TYPHOID FEVER AND PARATYPHOID FEVER

Guoli Lin Department of Infectious Diseases The Third Affiliated Hospital of SYSU

Typhoid and Paratyphoid

Definition Etiology

Complications

Pathogenesis
Epidemiology

Diagnosis and differential diagnosis

Prognosis

Clinical manifestations
The laboratory and other examinations

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.

Etiology
Serotype: D group of Salmonella Gram-negative non-spore flagella aerob/fakultatif anaerob

Antigens: located in the cell capsule

H (flagellar antigen) Protein,

termolabil

O (Somatic or cell wall antigen)

lipopolisakarida, termostabil

Vi (polysaccharide virulence)
S.Typhi, S. Paratyphi C

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

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.

Demam, anoreksia, mual, muntah, obstipasi, cefalgia, myalgia

Infeksi Salmonella per oral

Masa Inkubasi 10-14 hari

Minggu I
Gejala Prodromal

Bradi relatif Typhoid tounge Organomegali

Minggu II dan selanjutnya

Gang. Kesadaran Roseole spot

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, Oand 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 hostpathogen interactions The amount of bacilli infection (>105baeteria).

Pathogenesis
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
enter spleen, liver and bone marrow (reticulo-endothelial system) further proliferation occurs

A lot of bacteria enter blood again.

(second bacteremia).

Recovery

S.Typhi.
2nd bacteremia

liverspleengall BM ,ect early stage&acme stage (1-3W

stomach

(monon

Bac. In gall

uclear phagoc ytes )

Lower ileum

Bac. In feces

peyer's patches & mesenteric lymph nodes

LN Proliferate,swell
necrosis defervescence stage

S.Typhi eliminated convalvescence stage (4-5w) 1st bacteremia (Incubation stage) 10-14d

thoracic duct

Enterorrhagia,i ntestinal perforation

3-4w

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 Peyers patches of the small intestine


(PEYERSPATC HES)

 (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 manifestations Incubation period: 360 days(714). The initial period (early stage) First week. Insidious onset. Fever up to 39~400C in 5~7 days chillsailmenttiredsore throat cough ,abdominal discomfort and constipation et al.

The fastigium satge

second and third weeks. Sustained high feverpartly remittent fever or irregular fever. Last 1014 days. Gastro-intestinal symptoms: anorexia abdominal distension or paindiarrhea or constipation Neuropsychiatric manifestations: confusionblunt respond even delirium and coma or meningism

Circulation system:
relative bradycardia or dicrotic pulse.

splenomegalyhepatomegaly
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.
the fifth week. disappearance of all symptoms, but can relapse

convalescence stage

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.

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.

Recrudescence

clinical manifestations reappear less severe than initial episode Its 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 13 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 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)

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 pulseand 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.

DIAGNOSTIK TYPHOID

Typhoid Cardinal Sign

Febris continua Bradikardi relatif Organomegali Typhoid tounge Roseole Konstipasi/diare

Pemeriksaan lab hanya penunjang

Leukopenia Trombositopenia ringan SGOT/SGPT meningkat Widal Test + (dapat + pada 6 bulan-1 tahun post typhoid)

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.

Prognosis:

Case fatality 0.51%.

but high in old agesinfantand 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

its highly against S.typhi

penetrate well into macrophages,and achieve high concentrations in the bowel and bile lumens

Norfloxacin (0.10.2 tidqid/1014 days). Ofloxacin (0.2 tid 1014days). ciprofloxacin (0.25 tid)

caution: not in children and pregnant

2.Chloramphenicol:

For cases without multiresistant S.typhi.

Children in dose of 5060mg/kg/per day.

adult 1.52g/day. tid.

Unable to take oral medication, the same dosage given introvenously

after defervescence reduced to a half. complete a 1014 day course.

But ,drug resistance, a high relapse rate,bone

marrow toxicity.

3.Cephalosporines:
Only third generation effective Cefoperazone and Ceftazidime.

24g/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, 46

weeks.

Ampicillin 36g/day tid plus probenecid 1 1.5g/day. 46 weeks.

TMP+SMZ 2 tabs. Bid. 13 months. Cholecystitis may require cholecystectomy.

Prophylaxis
Isolation and treatment of patients stool culture one time per 5 days. if negative continued two times ,without isolation.

1.control source of infection

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.