TYPHOID FEVER

INTRODUCTION
 Typhoid fever is an acute
systemic illness characterized
by fever, headache and
abdominal discomfort.
 It is caused by salmonella
typhi (gram negative bacilli).
Family of enterobacteriacea.
 A similar but less severe
illness known as paratyphoid
fever, caused by salmonella
paratyphi (A, B, C)
 Generally transmitted by the ingestion of
food/water contaminated by feces of an
infected person
 Once ingested the organism perforates the
intestinal wall and enters the bloodstream
temporarily then phagocytosed by
macrophages
Characterized by

 prolonged fever
 relative bradycardia
 apathetic facial expressions
 Roseola
 Splenomegaly
 Hepatomegaly
 Leukopenia.
ETIOLOGY
Salmonellae
 gram negative
 non-spore forming
 facultatively anaerobic bacilli that measure 2–3 by 0.4–0.6 m
 produce acid on glucose fermentation
 reduce nitrates
 do not produce cytochrome oxidase.
 all salmonellae except S. Gallinarum-Pullorum are motile by means
of peritrichous flagella
 and all but S. Typhi produce gas (H2S) on sugar fermentation.
 Notably, only 1% of clinical isolates ferment lactose; a high level of
suspicion must be maintained to detect these rare clinical lactose-
fermenting isolates.
 Antigens: located in the cell capsule

H (flagellar antigen).

O (Somatic or cell wall antigen).

Vi (polysaccharide virulence)

“widel test”
A schematic diagram of a single Salmonella typhi cell showing the
locations of the H (flagellar), 0 (somatic), and Vi (K envelope)
antigens.
 Endotoxin
 A variety of plasmids
 Resistance: Live 2-3 weeks in water. 1-2
months in stool. Die out quickly in
summer
Resistance to drying and cooling
EPIDEMIOLOGY
Epidemiology:
 T.F. is prevalent in areas of developing
countries lacking adequate waste disposal
and clean drinking water facilities.
 16,000,000 new cases annually, causing
around 600,000 death per year.
 Humans are the only host for S. Typhi
 Mode of transmission is by fecal-oral rout,
through ingestion of contaminated food or
water, health care workers & lab workers
acquire infection by accidental exposure to
s.typhi-containing specimen
 Incubation period: around 10-14 days.
Transmission

fecal-oral route

close contact with patients or carriers

contaminated water and food

flies and cockroaches.

PATHOGENESIS
Pathogenesis

 gastrointestinal tract host-

pathogen interactions
 The amount of bacilli infection
(>105baeteria).
 Pathogenesis
ingested orally
® Stomach barrier (some Eliminated)
® enters the small intestine
Penetrate the mucus layer
 enter mononuclear phagocytes of ileal peyer's
patches and mesenteric lymph nodes
 proliferate in mononuclear phagocytes
spread to blood. initial bacteremia (Incubation
period).
Pathogenesis
 enter spleen, liver and bone marrow (reticulo-
endothelial system)
further proliferation occurs
 A lot of bacteria enter blood again.
(second bacteremia).
 Recovery
 S.Typhi. liver 、 spleen 、 gall 、
BM ,ect
2nd bacteremia early stage&acme stage
(1-3W ）

stomach

(monon Bac. In gall

uclear
phagoc
ytes )
Bac. In
Lower feces
ileum

peyer's patches & S.Typhi eliminated

mesenteric lymph nodes convalvescence stage
(4-5w)
LN Proliferate,swell 1st bacteremia
necrosis
defervescence stage thoracic
(Incubation stage)
Enterorrhagia,i
（ 3-4w ） duct 10-14d
ntestinal
perforation
 Pathology
 essential lesion:
proliferation of RES (reticuloendothelial system )
specific changes in lymphoid tissues
and mesenteric lymph nodes.
"typhoid nodules“
 Most characteristic lesion:
ulceration of mucous in the region of the Peyer’s
patches of the small intestine
Major findings in lower ileum

 Hyperplasia stage(1st week):

swelling lymphoid tissue and
proliferation of macrophages.
 Necrosis stage(2nd week):
necrosis of swelling lymph nodes or
solitary follicles.
Major findings in lower ileum

 Ulceration stage(3rd week):

shedding of necrosis tissue and formation of
ulcer ----- intestinal hemorrhage,
perforation .
 Stage of healing (from 4th week):
healing of ulcer, no cicatrices and no
contraction
CLINICAL MANIFESTATION
 Stages of Infection
 Typically, infection of untreated typhoid fever
is divided into 4 individual stages (each
lasting ~1 week)
Clinical picture:
 1st week:
 Onset is insidious.
 Fever (>70%) is slow rising, increasing
progressively in step ladder fashion over 4-5 days
(38,8-40,5 c), with relative bradycardia.
 Non-specific constitutional symptoms: headache,
fatigue, myalgia, cough, sore throat.
 G.I. symptoms: abdominal pain (20-40%),
constipation, diarrhea.
 Early signs: relative bradycardia, abd.tenderness
(diffuse or localized, usually right lower
quadrant).
End of 1st week, beginning of 2nd week:

 Abd.distension & tenderness.

 Hepato-splenomegaly.
 Rose-spots: maculopapular rash, 2-3 mm, in
the trunk (chest & upper abdomen), fade on
pressure, remains 4-5 days, disappear
without scars, occur in 30% of cases, difficult
to notice in dark-skinned patients.
Rose spots
 3rd & 4th week.
 Patient is profoundly ill, complications appear.
 Disturbance in consciousness, neuro-psychiatric
symptoms (picking bed clothes or imaginary
objects), called muttering delirium, coma vigil,
typhoid psychosis.
 Intestinal perforation or bleeding: shock state,
fever disappears, fresh or dark bloody stool.
 Cholecystitis, hepatitis, pneumonia, carditis,
meningitis, nephritis, arthritis, osteomylitis…etc.
 Death.
Typhoid terminal state (typhoid face).
 Majority of patients recover without complications by
receiving adequate antibiotics without delay.
 1-5% of cases become asymptomatic chronic carriers,
shedding S.typhi in stool and less frequently in urine.
 In those carriers, S.typhi reside in gallbladder
especially if associated with gallstones or
Ca.gallbladder, because anatomical abnormalities
allow for prolonged colonization of the organism.
 In areas where schistosoma hematobium is prevalent,
chronic carriage of S.typhi in urinary bladder is
common.
DIAGNOSIS
 clinical presentation of enteric fever is relatively nonspecific
 the diagnosis needs to be considered in any febrile traveler returning
from a developing country, especially the Indian subcontinent, the
Philippines, or Latin America.
 Other diagnoses that should be considered in these travelers include
malaria, hepatitis, bacterial enteritis, dengue fever, rickettsial
infections, leptospirosis, amebic liver abscesses, and acute HIV
infection
 no specific laboratory test is diagnostic for enteric fever.
 In 15–25% of cases, leukopenia and neutropenia are detectable.
 Leukocytosis is more common among children, during the first 10
days of illness, and in cases complicated by intestinal perforation
or secondary infection.
 Other nonspecific laboratory findings include moderately
elevated liver function tests and muscle enzyme levels.
 The definitive diagnosis of enteric fever
requires the isolation of S. Typhi or S.
Paratyphi from blood, bone marrow, other
sterile sites, rose spots, stool, or intestinal
secretions.
 sensitivity is as high as 90% during the first
week of infection and decreases to 50% by
the third week.

 Blood culture: is the gold standard for diagnosis
in the 1st week (90% positive). It drops to 50%
during 3rd week of infection.
Since almost all S. Typhi organisms in blood are
associated with the mononuclear-cell/platelet
fraction, centrifugation of blood and culture of
the buffy coat can substantially reduce the time
to isolation of the organism but does not
increase sensitivity.
 Stool culture: usually negative during 1st
week of infection, becomes highly positive
during 2nd & 3rd week. The disadvantage is
that, it does not distinguish between acutely
infected patient and a chronic carrier.
 Stool cultures, while negative in 60–70% of
cases during the first week, can become
positive during the third week of infection in
untreated patients.
 Bone marrow culture: highly sensitive,
remain positive even after 5 days of
antibiotic use. Rarely required due to its
invasive nature, except in patient highly
suspicious of T.F. who has received
antibiotic and his blood culture is negative.
 Unlike blood culture, bone marrow culture
remains highly (90%) sensitive despite 5 days
of antibiotic therapy.
 Culture of G.I. secretion: using duodenal
string test.
 Culture of intestinal secretions (best
obtained by a noninvasive duodenal string
test) can be positive despite a negative
bone marrow culture.
 If blood, bone marrow, and intestinal
secretions are all cultured, the yield is
>90%.
 Urine culture: less frequent, less sensitive.
 Culture of rose spots: positive in two thirds of
patients remains positive even after receiving
antibiotics.
 Several serologic tests, including the classic
Widal test for "febrile agglutinins," are available.
 None of these tests is sufficiently sensitive or
specific to replace culture-based methods for
the diagnosis of enteric fever in developed
countries.
 Polymerase chain reaction and DNA probe
assays to detect S. Typhi in blood are being
developed.
 WIDAL test: is a serological test that detects Ab
against S.typhi somatic Ag (anti-O), or flagellar Ag
(H).
 It is unreliable, nonspecific, insensitive, with high
false positive results due to cross-reaction with
many other types of salmonella.
 Widal test is considered positive, if anti-O titer
>1:320 (other references >1:80) or anti-H titer >1:
640. or if there is four fold rise of titer between
acute infection and convalescent period.
 Additional lab findings:
 Hb : variable anemia. Platelets: often diminished.
 WBC: typically leucopenia with nuetropenia (15-25%), but
can be normal, or leucocytsis with lymphocytosis in little
children or secondary infection or complication occur
(such as intestinal perforation).
 LFT: abnormal results with elevated AST, ALT and Alk.Ph.
 ECG: prolonged PR interval, nonspecific ST, T
wave changes.
 New diagnostic methods:
 Polymerase chain reaction PCR, and DNA probe
test, that detect S. typhi DNA, they are highly
sensitive and specific, but not widely used.
MANAGEMENT
Treatment of chronic carrier:

 Prolonged anti-biotic course (e.g. ciprofloxacine

500mg/ BD/ 6-8weeks) might eliminate the
carrier state
 But in patients with anatomical abnormalities
(e.g. gall stones) the medical eradication usually
not successful, and a surgical solution (e.g.
cholecystectomy) should be taken into
consideration.
prevention:
 Improved sanitation and health education.
 Checking food-handlers by periodic stool culture.
 Vaccination: two parenteral (inactivated, killed),
one oral (live attenuated). No life-long protection.
 Recommendation for vaccination:
 Traveling to endemic area.
 Household contact with infected patient or carrier.
 Lab worker with contact to S. typhi specimen.
 Epidemic outbreak.
 Vaccination

 1st parenteral has many side-

effects. Given in 2 injections
4weeks apart, with booster
dose every 3-5 years.
 2nd parenteral (viCPS): less
S.E. 1 inj. Booster dose every
2 years.
 Oral (ty21a): the safest, 1
dose, alternate day for atotal
of 4doses, then booster dose
every 5 years( C/I in children
<6y, immunocompromised,
and acute TF inf.)
COMPLICATION
Intestinal hemorrhage

 Commonly appear during the second-third

week of illness
 difference between mild and greater bleeding
often caused by unsuitable food, diarrhea et
al
 serious bleeding in about 2~8%
 a sudden drop in temperature 、 rise in
pulse 、 and signs of shock followed by dark
or fresh blood in the stool.
Intestinal perforation:
 The more serious .Incidence,1-4%
 Commonly appear during 2-3 weeks.
 Take place at the lower end of ileum.
 Before perforation : abdominal pain or diarrhea,intestinal
bleeding .
 When perforation : abdominal pain, sweating, drop in
temperature, and increase in pulse rate, then, rebound
tenderness when press abdomen,
abdomen muscle entasia, reduce or disappear in the sonant
extent of liver, leukocytosis .
 Temperature rise .peritonitis appear.
 celiac free air under x-ray.
Hematologic complication

 Trombositopenia
 Hipofibrinogenemia
 Elevated protrombin time
 Elevated partial thromboplastin time
 Elevation of fibrin degradation products
 DIC
Typhoid Hepatitis

 common,1-3 weeks
 hepatomegaly, ALT elevated
 get better with improvement of diseases in 2~3
weeks
 Elevation of transaminase not relevant by the
increasing of serum bilirubin
Typhoid pancreatitis

 Rare case
 Diagnosed by amilase and lipase enzym
assays, CT scan, USG
Miokarditis

 1-5% patient with typhoid fever

 EKG abnormalities in 10-15% patient
 seen in 2-3 weeks, usually severe toxemia
 Found in patient with severe disease, fulminant
and acute condition
 Chest pain, congestive heart failure, aritmia,
cardiogenic shock
Bronchitis, bronchopneumonia

 seen in early stage

toxic encephalopathy

 Impaired in consciousness : apatis, somnolen,

sopor, semi koma, koma
 Other neurologic disorder: delirium,
convulsion, parkinson rigidity, meningitis,
GBS, psikosis
 Normal CSF evaluation
Thank You