Typhoid fever

Tuesday, May 7, 2019
2nd year MBBS

 Systemic infection by bacteria Salmonella Typhi
found in man
 Disease is clinically characterized by
continuous fever for 3-4 days
 Bradycardia
 Involvement of lymphoid tissues
 Term enteric fever includes both typhoid and
paratyphoid fevers
 Disease may occur sporadically, epidemically
or endemically

 Occurs in all parts of world where water and
sanitation are substandard
 Disease is uncommon in developed countries
due to improved living condition and
introduction of antibiotics in late 1940
 In developing areas Asia and Africa the disease
is a public health problem
 Since 1950 organism resistance to antibiotics is
a growing problem
 Due to organism resistance to antibiotics by
1989 have caused outbreaks of disease in India
and Pakistan in recent years

 Typhoid fever caused by multidrug
resistant(MDR) strains of S.Typhi that is
resistance to all 3 of first line of antibiotics
Chloramphenicol, Ampicillin and Co-
Trimoxazole) is associated with more severe
illness and highest rates of complications
and death especially in children less than 2
years

 AGENT
A. Salmonella Typhii
B. Survives intercellular in the tissues of
various organs
C. Readily killed by drying,
D. pasteurization and common disinfectants
E. Factors which influence the onset of typhoid
fever in man is infecting dose and virulence
of organism

 S.Typhi has three main antigens
 O
 H
 Vi
 A number of phage types at least 80.
 Phage typing has proved a useful
epidemiological tool in tracing the source of
epidemic

RESERVOIR OF INFECTION
A. Man is the only known reservoir of infection
B. Case may be mild missed or severe
C. Case is infectious as long as bacilli appear in
stools or urine
D. Carriers may be temporary or chronic
E. Convalescent carriers excrete the bacilli for 6-8
weeks
F. Persons who excrete the bacilli for more than a
year after clinical attack are chronic carriers
G. Organism persists in gall bladder and biliary
tract

 A chronic carrier state may be expected to
develop in 2 to 5% of cases
 A chronic carrier may excrete the bacilli for
several years may be as long as 50 years
either continuously or intermittently
 The famous case of Typhoid Mary who gave
rise to 1300 cases in her life time is a good
example of chronic carriers
 Fecal carriers are more frequent than urinary
carrier
 Chronic carrier state is often associated with
some abnormality of urinary tract

 SOURCE OF INFECTION
A. Primary source of infection are feces and
urine of cases and carriers
B. The secondary sources are
C. Contaminated water
D. Food
E. Fingers 4F
F. Flies
G. Feces

AGE
A. May occur at any age
B. 5-19 years is highest incidence
C. Pre school age
D. After 20years incidence falls due to
acquisition of immunity from clinical or
subclinical cases
SEX
A. More case among males
B. Carrier rate is more in females

 IMMUNITY
 Antibodies may be stimulated by the
infection or by immunization
 Natural typhoid fever does not always confer
solid immunity
 Second attack may occur
 Host factors that contribute to resistance to
S. Typhi are gastric acidity and intestinal
immunity
 INCUBATION PERIOD is 3 days to 3 weeks

 Enteric fever are observed all through year
 Peak incidence is reported during July to
September coincides with rainy season and
increase fly population
 Bacilli are found in water, ice ,food, milk and soil
for some period of time
 Bacilli survive for month in ice and ice-cream
 Bacilli may survive for 70 days in soil irrigated
with sewage under moist winter and half that
period in drier summer

 Typhoid bacilli grow rapidly in milk without
altering its taste or appearance
 Vegetables grown in sewage farms or washed
in contaminated water are a positive health
hazard
 Social factors includes
A. Pollution of drinking water supplies
B. Open air defecation and urination
C. Low standard of food and personal hygiene
D. Health ignorance
E. Typhoid fever regarded as an index of general
sanitation

FECES OR
URINE
FROM
CASES AND
CARRIERS
WATER
SOIL
FLIES
FINGERS
FOODS
RAW OR
COOKED
MOUTH
S OF
WELL
PERSO
N

 Onset is insidious but in children may be
abrupt with chills and high fever malaise
headache and sore throat
 The fever ascends in step ladder fashion
After 7-10 days the fever reaches a plateau
and the patient looks toxic appearing
exhausted
 There may be marked constipation
especially in early stage or “PEA SOUP”
diarrhea

 Marked abdominal distention
 Leucopenia and blood, urine and stools
culture is positive for salmonella
 If no complication patient condition improves
over 7-10 days
 Relapse may occur for up to 2 weeks after
termination of therapy
 Splenomegaly ,abdominal distention and
tenderness relative bradycardia
 ROSE SPOT rash appears during second
week of disease

 The individual spot found principally on the
trunk, is a pink purple 2-3 mm in diameter
that fades on pressure
 It disappear in 3-4 days
 Intestinal hemorrhages occur in 10% of
patients who have been ill longer than 2
weeks and who have not received proper
treatment
 Intestinal perfgoration is most likely to occur
in third week

 Less frequent complications are
 Urinary retention
 Pneumonia
 Thrombophlebtis
 Myocarditis
 Psychosis
 Chlecystitis
 Nephritis
 Osteomylitis
 Case fatality is 1-4% in children less than 4
years it is 1o times higher

 Microbiological procedures
 Isolation of S.typii from blood,bone marrow
and stools
 Blood culture is main stay of diagnosis of this
disease
 Serological procedures
 Felix widal test measures aggluntinating
antibodies level against O and H antigen

 Usually O antibodies appear on day 6-8 and
H antibodies on day 11-12 after the onset of
disease
 Test is usually performed on an acute
serum(at first contact with patient)
 It can be negative in 30% 0f cultures proven
case of typhoid
 This may be prior antibiotics therapy
 That has blunted the antibody response

 New diagnostic tests
 IDL Tubex test marketed by swedish
company can detect IgM09 antibodies from
patients within minutes
 Typhidot takes three hours to perform for
detection of Igm and IgG antibodies against
a 50kD antigen of S.Typhi

 Control of reservoirs
 Control of sanitation
 Immunization
 The weakest link in the chain of transmission
is sanitation which is amenable to control
Control of reservoirs
 The usual method of control of reservoir are
their identification ,isolation treatment and
disinfection

CASES
 Early diagnosis is important
 Culture of blood and stools
 Notification is mandatory
 Isolation of case and hospital transfer
 As a rule case should be isolated till three
bacteriological negative stool and urine reports are
obtained on three separate days
 Fluoroquinolones are the drug of choice
 Patients seriously ill may be given an injection of
hydrocortisone 100mg daily for 3 to 4 days

 Stools and urine are the source of infection
 They should be received in closed
containers and disinfected with 5% cresol
for at least 2hours
 All soiled clothes and linen should be soaked
in solution of 2% chlorine and steam
sterilized
 Nurses and doctors should not forget to
disinfect their hands

 Follow up examination of stools and urine
should be done for S.Typhi 3-4 months after
discharge of the patient and again after 12
months to prevent the development of carrier
state
CARRIERS
 Carriers should be identified by culture and
serological examinations
 Duodenal drainage establishes the presence of
Salmonella in Biliary tracts in carriers
 Vi antibodies are present in about 80% of
chronic carriers

 Carriers should be given a intensive course
of Ampicillin or Amoxicillin 4-6 grams a day
together with probenicid (2g/gay) for 6 weeks
 These drugs are concentrated in bile and
achieve eradication of carrier state in 70%
of carriers
 Cholecystectomy is most successful
approach to the treatment of carriers
 Cure rate may be 80%

 Surveillance of the carriers is necessary
 They should be prevented from handling
food, milk or water
 Health education
 Proper washing of hands with soap after
defecation or urination and before preparing
food
Control of sanitation
 Protection and purification of drinking water
supplies

 Improvement of basic sanitation
 Promotion of food hygiene
 Sanitation combined with health education
tends to be cumulative results in steady
reduction of typhoid fever
 Immunization
 Specific preventive measures but does not give
100% protection
 Lowers both the incidence and seriousness of
the infection

 Immunization is recommended to those
i. Living in endemic areas
ii. Household contacts
iii. Groups at risk such as school children and
hospital staff
iv. Travelers proceedings to endemic areas
v. Those attending meals and gatherings

 Anti typhoid vaccine
 The old Killed whole cell vaccine was
effective but produce strong side effects
 Two safe and effective vaccines are now
licensed and available
 One is based on defined subunit antigen the
other on the whole cell live attenuated
bacteria

 The Vi Polysaccharide vaccine
 First licensed in united states in 1994
 Composed of purified Vi capsular
polysaccharide from Ty2 S.Typhi strain and
elicit a T-Cell independent IgG response
 Administered S/C or I/M
 Vaccine is stable for 6 months at 37Cand for 2
years at 22C
 Recommended storage temperature is 2-8Cthe
Vi vaccine does not elicit adequate immune
responses in children aged less than 2 years

 Schedule
 Only one dose is required
 Confers protection 7 days after injection
 Revaccination every 3 years
 The Vi polysaccharide vaccine can be co
admionistered with other vaccine relevant for
international travellers such as yellow fever
and hepatitis A and vaccines of childhood
immunization programmes

 Safety
 No serious side effects are associated with
Vi vaccination
 No contraindication to the use of this vaccine
other than hyper sensitivity reaction to
vaccine components
 It is safe for HIV infected individuals, the
induction of protective antibodies is directly
correlated t o the level of CD4 positive T
cells

 The Ty21 a Vaccine
 First licensed in Europe in 1983 and in USA in
1989
 An orally administered live attenuated Ty2
strain of S,Typhi in which multiple genes
including the genes responsible for the
production of Vi have been mutated chemically
 The lyophilized vaccine is available as enteric
coated capsules
 Protection is markedly influenced by number of
dosed and their spacing

 Ty21a requires storage at 2-8C
 It retains potency for 14 days at 25C
 Schedule
 Licensed for use in individuals aged >5 years
 Administer every other day on 1,3 and 5th day, a
three dose regimen is recommended
 Protective immunity is achieved 7 days after last
dose
 Repeat these series every three years for people in
endemic areas
 Can be given with Polio,Cholera,Yellow fever and
MMR combination

 Safety and precautions
 Proguanil and antibacterial drugs should be
stopped from 3 days before until 3 days after
Ty21 as such drugs may harm live bacterial
vaccine
 The vaccine is unlikely to be efficacious if
administered at the time of ongoing diarrhea
 Ty21a can be administer to HIV positive
asymptomatic individuals as long as t cell count
is >200mm

Typhoid fever

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