MICR 201 Microbiology for Health Related Sciences

Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010

Chapter 22: Infections of the digestive system

The digestive system is the second leading portal of entry into the body. As a health care professional you will see many patients with infections of the digestive system.

Why is this chapter important?

Map for chapter 22

Anatomy of the digestive system

The digestive system is a major portal of entry. Many pathogens enter the body when we ingest

water and food. Defenses of the digestive system are very

strong.◦ Lysozyme, low gastric pH, bile salts◦ Paneth cells in small intestine◦ GALT◦ IgA◦ Normal microbiota◦ Keep many infections from ever happening.

Digestive infections and food poisoning are a major cause of morbidity and mortality.◦ Cause the death of millions of children◦ Immune system is not mature.

Overview

Most common symptoms are:◦ Abdominal pain◦ Diarrhea ◦ Vomiting◦ Fever

Food poisoning◦ Preformed toxins, act rather as neurotoxins◦ Nausea and vomiting may be main symptoms◦ Rapid onset is rapid and short duration◦ Typically without fever

Infection◦ Bacteria have to colonize, establish infection before toxins are

produced and can act◦ Onset several days after uptake and ~ 1 week duration◦ Two major types of toxins

Enterotoxin: watery diarrhea Cytotoxin: fever, bloody diarrhea

Clinical symptoms of gastrointestinal infections and food poisoning

Usually connected to one meal◦ Single source of contamination◦ Typically involves multiple patients

Almost always involves improper food handling

Has increased with the popularity of fast food

Main sources for toxin◦ Staphylococcus aureus enterotoxin (superantigen)

Salads containing mayonnaise, custards◦ Bacillus cereus enterotoxin

Undercooked rice

Food poisoning

The central feature in all cases is diarrhea. The nature of the diarrhea is used to classify

gastrointestinal infections into three categories:◦ Watery diarrhea: enterotoxin mediated such as in

ETEC in traveler's diarrhea or in cholera◦ Dysentery: cytotoxin mediated such as in Shigella

dysentery ◦ Enteric fever: translocation of pathogen from

intestinal lumen into circulation and systemic spreading; diarrhea less prominent; such as in typhoid fever caused by Salmonella typhi

Clinical symptoms of gastrointestinal infections

Transmitted via food and water Fecal-oral cycle can be broken by:

◦ Proper sewage disposal◦ Disinfection of drinking water◦ Proper food preparation and storage

Epidemiology of gastrointestinal infections

Acquired in a hospital and usually traced to: Clostridiun difficile accounts for 90% of

infections.◦ Symptoms range from mild diarrhea to fulminant

pseudomembranous colitis. ◦ Colitis arises either during or after treatment with

antibiotics.

Nosocomial gastrointestinal infections

Mainly supportive care with liquid replacement and rest◦ Substantial liquid loss requires intravenous

replacement. Infection with E. coli O157:H7 can result in

renal failure.◦ Requires dialysis or transplant.

If bacteria spread from the intestine antibiotics are given.

Treatment of food poisoning and gastrointestinal infections

Most commonly seen infections in the mouth are:◦ Dental caries.◦ Infections of the gum tissue.

In both cases, the major source of infection is plaque.◦ Forms as a result of bacterial colonization on surface of

teeth originating from normal microbiota

Dental and periodontal infections

Tooth surface is normally covered by pellicle (lipids, protein)

Bacteria adhere to the pellicle.◦ Facilitated by

bacterial adhesion molecules

◦ Initial adherent is usually Streptococcus mutans

◦ Additional species are recruited

Biofilm develops

Formation of dental plaque

Formation of dental plaque

Organisms that produce acid can cause dental caries.◦ Streptococcus mutans is the major cause.◦ Other organisms contribute.

Carbohydrates easily enter the plaque and are readily metabolized.◦ Acid damages tooth enamel.◦ Repeated snacking on sugar keeps acid level

high.◦ This continues demineralization of the tooth.

Chewing sugar free gum reduces caries

Dental caries

There are two forms of plaque-induced periodontal disease.◦ Gingivitis

Inflammatory condition limited to the surfaces of the gingiva

Does not involve loss of bone Can be corrected Will continue as long as dental plaque remains

◦ Periodontitis Infection of the gingiva Results in loss of supportive bone and ligaments Responsible for most tooth loss in adults

Gingivitis and periodontitis

Which of the following statements regarding caries is incorrect?

A. S. mutans is solely responsible for caries development.

B. In caries acids damage the enamel.

C. Caries is considered an infectious disease because microbes are the ones converting sugars into the damaging acid.

D. Caries involves biofilm formation on the teeth.

E. All statements are correct.

In contrast to periodontitis, gingivitis________.

A. Is a disease between the teeth.

B. Is not an infectious disease.

C. Does not involve bone loss.

D. All are correct.E. None of the above

is correct.

Helicobacter pylori Enterobacteriaceae

◦ Escherichia coli◦ Salmonella◦ Shigella◦ Yersinia

Campylobacter spec. Vibrio cholerae

Bacterial infections of the digestive system

Gram-negative curved rod

Microaerophilic Polar flagella Produces urease

◦ Generates ammonia◦ Allows it to survive in

very acidic environments

Vacuolating cytotoxin◦ Causes apoptosis in

eukaryotic cells

Helicobacter pylori

Helicobacter pylori infection causes ulcers.◦ Treat with antibiotics

(tetracycline plus clarithromycin )

Found in 30-50% of all adults in developed countries◦ Practically 100% of adults in

developing countries Mode of transmission is

not known.◦ Presumed to be person-to-

person by the fecal-oral route

Can develop into gastric cancer

Helicobacter pylori

Diverse family of Gram-negative rod-shaped bacteria

Facultative anaerobic Some are part of the

indigenous microflora in the intestine: Escherichia coli

Some are human primary pathogens: Salmonella, Shigella, Yersinia

May produce various virulence factors◦ Enterotoxin, cytotoxin (shiga

toxin), type III secretion apparatus

Identification biochemically and serologically◦ Antigens: LPS, flagellin, capsule◦ Many serotypes (Salmonella

over 2000)

Enterobacteriaceae

Over 150 different serogroups of E. coli◦ Classified according to O, K, and H antigens

Many use fimbriae and pili to attach to host cells.

E. coli can be divided into the following:◦ Enterotoxigenic E. coli (ETEC): watery diarrhea◦ Enteropathogenic E. coli (EPEC): often in

newborns◦ Enteroinvasive E. coli (EIEC): dysentery◦ Enteroaggregative E. coli (EAEC)◦ Enterohemorrhagic E. coli (EHEC): bloody diarrhea

E. coli

E. coli O157:H7 is a well known enterohemorrhagic E. coli.◦ Low ID50 (around 103) ◦ Causes bloody diarrhea◦ Associated with ground meat and unpasteurized

juices (vegetable and fruit)◦ Person-to-person transmission can occur.◦ Infection is more common in developed

industrialized countries.

Enterohemorrhagic E. coli (EHEC)

Distinguishing clinical factors are:◦ Production of shiga-like toxin.◦ Effacement of intestinal microvilli.

Attack the colon by adhering through attachment proteins◦ Use the secretion infection system to deliver

proteins into target cells◦ These proteins alter cytoskeletal components.

Enterohemorrhagic E. coli (EHEC): Pathogenesis

Certain strains produce shiga like toxin

Toxin is resorbed and enters circulation

Bacteria remain in the intestine on top of the cells, not inside

Toxin is transported to small vessel

Microvascular endothelial cell damage◦ Inhibition of protein

synthesis◦ Apoptosis◦ Platelet activation

Enterohemorrhagic E. coli (EHEC)Pathogenesis

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Kidney damage in hemolytic uremic syndrome

DiseasedNormal

Shigella species cause severe dysentery.◦ Spread from person to person in unsanitary

conditions Shigella species are closely related to E. coli

but: ◦ Cannot ferment lactose.◦ Lack flagella.

All species produce Shiga toxin, a cytotoxin.

Shigella

ID50 is fewer than 200 organisms. It is easily transmissible. 40% of patients get infection from family

member.

Shigella: Epidemiology

Shigella is acid-resistant.◦ Survives passage through the stomach

Invade the cells of the colonic mucosa Intense acute inflammatory response,

leukocytes in feces Causes mucosal ulcerations and abscess

formation

Shigellosis

All types of Salmonella infecting humans are now classified as one species, enterica.

Salmonella enterica is divided into serotypes based on its antigens.◦ O antigens identify the serogroup.◦ K and H antigens are used for further subdivision.

Can also distinguish Salmonella by host range◦ Some are strictly adapted to humans.◦ Many colonize various animals

Salmonella

Salmonella invasion

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Salmonellosis Ingested

Requires large dose (105)

Sources include chicken and reptiles like turtles

Salmonella enterica serovars such as S. enterica Typhimurium

Affects small intestine Mortality (<1%) due to

septic shock caused by endotoxin

Systemic in immunocompromised

Salmonella enterica Typhi Human adapted Low infectious dose (~1000) Enter through small intestine Bacteria routinely spread throughout

body in phagocytes High fever, continued headaches Diarrhea only during 2.. and 3. week

when fever declines 1-3% recovered patients become

chronic carriers, harboring Salmonella in their gallbladder

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Typhoid Fever

Can reproduce at 4°C Usually transmitted in meat and milk Associated with arthritis

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Yersinia gastroenteritis

Microaerophilic gram negative rods (not a member of Enterobacteriacea)

Usually transmitted in cow's milk

Linked to Guillian-Barre syndrome, an autoimmune neurological disorder with temporary paralysis

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Campylobacter gastroenteritis

http://en.wikipedia.org/wiki/Campylobacter

Gram-negative, non spore-forming, and rod-shaped

Not a member of the family of Enterobacteriaceae

Commonly found in salt water

Have a unique morphology◦ Form S shapes and

half spirals Highly motile by

means of a single polar flagella

Vibrio

Low tolerance for acidic conditions◦ Grow well in mildly alkaline environments

Vibrio cholerae produces an enterotoxin.◦ Acts on enterocytes◦ Causes a devastating fluid loss without actually

damaging the enterocytes

Vibrio

Cholera has a rapid onset characterized by:◦ Abdominal fullness.◦ Discomfort.◦ Rushes of peristalsis.◦ Loose stools.

Stools quickly become watery, voluminous, and almost odorless.◦ Can progress to rice stool containing mucus

No fever No blood in stool Treatment: liquid replacement

Cholera

Cholera bed

Turtles have been found to serve as reservoir for which pathogen?

A. YersiniaB. EHECC. ShigellaD. CampylobacterE. Salmonella

Mumps Gastroenteritis Hepatitis

Viral diseases of the digestive system

Mumps Mumps virus Enters through respiratory

tract Infects parotid glands and

leads to painful swelling and fever

May cause orchitis (infection of the testis that may lead to infertility), even less frequently meningitis, inflammation of ovaries, and pancreatitis

Prevented with MMR vaccine

Digestive system is an important portal of entry for viruses.

For some it is only an entry point◦ Disease occurs somewhere else.

Most common sign of enteric viral infection is diarrhea.◦ Fecal -oral transmission◦ Rapid onset – within hours◦ Vomiting along with diarrhea◦ Lasts for less than three weeks◦ Abundant excretion of virions in the stool

108 per gram of stool

Viral gastroenteritis

Several groups of viruses cause gastrointestinal infections

Rotavirus Enterovirus

Viral infections of the digestive system

Not discovered until 1973◦ Now found around the world

Believed to account for 40 - 60% of cases of acute gastroenteritis◦ Watery stools, low grade fever

Can undergo genetic re-assortment◦ Difficult to deal with immunologically

Outbreaks of rotavirus infections common in infants and children under 2 and often causing death in underdeveloped countries.

Adults are usually only minimally affected.◦ Can affect the elderly or institutionalized

Rotavirus

Hepatitis describes any disease that affects the hepatocytes of the liver.

Diseases can be caused by a variety of agents:◦ Bacteria◦ Protozoans◦ Viruses◦ Toxins◦ Drugs

At least 6 different viruses cause hepatitis◦ They are distinctly different from one another.

Therapy is mainly symptomatic Interferon-alpha therapy for HCV Vaccines available for HAV and HBV

◦ HBV required for all healthcare workers

Hepatitis viruses

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Hepatitis virusesTransmissio

nChronic

liver disease

Carrier stage

Vaccine

Hepatitis A Fecal-oral No No Inactivated virus

Hepatitis B Parenteral, STD

YesLiver cancer

Yes Recombinant

Hepatitis C Parenteral YesLiver cancer

Yes No

Hepatitis D Parenteral, HBV coinfection

Yes Yes HBV vaccine

Hepatitis E Fecal-oral No No No

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Liver cirrhosis as complication of hepatitis

Belongs to Flaviviridae + ssRNA, enveloped, entirely cytoplasmic

replication Transmitted mainly by transfusion (including

needle sharing and hemodialysis, also sexual Is considered persistent (infects mainly

hepatocytes, but also documented for peripheral blood mononuclear cells)◦ CTL escape mutations◦ Interfere with interferon regulatory factor

Usually mild hepatitis or asymptomatic 80% of the infected become chronically

infected and of these up to 20% develop cirrhosis and of these up to 5% hepatocellular carcinoma.

Hepatitis C virus

Diagnostic◦ Antibody detections (RIBA) and detection of viral

RNA in blood (RT PCR) Therapy

◦ Sympotmatic◦ INFa + ribavirin, but only 50% success◦ INFa induces natural antiviral proteins◦ Ribavirin is a nucleoside analogue and inhibits

viral nucleic acid replication

Hepatitis C virus

Several protozoan and helminthic infections of the human digestive system are known

Common parasitic diseases are caused by:◦ Giardia◦ Cryptosporidium◦ Whipworms◦ Hookworms

Parasitic infections of the digestive system