Typhoid Fever Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: This is a notifiable disease under the Prevention and Control of Infectious Diseases Act 1988. It's a key differential for any patient presenting with undifferentiated fever for more than five days, especially with a history of consuming food from questionable sources.
High-Yield Definition: Typhoid (or Enteric) fever is a systemic infection caused predominantly by Salmonella enterica serovar Typhi. It is transmitted via the feco-oral route. (Source: Malaysian CPG on Management of Typhoid Fever, 2nd Ed., 2020).
Clinical One-Liner: Basically, it's a nasty bacterial gut infection that goes systemic, causing prolonged high fever and potentially life-threatening complications if you miss it.
II. Etiology & Risk Factors
Etiology: Caused by gram-negative bacteria Salmonella enterica serovar Typhi (most common) and serovar Paratyphi A, B, and C.
Risk Factors (Local Context):
Consumption of contaminated food or water (common culprits: street food, untreated water, contaminated ice).
Poor personal hygiene (failure of handwashing).
Close contact with a known Typhoid patient or a chronic carrier.
Recent travel to other endemic areas.
III. Quick Pathophysiology
Forget the deep molecular stuff. Clinically, what you need to know is this: The bacteria is ingested, breaches the intestinal mucosa via Peyer's patches, and then disseminates via the bloodstream. It seeds in the reticuloendothelial system (liver, spleen, bone marrow), which is why you get hepatosplenomegaly. The prolonged bacteremia and release of endotoxin from the bacteria are what drive the high, sustained fever and systemic symptoms.
IV. Clinical Assessment
Red Flags & Immediate Actions:
Hypotension / Shock (SBP < 90 mmHg): Alert senior immediately, secure two large-bore IV cannulas, start fluid resuscitation with crystalloids.
Severe Abdominal Pain / Peritonism (guarding, rebound tenderness): Suspect intestinal perforation. Keep nil by mouth (NBM), alert senior and the on-call surgical team. This is a surgical emergency.
Altered Mental Status (delirium, confusion): Suspect typhoid encephalopathy. Check random blood sugar to rule out hypoglycemia, ensure airway is patent, and escalate to your senior.
Massive GI Bleeding (melena, hematochezia): Alert senior, start IV fluids, send urgent GXM and FBC, and consider a gastroenterology consult.
History:
Common (>50%): Insidious onset of fever (classically "step-ladder," but often just sustained high fever), headache, malaise, anorexia, myalgia.
Less Common (10-50%): Abdominal pain (often vague), constipation (more common in the first week), followed by diarrhea ("pea soup" stool, less common) in the second or third week, dry cough.
Pertinent Negatives: Ask about recent travel, sick contacts, and specific food intake in the last 1-3 weeks.
Physical Examination:
General: Febrile, may appear toxic or apathetic ("typhoid state").
Vitals: Sustained fever (39-40°C). Look for Faget's sign (relative bradycardia) - a pulse rate that is slower than expected for the degree of fever. This is a classic sign.
Abdomen: Soft, non-specific tenderness is common. Hepatosplenomegaly may be present in up to 50% of cases.
Skin: "Rose spots" (faint, salmon-coloured, blanching maculopapular rash on the trunk) are rare, transient, and very difficult to appreciate on our patients' skin tones. Don't rely on finding them.
Clinical Pearl: Don't hang your hat on the "step-ladder" fever or "pea soup" stools. In practice, many patients present with a non-specific sustained high fever. The relative bradycardia is a much more useful clinical clue when you see it.
V. Diagnostic Workflow
Differential Diagnosis:
Dengue Fever:
Points For: High fever, headache, myalgia.
Points Against: Dengue fever is usually shorter in duration (<7 days), associated with leukopenia, thrombocytopenia, and often has a rash.
How to Differentiate: Dengue combo test (NS1 Ag, IgM/IgG). FBC looking for thrombocytopenia.
Leptospirosis:
Points For: High fever, myalgia (especially calf tenderness), headache, conjunctival suffusion.
Points Against: Typhoid lacks the classic conjunctival suffusion and severe myalgia of Leptospirosis.
How to Differentiate: History of exposure to contaminated water/soil. Leptospirosis serology (MAT).
Malaria:
Points For: Fever, headache, splenomegaly.
Points Against: Malaria fevers are often cyclical, but can be continuous with P. falciparum.
How to Differentiate: Blood film for malaria parasites (BFMP).
Investigations Plan:
Bedside / Initial (First 15 Mins):
Vital signs (specifically check for relative bradycardia).
First-Line Labs & Imaging:
Blood Culture & Sensitivity (C&S): The gold standard for diagnosis. Crucially, this MUST be taken before starting antibiotics. Take at least two sets from different sites. Yield is highest in the first week of illness.
Full Blood Count (FBC): May show anemia, leukopenia, or a normal white cell count (a lack of leukocytosis in the face of high fever is suggestive).
Liver Function Test (LFT): Mild transaminitis is common.
Renal Profile (RP): To assess for dehydration and renal impairment.
Confirmatory / Gold Standard:
Blood Culture: This is the most important test.
Bone Marrow Aspirate & Culture: More sensitive than blood culture (>90%) and can remain positive even after a few days of antibiotics. However, it is invasive and reserved for difficult cases.
Widal Test / Typhidot: These are serological tests. They have very limited utility in endemic areas like Malaysia due to high baseline antibody levels from previous exposure. Do not use them to rule in or rule out acute Typhoid. The CPG specifically advises against relying on them.
VI. Staging & Severity Assessment
Classification is straightforward and clinically relevant.
Uncomplicated Typhoid Fever: The patient has a sustained fever and the associated constitutional symptoms, but no evidence of the major complications listed below. Management is primarily medical with antibiotics.
Complicated Typhoid Fever: Defined by the presence of one or more severe complications. These patients are very sick and require intensive monitoring, often in a high-dependency setting.
Gastrointestinal Bleeding
Intestinal Perforation
Typhoid Encephalopathy
Myocarditis, Shock
Impact on Management: The presence of any complication mandates inpatient admission, IV antibiotics, and consultation with the relevant specialty (e.g., Surgery, Gastroenterology).
VII. Management Plan
(Doses are for non-pregnant adults with normal renal function. Always double-check with your senior or formulary.)
Immediate Stabilisation (The ABCDE Plan):
Airway/Breathing: Administer high-flow oxygen if patient is hypoxic or in shock.
Circulation: Secure IV access. For hypotensive patients, give a fluid bolus (e.g., 250-500ml Normal Saline over 15-30 minutes) and monitor response.
Disability: Check GCS and blood glucose.
Exposure: Look for signs of bleeding or peritonism.
Take blood cultures before giving the first dose of antibiotics.
Definitive Treatment (The Ward Round Plan):
Antibiotics (First-Line):
For admitted patients / severe disease: IV Ceftriaxone 2g once daily (OD) for 7-14 days. This is the drug of choice in Malaysia due to high rates of fluoroquinolone resistance.
For stable, uncomplicated cases (suitable for oral therapy): Azithromycin 1g on Day 1, then 500mg OD for 6 days OR Cefixime 400mg twice daily (BD) for 14 days.
Fluoroquinolones (e.g., Ciprofloxacin): Use only if blood culture sensitivities confirm susceptibility. Do not use empirically.
Supportive Care:
Hydration: Oral or IV fluids to maintain adequate hydration.
Antipyretics: Paracetamol as needed for fever and discomfort.
Nutrition: Encourage oral intake as tolerated.
Public Health:
Notification: This is mandatory. Fill in the notification form (Borang Notis) and inform the district health office within 24 hours of suspicion.
Isolation: Practice contact precautions for hospitalized patients.
Long-Term & Discharge Plan:
Complete the full course of antibiotics.
Educate on personal hygiene, especially handwashing.
Advise on safe food and water practices.
Food handlers must have stool cultures to prove clearance before returning to work.
VIII. Complications
Short-Term (usually 2nd-3rd week):
Intestinal Perforation: Management: Immediate surgical consultation, IV fluids, broad-spectrum IV antibiotics.
GI Hemorrhage: Management: IV resuscitation, blood transfusion as needed, urgent endoscopy may be required.
Typhoid Encephalopathy: Management: Supportive care, rule out other causes, ensure airway protection.
Long-Term:
Chronic Carrier State: (Bacteria persist in the gallbladder). Management: Prolonged course of antibiotics (e.g., Ciprofloxacin for 4 weeks). Cholecystectomy may be considered.
Relapse: Management: Retreat with an appropriate antibiotic regimen based on initial culture sensitivity.
IX. Prognosis
With appropriate and timely antibiotic treatment, mortality is less than 1%.
If untreated, mortality can be as high as 10-30%.
Key Poor Prognostic Factors: Extremes of age, delayed initiation of treatment, antibiotic resistance, and the development of complications like perforation.
X. How to Present to Your Senior
"Dr, for review please. This is Patient [Name/Bed], a [Age] year old [man/woman] with no significant past medical history, who presented with a 9-day history of high-grade fever and headache.
On examination, he is febrile to 39°C but hemodynamically stable. His pulse is 80, which is relatively bradycardic for his temperature. The abdomen is soft with mild splenomegaly.
My main differential is enteric fever. Other differentials include Dengue and Leptospirosis.
I have already taken blood cultures, FBC, RP, LFT and sent a dengue combo test. I plan to start IV Ceftriaxone 2g OD as per the national CPG, pending the culture results. I would also like to notify this case to the health department."
XI. Summary & Further Reading
Top 3 Takeaways:
Think Typhoid in any patient with a fever lasting more than 5 days.
Blood culture before antibiotics is the single most important diagnostic step. Do not rely on serology.
IV Ceftriaxone is the empirical treatment of choice for admitted patients in Malaysia. Notify the case.
Key Resources:
Primary Guideline: Management of Typhoid Fever in Adults (Second Edition, 2020) - Ministry of Health Malaysia.
UpToDate: Search for "Typhoid fever".
Amboss: Search for "Enteric fever".
