Typhoid fever

Infectious
Disease

DR.VIKRANNTH.V
ASSISTANT PROFESSOR
 Definition

 An infectious feverish disease caused by the bacterium Salmonella

typhi(Salmonella enterica Serovar Typhi ) and less commonly by
Salmonella paratyphi.

 Acute generalized infection of the

reticulo endothelial system,
intestinal lymphoid tissue, and the gall bladder.

 The infection always comes from another human, either an ill person or a
healthy carrier of the bacterium. The bacterium is passed on with water
and foods and can withstand both drying and refrigeration.
 History

Antonius Musa, a Roman physician who

achieved fame by treating the Emperor
Augustus 2,000 year ago, with cold baths
when he fell ill with typhoid.

Thomas Willis who is credited with the first

description of typhoid fever in 1659.
 French physician Pierre Charles
Alexandre Louis first proposed
the name “typhoid fever”

William Wood Gerhard who was the first

to differentiate clearly between typhus
fever and typhoid in 1837.
 Carl Joseph Eberth who discovered the
typhoid bacillus in 1880.

Georges Widal who described the

‘Widal agglutination reaction’ of the blood in 1896.
1. The best known carrier was "Typhoid
Mary“; Mary Mallon was a cook in Oyster
Bay, New York in 1906 who is known to
have infected 53 people, 5 of whom died.

2. Later returned with false name but

detained and quarantined after another
typhoid outbreak.

3. She died of pneumonia after 26 years in

quarantine.
 Causes
1. Caused by the bacterium Salmonella Typhi .

2. Ingestion of contaminated food or water.

3. Contact with an acute case of typhoid fever.

4. Water is contaminated where inadequate sewerage systems and poor sanitation.

5. Contact with a chronic asymptomatic carrier.

6. Eating food or drinking beverages that handled by a person carrying the bacteria.

7. Salmonella enteriditis and Salmonella typhimurium are other salmonella bacteria,

cause food poisoning and diarrhoea.
 Morphology of
Salmonella
• Gram negative
bacilli
• 1-3 / 0.5

microns,
• Motile by flagella

Dr.T.V.Rao MD

15
S.typhi with
Flagella

Dr.T.V.Rao MD 16
 Salmonella Entrica

 Member of the genus Salmonella.

 Rod shaped, flagellated, aerobic,
Gram negative bacterium.
 Large number of fimbrial and non-fimbrial adhesins
are present, mediate biofilm formation and contact to host cells.
 Secreted proteins involved in host cell invasion and intracellular
proliferation.
 Infects cattle, poultry, domestic cats, hamsters, humans etc.
 Refrigeration and freezing substantially slow or halt their growth.
 Pasteurizing and food irradiation kill Salmonella for commercially-
produced foodstuffs containing raw eggs such as ice cream.
 Foods prepared in the home from raw eggs can spread salmonella if
not properly cooked before consumption.
How does the bacteria cause disease ?
 Ingestion of contaminated food or water

Salmonella bacteria

Invade small intestine and enter the bloodstream

Carried by white blood cells in the liver, spleen, and bone marrow

Multiply and reenter the bloodstream

Bacteria invade the gallbladder, biliary system, and the lymphatic tissue of
the bowel and multiply in high numbers

Then pass into the intestinal tract and can be identified for diagnosis in
cultures from the stool tested in the laboratory
Pathology
Essential lesion:
 proliferation of RES
 specific changes in lymphoid tissues
 and mesenteric lymph nodes.
"typhoid nodules“
Most characteristic lesion:
 ulceration of mucous membrane in the
region of the Peyer’s patches of the small
intestine
 Symptoms
 No symptoms - if only a mild exposure; some people become "carriers" of
typhoid.
 Poor appetite,
 Headaches,
 Generalized aches and pains,
 Fever
 Lethargy,
 Diarrhea,
 Have a sustained fever as high as 103 to 104 degrees Fahrenheit (39 to 40
degrees Celsius),
 Chest congestion develops in many patients, and abdominal pain and
discomfort are common,
 Constipation, mild vomiting, slow heartbeat.
Rose spots Aches and pains High fever

Diarrhea

Chest congestion
Typhoid Meningitis
Clinical presentation
 The incubation period for typhoid fever
is 7-14 days (range 3-60 days)
 If not treated, the symptoms develop
over four weeks, with new symptoms
appearing each week but with
treatment, symptoms should quickly
improve.
 Clinical manifestations
The initial period (early stage due to bacteremia)
 First week: non-specific, insidious onset of fever

Fever up to 39-400C in 5-7 days, step-

ladder( now seen in < 12%), headache
chills, toxic, tired, sore throat, cough, abdominal
pain and diarrhea or constipation.
The fastigium stage
 second and third weeks.
 fever reaches a plateau at 39-40. Last 10-14 days.
 more toxic and anorexic with significant weight loss. The
conjunctivae are injected, and the patient is tachypneic with a
thready pulse and crackles over the lung bases. Abdominal
distension is severe. Some patients experience foul, green-
yellow, liquid diarrhea (pea soup diarrhea). The( typhoid state)
is characterized by, confusion, and even psychosis. Necrotic
Peyer patches may cause bowel perforation and peritonitis.
This complication may be masked by corticosteroids. At this
point, overwhelming toxemia, myocarditis, or intestinal
hemorrhage may cause death.
 Rash in Typhoid

 Rose- spots: found

in front of chest
 Appear in crops of
upto a dozen at a
time
 By the fourth week of infection:
If the individual survives , the fever, mental
state, and abdominal distension slowly
improve over a few days. Intestinal and
neurologic complications may still occur.
Weight loss and debilitating weakness last
months. Some survivors become
asymptomatic carriers and have the
potential to transmit the bacteria
indefinitely
 the fifth week: disappearance of all symptoms, but

can relapse
 Persistent infection:
disease continue > 5 weeks
 Ambulatory infection:
mild symptoms,early intestinal bleeding or perforation.
 Fulminant infection:
rapid onset, severe toxemia and
septicemia.
High fever, chill, circulatory failure,
shock, delirium, coma, myocarditis,
bleeding and other complications, DIC.
Complications
Complications
Intestinal hemorrhage
Commonly appear during the second-third week
may be mild or severe bleeding
often caused by unsuitable food, and diarrhea

serious bleeding in about 2~8%

clues: sudden drop in temperature, rise in pulse, and signs
of shock followed by dark or fresh blood in the stool.
Intestinal perforation:
 more serious. Incidence:1-4%
 Commonly appear during 2nd-3rd week.
 Take place at the lower end of ileum.
 Before perforation,abdominal pain or
diarrhea,intestinal bleeding .
 When perforation: ↑ abdominal pain, sweating, drop in temperature, and
increase in pulse rate, then rebound tenderness +ve
reduce or disappear in the dullness of liver, leukocytosis .
 Temperature rise when peritonitis appear.
 free air in abdominal x-ray.
 Toxic hepatitis:
common,1-3 weeks
hepatomegaly, ALT elevated
get better with improvement of disease in 2~3 weeks
 Toxic myocarditis.
seen in 2nd-3rd week, usually severe toxemia.
 Bronchitis, bronchopneumonia.
seen in early stage
 Diagnosis

Diagnosis of typhoid fever is made by

 Blood, bone marrow, or stool cultures test

 Widal test

 Slide agglutination

 Antimicrobial susceptibility testing

 Blood cultures in Typhoid
fever
 In Adults 5-10 ml of Blood is inoculated into 50
– 100 ml of Bile broth ( 0.5 % ).
 Larger volumes 10-30 ml and clot cultures

increase sensitivity
 Blood culture is positive as follows:

1st week in 90%

2nd week in 75%
3rd week in 60%
4th week and later in 25%
 Bone marrow culture
the most sensitive test
even in patients pretreated (up to 5 days) with antibiotics.
 Urine and stool cultures
increase the diagnostic yield
positive less frequently
stool culture better in 3rd~4th weeks

Duodenal string test to culture bile useful for the
diagnosis of carriers.
Widal test
 Serum agglutinins raise abruptly during the
2nd or 3rd week, it is +ve by 10th day, but
max. during 18-23rd day
 The widal test detects antibodies against O
and H antigens
 Two serum specimens obtained at intervals of
7 – 10 days to read the rise of antibodies.
 The test is neither sensitive nor specific
 Widal test

" A test involving agglutination of typhoid bacilli when they are

mixed with serum containing typhoid antibodies from an
individual having typhoid fever; used to detect the presence
of Salmonella typhi and S. paratyphi."
 How do you read Widal test
results for typhoid fever?

 The highest dilution of the patients serum in which agglutinations occurs is

noted, ex. if the dilution is 1 in 160 then the titer is 169.

 Agglutination in dilution up to <1:60 is seen in normal individuals .

Agglutination in dilution 1:160 is suggestive of Salmonella infection.

 Agglutination in dilution of and more than 1:320 is confirmatory of Enteric

fever .
Prevention
And
Treatment
 Prevention
Two main typhoid fever prevention strategies:

1. Vaccination

First type of vaccine:

 Contains killed Salmonella typhi bacteria.
 Administered by a shot.

Second type of vaccine:

 Contains a live but weakened strain of the Salmonella bacteria that causes
typhoid fever.
 Taken by mouth.
 Be vaccinated against typhoid while traveling to a country where typhoid is common.
 Need to complete your vaccination at least one week before travel.
 Typhoid vaccines lose their effectiveness after several years so check with your
doctor to see if it is time for a booster vaccination.

2. Avoid risky food and drinks

 Buy bottled drinking water or bring it to a rolling boil for one minute before drinking it.
 Ask for drinks without ice, unless the ice is made from bottled or boiled water.Avoid
Popsicles and flavored ices.
 Eat food that have been thoroughly cooked and that are still hot and steaming.
 Avoid raw vegetables and food that cannot be peeled like lettuce.
 When eat raw fruit and vegetables that can be peeled, peel yourself. Don’t eat the
peelings.
 Avoid foods and beverages from street vendors.
 Treatment

Surgical Care

 Usually indicated in cases of intestinal perforation.

 Most surgeons prefer simple closure of the perforation with drainage of
the peritoneum.
 Small-bowel resection is indicated for patients with multiple perforations.
 If antibiotic treatment fails to eradicate the hepatobiliary carriage, the
gallbladder should be resected.
 Cholecystectomy is not always successful in eradicating the carrier state
because of persisting hepatic infection.
 Medication
Antibiotics
 Antibiotics, such as ampicillin, chloramphenicol, fluoroquinolone
trimethoprim-sulfamethoxazole, Amoxicillin and ciprofloxacin etc used to
treat typhoid fever.

 Prompt treatment of the disease with antibiotics reduces the case-

fatality rate to approximately 1%.
1
2
 Fluoroquinolones
 Optimal for the treatment of typhoid fever

 Relatively inexpensive, well tolerated and more rapidly and reliably

effective than the former first-line drugs, viz. chloramphenicol, ampicillin,
amoxicillin and trimethoprim-sulfamethoxazole.

 The majority of isolates are still sensitive.

 Attain excellent tissue penetration, kill S.typhi in its intracellular stationary

stage in monocytes/macrophages and achieve higher active drug levels in
the gall bladder than other drugs.

 Rapid therapeutic response, i.e. clearance of fever and symptoms in three

to five days, and very low rates of post-treatment carriage.
 Cephalosporins

 Ceftriaxone: 50-75 mg per kg per day one or two doses

 Cefotaxime: 40-80 mg per kg per day in two or three doses

 Cefoperazone: 50-100 mg per kg per day

 Amoxicillin (Trimox, Amoxil, Biomox)
 Interferes with synthesis of cell wall mucopeptides during active
multiplication, resulting in bactericidal activity against susceptible bacteria.
 At least as effective as chloramphenicol in rapidity of defervescence and
relapse rate.
 Convalescence carriage occurs less commonly than with other agents when
organisms are fully susceptible.
 Usually given PO with a daily dose of 75-100 mg/kg tid (three times a day)
for 14 d.
Adult
1 g PO q8h
Pediatric
20-50 mg/kg/d PO divided q8h for 14 d
Epidemiology

♦ strongly endemic
♦ endemic
♦ sporadic cases
 Carriers may
be

Carriers may be temporary or chronic.

Temporary
carriers usually excrete bacilli up to 6-8

weeks. By the end of one year, 3-4 per cent

of cases continue to excrete typhoid bacilli.
Persons who excrete the bacilli for more

than a year after a clinical attack are called

chronic carriers.
Carrier
Asymptomatic and have positive stool
or rectal swab cultures for S. typhi a
year following recovery from acute
illness.
Treatment: co-trimoxazole 2 tab
twice/d for 6 wk, OR
ciprofloxacin 750 mg twice/d for 4 wk
Carrier
Carriers should be excluded from activities
involving food preparation and serving.
Food handlers should not resume their
duties until they have had three negative
stool cultures at least one month apart.
 Vi Ab is used as a screening technique to

identify carriers among food handlers

and in outbreak investigations. Vi Abs
are very high in chronic S. typhi carriers
Prognosis:
 Case fatality 0.5-1%.
 but high in old ages, infant, and serious
complications
 immunity long lasting
 About 3% of patients become fecal carriers .
Vaccines for Typhoid Prevention

 Two types :
1. Oral – A live vaccine ( typhoral )
One capsule given orally taken before food,
with a glass of water or milk, on day 1, 3, 5
( three doses )
No antibiotics should be taken during the period
of administration of vaccine
2. The injectable vaccine, ( typhim –vi)
Given as single sc or im injection
Vaccines for Typhoid

Both vaccines are given to only children

> 5 years of age.
Immunity lasts for 3 years
Need a booster
Vaccines are not effective in prevention
of Paratyphoid fevers
Paratyphoid fever
 It is similar in its symptoms to typhoid fever,
but tends to be milder, with a lower fatality
rate.
 It is caused by Paratyphi A, B, and C
 Rash may be more abundant
 May present as gastroenteritis specially in
children
Prophylaxis
CHOLERA
 CHOLERA

Cholera is an acute diarrheal illness caused by

infection of the intestine with the bacteria Vibrio
cholerae.
 EPIDEMIOLOGY

•Cholera was prevalent in the 1800s, but due to proper

treatment of sewage and drinking water, has become rare in
developed countries.
•Cholera is a fecal disease, meaning that it spreads when the

feces of an infected person come into contact with food or

water.
•Incidence: 1 in 100,000 worldwide.

•Over 1 million cases and nearly 10,000

fatalities.
 VIBRIO CHOLERAE
• Gram negative.

• Distinguishing factors:
Oxidase- positive, motile via
polar flagellum.
• Organism can multiply freely
in water
 PATHOPHYSIOLOGY OF CHOLERA

V. cholerae activation of ion

accumulates increase
channels
in cAMP
stomach

NaCl influx into

G- protein intestinal
Produces
stuck in "on" lumen to drag
toxins position water into
lumen

Toxins will bind

Inactivation lead to
to G-protein
of watery
coupled
GTPase diarrhea
receptor
 SIGNS & SYMPTOMS

Most people remain asymptomatic. The symptoms

of cholera include :

profuse, stomach leg cramps Mild

watery pains fever
diarrhea

Vomitin Sunken Dry Decreased

g eyes and mucous urinary
 COMPLICATIONS

severe Shoc Renal

dehydration k failure

Death
 RISK FACTORS
 Poor sanitary • Rare in developed countries
conditions • Common in Asia, Africa, & Latin
America
 Raw or undercooked
food • Contaminated seafood, even in
developed countries.
• Especially shellfish.
 Hypochlorhydria • People with low levels of stomach acid
• Such as children, older adults, and some

medications.

 Type O blood • Reasons aren't entirely clear

• Twice more likely
CAUSES (TRANSMISSION MOOD)

Drinking eating
raw contaminat or
ed undercook
water. ed
shellfish
 DIAGNOSIS

Clinical Differential
diagnosis diagnosis
Cholera should be Enterotoxigenic e. Coli
considered in all cases with
severe watery diarrhea and
vomiting.
Bacterial food
poisoning
Traveling to affected areas
and
eating shellfish Viral gastroenteritis
No distinguishing
clinical manifestations
for cholera.
 LABORATORY DIAGNOSIS
• Vibrios often detected by dark
field or phase contrast
microscopy of stool
• Organisms are motile,
appearing like “shooting stars”
• Microscopy show sheets of
curved Gram negative rods.
• When plated on sucrose
dishes, yellow colonies appear
confirming cholera present
LABORATORY DIAGNOSIS

Additional methods of detection

include PCR and monoclonal
antibody-based stool tests.
 TREATMENT

Oral rehydration salts

•Up to 80% of cases can be treated through this.

Intravenous fluids (Ringer

lactate)
•For severe cases.

Antimicrobial Therapy
can diminish duration of diarrhea, reduce volume
•

of rehydration fluids needed, and shorten duration

of V. cholerae excretion.
 DRUG THERAPY
The goals of drug therapy are to eradicate
infection, reduce morbidity and prevent
complications.

The drugs used for adults include

tetracycline, doxycycline, cotrimoxazole &
ciprofloxacin.

For children erythromycin, cotrimoxazole and

furazolidone are the drugs of choice.
 PREVENTION

Basic health education and

•

hygiene
• Mass chemoprophylaxis
•Provision of safe water

and sanitation
• Comprehensive
Multidisciplinary Approach:
water, sanitation, education,
 VACCINES

Parenteral Vaccine :
•2 doses administered 2 weeks apart
•Efficacy of approximately 50% and hardly exceeds 6 months
•Not recommended

Killed WC/rBS Vaccine :

•Killed whole-cell V.cholerae in combination with a recombinant B-subunit of cholera
toxin
•Safe in pregnancy and breastfeeding
•Efficacy of approximately 50% after 3 years
•Only mild side-effects

Live, attenuated CVD 103-HgR Vaccine :

•Protection as early as 1 week after vaccination, with >90%
•Unknown efficacy for children under 2
•No adverse side-effects
 PROGNOSIS

The prognosis of cholera can range depending

on the severity of the dehydration and
how quickly the patient is given and
responds to treatments.
Death (mortality) rates in untreated cholera
can be as high as 50%-60% during large
outbreaks but can be reduced to about 1% if
treatment protocols are rapidly put into
action.
 CONTROLLING CHOLERA

Treatmen
t centers Set up treatment centers for
prompt treatment.

Sanitary
measures food safety and animal health
.
measures
Comprehensiv
e surveillance (adapt to each situation) for a
data comprehensive multidisciplinary
approach.
THANK YOU