|A 22-year old man complains of
continuous fever with chills since six days, headache, anorexia, malaise,
abdominal discomfort and mild diarrhea.
On examination coated tongue and slightly enlarged liver were observed.
What is your diagnosis?
It could be a case of enteric fever. Differential diagnosis
includes febrile conditions such as abdominal abscess, malaria,
amebic hepatic abscesses, appendicitis, brucellosis, tuberculosis,
dengue fever, and typhus.
What is the specimen collected and how is the condition
diagnosed with the aid of laboratory?
If enteric fever is suspected, diagnosis can be
made by blood and feces culture. Freshly passed feces is collected
in a sterile wide mouthed container. The enrichment medium
used is tetrathionate broth or
selenite F broth. Direct gram stained smear or
hanging drop preparation is not useful. Feces is inoculated on to MacConkey's agar,
low selective media such as XLD
Agar or DCA or SS AGar and highly selective medium such as Wilson
& Blair's Agar. The plates are incubated at 37oC
overnight. Subculture is made from enrichment broth on to MacConkey's agar for subsequent
overnight incubation. For blood culture, 5 ml of venous blood is
drawn and inoculated into blood culture broth such as bile broth
or brain heart infusion broth and incubated at 37oC.
Subcultures are made from blood culture broth to MacConkey's agar
and discarded if it fails to yield any growth even after one week
of incubation. To prevent contamination during subcultures,
biphasic medium may be used
(Castaneda method). Salmonella can also be isolated from urine,
bone marrow, rose spots, rectal swab and duodenal aspirate.
Culture of bone marrow aspirate is 90% sensitive until at least 5
days after commencement of antibiotics. Stool culture alone yields
a sensitivity of less than 50%, and urine culture alone is even
less sensitive. Blood, duodenal aspirate, and stool culture
results are positive for S. typhi in approximately 85-90% of
patients with typhoid fever within the first week of illness. S.
typhi has also been isolated from the cerebrospinal fluid,
peritoneal fluid, mesenteric lymph nodes, resected intestine,
pharynx, tonsils, abscess, and bone. Detection of Salmonella
antigen in blood by latex agglutination and coagglutination can
also be performed. Detection of antibody later in the course of
disease is by widal test, indirect hemagglutination, indirect
fluorescent Vi antibody, ELISA for IgM & IgG antibodies to S.
typhi polysaccharide, as well as monoclonal antibodies against S.
What is your observation?
Feces culture and subculture from blood culture broth on MacConkey's agar
yield pale (non-lactose fermenting), smooth, low convex, circular
colonies. XLD Agar shows pink coloured colonies
with black center. Black colonies with metallic sheen is seen on
Wilson & Blair's agar. Gram stained smear of the colony shows
gram negative bacilli,
hanging drop shows
motile bacilli. Results of biochemical
reactions include positive catalase test, negative oxidase
indole test, negative urea hydrolysis,
citrate utilization test, positive MR test and negative VP
test. TSI agar shows
alkaline slant/acid butt with a steak of H2S but no
What is your identification and how would you confirm it?
The isolate is identified as Salmonella typhi (Salmonella enterica
ssp typhi) and is confirmed by slide agglutination using factor 9
'O' antiserum and flagellar anti-d antiserum. Presence of capsule
may hinder agglutination; in such situations the suspension may be
boiled for 20 minutes and retested.
What is the pathogenesis of enteric fever?
Enteric fever is transmitted by feco-oral route. Following
ingestion of contaminated food or water (containing at least 104
bacteria), Salmonella gain entry into the small intestine after a
variable incubation period of 1-2 weeks. Bacteria attach
themselves to epithelium and subsequently penetrate lamina propria
and submucosa where they are engulfed by monocytes. Bacteria
resist intracellular killing and multiply in the monocytes. They
reach mesenteric lymph nodes, multiply there and reach blood
stream via thoracic duct resulting in primary bacteremia. During
this transient bacteremia bacteria are seeded in the liver, gall
bladder, spleen, lymph node, bone marrow, where they continue to
multiply. Following multiplication in large numbers, the bacteria
spill in to bloodstream again resulting in secondary bacteremia
and marks the onset of clinical disease. When bacteria are shed
from the gall bladder along with the bile juice, they reach the
small intestine again and infect the peyer's patches and lymphoid
follicles of ileum leading to inflammation and ultimately
What is the course of untreated illness and its complications?
Untreated typhoid fever normally lasts for 3-4 weeks. As the
disease progresses, febrile patient becomes more toxic and
anorexic with significant weight loss, conjunctivae are infected,
abdominal distension is severe and the patient may descend into
the typhoid state, which is characterized by apathy, confusion,
and even psychosis. Necrotic Peyer's patches may cause bowel
perforation and peritonitis. Overwhelming toxemia, myocarditis, or
intestinal hemorrhage may cause death. If the patient survives to
the fourth week, the fever, mental state, and abdominal distension
slowly improve over a few days. Some survivors become asymptomatic
S. typhi carriers.
What is the role of carriers in transmission of disease and how
are they detected?
Carriers are important source of disease as they disseminate
the bacteria in the community. Approximately 2-4% of patients
become carriers while some people become carriers after inapparent
infection. Those who shed bacteria for a duration less than a year
are called temporary carriers and those who shed for more than a
year are called chronic carriers. Development of carrier stage is
common in females and in elderly patients. A carrier may be fecal
carrier or urinary carrier depending on the site of bacterial
persistence. It is important to detect carrier state in food
handlers as well as in community. Bacterial shedding is
infrequent, hence repeated cultures may be required to recover
Salmonella from urine, bile or feces. Carriers in a community may
be traced by 'sewer-swab' technique. Demonstration of Vi
antibodies has been used to detect carrier state. Pefloxacin is
now considered an effective antibiotic in eradicating carrier
state. If antibiotic treatment fails to eradicate the
hepatobiliary carriage, the gallbladder should be resected.
Cholecystectomy is not always successful in eradicating the
carrier state because of persisting hepatic infection.
How is this condition treated?
Because of plasmid mediated development of resistance, antibiotics
such as chloramphenicol, ampicillin and
trimethoprim-sulfamethoxazole are no longer used. Drugs of choice
are either fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin)
or third generation cephalosporins (cefotaxime, ceftraxone,
ceftazidime). Unfortunately, resistance to both these groups are
emerging. Antibiotics must be prescribed only on the basis of
antibiotic susceptibility testing. Approximately 5-10% of
patients treated with antibiotics experience relapse of typhoid
fever after initial recovery. Relapses typically occur
approximately 1 week after therapy is discontinued. After
discharge, patients should be monitored for relapse or
complications for 3 months after treatment has commenced.
How can this disease be prevented?
Since typhoid is spread mainly be feco-oral route and is more
common in areas of poor hygiene, the disease can be controlled to
some extent by general sanitary measures such as safe cooking and
eating habits, proper disposal of excreta etc. For details on
immunoprophylaxis, read the
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