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.”

The Flu Types

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TYPE A

++++yesyesyesshift, driftyessensitivesensitive2

severity of illnessanimal reservoirhuman pandemicshuman epidemicsantigenic changessegmented genomeamantadine, rimantidinezanamivirsurface glycoproteins

TYPE B

++nonoyesdriftyesno effectsensitive2

TYPE C

+nonono (sporadic)driftyesno effect

(1)

Perbandingan tipe virus Flu

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

specific3. 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 hari3. Gambaran klinis Common cold, Croup, bronchiolitis,

pneumonia4. 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

Fever* or feeling feverish/chillsCoughSore throatRunny or stuffy noseMuscle or body achesHeadachesFatigue (tiredness)Some may have vomiting and diarrhea, (more common in children).

Symptoms

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TRANSMISSION

• AEROSOL• 100,000 TO 1,000,000

VIRIONS PER DROPLET

• 18-72 HR INCUBATION

• SHEDDING

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• DECREASED CLEARANCE

• RISK BACTERIAL INFECTION

• VIREMIA RARE

Lycke and Norrby Textbook of Medical Virology 1983

NORMAL TRACHEA

3 DAYS INFECTION

PERUBAHAN MUCOSA

Seasonal Flu

the term used to refer to the flu outbreaks that occur yearly, (the late fall and winter).

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

Avian (Bird) Fluthe 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.

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

Flu Complications

People at Higher Riskhigher 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.

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TYPES OF INTERFERON

TYPE IInterferon-alpha (leukocyte interferon, about 20 related proteins)

- leukocytes, etcInterferon-beta (fibroblast interferon)

- fibroblasts, epithelial cells, etcTYPE 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 2’5’oligo A synthase

induction of aprotein kinase

2’5’oligo A

induction of ribonuclease L

activated ribonuclease L

ATP

ds RNA ds RNA

activatedprotein kinase

activated2’5’oligo A synthase

ATP

2’5’oligo A

mRNA degraded

phosphorylated initiation factor (eIF-2)

inhibition of protein synthesis

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INTERFERON

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INTERFERON

antiviral stateantiviral state

antiviral state

antiviral state

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INTERFERON

antiviral stateantiviral state

antiviral state

antiviral state

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INTERFERON

antiviral stateantiviral state

antiviral state

antiviral state

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INTERFERONS

only made when needed

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OTHER EFFECTS OF INTERFERONSALL TYPES• INCREASE MHC I EXPRESSION

• CYTOTOXIC T-CELLS

• ACTIVATE NK CELLS• CAN KILL VIRALLY INFECTED CELLS

INTERFERON-GAMMAINCREASES MHC II EXPRESSION ON APC

HELPER T-CELLSINCREASES ANTIVIRAL POTENTIAL OF MACROPHAGES

INTRINSICEXTRINSIC

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THERAPEUTIC USES OF INTERFERONSANTI-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

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 Vaccination types

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

FLU VACCINE.who are not at risk for severe illness from influenza should generally not receive 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)

CONTRA INDICATION FLU VACCINE.

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

LAIV (FluMist®) runny nose,headache.sore throat,cough

Vaccine Side Effects

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RECOMMENDATIONSPersons 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

physicians, nurses, and other personnel hospital and outpatient-care employees of nursing homes and chronic-care facilities who have contact with patients or residentsemployees of assisted living and other residences for persons in high-risk groupspersons who provide home care to persons in high-risk groups household members (including children) of persons in high-risk groups.

Persons aged 50-64 yearsincreased prevalence of high-risk conditionseasier to target by age than by high-risk condition (which may not have been discovered)

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RECOMMENDATIONS

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.

• others, including travellers and the general population may wish to be vaccinated

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 Tindakan Internasional

Apabila orang berada pada lingkungan hunian yang berdesakan maka begitu virus influenza masuk maka akan terjadi KLB

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

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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