11/14/24, 10\:56 AM Malaria

Malaria

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Malaria\: mosquito-borne illness caused by P l a s m o d i u m protozoa; noti
Prevalence\: highest in sub-Saharan Africa, Southeast Asia, and parts of South America; 249 million cases and 608,800
deaths globally in 2022.
UK incidence\: average of 1,425 cases annually between 2012-2021; risk to travellers from endemic areas.
Vulnerable groups\: pregnant individuals, young children, and the elderly are most susceptible to severe complications.
Transmission\: through bites of infected female Anopheles mosquitoes; incubation period 7-30 days.
Pathophysiology\: involves liver stage (asymptomatic), blood stage (RBC destruction and cytokine release), and
gametocyte formation (for mosquito transmission).
Risk factors\: travel to endemic regions, pregnancy, young age, elderly, immunocompromised status, inadequate
chemoprophylaxis.
Symptoms\: fever with chills/sweats, headache, myalgia, fatigue, GI symptoms (nausea, vomiting), respiratory symptoms
(cough).
Diagnosis\: travel history, clinical examination (fever, jaundice, hepatosplenomegaly), rapid diagnostic tests, blood smear
examination, PCR, full blood count, liver/renal function tests.
Treatment\:
Non-falciparum malaria\: oral artemisinin combination therapy (ACT) or chloroquine.
Uncomplicated falciparum malaria\: ACT (artemether with lumefantrine).
Severe falciparum malaria\: intravenous artesunate or intravenous quinine.
Prevention\:
Chemoprophylaxis\: tailored to destination and individual risk factors (chloroquine, me
doxycycline).
Mosquito bite prevention\: DEET insect repellent, long-sleeved clothing, insecticide-treated bed nets.
Vector control\: mosquito breeding site reduction, indoor residual spraying.
Complications\: cerebral malaria, renal impairment, acidosis, hypoglycaemia, pulmonary oedema, anaemia, splenic rupture,
DIC, shock, haemoglobinuria, multiple organ failure, death.
Cerebral malaria\: severe neurological complication; features altered mental status, seizures, coma; requires IV
antimalarials and intensive supportive care.
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A comprehensive topic overview

Introduction

Malaria is a mosquito borne illness caused by a protozoa called P l a s m o d i u m . It is a noti
Kingdom.
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Its prevalence is the highest in regions such as sub-Saharan Africa, Southeast Asia and parts of South America. There were
an estimated 249 million cases of malaria worldwide in 2022 and approximately 608,800 fatalities due to the disease.
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In the United Kingdom, malaria is relatively rare but still poses a risk to travellers returning from endemic areas. An average
of 1,425 cases were seen in the United Kingdom between 2012 to 2021.
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While malaria can a
severe complications.
4

Aetiology

Malaria is a vector borne disease caused by a protozoa of the genus P l a s m o d i u m . Five species of Plasmodium cause
malaria\: P . f a l c i p a r u m , P . v i v a x , P . m a l a r i a e , P . o v a l e and P . k n o w l e s i .
4
The transmission of malaria occurs through the bite of an infected female Anopheles mosquito. They transmit the
parasites from infected humans to healthy individuals during blood feeding and act as vectors.
3
The incubation period of malaria varies for each species of Plasmodium and ranges from 7 to 30 days or longer.
5
A person infected with malaria can remain infectious to mosquitoes for the entire duration of the infection. If the person
does not receive proper treatment, malaria can persist in the body for months or even years, causing recurrent episodes of
illness.
Repeated exposure to malaria can result in the development of partial immunity in endemic regions, although complete
immunity is rarely achieved.
6

Pathophysiology

Plasmodium has a life cycle that involves a transition between human hosts and female Anopheles mosquitoes.
Transmission
An infected female Anopheles mosquito injects sporozoites into the human bloodstream during a blood meal.
Liver stage
Sporozoites travel to the liver and infect hepatocytes, where they replicate asexually to form merozoites. This is known as
the hepatic or schizogony stage. It lasts for 5-7 days in P. falciparum and between 6-18 days in other species and is an
asymptomatic stage.
A single sporozoite can produce between 10,000 to more than 30,000 merozoites.
Blood stage
erythrocytic stage.
Merozoites are released into the bloodstream, invade red blood cells and turn into trophozoites. This is called the
This initiates a cycle of replication, leading to RBC rupture and release of more merozoites. During this phase, RBC
destruction leads to the release of cytokines such as TNF from macrophages and neutrophils, which causes clinical
manifestations such as fever, anaemia, and organ dysfunction.
Gametocyte formation
Alongside the asexual replication cycle, some merozoites di
mosquito ingests these gametocytes during a blood meal, they can undergo sexual reproduction in the mosquito's gut,
producing new sporozoites that migrate to the salivary glands and are ready to infect another human host.
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Figure 1. Life cycles of Plasmodium.

Risk factors

Risk factors for malaria include\:
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Travel to or residence in endemic regions such as sub-Saharan Africa, Southeast Asia and parts of South America
Pregnant people, young children and older people
Immunocompromised people
Inadequate use of chemoprophylaxis

Clinical features

Clinical features of malaria can be vague and non-speci
considered in all patients presenting with non-speci

History

After being bitten by an infected mosquito, the incubation period ranges from 7 to 30 days. The prodromal phase follows
and lasts for 1 to 2 days.
Typical symptoms of malaria include\:
Fever spikes with chills and/or sweats (characteristically, cyclic fevers are seen in malaria)
Headache
Myalgia and arthralgia
Fatigue
Gastrointestinal symptoms\: nausea, vomiting, anorexia
Respiratory symptoms\: cough, respiratory distress
Other important areas to cover during the history include\:
4
Travel history\: recent travel to malaria-endemic regions, duration of stay, preventive measures such as
chemoprophylaxis and mosquito bite prevention
Past medical history\: previous episodes of malaria increase susceptibility to future infections, individuals with sickle cell
trait have some protection against severe malaria

Clinical examination

Typical clinical
4
Fever
Jaundice
Hepatomegaly and/or splenomegaly
Hypotension and/or tachycardia
Reduced consciousness/seizures/focal neurological de

Di

Due to the vague symptoms, there are a wide range of di
Meningitis or encephalitis
Lower respiratory tract infection
COVID-19
In
Gastroenteritis
Urinary tract infection
Lymphoma
Sepsis
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Viral hepatitis
HIV seroconversion
Legionella
Leptospirosis
If the patient has a positive history of travel, the following di
1
Viral haemorrhagic fevers such as Lassa fever, Crimean-Congo haemorrhagic fever, Marburg, and Ebola
Enteric fevers such as typhoid or paratyphoid
Arboviruses - Dengue, West Nile virus, and Japanese encephalitis
Rickettsial infection - Scrub typhus and relapsing fever
Trypanosomiasis
Rabies

Investigations

Bedside investigations

Relevant bedside investigations in the context of malaria include\:
Rapid diagnostic tests (RDTs)\: widely used for rapid and point-of-care diagnosis of malaria, detecting parasitic antigens
produced by Plasmodium

Laboratory investigations

Relevant laboratory investigations in the context of malaria include\:
Blood smear examination\: microscopic examination of thick and thin blood smears is the gold standard
Polymerase chain reaction (PCR)\: can be used to detect low levels of parasites
Full blood count\: thrombocytopenia and anaemia
Liver and renal function tests\: usually abnormal
Blood cultures\: can exclude other causes of infection/fever (will be normal in malaria)
G6PD activity\: before giving primaquine
All malaria cases should be notimalaria
reference laboratory for con
4

Management

Hospital admission may be necessary depending on the severity, the strain of Plasmodium involved and the complications.

Non-falciparum malaria

Oral artemisinin combination therapy (ACT) or chloroquine can be used to treat non-falciparum malaria.

Falciparum malaria

All patients with falciparum malaria should be admitted to hospital for the
Uncomplicated falciparum malaria
The
Alternative drugs include dihydroartemisinin-piperaquine, quinine or atovaquone proguanil, if ACT is not available.
Severe or uncomplicated falciparum malaria
The
4

Prevention

Chemoprophylaxis
Chemoprophylaxis should be taken before travelling to malaria-endemic areas. Antimalarial medications can be tailored to
the destination's drug resistance patterns and individual risk factors.
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Commonly used drugs for chemoprophylaxis and timeline on when to start them\:
1 week before travel for chloroquine and proguanil hydrochloride
2-3 weeks before travel for me
1-2 days before travel for atovaquone with proguanil hydrochloride or doxycycline
Prophylaxis should be continued for 4 weeks after leaving the area for all drugs except atovaquone with proguanil
hydrochloride. For atovaquone with proguanil hydrochloride, the prophylaxis should be stopped 1 week after leaving the
endemic area.
Mosquito bite prevention
Key mosquito bite prevention measures include\:
Insect repellents - Diethyltoluamide (DEET)
Wearing long-sleeved clothing
Using bed nets treated with insecticides such as permethrin
Vector control
Vector control involves implementing environmental measures such as mosquito breeding site reduction and indoor
residual spraying to decrease mosquito populations.
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Complications

Complications are almost always associated with P . f a l c i p a r u m infection and include\:
4
Impaired consciousness or seizures (cerebral malaria)
Renal impairment
Acidosis
Hypoglycaemia
Pulmonary oedema or acute respiratory distress syndrome.
Anaemia
Splenic rupture
Disseminated intravascular coagulopathy
Shock secondary to complicating bacteraemia/sepsis (algid malaria)
Haemoglobinuria ('black water fever')
Multiple organ failure
Death
Cerebral malaria
Cerebral malaria is a severe neurological complication of malaria caused by the infection of blood vessels of the
brain.
Infected red blood cells adhere to brain microvasculature, leading to microcirculatory obstruction, hypoxia, and
cerebral oedema.
Clinical features include altered mental status, seizures, coma, focal neurological de
intracranial pressure.
Management involves immediate treatment with IV antimalarial drugs, supportive care to manage complications such
as seizures and cerebral oedema, and close monitoring in an intensive care setting.
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References

NICE CKS. Malaria. Last revised in January 2024. Available from\: [LINK]
WHO. Malaria. Last revised on 4 December 2023. Available from\: [LINK]
GOV.UK Malaria imported into the UK\: 2021. Last revised on 9 June 2023. Available from\: [LINK]
Patient.info Malaria. Last revised on 2 April 2022. Available from\: [LINK]
CDC.GOV. Malaria. Last revised on 24 April 2024. Available from\: [LINK]
WHO.int. Malaria Q&A. Last revised on 12 January 2024. Available from\: [LINK]
NHS. Malaria. Last revised on 18 February 2022. Available from\: [LINK]
NIH (Arbeitskreis Blut, Untergruppe) Malaria. Published in 2009. Available from\: [LINK]
NICE BNF. Malaria, prophylaxis. Available from\: [LINK]
NIH (Idro R, Marsh K, John CC, Newton CR). Cerebral malaria\: mechanisms of brain injury and strategies for improved
neurocognitive outcome. Published in 2010. Available from\: [LINK]

Image references

Bbkkk. Available from\: [LINK]. L i f e c y c l e o f P l a s m o d i u m . Licence\: [CC BY-SA 4.0]

Reviewer

Dr Ramlingareddy
Senior Registrar Internal Medicine

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Contents

Introduction
Aetiology
Risk factors
Clinical features
Di
Investigations
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