Transcript Typhoid

Case no.30

A 10 y/o patient was admitted because
of high fever associated with
headache,malaise and chills.Based
form the examinations and procedure
done, patient was found to be having
Typhoid fever.
Outline








Background
Mode of Transmission
Pathophysiology
Clinical manifestation
Diagnosis
Medical treatmant and related precautions
Prevention and vaccination
Case study and its legendary stories
Typhoid
BY
Chitchai Pumchandh
•Background


Typhoid fever,also known as enteric
fever, is a systemic infection by
Samonella typhi or by the related but
less virulent Samonella parathyphi.
Samonella parathyphi causes
Parathyroid fever,a similarity in
symptom but much milder disease.
The case-fatality rate is also less
lower.

Salmonella is a genus in the family Enterobacteriaceae
that has more than 2300 serotypes, Of all Salmonella
serotypes, only S typhi and S paratyphi are pathogenic
exclusively in humans. Typhoid fever is a severe
multisystemic illness characterized by the classic
prolonged fever, sustained bacteremia without
endothelial or endocardial involvement, and bacterial
invasion of and multiplication within the mononuclear
phagocytic cells of the liver, spleen, lymph nodes, and
Peyer patches. Typhoid fever is potentially fatal if
untreated.

More than 2,400years ago or around 430-426
B.C.,a devastating plague of these bacteria
kill one third of the population of Athens
during wartime and during the breakdown of
sanitation, including their leader,Pericles. The
balance of power shifted from Athens to
Sparta,ending the Golden age of Pericles that
marked Athenian dominance in the ancient
world.



An ancient historian and General in the war
,Thucydides also contracted the disease,but
he survived to write about the plague. His
writing are the primary source on the
outbreak, History Of The Peloponnesian War.
But he did not leave a precise enough
description to decide definitively whether the
disease was bubonic plague, smallpox or
other ailments.
In 1994,DNA collected from teeth in an
ancient mass grave was proved to be Typhoid
fever by Manolis Papagrigokis and her
colleagues at the University of Athens.
Mode of transmission

People are typically infected with S
typhi and S paratyphi through food and
beverages contaminated by a chronic
stool carrier. Less commonly, carriers
may shed the bacteria in urine.
Individuals may also be infected by
drinking sewage-contaminated water or
by eating contaminated shellfish or
faultily canned meat.

Salmonellae are gram-negative, flagellate,
nonsporulating, facultative anaerobic bacilli
that ferment glucose, reduce nitrate to nitrite,
and synthesize peritrichous flagella when
motile. All but S typhi produce gas upon
sugar fermentation.
Pathophysiology


After ingestion by the host, S typhi invades
through the gut and multiplies within the
mononuclear phagocytic cells in the liver,
spleen, lymph nodes, and Peyer patches of
the ileum.
After successfully passing through the
stomach, any Salmonella subspecies may be
phagocytized by the gut's intraluminal
dendritic cells, causing inflammation that
leads to diarrhea.

Only the subspecies S enterica causes severe
disease in the rest of the body. Its specialized
fimbriae adhere to the epithelium that
overlies Peyer patches. Peyer patches are
grossly visible aggregates of 5-100 lymphoid
follicles in the small bowel submucosa; these
patches are larger and more numerous
distally. They are the primary mechanism for
sampling antigens in the gut and initiating
response.

The infected macrophage provides Salmonella
a vehicle safe from other elements of the
immune system and in which it can multiply
and travel. It passes through the mesenteric
lymph nodes into the thoracic duct and the
lymphatics beyond to seed the
reticuloendothelial tissues—liver, spleen, bone
marrow, and lymph nodes. In these havens, it
multiplies until some critical density is
reached.


It causes the apoptosis in the macrophages
and enters the bloodstream to attack the rest
of the body. At this stage, the Vi antigen
comes into play. It forms a capsule to protect
the bacterium from complement and from
phagocytic immune cells.
From blood or from the liver via bile ducts, it
infects the gallbladder and reenters the
gastrointestinal tract in the bile, spreading to
other hosts via stool. In addition, it
occasionally invades the urinary tract and
spreads via urine.


After primary intestinal infection, further
seeding of the Peyer patches occurs through
infected bile. They may become hyperplastic
and necrotic with infiltration of mononuclear
cells and neutrophils, forming ulcers that may
hemorrhage through eroded blood vessels or
perforate the bowel wall, causing peritonitis.
The host recognizes the invader with toll-like
receptors 2, 4, and 5. These induce cytokines
such as interferon alpha, interleukin (IL)–12,
and tumor necrosis factor-alpha, which recruit
macrophages and cause the high fevers of the
disease. Macrophages and neutrophils suppress
the active infection. Later, humoral and CD4 Tcell–mediated immunity clears it.
Risk factor

Salmonella has mechanisms against acidic
environments, but a pH level of 1.5 or less
kills most of the bacilli. People who
continually ingest antacids, histamine-2
receptor antagonists (H2 blockers), or proton
pump inhibitors; who have undergone
gastrectomy; or who have achlorhydria due
to aging or other factors require fewer bacilli
to produce clinical disease.

Acquired immune deficiencies or
hereditary deficiencies in immune
modulars such as IL-12 and IL-23
increase risk for infection,
complications, and death
Clinical manifestration

The incubation period of typhoid fever varies
with the size of the infecting dose and
averages 7-14 (range, 3-60) days. In
paratyphoid infection, the incubation period
ranges from 1-10 days. During the incubation
period, 10-20% of patients have transient
diarrhea (enterocolitis) that usually resolves
before the onset of the full-fledged disease.

As bacteremia develops, the incubation
period ends. Patients often experience chills,
diaphoresis, anorexia, dry cough, a dull
frontal headache, and myalgias before the
onset of a high fever. About 20-40% of
patients present with abdominal pain. In
immunocompetent adults, constipation is
common and is most likely due to
hypertrophy of Peyer patches.


The classic signs of enteric fever
include fever, toxemia, delirium,
abdominal pain, constipation, and
hepatosplenomegaly.
The individual's temperature often rises
to as high as 103-104°F (39-40°C) by
the beginning of week 2. Constipation
often develops early and is likely due
to obstruction at the ileocecal valve by
swollen Peyer patches. It may last for
the entire duration of illness.

At approximately the end of the first
week of illness, about a third of patients
develop bacterial emboli to the skin
known as rose spots. These are
considered a classic symptom in typhoid
fever, but they occasionally appear in
shigellosis and nontyphoidal
salmonellosis.


Rose spots constitute a subtle, extremely sparse
(often <5 spots), salmon-colored, blanching,
truncal, maculopapular rash with 1- to 4-cm
lesions that generally resolve within 2-5 days.
Relative bradycardia and a dicrotic pulse are also
common during this stage of illness.
During the second week of illness, the patient is
toxic-appearing and apathetic with sustained fever.
The abdomen is slightly distended, and soft
splenomegaly is common.

In the third week, the patient grows more
toxic and anorexic with significant weight
loss. The patient may have a thready pulse,
tachypnea, conjunctivitis, and crackles over
the lung bases. Pyrexia persists. The patient
may enter into a typhoid state of apathy,
confusion, and even psychosis. Patients may
develop polyneuropathy. Abnormal
cerebrospinal fluid should prompt a search for
a different cause.

Meanwhile, the patient commonly has
pronounced abdominal distension. Some
individuals may produce liquid, foul, greenyellow diarrhea (pea soup diarrhea). At this
stage, the patient may die from
overwhelming toxemia, myocarditis, intestinal
hemorrhage, or perforation due to necrotic
Peyer patches. Rare complications of enteric
fever include pancreatitis, meningitis, orchitis,
and osteomyelitis.

During the fourth week, the fever,
mental state, and abdominal distension
slowly improve over a few days, but
intestinal complications may still occur
in surviving untreated individuals.
Weight loss and debilitating weakness
last months. Relapses occur in 10% of
patients, mostly during the first 2-3
weeks of convalescence.

One to four percent of untreated patients
become chronic carriers, defined as
individuals who excrete Salmonella for more
than 1 year. Some individuals may continue to
excrete the bacterium for decades. Bladder
infection with Schistosoma haematobium
predisposes to urinary carriage. The parasite
itself becomes a carrier.

Stool carriage is more frequent in people with
preexisting biliary abnormalities, perhaps
because S enterica survives in gallstones, and
these people have a greater incidence of
cholecystitis. Chronic carriers have a greater
risk for carcinoma of the gallbladder and
other gastrointestinal malignancies; chronic
carriers had a 6-fold increase in the risk of
death due to hepatobiliary cancer.
Diagnosis


The diagnosis is suggested by assays that
identify Salmonella antibodies and antigens
and is then confirmed by isolation of the
organism.
If patients present within the first week of the
disease, blood, intestinal secretions, and stool
culture results are usually positive in
approximately 85-90% of patients with
typhoid fever. They decline to 20-30% later in
the course of the disease.
Medical treatment


Antibiotics should be started empirically while the
results of confirmatory tests are pending.
Antibiotics -- Chloramphenicol was introduced in 1948
and was once the mainstay of treatment. By the
1970s, widespread resistance to the drug developed.
Ampicillin and co-trimoxazole became treatments of
choice. However, in the late 1980s, some S typhi
strains developed simultaneous plasmid-mediated
resistance to all 3 drugs. Fluoroquinolones and thirdgeneration cephalosporins have filled the breach, but
some resistance exists to both.




Resistance to ciprofloxacin is increasing.
Southeast Asia has reduced susceptibility
to ciprofloxacin.
Ciprofloxacin is no longer a good first-line
treatment for S typhi infection that arises
in Southeast Asia.
Uncomplicated typhoid fever from the
western hemisphere should be treated
empirically with ciprofloxacin for 7 days.
The treatment for cases from Southeast
Asia is controversial. Some authorities
recommend high-dose ciprofloxacin.


Some consider this inadequate, as
reports of treatment failure under those
conditions have increased. Then it is
recommended empiric first-line therapy
with trimethoprim/sulfamethoxazole
and second-line therapy with ampicillin
or chloramphenicol.
Resistance to ceftriaxone is only
sporadic in Southeast Asia and
elsewhere. Ceftriaxone should be the
first-line empiric treatment for severe
typhoid fever, and the course should
last 10-14 days

Clinicians should consider a 48-hour
course of dexamethasone if the patient
has shock or altered mental status. This
may reduce the mortality risk from 56%
to 10%. Corticosteroids are reserved for
the only the most ill patients because
they may increase the risk of relapse.
Drugs


Chloramphenicol (Chloromycetin) -- Binds to 50S
bacterial-ribosomal subunits and inhibits bacterial
growth by inhibiting protein synthesis. Effective
against gram-negative and gram-positive bacteria.
Since its introduction in 1948, has proven to be
remarkably effective for enteric fever worldwide. For
sensitive strains, still most widely used antibiotic to
treat typhoid fever. In the 1960s, S typhi strains with
plasmid-mediated resistance to chloramphenicol
began to appear and later became widespread in
many endemic countries of the Americas and
Southeast Asia, highlighting need for alternative
agents.
Contraindications Documented hypersensitivity


Trimethoprim and sulfamethoxazole (Bactrim
DS, Septra) -- Inhibits bacterial growth by
inhibiting synthesis of dihydrofolic acid.
Antibacterial activity of TMP-SMZ includes
common urinary tract pathogens, except
Pseudomonas aeruginosa. As effective as
chloramphenicol in defervescence and
relapse rate. Trimethoprim alone has been
effective in small groups of patients.
Contraindications Documented
hypersensitivity; megaloblastic anemia due
to folate deficiency


Ciprofloxacin (Cipro) -- Fluoroquinolone with activity
against pseudomonads, streptococci, MRSA,
Staphylococcus epidermidis, and most gramnegative organisms but no activity against
anaerobes. Inhibits bacterial DNA synthesis and,
consequently, growth. Continue treatment for at
least 2 d (7-14 d typical) after signs and symptoms
have disappeared. Proven to be highly effective for
typhoid and paratyphoid fevers. Defervescence
occurs in 3-5 d, and convalescent carriage and
relapses are rare. Other quinolones (eg, ofloxacin,
norfloxacin, pefloxacin) usually are effective. If
vomiting or diarrhea is present, should be given IV.
Fluoroquinolones are highly effective against
multiresistant strains and have intracellular
antibacterial activity.
Contraindications Documented hypersensitivity


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.
Contraindications Documented
hypersensitivity


Cefotaxime (Claforan) -- Arrests
bacterial cell wall synthesis, which
inhibits bacterial growth. Thirdgeneration cephalosporin with gramnegative spectrum. Lower efficacy
against gram-positive organisms.
Excellent in vitro activity against S
typhi and other salmonellae and has
acceptable efficacy in typhoid fever.
Only IV formulations are available.
Contraindications Documented
hypersensitivity


Ceftriaxone (Rocephin) -- Thirdgeneration cephalosporin with broadspectrum gram-negative activity against
gram-positive organisms; Excellent in
vitro activity against S typhi and other
salmonellae.
Contraindications Documented
hypersensitivity
Other drugs



Azithromycin (Zithromax)
Cefoperazone (Cefobid)
Levofloxacin (Levaquin)


Corticosteroids -- These agents reduce
mortality in severely ill patients with
depressed levels of consciousness or shock.
Dexamethasone (Decadron) -- 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.
Prevention


Travelers to endemic countries should avoid
raw unpeeled fruits or vegetables since they
may have been prepared with contaminated
water; in addition, they should drink only
boiled water.
Routine typhoid vaccination is not
recommended in the United States.
Vaccination is indicated for travelers to
endemic areas, persons with intimate
exposure
Vaccines




The following 3 typhoid vaccines are
used:
Vi capsular polysaccharide (ViCPS)
antigen vaccine (Typhim Vi, Pasteur
Merieux)
Ty21a (Vivotif Berna, Swiss Serum and
Vaccine Institute)
Acetone-inactivated parenteral vaccine
Case study and its legends

A wealthy middle-aged man presented to his
physician a few days after the onset of flulike
symptoms, including fever, myalgias, chills,
severe abdominal pain, and a cough, in
addition to severe abdominal pain. Over the
next 2 weeks, he lost a great deal of weight.
He had intermittent but ever-increasing
fevers. About 3 weeks after the onset of
symptoms, he developed a few pale, salmoncolored macules on his trunk.

His cough became much more frequent
and severe. He became delirious,
listlessly wandering around the house
fiddling with doorknobs. During the
fourth week of his illness, he rapidly
declined with increasing somnolence.
After nearly 4 weeks of illness, he died
surrounded by his loving family.

The patient was Prince Albert, the
Consort to Queen Victoria. He was
diagnosed with typhoid fever. His
personal physician, Sir William Jenner, a
leading expert on the disease, made the
diagnosis of typhoid fever. Prince Albert
received the best therapy of the day.
Typhoid Mary

The most notorious carrier of typhoid
fever—but by no means the most
destructive—was Mary Mallon, also
known as Typhoid Mary. In 1907, she
became the first American carrier to be
identified and traced. She was a cook in
New York; some believe she was the
source of infection for several hundred
people.

She is closely associated with forty
seven cases and three deaths.[7] Public
health authorities told Mary to give up
working as a cook or have her gall
bladder removed. Mary quit her job but
returned later under a false name. She
was detained and quarantined after
another typhoid outbreak. She died of
pneumonia after 26 years in quarantine.

Part of the problems Mary had stemmed
from her vehement denial of the
situation. She maintained that she was
healthy and had never had typhoid
fever. Historians say it also stemmed
from the prejudice that existed against
working-class Irish immigrants at the
time.

Today, a Typhoid Mary is a generic
term for a carrier of a dangerous
disease who is a danger to the public
because they refuse to take appropriate
precautions.
Famous typhoid victims







Famous people who have succumbed to the disease
include:
Anurag Goel of India
Alexander the Great (Typhoid is one of many
possibilities of his cause of death, including malaria,
West Nile virus, pancreatitis, and poisoning.)
Pericles
Archduke Karl Ludwig of Austria
Franz Schubert (disputed)
Charles Trenet













Margaret Breckenridge, highest-ranking Army nurse
under Ulysses S. Grant
Evangelista Torricelli
Benjamin Harrison's wife Caroline
Robert E. Lee's daughter Annie
Mary Henrietta Kingsley
Herbert Hoover's father and mother
Mark Hanna
William McKinley's daughter Katherine
Wilbur Wright
Leland Stanford, Jr.
William T. Sherman's father
Albert of Saxe-Coburg-Gotha, British prince consort,
Queen Victoria's husband
Ann Rutledge, alleged fiancée of Abraham Lincoln













William Wallace Lincoln, third son of President Abraham Lincoln
and Mary Todd Lincoln
Stephen A. Douglas
Louis Pasteur's daughters Cecile and Jeanne
President John Adams's wife Abigail Adams
K.B. Hedgewar, founder of Rashtriya Swayamsewak Sangh
General Stonewall Jackson's mother, father and daughter
John Buford
Charles Darwin's daughter Annie
Joseph Lucas
Ignacio Zaragoza
Alexander Alexandrovich Friedman
Henry Frederick Stuart, Prince of Wales, original heir to the
throne of James I of England
Thomas Baker, Iowa Militia Colonel, California State Senator,
and founder of Bakersfield, Kern County, California
THANK YOU