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Typhoid fever

Dr KURNIA F. JAMIL, M.Kes, SpPD-KPTI, FINASIM

DIVISI TROPIK DAN INFEKSI

BAG/SMF.ILMU PENYAKIT DALAM

FK UNSYIAH

RSUD. Dr. ZAINOEL ABIDIN

BANDA ACEH

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Organism

Salmonella typhi, a Gram-negative bacteria.

Similar but often less severe disease is caused bySalmonella serotypeparatyphiA.

Many genes are shared with E. coliand at least90% with S. typhimurium,

Polysaccharide capsule Vi: present in about 90% ofall freshly isolated S. typhiand has a protective

effect against the bactericidal action of the serum ofinfected patients.

The ratio of disease caused by S. typhito thatcaused by S. paratyphiis about 10 to

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Pathogenesis

Entry in GIT localisation in Gut associated

lymphoid tissue Lymphatic channel

thoracic duct circulation primary silent

bacteremia localisation in macrophages of

RES in spleen, liver, bone marrow

(incubation period 8-14 days) secondary

bacteremia

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Acute non-complicated

disease

Characterized by

Prolonged fever,

Disturbances of bowel functionHeadache, malaise and anorexia.

Bronchitic cough

Exanthem (rose spots), on the chest,abdomen and back.

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Complicated disease

10% of typhoid patients

GIT: occult blood in 10-20% of patients, and

malena in up to 3%. Intestinal perforation has also

been reported in up to 3% of hospitalized cases. CNS: Encephalopathy, Typhoid meningitis,

encephalomyelitis, Guillain-Barr syndrome, cranial

or peripheral neuritis and psychotic symptoms

Others: Hepatitis, myocarditis, pneumonia,

disseminated intravascular

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Diagnosis

Culture: blood, bone marrow, bile

Bone marrow aspirate culture is the goldstandard for the diagnosis of typhoid fever

Failure to isolate the organism (i) the limitations of laboratory media

(ii) the presence of antibiotics

(iii) the volume of the specimen cultured (iv) the time of collection, patients with a history of

fever for 7 to 10 days being more likely thanothers to have a positive blood culture.

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Widal Test

O antibodies appear on days 6-8 and H antibodies on days 10-12

Negative in up to 30% of culture-proven cases of typhoid fever

S. typhi shares O and H antigens with other Salmonellaserotypes and has cross-reacting epitopes with other

Enterobacteriacae, and this can lead to false-positive results.Such results may also occur in other clinical conditions, e.g.malaria, typhus, bacteraemia caused by other organisms, andcirrhosis

This is acceptable so long as the results are interpreted with care

in accordance with appropriate local cut-off values for thedetermination of positivity.

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New serological test

Specific antibodies usually only appear a

week after the onset of symptoms and signs.

This should kept in mind when a negative

serological test result is being interpreted.

New serological tests

IDL Tubex

Typhidot (better), high negative predictive value

Dipstick test,

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Typhoid epidemiology

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Treatment of uncomplicated

typhoid

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Treatment of severe typhoid

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Oral drugs

Ofloxacin: 15-20 mg / kg for 7-14 days

Azithromycin:8-10 mg/kg for 7 days

Cefixime: 20 mg /day for 7-14 days Chloramphenicol: 50-75 mg /kg/day for 14-21

days

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Fluoroquinolones

Optimal for the treatment of typhoid fever

Relatively inexpensive, well tolerated and more rapidly andreliably effective than the former first-line drugs, viz.chloramphenicol, ampicillin, amoxicillin and trimethoprim-

sulfamethoxazole. The majority of isolates are still sensitive.

Attain excellent tissue penetration, kill S. typhi in its intracellularstationary stage in monocytes/macrophages and achieve higheractive drug levels in the gall bladder than other drugs.

Rapid therapeutic response, i.e. clearance of fever andsymptoms in three to five days, and very low rates of post-treatment carriage.

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Chloramphenicol

The disadvantages of using chloramphenicol include

a relatively high rate of relapse (57%), long

treatment courses (14 days) and the frequent

development of a carrierstate in adults. The recommended dosage is 50 - 75 mg per kg per

day for 14 days divided into four doses per day, or

for at least five to seven days after defervescence.

Oral administration gives slightly greaterbioavailability than intramuscular (i.m.) or

intravenous (i.v.) administration of the succinate salt.

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Cephalosporins

Ceftriaxone: 50-75 mg per kg per day one or

two doses

Cefotaxime: 40-80 mg per kg per day in two

or three doses

Cefoperazone: 50-100 mg per kg per day

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Dexamethasone for CNS

complication

Should be immediately be treated with high-

dose intravenous dexamethasone in addition

to antimicrobials

Initial dose of 3 mg/kg by slow i.v. infusion

over 30 minutes

1 mg/kg 6 hourly for 2 days

Mortality can be reduced by some 80-90% in

these high-risk patients

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GI complication

Patients with intestinal haemorrhage need intensive care, monitoring and blood

transfusion. Intervention is not needed unless there is significant blood loss.

Surgical consultation for suspected intestinal perforation is indicated. Ifperforation is

confirmed, surgical repair should not be delayed longer than six hours.Metronidazole

and gentamicin or ceftriazone should be administered before and after surgery ifa

fluoroquinolone is not being used to treat leakage of intestinal bacteria into the

abdominal cavity. Early intervention is crucial, and mortality rates increase asthe delay

between perforation and surgery lengthens. Mortality rates vary between 10%and

32% (69).

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Relapse

5-20% of typhoid fever cases that have

apparently been treated successfully.

A relapse is heralded by the return of fever

soon after the completion of antibiotic

treatment. The clinical manifestation is

frequently milder than the initial illness.

Cultures should be obtained and standardtreatment should be administered.

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Vaccination

Vi polysaccharide, is given in a single dose

Protection begins seven days after injection,

maximum protection being reached 28 days after

injection when the highest antibody concentration isobtained.

Protective efficacy was 72% one and half years after

vaccination and was still 55% three years after a

single dose.

In Asian countries where Vi-negative strains have

been reported at the low average level of 3%.

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live oral vaccine Ty2la

three doses two days apart on an empty stomach.

Protection as from 10-14 days after the third dose.

> 5 years.

Protective efficacy of the enteric-coated capsule

formulation seven years after the last dose is still

62% in areas where the disease is endemic;

Antibiotics should be avoided for seven days beforeor after the immunization

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Antibiotic resistance

MDR is mediated by plasmid

Quinolone resistance is frequently mediated

by single point mutations in the quinolone-

resistancedetermining region of the gyrA

gene

Nalidixic acid resistant: MIC of

fluoroquinolones for these strains was 10times that for fully susceptible strains.

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The future of typhoid (2002

NEJM)

Cheap,Rapid and reliable serological test

Fluoroquinolone and cephalosporin resistant

case

Combination chemotherapy

New drugs

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Refrrence