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HEPATITIS A

VIRUS

Prof. Dr. dr. Efrida Warganegara,


M.Kes., Sp.MK
HEPATITIS
VIRUS
1. Hepatitis Virus A
2. Hepatitis Virus B
3. Hepatitis Virus C
4. Hepatitis Virus D
5. Hepatitis Virus E
6. Hepatitis Virus F
7. Hepatitis Virus G
8. T T Virus
Introduction
Hepatitis means inflammation and damage to the
liver, and can be caused by infection by various
organism, inclufing bacteria (leptospira sp.), viruses
(hepatitis A, B, dan C), or parasites (Schistosoma
mansoni)
Viruses are the most common infectious causess of
hepatitis. at least 5 different viruses are referred to as
Hepatitis virus, and they generally cannot distinguish
clinically
The disease may manifest as acute hepatitis (hepatitis
A, B, or E) or chronic hepatitis (hepatitis B or C).
In hepatitis B or C infection, progressive liver damage,
liver failure, or even liver cancer may result.
KEY CONCEPTS

Display marked tropism for liver


cells
Use either :
hit & run infectious strategy
(Hepatitis virus A & E)
results in acute infection that is
cleared by the immune system
hide & infiltrate strategy
(Hepatitis virus B, C, Delta, G)
lead to chronic infection
KEY CONCEPTS
Cause similar symptoms during
the acute stage of infection that
result of liver damage
Can be identified by testing for
presence of specific viral proteins,
specific antibodies against these
proteins or viral nucleic acid
Can be treated with agents such
as interferon, however treatment
for chronic carriers of hepatitis B,
C, D and G generally ineffective
Vaccine exist : A & B
Viral Hepatitis - Historical
Perspectives
Infectious Enterically
/ Catarrhal A E
E transmitted

Viral hepatitis NANB

Serum B
B D
D C Parenterally
transmitted

F, G, TTV
? other
Virus Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Family Picornaviridae Hepadnaviridae Flaviviridae None Caliciviridae
Genus Hepatovirus Orthohepadna eHep-c-virus Deltavirus
virus (Unnamed)
Virion Icosahedral Spherical, Spherical, Spherical, Icosahedral,
27 nm 42 nm 30-60 nm 35 nm 27-34 nm
Envelope No Yes (HBsAg) Yes Yes(HBsAg) No
Genome ssRNA dsDNA ssRNA ssRNA ssRNA
Size 7,8 kb 3,2 kb 9,4 kb 1,7 kb 7,5 kb
Stability Heat & acid Acid-sensitive Eter-sensitive Acid-sensitive Heat-stable
stable Acid-sensitive
Transmission Faecal-oral Parenteral Parenteral Parenteral Faecal-oral
Prevalence High High Moderate Low, Regional
regional
Fulminant Rare Rare Rare Rare In
disease pregnancy
Chronic Never Often Often Often Never
disease
Oncogenic No Yes Yes ? No
General symptoms of hepatitis virus
infection
Acute inflammation chronic

Prodromal signs :
Fever
Gastrointestinal symptoms
Jaundice/ icteric
Hepatitis virus type A
Hepatitisenteric
virus type E
Hepatitis
acutevirus type B
parenteral
Hepatitis virus type C
chronic
Hepatitis virus type D
cirrhosis
Hepatitis virus type G
hepatocellular-Ca
Introduction
Thedisease picture is a febrille illness of
prolong duration marked by jaundice, fatique
and malaise, abdominal pain, loss of appetite,
anorexia and nausea,
Chronic hepatitis can be associated with a
rash, due to immune complex-associated
vasculitis, and with arthritis.
Common risk factor include eating
contaminated seafood (hepatitis A), multiple
sexual partners unprotected intercouse
(hepatitis B), intravenous drug use (hepatitis
C), or blood transfusion.
HEPATITIS ACUTE
ASYMPTOMATIC
FULMINANT
Severity of the disease depend on :
* virus type
* individual
More than cases asymptomatically

Chronic hepatitis symptoms exist


increasing enzyme levels
> 6 months
Chronic persistent chronic active hepatitis
(mild)

Enzymes levelcirrhosis
Normal hepatic failure
hepatocellular-Ca
Introduction
Clinical diagnosis on the basis of jaundice must
be confirmed by 1) liver function test : level of
serum aminotransferase, bilirubin and alkaline
phosphatase; and 2) hepatitis serologis : virus-
specific antigen and antibody markers in serum.
Dramatic elevation of serum aminotransferase
(alanine dan aspartat aminotransferas) are
characteristic of acute viral hepatitis
Specific laboratory test for hepatitis A and B
viruses have been available for some years,
originally referred to as nonA-nonB viruses are
now becoming available.
Introduction
More than half the liver must be damaged or
destroyed before liver function fails.
Regeneration of liver cells is rapid but fibrous
repair, especially when infection persist can lead to
cirrhosis
Managemen is mostly symptomatic,
Except in the cases of hepatitis A and B, there are
no licensed vaccine, and
although specific treatments are available chronic
stage of hepatitis B and C (e.g. interferron), there
are no specific treatmens for this disease.
Chronic hepatitis C is the most common cause of
liver failure and subsequent liver transplantation
Control
Screening blood
donor for hepatitis
viruses B, C
Immunization (active
or passive)
Treatment :
Interferon
HEPATITIS A VIRUS (HAV)
Discovered by Cockayne tahun 1912
Cause infectious hepatitis, acute
Formerly called : Infectious hepatitis
A distinct member of the Picornaviridae
family (previously Enterovirus 72), a new
genus : Hepatovirus
Only 1 serotype
27 32 nm, spherical particle, cubic
symetry
Containing a linear ss-RNA genome with a
size 7.5
kb, surround by capsid consist of 4
Virus stability :
Virus is destroyed by :
Autoclaving 121oC, 20 minutes
Boiling in water for 5 minutes
Oven (dry heat 1800C), for 1 hour
UV irradiation, 1 minute at 1,1 watts
Treatment with formalin 1 : 4000 for
3 days at
370C or chlorine 10 15 ppm, 30
minutes
Stable to treatment with 20% ether,
acid (pH 1.0
for 2 hours)
Infectivity can be preserved
Sign and Symptoms
The most likely mode of transmission : fecal-
oral route through close personal contact
Acute infection, incubation period 2 6 weeks
Hepatitis A : accute illness with no chronic form
or carrier state
Older children and adults develop jaundice,
fever, fatique, clay-color fices, and vomiting after
incubation period of about 1 month
Most young children (< 6 years old) and many
older children (ages 6-14) are asymptomatic
About one in five infected adult requires
hospitalization
Patient generally recover within 2 months, but
some take up to 6 months
Pathogenesis
Following ingestion, the virus
reaches the liver by unknown route.
The liver is the main site of
replication and the only tissue
known to be damaged by the
infection
The virus is released into the bile
and eliminated with the feces.
Epidemiology
Hep. A virus spread by fecal-oral
route, principally via fecal-
contaminated hand, food, or water
Many outbreak have been traced to
restaurant where infected food-
handler failed to wash their hands
Raw sellfish are also a frequent
source of infection because they
concentrate the virus from fecally
polluted sea-water.
Epidemiology
Group at high risk of contracting the
disease :
- children in day care centers
- resident in nursing homes
- international travelles, and
- individual having sexual contact with an
infected person
Because incubation periode averages 30
days, HAV can spread widely through a
population before being detected.
Infected infant and children can shed the
virus in their feces for several months
Treatment and
Prevention
No antiviral treatment for HAV is available
However, immune globulin can be given by
injection after exposure
This passive immunization gives short-term
protection against the disease if administered
within 2 weeks.
An effective vaccine, 1995, recommended :
- all children 1 years of age
- several high-risk group people travelling to
area
of high incidence, or
- in occupations that put them at high risk of
exposure
LABORATORY DIAGNOSIS

Virus particles have been detected


by immune electron microscopy in
fecal extracts of
hepatitis A patients

Virus appears early in the disease,


and disappears within 2 weeks
following onset
of jaundice

HAV can be detected in the liver,


stool, bile, and blood of naturally
infected humans and experimental
Serology :
IgM specific anti-HAV fraction
appears during the acute phase
peaking about 2
weeks after elevation of liver
enzyme
Anti-HAV IgM usually decline to
undetectable levels within 3 6
months
Anti-HAV IgG appears soon after the
onset of the disease and eventually
replace IgM
IgG persist for decades
Methods for measuring Ab :
- RPHA - ELISA -R I A
HEPATITIS B VIRUS
(HBV)
Discovered by Blumberg
(1923)
Patients & aborigin

Australian Ag.
Cause serum hepatitis
Australian antigen
HBV Morphology
Structure & antigen
complex
3 shapes in serum
. Dane particles : 42
nm
. Spherical particles :
Hepatitis B virus particle
22 nm
. Filament particles :
22 nm
Virion 42 nm Nucleus Lysis nucleus
HBsAg / Dane virion 28 nm
virion (HBeAg)
particle HBcAg
Antigen structure :

1. HBsAg Anti-
HBs

2. HBcAg Anti-
HBc
STABILITY
Temperature 20oC more than
20 years
Dry, 25oC stay for 1 week
Temperature 100oC, 1 minute
pH 2,4 for 6 hours
Sodium hypochlorite 5% for 3
minutes
Attachment

Reenter cycle
Uncoating

Host DNA repair AAA Positive-


AAA
AAA strand
cccDNA DNA
mRNA synthesis
Nucleus

Translation
Encapsidation Negative-strand
DNA synthesis
Cytoplasm
3.5 kb RNA

HBV replication cycle


MODE OF
TRANSMISSION

- Parenteral

- Mucosal (per oral &


sexual contact)

- Vertically from
Laboratory examination

Isolation : cell culture


difficult
Diagnosis :
Serology (Ag Ab)
Transaminase enzyme
(LFT)
Histology (biopsy)
PCR (molecular)
Electron Microscopy
SEROLOGICAL INTERPRETATION OF HBV

INFECTION
Results Interpretation
HBsAg (+) Hepatitis B infection active, acute/ chronic
Anti-HBs (+) Protection to reinfection (immunity)
HBsAg (-) (+) after > 16 weeks, persist for years
Anti-HBc (+) Might be HBV active infection
Anti-HBs (-) Should be confirm IgM anti-HBc, 3 months
Total anti-HBc persist 5-6 years
HBeAg (+) Infectious active hepatitis, acute / chroni
HBsAg (+) Potential infectious
Anti-HBe (+) Non infectious blood
Carrier state
Prevaccination screening hepatitis B
HBsAg (+) HBsAg (-) HBsAg (-) HBsAg (-) HBsAg (-)
Anti-HBs (-) Anti-HBs (-) Anti-HBs (+) Anti-HBs (+) Anti-HBs (-)
Anti-HBc (-/+) Anti-HBc (+) Anti-HBc (+/-) Anti-HBc (+/-) Anti-HBc (-)
Titer > 10 mU/ml Titer < 10 mU/ml

No Postpone No Booster Vaccination


Vaccination vaccination vaccination

LFT Check Measure titer Measure titer Measure titer


examination anti-HBs anti-HBs anti-HBs anti-HBs
3-6 months
Typhoid Fever

Oleh :

Prof. Dr. dr. Efrida Warganegara, M.Kes., Sp.MK


SALMONELLA
* Genus Salmonella bersifat :
- Bergerak, Non-fermentasi
laktosa, Batang Gram Negatif
* Kebanyakan spesies
diidentifikasi dgn
produksi : asam, gas dan
H2S dari glukosa
* Parasit saluran pencernaan
pada manusia dan hewan
SALMONELLA
Genus Salmonella menyebabkan :
1. Typhoid fever / Enteric fever / Typhus
Abdominalis : adalah penyakit
sistemik dan berat yang
disebabkan oleh S.typhi, S.paratyphi

2. Gastroenteritis atau keracunan


Makanan disebabkan oleh :
S.typhimurium, S.enteritidis
3. Penyakit Septikaemia
(extraintestinal) dsebabkan o/
bnyk spesies Salmonella
SALMONELLA
Sensitivity and survival
* M.o. dapat hidup dlm air dan makanan
utk waktu berminggu-minggu
* M.o. dibunuh oleh temperatur 60 0 C in
15 20 menit; desonfektas, dan khlorin
* Struktur antigenik : M.o. mempunyai
Antigen somatik ( O )
Antigen flagelar ( H )
Antigen virulen ( Vi )
SALMONELLA
Faktor Pathogenisitas
* Memproduksi endotoxin
(lipopolysaccharide); yang menyebabkan
demam, leukopeni, hemorrhagi, hipotensi
& shock
* Memproduksi eksotoksin atau enterotoksin
* Terutama menginfeksi man., masuk mel.
oral (mak. & min. terkontaminasi)
* Faktor tubuh yang menyebabkan resisten
thdp Salmonella : asam lambung, flora
normal usus, imunitas usus lokal
SALMONELLA
Transmission
Sumber : Carrier dan Pend. Typhoid fever
faeces fluid; flies people food
fingers
Penyakit Klinik :
1. Typhoid fever / Enteric fever / Typhus
abdominalis :
- terjadi mel. masuknya makanan dan air;
biasanya dikontaminasi dari carrier atau
pend. Typhoid fever
- selama periode inkubasi 7-10 hari m.o.
akan multiplikasi didalam usus kecil
SALMONELLA
1. Typhoid fever : (lanjutan)
- masuk kedlm pemb. limpe usus dan ke
aliran darah. Lalu dibawa ke berbagai organ
termasuk usus
- terjadi multiplikasi di jar. Limpe usus dan
dikeluarkan dlm feses
- Sesudah inkubasi 10-14 hr, timbul gejala
malaise, sakit kepala, demam naik turun,
constipasi, bradycardi & myalgia, rose spot
dpt terlihat pd kulit dada & perut, dalam
minggu ke-2 sp ke-3
SALMONELLA
1. Typhoid fever : (lanjutan)
- Khas penyakit ini terjadi 3-5 minggu
- komplikasi utama : perdarahan
gastro- intestinal & perforasi usus
dengan peritonitis
- Setelah penyembuhan, 3 %
penderita menjadi carrier, m.o.
terdapat di kandung empedu dan
salurannya
- Angka kematian sekitar 10%
SALMONELLA
Diagnosis
Spesimen dari :
- darah (+) pd mgg ke-1
- urine (+) pd mgg ke-2
- Sumsum tlg mgkn membantu
- feses (+) pd mgg ke- 2 dan 3
- drainase deodenum
mengetahui adanya m.o. dlm
kandung empedu pada carrier
SALMONELLA
Kultur :
- Pada medium diferensial EMB,
MacConckey, deoxycholate agar (mengetahui
nonfermentase laktose). Bismuth sulfid
medium (koloni hitam ok produksi gas H2S)
- Pada selektif medium SS agar, Hectoen
enteric agar, XLD, deoxycholate-citrat agar
- Pada enrichment medium Selenit F,
tetrathionat broth sesudah itu ditanam
pada medium diferensial dan selektif
- Baru diuji biokimiawi
SALMONELLA
Test serologis :
Utk identifikasi kultur yg tdk dik dgn
serum yg dik.
1.Test agglutinasi :
- Serum dik + kultur yg tdk dik
clumping dlm bbp menit
2.Test Tube Dilution Agglutination (Widal )
- serum agglutinin timbul mgg ke-2 3
- paling tidak diperiksa serum 2 kali
interval 7-10 hari
SALMONELLA
Interpretasi Hasil :
1. Titer O tinggi atau meningkat
( 1:160) ada infeksi
aktif
2. Titer H tinggi ( 1:160) post
imunisasi atau post infeksi
3. Titer antibody tinggi thdp Vi Ag
terjadi pd carrier
SALMONELLA
Clinical specimens :
bile culture microscopic exam
24 48 hr fermentation
test glucose
Mc Conkey colony Lactose

Maltose
Saccharose
motility test
agglutination test
SALMONELLA
Serology : Widal
1/20 1/40 1/80 1/160 1/320
O + + - - -
H + - - - -
Vi + - - - -

O + + + + -
H + - - - -
Vi + - - - -
showing increasing titers of O ( 4x )
SALMONELLA
Kekebalan :
- Infeksi dgn S. typhi & S. paratyphi
biasanya memberikan derajad
kekebalan tertentu
- Reinfeksi sering terjadi tapi dgn gejala
lebih ringan dari infeksi pertama
- Adanya antibodi terhadap O dan Vi
dlm darah berhubungan dgn derajad
kekebalan thdp infeksi & penyakit.
- Relaps mungkin dlm 2-3 mggsesudah
penyembuhan
- Ab thdp IgA secretory mencegah
penempelan m.o. pada epitel usus
SALMONELLA
Pencegahan dan
Pengobatan
Pencegahan :
melalui peningkatan higiene
perorangan & sanitasi; pengobatan
carrier & vaksinasi
Pengobatan
obat pilihan adalah chloramphenicol;
trimethoprim-sulfamethoxazole &
amoxycillin juga efektif terhadap
kebanyakan strain
Terima
Kasih