Infections in the returning traveller, such as dengue fever, malaria, and parasitic infections
Description
- Fever in a returned traveller is malaria until excluded - the only common imported infection that kills within days
- Most imported fever falls into four buckets:
- Malaria (~20-30%), dengue and other arboviruses, enteric fever (typhoid/paratyphoid), traveller's diarrhoea / gastroenteritis
- Plus the ordinary: respiratory infection, UTI, influenza, COVID - most returned travellers have a cosmopolitan infection**
Incubation period narrows the differential more than geography does
| Incubation | Consider |
|---|---|
| <10 days | Dengue, chikungunya, Zika, enteric bacterial diarrhoea, respiratory viruses, rickettsia, leptospirosis, viral haemorrhagic fever, meningococcaemia |
| 10-21 days | Malaria, enteric fever, leptospirosis, rickettsia, brucellosis, Q fever, acute HIV, viral haemorrhagic fever |
| >21 days | *Malaria (especially P. vivax/ovale)*, TB, viral hepatitis, amoebic liver abscess, visceral leishmaniasis, schistosomiasis, HIV, filariasis |
- *Dengue does not incubate longer than 14 days - fever starting >2 weeks after return is not dengue*
Epidemiology
- ~2/3 of fevers in returned travellers are from tropical destinations; sub-Saharan Africa -> malaria; South-East Asia -> dengue
- Falciparum malaria dominates African travel; vivax dominates Asia, PNG, the Pacific and South America
- Visiting friends and relatives (VFR) travellers are the highest-risk group - long stays, rural areas, low chemoprophylaxis uptake, false confidence in childhood immunity
- Dengue: ~400 million infections/year; *locally acquired dengue occurs in north Queensland when an Aedes aegypti population and a viraemic traveller coincide*
- Japanese encephalitis is now locally acquired in south-eastern Australia (from 2022) - not only an imported disease
Aetiopathogenesis
Malaria
- **Plasmodium falciparum (severe, no dormant liver stage), P. vivax/P. ovale (hypnozoites -> relapse), P. malariae, P. knowlesi (Borneo, can be severe)**
- Anopheles mosquito, biting dusk to dawn -> liver -> erythrocytic cycle
- Falciparum: cytoadherence and rosetting -> microvascular sequestration -> cerebral malaria, ARDS, AKI, lactic acidosis
- Partial immunity is lost within 1-2 years of leaving an endemic area
Dengue
- Flavivirus, 4 serotypes, transmitted by **Aedes aegypti (and Ae. albopictus) - a DAYTIME biter* (so bed nets do not protect*)
- Infection gives lifelong immunity to that serotype only
- **Antibody-dependent enhancement: a SECOND infection with a different serotype carries the highest risk of severe dengue** - non-neutralising antibody enhances viral uptake
- Plasma leakage from capillary endothelial dysfunction -> haemoconcentration, effusions, shock
Enteric fever
- **Salmonella Typhi/Paratyphi, faecal-oral, Indian subcontinent predominates; rising XDR** typhoid from Pakistan
- Bacteraemic illness, not diarrhoeal - constipation is as common as diarrhoea
Other
- Rickettsia (scrub typhus, African tick typhus) - eschar + rash
- Leptospirosis - freshwater exposure, conjunctival suffusion, jaundice with AKI
- Chikungunya - severe prolonged arthralgia; Zika - rash, conjunctivitis, teratogenic
- Schistosomiasis (Katayama fever), amoebic liver abscess, acute HIV, measles, mpox
Diagnosis
A. The travel history that matters
- Exact countries, rural vs urban, dates of travel and of symptom onset (for incubation period)
- Chemoprophylaxis - which drug, adherence, and completion ("I took doxycycline" but stopped at the airport = unprotected)
- Pre-travel vaccinations
- Exposures: mosquito bites, freshwater swimming (schistosomiasis, leptospirosis), unpasteurised dairy (brucellosis), undercooked food, sexual contact, animal or bat contact, tattoos/piercings/medical care, caves, farms, sick contacts
- Occupational and healthcare exposure abroad (MDRO colonisation)
B. Red flags demanding immediate isolation and public health involvement
- *Viral haemorrhagic fever risk: fever within 21 days of return from a VHF-endemic area with* exposure to blood/body fluids, healthcare settings, bushmeat or funerals
- Isolate, do NOT take blood until discussed, notify public health immediately
- Measles - fever, coryza, conjunctivitis, Koplik spots, rash: negative-pressure isolation
- Meningococcaemia, mpox, respiratory illness with an emerging pathogen
C. Investigations - in everyone with fever after tropical travel
- *Malaria thick and thin films + rapid antigen test*
- *Three negative sets 12-24 h apart are needed to exclude malaria* - a single negative film does not
- Thick film = detection and parasite density; thin film = species and percentage parasitaemia
- Blood cultures x2 (enteric fever), FBE with film, UEC, LFT, CRP, glucose, lactate, coagulation, urinalysis
- Dengue: NS1 antigen (days 1-5 - the acute test), dengue IgM/IgG (from day 5); cross-reacts with other flaviviruses
- Stool culture, ova/cysts/parasites and PCR panel if diarrhoea; HIV serology in everyone
- CXR; serology for rickettsia, leptospirosis, Q fever, brucellosis, schistosomiasis as directed by exposure
- Ultrasound/CT abdomen for amoebic liver abscess if RUQ pain
D. Clues from the blood picture
| Finding | Suggests |
|---|---|
| Thrombocytopenia | *Malaria, dengue* - the single most useful abnormality |
| Thrombocytopenia + raised haematocrit | Severe dengue with plasma leakage |
| Eosinophilia | Helminths - schistosomiasis, strongyloides, filariasis, hookworm |
| Leucopenia with relative bradycardia | Enteric fever, dengue |
| Raised transaminases | Dengue, hepatitis, leptospirosis, rickettsia |
| Eschar + rash | Rickettsial infection |
E. WHO dengue warning signs - the threshold for admission
- Abdominal pain or tenderness; persistent vomiting; clinical fluid accumulation (ascites, pleural effusion); mucosal bleeding; lethargy or restlessness; hepatomegaly >2 cm; and a rising haematocrit with a falling platelet count
- *Warning signs appear at DEFERVESCENCE (day 4-7) - the "critical phase". The patient who looks better as the fever settles is the one who crashes*
- Severe dengue = severe plasma leakage (shock, respiratory distress), severe bleeding, or severe organ impairment
Management
A. Malaria - treat urgently
- Severe/complicated falciparum malaria (impaired consciousness, seizures, shock, acidosis, AKI, ARDS, hypoglycaemia, parasitaemia >2-10%, jaundice, severe anaemia, bleeding)
- IV artesunate - the treatment of choice; ICU care
- Watch for delayed post-artesunate haemolysis at 1-3 weeks
- Uncomplicated falciparum: artemether-lumefantrine orally
- **P. vivax/ovale: chloroquine or ACT, PLUS radical cure to eradicate hypnozoites**
- Primaquine (14 days) or tafenoquine (single dose) - *test G6PD activity first: severe haemolysis in G6PD deficiency; both contraindicated in pregnancy*
- Monitor parasitaemia daily until negative; admit all falciparum malaria and anyone who cannot tolerate oral therapy
B. Dengue - no antiviral; fluid management is the treatment
- Paracetamol only - *avoid NSAIDs and aspirin (bleeding)*
- Careful, titrated isotonic crystalloid during the critical phase; both under- and over-resuscitation cause harm
- Monitor haematocrit, platelets and urine output; admit if warning signs, pregnancy, comorbidity or social isolation
- Notify; mosquito control measures if in a receptive area of north Queensland
- Qdenga (TAK-003) dengue vaccine is registered in some jurisdictions; serostatus and local epidemiology govern its use
C. Enteric fever
- Azithromycin or ceftriaxone empirically - fluoroquinolone resistance is now widespread in South Asia; adjust on susceptibilities
- Notifiable; food handlers and healthcare workers need clearance cultures
- Look for relapse (~5-10%) and chronic carriage (gallbladder)
D. Other syndromes
- Rickettsial infection or Q fever: doxycycline - treat empirically on suspicion; serology is retrospective
- Leptospirosis: benzylpenicillin or doxycycline
- Traveller's diarrhoea: oral rehydration; azithromycin if severe, febrile or dysenteric; avoid loperamide if there is blood or high fever
- Amoebic liver abscess: metronidazole + a luminal agent (paromomycin)
- Strongyloides: ivermectin - *screen before any immunosuppression: hyperinfection is fatal*
- Schistosomiasis: praziquantel (delay ~6-8 weeks after exposure)
E. Always
- Notify the relevant diseases to public health; involve infectious diseases early
- Isolate on suspicion of VHF, measles, mpox or an emerging respiratory pathogen
- Screen for MDRO colonisation if hospitalised overseas
- Address the missed opportunity: pre-travel advice, vaccination and chemoprophylaxis for next time
Associations
- Malaria - anaemia, splenic rupture, blackwater fever, hypoglycaemia (quinine-induced hyperinsulinaemia), nephrotic syndrome (P. malariae)
- Dengue, chikungunya and Zika share a vector and geography - co-infection occurs
- Zika - congenital microcephaly; avoid conception for a defined period after travel
- Enteric fever - intestinal perforation, chronic gallbladder carriage
- Strongyloides hyperinfection with corticosteroids or HTLV-1
- Schistosomiasis - portal hypertension, bladder squamous cell carcinoma
- Latent TB and chronic hepatitis B in long-stay and VFR travellers
- Antimicrobial-resistant organism colonisation after overseas hospitalisation
Natural history & complications
- Falciparum malaria can progress from well to dead within 24-48 hours - the reason for same-day films and empirical treatment
- Vivax and ovale relapse weeks to months later from hypnozoites - a "malaria" diagnosis without radical cure will come back
- Dengue is triphasic: febrile (days 1-3) -> critical/defervescence (days 4-6, plasma leakage) -> recovery (days 7-10, with a confluent "isles of white in a sea of red" rash and profound fatigue)
- Most recover fully; mortality of severe dengue <1% with good supportive care, ~20% without
- Chikungunya arthralgia may persist for months to years
- Enteric fever untreated: ~10-20% mortality; treated: <1%
- Most fevers in returned travellers resolve without a diagnosis being made - but only after malaria has been excluded three times
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