Introduction

Malaria is a disease caused by Plasmodium protozoa which is spread by the female Anopheles mosquito. There are four different species which cause disease in man:
  • Plasmodium falciparum
  • Plasmodium vivax
  • Plasmodium ovale
  • Plasmodium malariae

Plasmodium falciparum causes nearly all episodes of severe malaria. The other three types, of which Plasmodium vivax is the most common, cause 'benign' malaria.

Aetiology

The protection from malaria that sickle-cell trait offers is well documented. Other protective factors include
  • G6PD deficiency
  • HLA-B53
  • absence of Duffy antigens

Pathophysiology

Key points
  • following inoculation parasites (termed sporozoites) pass to the liver
  • in the liver they divide asexually over around 10 days, maturing into schizonts, following which they emerge from the liver (as merozoites) and infect red blood cells, appearing as tiny rings
  • as the parasites mature the infected red blood cells are sequestered by various tissues of the body
  • Plasmodium vivax and Plasmodium ovale (but not Plasmodium falciparum) lay down hypnozoites in the liver
  • these dormant forms are not affected by conventional antimalarial drugs and can hence reactivate after months or years

An illustration of the life cycle of the malaria parasite. Credit: NIAID

Although there is no hypnozoite stage in Falciparum, resurgences may occur due to asexual parasites resistant to quinine. Falciparum may be resistant to pyrimethamine + sulfadoxine (Fansidar) therefore doxycycline is often given

Clinical features

Investigations

The gold standard for diagnosis of malaria remains the blood film. Rapid diagnostic tests (detecting plasmodial histidine-rich protein 2) are currently being trialled and have shown sensitivities from 77-99% and specificities from 83-98% for falciparum malaria

Blood film - if doubt about diagnosis should be repeated
  • thick: more sensitive
  • thin: determine species

Other tests
  • thrombocythaemia is characteristic
  • normochromic normocytic anaemia
  • normal white cell count
  • reticulocytosis

Screening and prevention

There are around 1,500-2,000 cases each year of malaria in patients returning from endemic countries. The majority of these cases (around 75%) are caused by the potentially fatal Plasmodium falciparum protozoa. The majority of patients who develop malaria did not take prophylaxis. It should also be remembered that UK citizens who originate from malaria endemic areas quickly lose their innate immunity.

Up-to-date charts with recommended regimes for malarial zones should be consulted prior to prescribing

DrugSide-effects + notesTime to begin before travel Time to end after travel
Atovaquone + proguanil (Malarone)GI upset1 - 2 days7 days
ChloroquineHeadache

Contraindicated in epilepsy
Taken weekly
1 week4 weeks
DoxycyclinePhotosensitivity
Oesophagitis
1 - 2 days4 weeks
Mefloquine (Lariam)Dizziness
Neuropsychiatric disturbance

Contraindicated in epilepsy
Taken weekly
2 - 3 weeks4 weeks
Proguanil (Paludrine)1 week4 weeks
Proguanil + chloroquineSee above1 week4 weeks

Pregnant women should be advised to avoid travelling to regions where malaria is endemic. Diagnosis can also be difficult as parasites may not be detectable in the blood film due to placental sequestration. However, if travel cannot be avoided:
  • chloroquine can be taken
  • proguanil: folate supplementation (5mg od) should be given
  • Malarone (atovaquone + proguanil): the BNF advises to avoid these drugs unless essential. If taken then folate supplementation should be given
  • mefloquine: caution advised
  • doxycycline is contraindicated

It is again advisable to avoid travel to malaria endemic regions with children if avoidable. However, if travel is essential then children should take malarial prophylaxis as they are more at risk of serious complications.
  • diethyltoluamide (DEET) 20-50% has been shown to repel up to 100% of mosquitoes if used correctly. It can be used in children over 2 months of age*
  • doxycycline is only licensed in the UK for children over the age of 12 years

*A BMJ review (BMJ 2015; 350:h99) suggest DEET could also be used in breastfeeding women and pregnant women in their 2nd or 3rd trimester

TYPES

Malaria (Falciparum)