TYPHOID FEVER AND

PARATYPHOID FEVER

Dr nawin kumarDr nawin kumar

Definition of Typhoid fever

• “mesenteric fever“ by BAGLIVI in 1696, • typhoid fever was given its universal name in

1834.

• Potentially fatal, multi-systemic illness caused

primarily by Salmonella typhi and paratyphi”

• Earlier 100% death rate for the perforations • Nowadays, 1 to 39%

Typhoid---ancient Greek Typhos, smoke or cloud that was

believed to cause disease or madness

430–426 B.C.

Killed 1/3 of the population of Athens, including their leader Pericles. The power shifted from Athens to Sparta. 2006

study detected DNA sequences similar salmonella

Etiology

Serotype: D group of Salmonella Gram-negative rod non-spore flagella

1. H (flagellar antigen).

2. O (Somatic or cell wall

antigen).

3. Vi (polysaccharide

virulence)

• “widel test”

Antigens: located in the cell capsule

Georges Fernand Isidor Widal (1862-1929)

Demonstrated specific agglutinins in the blood of Typhoid patient in 1896----

“The Widal Reaction”

Susceptibility and immunity

• all people equally susceptible to infection

• immunity is not associated with antibody level of “H”, “O”and “VI”.

• No cross immunity between typhoid and paratyphoid.

• 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

epidemiology

• sporadic occur usually, sometimes have epidemic outbreaks.

Susceptibility and immunity

• All seasons, usually in summer and autumn.

• Most cases in school-age children and young adults.

• both sexes equally susceptible.

Infects roughly 21.6 million people each

year

* International Estimate

Ramsden AE, Mota LJ, Münter S, Shorte SL, Holden DW. The SPI-2 type III secretion system restricts motility of Salmonella-containing vacuoles. Cell

Kills 200,000 people each year

62% of these occurring in Asia and 35% in

Africa

* International Estimate

* Taylor TE, Strickland GT. Malaria. In: Strickland GT, ed. Hunter’s Tropical Medicine and Emerging Infectious Diseases. 8th ed. Philadelphia: WB Saunders, 2000:614-43.

Highest in Pakistan & India in Asian countries

(451.7 per 100,000)

•fecal-oral route

•close contact

with patients or

carriers

•contaminated

water and food

•flies and

cockroaches.

Best prevention

Scrub of them off your handsBest prevention

Scrub them off your hands

S. typhi are able to survive a stomach pH as low as 1.5.

Antacids, (H2 blockers), PPI’s, gastrectomy, facilitate

S typhi infection

TYPHOID FEVER RISK FACTORS

ingested orally

Stomach barrier (some Eliminated)

enters the small intestine

Penetrate the mucus layer

enter mononuclear phagocytes of ileal peyer's patches and mesenteric lymph nodes

proliferate in mononuclear phagocytes spread to blood. initial bacteremia (Incubation period).

Pathogenesis

Pathogenesis enter spleen, liver

and bone marrow

(reticulo-endothelial

system)

further proliferation

occurs "typhoid

nodules“

A lot of bacteria

enter blood again.

(second bacteremia).

Recovery

S.Typhi.

stomach

Lower ileum

peyer's patches &mesenteric lymph nodes

thoracic

duct

1st bacteremia(Incubation stage)

10-14d

(monomononuclenuclear ar phagophagocytescytes )

2nd bacteremia

liver 、 spleen 、 gall 、BM ,ect

early stage&acme stage(1-3W ）

LN Proliferate,swell necrosis

defervescence stage

（ 3-4w ）

Bac. In gall

Bac. In feces

S.Typhi eliminatedconvalvescence stage

(4-5w)

Enterorrhagia,intestinal

perforation

PRESENTATION

Incubation period

is 7-14 days

FIRST WEEK TEMPERATURE PATTERN

Diffuse abdominal pain, Inflamed Peyer patches

narrow the lumen--Constipation.

Dry cough, dull frontal headache,

delirium, increasingly Stupor

& malaise

FIRST WEEK OTHER SYMPTOMS

Rose spots, blanching, truncal,

maculopapules usually 1-4 cm wide, < 5 in

number; these generally resolve within 2-5 days

(bacterial emboli to the dermis)

FIRST WEEK OTHER SYMPTOMS

Distended abdomen, Soft splenomegaly,

Relative bradycardia & dicrotic pulse

(double beat, the second beat weaker than the first)S

EC

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D W

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Patient may descend into the typhoid state---apathy,

confusion, and even psychosis

THIRD WEEK TYPHOID STATE

Necrotic Peyer patches, bowel perforation,

Peritonitis, intestinal hemorrhage

may cause death

THIRD WEEK Week of complications

Fever, mental state, and abdominal distension slowly

improve over a few days, complications may still occur

in surviving untreated individuals

FOURTH WEEK WEEK OF CONVALESCENCE

Clinical forms: • Mild infection:

– symptom and signs mild– good general condition– temperature is 380C

– short period of diseases

• Persistent infection: diseases continue than 5 weeks

• Ambulatory infection:– mild symptoms,early intestinal bleeding or perforation.

• Fulminate infection:– rapid onset, severe toxemia and septicemia.

– High fever,chill,circulation failure, shock, delirium, coma,

myocarditis, bleeding and other complications, DIC

• Recrudescence

• clinical manifestations reappear

• less severe than initial episode

• It’s temperature recrudesce when temperature start to

step down but abnormal in the period of 2-3 weeks and

persist 5~7 days then back to normal.

• seen in patients with short therapy of antibiotics.

• Relapse

• serum positive of S.typhi after 1 ～ 3 weeks of temperature down to normal.

• Symptom and signs reappear

Diagnosis

• Epidemiology data

• Typical symptoms and signs

• Laboratory findings.

Laboratory findingsRoutine examinations:

white blood cell count is normal or decreased.

Leukocytopenia(specially eosinophilic leukocytopenia).

Blood culture:

80~90% positive during the first 2 weeks of illness

Serological tests (Widal test)

The bone marrow culture

the most sensitive test specially in patients pretreated with antibiotics.

Urine and stool culturesincrease the diagnostic yieldpositive less frequentlystool culture better in 3~4 weeks

The duodenal string test to culture bile useful for the diagnosis of carriers.

BASU

Serological tests(Vidal test):

five types of antigens:somatic antigen(O),flagella(H) antigen, and paratyphoid

fever flagella(A,B,C) antigen.

• "O" agglutinin antibody titer ≥1:80 and "H"

≥1:160 or "O" 4 times higher supports a

diagnosis of typhoid fever

• "O" rises alone, not "H", early of the disease.

• Only "H" positive, but "O" negative

• nonspecifically elevated by immunization

• previous infections or

• anamnestic reaction.

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Bilateral Salmonella typhi breast abscess

unmarried 35-year-old female without any predisposing

conditions

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Morbidity 55.4%mortality 28.5 %

INTESTINAL PERFORATIONS

5% of people with typhoid fever experience

this complication

DS00538 April 10, 2008© 1998-2009 Mayo Foundation for Medical Education and Research (MFMER).

Typhoid enteric perforation, Dr Y. Akgun *, B. Bac, S. Boylu, N. Aban, I. Tacyildiz, British Journal of Surgery Volume 82 Issue 11, Pages 1512 - 1515Published Online: 8 Dec 2005

Pathology in ileum• essential lesion: proliferation of RES

(reticuloendothelial system ) specific changes in lymphoid tissues and mesenteric lymph nodes.

"typhoid nodules“• Most characteristic lesion: ulceration of mucous in the region

of the Peyer’s patches of the small intestine

(PEYER’S PATCHES)

(TYPHOID NODULE)

Major findings in lower ileum

• Hyperplasia stage(1st week): swelling lymphoid tissue and proliferation of macrophages.

• Necrosis stage(2nd week): necrosis of swelling lymph nodes or solitary follicles.

Major findings in lower ileum

• Ulceration stage(3rd week): shedding of necrosis tissue and

formation of ulcer ----- intestinal hemorrhage, perforation .

• Stage of healing (from 4th week):

healing of ulcer, no cicatrices and no contraction

MECHANISM OF INTESTINAL PERFORATION

Intestinal peyer’s patches

Ileum especially distal ileum, jejunum usually does not perforate in typhoid,usually happens in the third week

2 or 3 weeks hx of disease, with suddenly worsening

of pain & general conditions,

Tenderness starts in his right lower quadrant, spreads and eventually becomes generalized, Guarding , (seldom the board-like rigidity) Erect film, shows gas

Under diaphragm (50% positive)

lateral decubitus film, shows gas

under his abdominal wall PR

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PE

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The bradycardia and leucopenia of typhoid may

occasionally mask the tachycardia and leucocytosis

of peritonitis

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If peritonitis seems to be localized, signs confined to only part

abdomen, general condition is good, patient not deteriorating,

consider non-operative treatment.

CONSERVATIVE SURGICALVS

If signs of generalized peritonitis, do a laparotomy

“Suck and drip”

Resuscitation, antibiotics, pass a NG-tube, Monitor abdominal tenderness,

pulse, temperature, white blood count.

If any of these rise, suspect that peritonitis is extending, so take an

erect

X-ray film of his abdomen

CONSERVATIVE MANAGEMENT

MDR-area

MDR+NAR-area

MEDICATION TREATMENT WHO RECOMMENDATIONS

Operate as early as possible,

Do as much as necessory & as little as possible

SURGICAL MANAGEMENT

PREPARATIONAdequately resuscitate,

Maintain good urine output, passnasogastric tube down,

Start chemotherapy.

Su

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INTESTINAL HEMORRHAGE

Occurs in 10-20

per cent of the cases

Intestinal bleeding is often marked

by a sudden drop in blood pressure and shock, followed by the appearance of blood in stoolH

em

orr

hag

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pre

sen

tati

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replace the blood loses. Bleeding usually stops

spontaneously

Only operate if bleeding is persistent, or

alarmingly

INTESTINAL HEMORRHAGE

Surgery Intestinal Hemorrhage

Occurs in 1-2% of cases

*According to Indian study 8%

More common in children

Antibiotic resistance & virulence of bacteria

*M.L. Kulkarni, SJ. Rego, Department of Pediatrics, J.J.M. Medical College, Davangere 577 004.

Acute Acalculous Cholecystitis

TYPHOID

Acute Acalculous Cholecystitis

TYPHOID

*Thickened gall bladder wall, sonographic Murphy's

sign, pericholicystic collection in the absence of

gall stones

*Subha Rao SD, LewinS, Shetty B, et al. Acute acalculous cholecystitis in typhoid fever. Indian Pediatr 1992, 29: 1431-1435.

Chronic Cholecystitis (Carriers)

TYPHOID

Excretes bacteria in stools for more > 1

year1-4% of non-treated infected patients become

chronic carriers

Patients with cholelithiasis, biliary anomalies, females,

Salmonella can be cultured from stools,

duodenal aspirate, gall stones

Mary Mallon (September 23, 1869 – November 11, 1938)

Forcibly quarantined twice, she infected 47 people,

three of whom died. She died in quarantine.

Chronic CholecystitisTYPHOID

Biliary anomalies, stones--requires cholecystectomy +

antibiotics4-6 weeks antibiotic treatment

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• Prophylaxis

1.control source of infection

Isolation and treatment of patients

stool culture one time per 5 days.

if negative continued two times ,without

isolation.

Control of carriers.

observation of 25 days(15 days in

paratyphoid) when close contact

2. Cut of course of transmission

key way

avoid drinking untreated

water and food.

3.Vaccination

side-effect more, less use

Ty21a—Oral live attenuated vaccine

Vi-CPS— parenteral vaccine

Paratyphoid fever A,B,C• Caused by Salmonella paratyphoid

A,B,C.respectively.

• in no way different from typhoid fever in epidemiology, pathogenesis,

pathology,clinical manifestations,

diagnosis, treatment and

Prophylaxis

Paratyphoid A,B:• incubation period 2~15days, in

genaral,8~10 days.

• milder in severity

• fewer in complications.

• Better in prognosis,

• relapse more common in Paratyphoid A.

• Treatment same as in typhoid fever.

Paratyphoid C:• Always sudden onset.

• Rapid rise of temperature.

• Presented in different forms-- Septicemia,

Gastroenteritis and Enteric fever

• Complications--arthritis, abscess formation, cholecystitis, pulmonary complications are commonly seen.

• Intestinal hemorrhage and perforation not as common as in typhoid fever.

Complications

Intestinal hemorrhageCommonly appear during the second-third

week of illness

difference between mild and greater bleeding

often caused by unsuitable food, diarrhea etc

serious bleeding in about 2~8%

a sudden drop in temperature 、 rise in

pulse 、 and signs of shock followed by dark or

fresh blood in the stool.

Intestinal perforation:

• a very severe condition in tropical countries • incidence ranges from 0.9 to 39% (8), • mortality rate ranging from 27% to 77% • the mortality and the morbidity rate depend

– on the general status of the patient, – the virulence of the germs– the duration of disease evolution – Less on the surgical technique,

• adequate pre-operative management • aggressive resuscitation with antibiotherapy

• Rent closure• Resection anastomosis

– Last 60 centimeters of the ileum -high concentration of peyer’s patches whose infection is a source of intestinal perforation

– Digestive fistula - most threatening – anastomotic leakage- suturing is performed in a

septic environment– new perforation

postoperative complications

• Resection with temporary ileostomy– avoiding any intestinal suture in septic tissues– management of stoma– Peristomal ulceration – awful skin pain –self

limitation of food intake. denutrition, cachexia and death

• postoperative septic shock

Intestinal perforation: • 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 the sonant extent of liver, leukocytosis .

• Temperature rise .peritonitis appear.

• celiac free air under x-ray.

• Toxic hepatitis:

common,1-3 weeks

hepatomegaly, ALT elevated

get better with improvement of

diseases in 2~3 weeks

• Toxic myocarditis.

seen in 2-3 weeks, usually severe

toxemia.

• Bronchitis, bronchopneumonia.

seen in early stage

Other complications:

• toxic encephalopathy.

• Hemolytic uremic syndrome.

• acute cholecystitis 、

• meningitis 、

• nephritis et al.

TREATMENT

General treatment

• isolation and rest

• good nursing care and supportive treatment

close observation T,P,R,BP,abdominal condition and stool .

suitable diet include easy digested food or half-liquid food.drink more water

intravenous injection to maintain water and acid-base and electrolyte balance

• Symptomatic treatment:

for high fever:• physical measures firstly

• antipyretic drugs such as aspirin

should be administrated with caution

• delirium,coma or shock,2-4mg

dexamethasone in addition to

antibiotics reduces mortality.

Etiologic and special treatment

1.Quinolones:

first choice

it’s highly against S.typhi

penetrate well into macrophages,and achieve

high concentrations in the bowel and bile

lumens

• Norfloxacin (0.1 ～ 0.2 tid ～ qid/10 ～ 14 days).

• Ofloxacin (0.2 tid 10 ～ 14days).

• ciprofloxacin (0.25 tid)

caution: not in children and pregnant

2.Chloramphenicol:

• For cases without multiresistant S.typhi.

• Children in dose of 50 ～ 60mg/kg/per day.

• adult 1.5 ～ 2g/day. tid.

• Unable to take oral medication, the same

dosage given introvenously

• after defervescence reduced to a half.

complete a 10 ～ 14 day course.

• But ,drug resistance, a high relapse

rate,bone marrow toxicity.

3.Cephalosporines:

Only third generation effective

Cefoperazone and Ceftazidime.

2 ～ 4g/day .10~14 days.

4.Treatment of complication.• Intestinal bleeding:

bed rest, stop diet,close observation T,P,R,BP.

intravenous saline and blood transfusion,and attention to acid-base balances.

sometimes,operative.

• Perforation:

early diagnosis.

stop diet.

decrease down the stomach

pressure.

intravenous injection to maintain

electrolyte and acid-base balances.

use of antibiotics.

sometimes operative.

• Toxic myocarditis:

bed rest, cardiac muscle protection drugs,

dexamethasone, digoxin.

5.Chronic carrier:

• Ofloxacin 0.2 bid or ciprofloxacin 0.5 bid, 4 ～6 weeks.

• Ampicillin 3 ～ 6g/day tid plus probenecid 1 ～ 1.5g/day. 4 ～ 6 weeks.

• TMP+SMZ2 tabs. Bid. 1 ～ 3 months.

• Cholecystitis may require cholecystectomy.