SALMONELLA INFECTIONS

(salmonelloses)
• The Enterobacteraceae comprise
Salmonella, Shigella, Escherichia,
Klebsiella, Enterobacter, Serratia,
Proteus, Morganella, Yersenia, and
other less common genera. This
oxidase-negative, Gr. (-), catalase-
positive organisms are readily cultured
on ordinary media, ferment glucose
and reduce nitrates to nitrites.
 The 2200 known serotypes of
Salmonella may be grouped into
these
• highly adapted to human hosts
• adapted to non-human hosts
• unadapted to specific host
• The first group includes S. typhi and S.
paratyphi A, B and C, which are pathogenic
only in humans and commonly cause enteric
fever.
• The second group causes disease almost
exclusively in animals, although 2 strains
within this group, S. dublin and S.
choleraesuis also cause disease in humans.
• The third group designated S. enteritidis,
includes > than 2000 serotypes that cause
gastroenteritis.
 TYPHOID FEVER
• A systemic disease caused by S. typhi
and characterized by fever, prostration,
abdominal pain, and a rose-colored
rash
 Pathogenesis

• S. typhi invades first the alimentary tract by

ingestion, then via the lymphatic system, via
the thoracic duct into the blood stream.
• This first septicemic phase leads to infection
of the reticuloendothelial system and the gall
bladder.
• Infection of the gall bladder causes discharge
of organisms into the intestine, with heavy
infection of the Peyer’s pathes and septicemia
- and the onset of symptoms.
 Symptoms and signs

• IP - 8-14 (14-21 days)

• Onset is usually gradual, with fever, headache,
arthralgias, pharyngitis, constipation, anorexia, and
abdominal pain and tenderness.
• If no therapy is began the temperature raises in steps
over 2 to 3 days, remains elevated (usually to
39-40°C) for another 10 to 14 days, begins to fall
gradually at the end of the 3rd wk, and reaches normal
levels during the fourth week.
• Prolonged fever is often accompanied by relative
bradycardia and prostration and CNS symptoms such
as delirium, stupor, or coma occur in severe cases.
• In about 10% of the patients discreet pink,
blanching lesions (rose spots) appear in
crops on the chest and abdomen during the
2nd wk and resolve in 2 to 5 days.
• Intestinal perforation, usually involving the
distal ileum, occurs in 1-2% of patients.
• Splenomegaly, leucopenia, anemia, liver
function abnormalities, proteinuria, and a mild
consumption coagulopathy are common
• Diarrhea is a late symptom, usually in the
third week of illness and still may contain
blood. In about 2% of patients, severe
bleeding occurs during the third week with a
mortality rate of about 25%.
• In addition bacteriemia, occasionally leads
to focal infections, such as osteomyelitis,
endocarditis, menengitis, soft tissue
abscesses, glumerulonephritis, or GU tract
involvement.
 Complications
• Relapse, intestinal perforation and
hemorrhage are the most serious.
Relapse is common, with recrudescence
of symptoms about a week after the end of
the primary illness
• Carriers - around 2-5% of patients with
typhoid fever become chronic carriers,
owing to persistent infection of the gall
bladder.
 Diagnosis
• Best made by isolation of the infecting
organism from feces, blood and urine.
Blood culture is positive in over 80% of
patients in the first week of illness.
• Blood and urine: Mac Conkey medium
• Feces: use selective and enrichment
media
Identification = biochemical reactions:
S typhi, unlike other salmonellae,
produces no gas on fermentation of
sugars.
= serological: preliminary
identification with salmonella polyvalent H
and O antisera
= phagotyping
• Serology: the classic test is the Widal test:
agglutination test for antibodies to flagellar
H antigens and somatic O antigens of S.
typhi and S. paratyphi A and B, but the
results are difficult to interpret, especially if
the patients has been immunized with
typhoid vaccine. This test is no longer
used in routine diagnostic laboratories.
 Treatment
• Ciprofloxacin 500mg po q12h; is the drug of
choice, especially with the emergence of
multiresistance involving other antibiotics -
but care is needed with children. Ceftriaxone
is a useful alternative in such cases.
• Ceftriaxone 30mg/kg/day im or iv in 2 divided
doses for 2 week (eg. 1 g iv q 12h for adults).
• Cefoperazone is given 60mg/kg/day iv in 2
divided doses for 2 weeks.
• Co-trimoxazole.
 PARATYPHOID FEVER
• Causal organisms: S. paratyphi A, B and C
• Clinically a milder febrile illness than typhoid fever, with a
shorter duration and incubation period. Transient diarrhea and
symptomless infection are common.
• Carriers: patients become carriers less frequently than after
typhoid fever.
• Diagnosis: best made by isolation of the infecting organism
from feces, blood and urine. Blood culture is positive in over
80% of patients in the first week of illness.
• Treatment: Ciprofluxacin is the drug of choice, but care is
needed with children. Ceftriaxone is a useful alternative in
such cases. Chloramphenicol is as effective, but resistance is
now a problem. Co-trimoxazole is less good than
Chloramphenicol, but has less serious side effects.
NON-TYPHOIDAL SALMONELLA
INFECTIONS
• Formerly the commonest cause of diarrhea in Europe
and the USA.
• Diarrhea due to Salmonella is traditionally called food
poisoning, although this term is somewhat misleading.
Infected meat-producing animals, poultry, raw milk,
eggs and egg products are common sources of
Salmonella.
• There are more than 2000 serotypes of Salmonella,
but only about 14 are important or common causes of
infection.
• In recent years the commonest serotype has been S.
enteritidis. Other common Salmonellae are S. typhi
murium, S. heidelberg, S. Newport, S. agona
 Pathogenesis
• Sight of infection is the small or large
intestine. Many strains produce
enterotoxins similar to those of toxigenic
strains of E. colli. NB!: The Salmonella
enterotoxins are still poorly defined. Other
Salmonellae invade the mucosa of the
small intestine like Shigellae.
 Symptoms and signs
• Salmonella infection may present clinically as
gastroenterits, enteric fever (S. paratyphi A, B
and C), a bacteremic syndrome, or focal
disease.
• IP is short: around 12-36-48 hours.
• Main symptoms are acute onset of abdominal
pain and diarrhea, sometimes with fever and
vomiting. Dehydratation may require
correction, especially in babies.
• Usually the stool is watery, but made be
paste - like semisolid. Rarely, mucus or
blood is present.
 Bacteremia
• (S. choleraesuis, S. typhimurium, S.
heidelberg). Although blood cultures are
positive, stool cultures are generally
negative.
 Focal manifestation
• of Salmonella infections may occur with or
without sustained bacteriemia. In patients
with bacteriemia localized infection may
occur, involving the GI tract (liver, gall
bladder and appendix), endothelial
surfaces.(heart valves), pericardium,
meninges, lungs, joints, bones, GU tract.
 Diagnosis
• Is made by isolating the organism from stool
or another infected site. The prognosis is
usually good unless severe underlying
disease is present. Asymptomatic carriage is
usually self-limited and antibiotics treatment
is rarely required. Eradication may be
attempted with Ciprofluxacin - 500 mg po
q12h for 1 month, but follow up stool cultures
should be obtained in the weeks after drug
administration to document elimination of
Salmonella.
 Treatment
• Rarely necessary: rehydratation may be required in
babies: oral isotonic fluid replacement can be life-
saving in infants with diarrhea.
• Antibiotics are contraindicated except in septicemia
cases: they do not affect symptoms and may prolong
convalescent carriage of the organism; they also
contribute to the emergence of antibiotic resistant
strains.
• Trimethoprim-Sulphamethaxazole (TMP-SMX) 5mg/kg
of TMP component po every 12h for children, or
Ciprofluxacin 500mg po q12 hours for adults.
• Neledix 50mg/kg
• Gentamycin - 2-5mg/kg
• Amikacin 5-15mg/kg.
 SHIGELLOSIS
(Dysenteriae)
• Shigellosis is an acute infectious
inflammatory colitis due to one of the
members of the genus Shigella. The
less severe illness predominates in
industrialized countries, whereas more
severe, often fatal dysenteria occurs in
patients in developing countries.
 The four species of Shigella
are:
• S. dysenteriae
• S. flexneri
• S. boydii
• S. sonnei
All the species except S. sonnei contain
several distinguishable serotypes.
 Pathogenesis and pathology
• Shigella are orally ingested and because they survive
low pH better than other enteric pathogens, they seem
to have little difficulty in passing the gastric acid barrier
• An essential step in pathogenesis is invasion of
colonic epithelial cells and cell-to-cell spread of
infection.
• Invasion and cell-to-cell spread involve the initial
attachment of the organism to colonic cells, entry by
and an endocytic mechanism, in which organisms are
initially incased in and then escape from plasma
membrane-enclosed vesicles, and a jet propulsion-like
movement to the epithelial cell surface that is powered
by bacteria-induced actin polymerization at the trailing
end of the bacterium
• A second property of apparent importance
in virulence, at least for S. dysenteriae
type I is the ability to produce cytotoxic
proteins. Shiga toxin composed of two
distinct peptide subunits, each with highly
conserved active regions.
• Shigella organisms penetrate the mucosa
of the lower intestini, causing mucous
secretion, hyperemia, leucocytic
infiltration, edema and often superficial
mucosal ulceration. The watery diarrhea
associated with shigella infection may be
mediated by an enterotoxin that causes
increased intestinal secration.
• S. dysenteriae has invasive properties and
produces a powerful neurological exotoxin,
but this probably does not play a role in shiga
dysenteriae. An enterotoxin and cytotoxin are
also produced: their role is uncertain, but they
may be partly responsible for invasiveness.
Shiga toxin, is very closely related to E. colli
verocytotoxin 1(VT1). Cytotoxins, which
cause destruction of mucosal cell and
associated inflammatory diarrhea; and
neurotoxins, which act directly on the central
or peripheral nervous system.
 Symptoms and signs
• IP: 1-9 days.
• Diarrhea with blood, mucus and often pus in the
stools, which varies from a severe life threatening
to a mild and symptomless infection.
• In young children onset is sudden, with fever,
irritability or drowsiness, anorexia, nausea or
vomiting, diarrhea, abdominal pain and distention
and tenesms. The number of stools may increase
to more than 20/day, and weight loss and
dehydratation may become severe.
• In adults first symptoms may be episodes of
abdominal pain, urgency to defecate and little or
no tenesms.
 Complications:
• severe mucosal ulcerations may cause
significant acute blood loss.
• Intestinal perforation
• Hemolytic-uremic syndrome in children
• Arthritis, myocarditis, toxic neuritis
 Laboratory findings and
diagnosis
• Diagnosis: isolation - culture feces and rectal
swabs on MacConckey medium and
selective media. Identify by biochemical tests,
then serology.
• WBC count is often reduced at onset;
hemoconcentration is common, as is
diarrhea-induced metabolic acidosis.
• The mucosal surface, as seen through a
prostoscope, is diffusely erithematous with
numerous small ulcers.
 DD
• Should include invasive E. colli,
Salmonella, Yersenia, Campylobacter,
Amebiasis, and viral diarrheas.
 Treatment
• Fluid therapy. Diarrhea usually causes isotonic
dehydratation (equal salt and water loss), with
metabolic acidosis and significant potassium loss.
Thirst from dehydratation can lead to a proportionately
excessive water intake, causing hypotonicity.
• Antibiotics. The decision to use antibiotics requires
consideration of disease severity, age of the patient
and other factors. In children, TMP-SMX at 4mg/kg/po
of the TMP component q12h is the treatment of
choice.
• In adults the dose is one double strand tablet q12h
(320 mg TMP). An alternative for adults is norfluxacin
or ciprofluxacin - 500mg po bid (two times a day).
Many shigella isolates are likely to be resistant to
Ampicillin and Tetracyclin
 CHOLERA
• An acute infection by Vibrio cholerae
involving the entire small bowel
characterized by profuse watery
diarrhea, vomiting muscular cramps,
dehydratation, oliguria, and collapse.
 Etiology
• The causative organism, V. cholerae, serogroups
01 and 1039. Epidemic cholera is caused by V.
cholerae serogroup 01. which is divided into three
serotypes, Ogava, Inaba, Hikojima. However,
antigenic structure may change within the human
gut.
• Biotypes: two biotypes of V. cholerae 01, classic
and El Tor. Any serotype can be of either classic
or El Tor biotype.
• Non-01 vibrios, deficient in the 01 antigen, were
classified as non-cholera vibrios - but a cholera
epidemic in Bangladesh in 1992 was due to
serogroup 0139.
 Pathogenesis
• V. cholerae produces a potent exotoxin - cholera
toxin (CT), vary similar to the LT enterotoxin of
ETEC, which is plasmid coded. The toxin
stimulates the activity of the enzyme
adenylcyclase, which raises the concentration of
cyclic AMP is cell; this causes an increase in the
flow of water and electrolytes into the bowel
lumen. The fluid lost has relatively high
concentration of bicarbonate and potassium.
• V. cholerae is not invasive and does not penetrate
the gut mucose membrane, although adhesion to
gut epithelium plays a part in its pathogenesity.
 Clinical feature
• IP - 6h to 5 days.
• Acute onset of abdominal pain and diarrhea - the
diarrhea being typically of exceptional severity,
progressing to the continuous passage of “rice-
water” stools.
• Vomiting, dehydratation, acidosis and collapse
may follow.
• Some cases are much les severe with only mild
diarrhea. Two forms of disease are recognized:
• severe classic cholera
• milder cholera associated with the 01 El Tor
biotype.
CHOLERA
 Diagnosis

Culture feces on alkaline selective

medium. Observe for typical colonies,
which can be identified by slight
agglutination, with polyvalent antiserum.
 Treatment

• Correction of dehydratation by intravenous

administration of fluid and electrolytes to
restore the acid-base balance. Mortality
can be reduced from more the 50% to 0
with fluid replacement treatment.
• Tetracycline, given orally or intravenously,
may help to limit the duration of diarrhea
and reduce fluid loss.
• Composition of World Health Organization
oral rehydratation solution (WHO ORS).

In 1000ml pre-boiled water:

20g glucose
3.5g NaCl
2.5g NaHCO3
1.5g KCl
Concentration (mmol/l): Na 90, K 20, HCO3
30
ex tempore
Rehydrin
- Phillips solution
ESHERICHIOSES
INTESTINALES
(COLIBACILLOSES)
Enteric infections are common cause of
diarrhea:
• infantile gastroenteritis
• travelers diarrhea
• hemorrhagic diarrhea
-hemorrhagic colitis
-hemolytic-uremic syndrome
• ETEC - enterotoxigenic E. coli - travelers
diarrhea (“Delhi belly”, “Tokyo two step”
etc)
• EPEC - enteropathogenic
(eneteroadherent) E. coli - childhood
diahhrea.
• EIEC - enteroinvasive E. coli - a
dysentery-like disease
• EHEC - enterohemorrhagic E. coli -
hemorrhagic colitis and HUS in children.
 EPEC (055; 0111) strains
• cause childhood diarrhea, especially in
underdeveloped countries and in nursery
outbreaks. These bacteria bind to the
membranous cells of Peyer’s patches and
disrupt the overlying mucous gel of the
host cell.
• EPEC do not produce toxins and are non-
invasive, but produce an attaching end
effacing lesion in the small intestine
• ETEC - there are more than 100 0
serogroups. Important examples are 06, 078.
• ETEC produce heat-labile toxin (LT) or heat-
stabile toxin (ST) or both. They also posses
colonization factors, which facilitate the
attachment of the organism to the epithelium
of the small intestine.
• EIEC (0124, 0164) invade the host cell and
provoke significant inflammatory response.
Manifestations are those of bacterial
dysentery with fever and bloody diarrheal
stool, containing polymorphonuclear
leukocytes.
 EHEC strains
• all belong to the serotype 0157:H7, cause
hemorrhagic colitis.
• These strains produce shiga-like toxins that kill
certain cells in tissue culture.
• Although the typical patient is afebrile the sequel
can be severe. In the elderly the disease is often
confused with ischemic colitis. It can lead to death.
Children (1-4 years) and occasionally adults with
EHEC infection can develop HUS, which also can
lead to death. HUS is seen occasionally with
bacteria other than 0157:H7, including other E.coli
serotypes and Shigella.
∀∗ HUS in children - diarrheal prodrome,
followed by uremia, throbocytopenia and
hemolytic anemia.
∀∗ Shiga-like toxins have a cytopathic effect on
Vero (monkey kidney) cells. There are two
Vero cytotoxins, VT1 and VT2, which are
antigenically distinct from each other. Vero
cytotoxin - producing E.coli strains are
known as VTEC. Over 80% phagotypes of
serogroup 0157 can be distinguished.
 Diagnosis
• Culture feces on MacConckey medium.
• Identify by serology and biochemical
tests.
 Treatment
• Rehydratation with correction of fluid loss and
electrolyte and acid base balance
• Antibiotics therapy is of doubtful value,
although it may be useful in severe cases
• Treatment may be started empirically, than
modified on the basis of antibiotic sensitivity
studies. Although many strains are still
sensitive to Ampicillin (Piperacillin,
cephalosporins, amynoglucosides, TMP-
SMX, and quinolons in adults).
 DEHYDRATION
SYNDROME
Rehydration
• oral rehydratation - WHO ORS
In 1000ml pre-boiled water:
20g glucose
3.5g NaCl
2.5g NaHCO3
1.5g KCl
Concentration (mmol/l): Na 90, K 20, HCO3 30, Cl
80
ex tempore
Rehydrin - a commercial solution
 i.v. fluids:
• Classification of dehydratation in infants:
• Ist grade - up to 5% loss of body weight
(infuse with 80-100ml/kg/24h)
• IInd grade - between 5-10% loss of body
weight (120-150ml/kg/24h)
• IIIrd grade - more than 15% loss of body
weight (150-170ml/kg/24h)
• At the end of the rehydratation period
(about 4 hours), the patient should be
reassessed. If signs of dehydratation
persist, rehydratation therapy should be
repeated until dehydratation is corrected
 Metabolic acidosis - ph<7.37
• The amount of NaHCO3 can be
approximated by the formula:
• NaHCO3 required (mEq) = BE(base
excess) x 0.4 x body wt(kg)
• First 1/3rd of the received quantity is
applied and if fails to correct the acidosis,
the rest is added.
 Hypokaliemia
• a decrease in the serum potassium
concentration, below 3.5 mEq/l. It is a
result of excessive losses of K from GI
tract. It is characterized my muscle
weakness and can lead to paralysis and
respiratory failure. ECG - ST depression.
• Treatment - i.v. KCl - amp.15% 10ml
2mEq/kg slowly!
• The use a antibiotics therapy in bacterial
diarrheas is controversial and generally
not necessary in patients with mild or
resolving disease, but should be
considered in patients with Shigellosis,
travelers diarrhea, cholera.