Viral Agents of

Gastroenteritis and Hepatitis

dr. A. R. Sultan, DMM., M.Sc., Ph.D., Sp.MK.

Department of Microbiology
Faculty of Medicine Hasanuddin University
2024
Sasaran pembelajaran

• Mampu mengaplikasikan pengetahuan dasar tentang etiologi dan

patomekanisme dalam menjelaskan timbulnya tanda dan gejala
pada kasus viral gastroenteritis and hepatitis

• Mampu mengidentifikasi faktor risiko yang berhubungan dengan

kasus viral gastroenteritis and hepatitis

• Mampu menentukan jenis spesimen dan meminta pemeriksaan

penunjang lab mikrobiologi klinik yang relevan untuk menunjang
diagnosis viral gastroenteritis and hepatitis
Global causes of death in children
in 2021

adolescents aged 5–19 years

younger than 5 years Vilaveciencio, F. et al. 2024. The Lancet Global Health.
Percentage of deaths caused by diarrhoea in children under 5 years of age
(2021)

UN IGME Child and Adolescent Causes of Death Estimation (CA CODE) project (2023).
 Microbial agents of
Gastroenteritis

Distribution of detected pathogens in

the patients with acute gastroenteritis
from Taiwan CDC surveillance data
(N = 2647)
Chung, Ning. Et al 2017. J. Microbiol, Immun and Inf.

19 maart 2024 5
Viral agents of gastroenteritis

Virus distribution in (a) 96 virus infected patients and (b) within different age groups
Source & Transmission?
Food-borne and
Viral Gastroenteritis
Replication strategies of
plus- and minus-strand
RNA viruses

S. Clancy & W. Brown. 2008. Scitable Nat. edu.

Li, D., et al. 2013. Microbiol Mol Biol Rev

 Most common
Viral agents of Human Gastroenteritis

Species (most
Virus Family Size (nm) DNA/RNA Enveloped Clinical Severity
common)
EM

Rotavirus sedoreoviridae 76.5 dsRNA No Severe 9 (majority A)

Dehidrating
diarrhea <5y.o

Norovirus Caliciviridae 23–40 (+)ssRNA No Epidemic diarrhea 7 (majority GI

& vomiting all and GII)
ages

Adenovirus Adenoviridae 90–100 dsDNA No Endemic diarrhea 7 (majority F

<5y.o and G)

Astrovirus Astroviridae 28–30 (+)ssRNA No Endemic diarrhea 22 (1-8)

in children or HIV-
related

Sapovirus Caliciviridae 27–40 (+)ssRNA No Gastroenterintis 5 (GI, GII, GIV,

<5y.o. and GV)
 Rotavirus “Childhood diarrhea”

Rotavirus moratality rate in children < 5 years (2013)

19 maart 2024 12
Rotavirus

• Family of sedoreoviridae
• dsRNA virus
• Has A (90% of all cases),
B, C, D, E, F, G, H, I and J type
• Stable in the environment
• “Endemic” worldwide
 Pathogenesis of Rotavirus
infection

Released NSP4 resulting in mobilization of

intracellular calcium by a PLC-dependent
pathway that activates chloride secretion

Gonzales-Ochos, G. et al. 2017 Arch Microbiol

Glass, R.I., 2006. Scientific american
Winter vomiting bug
(Norwalk Virus = NOROVIRUS)

CDC Data 1997-2000

Norovirus (+)ssRNA virus

Noroviruses can be classified :

GI, GII, GIII, GIV, GV, GVI, and GVII
Main human pathogen : GII
GI, II and IV : humans,
GIII : cattle such as bovine species,
GV : mice

Genotype
Distribution of
Norovirus Outbreaks
September 1, 2016 –
August 30, 2017
(n=693)

1
CDC Data 2017
Working model for NoV
intestinal infection

Karst SM, Wobus CE (2015) PLOS Pathogens

Bivalve molluscan
shellfish and
Sewage
Contaminated
water
In general, Sources and route of transmission

animal
Production (irrigation) Foodhandler
Start of chain (farm)
Start of chain (farm) End of chain (fork)
Oral, handling
Fecal oral transmission Fecal oral transmission
animal pathogens
Human and animal pathogens Human, common,
Global, rare
Global “local” endemic pathogens
Emerging infections
Mixed infections

Norovirus Norovirus Hepatitis E virus

Rotavirus Hepatitis A Virus Bird/swine influenza?
Koopmans 2012 19 maart Hepatitis
2024 A en E virus Sars, Nipah, Ebola
Lab tests during gastroenteritis outbreak:
Laboratory diagnosis of viral gastroenteritis:
A. Detection of viral antigen or nucleic acid in fresh,
whole stool samples obtained during the acute
illness:

1. Viral antigen detection: enzyme immunoassay

(EIA) or latex particle agglutination test such as
for group A rotaviruses, designed to detect the VP6
protein 4

2. Electron microscopy, viral isolation, and

polyacrylamide gel electrophoresis (PAGE) of
RNA extracted directly from stool.

3. Real-time (quantitative) Reverse transcriptase-

polymerase chain reaction (RT-PCR) has high
analytical sensitivity

B. Serologic testing for viral gastroenteritis infection is

possible but impractical in clinical applications.
Hepatitis Viruses
Types of Viral
Acute
Hepatitis
Hepatitis
Acute/chronic Liver
Viruses
inflammation due to
virus infection
HAV: endemicity Country with high HAV exposure rate

Enterically-transmitted
Hepatitis viruses
WHO, 2009
HEV “Endemic Countries”
Enterically-transmitted Viral Hepatitis
HAV and HEV

Properties HAV:
• Family picornavirus,
• (+)ssRNA,
• Virion 27-32 nm,
• Non-enveloped:
• heat & acid stable,

HEV
• Family Hepeviridae
• (+)ssRNA
• Virion 30-34 nm in diameter
• Non-enveloped
• Stability: heat stabile
Global Surveillance of Hepatitis A virus (HAV)

Kroeneman, A., et al. 2018. Euro Surveill

Global Surveillance of Hepatitis E virus
(HEV)

Lisa J. Krain et al. 2014. Clin. Microbiol. Rev.

Pathomechanism of acute viral hepatitis

Bo Wang and Xiang-Jin Meng, 2021. Comput Struct Biotechnol J

Minghang Wang a nd Zongdi Fen. 2021. Viruses

Acute Viral Hepatitis Outbreak
”Starting in November 2023, nine people have been
sickened in Washington State, California and Oregon,
and three people have been hospitalized”.

The F.D.A. investigation has traced Hepatitis A infections to frozen organic strawberries imported from
Mexico, and reported the first five cases of hepatitis A linked to them in March 2023. The strain was
genetically identical an outbreak of hepatitis A infections in 2022, which was also linked to fresh organic
strawberries imported Mexico
CDC Data 2024
Possible routes of introduction of HAV and HEV in the food chain
and sources of human infection

Di Cola, G., et al. 2021. J. Food Microbiol.

 LABORATORY DIAGNOSIS
Enterically-transmitted Hepatitis viruses :

• Liver function test: the increase of serum bilirubin, ALT and

AST level,

• Detection of IgM antibody,

• A 4 fold rise of IgG antibody titer can also be used; 2 times in 2

weeks apart,

• Amplification of viral nucleic acid (PCR) from gastrointestinal fluids.

 Seromarkers of acute viral hepatitis infections
Hepatitis A

Hepatitis E

Van Damme, P., et al. 2023. Nat. Rev.

Kamer, N., et al. 2012. Lancet

 Chronic
Hepatitis
Viruses
Chronic Hepatitis Viruses
HBV :
• Family Hepadnaviridae, genus
orthohepadnavirus,
• Circular dsDNA,
• Incomplete (+)ve strand,
• DNA polymerase - reverse transcriptase,
• Enveloped virion (acid sensitive)
• 8 genotype

HCV
• Family Flaviviridae, genus Hepacivirus
• (+)ssRNA,
• Enveloped virus,
• Ether and acid sensitive,
• Oncogenic,
• Six serotypes and multiple subtype;
– Genotypes 1a & 1b are the most
common
 Hepatitis B and C Pathogenesis

Jung, M. et al, 2002. Lancet Infectious diseases

Moradpour, D. et al. 2007, Nature Reviews Microbiology

Pathogenesis of chronic viral
hepatitis

Chisari, L.F., et al. Annurev. Pathol.

Guerrieri, F. et al. 2013. Semin Liver Dis.

 Laboratory Detections

• Serologic detection of HBV/HCV markers

• HBV/HCV detection by nucleic acid hybridization technique

like PCR

• Detection of HBV/HCV from blood by electron microscope

• Immunofluorescent staining → HBV core protein in the nucleus of

the host cell and infectious Dane particle in the cytoplasm
 Seromarkers of
Hepatitis B infection
 Seromarkers of
Hepatitis C infection

Papadakis, M.A., et al, 2019. McGraw-Hill education

Take home messages

Viral gastroenteritis
• Viruses are the most frequent pathogens of Gastroenteritis cases
• Water is the “vehicle”
• The ”enveloped” status of the virus particle link to their transmission ability

Viral Hepatititis
• Etiology of “Acute vs Chronic”
• Food-borne vs direct transmission
• Serologic assays are the keys of early diagnostic
Thank you

Q&A: ar_sultan2002@med.unhas.ac.id