TYPHOID FEVER �AND �PARATYPHOID FEVER

Guoli Lin

Department of Infectious Diseases

The Third Affiliated Hospital of SYSU

Typhoid and Paratyphoid

• Definition
• Etiology
• Pathogenesis
• Epidemiology
• Clinical manifestations
• The laboratory and other examinations

• Complications
• Diagnosis and differential diagnosis
• Prognosis
• Treatment
• Preventions
• Paratyphoid Fever

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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.
• intestinal perforation, intestinal hemorrhage

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Etiology

Serotype: D group of Salmonella

Gram-negative

rod

non-spore

flagella

Culture characteristics

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• Antigens: located in the cell capsule

H (flagellar antigen).

O (Somatic or cell wall antigen).

Vi (polysaccharide virulence)

“widel test”

A schematic diagram of a single Salmonella typhi cell showing the locations of the H (flagellar), 0 (somatic), and Vi (K envelope) antigens.

• 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

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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.

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Source of infection

�Cases and chronic carriers�Cases discharge from incubation, more in 2~4 weeks after onset, a few (about 2~5%) last longer than 3 months

chronic carrier Typhoid Mary

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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.

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Pathogenesis

• gastrointestinal tract host-pathogen interactions
• The amount of bacilli infection (>10⁵baeteria). �

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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

thoracic duct

1st bacteremia

(Incubation stage)

10-14d

(mononuclear phagocytes )

2nd bacteremia

liver、spleen、gall、

BM ,ect

early stage&acme stage

(1-3W）

LN Proliferate,swell necrosis defervescence stage

（3-4w）

Enterorrhagia,intestinal perforation

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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

回肠：

集合淋巴结(PEYER’SPATCHES)增生

伤寒小结(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

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Clinical manifestations

Incubation 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 et al.

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

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• 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

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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

图 典型伤寒自然病程示意图

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 et all.

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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.

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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
• the bacilli have not been completely removed
• Some cases relapse more than once

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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 cultures�increase the diagnostic yield�positive less frequently�stool 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)

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Complications

Intestinal hemorrhage�Commonly appear during the second-third week of illness�difference between mild and greater bleeding�often caused by unsuitable food, diarrhea et al

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.

图 典型伤寒自然病程示意图

Diagnosis�

• Epidemiology data

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• 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.

Malaria

history 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.

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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+SMZ�2 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

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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.

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