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GASTROINTESTINAL
TRACT INFECTIONS
E Hagni Wardoyo
Mataram, 23 Agustus 2021
 gerakan peristaltik: gerakan sentrifugal untuk mengirit energi

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◻ Ingested pathogens may cause disease confined to

the gut or involving other parts of the body 🡪 a
result of multiplication and/or toxin production 🡪
food-associated infection versus food poisoning
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Cause of disease Karakteristik

Food Infeksi m.o Makanan sebagai
infection vehicle patogen 🡪
multiplikasi 🡪 infeksi
Food Kerja toksin m.o penghasil toksin
poisoning (kemis, berasal mungkin mati saat food
dari bakteri processing tetapi toksin
tetap ada
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Harrison's Gastroenterology and Hepatology

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◻ Every day we swallow large numbers of microorganisms. Because of the body's defense
mechanisms, however, they rarely succeed in surviving the passage to the intestine in sufficient
numbers to cause infection
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Diare
Diare, dipertimbangkan sebagai :
Mekanisme host untuk
menghilangkan m.o
penyebab
Mekanisme penyebaran
infeksi ke host lain
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Infection of the gastrointestinal tract can cause damage locally or at distant sites
 Many cases of diarrheal disease are
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not diagnosed
Self limiting

medical and laboratory facilities are unavailable

patient's recent food and travel history, and

macroscopic and microscopic examination of the
feces for blood and pus can provide helpful clues
11 Clostridium difficile infections
Host factors
Indigenous intestinal microbial composition intestinal
dysbiosis results in a breakdown of the colonization resistance,
which favors C. difficile germination, growth and spreading within
the intestine

🡪 Antibiotic use!!
Host factors
Indigenous intestinal microbial composition intestinal dysbiosis
results in a breakdown of the colonization resistance, which favors C.
difficile germination, growth and spreading within the intestine

🡪 Antibiotic use!!

Antibiotic use overall (Hensgens 2011) OR 6.7–10.4

Cephalosporins 1e, 2e, 3e gen; OR 1.1, 3.4, 4.9
Carbapenems OR 5.4
Penicillines OR 2.3
Metronidazol OR 2.4
 Diagnostics

Only perform diagnostics

when the patient has diarrhea

= evacuation of loose stools, three or

more times in 24h or less
ficile infection

Smits, 2017
Bacterial factors
Virulence factors: 2 toxins (thermolabile proteins)
? toxin A (TcdA): enterotoxin. Gen: tcdA. Effects: chemotaxis neutrophils,
PMN, cytokine release, fluid hypersecretion, hemorrhagic necrosis.
? toxin B (TcdB): cytotoxin. Gen: tcdB. Effects: depolarisation of actine,
loss of cytoskelet.

Toxin B more ‘potent’ than toxin A.

? 3rd toxin: binary toxin (CDT). Gens: cdtA en cdtB.

Clinical picture
◻ Asymptomatic
◻ Mild diarrhea
◻ Moderate
◻ Pseudomembranous colitis
◻ Toxic megacolon / perforation
 There are six distinct groups of E. coli with different
pathogenetic mechanisms
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1. enteropathogenic E. coli (EPEC),

2. enterotoxigenic E. coli (ETEC),
3. enterohemorrhagic E. coli (EHEC),
4. enteroinvasive E. coli (EIEC),
5. enteroaggregative E. coli (EAEC), and
6. diffuse-aggregative E. coli (DAEC)
E. Production of Mech. of action Remarks
coli
EPEC Bundle forming pilli (Bfp), Attach epithel cells 🡪 Act in small intestine
intimin (adhesin) and protein disruption microvilli 🡪 diarrhea Do not make any toxins
(translocated intimin receptor,
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Tir)
ETE Heat-labile (LT), Heat-stable LT 1~cholera toxin Act in small intestine
C (ST) 🡪 enterotoxin STA activates guanylate cyclase
Collonization factors (fimbrial activity, 🡪 ↗cyclic guanosine
adhesin) monophosphate, 🡪 ↗ fluid
secretion
EHE Verotoxin Verotoxin ~ shiga toxin Act in large intestine, cause
C Verotoxin receptor found in hemorragic colitis (HC) and
renal epithelium Hemolityc uremic syndrome
(HUS)
EIEC Endocytosis factors specifically Lyse vacuole, multiply 🡪 spread Act in large intestine
to large intestine to adjacent cells 🡪 tissue
destruction 🡪 blood and mucus
in faeces
EAE Aggregative ability due to Act in small intestine
C plasmid associated fimbria Aggregatve or ‘stacked bricks’
formation
Enterotoxin and toxin E coli
hemplysin
DAE Alpha hemolysin & cytotoxic Known as diffuse-adherent or
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◻ EPEC and ETEC are the most important

contributors to global incidence of
diarrhea, while EHEC is more important in
developed countries
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◻ HUS is characterized by
? acute renal failure
? anemia
? thrombocytopenia, and
? there may be neurologic complications.
◻ HUS is the most common cause of acute renal failure
in children in the UK and USA.
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Harrison's Gastroenterology and Hepatology

 Salmonella
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◻ Diarrhea is produced as a result of invasion by the salmonellae of

epithelial cells in the terminal portion of the small intestine. Initial
entry is probably through uptake by M cells (the 'antigenic
samplers' of the bowel) with subsequent spread to epithelial cells.
◻ A similar route of invasion occurs in Shigella, Yersinia and reovirus
infections.
◻ The bacteria migrate to the lamina propria layer of the ileocecal
region, where their multiplication stimulates an inflammatory
response, which both confines the infection to the gastrointestinal
tract and mediates the release of prostaglandins.
◻ These in turn activate cyclic adenosine monophosphate (cAMP) and
fluid secretion, resulting in diarrhea.
 Campylobacter
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◻ The gross pathology and histologic appearances of

ulceration and inflamed bleeding mucosal surfaces in
the jejunum, ileum and colon (Fig. 22.14) are compatible
with invasion of the bacteria, but the production of
cytotoxins by C. jejuni has also been demonstrated.
Invasion and bacteremia are not uncommon, particularly
in neonates and debilitated adults
◻ The clinical presentation is similar to that of diarrhea
caused by salmonellae and shigella, although the
disease may have a longer incubation period and a
longer duration.
 Cholera
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Vibrio cholerae serotype O1, the cause of cholera, can be subdivided into different biotypes with
different epidemiologic features, and into serosubgroups and phage types for the purposes of
investigating outbreaks of infection. Although V. cholerae is the most important pathogen of the
genus, other species can also cause infections of both the gastrointestinal tract and other sites
 Cholera
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◻ El Tor biotype, named after the quarantine camp where

it was first isolated from pilgrims returning from Mecca,
differs from classical V. cholerae in several ways. In
particular it causes only a mild diarrhea and has a
higher ratio of carriers to cases than classical cholera;
carriage is also more prolonged, and the organisms
survive better in the environment.
◻ El Tor biotype, which was responsible for the seventh
pandemic, has now spread throughout the world and
has largely displaced the classical biotype
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◻ In 1992 a new non-O1 strain (O139) arose in south India

and spread rapidly. It is able to infect O1-immune
individuals and cause epidemics, and has been proclaimed as
the eighth pandemic strain of cholera.
◻ V. cholerae O139 appears to have originated from El Tor O1
biotype when the latter acquired a new O (capsular) antigen
by horizontal gene transfer from a non-O1 strain.
? This provided the recipient strain with a selective advantage in a
region where a large part of the population is immune to O1
strains.
◻ Other species of Vibrio cause a variety of infections in man.
V. parahaemolyticus is another cause of diarrheal disease, but
this is usually much less severe than cholera (see below).
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The production of an enterotoxin is central to the pathogenesis of cholera, but the organisms
must possess other virulence factors to allow them to reach the small intestine and to adhere
to the mucosal cells.
 Shigellosis
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 Shigellosis
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◻ Shigellosis is also known as bacillary dysentery because in its

more severe form it is characterized by an invasive infection
of the mucosa of the large intestine causing inflammation and
resulting in the presence of pus and blood in the diarrheal
stool.
◻ However, symptoms varied in range 🡪 species of Shigella
involved and on the underlying state of health of the host.
There are four species
? Shigella sonnei causes most infections at the mild end of the
spectrum.
? Shigella flexneri and S. boydii usually produce more severe
disease.
? Shigella dysenteriae is the most serious
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◻ Like V. cholerae, shigellae are human pathogens without an

animal reservoir, but unlike the vibrios, they are not found in the
environment,
? spread from person to person by the fecal-oral route 🡪 less
frequently by contaminated food and water.
◻ spread is easy in situations where sanitation or personal hygiene
may be poor (e.g. refugee camps, nurseries, day care centers
and institutions for the handicapped).
◻ initiate infection from a small infective dose (10-100 organisms)
◻ Shigellosis is primarily a pediatric disease. When associated
with severe malnutrition it may precipitate complications such as
the protein deficiency syndrome 'kwashiorkor'.
 Patogenesis
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Attach & invade epitel mukosa

Invasi distal ileum dan colon

Produksi
Multiplikasi Shiga
toxin~EEHEC

Kerusakan Kerusakan
Mekanisme epitel sel endotel
mukosa usus glomerular

Gejala : diare Inlamasi dan

HUS
dan anuria ulserasi usus
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◻ Shigellae attach to, and invade, the mucosal

epithelium of the distal ileum and colon, causing
inflammation and ulceration
◻ S. dysenteriae produce a (Shiga) toxin similar to that
associated with EHEC, which can cause damage to
the intestinal epithelium and glomerular endothelial
cells, the latter leading to kidney failure (HUS)
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 Rotaviruses
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The virus particles (65 nm in diameter) have a well-defined outer margin and capsules radiating
from an inner core to give the particle a wheel-like (hence 'rota') appearance. (Courtesy of JE
Banatvala
 Patogenesis Rotavirus
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Invasi Inkubasi Produce

rotavirus 1-2 hari diare
Mekanisme
transport usus
terganggu
kehilangan air,
Attach & invade Replikasi virus garam dan
glukosa

Atrofi vilus 🡪
↗tek osmotik
 Proteksi dan epidemiologi
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◻ IgA antibodies in colostrum give protection during the

first 6 months of life.
◻ Outbreaks are sometimes seen in nurseries.
◻ Older children are less susceptible to infection, nearly
all of them having developed antibodies, but occasional
infections occur in adults
◻ As few as 10 ingested particles can cause infection, and
by generating a diarrhea laden with enormous
quantities of infectious particles these organisms have
ensured their continued transmission and survival
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Diarrheal disease is a major cause of illness and death in children in developing countries. This
illustration shows the proportion of infections caused by different pathogens. Note that in as many
as 20% of infections a cause is not identified, but many of these are likely to be viral. (Data from
the WHO.) (EPEC, enteropathogenic Escherichia coli; ETEC, enterotoxigenic E. coli.)
 Sekian dan terimakasih
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