Malaria is a life-threatening illness caused by infection of red blood cells by Plasmodium parasites. Several species of Plasmodium cause malaria in humans:

• P. falciparum — found worldwide in tropical and subtropical areas. It is the most prevalent malaria parasite on the African continent and is responsible for the majority of malaria deaths.
• P. vivax — found in Asia, Latin America, and some parts of Africa. It is the most common malaria parasite outside sub-Saharan Africa. P. vivax has dormant liver stages which can cause ‘relapses’ of malaria months or years after the initial infection.
• P. ovale — found mostly in Africa (especially West Africa) and the islands of the western Pacific. P. ovale has dormant liver stages which can cause ‘relapses’ of malaria months or years after the initial infection.
• P. malariae — found in South America, Asia and Africa. If untreated, P. malariae can cause lifelong chronic infection.
• P. knowlesi — a malaria parasite of monkeys in South-East Asia which can cause severe and sometimes fatal illness in humans.

Malaria life cycle

• Transmission of malaria to humans occurs through the bite of infected female Anopheles mosquitoes.
• The infecting agent (sporozoite) is inoculated into humans in the saliva of infected mosquitoes during a blood meal.
• The sporozoites travel in the bloodstream to the liver where they enter liver cells and mature into schizonts which eventually rupture and release tens of thousands of merozoites into the bloodstream.
• Each merozoite can infect a red blood cell where they mature and divide to form more parasites. These are released into the bloodstream when the red blood cell ruptures and go on to infect other red blood cells. The number of parasites in the blood increases rapidly and produces clinical illness.
• Some parasites in the red blood cells form male and female gametocytes. These mate if taken up by a mosquito and mature to release sporozoites ready to be inoculated into a new human host.

Clinical features

Suspect malaria in anyone who has returned from, or previously visited an area endemic for malaria, who is unwell or has a fever or history of fever, regardless of malaria chemoprophylaxis. Almost all cases of P. falciparum malaria present within 6 months of exposure and most within 2 to 3 months.

Clinical features of malaria include:

• Fever (often 39°C or higher), sweats and/or chills
• Headache
• General 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

Features of severe or complicated malaria include:

• Cerebral malaria
• Renal impairment (may present with oliguria)
• Acidosis (may present with acidotic breathing)
• Hypoglycaemia (<2.2 mmol/l)
• Respiratory distress which may be due to pulmonary oedema or acute respiratory distress syndrome (ARDS)
• Severe anaemia (may present with pallor)
• Spontaneous bleeding/disseminated intravascular coagulation
• Shock (BP < 90/60 mmHg)
• Sepsis
• Haemoglobinuria — falciparum can cause severe haemolysis with dark red urine (‘blackwater fever’).
• Parasitaemia (>2% in children, >10% in adults)

Differential diagnosis

Malaria is difficult to diagnose as it may mimic other illnesses encountered in the UK, including:

• Meningitis or encephalitis
• Lower respiratory tract infection
• Influenza and other viral infections such as Epstein-Barr virus, or cytomegalovirus
• Gastroenteritis
• Urinary tract infection
• Lymphoma
• Sepsis
• Viral hepatitis
• HIV seroconversion
• Legionella
• Leptospirosis

Malaria may present with similar symptoms to other travel-related infections, including:

• Viral haemorrhagic fevers such as Lassa fever, Crimean-Congo haemorrhagic fever, Marburg and Ebola — patients suspected of having a viral haemorrhagic fever require strict isolation
• Enteric fevers such as typhoid or paratyphoid
• Arboviruses such as Dengue, West Nile virus and Japanese encephalitis
• Rickettsial infection such as scrub typhus and relapsing fever
• Trypanosomiasis
• Rabies

Investigations

Malaria is a medical emergency and if suspected, a blood test to confirm the diagnosis must be carried out without delay. Diagnosis of malaria is only possible with microscopy of thick and thin blood films (the gold standard) or an antigen detection test. If the first blood films are negative, further blood testing must be arranged 12 to 24 hours later and again after a further 24 hours to rule out infection. In pregnancy, thick films can be negative, despite the presence of parasites in the placenta. Expert advice should always be sought if malaria is suspected.

Management

• Malaria is a notifiable disease and all cases of malaria should be notified to public health.
• Expert advice must be sought in all patients suspected to have malaria. If malaria is diagnosed in a returned traveller, other members of the family or travelling group should be advised that they may have shared the same exposure risk and they should seek medical attention if they develop symptoms.
• The recommendations on treatment below reflect UK malaria treatment guidelines 2016, agreed by UK malaria specialists. They are aimed for residents of the UK and for use in a non-endemic setting.
• If the infective species is not known, or if the infection is mixed and includes falciparum parasites, initial treatment should be as for falciparum malaria.
• Falciparum malaria
  • Artemisinin combination therapy is recommended for the treatment of uncomplicated P. falciparum malaria. Artemether with lumefantrine is the drug of choice; artenimol with piperaquine phosphate is a suitable alternative. Oral quinine or atovaquone with proguanil hydrochloride can be used if an artemisinin combination therapy is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline.
  • Severe or complicated falciparum malaria should be managed in a high dependency unit or intensive care setting. Intravenous artesunate (available for ‘named-patient’ use from infectious disease units or specialist tropical disease centres) is indicated in all patients with severe or complicated falciparum malaria, or those at high-risk of developing severe disease (such as if more than 2% of red blood cells are parasitized), or if the patient is unable to take oral treatment. Following a minimum of 24 hours of intravenous artesunate treatment, and when the patient has improved and is able take oral treatment, a full course of artemisinin combination therapy should be given.
• Non-falciparum malaria
  • Non-falciparum malaria is usually caused by Plasmodium vivax and less commonly by P. ovale, P. malariae, and P. knowlesi.
  • Either an artemisinin combination therapy (such as artemether with lumefantrine or artenimol with piperaquine phosphate) or chloroquine can be used for the treatment of non-falciparum malaria.
  • Severe or complicated non-falciparum malaria should be treated with parenteral artesunate or quinine [unlicensed] as for treatment of severe or complicated falciparum malaria.

Complications

Complications of malaria include:

• Cerebral malaria — severe malaria due to P. falciparum with coma or malaria with coma persisting for more than 30 minutes after a seizure
• Acute respiratory distress syndrome
• Spontaneous bleeding and coagulopathy
• Septicaemia
• Severe anaemia
• Hypoglycaemia
• Metabolic acidosis
• Acute kidney injury
• Nephrotic syndrome
• Jaundice
• Splenic rupture
• In pregnancy:
  • Severe malaria is more likely, particularly in the second and third trimesters, and is often associated with pulmonary oedema and hypoglycaemia.
  • Cerebral malaria has a mortality rate of 50% (higher than non-pregnant adults).
  • Foetal death, premature delivery and intrauterine growth retardation may occur.