Typhoid Fever: Diagnosis and XDR Typhoid Treatment

Typhoid (enteric) fever is a systemic infection caused by Salmonella enterica serovar Typhi, and its cousin paratyphoid fever by S. Paratyphi. It spreads through food and water contaminated with human faeces. It is common in Pakistan, where extensively drug-resistant (XDR) typhoid has spread since 2016, making correct antibiotic choice very important.

Transmission and risk factors

• Contaminated drinking water and food.
• Poor sanitation.
• Close contact with carriers. Some people become chronic carriers, often with organisms in the gallbladder.

Clinical features

The incubation period is about 1–2 weeks, though it can be shorter or longer.

• Fever that rises gradually over several days ("step-ladder" pattern) and becomes sustained.
• Headache, malaise and loss of appetite.
• Abdominal pain.
• Constipation, or diarrhoea, especially in children.
• A dry cough.
• Possible signs:
  • relative bradycardia (pulse slower than expected for the fever)
  • a coated tongue
  • tender abdomen
  • enlarged liver and spleen
  • "rose spots" on the trunk (uncommon)

Complications (usually in the 2nd–3rd week)

• Intestinal perforation and GI bleeding, from ulceration of Peyer's patches in the ileum.
• Encephalopathy.
• Myocarditis.
• Hepatitis.
• Shock.
• Relapse.
• The chronic carrier state.

Diagnosis

• Blood culture is the main test, ideally before antibiotics. Its yield is highest in the first week.
• Bone marrow culture is the most sensitive, even after antibiotics, but rarely done.
• Stool and urine cultures may be positive later in the illness.
• The Widal test has poor sensitivity and specificity and should not be relied on for diagnosis.
• Full blood count: white cells are often normal or low. Liver enzymes are often mildly raised.

Treatment

Choose antibiotics according to local resistance patterns and national guidelines, and adjust to culture sensitivities.

• In Pakistan, because of XDR typhoid (resistant to chloramphenicol, ampicillin, co-trimoxazole, fluoroquinolones and third-generation cephalosporins):
  • azithromycin for uncomplicated typhoid
  • a carbapenem (for example meropenem), often with azithromycin, for complicated or severe typhoid
• Where strains are susceptible, ceftriaxone or other agents may be used.
• Supportive care: fluids, antipyretics and nutrition.
• Intestinal perforation needs urgent surgery.
• Dexamethasone has a role in selected severe cases, such as those with encephalopathy or shock.

Avoid unnecessary antibiotic use for every fever. Misuse drives resistance.

Prevention

• Typhoid conjugate vaccine (TCV) — included in Pakistan's routine immunisation programme.
• Safe drinking water (boiled or treated).
• Hand washing.
• Safe food handling.
• Improved sanitation.

Exam pearls

• Fever with relative bradycardia and abdominal symptoms: think typhoid.
• Blood culture is the investigation of choice in the first week. Do not rely on the Widal test.
• Sudden abdominal pain and rigidity in the 2nd–3rd week means perforation.

See also Dengue Fever, Malaria and the Medicine Companion.

Test yourself

5 exam-style single-best-answer questions. Choose your answer, then tap “Show answer”.

1. Investigation of choice in the first week of suspected typhoid:

   1. Stool culture
   2. Blood culture
   3. Urine culture
   4. Widal test
   5. Chest X-ray
   Show answer

   Answer: B. Blood culture
   Blood culture has the highest yield early; the Widal test is unreliable.

2. XDR typhoid in Pakistan is resistant to which antibiotics?

   1. Only meropenem
   2. Only amoxicillin
   3. Azithromycin and carbapenems
   4. Fluoroquinolones and third-generation cephalosporins (and older first-line drugs)
   5. None
   Show answer

   Answer: D. Fluoroquinolones and third-generation cephalosporins (and older first-line drugs)
   XDR strains resist chloramphenicol, ampicillin, co-trimoxazole, fluoroquinolones and ceftriaxone.

3. Suitable oral antibiotic for uncomplicated XDR typhoid:

   1. Ceftriaxone
   2. Ciprofloxacin
   3. Azithromycin
   4. Amoxicillin
   5. Co-trimoxazole
   Show answer

   Answer: C. Azithromycin
   Azithromycin is used for uncomplicated XDR typhoid; carbapenems for complicated disease.

4. Sudden abdominal pain and rigidity in the third week of typhoid suggests:

   1. Gastritis
   2. Hepatitis
   3. Relapse
   4. Constipation
   5. Intestinal perforation
   Show answer

   Answer: E. Intestinal perforation
   Ileal ulcers over Peyer's patches can perforate in the 2nd–3rd week; this needs urgent surgery.

5. Which classic sign is seen in typhoid?

   1. Kernig's sign
   2. Relative bradycardia
   3. Butterfly rash
   4. Clubbing
   5. Koplik spots
   Show answer

   Answer: B. Relative bradycardia
   A pulse slower than expected for the fever (relative bradycardia) is classic.

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Disclaimer

For education and exam preparation only. This is not medical advice and must not be used to diagnose or treat patients. Always follow current clinical guidelines and the advice of qualified senior colleagues.