Tropical Infection Diseases

Gatot Sugiharto, MD, Internist

Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma University
Surabaya

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Area kompetensi

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TYPHOID FEVER AND
PARATYPHOID FEVER

Gatot Sugiharto, MD, Internist

Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya

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 Typhoid and Paratyphoid
• Definition • Complications
• Etiology • Diagnosis and
• Pathogenesis differential diagnosis
• Epidemiology • Prognosis
• Clinical manifestations • Treatment
• The laboratory and • Paratyphoid Fever
other examinations

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 Definition of Typhoid fever
• Acute enteric & sistemic infectious disease caused by

Salmonella typhi (S.Typhi).

• Major symptom : prolonged fever, relative bradycardia,

apathetic facial expressions, roseola, splenomegaly,

hepatomegaly, leukopenia.

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 S. typhi
• Serotype : D group of Salmonella, Gram-negative, rod,
non-spore, flagella (+), produced endotoxin
• Antigens: located in the cell capsule :
– H (flagellar antigen).
– O (Somatic or cell wall antigen).
– Vi (polysaccharide virulence)
• Live 2-3 weeks in water. 1-2 months in stool. Die out
quickly in summer, resistance to drying and cooling
• Widal test : identified antigen H & O

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 A schematic diagram of a single Salmonella typhi cell
showing the locations of the H (flagellar), O (somatic), and
Vi (K envelope) antigens.
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Salmonella enterica.
Epidemiology

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 Transmission

• Route : fecal-oral route

• Risk : close contact with patients or carriers
• Media : contaminated water and food
• Vector : flies and cockroaches.

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 Pathogenesis(1)
• Need at least 105bacteria to develop infection
• Incubation period :
Agent 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

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 Pathogenesis(2)
• Second bacteriemia
After 1st bacteriemia  enter spleen, liver and bone
marrow (reticulo-endothelial system)  further
proliferation  a lot of bacteria enter blood
• Recovery

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 S.Typhi. liver 、 spleen 、 gall 、
BM ,ect
2nd bacteremia early stage&acme stage
(1-3W ）

stomach

(mononuclear Bac. In gall

phagocytes )

Bac. In
Lower feces
ileum

peyer's patches & S.Typhi eliminated

mesenteric lymph nodes convalvescence stage
(4-5w)
LN Proliferate, 1st bacteremia
swelling, necrosis (Incubation stage)
Enterorrhagi
defervescence thoracic
a, intestinal 10-14d
stage duct
perforation GSH - Tropmed - 2010 18
（ 3-4w ）
 Pathology (lower ileum)(1)

• Most characteristic lesion: ulceration of

mucous in the region of the Peyer’s patches
of the small intestine
• Hyperplasia stage (1st week): swelling
lymphoid tissue and proliferation of
macrophages.
• Necrosis stage (2nd week): necrosis of
swelling lymph nodes or solitary follicles.

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 Pathology (lower ileum)(2)
• 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

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 Clinical manifestations(1)
• Incubation period: 7 – 14 d (3 ～ 60 days)
• The initial period / early stage (first week)
– Insidious onset.
– Fever up to 39~400C in 5~7 days
– Chills, ailment, tire, sore throat 、 cough,
abdominal discomfort and constipation et al.

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 Clinical manifestations (2)

The fastigium stage (during 2nd & 3rd weeks)

• Sustained high fever, partly remittent fever or
irregular fever (10 ～ 14 days)
• Gastro-intestinal symptoms:
anorexia 、 abdominal distension or pain,
diarrhea or constipation
• Neuropsychiatric manifestations: confusion,
blunt respond, delirium and coma or meningism

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 Clinical manifestations(3)
• Circulation system: relative bradycardia or
dicrotic pulse.
• Splenomegaly, hepatomegaly toxic hepatitis.
• roseola : 30%, maculopapular rash a faint pale
color, slightly raised round or lenticular, fade
on pressure 2-4 mm in diameter, less than 10 in
number on the trunk, disappear in 2-3 days.

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• First week: The disease classically presents with step-
ladder fashion rise in temperature (40 - 41°C) over 4 to
5 days, accompanied by headache, vague abdominal
pain, and constipation.

• Second week: Between the 7 th -10 th day of illness,

mild hepato-splenomegally occurs in majority of
patients. Relative bradycardia may occur and rose-spots
may be seen.

• Third week: The patient will appear in the "typhoid

state" which is a state of prolonged apathy, toxaemia,
delirium, disorientation and/or coma. Diarrhoea will
then become apparent. If left untreated by this time,
there is a high risk (5-10%) of intestinal hemorrhage
and perforation.
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 Clinical manifestations(4)
Defervescence stage
• fever & most symptoms resolve by the forth
week of infection.
• Fever come down, gradual improvement in all
symptoms and signs, but still danger.
Convalescence stage
• the fifth week. disappearance of all symptoms,
but can relapse

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 Clinical spectrum (1)
• Mild infection:
– very common, symptom & signs mild, good general
condition, short period of diseases
– temperature is 380C
– recovery expected in 1~3 weeks
– seen in early antibiotics users, young children, easy to
misdiagnose
• Persistent infection: diseases continue than 5 weeks
• Ambulatory infection: mild symptoms, early intestinal
bleeding or perforation.

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 Clinical spectrum (2)

• Fulminate infection:
– rapid onset, severe toxemia and septicemia.
– High fever, chill,circulation failure, shock, delirium,
coma, myocarditis, bleeding and other complications,
DIC
– Sepsis & shock
• Asymtomatic carrier

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 Recrudescence
• Clinical manifestations reappear
• Less severe than initial episode
• It’s temperature recrudesce when temperature start
to step down but abnormal in the period of 2-3
weeks and persist 5~7 days then back to normal.
• Seen in patients with short therapy of antibiotics.

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 Relapse
• Serum positive of S.typhi after 1 ～ 3 weeks of
temperature down to normal.
• Symptom and signs reappear
• the bacilli have not been completely removed
• Some cases relapse more than once

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 Laboratory findings(1)
Routine examinations :
• Leukocytopenia
• Recovery with improvement of diseases decreased in relapse

Bacteriological examinations:
• Blood culture:
– The most common use

– 80~90% positive during the first 2 weeks of illness

– 50% in 3rd week

– Re-positive when relapse and recrudesce

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 Laboratory findings(1)
• The bone marrow culture
– The most sensitive test, specially in patients pretreated with
antibiotics.
• Urine and stool cultures (after 1st week)
– Increase the diagnostic yield, less frequently positive
– Stool culture better in 3~4 weeks
• Serological tests (widal test) :
– 5 types of antigens O, H, and paratyphoid fever flagella A,B,C)
– Appear during 1st-2nd week
– 70% positive in 3~4 weeks and can prolong to several months, in
some cases, antibodies appear slowly, or remain at a low level
– 10~30%) negative at all.
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 Widal test interpretation
• "O/H" agglutinin antibody titer ≥ 1:160 or "O" 4 times
higher supports a diagnosis
• "O" rises alone, not "H” : early of the disease
• Only "H" positive, but "O" negative : nonspecifically
elevated by immunization or previous infections or
anamnestic reaction.
• Antibody level maybe lower when have used antibiotics
early.
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 Complications
Intestinal hemorrhage
• Appear during the 2nd-3rd week
• Often caused by unsuitable food, diarrhea et al
• Serious bleeding : sudden drop in temperature, rise in pulse,
signs of shock followed by melena/hematochezia
Intestinal perforation:
• Appear during 2-3 week, involve lower end of ileum
• Abdominal pain, diarrhea, intestinal bleeding, sweating, drop in
temperature, and increase in pulse rate, rebound tenderness,
reduce or disappear bowel sound, liver dumping dissapear ,
leukocytosis (sign of peritonitis)
• Free air under x-ray.
Toxic hepatitis : 1st-3rd weeks , hepatomegaly, ALT elevated
Others : Myocarditis, encephalopathy, HUS, cholecystitis, meningitis,
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nephritis, etc
 Differential diagnosis
• Viral infections

• Malaria

• Leptospirosis

• Louse borne typhus

• Riketsiosis

• Gram negative bacilli septicemia

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 Prognosis

• Case fatality 0.5 ～ 1%, espesially in old

ages & infant
• About 3% of patients become fecal chronic
carriers

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 Management(1)
General management
• Bed rest, good nursing care and supportive
treatment
• Close monitoring VS, abdominal condition and
stool .
• Easy digested food or half-liquid food, good
hidration (enteral / par-enteral)
• Antipiretic drugs
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 Management (2)

Antibiotics
• Chloramphenicol : 500 mg, q6h (2 weeks) po/iv
• Thiamphenicol : 500 mg, q6h (10-14 days) po
• Cotrimoxazole : 2 adult tab, bid (2 weeks) po
• Ampicillin / amoxycillin : 50-150 mg/kg BW in 3-4
divided dose (2 weeks) po/iv
• 3rd generation Cephalosporin :
– Ceftriaxone 2-4 g iv single/divided dose (3-5 days)

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 Management(3)
• Quinolone :
– Norfloxacin : 400 mg, bid (2 weeks) po
– Ciprofloxacin : 500 mg, bid (7 days) po
– Ofloxacin : 400 mg, bid (7 days)
– Pefloxacin : 400 mg, OD (7 days)
• Corticosteroid
– Only for toxic/sepsis condition
– Dexamethasone 5 mg, tid iv
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 Paratyphoid fever A,B,C
• Caused by Salmonella paratyphoid A,B,C.
respectively.
• In no way different from typhoid fever in
epidemiology, pathogenesis, pathology, clinical
manifestations, diagnosis, treatment

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 Homework

• Vaccination for S. Typhi, is it effective ?

• Gall culture, what make it a gold standard test

& how to perform it ?
• New serologic test for S. Thypi

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 Yersinia infection
Focus on Pes / Plaque

Gatot Sugiharto, MD, Internist

Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma University
Surabaya

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 Pes / plaque
• A zoonotic infection cause by Yersinia pestis,
humans are accidental host
• Yersinia pestis : gram negative bacilli, facultatif
anerob, susceptible to drying, produce
endotoxin (lipid A
• Natural reservoir : rats, squirrel, rabbit &
domestic animal
• Speard by flea bites, direct contact w/ infected
tissue (blood, poultry) or inhalation aerosol
 Epidemiology of Plague

• Outbreaks are cyclical corresponding to rodent

reservoir and arthropod vector populations
• Plague recorded more than 2000 years ago
• The pandemics :
• 14th century; Black Death; 25 million dead in
Europe alone (>1/4 of entire population)
• 1990s; From Burma, China, Hong Kong
spread to other continents via rat-infected
ships; 20 million dead in India alone
 Clinical evaluation
• Clinical Forms of Plague
– Bubonic plague : with swollen and painful axillary
& inguinal lymph nodes (buboes)
» Transmitted from mammalian reservoirs by flea
(arthropod) bites or contact with contaminated
animal tissues
• Pneumonic plaque
» Person-to-person spread
• Diagnosis : culture & isolation
• Therapy : Streptomycin, tetracyclin,
chloramphenicol or cotrimoxazole
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 TETANUS
Gatot Sugiharto, MD, Internist
Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma University
Surabaya

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 Introduction
• Tetanus is an illness characterized by an acute
onset of hypertonia, painful muscular
contractions (usually of the muscles of the jaw
and neck), and generalized muscle spasms
coused by clostridium tetani infection
• Despite widespread immunization of infants and
children in the United States since the 1940s,
tetanus still occurs in the United States.
 Clostridium tetani
Genus Clostridium : gram-positive, spore-forming
species, several of which are able to produce
disease in humans.
Most species are obligate anaerobes, some will
grow under microaerophilic conditions.
Natural habitat: soil and the intestinal tracts of
animals and humans.
Very active metabolisms, ferment a variety of
sugars, very short generation times.
 C. tetani

• Large, spore-forming, motile, obligate anaerobic bacillus, gram

positive, drumstick appearence (see above)
• Ferments: proteins or amino acids.
• Produces: acetic acid, fatty acids, NH3, CO2, H2, and a strong
exotoxin  Tetanospasmin (a powerful neurotoxin) & tetanolysin
 Clostridium
tetani Gram
Stain

NOTE: Round terminal spores give cells a “drumstick” or

“tennis racket” appearance.
 Tetanus : characteristic
• Does not follow typical tranmission from host to host.
• Soils or materials in contact with animal wastes are usually
heavily contaminated with C. tetani
• Tetanus often resulted from wounds received in battle.
• In clean wounds with good blood supply and high oxygen
tension, germination rarely occurs.
• In necrotic and infected wounds, anaerobic conditions will
permit germination.
• Contaminated puncture wounds can be particularly dangerous,
especially when a foreign body is present.
• Spores may occasionally lay dormant in a healed wound for
months or years; trauma to the area may then cause
germination and disease.
 Symptoms & signs
• Tetanus is an acute, potentially deadly, systemic
infection characterized by painful involuntary
contraction of skeletal muscles.
• Other symptoms include
– Febrile (feverish), irritability, heavy sweating
– A stiff neck, a tight jaw (lockjaw/trismus)
– Facial muscle spasms (risus sardonicus) and
difficulty swallowing
– Spasm paravertebral muscle (opistotonus)
Mechanism of Action of
Tetanus Toxin
 Risus sardonicus

A soldier dying from tetanus. Painting by Charles Bell

• In advanced stages, tetanus

spasms can break bones.
• Respiratory complications are
common and death rates high,
Opisthotonos
especially in children and (spastic paralysis of the back)

elderly persons.
Opisthotonos in Tetanus Patient
 Diagnosis of tetanus
• Made on the basis of the clinical manifestation,
and the patient’s history may indicate
inadequate immunization.
• Since C. tetani is a common contaminant of
wounds and may be found in patients who do
not develop tetanus  isolation of the bacteria
from a patient may not be diagnostic.
 Treatment
• Antitoxin (tetanus immune globulin) to neutralized toxin
should be administered immediately.
• Wounds should be debrided to remove dead tissue or foreign
bodies.
• Antibiotics should be given to inhibit growth of C. tetani.
• A tetanus toxoid booster immunization should be given to
patients who have not received one within the last 5 years.
• If spasms occur, antispasmodic drugs should be used and
respiration maintained by a breathing apparatus if necessary.

As soon as clinical tetanus is suspected, steps to

neutralize existing toxin and prevent the formation of
new toxin must begin.
 Prevention
• Tetanus carries a 35% mortality rate,
making prevention very important!
• Death may occur from tetanus, often
from cardiac (heart) and respiratory
(lung) effects or secondary
complications from the infection
• The best course is childhood
immunizations, with consistent booster
doses, and prompt cleaning of wounds with
hydrogen peroxide.