Malaria

 

• Background

  Infection with the protozoa Plasmodium vivax, P. ovale, P. malariae, or P. falciparum.

  Plasmodium life cycle

  • Sporozoites injected through human skin by female anopheline mosquito, then migrate to liver.
  • In the hepatocytes, they multiply into merozoites. After 1-4 weeks incubation, the hepatocytes rupture and the merozoites are released into the blood. P. vivax and P. ovale can also become hypnozoites, incubating in liver for months or even years.
  • Enter RBCs and become trophozoites then schizonts, which form further merozoites, leading to rupture and hence haemolysis and fever in 48-72 hr cycles.
  • Some merozoites become gametocytes, which are taken up in RBCs by mosquitoes feeding on blood.
  • P. falciparum is the most pathogenic as it affects all RBC ages, including reticulocytes, while others only affect mature RBCs

  Epidemiology of cases imported to UK

  1500 cases annually, many from those visiting family members in country of origin.

  Species:

  • P. falciparum: 80%, usually Africa.
  • P. vivax: 10%, usually South Asia.
  • P. ovale and P. malariae: 10%.

• Signs and symptoms

  General:

  • Fever: all tertian (48-hourly) except quartan (72-hourly) in P. malariae. These classic patterns aren't always clearly seen.
  • Rigors
  • Headache
  • Diarrhoea and vomiting.
  • Hepatosplenomegaly

  Falciparum malaria:

  • Flu-like prodrome: myalgia, malaise, headache, anorexia.
  • Irregular fever initially.
  • Jaundice

  Complicated falciparum malaria:

  • Mortality approaches 100% if severe and untreated.
  • Cerebral malaria: altered mental status, seizures, coma, decerebrate posturing, ↑plantars, teeth-grinding.
  • AKI
  • Bleeding: haemoglobinuria ('blackwater fever'), DIC, retinal haemorrhages.
  • Metabolic: ↓glucose, metabolic acidosis, Kussmaul's breathing.
  • ARDS and pulmonary oedema.
  • Splenic rupture.
  • Shock

• Investigations

  Diagnosis using blood films:

  • Serial testing: up to 3 times if 1st -ve.
  • Thick film – quick yes or no malaria – and thin film – which subtype.
  • Also shows parasitaemia (%RBCs infected) and stage, with imminent decline in patient condition due if there are ↑schizonts. Dangerous if parasitaemia >2% and life-threatening if >5%.
  • Simple but less sensitive antigen detection kits are available too.

  Bloods:

  • FBC: anaemia, ↓platelets. Low platelets result from increased splenic activity during haemolysis, leading to excess platelet clearance.
  • Coag: DIC.
  • ↓Glucose
  • ABG: metabolic acidosis.
  • U+E: AKI.

  Other tests:

  • Urinalysis: blood.
  • Blood cultures to rule out bacterial sepsis.

• Management

  Prophylaxis

  Start 1 week before to check for side effects, and continue until 4 weeks after.

  Areas without chloroquine resistant falciparum:

  • Chloroquine (daily) plus proguanil (weekly).

  Areas with chloroquine resistance. Any 1 of:

  • Atovaquone/proguanil (Malarone). Few side effects, and is taken from 1 day before until 7 days afterwards. Expensive.
  • Doxycyline
  • Mefloquine (Lariam): once weekly.

  Also:

  • Long sleeves dusk till dawn.
  • Mosquito nets
  • DEET repellent.

  Treatment

  • P. vivax, P. ovale, and P. malariae: chloroquine plus primaquine.
  • Uncomplicated P. falciparum: 1st-line artemether/lumefantrine (Riamet). 2nd-line: quinine/doxycycline (quinine/clindamycin in kids), or atovaquone/proguanil.
  • Complicated P. falciparum (cerebral, renal, or shock): artesunate IV (preferably), or quinine IV + doxycycline IV/PO. Careful monitoring of fluid, lactate, U+E. Transfuse if anaemic.

• Complications

  • P. vivax and P. ovale can remain dormant in the liver as hypnozoites and relapse years later. Causes tropical splenomegaly syndrome if recurrent.
  • P. malariae can lie low in blood for years, with or without symptoms.

• Antimalarials

  Mechanism

  • Most prevent plasmodium conversion of haem to inert haemozoin, causing toxic haem accumulation
  • Primaquine is the only agent effective against hypnozoites.

  Side effects

  • Chloroquine: headache, psychosis, retinopathy. Contraindication: epilepsy.
  • Primaquine: epigastric pain, triggers hemolysis in G6PD deficiency (check 1st and give atovaquone/proguanil if +ve).
  • Atovaquone/proguanil: abdo pain, nausea, dizziness.
  • Mefloquine: nausea, dizziness, insomnia, vivid dreams, psychosis. Contraindications: epilepsy, psychosis.
  • Doxycycline: photosensitivity, diarrhoea, oesophagitis.