In an 18‑year‑old male with a two‑day history of fever, chills, weakness, nausea, loss of appetite, lower back pain, mild pharyngeal erythema, negative malaria and typhoid rapid diagnostic tests, and pending urinalysis and full blood count, what additional investigations are indicated and what are the likely differential diagnoses and recommended management?

Acute Febrile Illness with Lower Back Pain in Young Adult

Immediate Clinical Action

Given the constellation of fever, chills, weakness, nausea, and lower back pain with negative malaria and typhoid tests, you should immediately obtain blood cultures (at least two sets), complete blood count with differential, comprehensive metabolic panel including liver enzymes, and consider empiric antibiotic therapy while awaiting results. 1

Additional Investigations Required

Essential Laboratory Tests

• Blood cultures (minimum 2 sets) before initiating any antibiotics, as sensitivity for enteric fever reaches 40-80% within the first week of symptoms 1
• Liver function tests and renal function (urea, creatinine, electrolytes) to assess for hepatorenal involvement and guide differential diagnosis 1
• Creatine kinase given the myalgia-like symptoms (weakness, lower back pain) 1
• C-reactive protein may aid in distinguishing bacterial superinfection, though its value in undifferentiated fever is limited 1
• Serum save for paired serology for arboviral infections, brucella, leptospirosis, and rickettsial diseases if initial workup is negative 1

Urinalysis Interpretation (Pending)

When the urinalysis returns, look specifically for:

• Proteinuria and hematuria which suggest leptospirosis 1
• Pyuria (>10,000 WBCs/mL in uncentrifuged urine) which indicates urinary tract infection, though absence of dysuria makes this less likely 2, 3
• Specific gravity to assess hydration status given the nausea and decreased oral intake 2

Full Blood Count Interpretation (Pending)

Critical findings to assess:

• Thrombocytopenia (<150,000/mL) is the most frequent laboratory finding in malaria (70-79% of cases) but also occurs in dengue, typhoid, and rickettsial diseases 1
• Leukopenia suggests viral infection (dengue, HIV), typhoid fever, or rickettsial disease 1
• Lymphopenia is common in viral infections and typhoid 1
• Leukocytosis with left shift may indicate bacterial pneumonia or secondary bacterial infection 1

Differential Diagnoses (Prioritized by Likelihood)

1. Enteric Fever (Typhoid/Paratyphoid)

Most likely given the clinical presentation. Fever, chills, weakness, nausea, and loss of appetite are classic for enteric fever, which presents with non-specific symptoms and can have normal or deranged laboratory values in almost any pattern 1. The slightly inflamed pharynx is a non-specific finding that does not exclude this diagnosis 1. Lower back pain may represent myalgia or early complications 1.

2. Leptospirosis

Consider if there is history of exposure to contaminated water, animal contact, or flooding 1. The combination of fever, myalgia (manifesting as lower back pain), nausea, and renal involvement would be characteristic 1. Blood cultures should be obtained within 5 days of symptom onset and transferred at room temperature to reference laboratory 1.

3. Rickettsial Disease (Scrub Typhus, Murine Typhus)

Though less common, rickettsial diseases present with fever, headache, myalgia, and nausea 1, 4, 5. Absence of rash does not exclude rickettsial disease, as less than 50% have rash in the first 3 days 4. Thrombocytopenia, leukopenia, and elevated liver enzymes would support this diagnosis 1, 4, 5.

4. Dengue or Chikungunya

These are common causes of acute undifferentiated febrile illness in endemic areas, with chikungunya showing incidence of 24.6% and dengue 11.6% in recent studies 6. Fever with myalgia is the most common presenting complaint 6. The absence of rash does not exclude these diagnoses early in the disease course 6.

5. Acute Viral Syndrome

Including acute HIV, EBV, or other viral infections that can present with fever, pharyngitis, and constitutional symptoms 1. HIV testing should be offered given the undifferentiated fever presentation 1.

6. Urinary Tract Infection/Pyelonephritis

Lower back pain raises concern for upper urinary tract involvement, though the absence of dysuria makes this less likely 1. The pending urinalysis will be critical 2.

7. Brucellosis

If there is history of contact with livestock or consumption of unpasteurized dairy products 1. Requires extended blood culture and serology 1.

Empiric Management Strategy

If Patient Appears Stable (Outpatient Management Possible)

• Await blood culture and complete laboratory results before initiating antibiotics if the patient is hemodynamically stable and can reliably take oral medications 1
• Arrange follow-up within 24-48 hours to review laboratory results and reassess clinical status 1
• Instruct patient to return immediately if symptoms worsen, confusion develops, or new symptoms appear 1

If Patient Appears Unstable or Has Red Flags

Initiate empiric therapy immediately if any of the following are present:

• Hemodynamic instability, confusion, or altered mental status 1
• Severe thrombocytopenia or coagulopathy on pending FBC 1, 4
• Strong clinical suspicion of enteric fever with unstable condition 1

Empiric antibiotic choice:

• Intravenous ceftriaxone is now preferred first-line for suspected enteric fever, as >70% of S. typhi and S. paratyphi isolates are fluoroquinolone-resistant 1
• Add doxycycline 100 mg twice daily if rickettsial disease cannot be excluded based on epidemiology, as delay in treatment leads to severe disease and death 1, 4, 5

If Rickettsial Disease is Suspected

Doxycycline 100 mg twice daily (oral or IV) should be initiated immediately without waiting for laboratory confirmation, as tetracycline-class antibiotics are the only effective treatment and early treatment (within first 3 days) is critical 1, 4, 5. Other antibiotics including penicillins, cephalosporins, and fluoroquinolones are ineffective against rickettsiae 5.

Critical Pitfalls to Avoid

• Do not exclude enteric fever based on negative rapid diagnostic test alone, as blood cultures have higher sensitivity and the Widal test lacks sensitivity and specificity 1
• Do not delay treatment for rickettsial disease while awaiting serology, as early serologic testing is often negative and treatment delay increases mortality 1, 4, 5
• Do not assume absence of tick bite excludes rickettsial disease, as up to 40% of patients report no tick exposure 4, 5
• Do not use fluoroquinolone disc testing alone to determine Salmonella sensitivity; the organism must also be sensitive to nalidixic acid 1
• Do not start empiric antibiotics in stable patients before obtaining blood cultures, as this can mask the underlying diagnosis 1, 7

Monitoring Parameters

• Repeat temperature, vital signs, and clinical assessment every 24 hours initially 1
• If empiric antibiotics are started, persistent fever beyond 48 hours should prompt consideration of alternative diagnoses 5
• Recheck complete blood count and metabolic panel if patient is hospitalized or deteriorates 1