GASTROINTESTINAL TRACT INFECTION

SY. MIFTAHUL EL JANNAH

Flora normal
Enterobacteriaceae, kecuali Salmonella, Shigella, Yersinia, Vibrio dan Campylobacter Non dextrose fermenting Gram negative rods Enterococci Alpha hemolytic dan non hemolytic Streptococci Diphtheroids Sedikit S. aureus Sedikit Yeast Banyak anaerob

Saat lahir usus steril, mo masuk bersama makanan, tdd Streptococcus asam
laktat dan Lactobacillus .

For an infection to occur, the pathogen must be ingested in sufficient numbers or

possess attributes to elude the host defenses of the upper gastrointestinal tract and
reach the intestine Perkembangan pola makan merubah flora normal usus

Asam lambung menjaga jumlah mo seminimal mungkin [103-105/g isi lambung]

Seiring pH usus menjadi basa flora normal meningkat. Duodenum orang dewasa 108-1010 bakteri/g isi usus

Jejunum dan ileum 105-108 bakteri/g

Caecum dan kolon transversum 103-105 bakteri/g Kolon sigmoid dan rektum 1011 bakteri/g

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.

Peran
Sintesis vitamin K Konversi pigmen pigmen empedu dan asam asam empedu Penyerapan zat-zat makanan dan hasil pemecahannya Perlawanan terhadap mo patogen

Figure 22.1 As well as many colloquial expressions, several different clinical terms are used to describe infections of the gastrointestinal tract. Diarrhea without blood and pus is usually the result of enterotoxin production, whereas the presence of blood and/or pus cells in the feces indicates an invasive infection with

mucosal destruction.

A wide range of microbial pathogens is capable of

infecting the gastrointestinal

tract, and the important bacterial and viral pathogens They are acquired by the

fecal-oral route, from fecally

contaminated food, fluids or fingers Many different

pathogens cause infections

of the gastrointestinal tract.

Some are found in both humans and animals while others are strictly human

parasites.

Infections

of

the

gastrointestinal tract can be grouped into those that

remain localized in the gut and those that invade beyond the gut to cause infection in other sites in the body. In order to spread to a new host,

pathogens are excreted in large numbers in the feces and must survive in the

environment for long enough to infect another person

directly or indirectly through contaminated food or fluids.

The damaging effects resulting from infection of the gastrointestinal tract

Escherichia coli is a major cause of gastrointestinal infection, particularly in developing countries and in travelers. There is a range of pathogenic mechanisms within the species, resulting in more or less invasive disease. *Specialized tests are given in italics. (LT, heatlabile enterotoxin; ST, heat-stable enterotoxin.)

Bacterial causes of diarrhea

Escherichia coli
This is one of the most versatile of all bacterial pathogens.
Some strains are important members of the normal gut flora in man and animals, whereas others possess virulence factors that

enable them to cause infections in the intestinal tract or at

other sites, particularly the urinary tract Strains that cause diarrheal disease do so by several distinct

pathogenic mechanisms and differ in their epidemiology

There are six distinct groups of E. coli with different pathogenetic mechanisms Initially all diarrhea-associated Escherichia coli were termed enteropathogenic E. coli (EPEC). Enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), EPEC and ETEC are the most important contributors to global incidence of diarrhea

enterohemorrhagic E. coli (EHEC) more important in developed enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC), and diffuse-aggregative E. coli (DAEC).

The diarrhea produced by E. coli varies from mild to severe, depending upon the strain and the underlying health of the host. EIEC and EHEC strains both cause bloody diarrhea

Enteropathogenic E. coli (EPEC)

Do not appear to make any toxins. They do produce bundle-forming pili (Bfp), intimin (an adhesin) and an associated protein (translocated intimin

receptor, Tir). These virulence factors allow bacterial

attachment to epithelial cells of the small intestine, leading to disruption of the microvillus (an 'attaching-effacing' mechanism of action) leading to diarrhea.

Electron micrograph of enteropathogenic Escherichia coli adhering to the brush border of intestinal mucosal cells with localized destruction of microvilli. (Courtesy of S Knutton.)

The clinical features of bacterial diarrhea infection. It is difficult, if not impossible, to determine the likely cause of a diarrheal illness on the basis of clinical features alone, and laboratory investigatio ns are essential to identify the pathogen.

Enterotoxigenic E. coli (ETEC)

possess adhesins. ETEC diarrhea in children in developing countries may be clinically indistinguishable from cholera colonization factors (fimbrial

 These bind the bacteria to specific receptors on the cell membrane of the small intestine. These organisms produce powerful plasmid-associated enterotoxins which are characterized as being either heat labile (LT) or heat stable (ST):
Heat-labile enterotoxin LT-I is very similar in structure and mode of action to cholera toxin produced by V. cholerae, and infections with strains producing LT-I can mimic cholera, particularly in young and malnourished children.

Heat-stable enterotoxins (STs) in addition to or instead of LT. STs have a similar

but distinct mode of action to that of LT. STA activates guanylate cyclase activity, causing an increase in cyclic guanosine monophosphate, which results in increased fluid secretion. Immunoassays are commercially available for the identification of ETEC.

Electron micrograph of enterotoxin Escherichia coli, showing pili necessary for adherence to mucosal epithelial cells. (Courtesy of S Knutton.)

Enterohemorrhagic E. coli (EHEC)

Isolates produce a verotoxin The verotoxin (i.e. toxic to tissue cultures of 'vero'cells) is essentially identical to Shiga (Shigella) toxin. After attachment to the mucosa of the large intestine (by the 'attaching-effacing' mechanism also seen in EPEC) the produced toxin has a direct effect on intestinal epithelium, resulting in diarrhea EHEC cause hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS). In HC there is

destruction of the mucosa and consequent hemorrhage; this may be followed by HUS.
Verotoxin receptors have been identified on renal epithelium and may account for the kidney involvement. While there are many serotypes of EHEC, the most common one in the USA is O157:H7. HUS is characterized by acute renal failure, anemia and thrombocytopenia, and there may be neurologic complications HUS is the most common cause of acute renal failure in children in the UK and USA.

Verotoxin-producing Escherichia coli infection, showing fibrin 'thrombi' in glomerular capillaries in hemolytic-uremic syndrome. (Weigert stain.) (Courtesy of HR Powell.)

Enteroinvasive E. coli (EIEC)

Attach specifically to the mucosa of the large intestine Utilizing plasmid-associated genes, they invade the cells by endocytosis. Inside the cell they lyse the endocytic vacuole, multiply and spread to adjacent cells, causing tissue destruction, inflammation, necrosis and ulceration, resulting in blood and mucus in stools

Enteroaggregative E. coli (EAEC)

Derive their name from their characteristic attachment pattern to tissue culture

cells .
The pattern is an aggregative or 'stacked brick' formation. These organisms act in the small intestine to cause persistent diarrhea especially in children in developing countries. Their aggregative adherence ability is due to plasmid-associated fimbriae. EAEC also produce heat-labile toxins (an enterotoxin and a toxin related to E. coli hemolysin) but their role in diarrheal disease is uncertain.

Diffuse-aggregative E. coli (DAEC)

Produce an alpha hemolysin and cytotoxic necrotizing factor 1 They are also known as diffuse-adherent or cell-detaching E. coli.

Their role in diarrheal disease, especially in young children, is incompletely

understood and somewhat controversial, with some studies reporting no association.

Specific tests are needed to identify strains of pathogenic E. coli :

Because E. coli is a member of the normal gastrointestinal flora, specific tests are
required to identify strains that may be responsible for diarrheal disease. Infections are more common in children and are also often travel-associated, and these factors should be considered when samples are received in the laboratory.

It is important to note that specialized tests beyond routine stool cultures are required
to identify specific diarrhea-associated E. coli types. Such tests are not ordinarily performed with uncomplicated diarrhea, which is usually self-limiting.

Antibacterial therapy is not indicated for E. coli diarrhea Fluid replacement may be necessary, especially in young children. Treatment of HUS is urgent and may involve dialysis. Provision of a clean water supply and adequate systems for sewage disposal are fundamental to the prevention of diarrheal disease. Food and unpasteurized milk can be important vehicles of infection, especially for EIEC and EHEC, but there is no evidence of an animal or environmental reservoir.

Salmonella
Salmonellae common cause of food-associated diarrhea in many developed countries, in some countries (e.g. the USA and UK) they have been relegated to second place by Campylobacter. The most important of which, for human infection, is Salmonella enterica. All salmonellae except for Salmonella typhi and S. paratyphi are found in animals as well as humans. There is a large animal reservoir of infection, which is transmitted to man via contaminated food, especially poultry and dairy products. Waterborne infection is less frequent. Salmonella infection is also transmitted from person to person, and secondary spread can therefore occur, for example within a family after one member has become infected after consuming contaminated food Salmonellae are almost always acquired orally in food or drink that is contaminated

The recycling of Salmonellae. With the exception of Salmonella typhi, salmonellae are widely distributed in animals, providing a constant source of infection for man. Excretion of large numbers of salmonellae from infected individuals and carriers allows the organisms to be 'recycled'

MO lolos dari lambung

multiplikasi dlm sal. Cerna

menembus mukosa usus di fagosit oleh makrofag

menyebar, multiplikasi

keluar dari SDP

duktus toraksikus

aliran darah [bakteriaemia fase pertama/primer] pd hari ke-7 10 menginfeksi hepar, kandung empedu, limfe, ginjal dan sumsum tulang

multiplikasi dalam RES

aliran darah [jumlah semakin banyak, bakteriaemia fase kedua/sekunder],

Bakteri dari kandung empedu

usus halus & jaringan limfoid

perdarahan melepaskan endotoksin [demam tinggi & gejala tifoid lainnya] perforasi usus

The passage of salmonellae through the body. The vast majority of salmonellae cause infection localized to the gastrointestinal tract and do not invade beyond the gut mucosa. (cAMP, cyclic adenosine monophosphate.)

Salmonella diarrhea can be diagnosed by culture on selective media The organisms are not fastidious and can usually be isolated within 24 hours, although small numbers may require enrichment in selenite broth before culture. Preliminary identification can be made rapidly, but the complete result, including serotype, takes at least 48 hours

Fluid and electrolyte replacement may be needed for salmonella diarrhea Diarrhea is usually self-limiting and resolves without treatment. Unless there is evidence of invasion and septicemia, antibiotics should be positively discouraged because they do not reduce the symptoms or shorten the illness, and may prolong excretion of salmonellae in the feces

Salmonellae may be excreted in the feces for several weeks after a salmonella infection

Pengendalian
The large animal reservoir makes it impossible to eliminate the organisms, and preventive measures must therefore be aimed at 'breaking the chain' between animal and man, and from person to person. Such measures include: maintaining adequate standards of public health (clean drinking water and proper sewage disposal); Education programs on hygienic food preparation. Following an episode of salmonella diarrhea, an individual can continue to carry and excrete organisms in the feces for several weeks. Although in the absence of symptoms the organisms will not be dispersed so liberally into the environment, thorough handwashing before food handling is essential. People employed as food handlers are excluded from work until three specimens of feces have failed to grow salmonella.

Campylobacter
Campylobacters are among the commonest causes of diarrhea Campylobacter spp. are curved or S-shaped Gram-negative rods

They have long been known to cause diarrheal disease in animals, but are also
one of the most common causes of diarrhea in humans.

The enterobacteria as they are microaerophilic and thermophilic (growing well

at 42C); they do not therefore grow on the media used for isolating E. coli and
salmonellae. Several species of the genus Campylobacter are associated with human disease,

but Campylobacter jejuni is by far the most common. Helicobacter pylori,

previously classified as Campylobacter pylori, is an important cause of gastritis and gastric ulcers

Campylobacter jejuni infection. Gram stain showing Gram-negative, S-shaped bacilli. (Courtesy of I Farrell.)

As with salmonellae, there is a large animal reservoir of campylobacter in cattle, sheep, rodents, poultry and wild birds.

Infections are acquired by consumption of contaminated food, especially poultry, milk or water. Household pets such as dogs and cats can become infected and

provide a source for human infection, particularly for young children.

Person to person spread by the fecal-oral route is rare, as is transmission from food handlers. Campylobacter diarrhea is clinically similar to that caused by other bacteria such as salmonella and shigella Pathology and histologic appearances of ulceration and inflamed bleeding mucosal surfaces in the jejunum, ileum and colon 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.

Inflammatory enteritis caused by Campylobacter jejuni, involving the entire mucosa, with flattened atrophic villi, necrotic debris in the crypts and thickening of the basement membrane. (Cresyl-fast violet stain.) (Courtesy of J Newman.)

 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. Erythromycin is used for severe campylobacter diarrhea. Erythromycin is the antibiotic of choice for cases of diarrheal disease that are severe enough to warrant treatment. Invasive infections may require treatment with an additional antibiotic (e.g. quinolone, aminoglycoside, etc.).

Cholera
Cholera is an acute infection of the gastrointestinal tract Caused by the comma-shaped Gram-negative bacterium V.

cholerae. V. cholerae is a free-living inhabitant of fresh water, but

causes infection only in humans Cholera flourishes in communities with inadequate clean drinking water and sewage disposal The 1990s have witnessed the seventh pandemic of cholera spreading into Latin America. The disease remains endemic in southeast Asia and parts of Africa and South America.

Scanning electron micrograph of Vibrio cholerae showing commashaped rods with a single polar flagellum. 13000. (Courtesy of DK Banerjee.)

 Asymptomatic human carriers are believed to be a major reservoir. The disease is spread via contaminated food; shellfish grown in fresh and estuarine waters have also been implicated. Direct person to person spread is thought to be uncommon. V. cholerae serotypes are based on somatic (O) antigens Serotype O1 is the most important and is further divided into two biotypes: classical and El Tor.

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.

 The severe watery non-bloody diarrhea is known as rice water stool

because of its appearance and can result in the loss of one liter of fluid every hour.

It is this fluid loss and the consequent electrolyte imbalance that

results in marked dehydration, metabolic acidosis (loss of bicarbonate), hypokalemia (potassium loss) and hypovolemic shock resulting in cardiac failure. Untreated, the mortality from cholera is 40-60%; rapidly instituted fluid and electrolyte replacement reduces the mortality to less than 1%.

MO lolos dari barrier asam lambung usus halus, bermultiplikasi dan membentuk eksotoksin disebut enterotoksin

bereaksi dengan reseptor pada membran sel epitel usus

mengaktifkan adenilat siklase, mengakibatkan Meningkatnya siklik adenosin monofosfat/cAMP

merangsang perubahan ATP menjadi ADP

ADP merangsang pengeluaran air dan elektrolit oleh dinding usus ke dalam rongga usus dan menahan penyerapan Na+ oleh dinding usus

sekresi cairan isotonus dari dinding usus.

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.

Rice water stool in cholera. (Courtesy of AM Geddes.

SHIGELLA sp
Infeksi peroral, terutama melalui makanan jenis sayuran, susu dan protein tinggi Dosis infeksi 103 kuman

Berat

ringannya

tergantung
berat

spesies
S.

yang

meninfeksi

paling

dysentriae,

kemudian berturut-turut S. flexneri, S. boydii dan

yang paling ringan S. sonnei.

MO melewati lambung

usus halus kolon, ditangkap oleh epitel

multiplikasi, menyebabkan rusaknya sel epitel

menginfeksi jaringan sekitar

reaksi radang
nekrotik, pengelupasan epitel, perdarahan. [tidak pernah terjadi perforasi dan masuk ke organ dalam]

Shigella spp

Bentuk sel bakteri Koloni bakteri pada agar SSA

Shigellosis. Histology of the colon showing disrupted epithelium covered by pseudomembrane and interstitial infiltration. Mucin glands have discharged their contents and the goblet cells are empty. (Colloidal iron stain.) (E, epithelium; I, interstitial infiltration; M, mucin in glands; P, pseudomembrane.) (Courtesy of RH Gilman.)

Yersinia enterocolitica
member of the Enterobacteriaceae and is a cause of food-associated infection especially among infants and particularly in colder parts of the world

Y. enterocolitica is found in a variety of animal hosts including rodents, rabbits,

pigs, sheep, cattle, horses and domestic pets. Transmission to humans from household dogs has been reported. The organism survives and multiplies, albeit

more slowly, at refrigeration temperatures (4C) and has been implicated in

outbreaks of infection associated with contaminated milk as well as other foods. The mechanism of pathogenesis is unknown, but the clinical features of the

disease result from invasion of the terminal ileum, necrosis in Peyer's patches and
an associated inflammation of the mesenteric lymph nodes

Yersinia enterocolitica infection of the ileum, showing superficial necrosis of the mucosa and ulceration. (Courtesy of J Newman.)

CLOSTRIDIUM PERFRINGENS
Merupakan bakteri Gram positip yang membentuk endospora, anerob obligat, menghasilkan enterotoksin yang tidak dihasilkan pada makanan sebelum dikonsumsi, tetapi dihasilkan bila bakteri berkolonisasi di usus. Bakteri terdapat di tanah, usus manusia dan hewan, daging mentah, unggas dan bahan pangan kering. Gejala timbul 8-24 jam setelah mengkonsumsi pangan yang tercemar bentuk vegetatip bakteri dalam jumlah besar, berupa sakit perut, mual dan diare jarang disertai muntah. Gejala dapat berlanjut selama 1-2 minggu [terutama pada anak-anak dan manula]. Self limited

CLOSTRIDIUM PERFRINGENS
Jenis makanan yang mudah terkontaminasi: saus daging yang disimpan pada suhu yang menunjang perkecambahan spora [30-370C]

Belum ada pengobatan khusus

Pencegahan: Tidak menyimpan makanan yang sudah

matang pada suhu kamar untuk jangka waktu yang

lama.

Gram stain of Clostridium perfringens.

Downloaded from: StudentConsult (on 20 October 2009 07:04 AM) 2005 Elsevier

GAMBAR 2. Growth of Clostridium perfringens on sheep blood agar. Note the flat, spreading colonies and the hemolytic activity of the organism. A presumptive identification of C. perfringens can be made by detection of a zone of complete hemolysis (caused by the ;-toxin) and a wider zone of partial hemolysis (caused by the ;-toxin), combined with the characteristic microscopic morphology.
Downloaded from: StudentConsult (on 20 October 2009 07:04 AM) 2005 Elsevier

Type

A B C D E

Lethal Toxins Alpha Beta Epsilon + + + + + + + + + -

Iota +

Distribution of Lethal Toxins in Clostridium perfringens Types A to E

Clostridium perfringens is linked with two forms of food-associated infection. The common, enterotoxin-mediated infection (left) is usually acquired by eating meat or poultry that has been cooked enough to kill vegetative cells, but not spores. As the food cools, the spores germinate. If reheating before consumption is inadequate (as it often is in mass catering outlets), large numbers of organisms are ingested. The rare form associated with -toxinproducing strains (right) causes a severe necrotizing disease.

Bacillus cereus
Bakteri berbentuk batang. Gram

positip, aerob,membentuk
endospora yang tahan panas dan radiasi Keracunan

menelan bakteri atau bentuk

sporanya bakteri bereproduksi dan menghasilkan toksin di dalam usus mengkonsumsi pangan yang telah mengandung toksin

Bacillus cereus

Koloni di media agar darah

Sel B. cereus dengan mikroskop elektron

MIFTAHEL-2006

Bacillus cereus
Terdapat dua muntah/emesis
Toksin penyebab

tope
diare,

toksin:

menyebabkan

diare

dan

maka

gejala yang timbul berhubungan dengan saluran bagian bawah, berupa mual, nyeri perut seperti

kram,
jam

diare berair. Terjadi 8-16

setelah diare mengkonsumsi ini umumnya

pangan. Bakteri penghasil toksin penyebab

mencemari sayuran dan daging.

Toksin penyebab muntah, gejala yang timbul akan lebih bersifat lebih parah dan akut dan berhubungan dengan saluran pencernaan bagian atas berupa mual dan muntah yang dimulai setelah 1-6 jam setelah mengkonsumsi pangan yang tercemar. Bakteri pengahasil toksin ini mudah mencemari pangan yang banyak mengandung pati /nasi yang didinginkan secara lambat dan disimpan pada suhu kamar dan tunas sayuran

Bacillus cereus
Pencegahan: Pengendalian suhu yang efektif untuk mencegah pertunasan dan pertumbuhan spora mengolah makanan dengan pemanasan bertekanan, menggoreng, tidak menyimpan nasi pada suhu ruang

Bacillus cereus can cause two different forms of foodassociated infection. Both involve toxins

Viral diarrhea
Rotaviruses
These are morphologically characteristic viruses with a genome consisting of 11 separate segments of double-stranded RNA. Different rotaviruses infect the young of many mammals, including children, kittens, puppies, calves, foals and piglets, but it is thought that viruses from one host species occasionally cross-infect another. There are at least two human serotypes. Replicating rotavirus causes diarrhea by damaging transport mechanisms in the gut

Rotavirus. The virus particles (65 nm in diameter) have a welldefined outer margin and capsules radiating from an inner core to give the particle a wheel-like (hence 'rota') appearance. (Courtesy of JE Banatvala.)

Replicating rotavirus causes diarrhea by damaging transport mechanisms in the

gut. The replicating virus damages transport mechanisms in the gut, and loss of water, salt and glucose causes diarrhea

The incubation period is 1 to 2 days. After virus replication in intestinal epithelial cells there is an acute onset of vomiting, which is sometimes projectile, and diarrhea which lasts from 4 to 7 days

Infected cells in the intestine are destroyed, resulting in villous atrophy. The villi, long finger- like projections, become flattened resulting in the loss of both the surface area for absorption and the digestive enzymes, and raised osmotic pressure in the gut lumen causes diarrhea.

The mechanism of rotavirus diarrhea. Other viruses may have different mechanisms.

VIRUS POLIO
Didapat pada susu yang tidak dipasteurisasi

Menimbulkan penyakit poliomielitis

Virus masuk bersama susu multiplikasi di tonsil dan kelenjar orofaring aliran limfe/limfogen menyebar ke bercak peyer dalam dinding usus SSP serabut motorik ke sumsum tulang belakang atau otak

Virus dapat ditemukan dalam tonsil dan tinja

Virus polio

Morfologi sel

Struktur sel

VIRUS HEPATITIS A
Jenis makanan: susu, sayuran , daging dan kerang-kerangan masak Sumber kontaminan: air, feses, penjamah makanan yang carier virus hepatitis A dalam keadaan kurang

Virus Hepatitis

Struktur sel Bentuk sel

FOOD POISONING
'food poisoning' is restricted to the diseases caused by

toxins elaborated by contaminating bacteria in food

before it is consumed
B. cereus Staph. aureus enterotoxin Eight different enterotoxins are produced by different strains of Staph. aureus

Cl. botulinum toxin

Staphylococcus aureus produces at least eight immunogically distinct enterotoxins, the most important of which are listed here. Strains may produce one or more of the toxins simultaneously. Enterotoxin A is by far the most common in food-associated disease.