What are the potential causes and treatment options for a patient presenting with cough, chills, diarrhea, and fever after returning from a trip 2 weeks ago?

Fever, Cough, Chills, and Diarrhea After Recent Travel

This patient requires immediate malaria exclusion with three daily blood films, followed by empiric azithromycin therapy while awaiting diagnostic results, given the high-risk constellation of fever with gastrointestinal and respiratory symptoms in a returned traveler. 1, 2

Immediate Life-Threatening Diagnoses to Exclude

Every febrile illness after tropical travel must be considered malaria until excluded, even when diarrhea and respiratory symptoms are present. 2, 3 Malaria represents 22.2% of all febrile illness in returning travelers and 67.7% of tropical diseases. 2 The presence of gastrointestinal or respiratory symptoms does not rule out malaria—this is a critical pitfall to avoid. 3

• Obtain three daily blood films immediately to exclude malaria, regardless of other symptoms 1, 2
• Enteric fever (typhoid/paratyphoid) accounts for 2.3% of febrile returning travelers and characteristically presents with fever, headache, and abdominal pain—diarrhea is actually uncommon but can occur 2
• Viral hemorrhagic fever risk assessment is mandatory for all febrile returned travelers 1

Most Likely Diagnosis: Invasive Travelers' Diarrhea

The combination of fever with diarrhea strongly suggests invasive bacterial disease or amoebic dysentery. 1, 2 Acute traveler's diarrhea is the most common diagnosis in those returning from developing countries (222 cases per 1000 ill returned travelers), with fever self-reported in up to 30% of cases. 1

Common Bacterial Pathogens:

• E. coli (enterotoxigenic and enteroaggregative species) 1
• Campylobacter, Salmonella, and Shigella are common invasive causes 1, 2
• Amoebic colitis can cause bloody diarrhea with more indolent onset 1

Respiratory Component Considerations:

• Enteric fever and malaria may have respiratory features as part of their presentation 1
• If from Southeast Asia with respiratory symptoms and upper zone infiltrates, consider melioidosis (Burkholderia pseudomallei) 1
• Febrile patients with cough and peripheral eosinophilia should be investigated for Loeffler's syndrome, Katayama syndrome, or tropical pulmonary eosinophilia 1

Recommended Diagnostic Workup

Immediate Testing (Within Hours):

• Three daily blood films for malaria (mandatory) 1, 2
• Blood cultures for enteric fever 2
• Stool culture for Salmonella, Shigella, Campylobacter, and Yersinia 2
• Complete blood count with differential 2
• Chest X-ray given respiratory symptoms 1

Additional Testing if Initial Workup Negative:

• Wet preparation of fresh stool (within 15-30 minutes) looking for amoebic trophozoites 1
• If diarrhea persists ≥14 days, test for Giardia, Cryptosporidium, Cyclospora, and Entamoeba histolytica 2
• Molecular testing aimed at broad range of pathogens if rapid results needed or non-molecular tests fail 1

Empiric Treatment Recommendation

Start azithromycin immediately while awaiting diagnostic results, given the combination of fever with significant diarrhea suggesting invasive bacterial disease. 1, 4

Preferred Regimen:

• Azithromycin 1 gram single dose OR 500 mg daily for 3 days 1, 4, 5
• This is the preferred first-line agent for severe travelers' diarrhea, particularly for dysentery 1, 4
• Single-dose regimens are effective and improve compliance 1, 4

Alternative Regimens (Less Preferred):

• Cephalosporins or fluoroquinolones are effective for most cases of travelers' diarrhea 1
• However, fluoroquinolone resistance exceeds 85% for Campylobacter in Southeast Asia, making azithromycin clearly superior in this region 4
• If fluoroquinolones used, avoid in suspected invasive disease from Asia 2
• Macrolides should be considered for quinolone-resistant Campylobacter isolates from Asia 1

If Amoebic Dysentery Suspected:

• Tinidazole or metronidazole are effective 1

Symptomatic Management:

• Loperamide should NOT be used when fever or bloody diarrhea is present 4, 5
• Ensure adequate hydration with oral rehydration solutions 4, 5

Critical Infection Control Measures

This patient requires source isolation (side room, gloves, apron) as travelers with respiratory illness, infectious diarrhea, or pyrexia of unknown origin require isolation per local hospital guidelines. 1

Laboratory Safety:

• Warn laboratory staff if enteric fever, brucella, Q fever, melioidosis, or viral hemorrhagic fevers are being considered, as these require upgraded infection control procedures 1

Statutory Notification:

• Notify local health protection unit if enteric fever, dysentery (bacterial or amoebic), malaria, or other notifiable diseases are suspected or confirmed 1

When to Escalate Care

Seek immediate infectious disease consultation if:

• Symptoms do not improve within 24-48 hours despite empiric treatment 4, 2
• Bloody diarrhea develops 2, 5
• High fever with shaking chills occurs 4
• Severe dehydration is present 4
• Any positive malaria films 2

Common Pitfalls to Avoid

• Never assume simple travelers' diarrhea when fever is present—this constellation demands broader evaluation for invasive pathogens and tropical diseases 2
• Do not delay malaria testing—even one episode of diarrhea with fever requires malaria exclusion 2, 3
• Assess hydration status carefully, as volume depletion is a frequently identified risk factor for diarrhea-related deaths 2
• Remember that patients returning from tropical areas might suffer from banal infections such as pneumonia, urinary tract infections, or cholangitis as well 3
• Do not use loperamide when fever or bloody diarrhea is present, as this can worsen invasive disease 4, 5