What is the likely diagnosis and recommended workup for a patient with impaired renal function, anemia, and thrombocytopenia, presenting with nausea and vomiting for 7 days after recent travel to Kenya, with a negative malaria test?

Likely Diagnosis: Severe Malaria Despite Negative Initial Test

Despite the negative malaria test, this patient most likely has severe Plasmodium falciparum malaria and requires immediate repeat malaria testing with thick and thin blood films, plus consideration of empiric antimalarial treatment given the high mortality risk. 1

Clinical Reasoning

The constellation of findings strongly suggests severe malaria:

• Travel to Kenya (sub-Saharan Africa) where 28-47% of febrile illness in returning travelers is malaria 1
• Acute kidney injury (creatinine 3.09 → 2.59) is a hallmark of severe malaria 2, 3
• Thrombocytopenia (148,000/mL) has a likelihood ratio of 2.9-11 for malaria diagnosis 1, 4
• Anemia (Hgb 9.4) developing acutely 1
• Leukopenia (WBC 3.52) is consistent with malaria 1, 4
• 7-day symptom duration fits the typical presentation window 1

Why the Negative Malaria Test May Be Wrong

• Single negative test is insufficient - three thick films/rapid diagnostic tests over 72 hours are required to exclude malaria with confidence 1
• Sensitivity limitations exist, particularly if parasitemia is low or testing technique suboptimal 1
• Timing matters - parasitemia can fluctuate 1

Immediate Workup Required

Priority 1: Repeat Malaria Testing

• Three thick and thin blood films over 72 hours (gold standard) 1
• Rapid diagnostic test (RDT) if thick film expertise unavailable 1
• Send positive films to reference laboratory for confirmation and speciation 1

Priority 2: Assess for Severe Malaria Criteria

Check for additional severe malaria features 1:

• Metabolic acidosis (base deficit >8 mmol/L, lactate >5 mmol/L) 1
• Hypoglycemia (blood glucose <3 mmol/L) 1
• Altered consciousness (Glasgow Coma Scale assessment) 1
• Hyperbilirubinemia (likelihood ratio 5.3-7.3 for malaria) 1
• Respiratory distress or hypoxia 1

Priority 3: Alternative Diagnoses to Consider

Leptospirosis is the second most likely diagnosis given:

• Acute renal failure with thrombocytopenia 5
• Potential jungle/water exposure in Kenya 5
• Workup: Leptospira serology, urinalysis for proteinuria and hematuria 1, 5

Enteric fever (typhoid) considerations:

• Splenomegaly has likelihood ratio 5.9-10 for enteric fever 1
• Workup: Two sets of blood cultures before antibiotics 1
• Sensitivity up to 80% in typhoid 1

Dengue is less likely (more common from Asia, not Africa) but check for:

• Leucopenia and thrombocytopenia (likelihood ratio 6 and 5 respectively) 1
• Skin rash 1

Priority 4: Essential Laboratory Tests

• Complete blood count with differential 1, 4
• Comprehensive metabolic panel including glucose 1
• Liver function tests (ALT, bilirubin, LDH) 1
• Blood gas analysis (lactate, bicarbonate, base deficit) 1
• Urinalysis (proteinuria/hematuria suggests leptospirosis) 1, 5
• Two sets of blood cultures 1
• Serum save for arboviral/leptospira serology 1

Management Approach

If Repeat Malaria Testing is Positive

For severe malaria (renal failure qualifies as severe):

• Intravenous artesunate is the treatment of choice 1
• Admit to intensive care unit 1
• Monitor parasitemia every 12 hours until <1%, then every 24 hours 1
• Daily monitoring of renal function, glucose, blood gas 1
• Fluid management: Cautious volume resuscitation to avoid pulmonary edema 1
• Urine output <1 ml/kg/hour indicates inadequate renal perfusion 1
• Monitor for delayed hemolysis on days 7,14,21,28 1

If Malaria Remains Negative After Serial Testing

Consider empiric treatment for leptospirosis:

• High mortality when complicated by acute renal failure 5
• Early antibiotic treatment is critical 5
• Supportive care with fluid management 5

Critical Pitfalls to Avoid

• Never rely on single negative malaria test in a patient from endemic area with compatible syndrome 1
• Avoid fluid overload - can precipitate pulmonary edema and ARDS in severe malaria 1
• Avoid nephrotoxic drugs (ACE inhibitors, NSAIDs, aminoglycosides, cephalosporins) 2
• Monitor glucose closely - hypoglycemia is common and increases mortality 1
• Don't delay dialysis if indicated - early renal replacement therapy improves outcomes in severe malaria with renal failure 2, 3
• Renal failure in non-immune adults with P. falciparum occurs in 29-94% of severe cases 3