Typhoid Fever (Enteric Fever)

TYPHOID AND PARATYPHOID
ENTERIC FEVER
Dr. RAGHAVENDRA S.HEGDE,
PHARM.D(PB)
COMMUNITY PHARMACY PRACTICE

MORPHOLOGY
26/02/2020Dr.Hegde Lectures(DHL)
2
 The causative agent of typhoid
is a Salmonella typhi
belonging to family
Enterobacteriaceae.
 The bacteria is a gram
negative
 Rod shaped bacteria in single
arrangement.
 Rarely others, base, chains of
Rods.
 It has peritrichous flagella for
motility.
 It is non spore forming
 Facultative anaerobic, and
capsular organism.

Virulent factors:
3
 The bacteria causes the infection
due to the following virulent factors
:-
 H antigen present on the flagella
 O antigen is a somatic antigen
present on the body surface of the
organism.
 Vᵢ capsular antigen which is a
capsular producing antigen,
 Exotoxin called
lipopolysaccharide,
 Secretory protein called invasin
which enters the non-phagocytic
cells of the host.
 Due to these virulent factors the
bacteria can escape from the
host’s immune mechanism.

Typhoid and Paratyphoid
 Typhoid fever is an infection caused by the bacterium
Salmonella typhi.
 Paratyphoid is an infection which is similar but has
milder symptoms, which is caused by the bacterium
Salmonella paratyphi.
26/02/2020
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Dr.Hegde Lectures(DHL)

Mechanism of Infection
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In the intestine it crosses the epithelium and reaches systemic
circulation and enters into various tissues and organs.
From the stomach it enters into the intestine.
Salmonella typhi enters the host through the contaminated
food and water

Epidemiology
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Epidemiology
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Epidemiology and Transmission
 Typhoid fever incidence varies considerably in Asia. In India,
typhoid fever incidence has been found particularly in children
due to poor sanitation. They are usually transmitted from
contaminated food or water (food-water borne disease).
 Humans are the only carriers of these infections.
 The bacteria get into the body through the gut and reside in the
immune system (glands and lymph vessels) and multiply.
 The bacteria enter the bloodstream and this is when symptoms of
headache and fever appear.
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Signs and Symptoms
 The incubation period is usually between 7-14 days or
as long as 30 days.
1. The various signs and symptoms are as follows:
(1) Fever and headache are the common symptoms.
2. Typically, the temperature increases gradually day by
day during the first week thereafter rises mostly the
evenings (103-104 °F).
(2) Loss of appetite, nausea, non-productive cough (dry
cough), diarrhoea (more common in children) and
constipation (common in adults) may also occur,
abdominal pain, loss of appetite and weight loss and
weakness.
3. Rash (rose-coloured spots).
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Diagnosis
 Stool and Blood Culture:
 Diagnosis is by culturing the organism from stool or other
sources.
 Blood cultures are positive in 60-80% of cases.
 Serology: The traditional serological test is Widal's test. It
measures agglutinating antibodies against flagellar (H) and
somatic (O) antigens of S. typhi.
 In acute infection, the 'O‘ antibody appears first, rising
progressively, falls later, and often disappears within a few
months.
 The 'H' antibody appears slightly late but persists longer. High
or rising 'O' antibody titres generally indicate acute infection,
whereas 'H' antibody is used to identify the type of infection.
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Pharmacotherapy
 Empiric antibiotic treatment is started immediately and
clinically unstable patients are admitted to hospital for IV
treatment while those who are stable may be treated as
outpatients.
 Management consists of the following measures:
 Supportive therapy
 Hygiene
 Antibiotics therapy
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Management consists of the following
measures:
 Supportive therapy: Adequate rest, rehydration and
correction of electrolyte disturbances and Antipyretic
therapy (Paracetamol) as and when required.
 Hygiene: Carriers must be particular with hand washing
and the disposal of faeces and urine.
 Antibiotics therapy: If started early, antibiotics therapy
plays an important role to reduce the course of the
disease, rate of complications, and mortality.
 Drug resistance in typhoid bacteria is a problem and
challenging.
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Pharmacotherapy
 Ciprofloxacin (drug of choice) from long time following
the emergence of strains resistant to chloramphenicol,
ampicillin and trimethoprim (multidrug-resistant typhoid).
 Patients who are clinically unstable are empirically
treated with parenteral (IV) ceftriaxone.
 The antibiotic is appropriately changed once sensitivities
are available.
 Azithromycin and some of the newer fluoroquinolones
such as gatifloxacin are suitable alternatives to
ciprofloxacin in stable patients, and may be better for
reducing clinical relapse rates compared to
chloramphenicol.
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Pharmacotherapy
 However, increasing resistance to azithromycin has
been reported.
 Local resistance patterns need to be considered when
choosing the most appropriate antibiotic.
 After taking treatment for one week, a stool culture
should be done in asymptomatic patients to check that
these infections have cleared. It can be clinically
confirmed if follow up is done by the patient.
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Roles and Responsibilities of
Community Pharmacist
 A community pharmacist must be aware of the
resistance pattern of the bacteria and relapse rates of
typhoid in his/her endemic region.
 He can extend its role in sensitizing regarding the
disease and its prevention methods.
a) Community Education and Awareness:
Community pharmacist plays a very important role in
sensitizing public about prevention and early
management of typhoid.
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Community Education and
Awareness:
 This can be achieved by carrying out the following
activities, in the locality:
I. Distribution of typhoid information leaflets in community briefly the
disease, prognosis, complications and prevention etc.
II. Creating awareness about maintaining hygiene conditions and safe
drinking water programme by displaying posters/boards/stickers in
the pharmacy.
III. The community awareness or education must target the following
essential non-pharmacological measures so as to prevent the
transmission of this disease:
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Proper Hand Wash:
Techniques of hand washing
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Proper Hand Wash:
Techniques of hand washing
1. Wet both hands with water.
2. Rub soap between the palms.
3. Rub between the fingers and palm by interlocking them.
4. Clean back of the hand with another.
5. Rub hands palm to palm.
6. Rotate rubbing backward and forward with clasped
fingers.
7. Rub the wrists of both hands one at a time.
8. Wash the hands. The whole process takes 40-50
seconds.
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Safe disposal of urine and
faeces:
 It is best to flush urine and faeces into the toilet immediately.
 Make sure the toilet is cleaned with disinfectant daily.
 If a nappy is worn, change the nappy using gloves if possible.
 Flush if any faeces, into the toilet.
 Always make sure to wash hands thoroughly after changing the
nappy.
 If bedding or clothes are soiled, remove them as soon as possible.
Wash them separately from unsoiled items, with hot water.
 Wash hands after handling the soiled items.
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Safe disposal of urine and
faeces:
 It is very important to be careful of what to eat and drink
and to wash hands with sanitiser thoroughly after using
the toilet, before eating and before preparing food.
 Only eat food that is freshly prepared, cooked and
served hot, or fruit that can be peeled by oneself, such
as banana and mango.
 Only drink bottled or cooled boiled water. When drinking
bottled water, ensure the seal is unbroken to ensure the
bottle has not been refilled.
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(b) Patient Counseling:
 (i) Related to Disease: A community pharmacist apart
from spreading awareness can educate/counsel any
person who is seeking relevant information about the
disease.
 On the first meeting with a patient, he/she has to find out
whether the patient has previously been treated for
typhoid.
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The principle of counseling is based on
principles of 5 "A" that are:
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 ASK: Symptoms, its duration of appearance hygienic conditions,
drinking water source and safety, disposal of urine and faeces, any
drug treatment in recent period.
 ASSESS: Understanding of disease and drugs and Non-adherence
to antibiotics.
 ADVISE: Quit/reduce consumption of alcohol/tobacco, taking rest,
healthy personal hygiene, not to miss antibiotics and complete the
dosage regimen without default, safe disposal of Urine/faeces and
hand hygiene.
 ASSIST: Assist with drug interaction checking as well as medication
safety.
 ARRANGE: At the end, pharmacist should address any questions
that have arisen during the session and if needed talk with the
patient's physician.

(b) Patient Counseling:
 (ii) Related to Drug Therapy:
 Mostly antibiotics are mainstay of therapy in typhoid.
Detailed management is not the scope of the topic but
the choice of antibiotics may vary on the resistance
pattern and practice in specific region.
 Table provides an insight for side effects and specific
counseling for antibiotics
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Information on side effects and
counseling for antibiotics
 Azithromycin
 (Adults: Orally 500 mg
as single dose on first
day, then 250 mg/day on
days 2 through 5)
 Side Effects
 Diarrhoea
 Nausea
 Vomiting
 Abdominal pain
 Dyspepsia
 Flatulence
 Rash.
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Counseling Emphasis:
1. Instruct patient to take the doses on time. Inform that the medication
works best on empty stomach, but may be taken with food if there is
gastrointestinal upset.
2. Instruct patient to take medication with full glass of water.
3. Instruct to notify health care provider if rash develops or difficult
breathing occurs.
4. Explain that antacids should be avoided while this medication is
being taken. If antacids are taken then maintain a gap of 2 hours.
5. Emphasize and insist patient to complete the antibiotic course. This
will ensure complete cure and ask to follow up the doctor to ensure
infection has been cured.
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Counseling Emphasis:
 Fluoroquinolones
Ofloxacin (ADULTS:
Orally/intravenous 400
mg, 12 hours for 10 to
14 days)
 Orally/ intravenous
Ciprofloxacin (ADULTS:
Orally 500 mg, 12 hours)
 Headache
 Fatigue
 Lethargy
 Drowsiness
 Insomnia;
 Nervousness.
Rash and pruritus
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Counseling Emphasis.
1. Advise to take on empty stomach 1 hour before or 2 hours after
meals.
2. Antacids, iron salts, zinc salts, sucralfate, may decrease oral
absorption of ofloxacin. Instruct patient to avoid taking antacids
within 4 hours before or 2 hours after dose.
3. Caution: Patient to avoid exposure to sunlight, and to use sunscreen
or wear protective clothing to avoid photosensitivity reaction.
4. Advise/Patient should notify physician of signs of superinfection
(second infection imposed on an earlier one).
5. Ask the patient to report about any other unbearable signs or
symptoms arising during treatment.
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Prevention
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 Two typhoid vaccines are licensed and marketed
internationally:
 Ty21a, an oral live attenuated S. Typhi vaccine (given
on days 1, 3, 5, and 7, with a booster every 5 years)
 Vi CPS, a parenteral vaccine consisting of purified Vi
polysaccharide from the bacterial capsule (given in one
dose, with a booster every 2 years).

Prevention
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 Laboratory workers who work with S. Typhi and household contacts
of known S. Typhi carriers should be vaccinated.
 Because vaccine protective efficacy can be overcome by a high
inoculum common in food-borne exposure, immunization is an
adjunct and not a substitute for avoiding high-risk foods and
beverages.
 WHO recommends typhoid vaccination targeted to high-risk groups
and populations (e.g., pre-school and school-aged children), but to
date implementation of typhoid vaccination programs in high-
incidence countries has been limited.

See Table for dosages and
schedule for vaccination.
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Typhoid
vaccinatio
n
Age
(years)
Dose/rout
e
Number of
doses
Dosing
interval
Boosting
interval
Oral, live, attenuated Ty21a vaccine (Vivotif)
Primary
series
≥6 1 capsule,
oral
4 48 hours Not
applicable
Booster ≥6 1 capsule,
oral
4 48 hours Every 5
years
ViCapsular polysaccharide vaccine (Typhim Vi)
Primary
series
≥2 0.50mL,
intramuscul
ar
1 Not
applicable
Not
applicable
Booster ≥2 0.50mL,
intramuscul
ar
1 Not
applicable
Every 2
years

Typhoid Fever (Enteric Fever)

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