Typhoid Fever

1. Typhoid Fever
Prof. Nooruddin Jaffer
Professor of Medicine
Hamdard Medical College
Karachi Pakistan

2. Introduction
lTyphoid fever is a severe multisystemic illness
characterized by the classic prolonged fever, sustained
bacteremia, and bacterial invasion and multiplication
within the mononuclear phagocytic cells of the liver,
spleen, lymph nodes, and Peyer patches.

3. Introduction
lOccurs only in humans

lPotentially fatal if untreated.
lTyphoid fever is most prevalent in
underdeveloped countries

4. Epidemiology
lTyphoid and paratyphoid fever infections are
encountered worldwide but are primarily
found in those countries of the developing
world where sanitary conditions are poor.
lIndian subcontinent, Southeast and Far East
Asia, the Middle East, Africa, Central
America, and South America.

5. Epidemiology
l In endemic areas, children aged 1-5 years
are at the highest risk because of waning
passively acquired maternal antibody and a
lack of acquired immunity.

6. Etiologic Agent
lCausative agent is Salmonella typhi, a gram-negative
bacteria, member of genus Salmonella and
familyEnterobacteriaceae
lSalmonellae are grouped based on the somatic O and
further divided into serotypes based on flagellar H a
gram-negative and surface Vi (virulence) antigens.

7. Transmission
lContaminated food and beverages handled
by persons shedding S typhi from stool (or
less commonly urine)
lWater from sewage contaminated with S
typhi.

8. Transmission
lIncreased susceptibility is related to
•Increased bacterial load: Ingestion of 10
5

organisms led to clinical disease in 25%,
ingestion of 10
7
in 50%, and 10
9
organisms
in 95%.
•A gastric pH of > than 1.5
• Patients on antacids
•Gastrectomy
•Achlorhydria due to aging

9. Pathogenesis
lThe hallmark of typhoid fever is the
invasion of and multiplication within the
mononuclear phagocytic cells in the liver,
spleen, lymph nodes, and Peyer patches of
the ileum.

10. Pathogenesis
lFrom the Peyer patches S typhi is
internalized and transported to the underlying
lymphoid tissues.
lThen the organisms travel to the mesenteric
lymph nodes, multiply, and then enter the
blood stream via the thoracic duct (transient
primary bacteremia) to seed other tissues.

11. Pathogenesis
lThen the organisms may invade any organ
but most commonly are found in
reticuloendothelial tissues of the liver, spleen,
bone marrow, gallbladder, and Peyer patches
in the terminal ileum.

12. Pathogenesis
lThe Peyer patches become hyperplastic with
infiltration of chronically inflamed cells, which
may lead to necrosis of the superficial layer
and ulcer formation, with potential
hemorrhage from blood vessel erosion or
peritonitis from transmural perforation

13. Symptoms
lThe incubation period averages 10-20 (range
3-56) days.
lPatients remain asymptomatic during the
incubation period
lAs bacteremia develops, patient notices the
onset of fever, which typically increases in a
step-wise fashion over 2-3 days.

14. Symptoms
lConstipation and mild nonproductive cough
are common.
lAbdominal pain and diarrhea
lDelirium
lAnorexia, weakness, malaise.

15. Signs
lRelative bradycardia
lPink papules (rose spots)(2-4mm) that
fade with pressure develop on the
upper abdomen and lower chest
between the 7
th
and 12
th
days caused
by bacterial embolization

16. Signs
lDuring the second week of illness, the
patient has a toxic appearance and
seems apathetic with sustained pyrexia.
lThe abdomen is distended slightly, and
splenomegaly is common

17. Signs
lIn the third week, patient’s toxicity increases and
weight loss is common. A delirious state (typhoid
state) emerges.
lAbdominal distension develops, and liquid, foul,
green-yellow diarrhea occurs
lthready pulse and tachypnea,
lDeath occur at this stage from toxemia,
myocarditis, intestinal hemorrhage, or perforation.

18. Signs
lIn the fourth week, the fever, mental state,
and abdominal distension slowly improve but
intestinal complications may still occur.
lConvalescence is prolonged, and most
relapses occur at this stage

19. Complications
lIntestinal
•Intestinal hemorrhage
• perforation

20. Complications
lHepatobiliary
•Mild elevation of transaminases
•Jaundice
•Hepatitis with hepatomegaly
•Pancreatitis
lAcute renal failure

21. Complication
lCardiac
•Nonspecific electrocardiographic changes
•Toxic myocarditis
•Pericarditis

22. Complication
lNeuropsychiatric
•A toxic confusional state, characterized by
disorientation, delirium, and restlessness
•Facial twitching or convulsions
•Encephalomyelitis
•Multiple brain abscesses

23. Complications
lHematologic
•DIC
•Hemolytic-uremic syndrome
•Hemolysis

24. Investigations
lAnemia, Elevated ESR, Thrombocytopenia,
and relative Lymphopenia.
lElevated PT and APTT,
lLiver transaminase values are usually
elevated to twice the reference range, as is
serum bilirubin.
lMild hyponatremia and hypokalemia are
common.

25. Investigation
lClinical diagnosis is suggested by
assays that identify Salmonella
antibodies, antigens, or DNA and is
then confirmed by isolation of the
organism.

26. Investigation
lDefinitive diagnosis of typhoid fever
requires isolation of the organism from
blood or bone marrow.
l The most sensitive method of isolating
S typhi is obtaining a bone marrow
aspirate (BMA) culture (90% sensitive).

27. Investigation
lS typhi can be isolated from BMA even
if patients have been taking antibiotics
for several days
lThis test may be indicated in patients
whose initial blood culture results are
negative, presumably because of prior
antibiotic therapy.

28. Investigation
lIf BMA cannot be performed, blood,
intestinal secretions, and stool culture
findings are usually positive in
approximately 85-90% of patients with
typhoid fever during the first week,
declining to 20-30% later in the course
of the disease.

29. Investigation
lS typhi has been isolated from the
cerebrospinal fluid, peritoneal fluid,
mesenteric lymph nodes, resected
intestine, pharynx, tonsils, abscess,
bone, and urine, among others.

30. Investigation
•The Widal test is the traditional
serologic test. The test measures
agglutinating antibodies against
flagellar (H) and somatic (O) antigens
of S typhi.

31. Investigation
•Studies have shown that sensitivity,
specificity of this test vary among
laboratories, rendering test's value to the
clinician questionable. This variation is
caused by differences in patient
population, antigens, and techniques.
•The Widal reaction is indicative of typhoid
fever in only 40-60% of patients at the time
of admission.

32. Investigation
lIndirect hemagglutination, indirect
fluorescent Vi antibody, and indirect
enzyme-linked immunosorbent assay
for immunoglobulin M (IgM) and
immunoglobulin G antibodies to S typhi
polysaccharide are available.

33. Investigation
lAlthough not commercially available, DNA
probes have been developed for identifying S
typhi from bacterial culture isolates and
directly from blood.

34. Treatment
lAntibiotic therapy is essential and should
begin empirically if the clinical evidence is
strong.
lAntimicrobials shorten the course, reduce the
rate of complications if begun early, and
reduce the case-fatality rate.

35. Treatment
lBecause of the efficacy and low relapse and carrier
rates associated the fluoroquinolones and the third-
generation cephalosporins are the antibiotics of choice
to treat MDR typhoid fever.

lBecause of its low cost, chloramphenicol is still used
in other areas where local strains are sensitive.

36. Treatment
lThe cost and need for IV administration are significant
disadvantages of third-generation cephalosporins
lFurazolidone and azithromycin are also used to treat
typhoid in children

37. Treatment of carriers
•Prolonged courses of amoxicillin or co-
trimoxazole
•Ciprofloxacin (750 mg bid) and norfloxacin (400
mg bid) have been much more effective,
•In nonendemic countries, patients should be
kept under bacteriological surveillance after
clinical recovery until 6 consecutive negative
results are obtained on fecal and urine cultures.

38. Treatment
lSurgical intervention is favored for
management of intestinal perforation.
lEarly diagnosis is key to lower mortality.
lCholecystectomy can be performed for
eradicating the carrier state.

39. Prevention
lIn endemic countries, the most cost-effective
strategy for reducing the incidence of typhoid
fever is the institution of public health
measures to ensure safe drinking water and
sanitary disposal of excreta.

40. Prevention
lHealth care workers should pay strict
attention to adequate hand washing
and safe disposal of feces and urine.

41. Prevention
lImmunization with typhoid vaccines at regular
intervals also considerably reduces the
incidence of infections.
lVaccination is indicated for travelers to areas
associated with a risk of exposure , persons
with intimate exposure (eg, household) to a
documented S typhi carrier, and microbiology
laboratory personnel.

42. Vaccines
lVi capsular polysaccharide vaccine
lTy21is an oral vaccine containing live
attenuated S typhi Ty21a strains in an
enteric-coated capsule
lParenteral heat-phenol–inactivated vaccine

43. Vaccines
lVi capsular polysaccharide vaccine
composed of purified Vi antigen, the
capsular polysaccharide elaborated by
S typhi isolated from blood cultures.

44. Vaccines
lTy21is an oral vaccine containing live
attenuated S typhi Ty21a strains in an
enteric-coated capsule

45. Vaccines
lAcetone-inactivated parenteral vaccine
lParenteral heat-phenol–inactivated
vaccine

46. Patient Education
lTyphoid vaccination is recommended at least
1 week prior to travel to highly disease-
endemic areas
lBecause the protection offered by vaccination
is at best partial, close attention to personal,
food, and water hygiene should be
maintained.

47. Thank You