TYPHOID FEVER AND

PARATYPHOID FEVER

Dr nawin kumarDr nawin kumar

Typhoid and Paratyphoid

• Definition• Etiology

• Pathogenesis • Epidemiology

• Clinical manifestations

• The laboratory and other examinations

• Complications

• Diagnosis and differential diagnosis

• Prognosis

• Treatment• Preventions• Paratyphoid Fever

Definition of Typhoid fever

• Acute enteric infectious disease

• caused by Salmonella typhi (S.Typhi).

• prolonged fever, Relative bradycardia,

apathetic facial expressions, roseola,

splenomegaly, hepatomegaly, leukopenia.

• haemorrhage;• perforation;• cholecystitis;• phlebitis;• genitourinary inflammation;• arthritis• osteomyelitis.

Etiology

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

• Antigens: located in

the cell capsule

H (flagellar

antigen).

O (Somatic or cell

wall antigen).

Vi (polysaccharide

virulence)

“widel test”

• 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

• continues to be a global health problem

• areas with a high incidence include Asia, Africa and Latin America

• affects about 6000000 people with more than 600000 deaths a year. 80% in Asia .

• sporadic occur usually, sometimes have epidemic outbreaks.

Source of infection

Cases and chronic carriersCases discharge from incubation,

more in 2~4 weeks after onset, a

few (about 2~5%) last longer than

3 months

chronic carrier Typhoid Mary

Transmission

• fecal-oral route

• close contact with patients or

carriers

• contaminated water and food

• flies and cockroaches.

Susceptibility and immunity

• all people equally susceptible to infection

• acquired immunity can keep longer, reinfection are rare

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

• No cross immunity between typhoid and paratyphoid.

Susceptibility and immunity

• All seasons, usually in summer and autumn.

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

• both sexes equally susceptible.

Pathogenesis

• gastrointestinal tract host-pathogen interactions

• The amount of bacilli infection (>105baeteria).

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

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

Pathology• 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

Clinical manifestationsIncubation period: 3 ～ 60 days

(7 ～ 14).The initial period (early stage)• First week. • Insidious onset. • Fever up to 39~400C in 5~7 days

• chills 、 ailment 、 tired 、 sore throat 、 cough ,abdominal discomfort and constipation

The fastigium satge

• second and third weeks.

• Sustained high fever 、 partly remittent fever or irregular fever. Last 10 ～ 14 days.

• Gastro-intestinal symptoms: anorexia 、 abdominal distension or pain 、 diarrhea or constipation

• Neuropsychiatric manifestations: confusion 、 blunt respond even delirium and coma or meningism

• Circulation system:

relative bradycardia or dicrotic pulse.

• splenomegaly 、 hepatomegaly

toxic hepatitis.

• roseola :30%, maculopapular rash

a faint pale color, slightly raised

round or lenticular, fade on pressure

2-4 mm in diameter, less than 10 in number

on the trunk, disappear in 2-3 days.

• fatal complications: intestinal hemorrhage

intestinal perforation severe toxemia

defervescence stage• fever and most symptoms

resolve by the forth week of infection.

• Fever come down, gradual improvement in all symptoms and signs, but still danger.

convalescence stage• the fifth week. disappearance of

all symptoms, but can relapse

Clinical forms: • Mild infection: very common seen recently symptom and signs mild good general condition temperature is 380C short period of diseases recovery expected in 1~3 weeks seen in early antibiotics users young children mild more easy to misdiagnose

• 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

Special manifestations

• In children

Often atypical

sudden onset with high fever.

Respiratory symptoms and diarrhea, dominant.

Convulsion common in below 3.

relative bradycardia rare.

Splenomegaly, roseola and leucopenia less

common.

• In the aged

temperature not high, weakness

common.

More complications.high

mortality.

• 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.

Recrudescence

relapse

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

• Symptom and signs reappear

• the bacilli have not been

completely removed

• Some cases relapse more than once

Laboratory findings

Routine examinations:

white blood cell count is normal or

decreased.

Leukocytopenia(specially

eosinophilic leukocytopenia).

recovery with improvement of

diseases

decreased in relapse

Bacteriological examinations:

• Blood culture:

the most common use

80~90% positive during the first 2 weeks of

illness

50% in 3rd week

not easy in 4th week

re-positive when relapse and recrudesce

attention to the use of antibiotics

• 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.

• Rose spots: Not use routinely

Serological tests(Vidal test):

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

fever flagella(A,B,C) antigen.

• Antibody reaction appear during first

week

• 70% positive in 3~4 weeks and can

prolong to several months

• in some cases, antibodies appear slowly,

or remain at a low level,

• some(10~30%) not appear at all.

• "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, often nonspecifically elevated by

immunization or previous infections or

anamnestic reaction.

• Antibody level maybe lower when have

used antibiotics early.

• Some cross reaction between group “D” and “A”.

• False positive in some infectious diseases.

• Some positive in blood culture ,but negative in vidal test.

• 'Vi" often useful for carrier (1:40)

molecular biological tests: DNA probe or polymerase chain reaction (PCR)

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: • 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 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.

Diagnosis

• Epidemiology data

• Typical symptoms and signs

• Laboratory findings.

Differential diagnosis

• Viral infections: such as upper respiratory tract infection.

abrupt onset with fever, headache,

leucopenia, sore throat, cough, coryza.

no rose spots, no enlargement of liver &

spleen. The course of illness no more than

2 wks.

differential diagnosis depends on typical

manifestations and blood culture.

Malariahistory of exposure to malaria.

Paroxysms(often periodic) of sequential

chill,high fever and sweating.

Headache, anorexia, splenomegaly,

anemia, leukopenia

Characteristic parasites in

erythrocytes,identified in thick or thin

blood smears.

• Leptospirosis

Endemic area,contacted with urine of mice.

Abrupt fever,chills,severe headache,and

myalgias, especially of the calf muscles.

Leptospires can be isolated from

blood,cerebrospinal fluid.

Special agglutination titers develop after 7

days and may persist at high levels for

many years.

Epidemic Louse-Borne typhus

• prodromal of malaise and headache

followed by abrupt chills and fever.

• headaches,prostration,persisting high

fever.

• Maculopapular rash appears on the forth

to seventh days on the trunk and in the

axillas, spreading to the rest of the body

but sparing the face,palms,and soles.

• Laboratory confirmation by proteins OX19

agglutination and specific serologic tests.

Tuberculosis

• continuous high or low

fever,fatigue,weight loss,night sweats.

• Mild cough

• pulmonary infiltration on chest

radiograph

• positive tuberculin skin test

reaction(most cases)

• acid-fast bacilli on smear of sputum

• sputum culture positive for

mycobacterium tuberculosis.

Septicemia of Gram-negative bacilli

• abrupt onset,high fever,symptom of

toxemia.

• Chill,sweats.

• Shock.

• Positive of gram-negative bacilli

from blood culture.

Prognosis:

• Case fatality 0.5 ～ 1%.

• but high in old ages 、 infant 、 and

serious complications

• Have immunity for ever after diseases

• About 3% of patients become fecal

carriers .

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.

• 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

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.