Typhoid fever

Dr. Sneh kumari

Assistant Professor
Department of Community Medicine
MAMC. Agroha
 Introduction
• The name Typhoid means
“typhus-like”/ "resembling typhus” & comes from
neuropsychiatric symptoms common to typhoid &
typhus.

• Typhos in Greek means smoke & typhus fever got its

name from smoke that was believed to cause it.
 Introduction

• Term enteric fever include both typhoid & paratyphoid fevers

• The disease has received various names -

 Gastric fever
 Abdominal typhus
 infantile remittant fever
 Slow fever
 Nervous fever
 Pythogenic fever
 Introduction
• Typhoid fever is a systemic disease transmitted by
ingestion of food or water contaminated with feces of
an infected person, which contain bacterium
Salmonella enterica enterica serotype Typhi

• It is an acute generalized infection of the

reticuloendothelial system, intestinal lymphoid tissue
& gall bladder.
 Introduction

Without effective treatment, typhoid fever has a case-

fatality rate of 10 –30 % & reduced to 1 – 4 % in those
receiving appropriate therapy
 Disease burden: Global
• WHO estimated global typhoid disease burden (2018)
11-20 million cases annually
128,000- 161,000 deaths / year
-Predominantly in children of school age or younger

• Majority of this burden occurs in asia.

 Disease burden: India

• Typhoid fever is endemic in India

• Reported data for year 2017 shows 2.22 million cases

& 493 deaths

Source- Report of the Working Group on Disease Burden for the 12th Five Year Plan GOI Planning Commission
 Agent factors
1.Causative agent
• Salmonella typhi (Mainly) &
S.paratyphi A,B,C(Infrequently)

• Salmonellae are
 Gram – ve rods
 Facultative aerobes
 Motile with peritrichate
flagella
 Non-spore forming
 2-3μm × 0.4-0.6 μm in size
Agent factors
 Agent factors
• Boiling or chlorination of water & pasteurization of
milk destroy bacilli

• Bacilli are killed at -

- 55º C in1 hour / at 60º C in 15 min.
-within 5 min. by mercuric chloride or 5% phenol

• Infectious dose is 103 – 106 colony- forming units

 Agent Factors
2. Reservoir of infection-
• Human beings are the only
known reservoir of infection.
Case
• May be
Carrier
• Mary Mallon (1869-1938)
nickname of “Typhoid Mary”
first healthy carrier in US who
gave rise to >1300 cases in her
life time
 Typhoid case ?
Typhoid carrier ?
 Confirmed case of typhoid fever
A patient with fever (38°C and above) that has lasted for
at least 3 days, with a laboratory- confirmed positive
culture (blood, bone marrow, bowel fluid) of S. typhi.
 Probable case of typhoid fever
A patient with fever (38°C and above) that has lasted for
at least 3 days, with a positive serodiagnosis or antigen
detection test but without S. typhi isolation.
 Suspected case
A patient that meets the criteria for Acute Febrile Illness
(AFI): current fever (38°C & above)that has lasted for at
least 3 days.
 Confirmed case of typhoid fever
• A patient with fever (38°C and above) that has lasted for at
least 3 days, with a laboratory- confirmed positive culture
(blood, bone marrow, bowel fluid) of S. typhi.

 Probable case of typhoid fever

• A patient with fever (38°C and above) that has lasted for at
least 3 days, with a positive serodiagnosis or antigen detection
test but without S. typhi isolation.

 Suspected case
• A patient that meets the criteria for Acute Febrile Illness (AFI):
current fever (38°C & above)that has lasted for at least 3 days.
 Chronic carrier
Excretion of S. typhi in stools or urine (or repeated
positive bile /duodenal string cultures) for >1 year after
onset of acute typhoid fever. Some patients excreting S.
typhi have no history of typhoid fever.
 Agent Factors
Secondary source
3.Source of infection -

o u rc e
a r y s
Prim
 Host Factors
1. Age
Typhoid may occur at any age.
Highest incidence in 5-19 years

2. Gender
Disease is M > F & carrier state is F > M
 Host Factors
3. Immunity
• Antibody to somatic antigen (O) is usually higher in the patient
with disease & antibody to the flagellar antigen (H) is higher in
immunized individuals.

• S.typhi being intracellular organism, cell-mediated immunity

plays role in combating the infection.

• Natural typhoid fever can not always confer solid immunity;

second attacks may occur when challenged with a large oral
dose.
 Host Factors
• Increased susceptibility to infection -
 Decreased intestinal integrity
-Inflammatory bowel disease
-Prior G.I surgery
-Alteration of intestinal flora
by antibiotic

 Decreased stomach acidity

- < 1yr age
- Antacid ingestion
- Achlorhydric disease
 Environmental & Social factors
• The peak incidence is reported during July –September

• May survive over a month in ice and ice-cream, up to 70

days in soil irrigated with sewage under moist winter
conditions, & for half that period under drier summer
conditions

• Typhoid bacilli grow rapidly in milk without altering its taste

or appearance in anyway.
 Environmental & Social factors
• Social factors responsible for prevalence of typhoid in
endemic form in our country such as -
Pollution of drinking water supplies
Open air defecation and urination
Low standards of food and personal hygiene and
Health ignorance

• Therefore typhoid is also called ‘social disease’ & regarded as

an index of general sanitation in any country
• Incubation period
- Usually 10-14 days.
- Ranges from 3 days - 3 weeks depending upon
infectious dose , host’s health & immune status

• Modes of transmission-
‘feco-oral route’
 Clinical features
1st week
• Fever - gradual onset ,continuous,
increases gradually in ‘step
ladder’ fashion (38 - 400C)
• Prodromal symptoms –
- Headache
- Bodyache
- Malaise
- Joint pains
-Occasional vomiting
 Clinical features
2nd week
- Temperature reaches its plateau
(40 C / 104 F)
- Relative bradycardia
- Dry & hot skin
- Coated tongue
- Distended abdomen
- Splenomegaly
- “pea soup” diarrhea or
marked constipation
- Rose spots
 Rose spots

Pink papule 2-3 mm in diameter ,fades on pressure ,disapear in 3-4 days

 Clinical features
3rd week - Signs of toxemia such as
-Very high fever
-Rapid thready pulse
-Delirious (Typhoid state) , Disoriented, sleepy, confused
-later becomes stuporous, develops coma & dies
Complications (10 -15 % of patients)
- Intestinal hemorrhage , Intestinal perforation
- Encephalitis
- Neuropsychiatric symptoms (described as "muttering delirium"
or "coma vigil"), with picking at bedclothes or imaginary objects.
- Metastatic abscesses, cholecystitis, endocarditis and osteitis
 Clinical features

Complications (10 -15 % of patients)

- Intestinal hemorrhage , Intestinal perforation
- Encephalitis
- Neuropsychiatric symptoms (described as "muttering
delirium" or "coma vigil") with picking at bedclothes or
imaginary objects.
- Metastatic abscesses, cholecystitis, endocarditis and
osteitis
 Investigations

Cases -
• 1st week- Blood culture
• 2nd week – Widal test
 Felix-Widal test measures titres of serum agglutinins against
somatic (O) and flagellar (H) antigens which usually begin to
appear during the 2nd week
• 3rd week – Blood for repeat Widal, stool & urine for culture
• Other samples- S. typhi can be detected in stool, bone marrow
aspirate & punch biopsy of rose spots
 Investigations
Carriers-
• Vi antibodies determination has been used as a screening
technique to identify carriers among food handlers & in
outbreak investigations.
• Vi antibodies are very high in chronic S. typhi carriers
• But confirmation is made by culture
• Locating carriers in cities through “sewer swab technique”
(gauge pads left in sewers & drains are cultured)
• Other technique for Isolation of salmonella from sewage is
filtration through millipore membrane & culturing the
membrane on highly selective media (Wilson & Blair media)
 New Rapid tests for diagnosing typhoid :
• Tubex® test (Swedish company) - detects IgM O9
antibodies from patients within a few minutes.

• Typhidot® (developed in Malaysia) takes 3 hours to

perform. Detects specific IgM & IgG antibodies against
a 50 kD antigen of S. typhi.

• Typhidot-M® - detects specific IgM antibodies only.

• The dipstick test, (developed in the Netherlands)
 Management of typhoid fever
General - Supportive care includes
• Maintenance of adequate hydration.
• Antipyretics.
• Appropriate nutrition

Specific - Antimicrobial therapy

Indication Agent Dosage (Route) Duration, Days
Empirical Treatment
Ceftriaxone 1–2 g/d (IV) 7–14
Azithromycin 1 g/d (PO) 5
Fully Susceptible 
Ciprofloxacin(1st line) 500 mg bid (PO) / 400 mg q12h (IV) 5-7
Amoxicillin (2nd line) 1 g tid (PO) or 2 g q6h (IV) 14
Chloramphenicol 25 mg/kg tid (PO or IV) 14-21
cotrimoxazole 160/800 mg bid (PO) 14
Multidrug-Resistant
Ciprofloxacin 500 mg bid (PO) or 400 mg q12h (IV) 5-7
Ceftriaxone 2–3 g/d (IV) 7-14
Azithromycin 1 g/d (PO) 5
Nalidixic Acid Resistant
Ceftriaxone 1–2 g/d (IV) 7-14
Azithromycin 1 g/d (PO)c 5
Ciprofloxacin 750 mg bid (PO) or 400 mg q8h (IV) 10-14
Relapses
• Involving acute illness occur in 5-20% of typhoid fever cases that
have apparently been treated successfully. A relapse is heralded by
the return of fever soon after the completion of antibiotic treatment.

Typhoid in pregnancy - few data

• Case reports of the successful use of fluoroquinolones but these have
generally not been recommended in pregnancy
• Ampicillin is safe in pregnant or nursing women, as is ceftriaxone in
such women with severe or MDR disease
 Prevention & Control
• The control or elimination of typhoid fever is well within the
scope of modern public health. This is an accomplished fact
in many developed countries .
• Lines of defense
 Prevention & Control
1. Elimination of reservoir
CASES CARRIERS
• Early diagnosis • Identification
• Notification
• Treatment
• Isolation
• Surgery
• Treatment
• Disinfection • Surveillance
• Follow up • Health education

2. Breaking the channel of transmission

3. Protection of susceptible
• Health promotion
• Specific protection - Vaccination
 Control of carriers
• Up to 10% of untreated patients excrete S. Typhi in the feces
for up to 3 months, and 1–5% develop chronic asymptomatic
carriage, shedding S. Typhi in either urine or stool for >1
year.
• The rate of carriage is higher among female patients, >50
years, & patients with cholelithiasis or schistosomiasis.

• If cholelithiasis or schistosomiasis is present eradication often

requires both antibiotic therapy & surgical correction
 Control of carriers

Antibiotics –
• Amoxicillin or ampicillin (100 mg/ kg/ d) plus probenecid (1
g orally or 23 mg/ kg for children) or TMP-SMZ (160 - 800
mg twice daily) for 6 weeks

• About 60% of persons treated with either regimen can be

expected to have negative cultures on follow-up.

• Clearance of up to 80% of chronic carriers can be achieved

with the administration of 750 mg of ciprofloxacin twice
daily for 28 days or 400 mg of norfloxacin.
 Control of carriers
• Carriers should be excluded from any activities
involving food preparation and serving, as should
convalescent patients and any persons with possible
symptoms of typhoid fever.

• Food handlers should not resume their duties until they

have had 3 negative stool cultures at least 1 month
apart.
2. Breaking the channel of transmission

Chlorinated water, pasteurized milk

Sanitation latrine

m ent
viron
n
Cle an e
 Prevention & Control
• Health promotion -consist of
- Provision of protected (chlorinated )water supply
- Sanitary disposal of sewage
- Health education of the people

• Specific protection – Vaccination

Typhoid outbreaks
Different types of Vaccine
 Vaccine

Live vaccine / Typhoral

• Live, lyophilized vaccine available in pack of 3 capsules

• Each capsule contain not less than 109 viable attenuated

salmonella typhi 21 a strain

• Indicated for all adults & children aged at least 5 yr

• Schedule - 1 capsule on alternate days empty stomach with a

glass of water or milk for 3 days i.e. on day 1,3 & 5
 Vaccine

• Antibiotics should be avoided for seven days before or after

the immunization series.

• Protection is influenced by no. of doses & their spacing

• Immunity starts 2 wks after taking 3rd capsule & lasts for 3 yr

• Protective efficacy is 60% - 70 %

• A booster dose – same 3 capsules once in 3 years

 Vaccine

• Best stored at 2-80C , retains potency for 14 days at 250C

• It can be given to HIV + VE , asymptomatic as long as CD4

count is >200/mm3

• It is well tolerated & side effects are rare

• Contraindication - acute febrile illness , acute intestinal

infection , congenital or acquired immunodeficiency
 Vaccine

Vi polysaccharide vaccine / Typhim -Vi

• Liquid vaccine , composed of purified Vi capsular
polysaccharide from Ty2 S.Typhi strain

• It is given in a single shot of 0.5 ml (containing 25 microgram

Vi antigen) S.C or I.M
• Immunity develops 10-15 days after injection & lasts for 3 y
• Booster dose – once in 3 yr
• Protective efficacy is 70%
• The recommended storage temp. 2-8 C
• The vaccine is approved for > 2 years of age
 Vaccine

• New generation Typhoid conjugate vaccine -induces 'T' cell

dependent response with much higher antibody levels
providing a very high rate of immunity.

• For infants above 6 months as well as adults.

• The Typbar-TCV vaccine is safe & more effective than Typbar

vaccine.
 Vaccine
 Peda typhi -Contain purified Vi capsular polysaccharide of
S.typhi conjugated with Tetanus toxoid protein
• Composition One dose (0.5 ml) contains : Vi polysaccharide
of Salmonella typhi 5 ug conjugated to 5 ug of Tetanus
toxoid protein in isotonic saline.
 Contra –indications
-Hypersensitivity to any constituent of the vaccine
-Pregnant & lactating women
-fever or severe infection
• Inject 0.5ml intramuscularly.
• Prevention becomes effective 2-3 weeks after immunization.
 Vaccine
 Dosage
Between 3 months - 2 years
• 2 injections of 1 dose each at interval of 4-8 weeks, followed
by booster at 2 to 2.5 years age. Booster vaccination every 10
years. Peda Typh™ can be administered to infants after the age
of 3 months
Above 2 years
• 2 injections of 1 dose each at interval of 4-8 weeks. Booster
vaccination every 10 years
 Possible Side effects
• Mild local pain, redness, induration & mild fever may occur
during the 48 hours following injection. Store between 2-8 o C.
Recommendations on vaccine use
• WHO recommends vaccination for people travelling in
endemic areas
• People living in high risk areas, in refugee camps,
microbiologists, sewage workers & children should be the
target groups for vaccination.
Recommendations on vaccine use

 Routine immunization
• WHO recommends immunization of school-age children be
undertaken wherever the control of the disease is a priority.
• In routine immunization, therefore, the use of the available
typhoid vaccines should be considered in areas where
typhoid fever is endemic in children aged over 2 years.
• Either Vi or Ty21a vaccine should be used.
 Conclusion

• Wash your hands.

• Keep your food safe
“Cook it, boil it ,peel it or forget it”

• Available Vaccine can be used

• The fluoroquinolones are widely regarded as optimal for

the treatment of typhoid fever
Thank You