The Flu Types

Influenza, or flu,
is a respiratory infection caused by several flu viruses.
Flu viruses are classified as types A, B, and C;
(type A has a number of subtypes).

The flu is not the same as the common cold,

nor is it related commonly called the “stomach flu.”
 Perbandingan tipe virus Flu
TYPE A TYPE B TYPE C

severity of illness ++++ ++ +

animal reservoir yes no no
human pandemics yes no no
human epidemics yes yes no (sporadic)
antigenic changes shift, drift drift drift
segmented genome yes yes yes
amantadine, rimantidine sensitive no effect no effect
zanamivir sensitive sensitive
surface glycoproteins 2 2 (1)

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 Penyebab Penyakit

Tiga tipe virus influenza yang dikenal yaitu:

A, B dan C.

1. Tipe A terdiri dari 3 subtipe (H1N1, H2N2 dan

H3N2) yang dikaitkan dengan terjadinya
epidemi dan pandemi yang luas.
2. Tipe B jarang sekali menyebabkan terjadinya
KLB regional atau yang menyebar luas
3. Tipe C dikaitkan dengan timbulnya kasus
sporadis dan KLB kecil yang terlokalisir
 Kerentanan dan Kekebalan

1. semua anak dan orang dewasa rentan

2. Infeksi menimbulkan kekebalan terhadap virus
specific
3. lamanya antibodi bertahan dan luasnya spektrum
kekebalan tergantung pada tingkat perubahan
antigen dan banyaknya infeksi sebelumnya
 Identifikasi Penyakit

1. Influenza adalah penyakit virus akut yang menyerang

saluran pernafasan ditandai timbulnya demam, sakit
kepala, mialgia, lesi, coryza, sakit tenggorokan dan batuk
2. Penyakit ini sembuh dalam waktu 2-7 hari
3. Gambaran klinis Common cold, Croup, bronchiolitis,
pneumonia
4. gejala terjadi menyertai fase pernafasan pada anak yang
terserang influenza, dan dilaporkan lebih dari 25% anak-
anak pada KLB yang terjadi di sekolah disebabkan
influenza B dan A (H1N1) mengalami gejala
gastrointestinal
 Symptoms

Fever* or feeling feverish/chills

Cough
Sore throat
Runny or stuffy nose
Muscle or body aches
Headaches
Fatigue (tiredness)
Some may have vomiting and diarrhea,
(more common in children).
TRANSMISSION
• AEROSOL
• 100,000 TO 1,000,000
VIRIONS PER
DROPLET

• 18-72 HR INCUBATION

• SHEDDING
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PERUBAHAN MUCOSA
• DECREASED
CLEARANCE

NORMAL TRACHEA
• RISK BACTERIAL
INFECTION

• VIREMIA RARE

3 DAYS INFECTION
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Lycke and Norrby Textbook of Medical Virology 1983
 Seasonal Flu
the term used to refer to the flu outbreaks that occur yearly,
(the late fall and winter).

Pandemic Flu
virulent strains of flu that spread rapidly
create a world-wide epidemic (pandemic).

Avian (Bird) Flu

the flu virus in wild aquatic birds
The virus can pass on the flu to humans.
In 1997,a virulent bird influenza had skipped the pig step
and had infected humans directly
Genetic origins of the en:2009 swine flu outbreak, 8 genes:

HA: Hemagglutinine type 1 (or H1),

swine,also in the 1918 influenza.
Catch host's cell receptors.

NA: Neuraminidase type 1 (or N1), swine,

eurasian, help start the infection.

PA: avian, north america.

PB1: human, likely from the 1993 H3N2

influenza.

PB2: avian, from north america.

NP: swine, north america.

M: swine, eurasia.

NS: swine, north america.

Source: La fiche d'identité d'un virus inédit, LEMONDE.FR, 30.04.2009.
 Flu Complications

Most people recover in a few days to less than two weeks,

Pneumonia, bronchitis, and sinus and ear infections
Chronic health problems worse.
asthma may experience asthma attacks
chronic congestive heart failure may have worsening

People at Higher Risk

higher risk of developing serious flu-related complications.
1. 65 years and older,
2. chronic medical conditions
(such as asthma, diabetes, or heart disease),
pregnant women, and young children.
 TYPES OF INTERFERON
TYPE I
Interferon-alpha
(leukocyte interferon, about 20 related proteins)
- leukocytes, etc
Interferon-beta
(fibroblast interferon)
- fibroblasts, epithelial cells, etc
TYPE II
Interferon-gamma (immune interferon)
- certain activated T-cells, NK cells

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 INDUCTION OF INTERFERON

interferon-alpha and interferon-beta

- viral infection (especially RNA viruses),
- double stranded RNA, certain bacterial components
- strong anti-viral properties

interferon-gamma
- antigens, mitogenic stimulation lymphocytes

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 interferon-alpha, interferon-beta
interferon receptor

induction of induction of induction of a

2’5’oligo A synthase ribonuclease L protein kinase

ds RNA 2’5’oligo A ds RNA

activated activated activated

2’5’oligo A synthase ribonuclease L protein kinase

ATP ATP

phosphorylated initiation factor

2’5’oligo A
(eIF-2)

mRNA degraded inhibition of protein synthesis

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INTERFERON

20
INTERFERON

antiviral state

antiviral state antiviral state

antiviral state
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INTERFERON

antiviral state

antiviral state antiviral state

antiviral state
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INTERFERON

antiviral state

antiviral state antiviral state

antiviral state
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INTERFERONS

only made when needed

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OTHER EFFECTS OF INTERFERONS
ALL TYPES
• INCREASE MHC I EXPRESSION
• CYTOTOXIC T-CELLS

• ACTIVATE NK CELLS
• CAN KILL VIRALLY INFECTED CELLS

INTERFERON-GAMMA
INCREASES MHC II EXPRESSION ON APC
HELPER T-CELLS
INCREASES ANTIVIRAL POTENTIAL OF MACROPHAGES
INTRINSIC
EXTRINSIC
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 THERAPEUTIC USES OF INTERFERONS
ANTI-VIRAL
e.g. interferon-alpha is currently approved for certain cases of acute and chronic HCV
and
chronic HBV

MACROPHAGE ACTIVATION
interferon-gamma
e.g. lepromatous leprosy, leishmaniasis, toxoplasmosis

ANTI-TUMOR
used in e.g. melanoma, Kaposi’s sarcoma, CML

MULTIPLE SCLEROSIS
interferon-beta

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VIRAL RESPONSE TO HOST IMMUNE SYSTEM

Viruses may :
1.block interferon binding
2.inhibit function of interferon-induced proteins
3.inhibit NK function
4.interfere with MHC I or MHC II expression
5.block complement activation
6.inhibit apoptosis, etc!

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SIDE EFFECTS OF INTERFERONS

• FEVER
• MALAISE
• FATIGUE
• MUSCLE PAINS

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PROTECTION AGAINST RE-INFECTION

• IgG and IgA

• IgG less efficient but lasts longer

• antibodies to both HA and NA important

• antibody to HA more important (can neutralize)

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PULMONARY COMPLICATIONS

• CROUP (YOUNG CHILDREN)

• PRIMARY INFLUENZA VIRUS PNEUMONIA
• SECONDARY BACTERIAL INFECTION
• Streptococcus pneumoniae
• Staphlyococcus aureus
• Hemophilus influenzae

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 NON-PULMONARY COMPLICATIONS
• myositis (rare, > in children, > with type B)
• cardiac complications
• recent studies report encephalopathy
• studies of patients <21 yrs in Michigan - 8 cases
seen last season
• liver and CNS
• Reye syndrome
• peripheral nervous system
• Guillian-Barré syndrome
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 REYE’S SYNDROME
• liver - fatty deposits
• brain - edema
• vomiting, lethargy, coma
• risk factors
• youth
• certain viral infections (influenza, chicken pox)
• aspirin

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 GUILLIAN-BARRÉ SYNDROME
• 1976/77 swine flu vaccine
• 35,000,000 doses
• 354 cases of GBS
• 28 GBS-associated deaths
• recent vaccines much lower risk

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MORTALITY

• MAJOR CAUSES OF INFLUENZA VIRUS-

ASSOCIATED DEATH
• BACTERIAL PNEUMONIA
• CARDIAC FAILURE
• 90% OF DEATHS IN THOSE OVER 65 YEARS OF
AGE

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 DIAGNOSIS
• ISOLATION
• NOSE, THROAT SWAB
• TISSUE CULTURE OR EGGS
• SEROLOGY
• RAPID TESTS
• provisional - clinical picture + outbreak

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WHERE DO “NEW” HA AND NA COME FROM?
• 13 types HA
• 9 types NA
• all circulate in birds
• pigs
• avian and human

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VACCINE
• ‘BEST GUESS’ OF MAIN ANTIGENIC TYPES
• CURRENTLY
• type A - H1N1
• type A - H3N2
• type B
• each year choose which variant of each subtype
is the best to use for optimal protection

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 Flu Vaccination types
Two types of vaccines:
I. The “flu shot” — an inactivated vaccine ( killed virus)
use in people older than 6 months, healthy people and
chronic medical conditions.
Three different flu shots available:
1.a regular flu shot (ages 6 months and older)
2.a high-dose flu shot (people 65 and older),
3.an intradermal flu shot (people 18 to 64 years) .
II.The nasal-spray flu vaccine
( LAIV - “Live Attenuated Influenza Vaccine”).
The nasal spray vaccine do not cause the flu.
use in healthy people 2 through 49 years of age not pregnant.
The single best way is vaccinated each year.
 FLU VACCINE.
who are not at risk for severe illness from influenza
should generally not receive vaccine.

1.A flu vaccine is needed every year

because flu viruses are constantly changing.

2.The flu vaccine is formulated each year

to keep up with the flu viruses as they change.

3.The body’s immunity to influenza viruses

( natural infection or vaccination) declines over time.

4.Getting vaccinated each year

provides the best protection against influenza
 CONTRA INDICATION FLU VACCINE.

1. a severe allergy to chicken eggs.

2. a severe reaction to an influenza vaccination.
3.Children younger than 6 months of age
4. a moderate-to-severe illness with a fever
(they should wait until they recover to get
vaccinated.)
5. with a history of Guillain–Barré Syndrome
(a severe paralytic illness, also called GBS)
 Vaccine Side Effects

The flu shot VACCINE

The viruses in the flu shot are killed (inactivated),
Some minor side effects :
Soreness, redness, or swelling where the shot was given
Fever (low grade),Aches

LAIV (FluMist®)
runny nose,headache.sore throat,cough
 RECOMMENDATIONS
Persons at High Risk for Influenza-Related Complications
· $ 65 years
· residents of nursing homes and other chronic-care facilities
· adults/children who have chronic pulmonary or cardiovascular
disorders, including asthma
· adults/children required regular medical follow-up or hospitalization
during the last year because of chronic metabolic diseases (including
diabetes mellitus), renal dysfunction, hemoglobinopathies, or
immunosuppression (including immunosuppression caused by
medications)

· children and teenagers (6 mths to 18 yrs) receiving long-term aspirin

therapy - be at risk for Reye syndrome after influenza
· women who will be in the 2nd or 3rd trimester of pregnancy
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 RECOMMENDATIONS
Persons aged 50-64 years
increased prevalence of high-risk conditions
easier to target by age than by high-risk condition
(which may not have been discovered)

physicians, nurses, and other personnel hospital and outpatient-care

employees of nursing homes and chronic-care facilities who have contact with
patients or residents
employees of assisted living and other residences for persons in high-risk
groups
persons who provide home care to persons in high-risk groups
household members (including children) of persons in high-risk groups.

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 RECOMMENDATIONS

• others, including travellers and the general

population may wish to be vaccinated

Children from 0-23 mths are at increased risk for

hospitalization from influenza, vaccination is
encouraged for their household contacts and out-of-
home caretakers, particularly for contacts of children
aged 0–5 months because influenza vaccines have not
been approved for use among children aged <6 months.

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 Upaya pencegahan

1. penyuluhan kepada masyarakat dan tenaga

pelayanan kesehatan tentang kebersihan
perorangan saat batuk

2. Imunisasi vaksin virus tidak aktif memberikan

70%-80% perlindungan terhadap infeksi pada
orang dewasa muda
 Pengawasan penderita, kontak dan
lingkungan sekitarnya

1. laporan terjadinya KLB dan konfirmasi

laboratorium membantu surveilans penyakit
2. Isolasi: Tidak dilakukan karena tidak praktis
oleh keterlambatan diganosa
3. Pemberian obat kemofrofilaksis seperti
amantadine atau rimantadine cukup
bermanfaat terhadap strain tipe A
 Penanggulangan Wabah

1. penyuluhan kesehatan dan membuat

perencanaan kesehatan yang efektif
2. Manajemen rumah sakit mengantisipasi
peningkatan kebutuhan akan pelayanan
kesehatan lainnya selama masa
berlangsungnya wabah
3. Penyediaan obat antiviral dalam jumlah yang
cukup mengobati penderita yang berisiko
tinggi
Implikasi Bencana
Apabila orang berada pada
lingkungan hunian yang
berdesakan maka begitu virus
influenza masuk maka akan
terjadi KLB
Tindakan Internasional
1. Laporkan apabila terjadi wabah
(epidemic) disuatu negara kepada
WHO.
2. Sebutkan jenis virus penyebab
terjadinya KLB/wabah pada
laporan dan kumpulkan 4
prototype dari strain
3. Lakukan studi epidemiologi dan
laporkan virus penyebab dengan
segera kepada otoritas kesehatan
4. tersedia fsilitas pemerintah dan
atau fasilitas swasta yang
memadai untuk penyediaan
vaksin dan obat antiviral dalam
jumlah yang cukup
TREATMENT - DRUGS
• RIMANTADINE (M2)
• type A only, needs to be given early
• AMANTADINE (M2)
• type A only, needs to be given early
• ZANAMIVIR (NA)
• types A and B, needs to be given early
• OSELTAMIVIR (NA)
• types A and B, needs to be given early
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