ENTERIC FEVER

Salmonella typhi, a Gram-negative bacteria.
Similar but often less severe disease is caused by Salmonella serotype paratyphi A.
Many genes are shared with E. coli and at least 90% with S. typhimurium,
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.
The ratio of disease caused by S. typhi to that caused by S. paratyphi is about 10 to 1
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
Acute non complicated disease:

Characterized by
Prolonged fever,
Disturbances of bowel function Headache, malaise and anorexia.
Bronchitic cough
Exanthem (rose spots), on the chest, abdomen and back.
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-Barré syndrome, cranial or peripheral neuritis and psychotic symptoms
Others: Hepatitis, myocarditis, pneumonia, disseminated intravascular
Diagnosis:
Culture: blood, bone marrow, bile
Bone marrow aspirate culture is the gold standard 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 than others to have a positive blood culture.
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 Salmonella serotypes 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, and cirrhosis
This is acceptable so long as the results are interpreted with care in accordance with appropriate local cut-off values for the determination of positivity.
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
Fluoroquinolones:
Optimal for the treatment of typhoid fever
Relatively inexpensive, well tolerated and more rapidly and reliably 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 intracellular stationary stage in monocytes/macrophages and achieve higher active drug levels in the gall bladder than other drugs.
Rapid therapeutic response, i.e. clearance of fever and symptoms in three to five days, and very low rates of post-treatment carriage.
Chloramphanicol:
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 greater bioavailability than intramuscular (i.m.) or intravenous (i.v.) administration of the succinate salt
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
Dexamethasone:
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
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 before or after the immunization
Antibiotic resistance:
MDR is mediated by plasmid
Quinolone resistance is frequently mediated by single point mutations in the quinolone-resistance–determining region of the gyrA gene
Nalidixic acid resistant: MIC of fluoroquinolones for these strains was 10 times that for fully susceptible strains.
The future of typhoid
Cheap,Rapid and reliable serological test
Fluoroquinolone and cephalosporin resistant case
Combination chemotherapy
New drugs