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

• Clinical Cases – Mega Malaria Extravaganza

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.