Typhoid Fever

Year III lecture

May 2010
Epidemiology

 Typhoid/enteric fever is endemic in most developing

countries in Africa, Asia and Latin America
 It is primarily a disease of children and young adults
 In developed countries it occurs in travelers to
endemic regions
 Man is the ONLY reservoir of Salmonella typhi
 It is transmitted by ingestion of food/water
contaminated by feces of patients/carriers
Epidemiology contd.

 Up to 10% of patients continue to excrete the

organism in feces for three months
 2-3% become chronic carriers; excrete the
organism for > six months
 S. typhi had become increasingly resistant to
a number of 1st line antibiotics
Etiology

 Typhoid fever is caused by S. typhi;

S. enterica, subspecies enterica, serotype typhi
 It is a Gram negative, aerobic, non spore forming
organism
 It contains:
– LPS, lipolysaccharide
– Oligosaccharide somatic antigen “O” antigen
– Flagella “H” antigen
– Virulence “Vi’ antigen
Pathogenesis

 The portal of entry is the gastrointestinal tract

– Infecting dose, ID50, is 1000,000 organism
– Organism destroyed by acid in stomach
– Achlorhydria, treatment with H-2 receptor
antagonists lowers the infecting dose
 Incubation period is 7-10 days
 Organism multiplies within mononuclear
phagocytic cells of the intestinal lymphoid
follicles
Pathogenesis contd.

 After initial intracellular replication the organism is

released into the circulation:
– Sustained bacteremia
– Widely disseminated and seeds the liver, spleen, bone
marrow, gall bladder, Peyer’s patches
– It induces local and systemic humoral and cellular
responses
– Endotoxin may activate clotting/fibrinolytic cascade
– Local inflammation at Peyer’s patches may cause
tissue necrosis
Clinical manifestations

 The onset is usually sub acute

– During the 1st week, temperature rises in
stepladder fashion, and remains constant
– Patients develop headache, dry cough, abdominal
pain
– By the end of the 1st week patients become
ill/confused
– Liver and spleen palpable in about 50% of cases
Clinical manifestations contd.

– Relative bradycardia, pulse temperature

dissociation may be observed
– Rose spots, pink macules, may be present
– During the 2nd and 3rd week patients are more
ill
– They have apathetic affect, “typhoid facies”
– Various neurological complications may occur
in 10-40% of cases
Complications

 With appropriate therapy mortality <1%

– In some endemic regions it may be as high as
30%
 Perforation is the most serious complication
– Occurs in about 1-3% of patients
 GI bleeding, in about 10% of patients
 Relapse occurs in 5-10% of patients
 Chronic carriers in about 3%
Laboratory diagnosis

 In the 1st week blood culture positive in nearly all

patients
– Bone marrow cultures may be positive
 Serological test, the Widal test becomes positive
in 7-10 days
– A four-fold rise in titer
– A single titer of >1/160 WITH compatible clinical
illness
– False positive/negative results are common
 Blood culture
Urine Culture
Stool culture
100
Serum agglutinins

90

80
% Positive

70

60

50

40
Presence of S. typhi in blood urine and
30 stool, and rise of antibodies after
ingestion of the organism
20

10

0
1 2 3 4 5 6 7 8 Weeks
Management

 The aim of management is to kill the

organism and correct effect of septicemia
– Most patients are treated at home
– For hospitalized patients, good nursing care,
adequate nutrition, fluid/electrolytes
– Recognition and management of complications
– Multi drug resistant S. typhi increasing
Antibiotic treatment

 1st line drugs

– Amoxicillin,50-100mg/kg, 14 days
– TMP/SMX,8/40mg/kg, 14 days
– Chloraphenicol, 50-75mg/kg, 14 days
 2nd line drugs
– Floroquinolones, ciprofloxacin 15mg/kg, 5-7 days
– 3rd generation cephalosporin, ceftrixone
50mg/kg/day, IV/IM
Adjunct therapy

 Dexamethasone, 3mg/kg, IV for 48 hours

 Perforation is usually managed by surgery

 Sever GI bleeding may require blood

transfusion
Prevention and control

 Provision of clean, piped water supply

 Proper waste disposal

 Vaccines
– TAB, parentral inactivated whole organism
– Ty21A, oral mutant strain, 60-70% protection for up to 3
years
– Vi based, single injection, 65-70% protection after 1 year