2021, the virus spread to North America, and in 2022, to Central and South America.
In 2022, about sixty seven countries in five continents globally reported H5N1 high
pathogenicity avian influenza outbreaks in poultry and wild birds to WOAH, with more
than one hundred and thirty one million domestic poultry lost to death or culling in
affected farms and villages which impacted very negatively to the economy in those
regions and globally at large.
In 2023, another fourteen countries globally reported outbreaks, mainly in the Americas,
as the disease continues to spread.
MONITORING THE RECENT SURGE IN OUTBREAKS AMONG MAMMALS PROFFERS A
PROBIT ESTIMATE OF THE AIV IN THOSE REGIONS AND GLOBALLY.
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Recently, there have been increasing reports of deadly outbreaks
among mammals also caused by influenza A (H5),including influenza
A(H5N1)viruses.
Ten countries across three continents globally have reported
outbreaks in mammals to WOAH since 2022.
There are likely to be more countries where outbreaks exist but
have not yet been detected or reported yet for several challenging
reasons.
H5N1 viruses have also been detected in domestic animals such as
the feline and canindes in several countries, with recent detections
of H5N1 in cats announced by authorities in Poland.
Infections in humans can cause severe disease with a high mortality
rate.
The human cases detected thus far are mostly linked to close
contact with infected birds and contaminated environments.
WHO is working closely with FAO and WOAH, and laboratory
networks to monitor the evolution of these viruses, looking for
signals of any change that could be more dangerous to Homo
sapiens.
In essence, all countries are encourages to scale up their ability to
monitor these viruses and to detect any Homo sapiens cases.
THE IMPACT OF THE AVIAN FLU ON THE WORLD TODAY SUGGESTS
EPIDEMIOLOGICAL DATA SHARING AND SUPPORT GLOBALLY.
• This is especially important as the virus is now affecting countries with
limited prior experience in avian flu surveillance."
• Studies are underway to identify any changes in the virus that may help the
virus to spread more easily among mammals, including humans.
• FAO brings attention to the need for vigilance and timely sharing of genetic
sequences to monitor the molecular epidemiology for risk assessment and
better disease control.
• CURBING THE SPREAD OF AVIAN INFLUENZA WILL HAVE A POSITIVE
EFFECT ON ITS NEGATIVE UNTOWARD GLOBAL IMPACT.
• Given the unprecedented spread of the A(H5N1) avian influenza virus among
the Avian and mammals, and the potential risk to Homo sapiens health, the
multilateral partners(FAO, WHO and WOAH),recommends and tasks all
countries to take the following given actions:
• Prevent avian influenza at its origin, mainly through scaled up biosecurity
measures in farms and in poultry value chains, and apply good hygiene
practices.
• WOAH members, in consultation with the poultry sector, may consider the
vaccination of poultry as a complementary disease control tool based on
sound surveillance and taking into account local factors such as circulating
virus strains, risk assessment and vaccination implementation conditions.
• Rapidly detect, report and respond to animal outbreaks as the first line of
defence. When an infection is detected in animals, countries are encouraged
to implement control strategies as described in WOAH standards which are
readily handy and widely available.
PREVENTIVE MEASURES THROUGHSTRENGTHEN INFLUENZA
SURVEILLANCE IN ANIMALS AND HOMO SAPIENS.
It is recommended that in order to allow for early response, risk-based surveillance in
animals should be enhanced before and during high-risk periods. Animal cases of avian
influenza should be reported to WOAH in a timely manner.
Genetic sequencing should be conducted periodically to detect any alterations in the
viruses already present in the area or the introduction of new viruses of undetermined
biological behaviour.
The following worthy epidemiological interventions of public health preventive importance
should be prioritized in Homo sapiens, including but not confined to:(i) surveillance for
severe acute respiratory infections and influenza-like illnesses, (ii) diligent and
meticulous review of any unusual epidemiological patterns, (iii) reporting of Homo
sapiens infections under the International Health Regulations, and (iv) sharing of
influenza viruses epidemiological data with WHO Global Influenza Surveillance and
Response System (GISRS) Collaborating Centres for Reference and Research on
Influenza.
Although preventive consideration will include the conduct of bepidemiological and
virological investigations around animal outbreaks and Homo sapiens infections.
Surveillance should be enhanced to rapidly detect and investigate further suspected animal
and Homo sapiens cases.
Share the genetic sequence data of viruses from Homo sapiens, animals or their
environments in publicly accessible databases rapidly, even before peer-reviewed
publication.
Encourage collaboration between the animal and Homo sapiens health sectors, especially
in the areas of information sharing, joint risk assessment and response etc.
CONCLUSION,FUTURE TRENDS AND RESEARCH DIRECTIONS.
• IMPACT OF HUMAN AVIAN INFLUENZA.
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As intimated above the species of mammals known to be infected with
A(H5N1) clade 2.3.4.4b viruses to date is quite enormous almost no
mammalian species appears including Homo sapiens appears to be spared
as such.
However, it is expedient that more studies will be needed to understand
baseline levels of infection in wild mammals and Homo sapiens.
HPAI H5N1 remains a significant global challenge due to its widespread
circulation and high mortality rates.
The ongoing challenges posed by HPAI H5N1 necessitate a proactive
approach to address future trends.
Several key areas require focused attention and research to effectively
manage the spread and impact of the virus globally and these include but not
confined to:
[I]-.ACTIVE SURVEILLANCE AND EARLY DETECTION:
Strengthening global surveillance systems for avian influenza is crucial to
promptly identify and monitor emerging strains, especially those with
zoonotic potential.
Continuous and diligent monitoring of wild avian populations, domestic
poultry, and high-risk areas will provide early warning signs of virus
circulation and facilitate timely intervention measures,
[II]-. THE INDEPTH ANALYSIS AND STUDY OF THE GENETIC VARIATIONS AND VIRAL EVOLUTION:
The occurrence of genetic variations among HPAI H5N1 strains underscores the need
for ongoing genetic analysis and monitoring.
Studying the mutations and reassortment events in the virus can provide insights into
its evolutionary potential, transmission dynamics, and pathogenicity.
TO COMMUNICATE THE RISK OF AIV INFECTION
AND INVASION EFFECTIVELY AND PROMPTLY .
• This implies to alert and train healthcare workers and
occupationally-exposed persons on ways to protect
themselves.
• The general public as well as animal workers should be
advised to avoid contact with sick and dead animals, and to
report these to animal health authorities.
• They should also be advised to seek medical care if unwell
and to report any exposure to animals to their healthcare
provider.
• Ensure influenza pandemic preparedness at all levels.
• FAO, WHO and WOAH have been convening experts to review
the situation, monitor the rapidly evolving nature of the virus,
and update recommendations for curbing its spread, in
addition to working with countries in preparedness and
response, and facilitating collaboration across countries and
sectors.
• The spread of the virus to five continents speaks to the need
for global cooperation and alertness to protect animals,
people and economies.
[III]-.CONTROLLING,REGULATING AND MONITORING OF THE
CROSS-SPECIES TRANSMISSION AND RESERVOIRS:
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The widely observed cross-species transmission between mammalian
species and avian populations evokes concerns about the establishment of
viral reservoirs and ongoing risks to both animals and Homo sapiens.
Future research should explore the mechanisms and factors facilitating
cross-species transmission, with a particular emphasis on identifying
potential reservoir species and understanding the dynamics of transmission
in these populations,
[IV]-STRENTHENING PREVENTIVE MEASURES AND VACCINES:
The development and deployment of effective vaccines against HPAI H5N1
are of paramount importance.
Education, practice and research should focus on improving vaccine
efficacy, broadening the scope of protection across various viral strains, and
optimizing vaccine delivery strategies,
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[V]-RATIONAL AND SCIENTIFIC APPLICATION AND EMPLOY OF
ANTIVIRAL THERAPEUTICS AND TREATMENT STRATEGIES:
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Further exploration of antiviral therapeutics and management strategies is
pivotal and crucial for the utmost management HPAI H5N1 infections.
Education and Research should focus on identifying and developing novel
antiviral agents with broad-spectrum activity against avian influenza viruses.
Additionally, investigating host immune responses and developing
immunomodulatory therapies could aid in reducing disease severity and
improving patient outcomes.
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[VI]-EFFECTIVE,OPTIMAL ,RATIONAL AND UTMOST MANAGEMENT OF SECONDARY BACTERIAL COPATHOGENS IN AFFECTED HOMO SAPIENS CASAES BUT ALSO THEIR DOMESTIC AVIAN MAMMALIAN
COUNTERPARTS AS SUCH(THROUGH IMMUNOTHERAPY AND PHARMACOTHERAPY)
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As I have intimated and discussed above and below, there is always the crucial and
urgent need to consider the utmost interventions for the secondary bacterial copathogens in all cases of viral infections including the AIV infections,infact several
evidential studies have demonstrated that these co-pathogens contribute significantly
to the AIVs morbidity and mortality impact.(Onyekwelu E. 2009)
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[VII]-.THE FACILITATION AND SUPPORT FOR
INTERNATIONAL COLLABORATION AND PREPAREDNESS:
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It is an axiom that the fortification and strengthening of international collaboration and information
sharing among countries is vital in effectively and optimally addressing the global challenges posed by
HPAI H5N1.
Establishing robust communication networks, sharing surveillance data, and coordinating response
efforts will facilitate rapid response, early containment, and effective control of outbreaks.
Currently, several antivirals such as neuraminidase inhibitors and cap-snatching inhibitors that
efficiently target influenza viruses including H5N1 are available.
Also, there is likely at least partial immunity in the adult population of Homo sapiens to the N1 NA
component of the virus as Homo sapiens have been repeatedly exposed to the 2009 pandemic H1N1
virus through infection and vaccination.
In addition, it is also heartening that the virus strain that was able to spread among mink was likely
eradicated when these animals were culled in November 2022.
It is worthwhile for clinicians to be vigilant about non-seasonal influenza virus infections and a
specific vaccine for clade 2.3.4.4b H5N1 should be produced and stockpiled, which is routine for avian
influenza viruses with pandemic potential.
In addition, the public should be adviced to be aware of H5N1 and should not come in contact with
dead, sick or strangely behaving avians or mammals if they are not trained and equipped to handle
these animals safely.
It would also be advisable to keep pets, such as dogs, away from potentially infected animals.
Importantly, this includes urban areas, which often have dense wild avian populations in parks and
green spaces.
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SAFE POUTRY FARMING AND ANIMAL HUSBANDRY
PRACTICES SOULD BE ENCOURAGED AND FOSTERED.
This need for a hygienic and wholesome poultry farming and animal husbandry
has been buttressed by the case of the mink farm in Spain, as well as the
demonstrations of other archetypical instances from poultry farms in Indiana
and Tennessee), influenza virus outbreaks in farms with large numbers of
susceptible animals can lead to the emergence of novel and potentially
dangerous viral strains that may have pandemic potential.
There has recently been a lot of debate about revising regulations for
experiments with viruses in laboratories, and this discussion is good to have.
The concept of a unified collaborative approach to integrate animal, planetary,
and Homo sapiens health appears to be the most fruitful one.
The UK Department for Environment Food and Rural Affairs uses a surveillance
system that relies on notifications, isolating farms or other places of captivity,
and culling infected healthy avians species in close contact with infected
avians.
These methods are obstrusive when the primary objective is to protect Homo
sapiens, particularly those working with the Avian species and livestock.
However, the spread of H5N1 avian influenza among animals with no real policy
for prevention, other than culling, is not sustainable for people or the planet.
This present strategy does not address how climate change is driving outbreaks
of zoonotic disease.
SAFE POUTRY FARMING AND ANIMAL HUSBANDRY
PRACTICES SOULD BE ENCOURAGED AND FOSTERED.
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Avian influenza has always been associated with migratory birds that might intermingle
and interbreed with domestic poultry.
However, rising sea levels and temperature changes due to the unprecedented impact
of climate change are also affecting the migration patterns of many migratory birds,
potentially causing them to integrate with other species.
Although, there is little systematic surveillance of bacterial coinfections during
seasonal influenza, but this continued threat to public health has led to increased body
of evidential research on the co-pathogenesis of pneumonia due to influenza viruses
and bacterial pathogens, especially employing experimental animal test system models.
These researches attempts to improve the current state of knowledge of influenza
coinfections through the use of experimental animal tests system models and, more
recently, through the use of multifaceted hypothetical, conceptual and theoretical
models.
Identifying how a bacterial coinfection renders mild influenza infections fatal is key to
effectively combating pneumonia and preparing for futuristic influenza pandemics.
•
Infact the impact of the AIV invasion such as the RTI, pneumonia, encephalitis etc
could be a lot more than anticipated and estimated, due to the obvious challenges with
achieving exact diagnostic distinction between viral interstitial pneumonia and
secondary bacterial copathogenic pneumonia, besides the few theoretical dogmatic
clinical and radiological clues .This distinction is considered seminally important since
their exact interventions remarkable differs. (Onyekwelu.E. 2009)
•
However, key questions regarding the AIVs transmission, invasion, and pathogenicity
and biological behaviour remain unanswered.
REFERENCES,BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
LINKS TO THE SITES AND ARTICLES EMPLOYED AS REFERENCES.
•
•
•
•
•
•
•
•
•
•
•
•
CDC.Reporting for bird detections across the United States.Cent Dis Control Prev
(2023)https://t.cdc.gov/2S4H, Accessed 13th Aug 2023.Google Scholar
CDC.Technical report: highly pathogenic avian influenza A(H5N1) viruses. Cent Dis Control Prev
(2023).https://www.cdc.gov/flu/avianflu/spotlights/2022 2023/h5n1-technical-report_june.htm, Accessed
12th Aug 2023.Google Scholar
Centers for Disease Control and Prevention. Update on H5N1 bird flu in Cambodia.
https://www.cdc.gov/flu/avianflu/spotlights/2022-2023/avian-flu-cambodia.htm (2023).
Centers for Disease Control and Prevention. Technical Update: Summary Analysis of Genetic
Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses in Texas: CDC-US: 2024. Available
from: https://www.cdc.gov/flu/avianflu/spotlights/2023-2024/h5n1-analysis-texas.htm
Centers for Disease Control and Prevention. Highly Pathogenic Avian Influenza A (H5N1) Virus
Infection Reported in a Person in the U.S. Atlanta: CDC-US: 2024. Available from:
https://www.cdc.gov/media/releases/2024/p0401-avian-flu.html
Centers for Disease Control and Prevention. Highly Pathogenic Avian Influenza A(H5N1) Virus in
Animals: Interim Recommendations for Prevention, Monitoring, and Public Health Investigations: CDCUS: 2024. Available from: https://www.cdc.gov/flu/avianflu/hpai/hpai-interim-recommendations.html
.n.d.Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 20032023 (2023)
https://www.who.int/publications/m/item/cumulative-number-of-confirmed-human-cases-for-avianinfluenza-a(h5n1)-reported-to-who--2003-2023-14-july-2023, Accessed 11th Aug 2023
CDC.Current bird flu situation in wild birds.Cent Dis Control Prev
(2022).https://www.cdc.gov/flu/avianflu/wildbirds.htm, Accessed 12th Aug 2023.Google Scholar
Current technical information including monthly risk assessments at the Human-Animal Interface.
EFSA (European Food Safety Authority), ECDC (European Centre for Disease Prevention and Control),
EURL (European Reference Laboratory for Avian Influenza.
Emergence and Evolution of H5N1 Bird Flu Avian influenza
(flu)https://www.cdc.gov/flu/avianflu/communication-resources/bird-flu-origin-infographic.html (2023),
Accessed 10th Jun 2023.Google Scholar
REFERENCES,BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
LINKS TO THE SITES AND ARTICLES EMPLOYED AS REFERENCES.
• European Food Safety Authority. European Centre for Disease Prevention and Control,
European Union Reference Laboratory for Avian Influenza, Adlhoch C, Fusaro A,
Gonzales JL, Kuiken T, Marangon S, et al. Avian influenza overview September –
december 2022.EFSA J, 21 (2023), 10.2903/j.efsa.2023.7786. View at publisher .Google
Scholar
• European Food Safety Authority. European Centre for Disease Prevention and Control,
European Union Reference Laboratory for Avian Influenza, Adlhoch C, Fusaro A,
Gonzales JL, et al. Avian influenza overview December 2022 – March 2023EFSA J, 21
(2023), 10.2903/j.efsa.2023.7917.View at publisher .Google Scholar
• FAO Global consultation on Highly Pathogenic Avian Influenza, 2-5 May 2023
• H5N1 Bird Flu Detections across the United States (Wild Birds).Avian influenza
(flu).https://www.cdc.gov/flu/avianflu/data-map-wild-birds.html (2023), Accessed 13th
Aug 2023.Google Scholar
• H5N1 High pathogenicity avian influenza in wild birds - Unprecedented conservation
impacts and urgent needs | CMS n.d. https://www.cms.int/en/publication/h5n1-highpathogenicity-avian-influenza-wild-birds-unprecedented-conservation-impacts (accessed
August 12, 2023).Google Scholar.
• Highlights in the History of Avian Influenza (Bird Flu) Timeline
• Avian influenza (flu).n.d..https://www.cdc.gov/flu/avianflu/timeline/avian-timeline2020s.htm (2020-2023), Accessed 10th Jun 2023.Google Scholar
• Human Infection caused by Avian Influenza A (H5N1) – Chile
n.d.https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON461,
Accessed 10th Jun 2023.Google Scholar
• Human infection caused by avian influenza A(H5) - Ecuador
• n.d-https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON434,
Accessed 10th Jun 2023.Google Scholar.
• Influenza A(H5N1) in cats – Poland n.d.https://www.who.int/emergencies/diseaseoutbreak-news/item/2023-DON476, Accessed 12th Aug 2023.Google Scholar
REFERENCES,BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
LINKS TO THE SITES AND ARTICLES EMPLOYED AS REFERENCES.
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Information for molecular diagnosis of influenza virus n.d https://www.who.int/teams/global-influenza
programme/laboratory-network/quality-assurance/eqa-project/information-for-molecular-diagnosis-of-influenzavirus, Accessed 10th Jun 2023.Google Scholar
Information on avian influenza.Cent Dis Control Prev (2023)https://t.cdc.gov/VAY, Accessed 11th Aug
2023.Google Scholar
Interim guidance on testing and specimen collection for patients with suspected infection with novel influenza
A viruses with the potential to cause severe disease in humans | avian influenza (flu)
https://www.cdc.gov/flu/avianflu/severe-potential.htm (2022), Accessed 10th Jun 2023.Google Scholar
News & Spotlights Avian influenza (flu) https://www.cdc.gov/flu/avianflu/spotlights/index.htm (2023), Accessed
12th Aug 2023.Google Scholar
OFFLU meeting to discuss avian influenza events in mammals, 2 March 2023
[Onyekwelu.E.2019.Monographs on Avian Influenzae of Epidemiological, Ecological and Public and Preventive
Health Impact. Seminars, Lectures, Tutorials and Concourses. College of Health Sciences Legacy University
and Classics and Revisits in Scientific Medicine. (Monographs in Press)
Onyekwelu,E.(2009).Chest Roentgenographic Features In Paediatric Clinical Measles, and Its implications on
Nomenclature Management and Outcome (Morbidity and Mortality) in The Tropics,Paediatric Infectious Disease
Journal (LWW),28(6),560-e258.
PAHO/WHO. Influenza at the Human-Animal Interface: PAHO Recommendations to Strengthen Intersectoral
Work for Surveillance, Early Detection, and Investigation, 9 July 2020.
Pan American Health Organization / World Health Organization. Epidemiological Update Outbreaks of avian
influenza caused by influenza A(H5N1) in the Region of the Americas, 18 May 2023. Washington, D.C.:
PAHO/WHO; 2023. Available from: https://www.paho.org/en/documents/epidemiological-update-outbreaks-avianinfluenza-caused-influenza-ah5n1-region-americas.
Pan American Health Organization / World Health Organization. Epidemiological Update Outbreaks of avian
influenza caused by influenza A(H5N1) in the Region of the Americas - 20 March 2024. Washington, DC:
PAHO/WHO; 2024.
Pan American Health Organization / World Health Organization. Risk Assessment for public health related to
outbreaks caused by Highly Pathogenic Avian Influenza (HPAI) A(H5N1), clade 2.3.4.4b, in animal species in the
Region of the Americas - 20 September 2023. Washington, D.C.: PAHO/WHO; 2023.
Pan American Health Organization / World Health Organization. Strengthening the intersectoral work for
Influenza at the Human Animal Interface in the Region of the Americas: Technical Questions and Answers.
Washington, D.C.: PAHO/WHO; 2023.
Pan American Health Organization / World Health Organization. Report of the Regional Consultation for the
Strengthening of Intersectoral Work in the Human-Animal Interface of Influenza. Washington, DC: PAHO/WHO;
2023
Pan American Health Organization / World Health Organization. Call to action to establish the Intersectoral
Commission for the Prevention and Control of Zoonotic Influenza in the Americas.
REFERENCES,BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
LINKS TO THE SITES AND ARTICLES EMPLOYED AS REFERENCES.
•
•
•
•
•
•
•
•
•
•
Pereira H G, Tumova B, Webster R G.(1967) Antigenic relationship between influenza A viruses of
human and avian origins.Nature,1967 Aug 26; 215(5104):982-3. doi: 10.1038/215982a0.PMID: 6055434
DOI: 10.1038/215982a0)
Pereira HG.Influenza: antigenic spectrum.Prog Med Virol. 1969; 11:46-79.PMID: 4906872 Review. No
abstract available.)
Schafer W. (1955). Vergleichende sero-immunologische Untersuchungen über die Viren der Influenza
und klassischen Geflügelpest [Comparative sero-immunological studies on the viruses of influenza and
classical avian influenza]. Zeitschr. Naturforsch. 10, 81–91 (in German). ( 10.1515/znb-1955-0205)
[CrossRef] [Google Scholar]
Situation analysis and advice to countries from FAO, WHO, WOAH,12 July 2023 Statement
Geneva/Paris/Rome .
Sreenivasan CC, Thomas M, Kaushik RS, Wang D, Li F. Influenza A in Bovine Species: A Narrative
Literature Review. Viruses. 2019;11(6):561. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631717/
Terms of Reference for National Influenza Centers of the Global Influenza Surveillance and Response
System.
Tůmová .B and Pereira H. G.(1968). Antigenic relationship between influenza A viruses of human and
animal origin. Bull World Health Organ. 1968; 38(3): 415–420.PMCID: PMC2554487.PMID: 5302333
United States of America International Health Regulations National Focal Point. Email communication
dated 2 April 2024. Washington D.C.; 2024. Unpublished.
United States Department of Agriculture, Animal and Plant Health Inspection Service. Federal and
State Veterinary, Public Health Agencies Share Update on HPAI Detection in Kansas, Texas Dairy
Herds. Washington, D.C.: USDA; 2024. Available from: https://www.aphis.usda.gov/news/agencyannouncements/federal-state-veterinary-public-health-agencies-share-update-hpai
United States Department of Agriculture, Animal and Plant Health Inspection Service. USDA, FDA and
CDC Share Update on HPAI Detections in Dairy Cattle. Washington, D.C.: USDA; 2024. Available from:
https://www.aphis.usda.gov/news/agency-announcements/usda-fda-cdc-share-update-hpai-detectionsdairy-cattle.
REFERENCES,BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
LINKS TO THE SITES AND ARTICLES EMPLOYED AS REFERENCES.
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
United States Department of Agriculture, Animal and Plant Health Inspection Service. Highly Pathogenic
Avian Influenza (HPAI) Detections in Livestock. Washington, D.C.: USDA; 2024. Available from:
https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/livestock
United States Department of Agriculture, Animal and Plant Health Inspection Service. Detection of Highly
Pathogenic Avian Influenza. Washington, D.C.: USDA; 2024. Available from:
https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections
US CDC. Influenza Type A Viruses.
U.S. CDC. Case of Human Avian Influenza A(H5) Virus Reported.
U.S. CDC. Intercontinental Movement of Highly Pathogenic Avian Influenza A (H5N1) Clade 2.3.4.4 Virus to
the United States, 2021.
Viruses GC for H and RI.Role for migratory wild birds in the global spread of avian influenza H5N8.Science,
354 (2016), pp. 213-217.Google Scholar
Webster R.G., Campbell, C.H. Granoff A.(1971), The “in vivo” production of “new” influenza a viruses: I.
Genetic recombination between avian and mammalian influenza viruses,Virology,Volume 44, Issue 2, May
1971, Pages 317-328
Will the largest bird flu outbreak in history lead to a human pandemic? n.d https://scitechdaily.com/will-thelargest-bird-flu-outbreak-in-history-lead-to-a-human-pandemic/, Accessed 10th Jun 2023.Google Scholar
World Health Organization. Avian influenza weekly update number 884. https://www.who.int/docs/defaultsource/wpro---documents/emergency/surveillance/avian-influenza/ai_20230224.pdf?sfvrsn=5f006f99_111
(2023).
World Health Organization (9 April 2024). Disease Outbreak News; Avian Influenza A (H5N1) – the United
States of America. Available at: http://www.who.int/emergencies/disease-outbreak-news/iten/2024-DON512
World Health Organization. Disease Outbreak News; Avian Influenza A (H5N1) – the United States of America.
Geneva: WHO; 2022. Available from: https://www.who.int/emergencies/disease-outbreak-news/item/2022DON379
World Health Organization. Cumulative number of confirmed human cases of avian influenza A(H5N1)
reported to WHO. Geneva: WHO; 2024. Available from: https://www.who.int/publications/m/item/cumulativenumber-of-confirmed-human-cases-for-avian-influenza-a(h5n1)-reported-to-who--2003-2024-26-february-2024
WHO. Zoonotic Influenza Outbreak Toolbox.
WHO. International Health Regulations (2005).
WHO. Manual for the laboratory diagnosis and virological surveillance of influenza (2011).
WHO assessment of risk associated with recent influenza A(H5N1) clade 2.3.4.4b viruses, 21 December 2022
WHO Factsheet on avian and other zoonotic influenza, WHO Q&A on avian influenza
WOAH Animal Health Forum on avian influenza, 22-23 May 2023
WOAH Infographic on the new dynamics of avian influenza
World Health Organization/World organisation for animal health/food and agriculture organization
(WHO/OIE/FAO) H5N1 evolution working group. Revised and updated nomenclature for highly pathogenic
avian influenza A (H5N1) viruses Influenza Other Respir Viruses, 8 (2014), pp. 384-388,
10.1111/irv.12230.View at publisher, Google Scholar
ACKNOWLEDGEMENTS
THE HISTRIOGRAPHY,PHYSIORAPHIC
RANGES AND MOLECULAR GENETIC
EPIDEMIOLOGIC CONSIDERATIONS FOR THE
AVIAN(BIRD) FLU AND ITS MULTIMODAL
AMELIORATION AND DETERRENT OPTIONS.
P R O F. D O T T. E M M A N U E L U D E M E Z U E O N Y E K W E L U .
CSci,CSciTeach,ChirB(Hons),MB(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon)
C L A S S I C S A N D R E V I S I T S I N S C I E N T I F I C M E D I C I N E U P D AT E D 2 0 2 4 .
ACKNOWLEDGEMENTS
THE HISTRIOGRAPHY,PHYSIORAPHIC
RANGES AND MOLECULAR GENETIC
EPIDEMIOLOGIC CONSIDERATIONS FOR THE
AVIAN(BIRD) FLU AND ITS MULTIMODAL
AMELIORATION AND DETERRENT OPTIONS.
P R O F. D O T T. E M M A N U E L U D E M E Z U E O N Y E K W E L U .
CSci,CSciTeach,ChirB(Hons),MB(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon)
C L A S S I C S A N D R E V I S I T S I N S C I E N T I F I C M E D I C I N E U P D AT E D 2 0 2 4 .
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