Malaria

Anopheles mosquito-borne protozoal infection endemic in tropical and subtropical regions, caused by four species of the Plasmodium genus:

Epidemiology and Risk Factors

Risk factors for malaria:

  • Patient factors
    • Age <3
    • Non-immune
  • Environmental factors
    • Mosquito carrier
      Specifically the female Anopheles, which are:
      • Night feeders
        Dawn to dusk is the most dangerous time.
      • Rural breeders
        Generally ↓↓ risk in urban areas, even in endemic regions.

Severe malaria associated iwth:

  • Children <5
  • Non-immune travelers
  • Immunosuppression
    • Pregnancy

Pathophysiology

Life-cycle:

  • Uninucleate sporozoites resident in mosquito salivary glands are injected into a human host during feeding
  • Sporozoites rapidly invade liver parenchyma and mature into schizonts
    • Bursting of schizonts releases 2,000 to 40,000 merozoites, each of which can infect a single RBC
    • Maturation may take 1-2 years in P. vivax and P. ovale infections
  • Merozoites mature in the RBC into either:
    • Gametocyte
      If ingested by a mosquito during feeding, will mature in the mosquito gut over 2-3 weeks into new sporozoites.
    • Erythrocytic schizont
      Contain more merozoites; subsequent rupture releases merozoites and causes the cyclical fever.

The erythrocytic stage is the disease-causing stage; sporozoites and gametocytes are not associated with disease.

Sickled cells (see Sickle Cell Disease) haemolyse prematurely, interrupting the Plasmodium life-cycle.

Aetiology

Clinical Features

Presentations are divided into:

Cyclical symptoms occur when maturing malarial schizonts rupture their erythrocyte host, the timing of which varies on the strain:

  • Tertian malaria
    Maturation every 48 hours.
    • P. vivax
    • P. ovale
  • Quartan malaria
    Maturation every 72 hours.
    • P. malariae
  • P. Falciparum
    Typically irregular fever spikes every 48 hours on the background of a continuous fever, but may also produce tertian malaria.
Cyclical Fevers

  • Uncomplicated
    Generic viral symptoms, progressing to classical cyclical fevers.
  • Severe malaria
    Progression to organ dysfunction, most common with P. falciparum infection.
Features of Malaria
Uncomplicated Severe
  • Cyclical fever
    In established disease.
  • Headache
  • Jaundice
  • Hepatosplenomegaly
  • Myalgia
  • Pulmonary oedema
  • ARDS
  • Septic shock
    Lactic acidosis.
  • Coma
  • Severe weakness
    “Prostration.”
  • AKI
  • Haemoglobinuria
  • Haemolysis
  • DIC

Cyclical fevers are the classical finding, and occur in three stages:

  • 15-60 minutes cold shivering
  • 2-6 hour fever (up to 41°C)
  • 2-4 hour sweating 
    Normalisation of temperature.

Diagnostic Approach and DDx

Investigations

Bedside:

Laboratory:

  • Blood
    • FBE
      • Normochromic normocytic anaemia
      • Thrombocytopaenia
    • LFTs
    • UECs
    • Blood smears
      Thick and thin films are gold standard of diagnosis:
      • Thin films identify parasites within red cells
      • Thick films allow parasite counting
        >10% of RBCs containing parasites indicates severe disease.
    • Rapid diagnostic tests
      Look for parasite-specific antigen. Qualitative evidence of disease.
    • Malaria PCR
      More sensitive than antigen testing with similar limitations.

Thick and thin films refer to the thickness of the blood on the slide.

Thin Films

Imaging:

Other:

Management

  • Preventative antimalarials when visiting endemic areas
  • Standard sepsis management
    Covered under Management.
  • Antimalarials

Resuscitation:

  • C
    • Fluid boluses ↑ mortality in children

Specific therapy:

  • Pharmacological
    • Antimalarials
      • Combination therapy recommended due to P. falciparum resistance
      • Chloroquines kill mature parasites, immature parasites mature despite ongoing treatment

Preventative:

  • Pharmacological
    • Malarial prophylaxis
  • Physical
    • Mosquito nets

Marginal and Ineffective Therapies

  • Steroids
    Worsen outcome.
  • IVIG
    Worsen outcome.
  • Exchange transfusion
    Cytapheresis with replacement of native RBCs with donor RBCs, sometimes used if >10% parasitaemia. No indication of mortality benefit.

Anaesthetic Considerations

Complications

  • B
    • ARDS
  • C
    • Septic shock
  • D
    • Cerebral malaria
      Mental status abnormality in a patient with malaria without another cause.
      • Due to obstruction of cerebral capillary blood flow, or efffect of malarial toxin
      • Coma
      • Convulsions
      • ↑ ICP
      • ↓ BSL
      • Tone and postural abnormalties
        Symmetrical pyramidal signs.
      • Retinopathy
      • 15-50% mortality
  • E
    • Hypoglycaemia
    • Electrolyte derangements
    • Rhabdomyolysis
  • F
    • AKI
    • ATN
      Secondary to haemoglobinuria and rhabdomyolysis.
  • H
    • DIC
    • Thrombocytopenia

Prognosis

Death associated with:

  • Age <3
  • Cerebral malaria
  • Organ failures
  • Anaemia

Key Studies

  • FEAST (2011)
    • 3170 African children aged 60 days to 12 years with febrile illness, ↓ conscious state, and ↓ perfusion; without malnourishment, gastroenteritis, or non-infectious shock
    • Multicentre (6), un-blinded, allocation concealed, block-randomised trial
    • 3600 patients would provide 80% power for 5% ↓ ARR of death, assuming control mortality of 11%
    • Patients without severe hypotension (3141) randomised to one of:
      • 20-40mL/kg 0.9% saline
      • 20-40mL/kg 5% albumin
      • No fluid
      • Volumes of fluid were ↑ (from 20 to 40mL) after a protocol amendment partway through the trial
      • Fluid groups received additional fluid if impaired perfusion
      • All patients treated on general paediatric wards (no ICU available), and transfused if Hb <5g/dL
    • 48 hour mortality was significantly ↑ in fluid groups
      Saline 10.5%, albumin 10.6%, control 7.3%.
      • RR for saline vs. control: 1.44 (CI 1.09-1.9)
    • Stopped early for harm
    • Most deaths occurred at <24 hours
    • Weaknesses:
      • Clinical criteria for shock diagnosis are non-specific
      • >50% had malaria, which behaves differently with IVT
      • Significant anaemia may be made worse by haemodilution

A separate arm of FEAST protocolised management of severe hypotension, but there were only 29 patients and the discussion adds complexity disproportionate to insight so I have excluded it from this summary.

References

  1. Crutcher JM, Hoffman SL. Malaria. In: Baron S, editor. Medical Microbiology [Internet]. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996 [cited 2023 May 1].
  2. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  3. Harvey RA, Cornelissen CN, Fisher BD. Lippincott Illustrated Reviews: Microbiology (Lippincott Illustrated Reviews Series). 3rd Ed. LWW.
  4. White NJ. Sharing malarias. The Lancet. 2004;363(9414):1006. doi:10.1016/S0140-6736(04)15879-0