Malaria

Reviewed and revised 5 September 2014

OVERVIEW

  • malaria is a protozoan infection caused by plasmodium species that are transmitted by female anopheles mosquitoes, severe forms of which can lead to multi-organ dysfunction and death
  • anyone who has been to a endemic area in last year who presents with a fever should be considered to have malaria until proven otherwise (relapse can occur years later in vivax and ovale)
  • malaria areas: Africa, India, New Guinea, South east Asia, tropical climates

TYPES OF MALARIA

5 species infect humans

  • Plasmodium vivax, malariae, ovale, falciparum, knowlesi (the latter is a simian species and is still considered a zoonosis)

Falciparum

  • P. falciparum is the most pathogenic and resistant to standard antimalarials
  • can be rapidly fatal
  • lacks a liver phase (hypnozooites)
  • typically develops within 6 weeks of return from an endemic area, unless on prophylaxis which may delay presentation up to 6 months

Others

  • vivax, ovale, and malariae may cause significant distress but tend to have a benign prognosis
  • vivax ovale have hypnozoites and thus require primaquine to prevet relapsing malariae from reactivation of liver hypnozooites
  • knowlesi is potentially lethal and should be treated similarly to falciparum malaria, it is morphologically similar to P. malariae but has a rapid cycling time

LIFE CYCLE

Overview

  • mosquito bite -> blood stream -> RBCs -> haemolysis and release

See DPDx -Malaria

  • vector is the female Anopholes mosquito
  • involves sporozoites that invade the liver from mosquito saliva, schizonts that mature in the liver and merozoites that replicate in the blood and form trophozoites then more shizonts
  • exo-erythrocytic schizogony occurs in the liver
  • asexual erythrocytic schizogony occurs in the RBCs
  • some trophozoites undergo sexual erythrocytic schizogony resulting in gametocytes that are taken up by the mosquito vector where the sporogonic cycle takes place creating more sporozoites
  • P. ovale and vivax have hypnozoites that can persist in the liver for many years

RISK FACTORS

Risk factors for severe malaria:

  • pregnancy
  • splenectomy
  • extremes of age (newborns and the frail elderly)

ASSESSMENT

History and examination

  • travel history (usually within 6 weeks for falciparum, a year for non falciparum species – assume all malarial areas could lead to falciparum infection)
  • fever and rigors
    • may be continuous in the first week
    • classically described cyclical fever (every 2-3 days) is often absent, but is said to be due to release from liver and reticuloendothelial system
  • non-specific constitutional symptoms: malaise, anorexia, headache, lethargy, myalgia
  • cough and diarrhoea may occur (may mimic LRTI or gastroenteritis)
  • splenomegaly
  • patient may feel well when afebrile
  • atypical symptoms if exposure to prophylaxis or partial immunity
  • ‘relapse’ may be due to relapsing malaria (hypnozooites of vivax or ovale), incomplete treatment or reinfection

Severe malaria

  • CNS: Altered consciousness, (+/- meningism) seizures, focal deficits (cerebral malaria)
  • GI: Vomiting, jaundice
  • RESP: Respiratory distress +/- ARDS
  • RENAL: AKI
  • CVS: Shock
  • HAEM: Severe hemolytic anaemia with jaundice, coagulopathies and spontaneous haemorrhage
  • METABOLIC: acidosis and hypoglycemia
  • high parasite load: >2% RBCs infected or >100,000 parasites/mm3

Other presentations

  • haemoglobinuria (“black water fever”)
  • nephrotic syndrome (P. malariae only)

Complications

  • blackwater fever (haemoglobinuria)
  • cinchonism (due to qunine)

INVESTIGATIONS

General

  • glucose
  • FBC: haemolysis, normochromic normocytic anemia
  • UEC
  • LFTs
  • Coags and cross match,
  • Haemolysis screen
  • Septic screen to exclude other causes (e.g. blood culture, throat swab, urine MCS, LP as needed)
  • CT head +/- LP +/-
  • EEG if suspected seizures
  • CXR

Specific

  • thick and thin blood films (EDTA tubes)
    • perform urgently, even after hours (call in a qualified technician if not in house)
    • thick film used to detect parasites, thin films used to determine the species and quantify
    • send multiple samples (typically 3 samples 12 hours apart), a single sample does not exclude malaria
    • may be negative if patient on antimalarials or received antibiotics recently
  • ICT (immuno-chromatograph testing)
    • sensitive and specific test for HRP2 (histidine rich protein) from falciparum; persists for 2-3 weeks post-treatment
    • also detects a protein common to all malaria species
    • usually weakly positive early in infective, may be strongly positive following recent infection
  • PCR
    • not routine but assays available to detect all species

MANAGEMENT

General

  • Early consultation with ID
  • Don’t treat with the same agent that patient was on for prophylaxis and check resistance patterns of endemic region
  • Urgent treatment is needed if:
    — any degree of altered consciousness, jaundice, oliguria, severe anaemia or hypoglycaemia
    — parasite count > 100 000/mm3 or >2% of red blood cells parasitised
    — patient is vomiting or clinically acidotic

Resuscitation

  • ABC approach
  • treat immediate life-threats: respiratory failure, shock, hypoglycemia, seizures and raised ICP, DIC and bleeding, MODS

Specific therapy

  • Severe Falciparum Malaria
    — IV artesunate 2.4mg/kg Q 12 hrly for 3 doses + Lumefantrine is first choice
    — IV quinine dihydrochloride 20mg/kg LD over 4 hours then 10mg/kg Q8hrly – watch for hypoglycaemia, arrhythmias and cinchonism
    — PO artemether + lumefantrine  OR quinine + clindamycin/doxycycline once eating
  • Uncomplicated Falciparum Malaria
    — Artemether + Lumefantrine – first choice oral agent (covers all plasmodium species; given ASAP)
    — Quinine sulphate + either: doxycycline, clindamycin, atrovaqone+proguanil, mefloquine
  • Vivax, malariae and ovale
    — chloroquine 10mg/kg PO -then 5mg/kg Q6hrly + primaquine 0.5mg/kg Q12 hrly (to clear liver disease)

Supportive care and monitoring

  • organ support
  • invasive monitoring

Seek and treat complications

Disposition

  • admit severe malaria to ICU
  • in the developed world most patients with a first presentation should be admitted, at least until review by an infectious diseases specialist

Notification

  • malaria is a group B disease in Australia and requires notification within 5 days

PREVENTION

  • avoid exposure
  • stay covered at night
  • permethrin-coated bed nets
  • Prophylaxis – co-trimoxazole, tetracyclines, fluoroquinolones, malarone, mefloquine

References and Links

LITFL

Journal articles

  • Dondorp A, et al; South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) group. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet. 2005 Aug 27-Sep 2;366(9487):717-25. PMID: 16125588.
  • Dondorp AM, et al; AQUAMAT group. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010 Nov 13;376(9753):1647-57. PMC3033534.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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