Enteric fever

1. Enteric fever(Typhoid Fever)
John Stephen

2. Area to be covered
• DEFINITION
• EPIDEMIOLOGY
• ETIOLOGY
• PATHOGENESIS
• CLINICAL FEATURE
• DIAGNOSIS
• COMPLICATION
• TREATMENT
• PREVENTION

3. Definition
• Typhoid fever is a systemic infectious disease, caused by
bacteria Salmonella typhi,characterized by slowly progressive
fever as high as 40 °C, malaise involvement of lymphoid tissues
and spleen
• It is transmitted through the ingestion of food or drink contaminated
by the faeces or urine of infected people.
• A similar but generally less severe illness known as paratyphoid is due
to infection with S. paratyphi A, B or C. Man is the only natural host
for S. typhi , which is transmitted in contaminated food or water. The
incubation period is 10–14 days but can be longer.

4. Epidemiology
• Typhoid and paratyphoid fevers are endemic in our country as
well as many parts of the world like South-East, Far East Asia,
Central and South America and Middle East Africa.

5. Etiology
• The Enteric fevers are caused by bacteria of the genus
Salmonellae i.e. Salmonella typhi causes typhoid in humans
who are the only source and reservoir.

6. Pathogenesis
• All Salmonella infections begin with ingestion of organisms,
most commonly in contaminated food or water. The infectious
dose is 10 3 –10 6 colony-forming units. Conditions that decrease
either stomach acidity (an age of <1 year, antacid ingestion, or
achlorhydric disease) or intestinal integrity (inflammatory bowel
disease, prior gastrointestinal surgery, or alteration of the
intestinal flora antibiotic administration) increase susceptibility to
Salmonella infection.

7. • Once S. typhi and S. paratyphi reach the small intestine, they
penetrate the mucus layer of the gut and traverse the intestinal
layer through phagocytic microfold (M) cells that reside within
Peyer’s patches. Salmonellae can trigger the formation of
membrane ruffles in normally nonphagocytic epithelial cells. These
ruffles reach out and enclose adherent bacteria within large
vesicles by a process referred to as bacteria-mediated
endocytosis (BME). BME is dependent on the direct delivery of
Salmonella proteins into the cytoplasm of epithelial cells by a
specialized bacterial secretion system ( type III secretion ). These
bacterial proteins mediate alterations in the actin cytoskeleton that
are required for Salmonella uptake.

8. • After crossing the epithelial layer of the small intestine, S. typhi
and S. paratyphi, which cause enteric (typhoid) fever, are
phagocytosed by macrophages. These salmonellae survive the
antimicrobial environment of the macrophage by sensing
environmental signals that trigger alterations in regulatory
systems of the phagocytosed bacteria. For example, PhoP/PhoQ
(the best-characterized regulatory system) triggers the
expression of outer-membrane proteins and mediates
modifications in LPS so that the altered bacterial surface can
resist microbicidal activities and potentially alter host cell
signaling. In addition, salmonellae encode a second type III
secretion system that directly delivers bacterial proteins across the
phagosome membrane into the macrophage cytoplasm. This
secretion system functions to remodel the Salmonella -containing
vacuole, promoting bacterial survival and replication.

9. • Once phagocytosed, typhoidal salmonellae disseminate throughout
the body in macrophages via the lymphatics and colonize
reticuloendothelial tissues (liver, spleen, lymph nodes, and bone
marrow). Patients have relatively few or no signs and symptoms
during this initial incubation stage. Signs and symptoms, including
fever and abdominal pain, probably result from secretion of
cytokines by macrophages and epithelial cells in response to
bacterial products that are recognized by innate immune receptors
when a critical number of organisms have replicated. Over time, the
development of hepatosplenomegaly is likely to be related to the
recruitment of mononuclear cells and the development of a specific
acquired cell-mediated immune response to S. typhi colonization.
The recruitment of additional mononuclear cells and lymphocytes to
Peyer’s patches during the several weeks after initial colonization/
infection can result in marked enlargement and necrosis of the
Peyer’s patches, which may be mediated by bacterial products that
promote cell death as well as the inflammatory response.

11. Clinical features
• Fever that starts low and increase dairly, often to us high us 39.4 c or 40
• Headache
• Weakness and fatigue
• Dry cough
• Loss of appetite
• Abdominal pain
• Diarrhea (22-28%)
• constipation (13–16%)
• hepatosplenomegaly, lymphadenopathy and a scanty maculopapular rash (‘rose spots’).
• Coated Tongue
• Epistaxis and relative bradycardia
• Neurological manifestation occurs in 2 to 40% these includes Meningitis,neuritis, Guillain Barre
syndrome, Delirium and Coma

14. Diagnosis
• The gold standard of diagnosis is culture of blood, stool, urine or bone marrow
aspirates.
• Blood cultures may be positive during the first week and for a variable period after this.
• Stool and urine cultures are positive after the first week
• The Widal test becomes positive by the end of first week, and a rising titre shown by
two tests performed 4-5 days apart may indicate active typhoid
• The test has limited sensitivity (i.e. does not correctly detect most cases) and specificity
(i.e. a negative test does not rule out infection in most cases)
• Helpful laboratory test include:-
• o WBC count: low (leukopenia) with a relative lymphocytosis (more common among
children, during the first 10 days of illness, and in cases complicated by
intestinal perforation or secondary infection)
o Stool: in 100% of cases, occult blood is present in the stool
• Exclude malaria then refer patient to hospital where the above investigations can be
done to confirm the diagnosis

16. Complication
• Bowel perforation
• intestinal Hemorrhage
• Peritonitis
• Cholecystitis
• Hepatitis
• Meningitis
• lobar pneumonia
• osteomyelitis
• Orchitis
• Glomerulonephritis, Pyelonephritis
• Pericarditis,myocarditis, endrocarditis
• Hemolytic Uremic Syndrome (HUS)

17. Treatment
• Pharmacological Treatment
A: Ciprofloxacin (PO) 500mg 12 hourly for 10 days
OR
B: Azithromycin (PO) Adult 500mg 24hrly for 7 days
• Chloramphenicol, cotrimoxazole and amoxicillin may all still be effective in
some cases, but quinolones (e.g. ciprofloxacin 500 mg twice daily) are
now the treatment of choice, although increased resistance to these
agents is being seen: in such cases azithromycin may be effective.
• The patient’s temperature may remain elevated for several days after
starting antibiotics and this alone is not a sign of treatment failure.

18. Prevention
• General prevention is as for faeco-oral diseases: cook food thoroughly,
boil water, and wash hands before preparing food, after preparing food
and before eating.
• It is important to identify carriers who work as food handlers as they are
especially likely to transmit the infection (although searching for carriers is
impracticable in endemic areas).
• In some countries, vaccines are currently in use (VI capsular
polysaccharide antigen vaccine and live attenuated oral vaccine).
• It is not part of immunization program of Tanzania.
• Early diagnosis and treatment of cases is important