Fifty Shigella species which fall into one of four serological groups.
Group A - S. dysenteriae (S. shiga)
which is not encountered in the U.S. except for rare
instances of imported disease.
Group B - S. flexneri, a species commonly isolated in the U.S.
Group C - S. boydii and related species which are rarely isolated in the U.S.
Group D - S. sonnei, the most commonly isolated cause of shigellosis in the U.S.
Shigella are gram-negative rods whose natural
and sole habitat is the intestine of humans and
Shigellosis is primarily a disease of direct anal-oral transmission, although food-borne and water-borne and insect-borne epidemics have occurred. Despite modern environmental hygiene shigellosis persists because
1. Shigella are present in large numbers around the bases of toilets used by infected persons.
2. They readily pass through toilet paper onto the fingers.
3. As few as 2000 ingested organisms can cause disease.
4. It can be spread by horseflies
5. Closed population groups
often have substandard sanitation (e.g., prisoner-of-war camps,
homes for mentally retarded, Indian reservations).
Shigellae are closely related to Escherichia coli and share antigens and toxin-producing capability with them. They produce both an endotoxin and an exotoxin. The exotoxin is an enterotoxin that produces diarrhea like the E. coli LT toxin and the cholera toxin. Acting as a neurotoxin, this exotoxin causes meningismus and coma. It can also cause an ulceration of the intestine. Upon invasion of a cell, shigellae produce and excrete another major virulence factor, NAD glycohydrolase, which destroys all of the NAD of the human cell and virtually shuts down cellular metabolism, causing cell death.
Shigellosis is mainly a disease of children between
1 and 4 years of age. It is transmitted by the 4-F's: food; fingers; feces;
Upon ingestion the microorganisms pass to the large
intestine where they must penetrate the cells of the epithelial lining
in order to cause diarrhea. Non-invasive shigellae are not pathogenic.
Non-toxin producing shigellae are also not pathogenic. Pathogenesis requires
invasion and toxin production. Following intracellular penetration, multiplication
occurs in the submucosa or lamina propria. Distortion of crypts occurs
as clumps of cells are sloughed. This causes blockage. The accumulation
of inflammatory cells behind the obstruction leads to the formation of
microabscesses. Through spread and coalescence, larger abscesses form.
Long sections of affected colon or sigmoid may be covered by a fibrous
exudate containing huge numbers of neutrophils. Bleeding occurs from superficial
ulcerations that are about 5 mm in diameter. Perforation is NOT a complication
because of the superficial localization of the infection. Invasion of the
blood stream is uncommon.
After an incubation period of 36-72 hours, the initial non-specific symptoms of fever and cramping abdominal pain are prominent. Diarrhea usually appears after 48 hours, with dysentery supervening about 2 days later. Abdominal tenderness is usually general, and the abdominal wall is not rigid. Sigmoidoscopy reveals intense hyperemia, multiple small bleeding sites, loss of transverse mucosal folds and thick, purulent mucous secretions. Tenesmus is present and the feces are bloody, mucoid and of small volume.
Fluid and electrolyte loss may be quite significant,
particularly in pediatric and geriatric populations. There may be a peripheral
neurites and convulsions. Escherichia coli septicemia may be initiated
Presumptive diagnosis is based on the acute onset of fever and diarrhea with bloody and mucoid feces. Definitive diagnosis requires the isolation of Shigella from the feces. Microabscesses in a rectal biopsy are suggestive of shigellosis. Diffuse involvement of the mucosa with multiple shallow ulcers 3-7 mm in diameter is suggestive of shigellosis. A rectal swab of an ulcer will reveal clumps of neutrophils, macrophages and erythrocytes.
Shigella are commonly isolated on S-S agar
(Salmonella - Shigella agar).
Shigellosis is usually a self-limited disease. However,
trimethoprim-sulfamethoxazole will kill
S. dysenteriae and ampicillin
will kill S. flexneri. Fluid and electrolyte replacement is necessary
in severe cases. Antidiarrheal compounds which inhibit peristalsis are
The cause of typhoid fever is Salmonella typhi.
This is a cytophilic, gram-negative, aerobic, noncapsulated, non-spore-forming,
motile rod. Presumptive identification is based on serological tests for
the somatic (0) and flagellar (H) antigens.
The sole source of S. typhi is the human intestinal
tract. The organism is ingested in fecally-contaminated food or water.
It passes to the duodenum where the organism rapidly penetrates the intestinal
mucosa into the regional lymphatics, where it is phagocytized. Neutrophils
are unable to kill ingested bacteria and they gain entry to the circulatory
system. The resulting septicemia is quickly terminated through removal
by reticuloendothelial cells in liver, spleen, bone marrow and lymph nodes.
However, the bacteria multiply within these cells giving rise to a sustained
bacteremia. During this sustained bacteremia; the biliary tract is infected
and the organisms are excreted in the bile which seeds the intestinal tract
with millions of bacteria, setting up a cycle of infection. In 14% of people
infected, there is asymptomatic colonization of the gall bladder, with
these people becoming carriers who spread the disease. The major virulence
factor of S. typhi is the Vi antigen, a surface antigen which interferes
with phagocytosis and, if the cell is still phagocytized, inhibits the
respiratory burst which is instrumental in killing ingested bacteria. Endotoxin
is another virulence factor.
Click on image to see enlarged version.
The proliferation of large mononuclear cells derived
from reticuloendothelial tissue is the most prominent feature of the pathology
of typhoid fever. Involvement of lymphoid tissue in the intestinal tract,
principally Peyer's patches in the terminal ileum, may lead to necrosis
and ulceration at these sites. The erosion of blood vessels in the lesions
may give rise to intestinal hemorrhage. Although intestinal lesions are
usually confined to the mucosa and submucosa, muscular and serosal layers
are occasionally penetrated, leading to intestinal perforation.
The liver is enlarged during typhoid fever; there
are focal areas of necrosis with cloudy swelling of hepatic cells. The
spleen and mesenteric lymph nodes are enlarged, and there is hyperplasia
of reticuloendothelial cells. Bronchitis is common and pneumonia is not
unusual. The maculopapular skin lesions are infiltrated with mononuclear
cells, and there is vascular congestion.
After an incubation period of 8-14 days, fever is usually the earliest indication of typhoid fever, rising in a step wise fashion during the first week. The onset of symptoms is gradual; they include:
general aches and pains
dull, continuous headache usually confined to the frontal regions
nosebleed (10% of patients)
vague abdominal pain and discomfort
constipation (20% of patients have mild diarrhea)
During the physical exam at this stage of the disease there is tenderness upon palpation of the lower quadrants of the abdomen. Distension is frequently present, and the examiner may experience a sensation of displacing loops of bowel filled with air and fluid on palpation of the abdomen.
During the second week of illness the temperature is sustained at 104° F. The patient is frequently severely ill during this phase of illness; weakness, mental dullness or even delirium may be prominent. Abdominal discomfort and distension increase, and diarrhea is more common then during the first week. The feces may contain blood.
The face is dull and expressionless. Rhonchi and scattered moist rales occur in as many as 50% of patients. Splenomegaly and rose-colored spots on the abdomen are common. These are small maculo-papular lesions that blanch on pressure. The lesions are usually sparse, not exceeding 20.
As the illness extends into the third week, the patient
continues to be febrile and becomes increasingly exhausted and weak. If
no complications occur, the patient may begin to improve toward the end
of the third week. The temperature gradually begins to decline and may
reach normal levels by the end of the fourth week.
Typhoid fever may be confused with a wide variety of infections diseases characterized by fever. A history of travel in endemic areas or a prolonged febrile illness with or without typical manifestations of typhoid should arouse suspicion. Rose colored spots on the abdomen which persist for 2-4 days and recur in crops is the best diagnostic clue. Examination of blood reveals:
leukopenia with a relative decrease in polymorphonuclear leukocytes and an absence of
presence of S. typhi which can be isolated on S-S agar.
positive Widal reaction - this is agglutination of somatic and flagellar antigens
Examination of feces reveals:
presence of S. typhi
Examination of urine reveals:
presence of S. typhi
Confirmative diagnosis requires the isolation of
typhi or the demonstration of a four-fold or greater rise in antibody
to the "O" antigen.
The drug of choice is chloramphenicol. Secondary
antibiotics include ampicillin, amoxicillin, trimethoprim - sulfamethoxazole
and gentamicin. Laxatives and enemas are CONTRAINDICATED because of the
danger of inciting intestinal perforation or hemorrhage.
A vaccine consisting of killed S. typhi is
given parenterally in two doses 4 weeks apart. A single booster dose can
then be given every 3 years. Vivotif, a newly licensed vaccine, is an oral
live-attenuated one with fewer adverse reactions. It is administered as
one enteric-coated capsule taken on alternate days to a total of 4 capsules.
Each capsule should be taken with cool water, no warmer than 37° C
approximately 1 hour before a meal.
Entamoeba histolytica is the cause of amebiasis
or amebic dysentery. It occurs in three stages: the active amoeba, the
inactive cyst and the intermediate precyst. The ameboid trophozoite is
the only form present in tissue. The cytoplasm is granular and may contain
red blood cells (presence of intracytoplasmic red blood cells is pathognomonic).
Infection is acquired by ingestion of cysts of E.
histolytica in contaminated food or water. Excystation occurs in the
small intestine, and trophozoites become established in the lumen of the
proximal colon in which they often live without causing symptoms. Symptoms
only result from invasion of the colon by trophozoites.
Click on image to see enlarged version.
When mucosal resistance becomes lowered, trophozoites can invade colonic epithelium. Ameboid movement and amebic enzymes such as proteases, hyaluronidase and mucopoly-saccharidases facilitate penetration from the surface or within crypts of the mucosa. Eventually the venules and lymphatics are penetrated and the trophozoites gain access to the liver via the portal vein. The liver becomes the chief site of extraintestinal amebic disease.
Involvement of nonhepatic extraintestinal organs
is much less frequent. Trophozoites may disseminate to other organs, especially
from a liver abscess, by direct rupture into lung, pleural cavity or pericardium,
or through the bloodstream to lung or brain. Cutaneous lesions may result
from direct invasion of macerated epithelium in the perianal area when
trophozoite-containing liquid feces contaminate the skin.
The major lesions are colonic ulcers, colonic granulomas, diffuse hepatitis, hepatic abscess, brain abscess and rectal ulcerations. The primary lesions of the intestinal tract are ulcerations in the cecum, appendix and adjacent ascending colon. The unique feature of these ulcers is that they are flask-shaped. These lesions enlarge, gradually losing their characteristic form, and develop elevated margins with a white exudate on the base of the ulcer.
The organisms in the hepatic microcirculation produce
necrosis of the endothelium and penetrate into the periportal sinusoids,
where they may digest pathways into the hepatic lobules. Initially there
is no inflammatory reaction but as necrosis progresses polymorphonuclear
leukocytes gradually surround the lesion without formation of a definite
wall. The lesions may remain focal or progress to form large solitary abscesses.
Lung and brain abscesses are similar to those in the liver. Skin ulcerations
show little inflammatory reaction.
After an incubation period of 1-5 days, the disease begins with a prodromal episode of diarrhea, abdominal cramps, nausea, vomiting and tenesmus; there may be vague abdominal discomfort, general malaise, loss of appetite, lose of weight and mental apathy. The feces may be watery or formed, but with dysentery they are generally watery, containing mucous and blood.
The association of an enlarged tender liver with
fever and colitis is classic amebic hepatitis. Brain abscesses give rise
to the symptoms of meningitis.
The diagnosis of amebiasis is made by identifying
histolytica in the feces or in tissues obtained from lesions.
The choice of amebicides is based on the location and severity of infection:
Asymptomatic intestinal infection
- diloxanide furoate (Furamide) or iodoquinol (Yodoxin) or
Necrotizing amebic colitis
or ameboma - diloxanide furoate plus metronidazole (Flagyl) or
dehydroemetine plus emetine
Extraintestinal amebiasis - metronidazole plus iodoquinol.
Pleural involvement may require
drainage via a chest tube or thoracotomy.
Several species of Campylobacter cause gastrointestinal
infections. C. jejuni is the most common cause of gastroenteritis
worldwide. Helicobacter pylori (originally called
pylori) grows in the stomach and duodenum where it causes gastritis
and peptic ulcer disease. These are gram-negative, comma-shaped rods that
commonly occur in pairs.
C. jejuni is ingested with contaminated water, raw milk and food (especially poultry). It colonizes the jejunum where it elaborates:
Enterotoxin - similar to the LT toxin of Escherichia coli (causes diarrhea)
Verotoxin - similar to the Shigella toxin (causes hemorrhagic colitis)
Three to five days after ingestion, overt disease
occurs only if the organism penetrates the mucous coating the epithelial
cells and invades the cell.
The colitis syndrome produced by C. jejuni
is similar to that produced by Shigella and enteroinvasive Escherichia
Watery diarrhea is the most common manifestation.
Clinical findings are not diagnostic. Along with the diarrhea there is
sometimes pain, malaise and fever.
Diagnosis is based on the finding of gull-shaped
bacteria in watery, blood, leukocyte-filled feces.
Erythromycin may be useful but this is generally
a self-limited disease. Replacement of losses of water and electrolytes,
as in any diarrheal disease, is important.
ESCHERICHIA COLI INFECTION
Enteroinvasive Escherichia coli (EIEC) have
outer membrane proteins that are very similar to those of Shigella
and allow for cellular invasion. They produce clinical disease indistinguishable
from Shigella. An EIEC strain with the serotype 0157:H7 is the cause
of hemolytic uremic syndrome associated the eating undercooked meat in
the Northwestern U.S. in 1992-1993. This
E. coli initiates
ulcer formation in the intestinal epithelial lining. These ulcers allow
blood, including white blood cells, to pass into a patient's stool, initiating
a hemorrhagic colitis, the main symptom of which is diarrhea laced with
blood. There are also severe stomach cramps, dehydration and mild fever.
The shigella-like toxin permanently destroys kidney function, requiring
the patient to undergo dialysis for life.
PEPTIC ULCER DISEASE
Helicobacter pylori. This is a curved, rod-shaped
bacillus that is Gram-negative but stains best in tissue biopsies using
a modified Giemsa stain. It is motile, microaerophilic and a slow grower
(it takes at least 7 days to form a colony on agar medium at 37°C).
It contains an adhesin which is also a hemagglutinin. Its most unique characteristic
is copious production of urease.
The sources of Helicobacter pylori remain
obscure. However, it is known that ingestion of 105 or larger
number of organisms will cause peptic ulcer disease. By five to ten days
after the ingestion, the organisms have penetrated the stomach epithelium
with production of symptomology.
The epithelial cells of the pylorus of the stomach
are the primary target of chronic infection that may result in chronic
active gastritis and peptic ulceration. This correlates with adenocarcinoma
of the stomach. Ammonia from urea and nicotine potentiate the action of
the action of a cytotoxin produced by H. pylori. The end result
is vacuolization of the epithelial cell and induction of a chronic inflammatory
process and eventual ulcer formation. The inflammatory response is primarily
one of mononuclear cells.
Patients with peptic ulcer disease have an associated
gastritis. Gastritis results in dyspepsia, cramps, halitosis, ructus, nausea,
vomiting and flatulence.
Antibodies specific for H. pylori is suggestive
of helicobacteriosis. Histological identification of H. pylori in
gastric biopsy specimens buttressed by isolation in culture is confirmative.
Combination therapy, consisting of antimicrobics
and bismuth-containing drugs, is effective in eradicating H. pylori
from the stomach. Amoxicillin, tetracycline and ciprofloxacin are all effective.
However, the optimum therapy has not yet been defined.
NAMES OF DISEASE: Crohn's Disease
Mycobacterium paratuberculosis, a Gram+,
acid-fast+, plump rod.
This organism causes Johne's Disease in cattle and
sheep. The organism infects the intestinal mucosa of cattle, causing a
chronic diarrhea. It is transmitted to humans via ingestion of undercooked
After ingestion of the organism it invades the human intentional mucosa in the terminal ileum and the colon. A chronic inflammation extends through all layers of the intentional wall and involves the mesentery as well as regional lymph nodes. The bowel appears greatly thickened and leathery with the lumen narrowed. This may cause varying degrees of intentional obstruction. The mesentery is thickened, fatty, and often extends over the serosal surface of the bowel in characteristic finger-like projections. As the infections progresses the tissue, becomes granulomatosis. There is characteristic fistula and abscess formation. The disease is often discontinuous with patches of infected tissue separated by areas of normal tissue.
Diagnosis is generally achieved by fiber optic colonoscopy
for tiny longitudinal fissures or ulcers and a cobblestone appearance.
Isolation of Mycobacterium paratuberculosis requires specialized
cultural conditions, is difficult and unreliable and is not routinely done.
Antimicrobial treatment has not been universally
effective. Possibilities for treatment include sulfasalazine and metronidazole.
Commonly used anti-tuberculosis drugs have not proven effective.