1.

HEPATITIS A VIRUS
2. TYPHOID FEVER

Efrida Warganegara
 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 transmitted

Viral hepatitis NANB

Serum B 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 enteric
Hepatitis virus type E
acute
Hepatitis virus type B
parenteral
Hepatitis virus type C chronic
Hepatitis virus type D
cirrhosis
Hepatitis virus type G hepatocellular-Ca
 Introduction
The disease 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 level cirrhosis

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
Antiviral drugs
 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 polypeptide
: VP1 VP4, nonenveloped
Introduction vaccine in 1995 significantly lowered the
incidence of the disease
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
at least 1 month after being dried, and stores at
25oC and 42 % relative humidity
or for years at 200C
 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 infected nonhuman primates
by : PCR or Nucleic acid hybridization assay
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 HBsAg
Family Hepadnaviridae
Genus Orthohepadna virus
HBV Morphology
Structure & antigen complex
3 shapes in serum
. Dane particles : 42 nm
. Spherical particles : 22 nm
. Filament particles : 22 nm
Hepatitis B virus particle

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

3. HBeAg Anti-HBe
STABILITY
Temperature 20oC more than
20 years
Dry, 25 C stay for 1 week
o

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 mother to

baby
Laboratory examination

Isolation : cell culture difficult

Diagnosis :
Serology (Ag Ab)
Transaminase enzyme (LFT)
Histology (biopsy)
PCR (molecular)
Electron Microscopy (virus particle)
Leucopenia during pre jaundice phase
 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 600 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 )
Kekebalan :
SALMONELLA
- 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