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Utilization Of Ozone For Avian Influenza
(Bird Flu)
WHAT IS AVIAN FLU?
The avian flu is dangerous infection caused by avian influenza
virus called H5N1. This virus is very common among wild birds.
H5N1 actually lives in their intestine. However, these wild
birds can infect domesticated birds including CHICKENS, ducks,
and geese and kill them. The flu is spread among birds through
saliva and droppings. Chickens and other domesticated birds get
Avian Flu when they are in contact with infected birds or their
saliva and droppings. The virus can spread from infected hen to
the egg as well. Bird flu viruses do not usually infect humans,
but several cases have been reported since 1997.
OZONE, NITRIC OXIDE, AND AVIAN INFLUENZA:
Influenza is a recurrent global disease with, in pandemic
conditions, significant morbidity and lethality. The dynamics of
avian influenza are complicated by the fact that its virus is
capable of evolving in a variety of animal and human reservoirs.
Able to infect all members of the human population in its
pandemic phase, influenza presents supremely challenging
problems in light of its pathogenic capacity and mutational
potential. Recent advances in immunology have clarified some of
the complex mechanisms of antigen-antibody reactions. This paper
explores two main gases that, produced at the molecular level by
cellular elements of the immune system, perform crucial roles in
microorganism inactivation. The idea that gases are produced in
vivo to perform a panoply of essential biological functions has,
in the last few years, revolutionized concepts about cellular
signaling. These two physiological gases are nitric oxide and
ozone. Suggested is that, in view of the characteristics
inherent in avian flu, research into the dynamics of these
virucidal agents could assist in the public health response to
an influenza plague. The Avian influenza virus: Virion
architecture and molecular biology The influenza virus belongs
to the small family of Orthomyxoviruses. Myxo refers to the
Greek term for mucous and this family’s propensity for
attachment to the mucoproteins on cell surfaces. In the case of
Avian influenza, the target cells are the columnar epithelium of
the respiratory tree. The family includes Influenza A, the cause
of pandemics, distinguished by its antigenic surface components.
Influenza B, a milder disease, does not cause pandemics.
Influenza C has a somewhat different genetic structure, infects
children and Asian swine, and causes even milder pathology.
The
avian influenza virion, 100 to 200 nm in diameter is
approximately spherical because of its loose-fitting envelope.
Under the electron microscope it appears as an ovoid organism
studded with hundreds of spikes, the peplomers. If it were
expanded, it would look like a sea urchin. Within the viral core
are eight separate helical single strands of ribonucleoprotein,
the software for viral life and replication. This unusual
segmented RNA genome encodes the transcription of all viral
components, including structural proteins, enzymes, and lipids.
An intricate membrane, the envelope, surrounds the viral genome.
Matrix proteins provide internal attachment between the genomic
nucleocapsid and its envelope. The Avian influenza envelope has
an inner protein (M) shell covered by another shell composed of
a double layer of lipids. Approximately 60% of envelope lipids
are composed of phospholipids and the rest are cholesterols.
Embedded in the envelope are the roots of the peplomers.
Peplomer spikes are essential for viral attachment and
penetration into host cells. Peplomers are constructed of
carbohydrate and protein components, glycoproteins. Of the
several hundred peplomers studding an individual influenza
virion, 80% are the triangular-shaped hemaglutinin (HA)
glycoproteins, and the rest are the mushroom-shaped
neuraminidase (NA) glycoproteins.
HA and NA are vital for avian flu’s infectious capacity. With
regard to the host, HA and NA are the inimical antigens prodding
its immune system’s counter-offensiveness. The hemaglutinin HA
glycoprotein is able to coalesce the red blood cells of a
num-ber of animal species, hence its name. The neuraminidase
(NA) glycoprotein functions as an enzyme, facilitating virus to
host cell attachment and viral release from cells. NA has the
capacity to destroy a component of the host cell surface,
neuraminic acid. The signature proteinic composition of HA and
NA determines the virulence of influenza’s thrust into host
cells. Since 1971, influenza A viruses have been named according
to their HA and NA glycoprotein antigenic compositions. Thus,
the influenza H5N1 strain describes the molecular architecture
of its peplomers. Avian influenza: Genetic creativity and
infectious transmission.
The viral replication cycle follows the pattern seen in numerous
mammalian viruses. Virions, once attached to host cell
receptors, enter cells by engulfment - the endocytosis process -
or by viropexis, which entails a fusion of the viral and the
cell envelopes. Once entry into the cell is achieved, virions
commence their replication. The next task of newborn viral
nucleocapsids is to exit their incubator cell. During this
release process, their viral envelopes are formed. For this to
happen, the nucleocapsid fuses with the host cell membrane,
itself a lipid bilayer, appropriating its components. The lipid
composition of viral membranes thus reflects the lipid
composition of the cells through which the particles exit.
Virions are then released into the general blood and lymphatic
circulations, ready to infect new cells, other organ systems
and, eventually, new hosts. In another scenario, viral
particles, by way of their sheer numbers and the over taxation
of the cells they invade, may at times provoke cell lysis and
death. In an amount of time measured in hours, influenza can
flood the body with billions of viral particles. Transmission of
influenza viruses is by droplet, person-to-person contact, and
by transfer through fomites (objects). As is the case in many
RNA viruses, Orthomyxoviridae mutate at a high rate. Within any
one afflicted individual, influenza particles do not show a
homogeneous population. Instead, they function as a pool of
genetically variant strains known as quasispecies. This is due
to the high error frequency of RNA polymerases, the presence of
deletion mutants, the high frequency of RNA recombination and
point mutations, and the occurrence of defective-interfering RNA
(Holland 1993). The net result of these diverse mechanisms is
the continuous spawning of novel virions and divergent
quasispecies. Some of the genetic creations will find themselves
at an advantage in surmounting new host-antibody responses and
antiviral drug challenges. They will propagate accordingly, thus
expanding their ecological territory. Other genetic
configurations, by being too lethal will lead to the demise of
their hosts. If we can speak of a viral psychology, an efficient
viral survival balance aims somewhere between total defeat by
host defenses on one hand and viral suicide through aggressive
lethality on the other. Antigenic drift describes a gradual
accumulation of amino acid mutational changes. In the influenza
virion, HA and NA antigens slowly change over time. Antigenic
shift, on the other hand, represents a dramatic alteration in
genetic configuration resulting in the acquisition of completely
novel HA and NA antigens.
In a process called reassortment, an individual who harbors
concomitantly a human and an avian influenza virus can become an
incubator for novel, revolutionary viruses. It is possible, as
has happened in past pandemics (Taubenberger 2005), that one of
these viral creations becomes doted with the capacity for highly
virulent human-to-human transmission. Avian influenza: The
illness After an incubation of 1 to 5 days, influenza begins
with “cold-like” symptoms. “Colds,” however, are caused by
different viral families such as picornaviruses, rhinoviruses,
echoviruses, and coxsackieviruses, and do not escalate into the
acute symptomatology of influenza with malaise, fever, headache,
myalgia, sore throat, nasopharyngeal congestion, and
retro-orbital pain. In the presence of viral pneumonia, there is
chest pain and shortness of breath. The acute symptoms in
uncomplicated cases begin to abate in a few days. Recuperation,
however, may be slow in some individuals who show lingering
malaise. The syndrome is a great stress to the organism.
Individuals challenged by heart, liver, pulmonary, endocrine,
kidney, immune conditions, or age, are consequently more
vulnerable to viral lethality. Bodily organs injured by
influenza are more prone to suprainfections with bacterial
species. Staphylococcus aureus, Streptococcus pneumonia,
Klebsiella, and Hemophilus influenzae are commonly implicated in
bacterial pneumonia complicating influenza. In fact, mortality
in influenza pandemics has been significantly attributed to
bacterial onslaughts on the coattails of the viral invasion.
This fact is crucial in public health planning. Indeed, the
stockpiling of appropriate anti-bacterial agents is as important
as insuring adequate anti-viral supplies. The importance of
physiological gases in antiviral therapy Current antiviral
medications for influenza function via the inhibition of viral
components involved in attachment to, or release from, host
cells. Oseltamivir (Tamiflu) and zanamivir (Relenza) for
example, alter viral neuraminidase peplomers, bridling
replicative capacity. Amantadine (Symetrel) modifies M2
proteins, thus interfering with viral nucleic acid release into
the host cell. As effective as such agents may be, it is
recognized that viral genetic creativity has the capacity, in
time, to circumvent these drug strategies. Viral resistance to
amantadine is well documented, and recently, oseltamivir and
zanamivir have shown similar fates.
Antiviral drug therapies, whether aimed at directly denaturing
the virion to compromise its life cycle, or inactivating it
through vaccine-mediated immunosuppression are subject to the
constant challenge of viral mutational drift and shift. One
complementary line of research aims at understanding the
fundamental natural mechanisms of the body’s antiviral capacity
with a view to enhancing them. Antibody-antigen reactions have
long been central to concepts of primordial defense. Initiated
by viral challenges, the immune system, once set in motion,
activates its cellular elements and synthesizes antibodies.
Activated macrophages and leucocytes engulf virions. Antibodies
fasten themselves to viral particles to neutralize them. But how
do activated immune cells and antibodies really kill virions?
Recent research has focused on the role of gases in this
process. The idea that physiological gases are produced in our
bodies, albeit at the molecular level, has been so
counterintuitive that it is only recently that this notion has
gained gradual conceptual acceptance. The gases principally
involved in microorganism inactivation are nitric oxide and
ozone. A crucial physiological gas: Nitric oxide A gas, with a
half-life of only a few seconds, generated in vivo, as an
essential component of the immune system, with crucial functions
in the nervous and the cardiovascular systems? In only the last
few years, nitric oxide (NO) has received recognition for its
multidimensional physiological functions. Indeed, NO has been
documented to have a role in vasodilatation, neurotransmitter
and immune action, inflammation, angiogenesis (blood vessel
growth), smooth muscle relaxation, and apoptosis (programmed
cell death). Nitroglycerin, a century-old medication for angina
pectoris has been found to exert its beneficial action on blood
vessels via nitric oxide formation. By way of its genesis in the
arginine-nitric oxide pathway and its vasodilative action,
nitric oxide is implicated in the ongoing modulation of blood
pressure, and in erectile function. In the nervous system,
nitric oxide acts as a neurotransmitter. It regulates circadian
rhythms, assists in the formation of memory, and influences the
release of pituitary hormones.
Nitric
oxide is also a bactericide. Cytokine-activated macrophages
produce nitric oxide, as one component of defense against
bacteria, viruses, and nascent cancer cells. Nitric oxide exerts
its antipathogenic functions by disrupting bacterial enzymes, by
interfering with bacterial metabolic pathways such as the Krebs
cycle, and by disorganizing bacterial genes and mitochondrial
function (Snyder 1996). A critical physiological gas: Ozone The
fact that reactive oxygen species (ROS) are produced by immune
system cells during infectious processes has been appreciated
for a long time (Babior 2000; Kourie 1998; Valentine 1995). ROS,
including the hyroxyl radical, nitric oxide, and hydrogen
peroxide, were only thought to be toxic by-products of metabolic
redox reactions requiring rapid neutralization by enzyme
systems. Ozone had hitherto been seen as a molecule capable of
inducing the formation of ROS but certainly not as a molecule
specifically produced within the body to fight infection. The
crucial role of ozone in the task of staving off invading
microorganisms had not been as fully explained as in the
following landmark study. A greatly under-publicized article
with momentous implications (Wentworth 2002, Max 2002)
documented that ozone is indeed produced in the body in the
context of immune function. Its synthesis is triggered by
antigen-antibody reactions, generated by activated neutrophils.
At this molecular level, ozone thus becomes a pivotal factor in
the neutralization of microorganisms.
Additionally, ozone functions as a signaling agent by
stimulating production of nuclear factor kappa B, interleukin 6,
and tumor necrosis factor a. There is ample evidence for ozone’s
activation of cytokines (Bocci 2005). Although the coupling of
antibody to antigen – in this discussion, antibody to virus –
has been known for its outcome, namely the killing of virions,
its fundamental mechanics have largely been a mystery. Recent
research sheds light on this vital phenomenon. Cellular elements
of the immune system (e.g., neutrophils, macrophages), it is now
appreciated, have the capacity to generate singlet oxygen, a
single oxygen atom, which in turn reacts with tissue oxygen to
produce ozone. Fusing with water, ozone generates hydrogen
peroxide. A combination of ozone and hydrogen peroxide,
peroxone, is significantly more powerful in its virucidal power
than either agent alone. Ozone, hydrogen peroxide, peroxone, and
nitric oxide are powerful oxidants. They interact with the
lipids, lipoproteins, proteins, glycoproteins, RNA, and DNA of
virions to disrupt their morphology, their functional capacity,
and their infectivity. The detailed intricacies of these
reactions are far from clear. Certainly, the fact that gases, at
the molecular level, constitute the cornerstone for repelling
the relentless challenge of microorganisms and maintaining the
harmony of health has opened new conceptual vistas.
Gases, in the 90’s, have thus established themselves as a new
category of biological modulators, and are in the process of
revolutionizing medicine. Ozone: Physical and physiological
properties The oxygen atom exists in nature in several forms:
(1) as a free atomic particle (O), it is highly reactive and
unstable (2) Oxygen (O2), its most common and stable form, is
colorless as a gas and pale blue as a liquid (3) Ozone (O3), a
naturally occurring configuration of three oxygen atoms, has a
half-life of about one hour at room temperature, reverting to
oxygen. It has a molecular weight of 48, a density one and a
half times that of oxygen and contains a large excess of energy
in its molecule (O3 é 3/2 O2 + 143 KJ/mole). It has a bond angle
of 127º ± 3°, resonates among several hybrid forms, is
distinctly blue as a gas and dark blue as a solid (4) O4 is a
very unstable, rare, nonmagnetic pale blue gas which readily
breaks down into two molecules of oxygen. A powerful oxidant,
ozone has unique biological properties. Since medicinal ozone is
administered by interfacing it with blood, basic research on
ozone’s biological dynamics have centered upon its effects on
blood cellular elements (e.g., erythrocytes, leucocytes, and
platelets), and on its serum components (proteins, lipids,
lipoproteins, glycolipids, carbohydrates, and electrolytes).
The
effects of ozonation on whole blood are extraordinarily complex.
The contents of serum, with its multitudes of different
proteins, enzymes, immunoglobulins, clotting factors, hormones,
vitamins, lipids, carbohydrates, and electrolytes (Dailey 1998),
in the face of ozonation, yield a symphony of compounds yet
barely inventoried. Erythrocytes have been extensively studied
in relation to ozone administration. Many studies using
erythrocyte suspension in physiologic saline (Kourie 1998;
Fukunaga 1999) have found hemolysis at relatively low ozone
dosages (10 to 30 ug/ml). When ozone is administered in whole
blood, however, the dynamics of ozone interaction are altered
such that hemolysis is observed at significantly higher doses,
implying a buffering action by blood constituents. Moreover, the
functionality of erythrocyte enzymes is maintained, suggesting a
protective role of antioxidant systems (Cross 1992). Leucocytes
show good resistance to ozone because, unlike viruses, they
possess enzymes protecting them from oxidative damage. These
enzymes include superoxide dismutase, glutathione, and catalase.
A promising area of research centers on cytokine and interferon
stimulation in ozone administration and its implication for
enhancing immune function (Paulesu 1991; Bocci 2002; Larini
2001).
Ozone:
Antipathogenic properties
Recently, there has been renewed interest in the potential of
ozone for viral inactivation in vivo. It has long been
established that ozone neutralizes viruses in aqueous media and
it stands to reason that it would be studied for similar
applications in living systems. In vivo ozone applications,
however, present far greater challenges. Indeed, the technology
of medical ozone administration aims to respect the delicate
balance of patient safety on one hand and antimicrobial efficacy
on the other. All viruses are susceptible to ozone’s
neutralizing action. Viruses, however, differ in their relative
susceptibility to destruction by ozone. In one study, poliovirus
resistance was 40 times that of coxsackievirus. Relative
susceptibility in ascending order was found to be: poliovirus
type 2, echovirus type 1, poliovirus type 1, coxsackievirus type
B5, echovirus type 5, and coxsackievirus type A9. In pure water,
at maximal solubility of ozone and room temperature, echovirus
type 29 is inactivated in one minute, poliovirus type 1 in two,
type 3 in three, and type 2 in seven minutes (Roy 1982).
Analysis of viral components showed damage to polypeptide chains
and envelope proteins, which could result in attachment
capability compromise, and breakage of the single-stranded RNA,
producing replicating dysfunction. Other researchers, in similar
experiments, concluded that in ozonation, it is the viral capsid
that sustains damage (Riesser 1977).
Lipid-enveloped viruses are sensitive to treatment with ether,
organic solvents, and ozone, indicating that disruption or loss
of lipids results in impaired or destroyed infectivity. Viruses
containing lipid envelopes include the Hepadnaviridae (Hepatitis
B) Flaviviridae (Hepatitis C, West Nile virus, yellow fever);
Herpesviridae, a large family grouping the Simplex,
Varicella-Zoster, Cytomegalovirus, and Epstein-Barr viruses; the
Orthomyxoviridae (Avian influenza); the Paramyxoviridae (mumps,
measles); the Coronaviridae (SARS); the Rhabdoviridae (rabies);
the Togaviridae (Rubella, encephalitis); the Bunyaviridae
(Hantavirus); the Poxviridae (Smallpox); and the Retroviridae
(HIV), among others. Indeed, once the virion’s lipid envelope
becomes fragmented, its DNA or RNA core cannot survive. Viruses
that do not have an envelope are called “naked viruses.” They
are constituted of a nucleic acid core made of DNA or RNA, and a
nucleic acid coat, or capsid, made of protein. Some
non-enveloped viruses include: Adenoviridae (respiratory
infections), Picornaviridae (poliovirus, coxsackie, echovirus,
rhinovirus, hepatitis A), Caliciviridae (hepatitis E, Norwalk
gastroenteritis), and Papillomaviridae. Ozone, aside from its
well-recognized action upon the complex unsaturated lipids of
viral envelopes, can also interact with proteins and their
constituents, namely amino acids. Indeed, when ozone comes in
contact with viral capsid proteins, protein hydroxides and
protein hydroperoxides are formed and viral demise ensues.
Viruses, unlike mammalian cells, have no enzymatic protection
against oxidative stress. The enveloped viruses are usually more
sensitive to physico-chemical challenges than are naked virions.
This has been shown for ozone (Bolton 1982). Although ozone’s
effects upon unsaturated lipids are one of its best documented
biochemical action, ozone is known to interact with proteins,
carbohydrates, and nucleic acids. This becomes especially
relevant when ozone inactivation of non-enveloped virions is
considered.
Ozone:
Clinical methodology
Ozone may be utilized for the therapy of a spectrum of clinical
conditions (Viebahn 1999, Bocci 2005). Routes of administration
are varied and include external, and internal (blood
interfacing) methods. In the technique of oxygen/ozone blood
administration, an aliquot of blood (50 to 300 ml) is withdrawn
from a virally afflicted patient, anticoagulated, interfaced
with an ozone/oxygen mixture, and then returned to the patient.
This process, called major autohemotherapy (AHT), is repeated
serially in a manner consonant with the viral entity under
treatment, the clinical course, and the treatment protocol.
Importantly, another more experimental and more intensive
technique of ozone administration makes use of the
extracorporeal treatment of the entire blood volume using a
hollow-fibre oxygenator-ozonizer (Di Paolo 2000; Bocci 2002).
This approach is promising because the totality of blood and
lymphatic fluids is interfaced with oxygen/ozone mixtures, thus
providing integral anti-viral therapy. Research is needed to
determine appropriate ozone dosage and treatment duration
protocols relative to the viral entity under treatment. Many
studies have reported the safety of ozone administration. As
regards efficacy, Wells et al. showed that ozone-treated
HIV-spiked Factor VIII maintained its biological capacity and
that, concomitantly, an 11-log reduction in detectable virions
was achieved. The improvement of liver enzymes in hepatitis C
patients after several months of ozone therapy was described
(Viebahn 1999; Amato 2000). An 80% hepatitis C viral load
reduction in 82 patients using autohemotherapy was reported
(Luongo et al., 2000). Reports of many studies in various
conditions, albeit in many cases featuring small patient samples
and inadequate controls, may be found in the writings of a
number of authors (Bocci 2005; Altman 1995).
Ozone: Possible mechanisms of anti-viral action
The average adult has 5 to 6 liters of blood, accounting for
about 7% of body weight. How can any viral load reduction
reported via AHT ozone therapy be explained in the face of a
technique that treats a relatively small percentage of total
blood volume, albeit serially? And how could extracorporeal
ozone administration come to the aid of a patient beleaguered by
a virulent viral infection? The viral culling effects of ozone
in infected blood may recruit a variety of mechanisms. Research
is needed to ascribe relative importance to these, and possibly
other mechanisms of ozone’s anti-viral action: 1. The
denaturation of virions through direct contact with ozone.
Ozone, via this mechanism, disrupts viral lipids, lipoproteins,
and glycolipids. The presence of numerous double chemical bonds
in these molecules makes them vulnerable to the oxidizing action
of electron-hungry ozone. By readily donating one of its oxygen
atoms, ozone reconfigures the bonds of viral lipid envelopes,
fatally disrupting viral architecture. Deprived of an envelope,
virions cannot sustain nor replicate themselves. 2. Ozone
proper, and the peroxide, hydroxyl radical, and peroxone
compounds it creates, may alter the viral structures necessary
for attachment to host cells. Peplomers, the glycoproteins
protuberances gluing virions to host cell receptors are likely
sites of ozone action.
Even minimal alteration in peplomer integrity through
glycoprotein peroxidation could impair attachment to host
cellular membranes foiling viral attachment and penetration. 3.
Introduction of ozone into the serum portion of whole blood
induces the formation of lipid and protein peroxides. While
these peroxides are not toxic to the host in quantities produced
by the protocols of ozone therapy, they nevertheless possess
oxidizing properties of their own which persist in the
bloodstream for several hours. Peroxides created by ozone
administration show long-term antiviral effects that may serve
to further reduce viral load. 4. The immunological effects of
ozone have been documented (Bocci 1992; Paulesu 1991).
Cytokines, proteins manufactured by several types of immune
system cells, regulate the functions of other cells. Mostly
released by leucocytes, cytokines are important in mobilizing
immune reactivity. Ozone-induced release of cytokines may
constitute an avenue for the reduction of circulating virions
via the activation of immune cells. 5. Ozone action on viral
particles in infected blood yield several possible outcomes. One
outcome is the modification of virions so that they remain
structurally grossly intact yet sufficiently dysfunctional as to
be nonpathogenic. This attenuation of viral particle
functionality through slight modifications of the viral
envelope, and possibly the viral genome itself, not only
modifies pathogenicity but also allows the host to diversify its
immune response. The creation of dysfunctional viruses by ozone
may offer unique therapeutic possibilities. In view of the fact
that so many mutational variants exist in any one afflicted
individual, the creation of an antigenic spectrum of crippled,
fragmented, and attenuated virions could provide for a unique
host-specific stimulation of the immune system, thus permitting
the creation of what may be seen as a host-specific autovaccine.
6. Finally, a very exciting avenue of research suggests that the
fundamental virucidal properties of antibodies are predicated
upon their ability to catalyse singlet oxygen which, in its
reaction with tissue oxygen produces ozone (Marx 2002; Wentworth
2002). A key element in the viral-inactivating capacity of
antibodies may thus reside in the formation of ozone integral to
antigen- antibody reactions. Exogenously administered ozone may,
in this model, amplify the efficacy of antigen-antibody
dynamics.
Physiological gases: Implications for research and therapy for
influenza The importance of discovering how physiological gases
exert their virucidal action resides in finding methods of
enhancing their effects. Therapeutic strategies for increasing
the production of gaseous oxidants at the antibody-virion
interface could assist in countering a number of viral
pathologies, including influenza. One such approach could aim at
activating the immune system’s production of singlet oxygen.
This could be done in a variety of ways once the metabolic steps
for singlet oxygen production are discovered. Another method
makes use of administrating oxidative gases to bodily fluids,
the logical choice being blood, as performed in ozone
autohemotherapy and inextracorporeal ozone therapy. A question
perennially presents itself with these methods: Do exogenously
applied oxidative gases injure the cellular elements in blood
such as erythrocytes, leucocytes, and platelets, and its
molecular constituents? Ozone has a decades-long history of
practices involving its interfacing with blood for a variety of
clinical situations. At appropriate doses and protocols,
ozone/oxygen treatment produces no untoward effects in blood.
Its patient safety is well established. There are no references
to introducing nitric oxide in the circulation. The reason is
that nitric oxide, in even minute amounts, has propensities to
induce cellular damage, even though, at the molecular level, it
is essential to life.
Avian influenza, like most human viral pathogens, constantly
seeks to find breaches in the immunological defenses in its
target population, aiming to strike an optimal balance between
its dynamic propagation and its lethality. A universal strategy
in mastering viral infections is the culling of pathogenic
organisms to the point where they no longer represent a
replicative threat. Concomitantly, the actuation of host immune
memory serves to repel future infective attempts made by the
virus. In the case of influenza, however, the virus continuously
creates novel quasispecies, some of which may be so new, and so
virulent, that immune memory becomes superfluous. This is the
scenario for an influenza pandemic. Because of its acuteness,
avian influenza requires proactive viral culling as soon as the
first symptoms arrive. With billions of influenza viral
particles generated daily – a reproductive phenomenon commonly
observed in the viremic episodes of enveloped viruses – it is
apparent that anti-viral therapy needs to be administered in an
emergency mode. As regards an influenza antiviral strategy using
physiological gas therapy with ozone/oxygen mixtures, it is
suggested that research thrusts explore the following: The
effectiveness of autohemotherapy. Needed are studies on ozone’s
anti- influenza virions both in vitro and in vivo. This would
make possible the determination of optimal inactivation
parameters relative to ozone dosage and duration and frequency
of blood treatments. Intensive oxygen/ozone treatment of blood
aliquots in the acute phases of the influenza infection could
reduce morbidity and mortality via any one of the six possible
mechanisms of ozone anti-viral action enumerated above. The
effectiveness of extracorporeal treatment of the total blood
volume with ozone/oxygen.
If ozone administration to blood exerts a therapeutic influence
by boosting antigen-antibody oxidative dynamics, it stands to
reason that a therapeutic advantage could derive from this
method. A limiting factor in internal ozone administration has
been the total allowable ozone dosage that, according to some
authors, should not exceed 6 milligrams per treatment (Viebahn
1994). The German and Austrian societies for ozone therapy, on
the other hand, suggest a dose of 3 mg. Accordingly, respecting
these parameters, ozone-mediated enhancement of antigen-antibody
reactions in bodily fluids may only require minuscule ozone
dosages over long treatment times. Extracorporeal oxygen/ozone
treatment could thus provide for the safe and effective culling
of virions in the acute viremic phase of influenza, at a time
when it is most urgently needed. |
