internal medicine seminar (for students)

1. Typhoid fever
BALQEES MAJALI

2. INTRODUCTION
Typhoid fever (enteric fever) is characterized by severe systemic illness with
fever and abdominal pain.
The organism classically responsible for the enteric fever syndrome
is Salmonella enterica serotype Typhi (formerly S. typhi)
Other Salmonella serotypes, particularly S. enterica serotypes Paratyphi A, B,
or C, can cause a similar syndrome.
However, it is usually not clinically useful or possible to reliably predict the
causative organism based on clinical findings.

3. EPIDEMIOLOGY
 More common in children and young adults than in older
patients
 Most prevalent in impoverished areas that are overcrowded with
poor access to sanitation.
 South-central Asia, Southeast Asia, and southern Africa are
regions with high incidence of S. Typhi infection
 Indian subcontinent, sub-Saharan Africa and Latin America

4. MICROBIOLOGY
Salmonella enterica serotype
typhi
Salmonella enterica serotype
paratyphi
Nontyphoidal
salmonellae
• It is the classical organism
• Causes disease only in humans
• S.Paratyphi A , S.paratyphi B , S.paratyphi C , S. Choleraesuis
• Thought to cause milder illnesses
• E.g: S. enteritidis and S.typhimurium
• is often associated with underlying HIV infection

5. Modes of transmission
• Oral transmission via food or beverages handled by an often asymptomatic individual—a
• Hand-to-mouth transmission after using a contaminated toilet and neglecting hand hygiene
• Oral transmission via sewage-contaminated water or shellfish (especially in the developing
world)
S.Typhi
• Paratyphi is more commonly transmitted in food from street vendors
• Paratyphi is more common among newcomers to urban areas
S.Paratyphi

6. PATHOGENESIS
Source : human (case or carrier)
Factors affects possibility of infection :
-patient immunity , inoculum, acidity of the stmach
The organism goes to the pyres patches (terminal ileum) >
enteric lymph nodes > systemic circulation > bacteremia and
fever > reticuloendothelial system >liver > secretion in bile >
secretion in GIT

7. CLINICAL FEATURES
 Enteric fever is a febrile illness with onset of symptoms 5 to 21 days after
ingestion of the causative microorganism in contaminated food or
water. In general, lower inocula are associated with longer incubation
times
 The majority of patients with enteric fever present with abdominal pain,
fever, and chills.

8. Classical presentation
Classic reports described the characteristic stages of enteric
in untreated individuals
1st week
•fever and bacteremia -chills are typical-
•Relative bradycardia or pulse-temperature dissociation may be observed
•Constipation (in adults) , diarrhea and vomiting (in children)
2nd week
•abdominal pain , (diarrhea)
•rose spots (faint salmon-colored macules on the trunk and abdomen) , cough
•Splenomegaly
3rd week
•hepatosplenomegaly, intestinal bleeding
•perforation due to ileocecal lymphatic hyperplasia of the Peyer's patches may occur, together with secondary bacteremia and peritonitis.
•Septic shock or an altered level of consciousness may develop;
•Delirium
•Bone and joint infection is common in children with sickle cell anemia

9. Rose spots are small (1 to 5 mm), erythematous,
blanchable, nontender papules, which begin early during
the acute febrile period of typhoid fever. Crops of lesions
(10 to 20) appear at irregular intervals for approximately
10 to 14 days, typically distributed on the abdomen,
chest, and back. Rarely, vesicular or hemorrhagic lesions
appear. The lesions persist for two to three days.

10. Intestinal perforation
• occurs in the ileum during the third week of febrile illness and is
due to necrosis of the Peyer's patches in the antimesenteric bowel
wall
• Affected patients present with increasing abdominal pain,
distension, peritonitis, and sometimes secondary bacteremia
Neurological
• headache is a frequent symptom reported in 44 to 94 percent of
cases
• Patients with severe enteric fever may develop "typhoid
encephalopathy," with altered consciousness, delirium, and
confusion

11. Laboratory abnormalities
 Patients with enteric fever frequently have anemia and either leukopenia or
leukocytosis; leukopenia with left shift is typically seen in adults, while leukocytosis
is more common in children. If observed in the third week of illness, leukocytosis
should prompt suspicion of intestinal perforation.
 Abnormal liver function tests are frequently observed
 Cerebrospinal fluid studies are usually normal or reveal a mild pleocytosis
(<35 cells/mm3), even in patients with neuropsychiatric symptoms

12. Chronic carriage
 Chronic Salmonella carriage is defined as excretion of the organism in stool or urine >12 months
after acute infection.
 occurs more frequently in women and in patients with cholelithiasis or other biliary tract
abnormalities
 Chronic carriage in the urine is rare and almost always associated with an abnormality in the
urinary tract (eg, urolithiasis, prostatic hyperplasia) or concurrent bladder infection with
Schistosoma
 Chronic carriers represent an infectious risk to others, particularly in the setting of food
preparation. The story of "Typhoid Mary,“
 The S. Typhi carrier state may be an independent risk factor for carcinoma of the gallbladder as
well as other cancers

13. DIAGNOSIS
Culture
• Blood culture : +ve in 40-
80%
• Stool culture : +ve in 30-
• Bone marrow : the most
sensitive diagnostic modality
+ve in >90%
Serology (widal test)
• Anti O (surface
polysaccharide) antigens:
1/40
•
• Anti H (flagellar) antigens:
1/160
others
• (ELISA) for antibodies to the capsular
polysaccharide Vi antigen may be useful for
detection of carriers
• (PCR)-based diagnostics have had limited
sensitivity in most studies given the low
concentration of bacteria during bacteremia

14. TREATMENT
Severe complicated
• Empiric therapy with ceftriaxone (2g IV once or twice daily 10-14 days) , If not available, cefotaxime is a reasonable alternative (1
to 2 g IV every six or eight hours 10-14 days)
• Once symptoms improve, the patient can be transitioned to an oral agent, selected based on results of susceptibility testing, if
available
• Adjunctive corticosteroid is an additional consideration for patients with severe enteric fever.
Uncomplicated
• Fluoroquinolones (ciprofloxacin (Oral: 500 mg twice daily 7-10 days) or ofloxacin mg orally or IV twice daily) ) are the drugs of
choice for empiric therapy when infection is expected to be fluoroquinolone susceptible
• azithromycin,(1 g orally once then 500 mg orally daily OR 1 g orally once daily 5-7 days) when fluoroquinolones resistance is
suspected, if not available cefixime mg orally twice daily 10-14 days) is another alternative
• If multidrug resistance is not prevalent, trimethoprim-sulfamethoxazole, amoxicillin, and chloramphenicol (if available) are

15. Follow up
 Successful treatment in uncomplicated cases usually results in clinical improvement
within three to five days. In most clinical trials, the mean time to defervescence is four
to six days, so persistent fevers of this duration following treatment initiation does not
imply therapeutic failure. Patients should be subsequently monitored for or instructed
to report recurrent symptoms, which could reflect relapse.

16. Chronic carriage eradication
 Fluoroquinolone therapy (eg, ciprofloxacin 500 to 750 mg orally twice
daily or ofloxacin 400 mg orally twice daily) for four weeks is a
reasonable approach
 If eradication is not achieved but thought necessary from a public health
perspective, an additional prolonged antibiotic course and
cholecystectomy may be warranted

17. Vaccination
Live attenuated
• oral
• 3-4 capsules (1 capsule every 48h)
• At least 1 week before travel
Killed
• Subcutaneous
• 2 doses (1st dose 0.5ml , 2nd dose
1ml ) 1 month apart
• At least 2 weeks before travel

18. THANK YOU !