Malaria

Background & epidemiology

Malaria is a life-threatening disease caused by Plasmodium parasites, transmitted to humans through the bites of infected female Anopheles mosquitoes. Each year there are approximately 250 million malaria cases worldwide, with around 600,000 deaths. Sub-Saharan Africa bears a disproportionately high share of the global malaria burden. In 2023 a total of 2,106 cases of imported malaria were reported in returned travellers in the UK.

Malaria parasites are of 5 main types:

• Plasmodium falciparum
• Plasmodium vivax
• Plasmodium ovale
• Plasmodium malariae
• Plasmodium knowlesi (previously identified in monkeys but cases now seen in humans)

Plasmodium falciparum causes nearly all episodes of severe malaria. Of the other types Plasmodium vivax is the most common but typically causes a more 'benign' malaria.

Transmission and lifecycle

The malaria transmission cycle begins when an infected Anopheles mosquito bites a human, injecting sporozoites into the bloodstream. These sporozoites travel to the liver, invading hepatocytes (liver cells) where they replicate and mature into schizonts over 1 to 2 weeks. Schizonts then rupture and release merozoites into the bloodstream, which then invade red blood cells (RBCs). Within RBCs, parasites undergo asexual replication, leading to cell rupture and further merozoite release, perpetuating the cycle.



Dormancy in plasmodium vivax and plasmodium ovale
P. vivax and P. ovale have the unique ability to form a dormant liver stage known as hypnozoites. These hypnozoites can reactivate weeks, months, or even years after the initial infection, causing relapses. This dormancy mechanism complicates malaria eradication efforts and necessitates specific treatment strategies.

Clinical features

Clinical features of malaria include:

• Fever (often > 39°C)
• Sweats and/or chills
• Headache.
• Malaise, lethargy, and fatigue
• Anorexia
• Gastrointestinal disturbance (such as nausea, abdominal pain, vomiting, diarrhoea), and jaundice.
• Poor feeding in children.
• Myalgia and arthralgia.
• Sore throat, cough, lower respiratory tract symptoms, and respiratory distress.
• Confusion
• Hepatomegaly
• Splenomegaly

Features of severe or complicated malaria in adults include:

• Cerebral malaria: impaired conscious level (Glasgow coma score < 11) or seizures
• Renal impairment (may present with oliguria)
• Acidosis
• Hypoglycaemia (< 2.2 mmol/L)
• Respiratory distress syndrome (ARDS)
• Severe anaemia (may present with pallor).
• Spontaneous bleeding/disseminated intravascular coagulation.
• Shock (BP < 90/60 mmHg).
• Sepsis
• Haemoglobinuria (P. falciparum can cause severe haemolysis with dark red urine known as blackwater fever)
• Parasitaemia > 10%

Incubation period

The incubation period usually ranges from 9 to 30 days but depends on the species.

For P. falciparum, the incubation period is 7 to 14 days. For P. vivax and P. ovale infection, the incubation period is typically 12 to 18 days, but can be months or years in some cases due to a longer liver stage.

Considerations for returning travellers

Clinicians should maintain a high index of suspicion for malaria in individuals presenting with febrile illnesses after returning from malaria endemic areas.


Severe malaria: Plasmodium falciparum
Plasmodium falciparum is associated with the most severe form of malaria, potentially leading to:

• Cerebral malaria (altered consciousness, seizures)
• Severe anemia
• Acute respiratory distress syndrome (ARDS)
• Renal failure
• Hypoglycemia

These complications can progress rapidly and are frequently fatal if not promptly treated. The primary reason for this form of malaria being more severe is that Plasmodium falciparum-infected red blood cells (RBCs) express PfEMP1 (Plasmodium falciparum Erythrocyte Membrane Protein 1), which binds to endothelial receptors in capillaries and leads to sequestration of infected RBCs in small blood vessels in the brain (causing cerebral malaria), lungs (leading to pulmonary oedema), and other vital organs with resulting vessel micro-obstruction.

Diagnosis

Malaria diagnosis relies on the detection of parasites in the blood. Microscopic examination of blood smears remains the gold standard. Given the cyclical nature of parasitemia, serial blood films every 12-24 hours over 2-3 days may be necessary to detect the parasite. Rapid diagnostic tests (RDTs) detecting specific antigens are also available but may vary in sensitivity and specificity.

Classification of severity:

Management
Malaria is a notifiable disease in the UK.

Treatment depends on the Plasmodium species, severity of infection, and local drug resistance patterns. A summary of the drugs used is shown in the table below. Note severe malaria requires intravenous antimalarial medications and supportive care.

Summary of drugs used to treat malaria