INTRODUCTION
● Typhoid Fever is also known as enteric fever
● Typhoid fever is an acute illness associated with fever
CAUSE
● A bacteria called Salmonella typhi which comes from the family-enterobacteriaceae
(gram negative bacteria).
● caused by the Salmonella typhi bacteria. It can also be caused by Salmonella paratyphi,
a related bacterium that usually causes a less severe illness
TRANSMISSION
● Humans are only reservoir
● Direct contact or indirect contact via contaminated food/water.
● Fecal-oral-route the germs that cause illness are found in the stool (feces) of an infected
person, and are spread to another person. This occurs when a person touches the stool
of an infected person or an object contaminated with the stool of an infected person and
ingests the germs.
INCUBATION PERIOD
The incubation period ranges from 7-14 days on average, but can range from 3 days to
two months.
1st week
(Vanessa)
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2nd week
(Estremos)
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the body temperature rises slowly, and
fever fluctuations are seen with
relative bradycardia (Faget sign),
malaise, headache, and cough.
Bradycardia is having a small heart
rate while malaise is the feeling of
discomfort. Fagen sign is a
combination of fever and slow heart
rate.
Epistaxis and abdominal pain
a bloody nose is seen in a quarter of
cases, and abdominal pain is also
possible.
Leukopenia - A decrease in the
number of circulating white blood cells
blood cultures are positive for S.
enterica subsp. enterica serovar
Typhi. T
he Widal test is usually negative
the person is often too tired to get up,
with high fever in plateau around 40
°C (104 °F)
bradycardia (sphygmothermic
dissociation or Faget sign), classically
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3rd week
(Marxia)
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with a dicrotic pulse wave.
Dicrotic pulse is an abnormal carotid
pulse found in conjunction with certain
conditions characterised by low
cardiac output
Delirium can occur. This delirium has
given typhoid the nickname "nervous
fever"
Delirium is where the patient is often
calm, but sometimes becomes
agitated.
Rose spots appear on the lower chest
and abdomen in around a third of
patients.
Rhonchi (rattling breathing sounds)
are heard in the base of the lungs.
The abdomen is distended and painful
in the right lower quadrant, where a
rumbling sound can be heard.
Diarrhea can occur in this stage, but
constipation is also common.
The spleen and liver are enlarged
(hepatosplenomegaly) and tender,
and liver transaminases are elevated.
The Widal test is strongly positive,
with antiO and antiH antibodies.
Blood cultures are sometimes still
positive
The fever is still very high and
oscillates very little over 24 hours.
Oscillation is the movement back and
fourth at a regular speed.
Dehydration ensues along with
malnutrition, and the patient is
delirious. A third of affected people
develop a macular rash on the trunk.
Intestinal haemorrhage due to
bleeding in congested Peyer's
patches occurs; this can be very
serious, but is usually not fatal.
Intestinal perforation in the distal
ileum is a very serious complication
and often fatal. It may occur without
alarming symptoms until septicaemia
or diffuse peritonitis sets in.
Septicaemia is when bacteria enter
the bloodstream and cause blood
poisoning.
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Peritonitis is a redness and swelling
(inflammation) of the lining of your
belly or abdomen.
Respiratory diseases such as
pneumonia and acute bronchitis
Encephalitis inflammation of the
active tissues of the brain caused by
an infection or an autoimmune
response.
Neuropsychiatric symptoms
(described as "muttering delirium" or
"coma vigil"), with picking at
bedclothes or imaginary objects.
Metastatic abscesses, cholecystitis,
endocarditis, and osteitis.
Low platelet count (thrombocytopenia)
is sometimes seen.
RISK FACTORS
● Children and young adults
● Overcrowding
● Poor sanitation
● Work in or travel to area where typhoid fever is endemic
● Have close contact with someone who is infected or has recently been infected with
typhoid fever
● Drink water contaminated by sewage that contains S. typhi
TYPHOID FEVER AFFECTS
Typhoid fever is most common in rural areas of developing countries where there isn’t modern
sanitation.
● Countries in South and Southeast Asia, Central and South America, Africa and the
Caribbean are most affected by typhoid.
● Travelers are most at risk when visiting Pakistan, India or Bangladesh.
● Children are more likely to get typhoid than adults.
POSSIBLE COMPLICATIONS
Health problems that may develop include:
● Intestinal hemorrhage (severe GI bleeding)
● Intestinal perforation
● Kidney failure
● Peritonitis
B. Diagnosis
● A diagnosis of typhoid fever can usually be confirmed by analysing samples of blood,
poo, or pee.
● These will be examined under a microscope for the Salmonella typhi bacteria that cause
the condition.
● The bacteria aren't always detected the first time, so you may need to have a series of
tests.
● Testing a sample of bone marrow is a more accurate way of diagnosing typhoid fever.
● But getting the sample is both time-consuming and painful, so it's usually only used if
other tests are inconclusive.
● If typhoid fever is confirmed, other members of your household may also need to be
tested in case you have passed the infection on to them.
Widal Test
The Widal test is used to identify specific antibodies in the serum of people with typhoid by
using antigen-antibody interactions.
In this test, the serum is mixed with a dead bacterial suspension of salmonella with specific
antigens. If the patient's serum contains antibodies against those antigens, they get attached to
them, forming clumps. If clumping does not occur, the test is negative. The Widal test is
time-consuming and prone to significant false positives. It may also be falsely negative in
recently infected people. But unlike the Typhidot test, the Widal test quantifies the specimen
with titres.
An advanced way to check for antibodies that your body makes against salmonella bacteria. It
looks for O and H antibodies in a patient’s blood sample (serum)
O Antibody
Somatic
appears first, rising
progressively, later falling and
often disappearing within a
few months. Rising or high O
antibody titre generally
indicates acute infection.
H Antibody
Flagellar
appears a little later but
persists for longer raised H
antibody helps to identify the
type of enteric fever.
Sample Analysis
Widal test procedure involves the serum agglutination test to detect typhoid fever.
/Agglutination - refers to the clumping of particles together, is an antigen-antibody reaction
that occurs when an antigen (i.e., a molecule capable of triggering the adaptive immune
response) is mixed with its corresponding antibody at a suitable pH and temperature/
/Agglutinins - are antibodies. They bind multiple antigens together and form a lattice-like
structure seen as clumping by the naked eye. /
Tube Method
The Tube Widal test is more sensitive and specific than slide Widal test, especially for rule out
prozone phenomena,
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Collect a blood sample from the patient and let it clot.
After the clot has formed, centrifuge the sample to separate the serum from the cells.
Label 4 test tubes with the patient's name and the date.
Add a different dilution of the antigen solution to each of the test tubes.
Add a fixed amount of the patient's serum to each test tube.
Combine the contents of each test tube thoroughly.
Incubate the test tubes at 37°C for 24 hours.
Slide Widal Test
slide Widal agglutination test is found to good alternative screening test because less time
consuming, easy to perform, cost effective and can be applied in resource poor nations.
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Collect a blood sample from the patient and let it clot.
After the clot has formed, centrifuge the sample to separate the serum from the cells.
Place a drop of the serum on a clean glass slide and label it with the patient's name
and the date.
Add a drop of antigen solution (containing killed Salmonella typhi and Salmonella
paratyphi) to the serum drop.
Mix the two drops using a clean toothpick or glass rod, making sure they are
thoroughly combined.
Rotate the slide slowly for 4 minutes to allow agglutination to occur. Agglutination is
the clumping of bacteria caused by the interaction between the antibodies in the
serum and the antigens in the solution.
Examine the slide under a microscope at 40x magnification to look for agglutination.
The clumping of the bacteria indicates a positive result.
In both methods, a rising titer of antibodies over time indicates a positive diagnosis of
enteric fever. However, a single positive result is insufficient for diagnosis, as false
positives can occur due to other infections or previous exposure to the bacteria.
Therefore, the Widal test is often used with other diagnostic tests and clinical symptoms
to confirm the presence of enteric fever.
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For agglutination to occur, the ratio of antigen to antibody must be similar; otherwise,
clumping will not happen. Excessive amounts of antigens or antibodies in the solution
may prevent agglutination; a phenomenon called prozone and postzone effect,
respectively.
Results
● Widal blood test is both qualitative and quantitative diagnostic analysis
● A Widal test report is more commonly known as the typhoid test report.
Positive
more than or equal to 1:160
S typhi O positive
titre for antigen O and antigen means active infection of
H
typhoid fever. Active infection
indicates the patient has an
infection of Salmonella
enterica serovar typhi.
S typhi H positive
there is a past infection or it
shows the result of the
immunized person’s serum
test report.
Normal
When the test report lies in
the Widal test normal range
chart, then it is negative for
the typhoid fever.
If the titre value is less than
or equal to 1:20, 1:40, 1:80,
and less than 1:160
Negative
Widal test negative means
that a person does not have
enteric fever, and there is
another infection causing the
symptoms
The titre value of antigen O
and H is below 1:160 in the
sample.
Typhoid test result lies in
Widal test normal value.
Titre - concentration of solution as determined by titration. The concentration of an antibody, as
determined by finding the highest dilution at which it is still able to cause agglutination of the
antigen.
● Titers are usually expressed as ratios, such as 1:256, meaning that one part serum to
256 parts saline solution (dilutant) results in no antibodies remaining detectable in the
sample. A titer of 1:8 is, therefore, an indication of lower numbers of bacteria antibodies
than a 1:256 titer.
TyphiDot Test
A Typhidot Test is a screening test for typhoid fever performed using a blood sample.
It evaluates the presence of immunoglobulin M (IgM) in the blood. It can thus indicate the
presence or absence of the Salmonella species in the blood.
The Typhidot Test is a dot enzyme-linked immunosorbent assay (ELISA) that can detect
antibodies IgG and IgM in the human body. The body produces these antibodies against the
bacteria's outer membrane protein (OMP). The test becomes positive within two to three days of
Salmonella infection. It indicates the presence of IgG and IgM in the blood.
Tubex Test
UBEX (IDL Biotech) is a 5 min semi quantitative colorimetric test for typhoid fever
Results
Results Interpretation
<2
Negative
3
Inconclusive score, repeat analysis
4
Weak positive indication of current
typhoid fever infection
6-10
Strong indication of current typhoid
fever infection
Treatment
Even when the symptoms go away, people may still be carrying typhoid bacteria, meaning they
can spread it to others, through shedding of bacteria in their feces.
Commonly prescribed antibiotics
The medicine you get to treat typhoid fever may depend on where you picked up the bacteria.
Strains picked up in different places respond better or worse to certain antibiotics. These
medicines may be used alone or together. Antibiotics that may be given for typhoid fever are:
● Fluoroquinolones. These antibiotics, including ciprofloxacin (Cipro), may be a first
choice. They stop bacteria from copying themselves. But some strains of bacteria can
live through treatment. These bacteria are called antibiotic resistant.
● Cephalosporins. This group of antibiotics keeps bacteria from building cell walls. One
kind, ceftriaxone, is used if there is antibiotic resistance.
● Macrolides. This group of antibiotics keeps bacteria from making proteins. One kind
called azithromycin (Zithromax) can be used if there is antibiotic resistance.
● Carbapenems. These antibiotics also prevent bacteria from building cell walls. But
they focus on a different stage of that process than the cephalosporins. Antibiotics in
this category may be used with severe disease that doesn't respond to other
antibiotics.
Vaccines
Two typhoid vaccines are available: a Vi capsular polysaccharide vaccine (ViCPS) administered
intramuscularly and an oral, live, attenuated vaccine (Ty21a). Both vaccines induce a protective
response in 50%–80% of recipients.
All four doses should be ingested at least 1 week before potential exposure.
Abbreviated
vaccine name
(brand name,
manufacturer)
How it is
given
Number
of doses
recomme
nded
When
taken
How long to
complete
immunizatio
n before
travel
Minimum
age for
vaccinatio
n
Booster
needed
Ty21a (Vivotif,
Emergent
BioSolutions)
1 capsule
by mouth
4
Every
other
day
1 week
6 years
Every 5
years
ViCPS (Typhim
Vi, Sanofi
Pasteur)
Injection
1
2 weeks
2 weeks
2 years
Every 2
years
Prevention
All travelers to endemic areas are at potential risk of typhoid fever, although the risk is generally
low in tourist and business centers where standards of accommodation, sanitation and food
hygiene are high. Typhoid fever vaccination should be offered to travelers to destinations where
the risk of typhoid fever is high.
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Ensure food is properly cooked and still hot when served.
Avoid raw milk and products made from raw milk. Drink only pasteurized or boiled
milk.
Avoid ice unless it is made from safe water.
When the safety of drinking water is questionable, boil it, or if this is not possible,
disinfect it with a reliable, slow-release disinfectant agent (usually available at
pharmacies).
Wash hands thoroughly and frequently using soap, in particular after contact with pets
or farm animals, or after having been to the toilet.
Wash fruits and vegetables carefully, particularly if they are eaten raw. If possible,
vegetables and fruits should be peeled.
Control of the disease
Access to safe water and adequate sanitation, hygiene among food handlers and typhoid
vaccination are all effective in preventing typhoid fever.
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Water and sanitation infrastructure: safe drinking water and improved sanitation
Public health measures: correctly diagnosing and treating cases, finding and treating
carriers
Food safety
Health education: hand washing, food safety practices
Vaccination: the World Health Organization recommends that countries with very high
burdens of disease or high burdens of antibiotic resistant S. Typhi include typhoid
vaccination in their vaccination programmes. Typhoid vaccination can also be one of the
tools used for controlling outbreaks, along with providing safe water and improved
sanitation and other public health measures.