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Presented By
Dr.N.SudarmaniGayathri
Asst.Prof
Dept of Biochemistry
SNGC-CBE
PANDEMIC FLU HISTORY
• In the beginning of the 20th century, there have been four pandemic
influenza outbreaks.
• The most deadly of the outbreaks was the 1918 to 1919 "Spanish flu.
• This pandemic caused 20% to 40% of the worldwide population to
become ill, and an estimated 50 million people died.
• In the United States, 675,000 people died, with 3,688 of them in Oregon.
• The other three pandemics claimed many lives in the U.S. –
In 1957 to 1958 "Asian flu" resulted in 69,800 deaths, the 1968 to 1969
"Hong Kong flu" resulted in 33,800 deaths, and the 2009 to 2010 H1N1
“ swine flu"resulted in 12,469 deaths.
• According to the Centers for Disease Control and Prevention (CDC), the
H1N1 outbreak is estimated to have infected 60.8 million people globally,
although estimates as high as 89.3 million have been reported.
 This "swine flu" is a new strain is believed to have been first
contracted from pigs by people working closely with infected pigs,
such as pig farmers, where it is possible to inhale air-borne vital
particles.
 The influenza that affects pigs rarely causes swine death.
 The disease is not transmitted by eating cooked pig meat as the
virus cannot survive cooking temperatures.
 Swine flu is a respiratory disease that results from an influenza A virus
 It can affect both pigs and humans
 Although swine flu doesn't typically affect humans, there was a global pandemic in 2009 to 2010—the
first flu pandemic in more than 40 years.
 It was caused by a then-new flu virus known as H1N1, an influenza virus that's a combination of swine,
avian (bird), and human genes that mixed together in pigs and spread to humans.
 H1N1 is now considered a normal type of seasonal flu and is included in the flu vaccine.
 The influenza A variant subtype H1N1 is commonly the cause of swine flu in humans.
 It has similar genetic features to the H1N1 subtype of influenza virus that causes influenza in pigs.
 The flu is a highly contagious and common illness that is caused by the influenza virus.
 There are two main types of flu viruses: types A and B, both of which cause illness in humans.
 Other main subtypes known to occur and cause influenza in pigs include H1N2 and H3N2
 There have been infections in humans with these two variant subtypes as well.
 In 2009, the H1N1 variant became widespread in humans for the first time.
 Since 2009, the H1N1 virus has become one of the common viruses that
circulate each flu season.
 Many people now have some immunity to the virus.
 As a result, experts are now less concerned about this type of swine flu
than they were in 2009.
 The natural reservoir of the virus is the waterfowl.
 Most avian influenza viridae are incapable of directly infecting humans.
 Pigs have the unique characteristic of being host to both human as well as
avian species thus serving as ‘mixing hosts’ in which new strains adapted
to humans are created
INFLUENZA “A” VIRUS
UNDER
TEM
 The H1N1 influenza A virus (swine flu) is a novel influenza A virus, more properly termed a new subtype
of influenza A (H1N1) that was not previously detected in swine or humans.
 The H1N1 designation refers to hemagglutinin and neuraminidase -- proteins on the surface of the
influenza virus that enable the virus to enter and leave host cells.
 The conformation of these proteins determines the ability of the virus to infect humans; antibodies to
these proteins determine humans' ability to resist the infection.
 The influenza virus is a negative sense RNA virus of the family Orthomyxoviridae with three genera –
Influenza A, B and C.
 Influenza A is further sub-typed into 16 distinct H types and 9 distinct N types based on the
hemagglutinin and neuraminidase antigens on the surface of the virus.
 Every year new strains of the virus emerge as its genes undergo continuous point mutations leading to
an ‘antigenic drift’.
 This helps the virus evade host defences.
 Influenza A strains undergo genetic reassortment through contact with avian strains.
 The reassortment of an avian strain with a mammalian strain may produce a chimeric virus that is
transmissible between mammals; such mutation products may contain hemagglutinin and/or
neuraminidase proteins that are unrecognizable to the immune systems of mammals.
 This ‘antigenic shift’ is responsible for pandemics of influenza which have been observed in the past.
Pandemics on Spanish influenza in 1918 This antigenic shift results in a much greater population of
susceptible individuals in whom more severe disease is
possible.
 Such antigenic shifts as described on the previous slide can
cause a pandemic -- only 3 pandemics have occurred in
recorded history.
 The most striking of these pandemics was the 1918 Spanish
influenza, which infected one third of the world's population
(an estimated 500 million people) and caused approximately
50 million deaths.
 Despite its name, this pandemic may well have originated in
the United States; the first known outbreak occurred at an
Army base in Kansas
DISEASE TRANSMISSION
 Type A influenza virus which are
transmitted be small droplet nuclei.
 This virus is transmitted by large particle
respiratory droplets and hence requires a
less than 6 feet distance between the
source and the susceptible individual to
be present for effective spread.
 Rarely transmission by contact with
infected fomites and small droplet nuclei
may also occur.
 All bodily secretions are considered
potentially infectious
 The primary event after transmission of the virus is the invasion of the respiratory epithelium after an
incubation period which varies from 1 to 7 days.
 A study was done in the virus infected on the respiratory mucosa of weanling pigs and compared with those
of the H3N2 virus, it was seen that the lung lesions were more extensive in H1N1 infected animals.
 Histopathological changes were observed included epithelial cells damage, airway plugging and
peribronchial and perivascular mononuclear cell infiltration.
 After the initial illness, the host usually mounts an immune response which involves a rise in antibody titers
as well as T cell activation.
 The production of interferon in the respiratory mucosa is associated with a fall in virus shedding.
 The virus is shed for an average duration of a week (starting from 1 day before to 7 days after the onset of
illness).
 In children the duration of virus shedding is often longer, up to 2 weeks
CLINICAL CASE DESCRIPTION
 Acute febrile respiratory illness (fever >38°C) with the spectrum of disease from influenza-
like illness to pneumonia.
 Suspected case of swine influenza A (H1N1) virus infection A person with acute febrile
respiratory illness with onset
•Within 7 days of close contact with a person who is a confirmed case of swine influenza A
(H1N1) virus infection, or
• Within 7 days of travel to community where there are one or more confirmed swine influenza A
(H1N1) cases, or
• Resides in a community where there are one or more confirmed swine influenza cases.
Confirmed case of swine influenza A (H1N1) virus infection .
SUPPORTIVE CARE
• Patients should be monitored closely for signs of clinical deterioration such as dyspnea, chest pain, coughing
up altered sputum, altered sensorium and confusion and are thought to have higher risk of serious disease are
referred for hospitalization.
• They are provided with ventilator and inotropic support as per requirement.
• Steroids may be administered in critically ill patients in case of suspected adrenal insufficiency.
• Oxygen Therapy Oxygen is supplemented according to need by the monitoring of oxygen saturation by pulse
oximetry.
• Antivirals The swine origin influenza virus is resistant to adamantanes such as amantidine and rimantadine.
• It is oseltamivir and zanamivir.
• Oseltamivir is an orally administered drug which achieves much higher systemic levels than the inhaled
zanamivir.
• Thus oseltamivir is preferred for systemic infections.
SIDE EFFECTS OF THE DRUG
 IT include most commonly gastrointestinal intolerance, and infrequently neuropsychiatric manifestations and
serious skin reactions
 Treatment is recommended in patients with manifestations suggesting severe disease and those in high risk
groups – particularly those with asthma, obese patients and pregnant women
DOSE RECOMMENDATIONS
• Oseltamivir is indicated for treatment of patients one year of age and older.
• For adolescents (13 to 17 years of age) and adults the recommended oral dose
• is 75 mg oseltamivir twice daily for 5 days.
• For children the dosage is as follows
< 15 kg - 30 mg orally twice a day for 5 days
15-23 kg - 45 mg orally twice a day for 5 days
24-40 kg - 60 mg orally twice a day for 5 days
>40kg - 75 mg orally twice a day for 5 days
• In infants the drug is administered for five days and the dosage depends on the age of the child. 5 years).
• The recommended dose for treatment of adults and children from the age of 5 years is two inhalations (2 x 5mg)
twice daily for 5 days.
• There are no randomized controlled trials on efficacy (including prevention of complications and deaths) of these
drugs in swine origin H1N1 infections
VACCINATION
• At present there is no vaccine effective against swine origin H1N1 influenza virus.
• The seasonal flu vaccine is unlikely to provide protection against novel H1N1 influenza.
• Several researchers are working on development of vaccine.
• Few pharmaceutical companies are developing the vaccine and some have initiated
clinical trials as well.
• The vaccine virus is grown in egg cultures and is currently under trial for human use.
• CDC’s Advisory Committee on Immunization Practices has provided recommendations on
who should receive the new H1N1 vaccine when it becomes available.
GENERAL MEASURES
• The most cost effective measures include social distancing, practicing respiratory etiquette,
hand hygiene and good ventilation.
• Although studies evaluating the efficacy of masks in health care settings have validated
their use to prevent the spread of the virus, similar extrapolations cannot be made for the
community.
• However, when used they should be used correctly and disposed appropriately.
• Children with mild symptoms should be cared for at home by a designated care giver and
well individuals should be separated from the sick. In the health-care settings, triage, patient
separation, prioritization of use of antiviral medicines and personal protective equipment
(PPE) according to risk of exposure should be the focus
LABORATORY DIAGNOSIS
RT PCR- The RNA extracted from nasopharyngeal aspirate samples is amplified and detected by this assay.24 Other samples
which may be used include throat swabs and bronchial aspirates
The assay was seen to be highly specific for the swine origin H1N1 virus and was able to distinguish this from the seasonal H1N1
as well as non H1N1 organisms. These assays are rapid with results being available in a few hours
VIRAL CULTURE
The virus when grown on culture helps one make a 100% specific diagnosis. The sensitivity and negative predictive value is also
quite high at around 90%.
The virus grows on chick embryo as well as monkey kidney cell cultures within 48 to 72 hours of its inoculation.
Rapid diagnostic tests
The use of rapid diagnostic tests to detect antigens of the virus was compared with the standard RT PCR in 65 patients and it was
observed that the method had a 60% to 80% sensitivity.
• These findings indicate that although a positive test suggests a diagnosis of H1N1
influenza, a negative result does not rule out the same.
• Besides this, the test often requires a high virus concentration in the respiratory secretions,
and if negative, its results are interpreted based on the clinical suspicion of illness.
Rise in Antibody Titer
The comparison of antibody titer during the acute illness and 10 to 14 days later will help make
a diagnosis too but the test is not used for diagnostic purposes and is useful primarily in
retrospect.
Hematological and biochemical testing
• Suggest leucopenia, elevated lactate dehydrogenase and creatine kinase.
• Uncommonly, thrombocytopenia may also occur.
• Chest X ray abnormalities may be noted particularly in those severely affected and
hospitalized
Swine flu

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Swine flu

  • 2. PANDEMIC FLU HISTORY • In the beginning of the 20th century, there have been four pandemic influenza outbreaks. • The most deadly of the outbreaks was the 1918 to 1919 "Spanish flu. • This pandemic caused 20% to 40% of the worldwide population to become ill, and an estimated 50 million people died. • In the United States, 675,000 people died, with 3,688 of them in Oregon. • The other three pandemics claimed many lives in the U.S. – In 1957 to 1958 "Asian flu" resulted in 69,800 deaths, the 1968 to 1969 "Hong Kong flu" resulted in 33,800 deaths, and the 2009 to 2010 H1N1 “ swine flu"resulted in 12,469 deaths. • According to the Centers for Disease Control and Prevention (CDC), the H1N1 outbreak is estimated to have infected 60.8 million people globally, although estimates as high as 89.3 million have been reported.
  • 3.  This "swine flu" is a new strain is believed to have been first contracted from pigs by people working closely with infected pigs, such as pig farmers, where it is possible to inhale air-borne vital particles.  The influenza that affects pigs rarely causes swine death.  The disease is not transmitted by eating cooked pig meat as the virus cannot survive cooking temperatures.
  • 4.  Swine flu is a respiratory disease that results from an influenza A virus  It can affect both pigs and humans  Although swine flu doesn't typically affect humans, there was a global pandemic in 2009 to 2010—the first flu pandemic in more than 40 years.  It was caused by a then-new flu virus known as H1N1, an influenza virus that's a combination of swine, avian (bird), and human genes that mixed together in pigs and spread to humans.  H1N1 is now considered a normal type of seasonal flu and is included in the flu vaccine.  The influenza A variant subtype H1N1 is commonly the cause of swine flu in humans.  It has similar genetic features to the H1N1 subtype of influenza virus that causes influenza in pigs.  The flu is a highly contagious and common illness that is caused by the influenza virus.  There are two main types of flu viruses: types A and B, both of which cause illness in humans.  Other main subtypes known to occur and cause influenza in pigs include H1N2 and H3N2  There have been infections in humans with these two variant subtypes as well.
  • 5.  In 2009, the H1N1 variant became widespread in humans for the first time.  Since 2009, the H1N1 virus has become one of the common viruses that circulate each flu season.  Many people now have some immunity to the virus.  As a result, experts are now less concerned about this type of swine flu than they were in 2009.  The natural reservoir of the virus is the waterfowl.  Most avian influenza viridae are incapable of directly infecting humans.  Pigs have the unique characteristic of being host to both human as well as avian species thus serving as ‘mixing hosts’ in which new strains adapted to humans are created INFLUENZA “A” VIRUS UNDER TEM
  • 6.  The H1N1 influenza A virus (swine flu) is a novel influenza A virus, more properly termed a new subtype of influenza A (H1N1) that was not previously detected in swine or humans.  The H1N1 designation refers to hemagglutinin and neuraminidase -- proteins on the surface of the influenza virus that enable the virus to enter and leave host cells.  The conformation of these proteins determines the ability of the virus to infect humans; antibodies to these proteins determine humans' ability to resist the infection.
  • 7.  The influenza virus is a negative sense RNA virus of the family Orthomyxoviridae with three genera – Influenza A, B and C.  Influenza A is further sub-typed into 16 distinct H types and 9 distinct N types based on the hemagglutinin and neuraminidase antigens on the surface of the virus.  Every year new strains of the virus emerge as its genes undergo continuous point mutations leading to an ‘antigenic drift’.  This helps the virus evade host defences.  Influenza A strains undergo genetic reassortment through contact with avian strains.  The reassortment of an avian strain with a mammalian strain may produce a chimeric virus that is transmissible between mammals; such mutation products may contain hemagglutinin and/or neuraminidase proteins that are unrecognizable to the immune systems of mammals.  This ‘antigenic shift’ is responsible for pandemics of influenza which have been observed in the past.
  • 8. Pandemics on Spanish influenza in 1918 This antigenic shift results in a much greater population of susceptible individuals in whom more severe disease is possible.  Such antigenic shifts as described on the previous slide can cause a pandemic -- only 3 pandemics have occurred in recorded history.  The most striking of these pandemics was the 1918 Spanish influenza, which infected one third of the world's population (an estimated 500 million people) and caused approximately 50 million deaths.  Despite its name, this pandemic may well have originated in the United States; the first known outbreak occurred at an Army base in Kansas
  • 9. DISEASE TRANSMISSION  Type A influenza virus which are transmitted be small droplet nuclei.  This virus is transmitted by large particle respiratory droplets and hence requires a less than 6 feet distance between the source and the susceptible individual to be present for effective spread.  Rarely transmission by contact with infected fomites and small droplet nuclei may also occur.  All bodily secretions are considered potentially infectious
  • 10.  The primary event after transmission of the virus is the invasion of the respiratory epithelium after an incubation period which varies from 1 to 7 days.  A study was done in the virus infected on the respiratory mucosa of weanling pigs and compared with those of the H3N2 virus, it was seen that the lung lesions were more extensive in H1N1 infected animals.  Histopathological changes were observed included epithelial cells damage, airway plugging and peribronchial and perivascular mononuclear cell infiltration.  After the initial illness, the host usually mounts an immune response which involves a rise in antibody titers as well as T cell activation.  The production of interferon in the respiratory mucosa is associated with a fall in virus shedding.  The virus is shed for an average duration of a week (starting from 1 day before to 7 days after the onset of illness).  In children the duration of virus shedding is often longer, up to 2 weeks
  • 11.
  • 12. CLINICAL CASE DESCRIPTION  Acute febrile respiratory illness (fever >38°C) with the spectrum of disease from influenza- like illness to pneumonia.  Suspected case of swine influenza A (H1N1) virus infection A person with acute febrile respiratory illness with onset •Within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection, or • Within 7 days of travel to community where there are one or more confirmed swine influenza A (H1N1) cases, or • Resides in a community where there are one or more confirmed swine influenza cases. Confirmed case of swine influenza A (H1N1) virus infection .
  • 13. SUPPORTIVE CARE • Patients should be monitored closely for signs of clinical deterioration such as dyspnea, chest pain, coughing up altered sputum, altered sensorium and confusion and are thought to have higher risk of serious disease are referred for hospitalization. • They are provided with ventilator and inotropic support as per requirement. • Steroids may be administered in critically ill patients in case of suspected adrenal insufficiency. • Oxygen Therapy Oxygen is supplemented according to need by the monitoring of oxygen saturation by pulse oximetry. • Antivirals The swine origin influenza virus is resistant to adamantanes such as amantidine and rimantadine. • It is oseltamivir and zanamivir. • Oseltamivir is an orally administered drug which achieves much higher systemic levels than the inhaled zanamivir. • Thus oseltamivir is preferred for systemic infections. SIDE EFFECTS OF THE DRUG  IT include most commonly gastrointestinal intolerance, and infrequently neuropsychiatric manifestations and serious skin reactions  Treatment is recommended in patients with manifestations suggesting severe disease and those in high risk groups – particularly those with asthma, obese patients and pregnant women
  • 14. DOSE RECOMMENDATIONS • Oseltamivir is indicated for treatment of patients one year of age and older. • For adolescents (13 to 17 years of age) and adults the recommended oral dose • is 75 mg oseltamivir twice daily for 5 days. • For children the dosage is as follows < 15 kg - 30 mg orally twice a day for 5 days 15-23 kg - 45 mg orally twice a day for 5 days 24-40 kg - 60 mg orally twice a day for 5 days >40kg - 75 mg orally twice a day for 5 days • In infants the drug is administered for five days and the dosage depends on the age of the child. 5 years). • The recommended dose for treatment of adults and children from the age of 5 years is two inhalations (2 x 5mg) twice daily for 5 days. • There are no randomized controlled trials on efficacy (including prevention of complications and deaths) of these drugs in swine origin H1N1 infections
  • 15. VACCINATION • At present there is no vaccine effective against swine origin H1N1 influenza virus. • The seasonal flu vaccine is unlikely to provide protection against novel H1N1 influenza. • Several researchers are working on development of vaccine. • Few pharmaceutical companies are developing the vaccine and some have initiated clinical trials as well. • The vaccine virus is grown in egg cultures and is currently under trial for human use. • CDC’s Advisory Committee on Immunization Practices has provided recommendations on who should receive the new H1N1 vaccine when it becomes available.
  • 16. GENERAL MEASURES • The most cost effective measures include social distancing, practicing respiratory etiquette, hand hygiene and good ventilation. • Although studies evaluating the efficacy of masks in health care settings have validated their use to prevent the spread of the virus, similar extrapolations cannot be made for the community. • However, when used they should be used correctly and disposed appropriately. • Children with mild symptoms should be cared for at home by a designated care giver and well individuals should be separated from the sick. In the health-care settings, triage, patient separation, prioritization of use of antiviral medicines and personal protective equipment (PPE) according to risk of exposure should be the focus
  • 17. LABORATORY DIAGNOSIS RT PCR- The RNA extracted from nasopharyngeal aspirate samples is amplified and detected by this assay.24 Other samples which may be used include throat swabs and bronchial aspirates The assay was seen to be highly specific for the swine origin H1N1 virus and was able to distinguish this from the seasonal H1N1 as well as non H1N1 organisms. These assays are rapid with results being available in a few hours VIRAL CULTURE The virus when grown on culture helps one make a 100% specific diagnosis. The sensitivity and negative predictive value is also quite high at around 90%. The virus grows on chick embryo as well as monkey kidney cell cultures within 48 to 72 hours of its inoculation. Rapid diagnostic tests The use of rapid diagnostic tests to detect antigens of the virus was compared with the standard RT PCR in 65 patients and it was observed that the method had a 60% to 80% sensitivity.
  • 18. • These findings indicate that although a positive test suggests a diagnosis of H1N1 influenza, a negative result does not rule out the same. • Besides this, the test often requires a high virus concentration in the respiratory secretions, and if negative, its results are interpreted based on the clinical suspicion of illness. Rise in Antibody Titer The comparison of antibody titer during the acute illness and 10 to 14 days later will help make a diagnosis too but the test is not used for diagnostic purposes and is useful primarily in retrospect. Hematological and biochemical testing • Suggest leucopenia, elevated lactate dehydrogenase and creatine kinase. • Uncommonly, thrombocytopenia may also occur. • Chest X ray abnormalities may be noted particularly in those severely affected and hospitalized