1. Clinical approach and differential diagnosis
2. Causes in adults or children
3. Diagnostic tests and interpretation
4. Treatment and warning signs
5. Exam-style short note

Clinical approach to acute febrile illness

1. Identify patients who are critically ill.
2. Find a localizing syndrome or source.
3. Use epidemiology and exposures to narrow the differential.
4. Order targeted tests before treatment when safe.
5. Treat immediately when sepsis or a time-sensitive infection is suspected.
6. Reassess frequently if no diagnosis is initially apparent.

1. Confirm fever and establish severity

• Measured temperature and illness duration
• Pulse, respiratory rate, blood pressure, oxygen saturation, mental status, capillary refill, urine output
• Hydration and glucose, where appropriate

• Altered mental state, seizures, coma, or focal neurologic deficit
• Neck stiffness, photophobia, petechial or purpuric rash
• Hypotension, cold peripheries, delayed capillary refill, oliguria, raised lactate, or marked tachycardia
• Severe breathlessness, hypoxemia, cyanosis
• Severe abdominal pain, persistent vomiting, gastrointestinal bleeding, jaundice
• Rapidly progressive rash, severe myalgia with toxicity, disproportionate limb pain, skin necrosis
• Severe dehydration or inability to take oral fluids
• High-risk host: pregnancy, infancy, older age/frailty, immunosuppression, cancer chemotherapy, advanced HIV, transplant, asplenia, severe renal/liver disease

2. Stabilize first if the patient is unwell

• Assess and support airway, breathing, and circulation.
• Give oxygen if hypoxemic.
• Obtain IV access, send appropriate cultures and urgent blood tests, ideally before antibiotics, provided this causes no material delay.
• Give IV fluids cautiously and reassess perfusion, lungs, and urine output.
• Start empiric antimicrobials promptly if septic shock, bacterial meningitis, neutropenic sepsis, or another serious bacterial infection is suspected.
• Seek source control where relevant, for example drainage of an abscess or treatment of obstructed infected urinary tract.

3. Take a focused, high-yield history

A. Characterize the illness

• Exact day and mode of onset: abrupt or gradual
• Fever pattern, rigors, chills, night sweats
• Headache, retro-orbital pain, rash, myalgia, arthralgia
• Cough, sore throat, coryza, dyspnea, chest pain
• Dysuria, flank pain, diarrhea, abdominal pain, vomiting
• Jaundice, dark urine, bleeding, confusion
• Severe headache, neck pain, altered behavior, seizures
• Weight loss or prolonged symptoms, which may shift consideration toward tuberculosis, HIV-related illness, malignancy, or inflammatory disease

B. Identify exposures and epidemiology

• Place of residence, season, local outbreaks, occupation
• Recent travel, including transit locations and dates
• Mosquito/tick/mite exposure, camping, jungle or rural exposure
• Freshwater or floodwater exposure, rodents, livestock, animal bites
• Sick contacts, congregate living, food and water source
• Sexual exposure, injection drug use, recent procedures
• Drugs, including recent antibiotics, antimalarials, anticonvulsants, and new medicines that can cause drug fever
• Vaccination history
• Immunosuppression, pregnancy, HIV status, diabetes, chronic organ disease

4. Perform a complete examination, not only a “fever exam”

5. Classify the presentation into a syndrome

• Respiratory syndrome: pneumonia, influenza/COVID-19 or other viral respiratory illness, tuberculosis in appropriate contexts.
• Urinary syndrome: pyelonephritis, prostatitis, urinary obstruction with infection.
• CNS syndrome: meningitis, encephalitis, cerebral malaria, brain abscess.
• Gastrointestinal/hepatobiliary syndrome: enteric fever, viral hepatitis, cholangitis, intra-abdominal sepsis.
• Rash or hemorrhagic syndrome: dengue or other arboviral illness, rickettsial disease, meningococcemia, measles/viral exanthem, leptospirosis, drug reaction.
• Undifferentiated fever: malaria, dengue, enteric fever, rickettsioses including scrub typhus, leptospirosis, acute HIV, viral illnesses, and early bacterial sepsis. The specific list depends on geography.
• Fever in returning traveler: malaria must be considered urgently, along with dengue, enteric fever, rickettsioses, leptospirosis, viral infections, and region-specific pathogens.

6. Order targeted initial tests

• CBC with differential and platelet count
• Renal function, electrolytes, liver tests, glucose
• Urinalysis and urine culture if urinary symptoms or no clear source
• Blood cultures, preferably before antibiotics in patients who are systemically unwell or admitted
• Chest radiograph if respiratory symptoms, hypoxemia, or unclear source
• Pregnancy test when relevant
• Lactate, blood gas, coagulation tests in suspected sepsis/shock or bleeding
• HIV testing where clinically indicated and with appropriate consent procedures

• Malaria rapid diagnostic test and/or peripheral smear in endemic areas, following relevant travel, or when compatible with the presentation. A negative malaria test should trigger active consideration of other diagnoses, not automatic antimalarial therapy.
• Dengue testing according to day of illness and local protocol.
• Influenza, SARS-CoV-2, or other respiratory viral testing if respiratory syndrome or outbreak context.
• Lumbar puncture after stabilization when meningitis/encephalitis is suspected and there is no contraindication or imaging requirement.
• Targeted PCR, serology, cultures, or imaging for suspected leptospirosis, rickettsioses, enteric fever, viral hepatitis, tuberculosis, or focal deep infection.

7. Start appropriate treatment, but avoid reflex empiric antibiotics

• Give fluids, antipyretics, antiemetics, analgesia, and monitoring as needed.
• Treat a confirmed or strongly suspected focal infection according to local guidelines.
• Use immediate empiric antibiotics for patients with sepsis, shock, meningitis, febrile neutropenia, clear bacterial focus with systemic illness, or other high-risk clinical situations.
• Do not prescribe antibiotics solely because the patient has nonspecific fever. In AFI, unnecessary empirical antibiotics can be both ineffective and harmful, and may obscure cultures or worsen antimicrobial resistance (review of AFI diagnostic challenges).
• Do not delay treatment for suspected meningitis, septic shock, or severe malaria while awaiting confirmatory results.

8. Reassess and safety-net

• Review vital signs, mental status, perfusion, urine output, and new symptoms.
• Re-examine for a rash, eschar, localizing chest signs, abdominal tenderness, neurologic signs, or joint infection.
• Review microbiology and imaging promptly; de-escalate or change treatment when results clarify the diagnosis.
• If stable without a diagnosis, give explicit return precautions: worsening weakness, confusion, breathlessness, bleeding, persistent vomiting, reduced urine, severe abdominal pain, or fever that persists or recurs.

Practical one-line algorithm