Viral Infections

Gastro- Hepatic

Betty Suryawati
MD., MBiomedSc., PhD

Department of Microbiology,
Faculty of Medicine
Universitas Sebelas Maret
 Introduction
• Viral diseases is still one of the major causes of
morbidity and mortality
• The emergence of new viruses that affect human
• Virus affecting all the major tissue and systems in
human body
•  infection in Gastro-hepatic-pancreatic system
Gastrointestinal tract
 Viral Gastroenteritis
• Viral gastroenteritis  inflammation of the lining of the
stomach, small intestine, and large intestine.

• Several different viruses can cause viral gastroenteritis

highly contagious
(Rotavirus, norovirus (calciviruses), adenovirus, astrovirus)
• The New: Potential Pathogenic Viruses in the Gastrointestinal
Tract Aici Virus (Picornaviridae), Toroviruses (Coronaviridae)
Diarrhea

• Most viral infection  recover without any complications

unless become dehydrated
Viral Infection
 An overview of how the commensal microbiota influence viral pathogenesis.

Wilks J, Golovkina T (2012) Influence of Microbiota on Viral Infections. PLOS Pathogens 8(5): e1002681.
https://doi.org/10.1371/journal.ppat.1002681
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1002681
 What are the symptoms of viral
gastroenteritis?
• The main symptoms
– watery diarrhea
– vomiting
– Headache, fever, chills, abdominal pain
• Symptoms usually appear within 12 to 48 hours after exposure to a
gastroenteritis causing virus and last for 1 to 3 days.

• Dehydration symptoms:
– extreme thirst and dry mouth
– urinating less than usual
– feeling tired
– dark-colored urine
– decreased skin turgor, meaning that when a person’s skin is pinched and
released, the skin does not flatten back to normal right away
– sunken eyes or cheeks
– light-headedness or fainting
 What are the complications of viral
gastroenteritis?

• Dehydration is the most common complication

of viral gastroenteritis.
• Does not drink enough fluids to replace those
that are lost through vomiting and diarrhea
dehydration  imbalanced electrolytes.
• Infants, young children, older adults, and people
with weak immune systems have the greatest risk
of becoming dehydrated.
What causes viral gastroenteritis?

• Rotavirus and
noroviruses are shed
in stool as viral
clusters inside
vesicles
• Vesicles containing
virus clusters remain
intact during faecal-
oral transmission
• Vesicles achieve a
high multiplicity of
infection  induce
severe disease
 Rotavirus

Transmission electron micrograph of

rotavirus virions (viral particles).

• Rotaviruses are non-enveloped, double-shelled viruses.

• The genome is composed of 11 segments of double-stranded RNA, which code
for six structural and five nonstructural proteins.
• The virus is stable in the environment.
 Rotavirus infection : Clinical Symptoms
• Rotavirus is the leading cause of gastroenteritis
among infants and young children.
• Rotavirus infections are most common in infants 3 to
15 months old.
• Symptoms usually appear 1 to 3 days after exposure.
• Rotavirus typically causes vomiting and watery
diarrhea for 3 to 7 days, along with fever and
abdominal pain.
• Rotavirus can also infect adults who are in close
contact with infected children, but the symptoms in
adults are milder.
 Rotavirus: transmission
• People who are infected with rotavirus shed the virus
in their stool (poop).
• This is how the virus gets into the environment and
can infect other people.
• Prevention Good hygiene like hand washing and
cleanliness
 Rotavirus : Vaccine
• Rotavirus vaccines:
– RotaTeq® (RV5) is given in 3 doses at ages 2 months, 4
months, and 6 months
– Rotarix® (RV1) is given in 2 doses at ages 2 months and 4
months

• Children, even those who are vaccinated,

may get infected and sick from rotavirus
more than once. natural infection with
rotavirus nor vaccination provides full
protection from future infections.
• Children who are not vaccinated usually
have more severe symptoms the first
time they get rotavirus disease.
 Caliciviruses- Norovirus
• Caliciviruses cause infection in
people of all ages.
• Norovirus is the most
common calicivirus and the
most common cause of viral
gastroenteritis in adults.
• Norovirus is usually
responsible for epidemics of
viral gastroenteritis.
• Symtoms  nausea, vomiting,
diarrhea, abdominal cramps,
fatigue, headache, and muscle
aches. Highly
contagious,
• The symptoms usually appear vomiting,
1 to 2 days after exposure to diarrhea,
the virus and last for 1 to 3 fever
days.
 Enteric Adenovirus
• Fastidious enteric adenovirus types 40
(20%) and 41 (40%-80%) are associated
with gastroenteritis.
• Associated with cases endemic
gastroenteritis, usually in children and
neonates. cause occasional outbreaks.
• Adenovirus type 40 and 41 account for
Naked DNA viruses, 75 nm
up to 20% of the worldwide cases of
in diameter. Acute diarrheal disease.
• Diagnosed by electron microscopy or by
the detection of adenovirus antigen in
feces by ELISA.
Adenovirus gastroenteritis: symptoms

• Adenovirus mainly infects children younger than 2

years old.
• causing vomiting and diarrhea.  most commonly
associated with serotypes 40 and 41
• Symptoms typically appear 8 to 10 days after exposure
and last 5 to 12 days.
• Fever and watery diarrhea are usually limited to 1-2
weeks.

Adenoviruses replicate readily in the human intestine and

may be cultured from asymptomatic individuals;  their
presence in the setting of a diarrheal syndrome may be
incidental.
 Astrovirus
• Astrovirus primarily infects
infants and young children, but
adults may also be infected.
• This virus causes vomiting and
watery diarrhea.
• Symptoms usually appear 3 to
4 days after exposure and last
2 to 7 days.
• The symptoms are milder than
Astroviruses have a positive-sense, single-
stranded RNA genome. the symptoms of norovirus or
rotavirus infections.
After astrovirus cell entry, the genomic RNA is uncoated and is then translated into a polyprotein
precursor that is subsequently cleaved into the proteins required for replication of the virus
genome and assembly of progeny viruses. These processes most likely take place in association
with cellular membranes, and completion of the virus life cycle requires the action of caspases for
the virus particles to exit the cell.
 How is viral gastroenteritis transmitted?

• Viral gastroenteritis is transmitted from person to person.

• Viruses are present in the stool and vomit of people who
are infected.
• people may contaminate surfaces, objects, food, and drinks
with viruses, especially if they do not wash their hands
thoroughly after using the bathroom.
• When an infected person with unwashed hands shakes
hands with or touches another person, the virus can
spread.
• When an infected person vomits, the virus can become
airborne.
 How is viral gastroenteritis treated?

• Most cases of viral gastroenteritis resolve over time

without specific treatment.
• Antibiotics are not effective against viral infections.
• The primary goal of treatment is to reduce symptoms
and prevent complications.
• Over-the-counter medicines such as loperamide
(Imodium) and bismuth subsalicylate (Pepto-Bismol)
can help relieve symptoms in adults.
• These medicines are not recommended for children.
 Hepatitis
• Hepatitis : inflammation of the liver
• It's commonly caused by a viral infection
(It may be caused by drugs, alcohol use, or certain medical
conditions).
• The condition can be self-limiting or can progress to
fibrosis (scarring), cirrhosis or liver cancer.
• Viral hepatitis Hepatitis A, B, and C ( and D, E).
 Viral Hepatitis A, B, C, D, E

5 Types:
A : faecal – oral transmission
B : Sexual fluids and blood to blood
C : Blood to blood
D : travels with B
E : faecal – oral transmissions
 Hepatitis A
• Hepatitis A is a virus that
causes infection and
inflammation of the liver.
• It rarely results in serious
liver damage or death and
does not develop chronic
liver disease.
The virus can survive
for a month or more in
seawater, fresh water,
wastewater, and soil.
• Picornavirus (RNA)
• Human are only natural
host
• Stable at low PH
• Inactivated by high
temperature, formalin,
chlorine
 Pathogenesis HAV
• After ingestion, the HAV survive gastric acid,
moves to the small intestine and reaches the
liver via the portal vein
• Replicates in hepatocyte cytoplasm
– Not a cytopathic virus
– Immune mediated cell damage more likely
– Once mature the HAV travels through sinusoids
and enters bile canaculi, released into the small
intestine and systemic circulation, excreted in
faeces.
 Infection hepatitis A virus (HAV)
• Common in areas of low socioeconomic status with a lack of
adequate sanitation.
• Spreads  contaminated food and water or close person-to-
person contact.
• Once a person has had it, they will have immunity.
Symptoms:
– no symptoms
– nausea, loss of appetite, and vomiting
– abdominal pain and diarrhea
– Fever
– malaise and fatique
– joint pain HAV can be fatal in older patients
and in someone who already has
– jaundice chronic liver disease.
Hepatitis A Virus
 Laboratory Diagnosis
• Acute infection detection of HAV - IgM in
serum by EIA
• Past infection, immunity is determined by the
detection of HAV - IgG by EIA
• Direct detection:
– Electron Microscopy
– RT-PCR of faeces
 Prevention
• Good hygiene practices
• Immunization
– HAV immunization of:
• all children at 1 year of age
• adults who are at risk of exposure or who have chronic
liver disorder
– Two doses of the vaccine are given as an injection, 6
to 12 months apart.
– Most people will have protective levels of antibodies
within 1 month after a single dose. The second dose
acts as a booster.
 Hepatitis B
• Hepatitis B is a viral infection, which causes inflammation of the
liver
• It is transmitted through contact with semen, blood or other body
fluids from an infected person
• Most common means of transmission: unprotected sex, sharing
needles when injecting drugs, from mother to baby around the
time of birth
• Less common means of transmission: unscreened blood or blood
products (outside Ireland), accidental needle-stick/blood
exposure in healthcare settings, household/close contact, sharing
razors or toothbrushes
• Incubation period (time from infection to onset symptoms) is 6
weeks to 6 months, average 2-3 months
Incidence Hepatitis B
 HIB classification and morphology
• Hepadnaviridae
• 42 nm DNA virus with
outer envelope and
inner core
 Pathogenesis of HVB Infection
• Absence of an Innate Response by Infected Cells
• The Adoptive Immune Response
– The antibody response to the HBV envelope antigens
– C48 T Cell Response
– CD8 T Cell Response
• Mechanism of HVB Clearance
• Mechanism of HVB persistent
– Neonatal tolerance induced by HBeAg
– (Viral mutationHBeAg may suppress immune elimination
of infected cells by HBcAg-specific T cells)
– The size of viral inoculum
Noncytopathic clearance of HBV from the hepatocyte by T cell- derived cytokines.
On antigen recognition, CD8-positive CTL deliver an apoptotic signal to their
target cells, killing them. They also secrete IFNγ and TNF-α, cytokines that abolish
viral replication and HBV gene expression in vivo, potentially curing
them. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888709/
HBeAg is secreted and accumulates in
serum as an immunologically distinct
soluble antigen.

HBcAg (core antigen) is

considered "particulate" and it does not
circulate in the blood. However, it is
readily detected in hepatocytes after
biopsy.

The presence of both HBcAg and HBeAg

proteins together act as a marker of viral
replication, and antibodies to these
antigens are a marker of declining
replication.
 Serological of viral markers
• HBsAg
– First maker to appear in the blood
– Being detectable in blood even before onset of clinical
illness
– Disappears in 2 months
– Then anti-HBs appears
– Presence of anti-HBsAg alone indicates vaccination
Acute hepatitis B virus infection
with recovery
 Serological of viral markers

• HBcAg
– Antibody appears after 1-2 weeks of appearance
HBsAg.
– Earliest antibody marker to be seen in the blood
• IgM anti-HBc : acute infection
• IgG anti-HBc : remote infection
– HBeAg
• Appears concurrently with HBsAg.
• Indicator of active intrahepatic viral replication.
• Its presence denotes high infectivity.
Heoatitis B Virus
 Epidemiology
• Natural infection occurs only in human
• No animal reservoir
• Virus is maintained in large pools of carrier
• Carrier: person with detectable HBsAg in blood for more
than six months
• Super carrier:
– High titres of HBsAg + HBeAg + DNA polymerase + HBV in
circulation
– Elevated transaminases. Highly infectious
• Simple carrier:
– Low titres of HBsAg
– Negative for HBeAg, DNA polymerase, HBV. Low infectivity
 Mode of Transmission
• Parenteral:
– Blood and blood product of carrier and patients
– HBV is highly infectious
– Objects like shared syringe, needles, sharp items, endoscopes,
razors, nail clippers, comb, acupuncture
– Direct contact with skin lesions like eczema, pyoderma, and
scratches.
• Perinatal
– Carrier mother to baby
– Mother HBeAg +, high risk
– Mother HBeAg - . Low risk
– Infection during birth
• Sexual
– Promiscuous homosexual
– Saliva, breast ,ilk, vaginal secretion, urine, bile, faeces—contain
viruses
How HBV is transmitted?
 Immunisation

• Passive : HBIG (0.5 ml IM)

• Active : HBsAg vaccine (0.1 ml IM, 0, 1 , and 6
months)
• Prophylaxis : HBIG (3000-5000 IU within 48
hours)
 Hepatitis C Virus

• Single stranded RNA virus

• Small virus (50-60 nm)
• Enveloped virus with glycoprotein spike
 Hepatitis C Infection
• Contagious liver diseases caused by Hepatitis C
virus.
• Spread by blood infected Hepatitis C virus enter
the body of non infected person.

Hepatitis C
infection
 Diagnosis Hepatitis C
• Blood testing
– Hepatitis C antibody test
– Hepatitis C PCR test to find virus in blood
• Liver function test
• Serologic Test : detect HCV antibody
– ELISA
– RIBA
• Molecular Assay : PCR, qRT-PCR
Thank You