Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

J. Environ. Treat. Tech.

ISSN: 2309-1185

Journal web link: http://www.jett.dormaj.com

Antiviral Pneumonia to Treat Influenza Virus

3,1

1,2

Sargol Mazraedoost *, Seyyed Mojtaba Mousavi , Seyyed Alireza Hashemi , Ahmad

Gholami⁴

Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 71348-14336

Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

Department of Chemical Engineering, National Taiwan University of Science and Technology, Taiwan

Pharmaceutical Sciences Research Center and Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical

Sciences, Shiraz, Iran

Received: 03/02/2020

Accepted: 13/03/2020

Published: 20/05/2020

Abstract

Influenza, an infectious disease of the respiratory system, represents a tremendous sized burden for public health. Influenza was once

found not through a direct learn about the disorder in humans, but as a substitute from research on animal diseases. An ailment that can

resemble the frequent cold, influenza packs a powerful and on occasion deadly punch. As numerous as half-a-million people around the

world die yearly from flu. The perpetrator is a virus that mutates to steer clear of our immune systems, leaving vaccines and remedies

scrambling to preserve up. In many years, a mutation creates a pathogen that is specifically nasty, ensuing in pandemic flu. Influenza is

an acute respiratory disorder brought on by using the influenza A or B virus. It often happens in outbreaks and epidemics worldwide,

frequently in the course of the iciness season. Significant numbers of influenza virus particles exist in the respiratory secretions of

infected persons so that infection can be transmitted via sneezing and coughing using large-particle droplets. The imply duration of

influenza virus shedding in immunocompetent adult patients is around 5 days but may also proceed for up to 10 days or further mostly

in children, elderly adults, patients with chronic illnesses, and immunocompromised hosts. Influenza generally starts with the abrupt

onset of high-grade fever, myalgia, headache, and malaise. These manifestations are attended by way of signs of respiratory tract ailments

such as non-productive cough, sore throat, and nasal discharge. After an ordinary course, influenza can affect different organs such as

the lungs, brain, and heart more than it can affect the respiratory tract and motive hospitalization. The excellent way to stop influenza is

to administer annual vaccinations. For centuries, new strains of influenza have emerged to produce human pandemics, inflicting massive

illness, death, and disruption. There have been four flu pandemics within the earlier hundred a long time. Throughout this time,

globalization processes, globalisation processes, alongside advances in medicine and epidemiology, have altered the way these

pandemics are experienced.

Keywords: Pandemic; Influenza; Human; Infectious disease

Introduction¹

Influenza is a transmittable viral illness that influences the

harvest time and snowy climate in mild zones and influence a

massive factor of grown-ups and youngsters, anyway seasons

in an alternate way sway age associations and seriousness (Fig

apex respiratory tract, which envelops the upper and point of

respiratory confinement sections. It is accelerated by methods

for utilizing an enormous range of Influenza infections. A

portion of these infections can infect people, and some are

specific to notable species. These infections are transmissible

through respiratory beads ousted from the mouth and

respiratory machine all through hacking, talking, and sniffling.

The influenza disease can be transmitted by the ability to

contact lifeless things dirtied with the infection and contacting

the nostril or eye. Influenza can be transmitted heretofore than

the influenced individual is symptomatic and till 5 to 7 days

after disease. After disease, it takes a couple of days for the

majority of the empowering unfortunate casualties to show

signs of improvement. Ultimately, on the other hand,

inconveniences that comprise of pneumonia and death toll are

visited in positive high-chance gatherings. These associations

incorporate more youthful kids, old, immunocompromised, and

pregnant females. Indications of flu comprise of a runny nose,

high fever, hack, and sore throat. Flu spreads and effectively in

occasional pandemics. Influenza scourges occur every single

) (1-4).

2 Etiology

Influenza viruses belong to the household of viruses termed

“Orthomyxoviridae,” an RNA kind virus with various antigenic

characteristics. They are divided into three most important

types: A, B, and C (Fig 2). Furthermost of the epidemics and

outbreaks of influenza are induced by types A and B, with type

C being commonly accountable for sporadic moderate-higher

respiratory symptoms (5, 6). Infections have round or

filamentous shapes with an envelope, containing glycoproteins

and a single-stranded RNA quality. The 2 most extraordinary

fundamental glycoproteins over the outer layer of this season's

flu virus disease are hemagglutinin (H, or HA) and

neuraminidase (N, or NA). The two include quintessential parts

inside the pathogenesis of the sickness. For flu kind A, at

slightest sixteen in specific variable hemagglutinins (H1 to

H16) and 9 unimaginable NAs (N1 to N9) have been analyzed

so distant.

Corresponding author: Seyyed Alireza Hashemi, (a) Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences,

Shiraz, Iran. 71348-14336. (b) Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz

University of Medical Sciences, Shiraz, Iran.

Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

Fig 1. Structure of the influenza virus. 3D illustration displaying floor glycoprotein spikes hemagglutinin blue and neuraminidase green, M2 protein

red, capsid made of M1 protein pink and eight fragments of RNA

Fig 2. Influenza virus type

With the valuable asset of this one of a shape antigen, the flu

sort A infection is mainly subdivided into subtypes based on

total variable designs of their impressive H or N proteins (e.g.,

H1N1 or H3N2). By the by, within the terminology of the

infections, other factors for illustration the locale of preparatory

confinement and the yr of segregation are covered (7-10). The

influenza B virus has a related viral form to form A; however,

due to the constant antigenic characters of HA and NA, there

are no subtypes in this virus. Still, some small antigenic

variabilities have been stated on account that 1970 in this virus,

with the virus, had started out to diverge into 2 antigenically

awesome lineages (11).

Epidemiology

Researchers isolated Influenza A in 1933, seven years later,

they remoted influenza B. Influenza viruses in specific

geographic areas of the northern and southern hemispheres are

recognized as an influenza epidemic which takes place every yr

at some stage in the winter seasons.

Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

Fig 3. Summary of the ecology of influenza viruses (12)

The severity, size of influenza, and age organizations that

are profoundly impacted and complication expenses such as

hospitalizations and deaths range substantially all via one of a

kind influenza seasons. When H3N2 viruses predominate, the

season tends to be extra extreme, particularly amongst youth

and the elderly. World Health Organization (WHO) conducts

world influenza virologic surveillance that shows influenza

viruses are isolated each month from human beings in a

geographic region. In temperate regions, influenza endeavour

peaks for the duration of the wintry weather months.

automatically in hospitals involve further re-evaluation.

Furthermore, contact with contaminated surfaces containing

respiratory droplets is some other practicable supply of ailment

transmission. In adults barring other underlying diseases, the

shedding of the virus begins from 24 to forty-eight hours earlier

than disorder manifestation, and the shedding stops after 6 or 7

days according to most research and after 10 days in accordance

with some other investigations (18). It is viewed that longer

intervals of shedding and infectiousness can occur in children,

elderly adults, immunocompromised hosts, and patients with

chronic illnesses (Fig 3) (12, 19).

Transmission

In the respiratory secretion of the sufferers struggling from

Complications of Influenza

influenza, massive amounts of virus load are often present, and,

as a result, each contaminated man or woman can be

transmitting contamination to other folks by sneezing and

coughing. It has been posited that the disorder is transmitted

notably through large-particle droplets (>5 µ).(13) Owing to the

large dimension of infectious droplets, shut contact is wished

for the acquisition of the disease. These large particles usually

do not continue to be suspended in the air for a lengthy time,

and they tour only quick distances. Airborne transmission is,

therefore, now not often regarded for disorder unfold (14, 15).

Though confined data exhibit that small particle respiratory

droplets, which emerge as aerosolized and can stay deferred in

the air for a long time, also contain the influenza virus and can

potentially cause disease to unfold (16). In the latest study,

aerosol transmission accounted for around half of all the

transmission events. This suggests that activities to minimize

transmission with the aid of contact or large droplets may

additionally not be sufficient to manage the transmission of the

influenza A virus in households or communities (17).

Consequently, the prevention techniques that are drawn

.1 Pneumonia

The most critical and frequent complication of influenza is

pneumonia, now not least in high-risk individuals. Pneumonia

may also appear as a continuum of the acute influenza

syndrome when induced using the influenza virus (primary

pneumonia) or as a blended viral and bacterial contamination

after a hole of a few days (secondary pneumonia).

.2 Primary Influenza Viral Pneumonia

The illness happens after the regular route of influenza with

the quick development of fever, dyspnea, cough, cyanosis, and

challenging breathing. It takes place predominantly amongst

individuals with cardiovascular or underlying pulmonary

ailments such as asthma. Physical examination is in pick out of

bilateral lung involvement, and imaging findings in the lungs

represent reticular or reticulonodular opacities with or barring

superimposed consolidation. Sometimes the radiological look

of primary influenza pneumonia can be challenging to

distinguish from pulmonary edema due to the truth of the

presence of perihilar congestion and hazy opacification, at least

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Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

in the minimize lobes. Less commonly, radiographs

demonstration focal zones of infiltration (20-22).

attempted and the patients, reaching out from 4.4% to 80% in

contrast with cell culture as the best quality level test.

Commonly used pneumonia severity evaluation equipment

such as the CURB65 or the Pneumonia Severity Index are not

beneficial in finding out which patients to hospitalize due to

primary influenza pneumonia, considering that these tools have

now not been developed and validated at some point of an

influenza pandemic (23). Therefore, the sickness occurs after

the ordinary course of influenza with the quick development of

fever, dyspnea, cough, cyanosis, and severe breathing. It takes

place predominantly amongst humans with cardiovascular or

underlying pulmonary illnesses such as asthma. Physical

examination is in pick out of bilateral lung involvement, and

imaging findings in the lungs signify reticular or

reticulonodular opacities with or except superimposed

consolidation. Sometimes the radiological seems to be of

fundamental influenza pneumonia can be challenging to

distinguish from pulmonary edema due to the truth of the

presence of perihilar congestion and hazy opacification, at least

in the reduce lobes. Less frequently, radiographs demonstrate

focal areas of infiltration (24). The most severe instances grow

swiftly to acute respiratory misery syndrome and multilobar

alveolar infiltrations. These patients are ordinarily current with

new dyspnea and extreme hypoxemia 2 to 5 days after the onset

of common influenza symptoms. Hypoxemia will increase

swiftly and causes respiratory failure, requiring intubation and

mechanical ventilation, possibly after solely one day of

hospitalization (25, 26).

Diagnosis

Their clinical appearances analyze the lion's share of

influenza cases, and there is no requirement for research facility

tests. Be that because it may, in uncommon circumstances, the

conclusion of influenza requires research facility affirmation

utilizing available tests such as corrosive nucleic tests (e.g.,

polymerase chain response [PCR]) or quick determination units

or once in a while infection segregation by culture strategies.

.1 Rapid Diagnosis Influenza Tests

Quick influenza symptomatic tests distinguish flu viral

antigens and screen patients with suspected influenza

conveniently in comparison to other demonstrative modalities.

The first broadly utilized method is based on the detection of

viral antigens within the respiratory emissions of patients by

immunologic strategies. All quick tests are performed with ease

and can give comes about inside 30 minutes. Each test changes

concerning whether it can recognize between influenza A and

B. In any case, these tests have hence distant been incapable of

indicating sorts of flu A, such as H1N1 and H3N2. Then when

all is said in done, specificities achieved by these tests are tall

and practically identical between the makers. In any case, their

sensitivities have seemed magnificent heterogeneity over

considers relying upon the idea of the tests attempted and the

patients, reaching out from 4.4% to 80% in contrast with cell

culture as the best quality level test (33-35). As a familiar

concept, affectability in grown-ups is less than that detailed in

more youthful patients.

Furthermore, the affectability may be higher at the onset of

the malady, when the next stack of the infection exists.

Financial thinks about comparing fast testing to the clinical

determination of influenza stay uncertain. Without a doubt, a

few considers have proposed that, in most cases, clinical

judgment combined with antiviral treatment is the foremost

cost-effective procedure (36), whereas unused ponders have

proposed that testing may be the foremost cost-effective

methodology and appeared that oseltamivir treatment based on

the point-of-care (POC) test could be a prevailing alternative

compared to customary approaches without screening tests

within the pattern situation which they can be cost-effective in

.3 Secondary Bacterial Pneumonia

The occurrence of secondary bacterial pneumonia extended

from 2% to 18% throughout the influenza pandemic in 1957–

8 (27). A threefold amplify in the incidence of secondary

Staphylococcus aureus pneumonia during the influenza

pandemic of 1968–9 compared to a non-epidemic length of

pneumonia etiologies was determined (28).

As of late, community-acquired methicillin-resistant

Staphylococcus aureus was decided after regular influenza

(29); in any case, another widespread etiologic bacterium is

Streptococcus pneumonia. The influenced character

encompasses a first influenza disease, went with through

potential of an enhancement length enduring maximally 2

weeks. The rehash of the side impacts, for illustration, fever,

useful hack, and dyspnea and disclosures of unused unions in

chest imaging, can be found in included patients.

0% of cases concurring to the cost-effectiveness worthiness

bend. Besides, influenza antiviral treatment based on POC may

well be cost-effective in particular conditions of execution,

cost, and infection predominance (37).

.4 Non-Pulmonary Complications

Regardless of its respiratory impacts, the disease can apply

results for unmistakable body structures, for the case, the

musculoskeletal, cardiovascular, and neurologic systems.

Myocarditis and pericarditis speak to abnormal at that point

once more critical issues of regular or widespread influenza. In

a planned consider, half of grown-up flu sufferers but cardiac

complaints had beat score ECG discoveries at introduction

.2 Molecular Tests

Due to the restriction in other demonstrative modalities in

influenza location, atomic tests have progressively been

considered the gold standard symptomatic strategy for the

location of the influenza disease in healing center based

demonstrative research facilities. Even though

a few

(30). Myocarditis, for the most part, settles by 28 days, and the

enhancement strategies have been created, the more significant

part of the current assays—particularly those utilized in clinical

laboratories—is based on the PCR enhancement strategy. These

tests can check a few targets concurrently and subsequently

give sort and subtype data for each infection. Furthermore, they

can be adjusted quickly for the location of novel targets; these

highlights (38) played a primary part amid the influenza

widespread of 2009. PCR is possibly more delicate than cell

culture, and it can distinguish the nonviable infection in tests.

The affectability of these tests is subordinate to the test location

of the understanding and is comparable to that of the fast tests.

Swab tests of a nasopharyngeal beginning can get higher

affectability.

patients include great heart-muscle work without

diminished launch division. Noteworthy myositis and

rhabdomyolysis have seldom been detailed with regular flu

(31), but diverse sums of creatine phosphokinase rise have been

detailed in numerous considers after conventional or

widespread flues (32, 33). Mellow myositis and myoglobinuria

with delicate leg or back muscles can primarily be seen in

children, the when all is said in done specificities achieved by

these tests are tall and practically identical between the makers.

In any case, their sensitivities have seemed magnificent

heterogeneity over considers relying upon the idea of the tests

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Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

Diagnostic Tests

Fig 4. Diagnostic Tests

PCR-based atomic measures have yielded fabulous clinical

utility for the discovery and distinguishing proof of influenza

disease at the bedside as POC, and various Nourishment and

Sedate Organization (FDA)-cleared commercial gadgets are

presently accessible (39-41).

Pathophysiology

Influenza is an acute infection that points to the upper

respiratory tract and thought processes disease of the upper

respiratory tree and trachea. The great signs endure for seven to

ten days, and the sickness is self-limited in most solid people.

The resistant reaction to the viral disease and the intergalactic

reaction is dependable for the viral disorder that incorporates

over the top fever, coryza, and physical make-up hurts. High-

risk companies who have nonstop lung illnesses, cardiac

illness, and being pregnant are higher slanted to extraordinary

inconveniences such as imperative viral pneumonia, auxiliary

bacterial pneumonia, hemorrhagic bronchitis, and passing.

These extraordinary inconveniences can upgrade in as small as

forty-eight hours from the beginning of indications. The

infection duplicates within the more prominent and diminishes

respiratory sections starting from the time of immunization and

cresting after forty-eight hours, on average.

Part of the Research facility Conclusion of Flu

in Clinical Case Administration

Given the self-limiting nature of the infection in something

else reliable people, there is no requirement for demonstrative

tests in all showing cases. Demonstrative tests ought to be

conducted in case the comes about of the test is thought to be

able to impact consequent clinical administration, and in case

the comes about of the test are regarded persuasive in choices

on the start of particular antiviral treatment, effect on other

symptomatic tests, anti-microbial treatment decision-making,

and contamination control practices (42, 43). Moreover, amid

influenza seasons, hospitalized people of any age with fever and

Viral entry: How does the virion enter the

extreme respiratory symptoms—including those with

conclusion of community-acquired pneumonia—need research

facility testing independent of time from ailment onset.

host?

The excellent way in which influenza is transmitted is from

individual to individual by mist concentrates and beads.

Influenza at that point enters the have through the respiratory

tract. In a human lung, there are almost 300 million terminal

sacs, called alveoli, that work in vaporous trade between

motivated discussion and the blood—the entire absorptive

region of the human lung ranges from 80-120 m2. The resting

ventilation rate in people is around 6 liters of discussing per

miniature, which presents enormous numbers of outside

particles and aerosolized beads, possibly containing infection

into the lungs. Testimony of outside particles depends on their

estimate: inward breath of tiny particles does not result in

assimilation through the alveoli or bronchial framework. Little

beads with a breadth of approximately 1 to 4 µm accelerate

within the little aviation routes. Much bigger particles are either

not able to enter the respiratory contraption or are kept within

the best respiratory tract (Figure 5A).Various have defense

components comprising of mechanical deterrents piece

respiratory tract disease. The respiratory tract is included with

a mucociliary layer comprising of ciliated cells, mucus-

secreting cells, and organs (Figure 5B). Outside particles within

the nasal depth or best respiratory tract are caught in the bodily

fluid, carried lower back to the throat, and gulped. From the

diminish respiratory tract, foreign particles are brought up by

way of the ciliary action of epithelial cells. Within the alveoli

that need cilia or bodily fluid, macrophages are dependable for

wrecking particles (Figure 5).

Rapid Influenza Antigen (Nasal or Throat

Swab)

What is this test? This test rapidly checks for signs of the

influenza viruses A and B in a sample of secretions from your

nose or throat. Influenza or the "flu" is an illness of the

respiratory system. Influenza A is further common than

influenza B. It spreads effectively through water beads within

the discuss from hacks or sniffles of individuals who are

tainted. It regularly influences numerous individuals at the

same time throughout fall and winter.

Symptoms of the flu often show up suddenly. This is often

about 1 to 4 days after you're tainted. Most individuals will get

way better inside some days to less than 2 weeks. But those

with a debilitated resistant framework may get serious

pneumonia or other genuine issues. Your healthcare supplier

can test for the flu in a few ways. This test as a rule gives comes

about rapidly. Immunofluorescence is another test and

employments a recoloring procedure. Comes about from these

tests are not as precise as viral societies. But these tests are

speedier and less demanding. They are commonly utilized for

the primary screening. You do not continuously require a flu

test for your supplier to analyze the flu. Healthcare suppliers

may make the determination and start treatment based on your

side effects and a physical exam.

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Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

Fig 5. Locales of the influenza section within the respiratory tract. (A) The anatomical and viable structures of the human aviation routes appear. Influenza,

to begin with, contaminates the higher aviation route and the ciliated cells within the bronchus and bronchioli. Coming about logical disorders comprise

of tracheitis, bronchitis, bronchiolitis, and bronchopneumonia. The versatile, safe reaction is started in lymph hubs nearby the aviation routes. (B) The

respiratory epithelia are primarily outfitted to watch from approaching pathogens using a layer of bodily fluid (bronchus), ciliated cells (bronchus and

bronchioli), and alveolar macrophages (alveoli) (42).

acknowledgment of this perilous atom by cellular sensors,

Histopathology

which would something else trigger IFN α/β discharge (48-51).

The flexible, safe response requires several days to be

better than average, but at that point makes a distinction to

contain the viral spread, to destroy the disease, and at final to

set up a memory response coming approximately in a long-

lived resistance to re-infection with the homologous disease.

Cross-protection interior, a subtype of flu, has only scarcely

ever been found, and contaminations truly set off no

confirmation over subtypes or between sorts A and B (Treanor

Influenza disease imitate within the epithelial phone lining

of the beat and lower respiratory tracts. The pathology does no

longer extend between home grew or test contamination.

Conclusive conclusion of influenza serologic, immunologic,

and atomic testing through RT-PCR for higher or lower

respiratory tract examples. Mellow cases grandstand neurotic

changes within the respiratory tracts; in any case, extreme

occurrences exhibit explicit confirmation of pathologic

alterations of pneumonia. The tracheobronchial changes due to

influenza contamination can be summarized as redness and

contamination with mucous and purulent discharge

macroscopically, and desquamation and destruction of the

pseudostratified epithelium of the trachea and bronchi with

ultimately the basal layer remained viable however infected

microscopically (44).

005). Flu contamination activates each systemic and

neighbourhood

counteracting

specialist

(humoral

insusceptibility), as fittingly as cytotoxic

convenient

responses (cellular insusceptibility), each of which is

fundamental in patching from strongly debasement and

resistance to reinfection (52, 53).

0 Therapy

Immunology

Influenza causes intense contamination of the have and

Right now, at slightest four antiviral capsules are helpful for

the treatment and avoidance of flu. It is meriting of being

mindful that in energizing immunocompetent people with

intaglio resistance, there is a fast inconvenience within the

capability of the flu infection; hence, the subterranean insect

replication control of antiviral tablets is constrained and has no

hypothetical impact. Too, no think about to date has confirmed

a useful effect for antiviral retailers starting the past 48 hours of

indication onset. The most prominent effect is classically

viewed when cure is begun out within the, to begin with, 24

hours. Treatment is embraced for each grown-up and kids with

the flu infection defilement with the taking after criteria: 1)

persons with laboratory-confirmed or distinctly suspected

influenza virus contamination in high-risk corporations (table

starts a cascade of safe responses enacting about all parts of the

resistant defense framework. Most of the initial natural

reaction, comprehensive of cytokine discharge (IFNα/β), influx

of neutrophil granulocytes, or healthy executioner cells (45-

7), and cell actuation, is dependable for the intense onset of

the clinical indications (see over). Natural resistance is a

fundamental prerequisite for the versatile resistant reaction,

firstly, to constrain the starting viral replication and antigen

stack, and since the antigen-specific lymphocytes of the

versatile resistant reaction are enacted by co-stimulatory atoms

that are initiated on cells of the intrinsic resistant framework

amid their interaction with infections (Figure 6). Influenza

diseases, in any case, encode inside the non-basic protein 1

), inside 48 hours after symptom onset; 2) patients requiring

(NS1) segments to keep away from and offend the IFN α/β

hospitalization for laboratory-confirmed or outstandingly

response. NS1 is likely to sequester viral dsRNA, which avoids

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Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

suspected flu infection, in any case of fundamental ailments, in

case treatment can be started inside 48 hours after side effect

onset; and 3) outpatients at high chance of issues (table 1) with

a sickness that's not making strides and outpatients with high-

quality flu take a see at conclusion result from an example

gotten >48 hours after side effect onset. Individuals whose

onset of signs is >48 hours sometime recently introduction with

continuing moderate-to-severe illness.

available antiviral drugs are changing quickly. Clinicians ought

to be mindful of the nearby designs of flu circulations and

susceptibilities. For occurrence, a meta-analysis appeared that

NAIs were able to reduce mortality in patients conceded to the

healing center with An H1N1pdm09 disease. Scattered

oseltamivir-resistant contaminations have been recognized,

along with different side scenes of restricted transmission (62).

Given the as of now circulating flu A (H3N2) and 2009 H1N1

infection resistance to adamantanes, these solutions are not

suggested for utilizing against flu A virus-induced diseases. Be

that as it may, most influenza A and B infection strains are still

vulnerable to neuraminidases, for example, oseltamivir and

zanamivir, with these drugs being chosen for treatment in

demonstrated people (table 2). In expansion, it ought to be

considered that the improvement of resistance to oseltamivir

amid treatment was more common among regular flu A (H1N1)

infection contaminations (27%) than among regular influenza

A (H3N2) (3%) or B (0%) infection contaminations in a later

ponder (63). Due to the confinements within the current

restorative alternatives for the treatment of influenza.

Amid the final widespread wave, neuraminidase inhibitors

(NAIs)—primarily oseltamivir and zanamivir—were broadly

endorsed for patients with affirmed or suspected

H1N1pdm09 infection (54-56). Be that as it may, sometimes

newly the 2009–10 widespread, prove of their adequacy in

regular flu, whereas reliable for unassuming indication

diminishment, was less reliable for diminishes in pneumonia

rate or pneumonia result change (57-60). Later information

illustrated that patients with influenza-related pneumonia

treated early after ailment onset) with an NAI experienced

around one-third lower probability of biting the dust or

requiring ventilator help compared to those treated at afterward

hours (15, 61). Influenza viruses and their susceptibilities to

Fig 6. Innate immunity is a necessary prerequisite for the versatile resistant reaction, firstly, to constrain the starting viral replication and antigen stack,

and since the antigen-specific lymphocytes of the versatile resistant reaction are enacted by co-stimulatory atoms that are actuated on cells of the safe,

natural framework amid their interaction with viruses.

Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

Table 1: Recommended dosages and durations of influenza antiviral medications for treatment or chemoprophylaxis

Antiviral agent

Oseltamivir

Use

Adults

75 mg twice daily

Treatment (5 d)

Chemoprophylaxis (7 d)

mg once 75

daily

Zanamivir

Treatment (5 d)

Chemoprophylaxis (7 d)

10 mg (two 5-mg inhalations) twice daily

10 mg (two 5-mg inhalations) once daily

Virus infections, extra treatment choices with a diverse

instrument of activity have been examined as a treatment for

people with extreme influenza infection. For the case, a modest

bunch of mAbs against influenza infection proteins are as of

now within the early stages of assessment for human disease

control (64). These mAbs target the external portions (i.e.,

ectodomain) of the M2 protein (M2e). These mAbs target the

outside parcels (i.e., ectodomain) of the M2 protein (M2e). The

M2e is an alluring target for influenza immunizations and

therapeutic antibodies since the significantly moderated nature

of the corrosive amino groupings of its spaces among separates

from diverse subtypes of influenza A viruses (65).

too may be treated with antiviral drugs by their specialist

this season. Most otherwise-healthy individuals who get

flu, be that as it may, don't have to be be treated with

antiviral drugs.

3 Prevention

3.1 Vaccination

The first vital methodology for the anticipation of influenza

and its serious results is yearly immunization against regular

flu. The influenza infection is characterized by its high rate of

transformation, beating the safe system’s work against unused

variations (73), which is why novel vaccines are produced

annually to match circulating viruses (74). The choice of

influenza antigens to incorporate within the antibodies is based

upon the worldwide reconnaissance of flu infections in

circulation and the spread of available strains of the influenza

disease around the world (75). For the subsequent influenza

season within the southern side of the equator, proposals are

made in September and for the influenza season within the

northern side of the equator in February since around 6 to 8

months are required to fabricate and approve novel

immunizations. Recently, the World Wellbeing Organization

The instruments of anti-M2e Ab–mediated assurance is not

determined. Anti-M2 Abs do not have hemagglutination

restraint capacity or in vitro infection neutralization properties

(66). It is assumed that the most target for the hostile to- M2e

counter acting agent is virus-infected human cells, which

intensely express M2e on their surface (67). Most considers

have detailed that corticosteroid treatment unfavorably impacts

influenza-related results. Amid the 2009 flu widespread, 37%

to 55% of the patients conceded to ICUs in Europe gotten

corticosteroids as a portion of their treatment (68-70). In any

case, in a later meta-analysis report, prove from observational

studies—albeit with essential limitations— recommended that

corticosteroid treatment for assumed influenza-associated

complications was related to expanded mortality (71).

(

WHO) suggested that trivalent influenza immunizations for

utilize within the 2016 southern half of the globe flu season

contain the taking after infection antigens(76):

•

An A/California/7/2009 (H1N1) pdm09-like virus

An A/Hong Kong/4801/2014

(H3N2)-like virus

1 Clinical trials with influenza antiviral drugs

Most individuals with flu have gentle ailment and don't

A B/Brisbane/60/2008-like virus

The WHO stresses that vaccination is particularly vital for

people at higher hazard of genuine flu complications, with

the most noteworthy need managed to pregnant ladies—

taken after by children matured between 6 and 59 months,

elderly and people with particular unremitting restorative

conditions (e.g., renal disappointment and diabetes

mellitus), and at last people at tall chance (e.g., wellbeing

staff) (77).

require restorative care or antiviral drugs. On the off chance

that you basically get weakened with flu side effects, in most

cases, you have to be stay residential and keep up a key separate

from contact with other individuals but to actuate restorative

care. If, in any case, you have got side effects of flu and are in

a high-risk bunch, or are exceptionally debilitated or stressed

approximately your sickness, contact your wellbeing care

supplier (specialist, doctor collaborator, etc.). CDC suggests

provoke treatment for individuals who have flu contamination

or suspected flu contamination and who are at tall hazard of

genuine flu complications, such as individuals with asthma,

diabetes or heart disease (72).

In differentiate in 2010, the Joined together States’

Counseling Committee on Immunization Hones (ACIP)

expanded the proposal for yearly influenza immunization to

include all people six months of age and more seasoned people

who did not have contraindications without any need (78).

2 You might need antiviral medication to treat

3.2 Schedule

flu:

The episodes of flu, by and large, happen amid the final



Antiviral drugs can treat flu illness

harvest time and entirety winter months. A single dosage (0.5

ccs) of an influenza antibody ought to be infused to grown-ups

every year, ideally by October within the northern hemisphere

and May within the southern half of the globe. Children

matured between 6 months and eight a long time require two

dosages of flu antibody (with at slightest four weeks separated)

amid their first season of immunization for the typical reaction

Antiviral drugs are different from antibiotics. Flu antivirals

are prescription medicines (pills, liquid, intravenous

solution, or an inhaled powder) and are not available over-

the-counter

Antiviral drugs can make ailment milder and abbreviate the

time you're wiped out. They too can anticipate genuine flu

complications, like pneumonia



(

78).

It’s very significant that antiviral drugs be used early to

treat people who are very sick with flu (for instance, people

who are in the hospital) and people who are wiped out with

flu and have a more noteworthy chance of getting genuine

flu complications, either since of their age or since they

have a tall hazard therapeutic condition. Other individuals

3.3 Efficacy

The immunization adequacy of flu immunizations may be

a determinant of how much the regular influenza vaccine can

anticipate flu infection contaminations within the given

populace amid an influenza season (79). As of late, the

1ꢄ

Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

documentation of the antigenic drift from the antibody weight

in the lion's share of respected separates raised the subject that

immunization viability may be problematic, primarily in more

seasoned a long time or specific high-risk bunches. The Centers

for Infection Control and Anticipation (CDC) within the Joined

together the States of America had an estimation of 23% of

immunization viability for the northern side of the equator

chemoprophylaxis, and it's fitting utilize might too influence a

markdown in dreariness, and mortality partnered to influenza

in high-risk bunches (85).

5 Conclusion

We have considered how flu disease contamination leads to

the noteworthy progression of a febrile respiratory affliction.

The pathogenesis is characterized by way of the convenient

replication and scattering of the disease insides the lungs,

causing neighborhood and systemic defilement and cytokine

release. These events, collectively with the flexible safe

response, offer help to decrease the viral burden, to encourage

liberated of the disease, and to set off clutter recovery. The

humoral and cellular resistant reactions, incited by way of

disease or inoculation, outfit people and populaces with long-

lasting cautious insusceptibility in resistance to related viral

strains. Influenza, be that as it may, can weaken this

contamination- or vaccine-derived insusceptibility through

implies of antigenic move and float, coming about in plague

and widespread flare-ups. Specialized advancements, alongside

hereditary and down to earth ponders, will help to realize a

further profound discernment into the pathogenesis of

antiquated and directly circulating virulent influenza strains.

This understanding and a far reaching acknowledgment

roughly the viral safe security disobedient inside the human

lung will ideally energize the headway of prevalent treatment

choices and more unmistakable high-quality immunizations to

be allocated around the world against current and future flu

disease varieties.

014–15 regular flu antibody due to a jumble within the

circulating infections and antibody contained infections (80).

What ought to be taken into thought is that indeed if an

antibody is not wholly related to the overwhelming circulating

infection, it can watch various particular flu infections and can,

as such, bestow exact assurance and stop influenza-related

sicknesses. It is additionally a reality that flu immunizations are

secured and are particularly imperative for diminishing severe

illness in a few high-risk populaces. In like manner, the WHO

suggests regular flu antibodies indeed on the off chance that

they are not carefully related to the overwhelming circulating

flu infections each year for the organizations mentioned above

(24).

4 Chemoprophylaxis Strategy

Accessible antiviral drugs play a vital part in patients who

have not been immunized or who are nonresponsive to

antibodies. Oseltamivir and zanamivir are the prescribed drugs

for the avoidance of influenza based on their built up adequacy

and moo rates of resistance in comparison to adamantanes (81,

2). These operators are successful for the anticipation of

influenza in reliable people, people at high hazard of flu

complications, and those dwelling in long-term care offices.

The adequacy of oseltamivir and zanamivir has, however, to be

compared with each other (83). It ought to be emphasized that

when choosing a technique of antiviral chemoprophylaxis, a

few parameters such as anticipating complications in patients

at high hazard and lessening the chance of advancing sedate

antiviral resistance ought to be considered. There are, hence, a

few signs for this approach, as follows (84): 1) Influenza

prophylaxis amid influenza episodes in long-term care centers

within the elderly notwithstanding earlier influenza

vaccinations. 2) In unvaccinated people at the high chance of

influenza complications which have been uncovered to a

person with influenza diseases inside the past 48 hours. 3)

Antiviral prophylaxis for immunized people at the high chance

of influenza complications who have had near contact with a

person with influenza inside the previous 48 hours when there

is a destitute coordinate between the immunization and

circulating infections in a given year. 4) The Joined together

States’ ACIP suggests that antiviral chemoprophylaxis be

considered in pregnant women and in women up to 2 weeks

postpartum who have close contact with suspected or

confirmed influenza A-infected individuals. Zanamivir may be

the drug of choice for prophylaxis due to its limited systemic

absorption (84, 85).

Medicate resistance got to be respected on the off chance

that we select to bargain with all sufferers who are labeled as

battling from influenza. People with suspected pipe with an

extraordinary affliction such as those with side effects and signs

of diminishing respiratory tract contaminations (e.g., dyspnea,

tachypnea, and moo oxygen immersion) and these who have

side effects of quick clinical deterioration or these at great

danger of issues got to get hold of antiviral treatment. In all

cases, antivirals ought to be started <48 hours after side effect

onset. In pregnant patients due to more noteworthy mortality,

there is a counsel that all sufferers with suspected or affirmed

influenza-even those who were existing >48 hours after side

effect onset—be managed with provided that they are not

making strides. In expansion, an unused appear at antiviral

References

1. Alguacil-Ramos A, Portero-Alonso A, Pastor-Villalba E, Muelas-

Tirado J, Díez-Domingo J, Sanchis-Ferrer A, et al. Rapid

assessment of enhanced safety surveillance for influenza vaccine.

Public health. 2019;168:137-41.

Tennant RK, Holzer B, Love J, Tchilian E, White HN. Higher

levels of B‐cell mutation in the early germinal centres of an

inefficient secondary antibody response to a variant influenza

haemagglutinin. Immunology. 2019;157(1):86-91.

Marshall C, Williams K, Matchett E, Hobbs L. Sustained

improvement in staff influenza vaccination rates over six years

without a mandatory policy. Infection Control & Hospital

Epidemiology. 2019;40(3):389-90.

Mousavi S, Zarei M, Hashemi S. Polydopamine for Biomedical

Application and Drug Delivery System. Med Chem(Los Angeles).

018;8:218-29.

Mosnier A, Caini S, Daviaud I, Nauleau E, Bui TT, Debost E, et

al. Clinical characteristics are similar across type A and B

influenza virus infections. PLoS One. 2015;10(9):e0136186.

6. Poon LL, Song T, Rosenfeld R, Lin X, Rogers MB, Zhou B, et al.

Quantifying influenza virus diversity and transmission in humans.

Nature genetics. 2016;48(2):195.

Fuller TL, Gilbert M, Martin V, Cappelle J, Hosseini P, Njabo KY,

et al. Predicting hotspots for influenza virus reassortment.

Emerging infectious diseases. 2013;19(4):581.

Mousavi SM, Hashemi SA, Ghasemi Y, Amani AM, Babapoor A,

Arjmand O. Applications of graphene oxide in case of

nanomedicines and nanocarriers for biomolecules: review study.

Drug metabolism reviews. 2019;51(1):12-41.

9. Mousavi SM, Hashemi SA, Ghasemi Y, Atapour A, Amani AM,

Savar Dashtaki A, et al. Green synthesis of silver nanoparticles

toward bio and medical applications: review study. Artificial cells,

nanomedicine, and biotechnology. 2018;46(sup3):S855-S72.

0. Mousavi S, Hashemi S, Zarei M, Amani A, Babapoor A.

Nanosensors for Chemical and Biological and Medical

Applications. Med Chem (Los Angeles). 2018;8(8):2161-

444.1000515.

11. Kanegae Y, Sugita S, Endo A, Ishida M, Senya S, Osako K, et al.

Evolutionary pattern of the hemagglutinin gene of influenza B

viruses isolated in Japan: cocirculating lineages in the same

epidemic season. Journal of virology. 1990;64(6):2860-5.

1ꢅ

Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

2. Boivin G, Goyette N, Bernatchez H. Prolonged excretion of

amantadine-resistant influenza a virus quasi species after cessation

of antiviral therapy in an immunocompromised patient. Clinical

Infectious Diseases. 2002;34(5):e23-e5.

3. Степанова ЛА, Ковалева А, Потапчук М, Коротков А,

Куприянов В, Блохина Е, et al. Иммуногенные свойства

рекомбинантных белков, включающих эктодомен белка М2

вируса гриппа а. Вопросы вирусологии. 2013;58(3).

Prevention. Hospitalized patients with novel influenza A (H1N1)

virus infection--California. 2009:732-6.

34. Chu H, Lofgren ET, Halloran ME, Kuan PF, Hudgens M, Cole SR.

Performance of rapid influenza H1N1 diagnostic tests: a meta‐

analysis. Influenza and other respiratory viruses. 2012;6(2):80-6.

35. Chartrand C, Leeflang MM, Minion J, Brewer T, Pai M. Accuracy

of rapid influenza diagnostic tests: a meta-analysis. Annals of

internal medicine. 2012;156(7):500-11.

4. Brankston G, Gitterman L, Hirji Z, Lemieux C, Gardam M.

Transmission of influenza A in human beings. The Lancet

infectious diseases. 2007;7(4):257-65.

5. Mousavi SM, Hashemi SA, Zarei M, Bahrani S, Savardashtaki A,

Esmaeili H, et al. Data on cytotoxic and antibacterial activity of

synthesized Fe3O4 nanoparticles using Malva sylvestris. Data in

brief. 2020;28:104929.

36. Karthik L, Kumar G, Keswani T, Bhattacharyya A, Chandar SS,

Rao KB. Protease inhibitors from marine actinobacteria as a

potential source for antimalarial compound. PloS one. 2014;9(3).

37. Nagase H, Moriwaki K, Kamae M, Yanagisawa S, Kamae I. Cost-

effectiveness analysis of oseltamivir for influenza treatment

considering the virus emerging resistant to the drug in Japan. Value

in Health. 2009;12:S62-S5.

6. Choi W-S, Lee J, Lee H-Y, Baek J-H, Kim Y-K, Kee S-Y, et al.

Clinical Practice Guideline for Antiviral Treatment and

38. Nshimyumukiza L, Douville X, Fournier D, Duplantie J, Daher

RK, Charlebois I, et al. Cost‐effectiveness analysis of antiviral

treatment in the management of seasonal influenza A: point‐of‐

care rapid test versus clinical judgment. Influenza and other

respiratory viruses. 2016;10(2):113-21.

Chemoprophylaxis of Seasonal Influenza. Infection

Chemotherapy. 2012;44(4).

7. Cowling BJ, Ip DK, Fang VJ, Suntarattiwong P, Olsen SJ, Levy J,

et al. Aerosol transmission is an important mode of influenza A

virus spread. Nature communications. 2013;4:1935.

8. Wong BC, Lee N, Li Y, Chan PK, Qiu H, Luo Z, et al. Possible

role of aerosol transmission in a hospital outbreak of influenza.

Clinical infectious diseases. 2010;51(10):1176-83.

9. Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S,

Leach S, et al. Time lines of infection and disease in human

influenza: a review of volunteer challenge studies. American

journal of epidemiology. 2008;167(7):775-85.

0. Weinstock DM, Gubareva LV, Zuccotti G. Prolonged shedding of

multidrug-resistant influenza A virus in an immunocompromised

patient. New England Journal of Medicine. 2003;348(9):867-8.

1. Liu W, Peng L, Liu H, Hua S. Pulmonary function and clinical

manifestations of patients infected with mild influenza A virus

subtype H1N1: a one-year follow-up. PloS one. 2015;10(7).

2. Rello J, Pop-Vicas A. Clinical review: primary influenza viral

pneumonia. Critical Care. 2009;13(6):235.

39. Klugman K. Clinical Microbiology Reviews. Clin Microbiol Rev.

1990;3(2):171-96.

40. Teo J, Di Pietro P, San Biagio F, Capozzoli M, Deng Y-M, Barr I,

et al. VereFlu™: an integrated multiplex RT-PCR and microarray

assay for rapid detection and identification of human influenza A

and B viruses using lab-on-chip technology. Archives of virology.

2011;156(8):1371.

41. Tang Y-W, Lowery KS, Valsamakis A, Schaefer VC, Chappell JD,

White-Abell J, et al. Clinical accuracy of a PLEX-ID flu device for

simultaneous detection and identification of influenza viruses A

and B. Journal of clinical microbiology. 2013;51(1):40-5.

42. Loeffelholz M, Pong D, Pyles R, Xiong Y, Miller A, Bufton K, et

al. Comparison of the FilmArray Respiratory Panel and Prodesse

real-time PCR assays for detection of respiratory pathogens.

Journal of clinical microbiology. 2011;49(12):4083-8.

43. Gholami A, Shahin S, Mohkam M, Nezafat N, Ghasemi Y.

Cloning, characterization and bioinformatics analysis of novel

cytosine deaminase from Escherichia coli AGH09. International

Journal of Peptide Research and Therapeutics. 2015;21(3):365-74.

44. Moghadami M. A narrative review of influenza: a seasonal and

pandemic disease. Iranian journal of medical sciences.

2017;42(1):2.

3. Minodier L, Charrel RN, Ceccaldi P-E, Van Der Werf S, Blanchon

T, Hanslik T, et al. Prevalence of gastrointestinal symptoms in

patients with influenza, clinical significance, and pathophysiology

of human influenza viruses in faecal samples: what do we know?

Virology journal. 2015;12(1):215.

4. Vickers NJ. Animal Communication: When I’m Calling You, Will

You Answer Too? Current Biology. 2017;27(14):R713-R5.

5. Mancinelli L, Onori M, Concato C, Sorge R, Chiavelli S, Coltella

L, et al. Clinical features of children hospitalized with influenza A

and B infections during the 2012–2013 influenza season in Italy.

BMC infectious diseases. 2015;16(1):6.

6. Bahrani S, Hashemi SA, Mousavi SM, Azhdari R. Zinc-based

metal–organic frameworks as nontoxic and biodegradable

platforms for biomedical applications: review study. Drug

metabolism reviews. 2019;51(3):356-77.

7. Rello J, Rodríguez A, Ibañez P, Socias L, Cebrian J, Marques A,

et al. the H1N1 SEMICYUC working group: Intensive care

patients with severe novel H1N1 influenza viral pneumonia in

Spain. Crit Care. 2009;13:R148.

8. To K, Hung I, Li I, Lee K, Koo C, Yan W, et al. Pandemic H1N1

Study Group: Delayed clearance of viral load and marked cytokine

activation in severe cases of pandemic H1N1 2009 influenza virus

infection. Clin Infect Dis. 2010;50:850-9.

45. Behrens G, Stoll M, Kamps B, Hoffman C, Preisser W.

Pathogenesis and immunology. Monografía en Internet] Flying

Publisher Cologne, Holland. 2006;19.

46. Mandelboim O, Lieberman N, Lev M, Paul L, Arnon TI, Bushkin

Y, et al. Recognition of haemagglutinins on virus-infected cells by

NKp46 activates lysis by human NK cells. Nature.

2001;409(6823):1055-60.

47. Mousavi SM, Zarei M, Hashemi SA, Babapoor A, Amani AM. A

conceptual review of rhodanine: current applications of antiviral

drugs, anticancer and antimicrobial activities. Artificial cells,

nanomedicine, and biotechnology. 2019;47(1):1132-48.

48. García-Sastre A, Egorov A, Matassov D, Brandt S, Levy DE,

Durbin JE, et al. Influenza A virus lacking the NS1 gene replicates

in interferon-deficient systems. Virology. 1998;252(2):324-30.

49. Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solórzano A,

Swayne DE, et al. Characterization of the reconstructed 1918

Spanish influenza pandemic virus. science. 2005;310(5745):77-80.

50. Abbaszadegan A, Dadolahi S, Gholami A, Moein MR, Hamedani

S, Ghasemi Y, et al. Antimicrobial and cytotoxic activity of

Cinnamomum zeylanicum, Calcium Hydroxide, and triple

antibiotic paste as root canal dressing materials. The journal of

contemporary dental practice. 2016;17(2):105-13.

51. Gholami A, Rasoul-Amini S, Ebrahiminezhad A, Abootalebi N,

Niroumand U, Ebrahimi N, et al. Magnetic properties and

antimicrobial effect of amino and lipoamino acid coated iron oxide

nanoparticles. Minerva Biotecnologica. 2016;28(4):177-86.

52. Mousavi SM, Soroshnia S, Hashemi SA, Babapoor A, Ghasemi Y,

Savardashtaki A, et al. Graphene nano-ribbon based high potential

and efficiency for DNA, cancer therapy and drug delivery

applications. Drug metabolism reviews. 2019;51(1):91-104.

53. Abbaszadegan A, Gholami A, Abbaszadegan S, Aleyasin ZS,

Ghahramani Y, Dorostkar S, et al. The effects of different ionic

liquid coatings and the length of alkyl chain on antimicrobial and

9. Schwarzmann SW, Adler JL, Sullivan RJ, Marine WM. Bacterial

pneumonia during the Hong Kong influenza epidemic of 1968-

969: experience in a city-county hospital. Archives of internal

medicine. 1971;127(6):1037-41.

0. Kallen AJ, Brunkard J, Moore Z, Budge P, Arnold KE, Fosheim

G, et al. Staphylococcus aureus community-acquired pneumonia

during the 2006 to 2007 influenza season. Annals of emergency

medicine. 2009;53(3):358-65.

1. Ison MG, Campbell V, Rembold C, Dent J, Hayden FG. Cardiac

findings during uncomplicated acute influenza in ambulatory

adults. Clinical infectious diseases. 2005;40(3):415-22.

2. Foulkes W, Rees J, Sewry C. Influenza A and rhabdomyolysis.

Journal of Infection. 1990;21(3):303-4.

3. Chen K-F, Gaydos C, Rothman RE. Update on emerging

infections: news from the Centers for Disease Control and

1ꢆ

Journal of Environmental Treatment Techniques

0202, Volume 8, Issue 2, Pages: 610-620

cytotoxic properties of silver nanoparticles. Iranian endodontic

journal. 2017;12(4):481.

systematic review and meta-analysis. The Journal of infectious

diseases. 2015;212(2):183-94.

4. Muthuri Stella G, Sudhir V, Myles Puja R, Jo L-B, Al Khuwaitir

Tarig S. Effectiveness of neuraminidase inhibitors in reducing

mortality in patients admitted to hospital with influenza A

72. Zakeri A, Kouhbanani MAJ, Beheshtkhoo N, Beigi V, Mousavi

SM, Hashemi SAR, et al. Polyethylenimine-based nanocarriers in

co-delivery of drug and gene: a developing horizon. Nano reviews

& experiments. 2018;9(1):1488497.

73. Kilbourne ED. Influenza immunity: new insights from old studies.

The Journal of infectious diseases. 2006;193(1):7-8.

H1N1pdm09 virus infection:

a meta-analysis of individual

participant data. Lancet Respir Med. 2014;2(5):395-404.

5. Gasparini R, Amicizia D, Lai PL, Bragazzi NL, Panatto D.

Compounds with anti-influenza activity: present and future of

strategies for the optimal treatment and management of influenza

Part II: Future compounds against influenza virus. Journal of

preventive medicine and hygiene. 2014;55(4):109.

6. Mousavi SM, Hashemi SA, Salahi S, Hosseini M, Amani AM,

Babapoor A. Development of Clay Nanoparticles Toward Bio and

Medical Applications. Current Topics in the Utilization of Clay in

Industrial and Medical Applications. 2018;9:167.

7. Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F. Impact

of oseltamivir treatment on influenza-related lower respiratory

tract complications and hospitalizations. Archives of internal

medicine. 2003;163(14):1667-72.

8. Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP, et

al. Antivirals for treatment of influenza: a systematic review and

meta-analysis of observational studies. Annals of internal

medicine. 2012;156(7):512-24.

74. Glezen WP. Prevention and treatment of seasonal influenza. New

England Journal of Medicine. 2008;359(24):2579-85.

75. Ang LW, Tien WS, Lin RTP, Cui L, Cutter J, James L, et al.

Characterization of influenza activity based on virological

surveillance of influenza‐like illness in tropical Singapore, 2010–

2014. Journal of medical virology. 2016;88(12):2069-77.

76. Zhao B, Qin S, Teng Z, Chen J, Yu X, Gao Y, et al.

Epidemiological study of influenza B in Shanghai during the

2009–2014 seasons: implications for influenza vaccination

strategy. Clinical Microbiology and Infection. 2015;21(7):694-

700.

77. Kalkowska DA, Tebbens RJD, Pallansch MA, Cochi SL, Wassilak

SG, Thompson KM. Modeling undetected live poliovirus

circulation after apparent interruption of transmission:

implications for surveillance and vaccination. BMC infectious

diseases. 2015;15(1):66.

9. Doshi P, Jefferson T, Del Mar C. The imperative to share clinical

study reports: recommendations from the Tamiflu experience.

PLoS medicine. 2012;9(4).

0. Atapour A, Negahdaripour M, Ghasemi Y, Razmjuee D,

Savardashtaki A, Mousavi SM, et al. In Silico Designing a

Candidate Vaccine Against Breast Cancer. International Journal of

Peptide Research and Therapeutics. 2019:1-12.

78. Zimmerman RK, Nowalk MP, Chung J, Jackson ML, Jackson LA,

Petrie JG, et al. 2014–2015 influenza vaccine effectiveness in the

United States by vaccine type. Clinical Infectious Diseases.

2016:ciw635.

79. Ohmit SE, Petrie JG, Malosh RE, Fry AM, Thompson MG, Monto

AS. Influenza vaccine effectiveness in households with children

during the 2012–2013 season: assessments of prior vaccination and

serologic susceptibility. The Journal of infectious diseases.

2015;211(10):1519-28.

80. Flannery B, Clippard J, Zimmerman RK, Nowalk MP, Jackson

ML, Jackson LA, et al. Early estimates of seasonal influenza

vaccine effectiveness—United States, January 2015. MMWR

Morbidity and mortality weekly report. 2015;64(1):10.

81. Li T, Chan MC, Lee N. Clinical implications of antiviral resistance

in influenza. Viruses. 2015;7(9):4929-44.

82. Avval ZM, Malekpour L, Raeisi F, Babapoor A, Mousavi SM,

Hashemi SA, et al. Introduction of magnetic and supermagnetic

nanoparticles in new approach of targeting drug delivery and

cancer therapy application. Drug Metabolism Reviews. 2019:1-28.

83. Merritt T, Hope K, Butler M, Durrheim D, Gupta L, Najjar Z, et

al. Effect of antiviral prophylaxis on influenza outbreaks in aged

care facilities in three local health districts in New South Wales,

Australia, 2014. Western Pacific surveillance and response

journal: WPSAR. 2016;7(1):14.

1. Khandaker G, Al Mamun A, Anovadiya AP, Araujo W, Azziz-

Baumgartner E. Impact of neuraminidase inhibitors on influenza A

(H1N1) pdm09-related pneumonia: an individual participant data

meta-analysis. 2016.

2. Chen LF, Dailey NJ, Rao AK, Fleischauer AT, Greenwald I,

Deyde VM, et al. Cluster of oseltamivir-resistant 2009 pandemic

influenza A (H1N1) virus infections on a hospital ward among

immunocompromised patients—North Carolina, 2009. Journal of

Infectious Diseases. 2011;203(6):838-46.

3. Stephenson I, Democratis J, Lackenby A, McNally T, Smith J,

Pareek M, et al. Neuraminidase inhibitor resistance after

oseltamivir treatment of acute influenza A and B in children.

Clinical Infectious Diseases. 2009;48(4):389-96.

4. Ramos EL, Mitcham JL, Koller TD, Bonavia A, Usner DW,

Balaratnam G, et al. Efficacy and safety of treatment with an anti-

m2e monoclonal antibody in experimental human influenza. The

Journal of infectious diseases. 2015;211(7):1038-44.

5. Schotsaert M, De Filette M, Fiers W, Saelens X. Universal M2

ectodomain-based influenza A vaccines: preclinical and clinical

developments. Expert review of vaccines. 2009;8(4):499-508.

6. Jegerlehner A, Schmitz N, Storni T, Bachmann MF. Influenza A

vaccine based on the extracellular domain of M2: weak protection

mediated via antibody-dependent NK cell activity. The Journal of

Immunology. 2004;172(9):5598-605.

7. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw

F-M, Lim WS, et al. The effectiveness of convalescent plasma and

hyperimmune immunoglobulin for the treatment of severe acute

respiratory infections of viral etiology: a systematic review and

exploratory meta-analysis. The Journal of infectious diseases.

84. Louie JK, Salibay CJ, Kang M, Glenn-Finer RE, Murray EL,

Jamieson DJ. Pregnancy and severe influenza infection in the

2013–2014 influenza season. Obstetrics

Gynecology.

2015;125(1):184-92.

85. Tech JET. Investigating the Activity of Antioxidants Activities

Content in Apiaceae and to Study Antimicrobial and Insecticidal

Activity of Antioxidant by using SPME Fiber Assembly

Carboxen/Polydimethylsiloxane (CAR/PDMS). Journal of

Environmental Treatment Techniques. 2020;8(1):214-24.

015;211(1):80-90.

8. Diaz E, Martin-Loeches I, Canadell L, Vidaur L, Suarez D, Socias

L, et al. Corticosteroid therapy in patients with primary viral

pneumonia due to pandemic (H1N1) 2009 influenza. Journal of

Infection. 2012;64(3):311-8.

9. Brun-Buisson C, Richard J-CM, Mercat A, Thiébaut AC, Brochard

L. Early corticosteroids in severe influenza A/H1N1 pneumonia

and acute respiratory distress syndrome. American journal of

respiratory and critical care medicine. 2011;183(9):1200-6.

0. Linko R, Pettilä V, Ruokonen E, Varpula T, Karlsson S, Tenhunen

J, et al. Corticosteroid therapy in intensive care unit patients with

PCR‐confirmed influenza A (H 1 N 1) infection in F inland. Acta

anaesthesiologica scandinavica. 2011;55(8):971-9.

1. Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam JS, Lim WS. Effect

of corticosteroid therapy on influenza-related mortality:

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