FEVER IN A RETURNING TRAVELLER

• Initial assessment is aimed primarily at early detection and treatment of falciparum malaria, which can be rapidly fatal

Symptoms and signs

• Temperature >37.5°C in patient presenting after recent overseas travel (e.g. malaria occurring 6 months after travel)
• Falciparum malaria
• 10% of patients are afebrile at presentation
• symptoms take at least 6 days to manifest after arrival in endemic area.
• symptoms usually occur within 2 months of exposure, but may not present for up to 6 months
• Rigors or night sweats imply fever; myalgia or arthralgia do not
• Diarrhoea is non-specific and consistent with malaria, pneumonia, enteric pathogen or any other infective process

Travel history

• Where?– Country and exact locations visited including beaches, jungles, bush etc ( city vs rural)
• for information on outbreaks
• Why?– Business, holiday, visiting relatives
• Accommodation? (e.g. 5-star hotel vs camping)
• When? – Dates of departure and return, and their relation to onset of symptoms
• viral haemorrhagic fevers (VHF) can be excluded if onset of symptoms >21 days after leaving endemic area – for advice on viral haemorrhagic fevers
• for advice regarding Ebola infection
• for advice regarding Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Incubation periods

• Narrow differential diagnosis by considering incubation periods

Short (<10 days)

• Acute gastroenteritis (bacterial, viral)
• Respiratory tract infection (bacterial, viral including avian influenza)
• Meningitis (bacterial, viral)
• Arboviral infections (e.g. dengue, Chikungunya)
• Rickettsial infection (e.g. tick typhus, scrub typhus)
• Relapsing fever (borrelia)

Medium (10–21 days)

• Protozoal
• Malaria (Plasmodium falciparum)
• Trypanosomiasis (Trypanosoma rhodesiensae)
• Acute Chagas’ disease

• Viral
• HIV, CMV, EBV, VHF (including Ebola Virus Disease)
• Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

• Bacterial
• Enteric fever (typhoid and paratyphoid fever)
• Brucellosis
• Q Fever
• Leptospirosis

Long (>21 days)

• Protozoal
• Malaria (including Plasmodium falciparum)
• Amoebic liver abscess
• Visceral leishmaniasis

• Viral
• Viral hepatitis
• HIV
• Other
• Filariasis
• Schistosomiasis
• TB

What? – Risk activities

• Sexual history – HIV – see HIV testing guideline
• Swimming in fresh water – schistosomiasis (Africa) or rickettsial disease (eastern Europe, Asia and South America)
• Tick bites – rickettsial disease (North and South America, sub-Saharan Africa, coastal Mediterranean)
• Animal/bird contact – avian influenza
• Sickness occurring in fellow travellers or contacts: what? when? – especially important in outbreak situations

Pre-travel history

• Pre-travel immunisations, antimalarials and adherence to them
• Any previous medical history, specifically conditions/treatments that can induce immunosuppression

• Confirm presence of fever
• Look for rashes, bites, jaundice, lymphadenopathy, hepatosplenomegaly, bleeding/bruising

Recommended initial investigations in returning travellers presenting with (undifferentiated) fever

Malaria film +/- dipstick antigen test (RDT)

• Perform in all patients who have visited a tropical country within 1 yr of presentation
• Sensitivity of a thick film read by an expert is equivalent to that of an RDT. However, blood films are necessary for specification and parasite count
• Three thick films/RDTs over 72 hr (as outpatient if appropriate) to exclude malaria with confidence
• Blood films (thick and thin) to reference laboratory for confirmation

FBC

• Neutrophilia suggests bacterial infection
• Lymphopenia: common in viral infection (dengue, HIV) and typhoid
• Eosinophilia (>0.5 x 10⁹/L): incidental or indicative of infectious (e.g. parasitic, fungal) or non-infectious cause
• Thrombocytopenia: >75% of patients with falciparum malaria, dengue, acute HIV, typhoid, also seen in severe sepsis

Blood culture

• Two sets before administering antimicrobials
• Sensitivity of up to 80% in typhoid

Serum save

• Offer HIV test to all patients with pneumonia, lymphocytic meningitis, diarrhoea, unexplained fever – see HIV testing guideline
• If indicated, other serology (e.g. arboviral, brucella)

EDTA for PCR

• Consider if other features suggestive of arboviral infection, VHF

Other bloods

• U&E, LFT, CRP and Chest X-ray

Urinalysis

• Proteinuria and haematuria in leptospirosis
• Haemoglobinuria in malaria (rare)

Stool

• MC+S
• Ova, cysts and parasites (OCP)

Respiratory

• COVID-19 PCR
• Extended viral PCR

• Contact infectious diseases team on same or next working day
• If some conditions [e.g. Ebola and other viral haemorrhagic fevers or Middle East Respiratory Syndrome Coronavirus (MERS-CoV)] suspected, isolate the patient
• Resistance patterns among pathogens vary according to locality (e.g. pneumococcal penicillin resistance in Spain)
• If patient displays features of sepsis/severe sepsis, seek immediate advice from senior colleague and critical care – see Sepsis management guideline

Infection Control alerts

• Check for IC alert
• if IC alert not available, check previous 12 months of microbiology reports
• If MRSA present, treat as tagged for MRSA. See MRSA management
• If ESBL, MGNB, CARB present, treat as tagged for ESBL. See ESBL/MGNB/CARB management

Penicillin Allergy

• True penicillin allergy is rare
• Ask the patient and record what happened when they were given penicillin
• If any doubt about whether patient is truly allergic to penicillin, seek advice from a microbiologist or consultant in infectious diseases

Malaria

• Unless minor upper respiratory tract infection apparent, admit for assessment and exclude falciparum malaria in those who have travelled to endemic areas. Three negative films over 72 hours taken 12–24 hr apart are required to exclude malaria
• If malaria confirmed, follow UK malaria treatment guidelines 2016
• If malaria identified but doubt about type, treat as falciparum especially if patient has returned from a falciparum endemic area

Avian influenza or haemorrhagic fever

• If avian influenza or haemorrhagic fever suspected at time of GP referral or on admission out-of-hours, contact on-call microbiologist
• if avian influenza suspected refer to guideline

Typhoid

• If Gram-negative bacilli grown in blood of patient returning from a typhoid endemic area (e.g. Indian sub-continent),
• if not true penicillin/ceftriaxone allergy, give ceftriaxone 2 g IV by infusion daily;
• if true penicillin /ceftriaxone allergy, contact microbiologist/ID consultant
• do not use ciprofloxacin as many strains of Salmonella typhi are resistant

Imported fever service

• The imported fever service hosted jointly by Liverpool and London tropical medicine schools can be contacted for further advice – but only after discussion with local microbiology or infectious disease services