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Dr Rajesh Kumar
MD (PGI), DM (Neonatology)
PGI, Chandigarh, India
Rani Children Hospital, Ranchi
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þ Salmonella typhi, a Gram-negative bacteria.
þ imilar but often less severe disease is caused by
Salmonella serotype paratyphi A.
þ Many genes are shared with Œ coli and at least
90% with S. typhimurium,
þ Polysaccharide capsule Vi: present in about 90% of
all freshly isolated S typhi and has a protective
effect against the bactericidal action of the serum of
infected patients.
þ |he ratio of disease caused by S typhi to that
caused by S paratyphi is about 10 to

 
þ Œntry in GI| - localisation in Gut associated
lymphoid tissue - Lymphatic channel -
thoracic duct - circulation - primary silent
bacteremia - localisation in macrophages of
RΠin spleen, liver, bone marrow
(incubation period 8-14 days) - secondary
bacteremia
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Characterized by
Prolonged fever,
Disturbances of bowel function
Headache, malaise and anorexia.
Bronchitic cough
Œxanthem (rose spots), on the chest,
abdomen and back.
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þ 10% of typhoid patients
þ GI|: 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.
þ CN: Œncephalopathy, |yphoid meningitis,
encephalomyelitis, Guillain-Barré syndrome, cranial
or peripheral neuritis and psychotic symptoms
þ Others: Hepatitis, myocarditis, pneumonia,
disseminated intravascular
 
þ Culture: blood, bone marrow, bile
þ Bone marrow aspirate culture is the gold
standard for the diagnosis of typhoid fever
þ Failure to isolate the organism
þ (i) the limitations of laboratory media
þ (ii) the presence of antibiotics
þ (iii) the volume of the specimen cultured
þ (iv) the time of collection, patients with a history of
fever for 7 to 10 days being more likely than
others to have a positive blood culture.
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þ O antibodies appear on days 6-8 and H antibodies on days 10-12
þ Negative in up to 30% of culture-proven cases of typhoid fever
þ . typhi shares O and H antigens with other almonella
serotypes and has cross-reacting epitopes with other
Œnterobacteriacae, and this can lead to false-positive results.
uch results may also occur in other clinical conditions, e.g.
malaria, typhus, bacteraemia caused by other organisms, and
cirrhosis
þ |his is acceptable so long as the results are interpreted with care
in accordance with appropriate local cut-off values for the
determination of positivity.
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þ pecific antibodies usually only appear a
week after the onset of symptoms and signs.
|his should kept in mind when a negative
serological test result is being interpreted.
þ New serological tests
þ IDL |ubex
þ |yphidot (better), high negative predictive value
þ Dipstick test,
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þ Ofloxacin: 15-20 mg / kg for 7-14 days
þ Azithromycin:8-10 mg/kg for 7 days
þ Cefixime: 20 mg /day for 7-14 days
þ Chloramphenicol: 50-75 mg /kg/day for 14-21
days
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þ Optimal for the treatment of typhoid fever
þ Relatively inexpensive, well tolerated and more rapidly and
reliably effective than the former first-line drugs, viz.
chloramphenicol, ampicillin, amoxicillin and trimethoprim-
sulfamethoxazole.
þ |he majority of isolates are still sensitive.
þ Attain excellent tissue penetration, kill . typhi in its intracellular
stationary stage in monocytes/macrophages and achieve higher
active drug levels in the gall bladder than other drugs.
þ Rapid therapeutic response, i.e. clearance of fever and
symptoms in three to five days, and very low rates of post-
treatment carriage.
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þ |he 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.
þ |he 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.
þ Oral administration gives slightly greater
bioavailability than intramuscular (i.m.) or
intravenous (i.v.) administration of the succinate salt.
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þ Ceftriaxone: 50-75 mg per kg per day one or
two doses
þ Cefotaxime: 40-80 mg per kg per day in two
or three doses
þ Cefoperazone: 50-100 mg per kg per day
 
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þ hould be immediately be treated with high-
dose intravenous dexamethasone in addition
to antimicrobials
þ Initial dose of 3 mg/kg by slow i.v. infusion
over 30 minutes
þ 1 mg/kg 6 hourly for 2 days
þ Mortality can be reduced by some 80-90% in
these high-risk patients
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þ Patients with intestinal haemorrhage need intensive care, monitoring and blood
þ transfusion. Intervention is not needed unless there is significant blood loss.
þ urgical consultation for suspected intestinal perforation is indicated. If
perforation is
þ confirmed, surgical repair should not be delayed longer than six hours.
Metronidazole
þ and gentamicin or ceftriazone should be administered before and after surgery if
a
þ fluoroquinolone is not being used to treat leakage of intestinal bacteria into the
þ abdominal cavity. Œarly intervention is crucial, and mortality rates increase as
the delay
þ between perforation and surgery lengthens. Mortality rates vary between 10%
and
þ 32% (69).
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þ 5-20% of typhoid fever cases that have
apparently been treated successfully.
þ A relapse is heralded by the return of fever
soon after the completion of antibiotic
treatment. |he clinical manifestation is
frequently milder than the initial illness.
Cultures should be obtained and standard
treatment should be administered.
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þ Vi polysaccharide, is given in a single dose
þ Protection begins seven days after injection,
þ maximum protection being reached 28 days after
injection when the highest antibody concentration is
obtained.
þ Protective efficacy was 72% one and half years after
vaccination and was still 55% three years after a
single dose.
þ In Asian countries where Vi-negative strains have
been reported at the low average level of 3%.
 
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þ three doses two days apart on an empty stomach.
þ Protection as from 10-14 days after the third dose.
þ > 5 years.
þ Protective efficacy of the enteric-coated capsule
formulation seven years after the last dose is still
þ 62% in areas where the disease is endemic;
þ Antibiotics should be avoided for seven days before
or after the immunization
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þ MDR is mediated by plasmid
þ Quinolone resistance is frequently mediated
by single point mutations in the quinolone-
resistance±determining region of the =yrA
gene
þ Nalidixic acid resistant: MIC of
fluoroquinolones for these strains was 10
times that for fully susceptible strains.
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þ Cheap,Rapid and reliable serological test
þ Fluoroquinolone and cephalosporin resistant
case
þ Combination chemotherapy
þ New drugs
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