What is the diagnosis, investigation, and treatment for a patient presenting with abdominal fever, headache, joint pains, weakness, and lower back pain, with a negative malaria test result?

Diagnosis: Enteric Fever (Typhoid/Paratyphoid) Until Proven Otherwise

Despite the negative malaria test, this patient's constellation of fever, headache, joint pains, weakness, and lower back pain most likely represents enteric fever (typhoid or paratyphoid), which is the commonest serious tropical disease requiring treatment after malaria has been excluded, particularly if there is recent travel to Asia. 1

Differential Diagnosis Approach

Primary Consideration: Enteric Fever

• Enteric fever presents with fever, headache, myalgia, arthralgia, malaise, and abdominal pain—matching this patient's presentation exactly 1
• After excluding malaria, enteric fever is the most common serious tropical disease requiring treatment in travelers returning from Asia 1
• The incubation period is 7-18 days (range: 3-60 days), so symptoms typically appear after return from travel 1

Other Important Differentials to Consider

• Dengue fever: Presents with fever, headache, back pain, and joint pains ("breakbone fever"), but typically includes more prominent myalgias 1
• Brucellosis: Consider if contact with livestock or unpasteurized milk, presents with fever, back pain, and joint pains 1
• Leptospirosis: Presents with fever, headache, myalgia, and back pain, particularly if exposure to contaminated water 1
• Rickettsial infections: Consider if tick exposure in endemic areas, presents with fever, headache, and myalgia 1

Critical Investigations

Immediate Priority Tests

• Blood cultures (at least 2 sets): Up to 80% sensitive in the first week for enteric fever 1
• Repeat malaria testing: Three thick and thin blood films over 72 hours are necessary to definitively exclude malaria, as a single negative test is insufficient 2, 3
• Complete blood count: Look for thrombocytopenia (occurs in 70-79% of malaria cases) and leukopenia (common in enteric fever) 2
• Liver function tests: Check for hyperbilirubinemia (likelihood ratio 7.3 for malaria) and transaminitis 3

Additional Diagnostic Tests Based on Travel History

• Dengue PCR or IgM: If symptoms within 1-8 days of onset and travel to dengue-endemic areas 1
• Brucella serology and extended blood cultures: If livestock contact or unpasteurized dairy consumption 1
• Leptospirosis testing: CSF and blood cultures if exposure to contaminated water <5 days prior 1

Essential Clinical Information Required

• Detailed travel history: Specific countries visited, dates of travel, and dates of symptom onset must be documented 1
• Exposure history: Contact with animals, unpasteurized dairy, freshwater exposure, mosquito bites 1
• Vaccination history: Typhoid vaccination status 1

Treatment Recommendations

Empirical Treatment for Enteric Fever

If the patient is clinically unstable, start empirical treatment with ceftriaxone immediately while awaiting blood culture results. 1

• First-line empirical therapy: Ceftriaxone 2g IV daily for 14 days 1
• Alternative if travel from sub-Saharan Africa: Ciprofloxacin 500mg PO twice daily remains an option 1
• Oral follow-on therapy: If confirmed sensitive, switch to ciprofloxacin; if resistant, use azithromycin empirically 1
• Treatment duration: 2 weeks total 1

Supportive Care

• Fluid resuscitation and electrolyte management 4
• Antipyretics (avoid aspirin if dengue is in the differential) 1
• Monitor for complications: intestinal perforation, hepatitis, myocarditis 1

Critical Pitfalls to Avoid

Diagnostic Errors

• Do not rely on a single negative malaria test: Parasitemia can be intermittent, particularly early in infection; three negative blood films at 12-hour intervals are required to exclude malaria 2, 3
• Do not delay blood cultures: They must be drawn before antibiotics are started, as sensitivity drops dramatically after antibiotic administration 1
• Do not assume "viral syndrome": This nonspecific presentation can represent life-threatening infections including malaria, enteric fever, or dengue 5, 6

Treatment Errors

• Do not delay empirical antibiotics if clinically unstable: Delayed treatment of enteric fever increases morbidity 1
• Do not use fluoroquinolones empirically if travel from South/Southeast Asia: High rates of resistance require ceftriaxone or azithromycin 1

Disposition

• Admit for inpatient treatment and monitoring: Patients with suspected enteric fever or undiagnosed fever after tropical travel require hospitalization for definitive diagnosis and treatment 4
• Consult infectious diseases: Specialist input is essential for complex tropical infections 1