Influenza/Flu

               Influenza/Flu/ Seasonal Fever

The Flu/ epidemic catarrh, la grippe/ Grippe/Severe cold/sweating sickness/Spanish fever

          "COUGH, SNEEZE, FEVER, REPEAT? YOU MAY HAVE THE FLU."

The word influenza comes from the Italian word influenza, from medieval Latin influentia, originally meaning "visitation" or "influence", meaning "influence of the cold".  Since the mid-1800s, influenza has also been used to refer to severe colds.

Influenza/ (flu) is a highly contagious viral infection of the respiratory tract that can cause severe illness and life-threatening complications. Seasonal influenza outbreaks each year causes 3 -5 

million deaths globally, estimates the WHO. If there is a mismatch between the  vaccine and the circulating influenza strains, effectiveness falls further.

Very common more than 10million cases per year (India). Spreads easily. 5–10% of adults and 20–30% of children contract influenza each year. During seasonal epidemics, it is estimated that about 80% of otherwise healthy people who have a cough or sore throat have the flu. Approximately 30–40% of people hospitalized for influenza develop pneumonia, and about 5% of all severe pneumonia cases in hospitals are due to influenza, which is also the most common cause of ARDS in adults. About 3–5% of children each year develop otitis media due to influenza. During seasonal influenza, mortality is concentrated in the very young and the elderly,

 preventable by vaccine. Usually self treatable. Usually self diagnosable. Lab test or imaging rarely required. Short term, resolves within days or week.

An infected child can spread it to others even before they show symptoms, and for up to seven days after becoming ill. It is the responsiblity of parents, school authorities and health care professionals to ensure a child's vaccination is up to date as they are now venturing out. Given the overlapping symptoms between Covid 19 and Flu it is advisable to complete the vaccination schedule on time along with annual flu vaccination.

Since several different viruses cause seasonal influenza and these viruses are subject to continual antigenic changes ("antigenic drift"), world health organization WHO  every year recommends a new strain specific vaccine in February for the Northern hemisphere and  in September for the South to prevent infections. Each year  vaccines target 3-4 of the most deadly flu strains causing infection based on flu tracking data from previous 5-8 months. from 143 National influenza Centers in 113 countries, including India.

If the virus causing infection change,, so does the recommended strain specific vaccine.

Influenza is a viral disease caused by H1NI AND H1N5 virus. Flu shot your best bet to avoid influenza this festival season. As festivity, bringing together families and friends, with large family gathering and extended week end trips comes an increase risk of exposure to  seasonal infections like influenza especially  with monsoon.

Seasonal influenza is characterized by a sudden onset of fever, cough (usually dry), headache, muscle and joint pain, severe malaise (feeling unwell), sore throat and a runny nose. The cough can be severe and can last 2 or more weeks.

Introduction

With temperature dipping consistently, flu has become common. How to beat the influenza blues in winter, and how its different from cold.

Come December, Influenza season is  is officially upon us. While we gather upon bone fire and sip hot chocolate, the stubborn runny nose and malaise persist ! How Influenza get free hand in winter, its complications and how to keep it at bay.

Unlike common cold Seasonal Flu is a respiratory infection caused by the Influenza virus, which may lead to mild and severe illness. It affects the nose, throat and lungs. 

This contagious viral infection generally affects the upper and lower respiratory tracts. The most common Influenza viruses that infect the human body are  Influenza A &B. 

Why there is spike during Fall  and Winter?

The cold and dry air are to blame. The spike is typically between December and early March. The cold season weakens our  ability to clear the mucus in our noses, making easier for  viruses to infect our bodies. "Dry cold air may constrict the airways and aggravate the lungs, leading to difficulty in breathing. Cold air may also interrupt the layer of moisture lining our airways. Beside mucus, the protective layer of throat may become thicker than normal in winter, leading to obstruction of the airways, and making people prone to catching infections or cold.

In healthy individuals, influenza infection is usually self-limiting and rarely fatal. Symptoms usually last for 2–8 days. Influenza can cause people to miss work or school, and it is associated with decreased job performance and, in older adults, reduced independence. Fatigue and malaise may last for several weeks after recovery, and healthy adults may experience pulmonary abnormalities that can take several weeks to resolve. Complications and mortality primarily occur in high-risk populations and those who are hospitalized. Severe disease and mortality are usually attributable to pneumonia from the primary viral infection or a secondary bacterial infection, which can progress to ARDS.

 Kids are more prone to contract seasonal flu.. Those younger than 5 years old, especially 2 years old and below are  at a higher risk of developing serious flu related complications.. More over they also pass on the virus to other family members, putting them at risk.. Especially the elderly.

Flu Season Alert

It is caused by the influenza virus. In temperate regions of the world, the number of influenza cases peaks during winter, whereas in the tropics influenza can occur year-round. Since the late 1800s, large outbreaks of novel influenza strains that spread globally, called pandemics, have occurred every 10–50 years. Five flu pandemics have occurred since 1900: the Spanish flu in 1918–1920, which was the most severe flu pandemic, the Asian flu in 1957, the  Hong Kong flu in 1968, the Russian flu in 1977, and the Swine flu pandemic in 2009.

Influenza virus

Influenza commonly known as "the flu" is an infectious disease caused by the influenza viruses. There are four types of influenza virus. known as influenza virus A,B,C,D.  Aquatic birds are the primary source of Influenza A virus (IAV), which is also widespread in various mammals, including humans and pigs. Influenza B virus (IBV) and Influenza C virus (ICV) primarily infect humans, and Influenza D virus (IDV) is found in cattle and pigs. IAV and IBV circulate in humans and cause seasonal epidemics, and ICV causes a mild infection, primarily in children. IDV can infect humans but is not known to cause illness.

Factors affecting influenza

• Minimum temperature in winter season
• High humidity
• Maximum rainfall
• Lower humidity, lower temperature, and 
• Minor changes in virus proteins caused by antigenic drift contribute to annual epidemics that peak during the winter season
• Lower Vitamin D levels, presumably due to less sunlight.
• Asia being a key reservoir of influenza viruses.
• Depending on the level of pre-existing immunity in the population, novel influenza viruses can spread rapidly and cause pandemics with millions of deaths. 

Types of virus

4 species :

Orthomyxoviridae. 

• Influenza A virus (IAV), genus Alpha influenza virus
• Influenza B virus  (IBV), genus Beta influenza virus
• Influenza C virus  (ICV), genus Gamma influenza virus
• Influenza D virus  (IDV), genus Delta influenza virus

Incubation Period

• 1-4 days

                                         "Asia being a key reservoir of influenza viruses."

Duration

• 2-8  days

Virus Transmission

Droplets can either get into your hands or move through the air to get into your nose or mouth, 

finally moving into your lungs. While sinus and ear infections are  moderate complications from the flu,

 Pneumonia is a serious one., which can occur from either the flu virus alone or from co infection of  virus bacteria

Mode of transmission

 In humans, influenza viruses are primarily transmitted through :

•  Respiratory droplets produced from coughing and sneezing. 
• Transmission through Aerosols,  fomites, and contaminated water.
• Intermediate objects and 
• Surfaces contamination by the virus also occur.

Since the late 1800s, large outbreaks of novel influenza strains that spread globally, called pandemics, have occurred every 10–50 years. Five flu pandemics have occurred since 1900: the Spanish Flu  in 1918–1920, which was the most severe flu pandemic, the Asian Flu in 1957, the Hong Kong flu  in 1968, the Russian flu  in 1977, and the Swine flu pandemic  in 2009.

How does it spread

• The easiest way to catch the flu is if you're around someone who is constantly coughing or sneezing. 
• During winter most people prefer staying indoor and breath the same air as an  infected person would and therefore are at a higher risk of contracting the infection. 
• Also due to sparse sunlight people have lower level of vitamin D and melatonin which are directly linked to the patient's immunity rendering them more prone to illness..
• By airborne respiratory droplets (coughs or sneezes).
• By touching a contaminated surface that's contaminated by flu virus, than touching your face, nose, mouth or eyes. This includes object like door knobs, desks, computer and mobile phones. The virus thrives in cold and dry surroundings.
• By saliva (kissing or shared drinks).
• By skin-to-skin contact (handshakes or hugs).

High Risk

A common viral infection that can be deadly, especially in high-risk groups.

The flu attacks the lungs, nose and throat. 

• People who are at least 65 years of age
• Older adults
• Young children, 
• Obesity
• Pregnancy
• People who have underlying health conditions
• People with chronic disease or weak immune systems are at high risk.

The primary risk factor for infection with AIVs is exposure to birds in farms and live poultry markets. Typically, infection with an AIV has an incubation period of 3–5 days but can be up to 9 days. H5N1 and H7N9 cause severe lower respiratory tract illness, whereas other AIVs such as H9N2 cause a more mild upper respiratory tract illness,  H7N9 has been responsible for most human cases.

Influenza can affect pregnancy, including causing smaller neonatal size, increased risk of premature birth, and an increased risk of child death shortly before or after birth. Neurological complications have been associated with influenza on rare occasions, including aseptic meningitis, encephalitis, disseminated encephalomyelitis, transverse myelitis, and Guillain -Barre syndrome Additionally, febrile seizures and Reye syndrome can occur, most commonly in children. Influenza-associated encephalopathy can occur directly from central nervous system infection from the presence of virus in blood and presents as sudden onset of fever with convulsions, followed by rapid progression to coma.  In survivors of influenza-associated encephalopathy, neurological defects may occur. Primarily in children, in severe cases the immune system may rarely dramatically overproduce white blood cells  that release cytokines, causing severe inflammation.

People who are at least 65 years of age, due to a weakened immune system from aging or a chronic illness, are a high-risk group for developing complications, as are children less than one year of age and children who have not been previously exposed to influenza viruses multiple times. Pregnant women are at an elevated risk, which increases by trimester and lasts up to two weeks after childbirth. Obesity, in particular a body mass index greater than 35–40, is associated with greater amounts of viral replication, increased severity of secondary bacterial infection, and reduced vaccination efficacy. People who have underlying health conditions are also considered at-risk, including those who have congenital or chronic heart problems or lung (e.g. asthma), kidney, liver, blood, neurological, or metabolic (e.g. diabetes) disorders, as are people who are immunocompromised from chemotherapy, asplenia , prolonged steroid treatment, splenic dysfunction, or HIV infection, Current or past tobacco use also places a person at risk. The role of genetics in influenza is not well researched, but it may be a factor in influenza mortality.

"Seasonal flu infection peaks between June and October in India, and additional minor peak from December to February."

Symptoms

Many infections are asymptomatic. The onset of symptom is sudden. Flu symptom typically start to appear between 1-4 days after exposure, unlike common cold which last for a shorter duration and is milder.

• Sore throat
• Coughing is the most common symptom. Dry hacking cough, sore or dry throat, hoarse voice,
• Fever, chills, 
• Muscle aches, 
• Congestion, 
• Runny or stuffy nose
• Shortness of breath
• Headaches and Bodyache
• Fatigue.
• Feeling of discomfort
• Intestinal symptoms like  vomiting or diarrhea  can occur, particularly in children.
• Loss of appetite
• Confusion

Symptoms typically resolves after 3-7 days for majority of the population. Although cough and malaise can persist. for more than two weeks.

                                      "Influenza can cause long lasting symptoms."

To prevent flu infections the vulnerable population comprising children, elderly(65+ years) and those with co-morbidities such as diabetes and asthma, needs to take necessary precautions. 

Diagnosis

• Symptoms : Diagnosis is fairly accurate in otherwise healthy people during Seasonal epidemics and should be suspected in cases of pneumonia, acute respiratory distress syndrome (ARDS), sepsis, or if encephalitis, myocarditis, or  breaking down of muscle tissue occur. Because influenza is similar to other viral respiratory tract illnesses
• Laboratory diagnosis : laboratory diagnosis is necessary for confirmation. Common ways of collecting samples for testing include
• Nasal and throat swabs. Samples may be taken from the lower respiratory tract if infection has cleared the upper but not lower respiratory tract. Influenza testing is recommended for anyone hospitalized with symptoms resembling influenza during flu season or who is connected to an influenza case. For severe cases, earlier diagnosis improves patient outcome. 

Naso - pharyngeal Swab

Throat Swab

•  Viral Cultures : Diagnostic methods that can identify influenza include viral culture, antibody- and antigen-detecting tests.
•  Nucleic acid-based tests (NAT):  Cultures can be used to characterize novel viruses, observe sensitivity to antiviral drugs.  Amplify and detect viral nucleic acid. Most of these tests take a few hour. Among NATs, reverse transcription polymerase chain reaction (RT-PCR) is the most traditional and considered the gold standard for diagnosing influenza because it is fast and can subtype IAV, but it is relatively expensive and more prone to false-positives than cultures.
• Other NATs that have been used include loop-mediated isothermal amplification -based assays, simple amplification-based assays, and nucleic acid sequence-based amplification. Nucleic acid sequencing methods can identify infection by obtaining the nucleic acid sequence of viral samples to identify the virus and antiviral drug resistance. The traditional method is Sanger sequencing, but it has been largely replaced by next generation methods that have greater sequencing speed and throughput.
• Rapid molecular essay : (RIDT) As fast as RIDTS.
• Monitor antigenic drift.
• Serological assays : Serological assays can be used to detect an antibody response to influenza after natural infection or vaccination. Common serological assays include hemagglutination inhibition assays that detect HA-specific antibodies, virus neutralization assays that check whether antibodies have neutralized the virus, and enzyme-linked immuno-absorbent assays
• Direct fluorescent or immunofluorescent antibody (DFA/IFA) tests involve staining respiratory epithelial cells in samples with fluorescently-labeled influenza-specific antibodies, followed by examination under a fluorescent microscope. They can differentiate between IAV and IBV but can't subtype IAV.
• Rapid influenza diagnostic tests : (RIDTs) are a simple way of obtaining assay results, are low cost, and produce results quickly, at less than 30 minutes, so they are commonly used, but they can't distinguish between IAV and IBV or between IAV subtypes and are not as sensitive as nucleic-acid based tests.

• X Ray 

                                                     

X-ray of 29-year-old person with H1N1

Complications

• Pneumonia, which can be caused by the primary virus infection or by secondary bacterial infection. Other complications of infection include. Progression to pneumonia is common.

Primary pneumonia is characterized by rapid progression of fever, cough, labored breathing, and low oxygen levels that cause bluish skin. It is especially common among those who have an underlying cardiovascular disease such as rheumatic heart disease. 

Secondary pneumonia typically has a period of improvement in symptoms for 1–3 weeks. followed by recurrent fever, sputum production, and fluid buildup in the lungs, but can also occur just a few days after influenza symptoms appear. About a third of primary pneumonia cases are followed by secondary pneumonia, which is most frequently caused by the bacteria Streptococcus pneumoniae  and Streptococcus aureus. 

• Acute respiratory distress syndrome
• Meningitis
• Encephalitis
• and those with Asthma, lung disease  and Cardiovascular disease
• .Multi organ failure can kill people at risk, such as young children with respiratory problems, pregnant women, older adult above age of 65 years, and those with Asthma, lung disease, diabetes  and Cardiovascular disease

Vaccination of children and the elderly protects them and their family members.

Influenza is a viral infection that attacks your respiratory system — your nose, throat and lungs. Influenza is commonly called the flu. 

Co-morbidity and co-infections

The current seasonal disparity across the country raises the risk of  co-infections especially among high risk individuals like those with diabetes and asthma. Kids and the elderly. It is noted that co-infection of Covid 19 with other respiratory pathogens is being realized as a concern. C0-infection especially in high risk individuals and the elderly cannot be ignored. 

Influenza (Flu)

Influenza is a vital infection that spreads rapidly from one person to another. This disease seen more often during winters. The patient having flu is infectious to others from  the day before the onset of symptoms until the time  he recovers  from fever  and other symptoms. 

Symptoms

If  more than  one member of the family  has body ache, headache , fever, nasal discharge, , loss of appetite , severe weakness, and an upset stomach, we are most likely dealing with flu.

Genome & Structure

                                      

Structure of the influenza virion. hemagglutinin (HA) and  neuraminidase (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the  genome are shown as red coils inside the particle and bound to ribonucleoproteins (RNP).

Influenza viruses have a negative sense, single-stranded RNA genome. The virus particle, called a virion, is spherical 120nm in diameter. The virion consists of each segment of the genome bound to nucleoproteins in separate ribonucleoprotein (RNP) complexes for each segment, all of which are surrounded by a lipid bilayer membrane called the viral envelop . There is a copy of the RdRp, all subunits included, bound to each RNP. The envelope is reinforced structurally by matrix proteins on the interior that enclose the RNPs, and the envelope contains HA and NA (or HEF) proteins extending outward from the exterior surface of the envelope. HA and HEF proteins have a distinct "head" and "stalk" structure. M2 proteins form proton ion channels through the viral envelope that are required for viral entry and exit. IBVs contain a surface protein named NB that is anchored in the envelope, but its function is unknown

Life Cycle

Target cell / Host cell invasion and replication by the influenza virus

The viral life cycle begins by binding to a target cell. Binding is mediated by the viral HA proteins on the surface of the evelope, which bind to cells that contain sialic acid receptors on the surface of the cell membrane. For N1 subtypes with the "G147R" mutation and N2 subtypes, the NA protein can initiate entry. Prior to binding, NA proteins promote access to target cells by degrading mucous, which helps to remove extracellular decoy receptors that would impede access to target cells. After binding, the virus is internalized into the cell by an endosome that contains the virion inside it. The endosome is acidified by cellular vATPase to have lower pH, which triggers a conformational change in HA that allows fusion of the viral envelope with the endosomal membrane. At the same time, hydrogen ions diffuse into the virion through M2 ion channels, disrupting internal protein-protein interactions to release RNPs into the host cell's cytosol. The M1 protein shell surrounding RNPs is degraded, fully uncoating RNPs in the cytosol.

RNPs are then imported into the nucleus with the help of viral localization signals. There, the viral RNA polymerase  transcribes mRNA using the genomic negative-sense strand as a template. The polymerase snatches 5' caps for viral mRNA from cellular RNA to prime mRNA synthesis and the 3'-end of mRNA is polyadenylated at the end of transcription. Once viral mRNA is transcribed, it is exported out of the nucleus and translated by host ribosomes in a cap-dependent manner to synthesize viral proteins. RdRp also synthesizes complementary positive-sense strands of the viral genome in a complementary RNP complex which are then used as templates by viral polymerases to synthesize copies of the negative-sense genome. During these processes, RdRps of avian influenza viruses (AIVs) function optimally at a higher temperature than mammalian influenza viruses.

Newly synthesized viral polymerase subunits and NP proteins are imported to the nucleus to further increase the rate of viral replication and form RNPs. HA, NA, and M2 proteins are trafficked with the aid of M1 and NEP proteins to the cell membrane through the Golgi apparatus and inserted into the cell's membrane. Viral non-structural proteins including NS1, PB1-F2, and PA-X regulate host cellular processes to disable antiviral responses. PB1-F2 also interacts with PB1 to keep polymerases in the nucleus longer. M1 and NEP proteins localize to the nucleus during the later stages of infection, bind to viral RNPs and mediate their export to the cytoplasm where they migrate to the cell membrane with the aid of recycled endosomes and are bundled into the segments of the genome.

Progenic viruses leave the cell by budding from the cell membrane, which is initiated by the accumulation of M1 proteins at the cytoplasmic side of the membrane. The viral genome is incorporated inside a viral envelope derived from portions of the cell membrane that have HA, NA, and M2 proteins. At the end of budding, HA proteins remain attached to cellular sialic acid until they are cleaved by the sialidase activity of NA proteins. The virion is then released from the cell. The sialidase activity of NA also cleaves any sialic acid residues from the viral surface, which helps prevent newly assembled viruses from aggregating near the cell surface and improving infectivity. Similar to other aspects of influenza replication, optimal NA activity is temperature- and pH-dependent. Ultimately, presence of large quantities of viral RNA in the cell triggers apoptosis, i.e. programmed cell death, which is initiated by cellular factors to restrict viral replication.

Antigenic drift and shift

                                       

Antigenic shift, or reassortment, can result in novel and highly pathogenic strains of human

Influenza

Two key processes that influenza viruses evolve through are  antigenic drift and  antigenic shift. Antigenic drift is when an influenza virus's antigens change due to the gradual accumulation of mutations in the antigen's (HA or NA) gene. This can occur in response to evolutionary pressure exerted by the host immune response. Antigenic drift is especially common for the HA protein, in which just a few amino acid changes in the head region can constitute antigenic drift. The result is the production of novel strains that can evade pre-existing antibody-mediated immunity. Antigenic drift occurs in all influenza species. Antigenic drift is a major cause of seasonal influenza, and requires that flu vaccines be updated annually. HA is the main component of inactivated vaccines, so surveillance monitors antigenic drift of this antigen among circulating strains.

Antigenic shift is a sudden, drastic change in an influenza virus's antigen, usually HA. During antigenic shift, antigenically different strains that infect the same cell can reassort genome segments with each other, producing hybrid progeny. Since all influenza viruses have segmented genomes, all are capable of reassortment. Antigenic shift, however, only occurs among influenza viruses of the same genus and most commonly occurs among IAVs. In particular, reassortment is very common in AIVs, creating a large diversity of influenza viruses in birds, but is uncommon in human, equine, and canine lineages. Pigs, bats, and quails have receptors for both mammalian and avian IAVs, so they are potential "mixing vessels" for reassortment. If an animal strain reassorts with a human strain, then a novel strain can emerge that is capable of human-to-human transmission. This has caused pandemics, but only a limited number have occurred, so it is difficult to predict when the next will happen.

Transmission

Respiratory droplets

People who are infected can transmit influenza viruses through breathing, talking, coughing, and sneezing, which spread  respiratory droplets and aerosols  that contain virus particles into the air. A person susceptible to infection can then contract influenza by coming into contact with these particles. Respiratory droplets are relatively large and travel less than two meters before falling onto nearby surfaces. Aerosols are smaller and remain suspended in the air longer, so they take longer to settle and can travel further than respiratory droplets. Inhalation of aerosols can lead to infection, but most transmission is in the area about two meters around an infected person via respiratory droplets that come into contact with mucosa of the upper respiratory tract. Transmission through contact with a person, bodily fluids, or intermediate objects (fomites) can also occur, such as through contaminated hands and surfaces since influenza viruses can survive for hours on non-porous surfaces. If one's hands are contaminated, then touching one's face can cause infection.

Aerosol

Influenza is usually transmissible from one day before the onset of symptoms to 5–7 days after. In healthy adults, the virus is shed for up to 3–5 days. In children and the immunocompromised, the virus may be transmissible for several weeks. Children ages 2–17 are considered to be the primary and most efficient spreaders of influenza. Children who have not had multiple prior exposures to influenza viruses shed the virus at greater quantities and for a longer duration than other children. People who are at risk of exposure to influenza include health care workers, social care workers, and those who live with or care for people vulnerable to influenza. In long-term care facilities, the flu can spread rapidly after it is introduced. A variety of factors likely encourage influenza transmission, including lower temperature, lower absolute and relative humidity, less ultraviolet radiation from the Sun, and crowding. Influenza viruses that infect the upper respiratory tract like H1N1 tend to be more mild but more transmissible, whereas those that infect the lower respiratory tract like  H5N1 tend to cause more severe illness but are less contagious.

Pathophysiology

How the different sites of infection (shown in red) of H1N1 and H5N1 influences their transmission and lethality

In humans, influenza viruses first cause infection by infecting epithelial cells in the respiratory tract. Illness during infection is primarily the result of lung inflammation  and compromise caused by epithelial cell infection and death, combined with inflammation caused by the immune system's response to infection. Non-respiratory organs can become involved, but the mechanisms by which influenza is involved in these cases are unknown. Severe respiratory illness can be caused by multiple, non-exclusive mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity due to epithelial cell infection and death, and degradation of the extracellular matrix that maintains lung structure. In particular, alveolar cell infection appears to drive severe symptoms since this results in impaired gas exchange and enables viruses to infect endothelial cells, which produce large quantities of pro-inflammatory cytokines,

Pneumonia caused by influenza viruses is characterized by high levels of viral replication in the lower respiratory tract, accompanied by a strong pro-inflammatory response called a cytokine storm Infection with H5N1 or H7N9 specially produces high levels of pro-inflammatory cytokines. In bacterial infections, early depletion of microphages during influenza creates a favorable environment in the lungs for bacterial growth since these white blood cells are important in responding to bacterial infection. Host mechanisms to encourage tissue repair may inadvertently allow bacterial infection. Infection also induces production of systemic glucocorticoids  that can reduce inflammation to preserve tissue integrity but allow increased bacterial growth.

The pathophysiology of influenza is significantly influenced by which receptors influenza viruses bind to during entry into cells. AIVs prefer sialic acids with an α-2,3 linkage, which are most common in birds in gastrointestinal epithelial cells and in humans in the lower respiratory tract. 

Immunology

Cells possess sensors to detect viral RNA, which can then induce  interferon production. Interferons mediate expression of antiviral proteins and proteins that recruit immune cells to the infection site, and they also notify nearby uninfected cells of infection. Some infected cells release pro-inflammatory cytokines that recruit immune cells to the site of infection. Immune cells control viral infection by killing infected cells and phagocytizing viral particles and apoptotic cells. An exacerbated immune response, however, can harm the host organism through a cytokine storm. 

B cells, a type of white blood cell, produce antibodies that bind to influenza antigens HA and NA (or HEF) and other proteins to a lesser degree. Once bound to these proteins, antibodies block virions from binding to cellular receptors, neutralizing the virus. In humans, a sizeable antibody response occurs ~1 week after viral exposure. This antibody response is typically robust and long-lasting, especially for ICV and IDV. In other words, people exposed to a certain strain in childhood still possess antibodies to that strain at a reasonable level later in life, which can provide some protection to related strains. 

Tips to keep the Virus at bay

Lifestyle

• Six month old and older people should get a Flu vaccine every year to prevent its occurrence.
• Avoid spaces that have less than ideal ventilation and cramped spaces,
• Wear a face mask at social gathering.
• Refrain from coming in close contact with people who are sick. Those with symptom should also limit contact with others.
• Use a tissue to cover your nose and mouth while sneezing or coughing. Throw the tissue in the trash after use.
• Avoid touching your eyes, nose and mouth to restrict the  spread of germs.
• Use soap and water to wash your hands. You can also use an alcohol based hand rub.
• Ensure you remain hydrated.

Pranayama

Yoga

Yoga is extremely beneficial to keep the flu away, as it helps in clearing the airways, improves blood circulation and reduces inflammation.

Vipritkarni

                                                 

Bhujangasana

Balasana

Setu Bandasana

Diet

Eat right to fight back

• Ginger Tea & Tulsi tea

• Lemon  & Honey Tea

                                          

• Cinnamon Kadha an immunity booster

                                                

Boiled water with addition of cumin, carrom (ajwain)seeds  and black cardemum are effective drink to prevent and cure the flu.

• Turmeric Latte

Consumption of one glass of turmeric milk every day , helps in boosting immunity.

• Protein : 

Add rich source of protein like eggs, chicken, meat, fish to your diet. Dal chicken soup and mix veg soup combined with oats are also great.

Leafy green vegetables

Increase the intake of leafy green vegetables like broccoli,, spinach, kale, cabbage and mustard greens. And vitamin C enriched fruits orange, grape fruits, strawberries and kiwi.

Citrus fruits

Garlic

 

Garlic is also good ingredient to use due to its anti viral and anti microbial property. Use it in soups and other dishes.

Consult a Pulmonologist

Dr Avi Kumar Senior consultant pulmonology, Fortis, Escort Hospital. New Delhi.

Prevention

Greet with Namaste

Vaccination/Flu Jab / Flu Shot

An annual vaccine can help prevent the flu and limit its complications. Vaccines currently in use provide protection against IAV subtypes H1N1 and H3N2 and one or two IBV subtypes.

Influenza (flu) vaccines (often called “flu jab or flu shots”) are vaccines that protect against the four influenza viruses common during the upcoming season. Most flu vaccines are “flu shots” given with a needle, usually in the arm. 

When should the flu vaccine be given? Ideally, everyone should be vaccinated by the end of October. However, even if you are not able to get vaccinated until November or later, vaccination is still recommended because flu most commonly peaks in February and significant activity can continue into May. Protection lasts around 6 to 8 months, starting two weeks after you receive the vaccine. Once the season ends, the flu shot does not protect you any longer: you will need a new vaccination for the following year's season. The higher dose of antigen in the vaccine is intended to give people 65 years and older a better immune response to vaccination, and therefore, better protection against flu. Both Fluzone High-Dose and Fluzone Quadrivalent (standard dose) are produced by the same manufacturer and are quadrivalent vaccines.

Annual vaccination is the primary and most effective way to prevent influenza and influenza-associated complications, especially for high-risk groups. Vaccines against the flu are trivalent or quadrivalent, providing protection against an H1N1 strain, an H3N2 strain, and one or two IBV strains corresponding to the two IBV lineages. Two types of vaccines are in use: inactivated vaccines that contain "killed" (i.e. inactivated) viruses and live attenuated influenza vaccines (LAIVs) that contain weakened viruses. There are three types of inactivated vaccines: whole virus, split virus, in which the virus is disrupted by a detergent, and subunit, which only contains the viral antigens HA and NA. Most flu vaccines are inactivated and administered via intramuscular injection. LAIVs are sprayed into the nasal cavity. Vaccination recommendations vary by country. Some recommend vaccination for all people above a certain age, such as 6 months, whereas other countries recommendation is limited for high at risk groups, such as pregnant women, young children (excluding newborns), the elderly, people with chronic medical conditions, health care workers, people who come into contact with high-risk people, and people who transmit the virus easily. Young infants cannot receive flu vaccines for safety reasons, but they can inherit passive immunity from their mother if inactivated vaccines are administered to the mother during pregnancy. Influenza vaccination also helps to reduce the probability of reassortment.

In general, influenza vaccines are only effective if there is an antigenic match between vaccine strains and circulating strains. Additionally, most commercially available flu vaccines are manufactured by propagation of influenza viruses in embryonated chicken eggs, taking 6–8 months.  Flu seasons are different in the northern and southern hemisphere, so the WHO meets twice a year, one for each hemisphere, to discuss which strains should be included in flu vaccines based on observation from HA inhibition assays. Other manufacturing methods include an MDCK cell  culture-based inactivated vaccine and a recombinant subunit vaccine manufactured from  baculovirus overexpression in insect cells.

Anti Viral Chemoprophylaxis

Chemoprophylaxis :  It  is most useful for individuals at high-risk of developing complications and those who cannot receive the flu vaccine due to contraindications or lack of effectiveness. a . Tab Oseltamivir : Influenza can be prevented or reduced in severity by post-exposure prophylaxis with the antiviral drugs,  which can be taken orally by those at least three months old, b . Zanamivir : which can be inhaled by those above seven years of age.

Post-exposure chemoprophylaxis : Tab oseltamivir is only recommended if  is taken within 48 hours of contact with a confirmed or suspected influenza case and Zanamivir within 36 hours. It is recommended that it be offered to people who have yet to receive a vaccine for the current flu season, who have been vaccinated less than two week since contact, if there is a significant mismatch between vaccine and circulating strains, or during an outbreak in a closed setting regardless of vaccination history

Infection Control

Hand hygiene is important in reducing the spread of influenza. 

Hand Hygiene

Hand hygiene is important in reducing the spread of influenza. 

This includes frequent hand washing with soap and water, using alcohol -based hand sanitizer. 

Avoid touching one's eyes, nose, and mouth with one's hands. 

Respiratory etiquette : Covering one's nose and mouth when coughing or sneezing is important. 

                                                

Respiratory etiquette

Other methods to limit influenza transmission include staying home when sick,

Avoiding contact with others until one day after symptoms end.

And disinfecting surfaces likely to be contaminated by the virus, such as doorknobs.

Mask Wearing

Health education through media and posters is often used to remind people of the aforementioned etiquette and hygiene.

Social distancing : Measures such as school closures, avoiding contact with infected people via isolation or quarantine, and limiting mass gatherings may reduce transmission, but these measures are often expensive, unpopular, and difficult to implement. Pharmaceutical measures are effective but may not be available in the early stages of an outbreak. In health care settings, infected individuals may be cohorted or assigned to individual rooms. 

Protective clothing such as masks, gloves, and gowns is recommended when coming into contact with infected individuals if there is a risk of exposure to infected bodily fluids. 

Keeping patients in negative pressure room. Avoiding aerosol-producing activities may help In residential homes, new admissions may need to be closed until the spread of influenza is controlled. When discharging patients to care homes, it is important to take care if there is a known influenza outbreak. Since influenza viruses circulate in animals such as birds and pigs, prevention of transmission from these animals is important. Water treatment, indoor raising of animals, quarantining sick animals, vaccination, and biosecurity are the primary measures used. Placing poultry houses and piggeries on high ground away from high-density farms, backyard farms, live poultry markets, and bodies of water helps to minimize contact with wild birds. Closure of live poultry markets appears to the most effective measure and has shown to be effective at controlling the spread of H5N1, H7N9, and H9N2. Other biosecurity measures include cleaning and disinfecting facilities and vehicles, banning visits to poultry farms, not bringing birds intended for slaughter back to farms, changing clothes, disinfecting foot baths, and treating food and water. If live poultry markets are not closed, then "clean days" when unsold poultry is removed and facilities are disinfected and "no carry-over" policies to eliminate infectious material before new poultry arrive can be used to reduce the spread of influenza viruses. If a novel influenza viruses has breached the aforementioned biosecurity measures, then rapid detection to stamp it out via quarantining, decontamination, and culling may be necessary to prevent the virus from becoming endemic. Vaccines exist for avian H5, H7, and H9 subtypes that are used in some countries. In China, for example, vaccination of domestic birds against H7N9 successfully limited its spread, indicating that vaccination may be an effective strategy if used in combination with other measures to limit transmission. In pigs and horses, management of influenza is dependent on vaccination with biosecurity.

Treatment

In healthy individuals, influenza is typically self-limiting and rarely fatal, but it can be deadly in high-risk groups.

Allopathy

Corticosteroids likewise are not recommended except when treating Septic shock  or an underlying medical condition, such as chronic obstructive pulmonary disease or asthma exacerbation, since they are associated with increased mortality. If a secondary bacterial infection occurs, then treatment with antibiotics may be necessary.^[

Supportive measures : Flu is primarily treated with rest. Fluid intake to allow the body to fight the infection on its own. Liquids including  soups, coconut water and plain water should be given. To ensure  adequate urine output. 

• Adequate fluid intake to avoid dehydration.
• Resting at home :  Child should stay for a couple of days at home, even after fever settles, because flu can make  a child very weak.
• Fever : Sponging a whole body with little warm water  is very comforting. Paracetamol may help cure the symptoms but NSAIDs should be avoided.  
• Cough drops and throat sprays may be beneficial for sore throat.
•  It is recommended to avoid alcohol and tobacco use while sick with the flu.
•  Aspirin is not recommended to treat influenza in children due to an elevated risk of developing Reye syndrome.

• Anti Viral drug : Antiviral drugs are primarily used to treat severely ill patients, especially those with compromised immune systems. Antivirals are most effective when started in the first 48 hours after symptoms appear. Later administration may still be beneficial for those who have underlying immune defects, those with more severe symptoms, or those who have a higher risk of developing complications if these individuals are still shedding the virus. Antiviral treatment is also recommended if a person is hospitalized with suspected influenza instead of waiting for test results to return and if symptoms are worsening.

Antiviral drugs^[

Drug	Route of administration	Approved age of use
Oseltamivir	Oral	At least two weeks old
Zanamivir	Inhalation	At least five years old
Peramivir	Intravenous injection	At least 18 years old
Laninamivir	Inhalation	40 milligrams (mg) dose for people at least 10 years old, 20 mg for those under 10
Baloxavir marboxil	Oral	At least 12 years old

Most antiviral drugs against influenza fall into two categories: 

1 . Neuraminidase (NA) inhibitors

2 . M2 inhibitors. 

Baloxavir marboxil is a notable exception, which targets the endonuclease activity of the viral RNA polymerase and can be used as an alternative to NA and M2 inhibitors for IAV and IBV.

1 . Neuraminidase (NA) inhibitors
NA inhibitors target the enzymatic activity of NA receptors, mimicking the binding of sialic acid in the active site of NA on IAV and IBV virions so that viral release from infected cells and the rate of viral replication are impaired. NA inhibitors include oseltamivir, which is consumed orally in a prodrug form and converted to its active form in the liver, and zanamivir, which is a powder that is inhaled nasally. Oseltamivir and zanamivir are effective for prophylaxis and post-exposure prophylaxis, and research overall indicates that NA inhibitors are effective at reducing rates of complications, hospitalization, and mortality and the duration of illness. Additionally, the earlier NA inhibitors are provided, the better the outcome, though late administration can still be beneficial in severe cases. Other NA inhibitors include laninamivir and peramivir, the latter of which can be used as an alternative to oseltamivir for people who cannot tolerate or absorb it.

2 . M2 inhibitors. 
The adamantanes amantadine and rimantadine are orally administered drugs that block the influenza virus's M2 ion channel, preventing viral uncoating. These drugs are only functional against IAV but are no longer recommended for use because of widespread resistance to them among IAVs. Adamantane resistance first emerged in H3N2 in 2003, becoming worldwide by 2008. Oseltamivir resistance is no longer widespread because the 2009 pandemic H1N1 strain (H1N1 pdm09), which is resistant to adamantanes, seemingly replaced resistant strains in circulation. Since the 2009 pandemic, oseltamivir resistance has mainly been observed in patients undergoing therapy, especially the immunocompromised and young children. Oseltamivir resistance is usually reported in H1N1, but has been reported in H3N2 and IBVs less commonly. Because of this, oseltamivir is recommended as the first drug of choice for immunocompetent people, whereas for the immunocompromised, oseltamivir is recommended against H3N2 and IBV and zanamivir against H1N1 pdm09. Zanamivir resistance is observed less frequently,

Baloxavir marboxil i

And resistance to peramivir and baloxavir marboxil is possible.

• Antibiotic : If a secondary bacterial infection occurs, then treatment with antibiotics may be necessary

In severe cases :

• Corticosteroids likewise are not recommended except when treating septic shock septic shock or an underlying medical condition, such as chronic obstructive pulmonary disease  or asthma exacerbation, since they are associated with increased mortality

Other forms of therapy in development includes : 

• Monoclonal and Polyclonal antibodies that target viral proteins, 
• Convalescent plasma, different approaches to modify the host antiviral response,
• Stem cell based therapies to repair lung damage.

The high variability and rapid evolution of influenza virus antigens, however, is a major obstacle in developing effective vaccines. Furthermore, it is hard to predict which strains will be in circulation during the next flu season, manufacturing a sufficient quantity of flu vaccines for the next season is difficult. Migratory birds can spread influenza across long distances.   

Ayurveda

In rainy season it makes sense to know a little about the ayurvedic way to cope with fever.

For Ayurveda fever is caused by  an imbalance of  the pitta (fire), Vata (air) and Kapha (phlegm) energies. Stress, lifestyle disorders, incorrect nutrition, causes the imbalance leading to  a dysfunctional system of digestion. This means that toxins  in the small and large intestine putrefy and spread to the entire body. Add a bacterial or viral infections and you get a fever.

The Ayurvedic Method

• Ayurveda believes that low fevers are healing. They help burn the toxins in your body. But high fevers must be treated by relieving the strain on the digestive system with a light diet(Langhan or fasting) and some herbs.
• The ideal diet  for a person with fever incluses fruits, herbal decoctions and warm soups.
• Beneficial herbs for decoction include tulsi, ginger,black pepper, turmeric, raisins (kishmish) and methi seeds.

Different fevers and their cure

           "Fever is caused by Imbalance of vata, pitta and kapha. stress and incorrect nutrition."

 

Pitta

Pitta fevers are usually caused by sunstroke, but bacterial infections and Pneumonia can also cause similar symptoms of a burning forehead, high fever, bad smelling perspiration and usually loose motions and nausea. Sponge the patient with cold water and a few drops of peppermint oil.  Offer fruits such as musk melon, sweet lime (masambi) and drink lemon water with sugar. Make decoction of kutki and chandanadi.

Vata

Vata fever usually arrive in monsoon. Symptoms incluses :a racing pulse, great thirst, body aches and pain and fluctuating body temperatures. Diet includes a lot of water and warm soups. Make a decoction of sudarshan churana and guduchi (a febrifuge).

Kapha

Kapha fever displays symptoms such as heaviness and blocked sinuses indicating that the upper respiratory system is affected. Drink lots of water, Sip a decoction of Tulsi, ginger and long peper three or four times a day. Avoid heavy foods like bread, roti rice, milk, curd and ghee.

                                      "Tulsi or giloy decoction are beneficial in curing fever."

Preventive measures from building immunity and protection from flu like conditions :

• Sore throat : Food to be avoided in sore throat. Certain kinds of foods irritate the throat, lead to more congestion, cough and acid reflux and worsen sore throat. Therefore they are best avoided.

• Avoid Kapha provoking diet like curd, cold food, cold drinks, fruit juices, fermented foods, ice crème etc.
• Fried foods : cause more itching, throat irritation and also lowers the body's immunity
• Yogurt :   Worsens the cough by thickening the phlegm.
• Sour or acidic food:  items such as oranges, lemons, lime and tomatoes irritate the throat and cause more itching.
• Spicy food :  such as sauces, seasoning and spices cause more irritation, cough and throats congestion.
• Cold Foods :  like ice cream, cold drinks, and packed cold juices cause throat congestion, acid reflux and decrease local immunity as well. Thereby leading to  more  severe infection.
• Drink warm water instead of cold water.
• Drink decoction made up of any one or combination of Tulsi, Ginger, black pepper, long pepper (Pippali), Turmeric and Giloy /Guduchi (Tinospora cardifolia. in the morning and evening.
• Cinnamon tea in the morning and evening.
• Giloy tab (immunomodulator and febrifuge) mainly work by way of improving the host defence mechanism.
• For cough : lukewarm water morning and evening for 3-5 days.
• Liquid diet and personal hygiene ale also recommended.
• Fumigation : Environmental purification by smoking neem leaves,
• Immunity enhancer : Triphala powder. or Ashwagandha powder.
• Medicated smoking : Black pepper
• External oil medication : With camphor oil  it relieves congestion, Pinda tailam.

• Steam inhalation : Turmeric, Nirgundi (Vitex nirgundo), Malabar nut.

Prognosis

Respiratory complications that may occur include sinusitis, bronchitis, bronchiolitis, excess fluid buildup in the lungs, and exacerbation of chronic bronchitis and asthma. Middle ear infection and croup may occur, most commonly in children. Secondary S. aureus infection has been observed, primarily in children, to cause  toxic shock syndrome after influenza, with hypotension, fever, and reddening and peeling of the skin. Complications affecting the cardiovascular system are rare and include pericarditis, fulminant myocarditis with a fast slow irregular heart beat, and exacerbation of pre-existing cardiovascular disease. inflammation or swelling of muscles accompanied by muscle tissue breaking down occurs rarely, usually in children, which presents as extreme tenderness and muscle pain in the legs and a reluctance to walk for 2–3 days.

"Increased globalization has made it easier for novel viruses to spread, so there are continual efforts to prepare for future pandemics and improve the prevention and treatment of influenza."

"Let's celebrate responsiblity and make it our collective responsiblity to keep our loved ones safe by vaccination."

Update

10 March 2023

Amid the rising number of H3N2 virus cases, India reported its first death due to the infection in Karnataka. Hire Gowda 82 died due to virus on March 1st 2023.from Hasan Karnataka. Gowda was a Diabetic and also suffered from Hypertension. 

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