Typhoid Fever Fixed

8/6/2019 Typhoid Fever Fixed

1/58

TYPHOID FEVERTYPHOID FEVER


2/58


3/58

Typhoid fever is an acutesystemic illnesscharacterized by fever,headache and abdominaldiscomfort.

It is caused by salmonellatyphi (gram negative bacilli).Family of enterobacteriacea.

A similar but less severeillness known as paratyphoidfever, caused by salmonellaparatyphi (A, B, C)


4/58

Generally transmitted by the ingestion offood/water contaminated by feces of aninfected person

Once ingested the organism perforates theintestinal wall and enters the bloodstreamtemporarily then phagocytosed by

macrophages


5/58

Characterized byCharacterized by

prolonged fever

relative bradycardia

apathetic facial expressions

Roseola

Splenomegaly

Hepatomegaly

Leukopenia.


6/58


7/58

SalmonellaeSalmonellae

gram negative

non-spore forming

facultatively anaerobic bacilli that measure 23 by 0.40.6 m

produce acid on glucose fermentation

reduce nitrates

do not produce cytochrome oxidase.

all salmonellae except S.Gallinarum-Pullorum are motile by meansof peritrichous flagella

and all but

S.Typhi produce gas (H2

S) on sugar fermentation.

Notably, only 1% of clinical isolates ferment lactose; a high level ofsuspicion must be maintained to detect these rare clinical lactose-fermenting isolates.


8/58

Antigens: located in the cell capsule

H (flagellar antigen).

O (Somatic or cell wall antigen).

Vi (polysaccharide virulence)

widel test


9/58

A schematic diagram of a singleA schematic diagram of a single SalmonellaSalmonella typhityphicell showing thecell showing the

locations of the H (locations of the H (flagellarflagellar), 0 (somatic), and Vi (K envelope)), 0 (somatic), and Vi (K envelope)

antigens.antigens.


10/58

Endotoxin

A variety of plasmids

Resistance: Live 2-3 weeks in water.

1-2 months in stool. Die out quickly

in summer

Resistance to drying and cooling


11/58


12/58


13/58

Epidemiology:Epidemiology:

T.F. is prevalent in areas of developingcountries lacking adequate waste disposaland clean drinking water facilities.

16,000,000 new cases annually, causing

around 600,000 death per year. Humans are the only host for S. Typhi

Mode of transmission is by fecal-oral rout,through ingestion of contaminated food orwater, health care workers & lab workers

acquire infection by accidental exposure tos.typhi-containing specimen

Incubation period: around 10-14 days.


14/58

TransmissionTransmission

fecal-oral route

close contact with patients or carriers

contaminated water and food

flies and cockroaches.


15/58


16/58


17/58

PathogenesisPathogenesis

gastrointestinal tract host-

pathogen interactions

The amount of bacilli

infection (>105baeteria).


18/58

ingested orally

pStomach barrier (some Eliminated)

penters the small intestine

pPenetrate the mucus layer

p enter mononuclear phagocytes of ileal peyer's

patches and mesenteric lymph nodes

p proliferate in mononuclear phagocytes

spread to blood. initial bacteremia (Incubation

period).

Pathogenesis


19/58

PathogenesisPathogenesis

p enter spleen, liver and bone marrow

(reticulo-endothelial system)

further proliferation occurs

p A lot of bacteria enter blood again.

(second bacteremia).

p Recovery


20/58

S.Typhi.

stomach

Lower

ileum

peyer's patches &

mesenteric lymph nodes

thoracic

duct

1st bacteremia

(Incubation stage)

10-14d

(mononmonon

uclearuclearphagocphagocytesytes )

2nd bacteremia

liverspleengall

BM ,ect

early stage&acme stage

(1-3W

LN Proliferate,swellnecrosis

defervescence stage

3-4w

Bac. In gall

Bac. In

feces

S.Typhi eliminated

convalvescence stage

(4-5w)

Enterorrhagia,i

ntestinalperforation


21/58

Pathology

essential lesion:proliferation of RES (reticuloendothelial

system )

specific changes in lymphoid tissuesand mesenteric lymph nodes.

"typhoid nodules

Most characteristic lesion:ulceration of mucous in the region of the

Peyers patches of the small intestine


22/58

Major findings in lower ileumMajor findings in lower ileum

Hyperplasia stage(1st week):

swelling lymphoid tissue and

proliferation of macrophages.

Necrosis stage(2nd week):

necrosis of swelling lymph nodesor solitary follicles.


23/58

Major findings in lower ileumMajor findings in lower ileum

Ulceration stage(3rd week):

shedding of necrosis tissue and

formation of ulcer----- intestinalhemorrhage, perforation .

Stage of healing (from 4th week):

healing of ulcer, no cicatrices and nocontraction


24/58


25/58

Stages of InfectionStages of Infection

Typically, infection of untreated typhoid feveris divided into 4 individual stages (eachlasting ~1 week)


26/58

Clinical picture:Clinical picture:

1stweek: Onset is insidious. Fever (>70%) is slow rising, increasing

progressively in step ladder fashion over4-5 days (38,8-40,5 c), with relativebradycardia.

Non-specific constitutional symptoms:headache, fatigue, myalgia, cough, sorethroat.

G.I. symptoms: abdominal pain (20-40%),constipation, diarrhea.

Early signs: relative bradycardia,abd.tenderness (diffuse or localized,usually right lower quadrant).


27/58

Endof1Endof1stst week,beginningof2week,beginningof2ndndweek:week:

Abd.distension & tenderness.

Hepato-splenomegaly.

Rose-spots: maculopapular rash, 2-3 mm, inthe trunk (chest & upper abdomen), fade on

pressure, remains 4-5 days, disappear

without scars, occur in 30% of cases, difficultto notice in dark-skinned patients.


28/58

Rose spots


29/58

33rdrd&4&4ththweek.week.

Patient is profoundly ill, complications appear.

Disturbance in consciousness, neuro-psychiatricsymptoms (picking bed clothes or imaginary

objects), called muttering delirium, coma vigil,typhoid psychosis.

Intestinal perforation or bleeding: shock state,fever disappears, fresh or dark bloody stool.

Cholecystitis, hepatitis, pneumonia, carditis,meningitis, nephritis, arthritis, osteomylitisetc.

Death.


30/58

Typhoid terminal state (typhoid face).


31/58

Majority of patients recover without complications

by receiving adequate antibiotics without delay.

1-5% of cases become asymptomatic chronic

carriers, shedding S.typhi in stool and less

frequently in urine. In those carriers, S.typhi reside in gallbladder

especially if associated with gallstones or

Ca.gallbladder, because anatomical abnormalities

allow for prolonged colonization of the organism.

In areas where schistosoma hematobium isprevalent, chronic carriage of S.typhi in urinary

bladder is common.


32/58


33/58

clinical presentation of enteric fever is relatively nonspecific

the diagnosis needs to be considered in any febrile traveler returningfrom a developing country, especially the Indian subcontinent, thePhilippines, or Latin America.

Other diagnoses that should be considered in these travelers includemalaria, hepatitis, bacterial enteritis, dengue fever, rickettsialinfections, leptospirosis, amebic liver abscesses, and acute HIV

infection

no specific laboratory test is diagnostic for enteric fever.

In 1525% of cases, leukopenia and neutropenia are detectable.

Leukocytosis is more common among children, during the first 10days of illness, and in cases complicated by intestinal perforationor secondary infection.

Other nonspecific laboratory findings include moderatelyelevated liver function tests and muscle enzyme levels.


34/58

Thedefinitivediagnosisof enteric fever

requires the isolation ofS. Typhi or S.

Paratyphi from blood, bone marrow, other

sterile sites, rose spots, stool, or intestinalsecretions.

sensitivity is as high as 90% during the first

week of infection and decreases to 50% by

the third week.


35/58

Blood culture: is the gold standard fordiagnosis in the 1st week (90% positive). Itdrops to 50% during 3rd week of infection.

Since almost all S. Typhi organisms in bloodare associated with the mononuclear-cell/platelet fraction, centrifugation of bloodand culture of the buffy coat can substantiallyreduce the time to isolation of the organismbut does not increase sensitivity.


36/58

Stool culture: usually negative during 1st

week of infection, becomes highly positiveduring 2nd & 3rd week. The disadvantage isthat, it does not distinguish betweenacutely infected patient and a chroniccarrier.

Stool cultures, while negative in 6070% ofcases during the first week, can becomepositive during the third week of infectionin untreated patients.


37/58

Bone marrow culture: highly sensitive,

remain positive even after 5 days of

antibiotic use. Rarely required due to itsinvasive nature, except in patient highly

suspicious of T.F. who has receivedantibiotic and his blood culture is negative.

Unlike blood culture, bone marrow culture

remains highly (90%) sensitive despite 5 daysof antibiotic therapy.


38/58

Culture of G.I. secretion: using duodenalstring test.

Culture of intestinal secretions (bestobtained by a noninvasive duodenal stringtest) can be positive despite a negativebone marrow culture.

If blood, bone marrow, and intestinalsecretions are all cultured, the yield is>90%.


39/58

Urine culture: less frequent, less sensitive.

Culture of rose spots: positive in two thirds of

patients remains positive even after receivingantibiotics.


40/58

Several serologic tests, including the classicWidal test for "febrile agglutinins," areavailable.

None of these tests is sufficiently sensitive orspecific to replace culture-based methods forthe diagnosis of enteric fever in developedcountries.

Polymerase chain reaction and DNA probeassays to detect S.Typhi in blood are beingdeveloped.


41/58

WIDAL test: is a serological test that detects AbagainstS.typhi somatic Ag (anti-O), or flagellar Ag(H).

It is unreliable, nonspecific, insensitive, with highfalse positive results due to cross-reaction withmany other types of salmonella.


42/58

Widal test is considered positive, if anti-O titer>1:320 (other references >1:80) or anti-H titer >1:640. or if there is four fold rise of titer betweenacute infection and convalescent period.

Additionallab findings: Hb : variable anemia. Platelets: often diminished.

WBC: typically leucopenia with nuetropenia (15-25%), butcan be normal, or leucocytsis with lymphocytosis in littlechildren or secondary infection or complication occur

(such as intestinal perforation). LFT: abnormal results with elevated AST, ALT and Alk.Ph.


43/58

ECG: prolonged PR interval, nonspecific

ST, T wave changes.

New diagnostic methods:

Polymerase chain reaction PCR, and DNA

probe test, that detect S. typhi DNA, they

are highly sensitive and specific, but not

widely used.


44/58


45/58


46/58

Treatment of chronic carrier:Treatment of chronic carrier:

Prolonged anti-bioticcourse (e.g. ciprofloxacine500mg/ BD/ 6-8weeks) might eliminate thecarrier state

But in patients with anatomical abnormalities(e.g. gall stones) the medical eradication usuallynot successful, and a surgical solution (e.g.

cholecystectomy) should be taken intoconsideration.


47/58

preventionprevention::

Improved sanitation and health education.

Checking food-handlers by periodic stool

culture.

Vaccination: two parenteral (inactivated, killed),

one oral (live attenuated). No life-long

protection.

Recommendation for vaccination:

Traveling to endemic area.

Household contact with infected patient or carrier.

Lab worker with contact to S. typhi specimen.

Epidemic outbreak.


48/58

VaccinationVaccination

1stparenteral has many side-effects. Given in 2 injections4weeks apart, with boosterdose every 3-5 years.

2ndparenteral (viCPS): lessS.E. 1 inj. Booster dose every2 years.

Oral (ty21a): the safest, 1

dose, alternate day for atotalof 4doses, then booster doseevery 5 years( C/I in children


49/58


50/58

Intestinal hemorrhageIntestinal hemorrhage

Commonly appear during the second-third week of illness

difference between mild and greaterbleedingoften caused by unsuitable food,diarrhea et al

serious bleeding in about 2~8% a sudden drop in temperature rise

in pulseand signs of shock followedby dark or fresh blood in the stool.


51/58

Intestinal perforation:

The more serious .Incidence,1-4%

Commonly appear during 2-3 weeks.

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 when press abdomen,

abdomen muscle entasia, reduce or disappear in thesonant extent of liver, leukocytosis .

Temperature rise .peritonitis appear.

celiac free air under x-ray.


52/58

Hematologic complicationHematologic complication

Trombositopenia

Hipofibrinogenemia

Elevated protrombin time Elevated partial thromboplastin time

Elevation of fibrin degradation products

DIC


53/58

Typhoid HepatitisTyphoid Hepatitis

common,1-3 weeks

hepatomegaly, ALT elevated

get better with improvement of diseases

in 2~3 weeks

Elevation of transaminase not relevant bythe increasing of serum bilirubin


54/58

Typhoid pancreatitisTyphoid pancreatitis

Rare case

Diagnosed by amilase and lipase enzym

assays, CT scan, USG


55/58

MiokarditisMiokarditis

1-5% patient with typhoid fever

EKG abnormalities in 10-15% patient

seen in 2-3 weeks, usually severe toxemia Found in patient with severe disease, fulminant

and acute condition

Chest pain, congestive heart failure, aritmia,

cardiogenic shock


56/58

Bronchitis, bronchopneumoniaBronchitis, bronchopneumonia

seen in early stage


57/58


58/58

ThankYouThankYou

Typhoid Fever Fixed

Documents

Transcript of Typhoid Fever Fixed