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Typhoid fever

Infectious
Disease

Dr. SUHAEMI, SpPD, Finasim

Overview

Salmonella is a rodshaped, gramnegative, facultative


anaerobe in the
family
Enterobacteriaceae

Mary Mallon
(wearing glasses)
photographed
with
bacteriologist
Emma Sherman
on North Brother
Island in 1931 or
1932, over 15
years after she
had been
quarantined there
permanently.

Typhoid Mary

Known to have infected 47 people (including 3


deaths)
Mary Mallons nickname of Typhoid Mary has
become synonymous with the spread of
diseaseit became such legend that she was
credited with having infected hundreds,
maybe thousands
Was forced into quarantined on two separate
occasions on North Brother Island for a total of
26 years---without ever having been tried or
convicted of any crime!
Died11-11-1938

History

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.
Five years after her
release, she was found to
have been the source of
25 cases of typhoid at the
Women's Hospital in
Manhattan.

Contamination and transmission

Faeces and Urine


from infected
persons

Water
Soil

Foods
Raw or cooked
Consumed by Humans

Hands
Flies

Foods
Raw or cooked
Consumed by Humans

Foods
Raw or cooked
Consumed by Humans

In 1906, Irish immigrant Mary Mallon worked as a cook in the


Oyster Bay summer home of New York banker Charles Henry
Warren and his family. By the end of the summer, six members of
the household had contracted typhoid fever. The Warrens hired
sanitary engineer, George Soper, to determine the source of the
disease. Soper concluded that Mallon, while immune herself to the
disease, was its carrier. For three years, she was isolated on North
Brother Island, near Rikers Island, earning the nickname
"Typhoid Mary." Instructed not to cook for others upon her release,
she nevertheless changed her name and became a cook at a
maternity hospital in Manhattan. At least 25 staff members
contracted typhoid. "Typhoid Mary" returned to North Brother
Island, where she lived alone for 23 years, until her death in 1938.
She is shown here on the island in an undated photo. She died of a
stroke after 23 years in quarantine.

Typhos in Greek means ,smoke and typhus


fever got its name from smoke that was
believed to cause it. Typhoid means typhuslike and thus the name given to this disease.
The term Typhoid was given by Louis 1829
to distinguish it from typhus fever.
It is a disease of poor environmental
sanitation and hence occurs in parts of the
world where water supply is unsafe and
sanitation is substandard.

A schematic diagram of a single Salmonella typhi cell


showing the locations of the H (flagellar), 0 (somatic), and
Vi (K envelope) antigens.

S.Typhi.
2nd bacteremia

liverspleengall
BM ,ect
early stage&acme stage
(1-3W

stomach

(mono

Lower
ileum

Bac. In gall

nuclea
r
phago
cytes )

Bac. In
feces

S.Typhi eliminated
convalvescence stage
(4-5w)

peyer's patches &


mesenteric lymph nodes
LN Proliferate,swell
necrosis
defervescence stage

Enterorrhagia,i
ntestinal
perforation

3-4w

thoracic
duct

1st bacteremia
(Incubation stage)
10-14d

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.

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.

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.

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.

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 commerciallyproduced 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

Symptoms

No symptoms - if only a mild exposure; some people become "carriers" of


typhoid.
Poor appetite,
Headaches,
Generalized aches and pains,
Fever, Lethargy, Lethargy,
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

Time frame

Occurs gradually over a few weeks after exposure to the bacteria.


Sometimes children suddenly become sick.
The condition may last for weeks or even a month or longer without
treatment.

First-Stage Typhoid Fever


The beginning stage is characterized by high fever,fatigue, weakness,
headache, sore throat, diarrhea, constipation, stomach pain and a skin
rash on the chest and abdominal area. According to the Mayo Clinic,
adults are most likely to experience constipation, while children usually
experience diarrhea.

Second stage
Second-stage typhoid fever is characterized by weight loss, high fever,
severe diarrhea and severe constipation. Also, the abdominal region
may appear severely distended.

Typhoid State
When typhoid fever continues untreated for more than two or three
weeks, the effected individual may be delirious or unable to stand and
move, and the eyes may be partially open during this time. At this point
fatal complications may emerge.

Diagnosis
Diagnosis of typhoid fever is made by

Blood, bone marrow, or stool cultures test

Widal test

Slide agglutination

Antimicrobial susceptibility testing

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."

Standard test tube method


Take four sets of 8 test tubes and label them 1 to 8 for O,H,AH and BH antibody detection.

Pipette in to the tube No.1 of all sets 1.9 ml of isotonic saline.

To each of the remaining tubes (2 to 8) add 1.0 ml of isotonic saline.

To the tube No. 1 tube in each row add 0.1 ml of the serum sample to be tested and mix
well.

Transfer 1ml of the diluted serum from tube no.1 to tube no.2 and mix well.

Discard the 1ml of the diluted serum from tube no.7 of each set.

Tube no.8 in all sets,serves as a saline control. Now the dilution of the serum sample
achieved in each set is as follows:

Tube no. 1 2 3 4 5 6 7 8 (control)

Dilutions 1:20 1:40 1:80 1:160 1:320 1:640 1:1280

To all tubes (1 to 8) of each set add one drop of the respective WIDAL TEST antigen
suspension (O,H,AH,BH) from reagent vials and mix well.

Cover the tubes and incubate at 37 C overnight (approx. 18 hrs).

Dislodge the sedimented button gently and observe.

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. Dont eat the
peelings.
Avoid foods and beverages from street vendors.

Treatment
Consultations

An infectious disease specialist or surgeon should be consulted.


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.

Diet

Fluids and electrolytes should be monitored and replaced diligently.


Oral nutrition with a soft digestible diet is preferable in the absence of
abdominal distension or ileus.
Activity

No specific limitations on activity are indicated.


Rest is helpful, but mobility should be maintained if tolerable.
The patient should be encouraged to stay home from work until recovery.

Some common home remedies

Take two grains of Un nab, Munnakka 4, Kuhbkalan 3 gm's. and Misri 10


gm's. grind all of them and mix in 100 ml. of water, preferably boiled and
cooled. Strain the water and make the patient drink at four hourly interval.

Take 4 basil leaves, saffron 7 shreds, 7 grains of black pepper. Grind them
to a paste by adding water and form small tablets out of the whole lot. Take
each tablet twice or thrice everyday with lukewarm milk. The fever would
also subside and the patient would get the desired relief.

1 to 2 teaspoons of fresh juice of coriander leaves mixed in 1 cup buttermilk


and taken 2-3 times a day.

Mash a ripe banana along with 1 tablespoon honey and eat twice a day for a
few days.

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%.

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.

Chloramphenicol

Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth


by inhibiting protein synthesis.

The recommended dosage is 50 - 75 mg per kg per day for 14 days


divided into four doses per day, or for at least five to seven days after
defervescence.

Oral administration gives slightly greater bio availability than


intramuscular (i.m.) or intravenous (i.v.) administration of the succinate
salt.

The disadvantages of using chloramphenicol include a relatively high


rate of relapse (57%), long treatment courses (14 days) and the frequent
development of a carrier state in adults.

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

Dexamethasone

Prompt administration of high-dose dexamethasone reduces mortality in


patients with severe typhoid fever without increasing incidence of
complications, carrier states, or relapse among survivors.

Initial dose of 3 mg/kg by slow i.v. infusion over 30 minutes.

1 mg/kg 6 hourly for 2 days.

Antibiotic resistance

MDR is mediated by plasmid The genes for antibiotic resistance in S


typhi and S paratyphi are acquired into a region called an integron from
Escherichia coli and other gram-negative bacteria via plasmids.

Quinolone resistance is frequently mediated by single point mutations in the


quinolone-resistancedetermining region of the gyrA gene.

Nalidixic acid resistant: MIC of fluoroquinolones for these strains was 10


times that for fully susceptible strains.

Epidemiology

strongly endemic
endemic
sporadic cases

Misdiagnosis

Paratyphoid fever- similar to typhoid fever but usually less severe.


Paraenteric fever- a typhoid-like fever but not caused by Salmonella.
Gastroenteritis- mild case of typhoid fever may be mistaken for gastroenteritis.
Typhomalarial fever
Brucellosis
Tuberculosis
Infective endocarditis
Q fever
Rickettsial infections
Acute diarrhea (type of Diarrhea)
Viral Hepatitis
Lymphoma
Adult Still's disease
Malaria

First typhoid inoculation, 1909


United States Army Medical
School

Bottling typhoid vaccine, 1944


Division of Biologic Products, U.S.
Army of Medical Department
Professional Service Schools

Salmonella Microbiology

How Do You Catch Salmonella?

Food borne
Transmitted via improperly prepared,
previously contaminated food or water
- Meat: poultry, wild birds, pork
- Dairy: eggs
Pet turtles and lizards

How does Salmonella affect the


body?

Three clinical forms of salmonellosis


- Gastroenteritis (S. typhimurium)
- Septicemia (S. Choleraesius)
- Enteric Fevers (i.e. S. typhi Typhoid
Fever)

Prevention

Typhoid:
- Vaccinations available; the CDC currently recommends
vaccination for persons traveling to developing countries
- Education of general public, especially in developing
countries; identification of all carriers and sources of
contamination of water supplies
-Avoid risky foods & drinks:
buy bottled water or boil water for at least 1 minute;
COOK and CLEAN food thoroughly, avoid raw vegetables
and fruits
- WASH

YOUR HANDS WITH SOAP AND


WATER

Overview

www.unhmagazine.unh.edu

Availability of Water Resources

Imagine being unable to


turn on the tap when you
get thirsty
Now, imagine having to
carry water for hours
each day to have water
to drink
Or, imagine pinching
your nose as you drink to
avoid the waters foul
odor
And, imagine the real
possibility that taking a
drink of water exposes
you to disease

40%
of
worlds
population
(3B
people) will live in
countries classified
as water stressed by
hydrologists by 2015

http://www.iucn.org

Even though 2.4B


people got access to
safe drinking water
for first time during
1990s,
estimated
1.7B people still lack
safe drinking water

Impacts on Global Health

http://www.thespiritans.org

http://www.apec-vc.org.cn

About 1.8M people, mostly children, die annually from diarrhea


and related diseases with many deaths preventable if water
were not contaminated

The combination of safe drinking water, adequate sanitation


and good hygiene can reduce the number of deaths caused by
diarrhoeal diseases by an average of 65%
The simple act of washing hands with soap and water can
reduce diarrhoeal diseases by over 40%

http://www.nri.org

Cholera, a bacteria that lasts up to 3


weeks in soil, is spread by contaminated
water and food and occasionally by
person to person contact. Sudden large
outbreaks usually are due to a
contaminated water supply.
Bacillary dysentery caused by exposure
to Shigella bacteria from contaminated
drinking water, food , or flies is
contagious and more severe than
amoebic
dysentery.
Approximately
140M people are infected annually
causing about 300K deaths, mostly
among children under the age of five.
Typhoid fever is contracted when people
drink water or eat food contaminated by
Salmonella typhi bacteria found in
human waste.
It affects 17M people
worldwide annually, with approximately
600K deaths. Typhoid fever has been
virtually
eliminated
in
developed
countries.