Clinical Update on Influenza.
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
Clinical Update on Influenza
Dewi Dian Sukmawati
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine-Sanglah Hospital Denpasar
Influenza ia a viral infection commonly attack upper respiratory tract; nose, throat,
bronchi and occasionally spread to lungs. The viral spread easily from person to person
via droplets and small particles produced by infected person when they cough or sneeze.
The virus come from Orthomyxoviridae family, differentiated into three strain: Influenza
virus A, B and C with most virulent strains belongs to the type A. The classification of
Influenza virus A further based on the antigenic differences on their major surface
antigens: Hemagglutinins (H1 – H5) and Neuraminidase (N1 – N9) Figure 1.
Figure 1. Influenza A virion
INFLUENZA
VIRION
Nucleoprotein
(NP)
Nuclear Export
protein (NEP)
Hemagglutinin
(HA)
CM2 ion channel
Polymerase
complex (PA,
PB1,PB2)
Neuramidase
(NA)
Lipid bilayer
Matrix protein
Dewi Dian Sukmawati 2015
Some terms were use to describe the epidemiology of Influenza virus infection in human;
seasonal influenza, pandemic influenza and zoonotic or variant influenza (Figure 2)
Seasonal influenza
Seasonal influenza viruses circulate and cause influenza in humans annually
causing mild to severe illness and sometimes death, particularly in some high-risk
individuals. Persons at increased risk for severe disease include pregnant women, infants
and elderly, immune – compromised people, and people with co-morbidity chronic
underlying medical conditions.
The three large groupings or types of seasonal influenza viruses, labeled as
Influenza Virus A, B, and C. Type A influenza viruses are further divided into subtypes
according to the specific variety and combinations of two surface antigens proteins, the
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
hemagglutinin or “H” protein and the neuraminidase or “N” protein. Currently, influenza
A(H1N1) and A(H3N2) are the circulating seasonal influenza A virus subtypes. This
seasonal A (H1N1) virus is the same virus that caused the 2009 swine influenza
pandemic, as it is now circulating seasonally. In addition, there are two type B viruses that
are also circulating as seasonal influenza viruses, which are named after the areas where
they were first identified, Victoria lineage and Yamagata lineage. Type C influenza causes
milder infections and is associated with sporadic cases and minor localized outbreaks. As
influenza C poses much less of a disease burden than influenza A and B, only the latter
two are included in seasonal influenza vaccines.
Pandemic Influenza
Pandemic influenza is a global outbreak. An influenza pandemic occurs when a
new flu virus emerges for which humans have little or no immunity, which allows the virus
to spread easily from person to person worldwide. These viruses may emerge, circulate
and cause large outbreaks outside of the normal influenza season. As the majority of the
population has no immunity to these viruses, the proportion of persons in a population
getting infected may be quite large. Some pandemics may result in large numbers of
severe infections while others will result in large numbers of milder infections, but the
reasons behind these differences are not completely understood. Three influenza
pandemics occurred during the 20th century: the 1918 – 1919 “Spanish flu,” the 1957 –
1958 “Asian flu,” and the 1968 – 1969 pandemic or “Hong Kong flu.” In 2009, the World
Health Organization (WHO) declared a global pandemic of H1N1 flu “Swine Flu”. This
action was a reflection of the spread of the new H1N1 virus, not the severity of illness
caused by the virus.
Zoonotic or variant influenza
Humans can also be infected with influenza viruses that are routinely circulating in
animals, such as avian influenza virus subtypes A(H5N1) and A(H9N2) and swine
influenza virus subtypes A(H1N1) and (H3N2). Some may occasionally infect humans,
however, and may cause disease ranging from mild conjunctivitis to severe pneumonia
and even death. Usually these human infections of zoonotic influenza are acquired
through direct contact with infected animals or contaminated environments, and do not
spread very far among humans. If such a virus acquired the capacity to spread easily
among people either through adaptation or acquisition of certain genes from human
viruses, it could start an epidemic or a pandemic.
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
Figure 2. Influenza viruses in human
INFLUENZA VIRUS
Infection in human
SEASONAL
INFLUENZA
• Influenza Virus A
•H1N1, H3N2
• Influenza Virus B
•Victoria lineage,
Yamagata lineage
• Influenza Virus C
PANDEMIC
INFLUENZA
ZOONOTIC / VARIANT
INFLUENZA
• Spanish flu 1918
• Spanish flu 1957
• Spanish flu 1967
• Swine influenza
subtype A (H1N1) 2009
• Avian Influenza virus
subtypes A (H5N1) & A
(H9N2)
• Swine Influenza virus
subtype A (H1N1) & A
(H3N2)
Influenza virus infections in humans. WHO 2014
Clinical Manifestations
The majority of person infected with influenza virus exhibit self limiting, uncomplicated,
acute respiratory illness with fever or even asymptomatic (Figure 3).
Figure 3. Influenza virus infection timeline
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
The criterion standard for diagnosing influenza A and B is a viral culture of
nasopharyngeal samples or throat samples. In elderly or high-risk patients with pulmonary
symptoms, chest radiography should be performed to exclude pneumonia
Influenza Vaccine
Since the influenza seasons are unpredictable and influenza disease can have
severe consequences, annual vaccination remains the best way to prevent the flu.
Available vaccines including injectable and nasal spray form.
Seasonal Virus vaccine Trivalent types A and types B:
• Injectable vaccine
– Afluria. CSL Limited.
– Agriflu. Novartis Vaccines and Diagnostics, Inc.
– FluLaval. ID Biomedical Corporation of Quebec
– Fluarix. GlaxoSmithKline Biologicals
– Flublok. Protein Sciences Corporation
– Flucefax. Novartis Vaccines and Diagnostics, Inc.
– Fluvirin. Novartis Vaccines and Diagnostics Ltd.
– Fluzone, Fluzone highdose, Fluzone intradermal. Sanofi Pasteur, Inc.
• Intranasal spray
– FluMist. MedImmune, LLC
Seasonal Virus vaccine Quadrivalent types A and types B:
• Injectable vaccine
– Fluarix Quadrivalent. GlaxoSmithKline Biologicals
– Fluzone Quadrivalent. Sanofi Pasteur, Inc.
– FluLaval Quadrivalent. ID Biomedical Corporation of Quebec
• Intranasal spray
– FluMist Quadrivalent. MedImmune, LLC
Influenza virus vaccine for H5N1 (not available commercially, stock pile only used for
outbreak):
• Influenza virus vaccine H5N1 Sanofi Pasteur, Inc
• Influenza A (H5N1) Virus Monovalent Vaccine Adjuvanted. ID Biomedical
Corporation of Quebec
Antiviral Therapy
Influenza antiviral medications are prescription pills, liquids, or inhalers used to prevent or
treat flu. They are approved for adults, children and infants as young as two weeks. The
benefits in using antivirals;
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
•
•
Infected cases: Infected person will have milder sign and symptoms with shorter
duration of illness. Antiviral medications work best when started within the first two
days of flu onset.
Exposed to the flu: antiviral medication can prevent Illness. But must be
remember that antiviral drugs are not a substitute for the influenza vaccine.
Current approved antiviral for influenza including
• Tamiflu (oseltamivir phosphate)
• Relenza (zanamivir)
• Rapivab (peramivir)
Older drugs, such as amantadine and rimantadine possess resistance problem (including
to H1N1 influenza) thus not widely be used anymore.
Refferences
1. Fiore AE, Shay DK, Broder K, et al. Prevention and control of influenza:
recommendations of the Advisory Committee on Immunization Practices (ACIP),
2008. MMWR Recomm Rep 2008; 57(RR-7):1–60.
2. D’Heilly SJ, Janoff EN, Nichol P, Nichol KL. Rapid diagnosis of in- fluenza infection
in older adults: influence on clinical care in a routine clinical setting. J Clin Virol
2008; 42:124–8
3. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus
standard-dose influenza vaccine in older adults. N Engl J Med. 2014 Aug 14.
371(7):635-45
4. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E.
Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev.
2010 Jul 7. CD001269
5. Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis. 2006 Jan.
12(1):9-14
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
Clinical Update on Influenza
Dewi Dian Sukmawati
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine-Sanglah Hospital Denpasar
Influenza ia a viral infection commonly attack upper respiratory tract; nose, throat,
bronchi and occasionally spread to lungs. The viral spread easily from person to person
via droplets and small particles produced by infected person when they cough or sneeze.
The virus come from Orthomyxoviridae family, differentiated into three strain: Influenza
virus A, B and C with most virulent strains belongs to the type A. The classification of
Influenza virus A further based on the antigenic differences on their major surface
antigens: Hemagglutinins (H1 – H5) and Neuraminidase (N1 – N9) Figure 1.
Figure 1. Influenza A virion
INFLUENZA
VIRION
Nucleoprotein
(NP)
Nuclear Export
protein (NEP)
Hemagglutinin
(HA)
CM2 ion channel
Polymerase
complex (PA,
PB1,PB2)
Neuramidase
(NA)
Lipid bilayer
Matrix protein
Dewi Dian Sukmawati 2015
Some terms were use to describe the epidemiology of Influenza virus infection in human;
seasonal influenza, pandemic influenza and zoonotic or variant influenza (Figure 2)
Seasonal influenza
Seasonal influenza viruses circulate and cause influenza in humans annually
causing mild to severe illness and sometimes death, particularly in some high-risk
individuals. Persons at increased risk for severe disease include pregnant women, infants
and elderly, immune – compromised people, and people with co-morbidity chronic
underlying medical conditions.
The three large groupings or types of seasonal influenza viruses, labeled as
Influenza Virus A, B, and C. Type A influenza viruses are further divided into subtypes
according to the specific variety and combinations of two surface antigens proteins, the
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
hemagglutinin or “H” protein and the neuraminidase or “N” protein. Currently, influenza
A(H1N1) and A(H3N2) are the circulating seasonal influenza A virus subtypes. This
seasonal A (H1N1) virus is the same virus that caused the 2009 swine influenza
pandemic, as it is now circulating seasonally. In addition, there are two type B viruses that
are also circulating as seasonal influenza viruses, which are named after the areas where
they were first identified, Victoria lineage and Yamagata lineage. Type C influenza causes
milder infections and is associated with sporadic cases and minor localized outbreaks. As
influenza C poses much less of a disease burden than influenza A and B, only the latter
two are included in seasonal influenza vaccines.
Pandemic Influenza
Pandemic influenza is a global outbreak. An influenza pandemic occurs when a
new flu virus emerges for which humans have little or no immunity, which allows the virus
to spread easily from person to person worldwide. These viruses may emerge, circulate
and cause large outbreaks outside of the normal influenza season. As the majority of the
population has no immunity to these viruses, the proportion of persons in a population
getting infected may be quite large. Some pandemics may result in large numbers of
severe infections while others will result in large numbers of milder infections, but the
reasons behind these differences are not completely understood. Three influenza
pandemics occurred during the 20th century: the 1918 – 1919 “Spanish flu,” the 1957 –
1958 “Asian flu,” and the 1968 – 1969 pandemic or “Hong Kong flu.” In 2009, the World
Health Organization (WHO) declared a global pandemic of H1N1 flu “Swine Flu”. This
action was a reflection of the spread of the new H1N1 virus, not the severity of illness
caused by the virus.
Zoonotic or variant influenza
Humans can also be infected with influenza viruses that are routinely circulating in
animals, such as avian influenza virus subtypes A(H5N1) and A(H9N2) and swine
influenza virus subtypes A(H1N1) and (H3N2). Some may occasionally infect humans,
however, and may cause disease ranging from mild conjunctivitis to severe pneumonia
and even death. Usually these human infections of zoonotic influenza are acquired
through direct contact with infected animals or contaminated environments, and do not
spread very far among humans. If such a virus acquired the capacity to spread easily
among people either through adaptation or acquisition of certain genes from human
viruses, it could start an epidemic or a pandemic.
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
Figure 2. Influenza viruses in human
INFLUENZA VIRUS
Infection in human
SEASONAL
INFLUENZA
• Influenza Virus A
•H1N1, H3N2
• Influenza Virus B
•Victoria lineage,
Yamagata lineage
• Influenza Virus C
PANDEMIC
INFLUENZA
ZOONOTIC / VARIANT
INFLUENZA
• Spanish flu 1918
• Spanish flu 1957
• Spanish flu 1967
• Swine influenza
subtype A (H1N1) 2009
• Avian Influenza virus
subtypes A (H5N1) & A
(H9N2)
• Swine Influenza virus
subtype A (H1N1) & A
(H3N2)
Influenza virus infections in humans. WHO 2014
Clinical Manifestations
The majority of person infected with influenza virus exhibit self limiting, uncomplicated,
acute respiratory illness with fever or even asymptomatic (Figure 3).
Figure 3. Influenza virus infection timeline
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
The criterion standard for diagnosing influenza A and B is a viral culture of
nasopharyngeal samples or throat samples. In elderly or high-risk patients with pulmonary
symptoms, chest radiography should be performed to exclude pneumonia
Influenza Vaccine
Since the influenza seasons are unpredictable and influenza disease can have
severe consequences, annual vaccination remains the best way to prevent the flu.
Available vaccines including injectable and nasal spray form.
Seasonal Virus vaccine Trivalent types A and types B:
• Injectable vaccine
– Afluria. CSL Limited.
– Agriflu. Novartis Vaccines and Diagnostics, Inc.
– FluLaval. ID Biomedical Corporation of Quebec
– Fluarix. GlaxoSmithKline Biologicals
– Flublok. Protein Sciences Corporation
– Flucefax. Novartis Vaccines and Diagnostics, Inc.
– Fluvirin. Novartis Vaccines and Diagnostics Ltd.
– Fluzone, Fluzone highdose, Fluzone intradermal. Sanofi Pasteur, Inc.
• Intranasal spray
– FluMist. MedImmune, LLC
Seasonal Virus vaccine Quadrivalent types A and types B:
• Injectable vaccine
– Fluarix Quadrivalent. GlaxoSmithKline Biologicals
– Fluzone Quadrivalent. Sanofi Pasteur, Inc.
– FluLaval Quadrivalent. ID Biomedical Corporation of Quebec
• Intranasal spray
– FluMist Quadrivalent. MedImmune, LLC
Influenza virus vaccine for H5N1 (not available commercially, stock pile only used for
outbreak):
• Influenza virus vaccine H5N1 Sanofi Pasteur, Inc
• Influenza A (H5N1) Virus Monovalent Vaccine Adjuvanted. ID Biomedical
Corporation of Quebec
Antiviral Therapy
Influenza antiviral medications are prescription pills, liquids, or inhalers used to prevent or
treat flu. They are approved for adults, children and infants as young as two weeks. The
benefits in using antivirals;
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
•
•
Infected cases: Infected person will have milder sign and symptoms with shorter
duration of illness. Antiviral medications work best when started within the first two
days of flu onset.
Exposed to the flu: antiviral medication can prevent Illness. But must be
remember that antiviral drugs are not a substitute for the influenza vaccine.
Current approved antiviral for influenza including
• Tamiflu (oseltamivir phosphate)
• Relenza (zanamivir)
• Rapivab (peramivir)
Older drugs, such as amantadine and rimantadine possess resistance problem (including
to H1N1 influenza) thus not widely be used anymore.
Refferences
1. Fiore AE, Shay DK, Broder K, et al. Prevention and control of influenza:
recommendations of the Advisory Committee on Immunization Practices (ACIP),
2008. MMWR Recomm Rep 2008; 57(RR-7):1–60.
2. D’Heilly SJ, Janoff EN, Nichol P, Nichol KL. Rapid diagnosis of in- fluenza infection
in older adults: influence on clinical care in a routine clinical setting. J Clin Virol
2008; 42:124–8
3. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus
standard-dose influenza vaccine in older adults. N Engl J Med. 2014 Aug 14.
371(7):635-45
4. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E.
Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev.
2010 Jul 7. CD001269
5. Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis. 2006 Jan.
12(1):9-14
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015
BIDS-7 dan BAMHOI-3, Widhya Sabha, Denpasar 21 November 2015