 Enteric fever, or typhoid fever, is a

distinctive acute systemic febrile

infection of the mononuclear
phagocytes
 caused by S. Typhi, S. Paratyphi A,
S. Paratyphi B (Schottmuelleri),
and S. Paratyphi C (Hirschfeldii)
Etiology
Salmonellae
a genus that belongs to the family
Enterobacteriacae & contains 3
species:
S. typhi
S. choleraesuis
S. Enteritidis

has more than 2300 serotypes

gram-negative, flagellate,
nonsporulating, facultative anaerobic
bacilli
ferment glucose, reduce nitrate to
nitrite, and synthesize peritrichous
flagella when motile
Allbut S typhi produce gas upon sugar
fermentation
resistantto many physical agents but
can be killed by heating to 130°F
(54.4°C) for 1 hr or 140°F (60°C) for 15
min
salmonellae are grouped based on the
somatic O antigen and further divided
into serotypes based on flagellar H and
surface virulence (Vi) antigens
O antigens are the heat-stable
lipopolysaccharide components of the
outer membrane
H antigens are heat-labile proteins that
can be present in phase 1 or 2
S typhi, S paratyphi C, and Salmonella
Dublin are the only Salmonella
serotypes that carry Vi antigen
 Ranked 10th in the leading causes
of morbidity in the Philippines w/ a
rate of 19.5/100,000 population &
an almost equal prevalence
between male & female
 affects all ages including infants
 The WHO has estimated that at
least 12.5 million cases occur
annually worldwide
humans are the only natural
reservoir
direct or indirect contact with
an infected person (sick or
chronic carrier) is necessary for
infection
Ingestion of foods or water
contaminated with human feces
is the most common mode of
transmission
 Water-borne outbreaks due to
poor sanitation and direct fecal-
oral spread due to poor personal
hygiene are encountered, mainly
in developing countries
 Oysters and other shellfish
cultivated in water contaminated
by sewage are also a source of
widespread infection
Pathogenesis
 inoculum size: 105 –109 S. ser. Typhi organisms
(in volunteers)
ingestion of contaminated food

bacteria invade through the Peyer patches

multiplies within the mononuclear phagocytic

cells in the liver, spleen, lymph nodes, and
Peyer patches of the ileum
monocytes, unable to destroy the bacilli
early in the disease process, carry these
organisms into the mesenteric lymph
nodes

organisms then reach the bloodstream

through the thoracic duct, causing a
transient bacteremia

circulating organisms reach the

reticuloendothelial cells in the liver,
spleen, and bone marrow and may seed
other organs
 after proliferation in the
reticuloendothelial system, bacteremia
recurs
 from blood or from the liver via bile
ducts, it infects the gallbladder and
reenters the gastrointestinal tract in the
bile, spreading to other hosts via stool
 further seeding of the Peyer patches
occurs through infected bile
 hyperplasia of Peyer patches with
necrosis and sloughing of overlying
epithelium produces ulcers that may
bleed
 ulcers heal without scarring
 strictures and intestinal obstruction
virtually never occur after typhoid fever
 inflammatory lesion may occasionally
penetrate the muscularis and serosa of
the intestine and produce perforation,
causing peritonitis
 Several
virulence factors seem to
be important:
invasion of Peyer patches is encoded
by genes closely related to the
invasion genes of Shigella and
enteroinvasive E. coli
surface Vi capsular antigen found in
S. Typhi interferes with phagocytosis
by preventing the binding of C3 to
the surface of the bacterium
the ability of organisms to survive
within macrophages after
phagocytosis is an important
virulence trait encoded by the phoP
regulon
leading to modification of protein
and lipopolysaccharide elements of
the bacterial inner and outer
membranes
Salmonella resists lysis and decreases
host proinflammatory signaling
 macrophage provides Salmonella a
vehicle safe from other elements of
the immune system and in which it
can multiply and travel
 passes through the mesenteric
lymph nodes into the thoracic duct
and the lymphatics beyond to seed
the reticuloendothelial tissues—liver,
spleen, bone marrow, and lymph
nodes
 Salmonella multiply until some critical
density is reached
 causing the apoptosis in the
macrophages and enters the
bloodstream to attack the rest of the
body
 finally,
the Vi antigen (polysaccharide
capsule) forms a capsule to protect
the bacterium from complement and
from phagocytic immune cells
Clinical Manifestations

 incubation period: 7–14 days

 may range from 3–30 days,
depending mainly on the size
of the ingested inoculum
 the
clinical manifestations of
enteric fever depend on age
SCHOOL-AGED CHILDREN AND
ADOLESCENTS
 Insidious onset
 Incubation period: 8-14 days
Initial symptoms: 2–3 days
 May resemble an URTI
 Fever
- low grade which increases in a stepwise
fashion, becomes an unremitting and
high fever within 1 wk, often reaching
40°C
often pxs present w/ undiagnosed
fever several days to a week or more
w/c has not responded to treatment
 malaise,
anorexia, myalgia,
headache, and abdominal pain
 diarrheahaving a pea soup
consistency -early course of the
disease
 constipation
later becomes a more
prominent symptom
 cough and epistaxis may ensue

2nd week:
highfever is sustained, and fatigue,
anorexia, cough, and abdominal
symptoms increase in severity
Physical Examination:
 relative
bradycardia - disproportionate to
the high fever
 patients
appear acutely ill, disoriented,
and lethargic
 hepatomegaly, splenomegaly, and
distended abdomen with diffuse
tenderness - very common
a macular or maculopapular rash (rose
spots) appears on about the 7th–10th day
– in 50% of patients
 usually
discrete, erythematous, and 1–5
mm in diameter; the lesions are slightly
raised and blanch on pressure
 appear in crops of 10–15 lesions on the
lower chest and abdomen last 2–3
days
 leave a slight brownish discoloration of
the skin on healing
 cultures
of the lesions have a 60% yield
for Salmonella organisms
INFANTS AND YOUNG
CHILDREN (<5YR)
 relatively rare in this age group in endemic
areas
 disease is surprisingly mild at presentation,
making the diagnosis difficult
 mild fever and malaise, misinterpreted as a
viral syndrome, occur in infants with culture-
proven typhoid fever
 temperature may be of the septic spiking or
“saw-tooth” type of fever last 2-3days
 diarrhea is more common in young
children than in adults, leading to a
diagnosis of acute gastroenteritis
 abdominal
distention is an
accompanying manifestation
 rosespots & splenomegaly are
infrequent
 convulsions
or meningeal signs are
occasionally encountered
NEONATES

 cause abortion and premature

delivery
 enteric fever during late
pregnancy may be transmitted
vertically
 neonatal disease usually begins
within 3 days of delivery
 vomiting, diarrhea, and
abdominal distention are
common
 temperature is variable but may
be as high as 40.5°C
 seizures may occur;
hepatomegaly, jaundice,
anorexia, and weight loss can be
marked
Complications

 usually occur after the 1st week

of the disease
 severe intestinal hemorrhage - 1–
10%
 intestinal perforation - 0.5–3%
 hemorrhage
usuallyprecedes perforation
 manifested by a decrease in
temperature and blood pressure
and an increase in the pulse rate
 perforations
typicallyoccur in the distal ileum and
are accompanied by a marked
increase in abdominal pain, tenderness,
vomiting, and signs of peritonitis
 hepatitis
w/ jaundice and cholecystitis
may occur
 pneumonia caused by superinfection
with organisms other than Salmonella
is more common in children than in
adults - approximately 10%
Neurologic complications:
 increased intracranial pressure, cerebral
thrombosis, acute cerebellar ataxia,
chorea, aphasia, deafness, psychosis
Others:
 fatal bone marrow necrosis
 Pyelonephritis
 nephrotic syndrome
 endocarditis
 parotitis
 orchitis
 suppurative lymphadenitis
Criteria and Indications for
Admission
A. All patients suspected of having typhoid
fever with one or more of the ff:
 Persistent vomiting or unable to take
oral fluids
 Severe dehydration
 Spontaneous bleeding
 Persistent abdominal pain
 Listlessness
 Restlessness
  Changes in mental status
 Weak, rapid pulse
 Cold, clammy skin
 Circumoral cyanosis
 DOB
 Seizures
 Hypotension or narrowing pulse
pressure (<20 mmHg)
B. All patients suspected of having
complicated typhoid fever
Diagnosis
A. Lab Studies
1. CBC with platelet count
 Leukopenia- 4,000-6,000 cells/mm
 Leukocytosis- may be as high as
20,000-25,000 in the presence of
pyogenic complications or intestinal
perforation
 Thrombocytopenia
 normochromic, normocytic anemia -
related to intestinal blood loss or
bone marrow suppression
B. Culture
1. Blood cultures:
 Gold standard test for typhoid fever
 Should be taken anytime during the
illness but yield is highest during the 1st 2
weeks
 positive in 40-60% of patients during the
1st week
 Should be taken at least from 2 different
sites. The 2nd & 3rd blood spcimen will
increase the yield (73-97%)
2. Stool and urine cultures
 positive on 2nd-4th week of illness

3. Duodenal string test

 used to culture bile, in suspected cases
with negative results of stool cultures
a culture of aspirated duodenal fluid
 cannotbe performed on those too
young or too ill to cooperate
4. Bone marrow aspirate (BMA) culture
 most sensitive method of isolating S typhi
 sensitivity is 90% at any point in the disease
course
 lessinfluenced by prior antimicrobial
therapy
 positive in 85–90% of patients
 not done routinely but indicated in highly
suspicious cases with negative blood or
stool culture
 extremely painful
Serology
1. Typhidot-M test:
 diagnostictests for immunoglobulin M
(IgM) and immunoglobulin G (IgG)
antibodies
 with rapid results (2 minutes to 3 hours)
 hasa specificity of 75% and a sensitivity
of 95%
 the
Tubex test is rapid and detects the
O9 antigen
2. Widal test:
measures antibodies against O
and H antigens of S. ser. Typhi
rarely used because of its low
sensitivity and specificity
not recommended
DNA testing: Polymerase chain
reaction assays
used to amplify specific genes of S.
Typhi in the blood of patients
enabling diagnosis within a few hours
specific and more sensitive than
blood cultures, given the low level of
bacteremia in enteric fever
used mostly for research since the
test is generally too expensive
TREATMENT

1. Chloramphenicol
 gold standard
 initial drug of choice
 not commonly used because of
widespread resistance, high relapse rates,
and risk of bone marrow toxicity
 50mg/kg/dayPO or 75mg/kg/day IV in
four equal doses for 14 days (Nelson 17th)
 100 mg/kg/day for 2-3 weeks (Del Mundo)
 Adult: 3-4g/day in QID x 14 days
2. Ampicillin
 200 mg/kg/day IV in four to six doses

3. Amoxicillin
 100 mg/kg/day in three divided doses for
14 days
 Adult: 4-6 g/day TID x 14 days
4. Trimethoprim-sulfamethoxazole
 10 mg of TMP/kg/day and 50 mg of
SMZ/kg/day PO in two doses for 14 days
 Adult: 1-1 ½ tabs BID x 14 days
Short Courses:
1. Ceftriaxone
 current
drug of choice for children and
pregnant women
 Children: 50-80 mg/kg IM QID for 5-7 days
 Pregnant: 3-4 g IV as single dose for 5-7
days
2. Cefixime
 20 mg/kg/day BID for 7 days
3. Ofloxacin
 15 mg/kg/day for 2 days
Dexamethasone
3mg/kg for the initial dose, followed
by 1 mg/kg q 6hr for 48hr
 improvesthe survival rate of patients
with shock, obtundation, stupor, or
coma
 shortens the febrile course
Prognosis

 in developing countries, the mortality rate is

higher than 10%, usually because of delays in
diagnosis, hospitalization and treatment
 infants and children with underlying debilitating
disorders are at higher risk
 appearance of complications, such as
gastrointestinal perforation or severe hemorrhage,
meningitis, endocarditis, and pneumonia, is
associated with high morbidity and mortality rates
 Relapse after the initial clinical response
occurs in 4–8% of the patients who are not
treated with antibiotics – milder
 individuals who excrete S. ser. Typhi for 3
months after infection usually become
chronic carriers
 risk of becoming a carrier is low in children
and increases with age
 of all patients with typhoid fever, 1–5%
become chronic carriers
 incidence of biliary tract diseases is higher in
chronic carriers than in the general populatio
Prevention

 improved sanitation and clean running water

 personal hygiene measures
 handwashing
 attention to food preparation practices
 carriers should be prevented from working in
food- or water-processing activities, in kitchens,
and in occupations related to patient care
 Detection & treatment of carrier