Tropical and imported infections

Contents

Overview

As international travel increases, ICUs in the UK increasingly encounter infections acquired abroad. The clinician must maintain a high index of suspicion, obtain a detailed travel history, and contact microbiology and infectious disease specialists early. Some conditions — particularly viral haemorrhagic fevers — require immediate isolation and are notifiable. Malaria is the most common life-threatening imported infection and must be excluded rapidly in any febrile returning traveller.

Severe Malaria

Epidemiology

Plasmodium falciparum causes the vast majority of severe and fatal malaria. It is endemic in sub-Saharan Africa, South and South-East Asia, and parts of South America. Approximately 1,500–2,000 cases of malaria are imported to the UK annually; of these, P. falciparum accounts for 75%, and case fatality is approximately 1–2% overall, rising to 15–30% in severe disease.

Pathophysiology

P. falciparum causes unique pathology because infected erythrocytes express PfEMP1 (P. falciparum erythrocyte membrane protein 1) on their surface, mediating cytoadherence to endothelium (particularly in brain, lung, kidney, and placenta). Rosetting (infected cells binding uninfected cells) and sequestration of parasitised cells in the microcirculation cause obstruction and local ischaemia. Parasite lysis releases haemozoin (malaria pigment), causing inflammatory cytokine release. High parasite biomass leads to haemolysis, anaemia, and metabolic derangement.

Severe Malaria — WHO Criteria

At least one of the following in the presence of P. falciparum parasitaemia:

  • Cerebral malaria: unarousable coma (GCS <11 in adults, Blantyre Score <3 in children)
  • Severe anaemia: Hb <70 g/L with parasitaemia >10,000/µL
  • Respiratory distress: ARDS-pattern infiltrates on CXR
  • Hypoglycaemia: blood glucose <2.2 mmol/L
  • Circulatory collapse (algid malaria): severe septic shock with BP <70 mmHg systolic
  • Acute kidney injury
  • Jaundice: bilirubin >50 µmol/L with parasitaemia >100,000/µL
  • Abnormal bleeding: DIC
  • Hyperparasitaemia: >5% parasitised red blood cells (>10% indicates very high risk)
  • Impaired consciousness not meeting cerebral malaria criteria

Diagnosis

Thick and thin blood films: Gold standard. Thick film for sensitivity (concentration technique); thin film for species identification and parasitaemia quantification. Repeat every 12–24 hours if initially negative (parasitaemia fluctuates with the parasite lifecycle).

Rapid diagnostic tests (RDT): Detect HRP2 antigen (P. falciparum specific) or pLDH. High sensitivity for P. falciparum. Use alongside films, not instead.

PCR: Highly sensitive; useful for low-density parasitaemia, mixed infections, species confirmation.

Management

Immediate ICU admission for severe malaria.

IV artesunate: First-line treatment for severe malaria. 2.4 mg/kg IV at 0, 12, and 24 hours, then daily. Artesunate reduces parasite burden faster than quinine, has a better safety profile, and is associated with lower mortality in multiple trials including SEAQUAMAT (Africa) and AQUAMAT (Asia). Available via specialist centres and the Pharmacy Service; contact Public Health England (UKHSA) National Infections Service if artesunate is not immediately available — quinine IV can be used while artesunate is obtained.

IV quinine (if artesunate is not immediately available): Loading dose 20 mg/kg (max 1.4 g) over 4 hours via syringe pump, then 10 mg/kg every 8 hours. Monitor ECG (QTc prolongation) and blood glucose (hypoglycaemia — especially with quinine). Quinine is available immediately in UK pharmacies.

Avoid antipyretics other than paracetamol: NSAIDs worsen renal failure.

ICU supportive care:

  • Cerebral malaria: do NOT give corticosteroids (harmful in RCT data), manage raised ICP, seizure control with benzodiazepines/levetiracetam, avoid fluid overload (exacerbates cerebral oedema)
  • Respiratory: lung-protective ventilation for ARDS
  • Renal: CRRT for AKI
  • Glucose: monitor 4-hourly; treat hypoglycaemia (common with quinine and in severe disease)
  • Anaemia: transfuse if Hb <70 g/L
  • Exchange transfusion: no longer recommended (evidence did not support benefit)

Hyperparasitaemia (>10%): ICU admission mandatory; involve haematology; consider exchange transfusion only in exceptional circumstances with specialist advice.

Dengue

Dengue is caused by one of four dengue virus serotypes (DENV 1–4), transmitted by Aedes aegypti mosquitoes. It is the most common arboviral infection globally — approximately 400 million infections annually — and is endemic across tropical and subtropical regions.

Clinical Spectrum

Dengue fever: Febrile illness with severe myalgia ("breakbone fever"), arthralgia, headache, retroorbital pain, maculopapular rash. Leucopenia, thrombocytopenia, and mildly elevated liver transaminases are characteristic.

Dengue with warning signs: Abdominal pain, persistent vomiting, clinical fluid accumulation (pleural effusion, ascites), mucosal bleeding, lethargy, liver enlargement, rapid platelet fall.

Severe dengue: Severe plasma leakage (DHF/DSS), severe bleeding, severe organ impairment. Plasma leakage syndrome occurs characteristically between days 4–6 of illness, coinciding with defervescence — during this period, plasma proteins and fluid leak from the intravascular compartment, causing hypovolaemia and haemoconcentration, while pleural and abdominal cavities accumulate fluid.

Pathophysiology

Secondary infection with a different serotype carries greater risk of severe disease. Antibody-dependent enhancement (ADE): sub-neutralising antibodies from prior infection facilitate uptake of the new serotype by macrophages, amplifying viral replication and cytokine storm. A capillary leak syndrome results from endothelial activation by NS1 protein and inflammatory mediators.

Management

No specific antiviral therapy exists for dengue. Management is supportive:

Dengue fever: Oral hydration, paracetamol (avoid NSAIDs — worsen bleeding and renal function). Monitor platelet count and haematocrit daily during the critical phase.

Severe dengue / dengue shock syndrome (DSS):

  • Careful fluid resuscitation: isotonic crystalloid (Ringer's lactate or normal saline) in 5–10 mL/kg boluses, reassessing after each. Avoid fluid overload — plasma leakage means fluid can accumulate in third spaces and cause pulmonary oedema even with apparent hypovolaemia.
  • Haematocrit monitoring every 4–6 hours: a rising haematocrit indicates ongoing plasma leakage; a sudden fall may indicate occult haemorrhage.
  • Platelet transfusion only for active severe bleeding or platelet count <10–20 × 10⁹/L (prophylactic transfusion does not reduce bleeding risk in dengue).
  • Avoid steroids — no proven benefit.

Typhoid and Enteric Fever

Enteric fever is caused by Salmonella Typhi (typhoid) and S. Paratyphi (paratyphoid). It remains common in South Asia, sub-Saharan Africa, and parts of Latin America. Transmission is faecal-oral via contaminated water or food.

Clinical Features

Insidious onset: fever rising over 1–2 weeks in a step-ladder pattern, relative bradycardia (for degree of fever), headache, malaise, constipation (early) → diarrhoea (later), abdominal distension, rose spots (faint salmon-coloured macules on the trunk — seen in ~30%), hepatosplenomegaly.

Complications Requiring ICU

  • Intestinal perforation (~3%): sudden onset abdominal pain, peritonitis, surgical emergency
  • GI haemorrhage: from Peyer's patch ulceration
  • Encephalopathy: typhoid hepatitis, raised ICP
  • Septic shock
  • Haemolytic anaemia, DIC

Diagnosis

Blood cultures: most sensitive in the first week (80% sensitivity). Bone marrow culture: highest sensitivity (90%), useful in partially treated patients. Widal test: serological test with poor specificity due to cross-reactions; not recommended.

Management

Empirical treatment with a fluoroquinolone (ciprofloxacin) or third-generation cephalosporin (ceftriaxone). Extensive fluoroquinolone resistance now exists in South and South-East Asian strains — azithromycin or ceftriaxone may be required. Sensitivities from the local travel clinic or PHE should guide final antibiotic selection.

Viral Haemorrhagic Fevers

Viral haemorrhagic fevers (VHFs) are a group of severe viral illnesses characterised by fever, haemorrhage, and multi-organ failure. Most are zoonotic infections with high mortality. ICU staff must be alert to the possibility of VHF in any returning traveller with fever, haemorrhage, and relevant travel history — the potential for nosocomial transmission means early isolation is critical.

Important VHFs

Ebola and Marburg (filoviruses): Central and West Africa. Case fatality 25–90%. Transmitted by direct contact with blood and body fluids of infected persons or animals.

Lassa fever: West Africa (Sierra Leone, Nigeria). Case fatality 1–15% in hospitalised patients; higher in epidemic settings. Transmitted by contact with multimammate rat excreta.

Crimean-Congo haemorrhagic fever (CCHF): Africa, Middle East, Central Asia, South-Eastern Europe. Tick-borne (Hyalomma spp.). Case fatality 15–40%. Treatment: ribavirin.

Hantavirus: Pulmonary syndrome (Americas) or haemorrhagic fever with renal syndrome (HFRS, Europe/Asia). Transmitted by rodent excreta.

Infection Control

Any patient with fever and travel history to a VHF-endemic area with potential for exposure must be immediately isolated and the medical team must don appropriate PPE before any clinical contact. Standard PPE is insufficient — contact UKHSA specialist service (National Infections Service, Colindale) immediately.

UK High Consequence Infectious Disease (HCID) units are designated for confirmed VHF cases.

Ribavirin has evidence for Lassa fever and CCHF. No approved treatments for Ebola (though some investigational agents are used).

Approach to the Returning Traveller

Any febrile patient with recent travel to a tropical region requires:

  1. Detailed travel history: countries visited, duration, malaria prophylaxis (adherence, type), vaccinations, activities (rural vs urban, fresh water exposure, animal contact, insect bites)
  2. Malaria films and RDT immediately — exclude malaria in all febrile returning travellers. Do not wait for other investigations.
  3. Consider VHF risk: if travel to a VHF-endemic area with potential exposure, isolate and contact UKHSA before any invasive procedure.
  4. Blood cultures, FBC, liver function, renal function, clotting
  5. Consider: dengue NS1 antigen and IgM/IgG serology, rickettsial serology (fever + rash + tick exposure), Leptospira (freshwater/flood exposure, farmers), schistosomiasis, enteric fever (blood cultures)

Viva Questions

What defines severe malaria and how do you manage it acutely in the ICU?

Severe malaria is defined by the WHO as P. falciparum parasitaemia with at least one clinical or laboratory feature of end-organ dysfunction or severe disease: cerebral malaria (GCS <11), severe anaemia (Hb <70 g/L), respiratory distress or ARDS, hypoglycaemia (<2.2 mmol/L), circulatory collapse, AKI, jaundice, abnormal bleeding, or hyperparasitaemia (>5%). Immediate ICU admission is required. The antimalaria of choice is IV artesunate — it is more effective than quinine (lower mortality demonstrated in SEAQUAMAT and AQUAMAT trials) and has a better safety profile. It is given at 2.4 mg/kg IV at 0, 12, and 24 hours, then daily until oral treatment can be given. IV quinine remains the alternative if artesunate is not immediately available. Supportive care addresses the specific complications: cerebral malaria requires seizure management and avoidance of fluid overload (corticosteroids are harmful and contraindicated); ARDS is managed with lung-protective ventilation; AKI with CRRT; glucose should be monitored every 4 hours. Blood transfusion for Hb below 70 g/L. Exchange transfusion is no longer recommended.

How do you recognise and manage dengue shock syndrome?

Dengue shock syndrome (DSS) occurs during the critical phase of dengue, typically around days 4–6 of illness when fever resolves. Plasma leakage from the intravascular compartment occurs due to endothelial dysfunction from the NS1 protein and inflammatory mediators. Clinically, this presents as haemodynamic instability (tachycardia, narrow pulse pressure, hypotension), rising haematocrit (indicating haemoconcentration from plasma loss), and evidence of fluid accumulation in third spaces (pleural effusions, ascites). Paradoxically, significant fluid may be sequestered in the thorax and abdomen while the patient is intravascularly depleted. Management is carefully titrated isotonic crystalloid resuscitation — 5–10 mL/kg boluses with haemodynamic reassessment. Haematocrit should be monitored every 4–6 hours; a sustained rise indicates ongoing leakage, while a sudden fall may indicate haemorrhage. Fluid overload must be avoided as it causes pulmonary oedema from leakage of the administered fluid into the interstitium. Platelet transfusion is reserved for active significant haemorrhage — prophylactic transfusion at low platelet counts does not reduce bleeding in dengue. There is no specific antiviral. NSAIDs should be avoided.

A nurse returns from three weeks in Sierra Leone with fever, myalgia, pharyngitis, and a petechial rash. What is your immediate management?

Sierra Leone is endemic for Lassa fever, and this presentation in a returning traveller is consistent with potential VHF. The immediate priority is isolation — the patient must be placed in a side room with negative pressure if available, and the team must not perform any invasive procedures until UKHSA has been contacted. Standard PPE is not sufficient for a confirmed or highly probable VHF case; enhanced PPE including air-purifying respirators, coveralls, and double gloves is required. I would contact the UKHSA National Infections Service (Colindale) immediately and follow their guidance on risk stratification and testing. The risk assessment will consider the nature of exposure in Sierra Leone (healthcare worker vs tourist, community or hospital contact, freshwater exposure, contact with rodents), the incubation period (Lassa 6–21 days, Ebola 2–21 days), and the clinical features. If the risk is assessed as significant, samples will be sent to a designated Containment Level 4 laboratory for confirmatory testing. Lassa fever is treated with ribavirin if diagnosed early. Malaria must still be excluded urgently (concurrent malaria is possible and also life-threatening), but blood must be taken under appropriate containment conditions.