Malaria

Malaria Summary

Key Facts

Life-threatening parasitic infection
Transmitted by Anopheles mosquitoes
P. falciparum most dangerous species
Medical emergency - urgent diagnosis

Clinical Features

Fever (>39°C), chills, sweats
Headache, malaise, fatigue
GI symptoms, jaundice
Respiratory distress
Confusion (cerebral malaria)

Diagnosis

Blood films (thick & thin)
Antigen detection tests
Repeat if negative at 12-24h
Travel history essential

Treatment

P. falciparum: ACTs first-line
Severe cases: IV artesunate
Non-falciparum: ACTs or chloroquine
Expert advice always required

Severe Features

Cerebral malaria
Renal impairment
Severe anaemia
Respiratory distress
Hypoglycaemia

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. Most prevalent in Africa and responsible for majority of malaria deaths.

P. vivax

Most common outside sub-Saharan Africa. Has dormant liver stages causing relapses months/years after initial infection.

P. ovale

Found mostly in West Africa and western Pacific. Dormant liver stages can cause relapses.

P. malariae

Found in South America, Asia and Africa. Can cause lifelong chronic infection if untreated.

P. knowlesi: A malaria parasite of monkeys in South-East Asia which can cause severe and sometimes fatal illness in humans.

Malaria Life Cycle

Mosquito Bite

Sporozoites injected into human bloodstream during mosquito blood meal

Liver Stage

Sporozoites travel to liver, mature into schizonts releasing merozoites

Blood Stage

Merozoites infect red blood cells, multiply and cause clinical illness

Transmission

Gametocytes form in blood, taken up by mosquitoes to continue 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)

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.

Type	First-line Treatment	Severe Cases
P. falciparum	Artemisinin combination therapy (ACT)	IV artesunate in ICU/HDU
Non-falciparum	ACT or chloroquine	IV artesunate or quinine
Mixed/Unknown	Treat as P. falciparum	IV artesunate in ICU/HDU

Treatment Notes

Artemether with lumefantrine is the drug of choice for uncomplicated P. falciparum malaria
IV artesunate is indicated for all severe or complicated falciparum malaria
Follow UK malaria treatment guidelines 2016 for residents in non-endemic settings
Advise other travellers from same group to seek medical attention if symptomatic

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.