In the 18th century, many thought that malaria was caused by breathing in "bad air" and this is where the name stems from! Scientists later discovered that this communicable disease, which is the third largest killer of children, is in fact spread by parasites of an infected mosquito - but the name stuck!
According to the World Health Organisation (WHO), about 240 million people became infected with malaria, of which about 600,000 died in 2020 alone. Despite successes in reducing the fatality rate by 25% during this century due to the development of effective prevention and treatment strategies, malaria incidences have been increasing since the 1970s. As such, malaria remains one of the world’s biggest threats to public health, especially in tropical countries.
Fig. 1: Worldwide Malaria incidence
What is malaria?
Malaria is an infectious disease caused by the Plasmodium parasite. Malaria is transmitted between individuals via the female mosquito Anopheles. This mosquito bites humans to feed on their blood. If the bitten person is infected with malaria, the mosquito can inadvertently also collect the pathogen, which multiplies inside the mosquito. Anopheles mosquitoes can carry Plasmodium without becoming sick. The plasmodium infection is kept under control by the mosquito’s immune system, but when the infected insect feeds again, it will inject the pathogenic microorganism into an uninfected person.
Malaria is a serious and sometimes fatal acute febrile infectious disease caused by protoctist Plasmodium parasites that infect and are transmitted between humans via mosquito bites.
Approximately half of the world’s population currently live in regions where they are at risk of contracting malaria. Malaria incidence is bigger throughout the tropics and subtropical regions, particularly in sub-Saharan Africa and India. Up to 80% of malaria’s victims are children under 5, making this infectious disease one of the leading causes of child mortality worldwide.
The African continent accounts for 95% of all malaria cases and deaths, making this region disproportionately suffer from the burden of malaria disease. Four African countries alone including Nigeria, the Democratic Republic of the Congo, Tanzania, and Mozambique, account for half of the worldwide malaria fatalities.
The causes of malaria
Malaria is caused by five different species of the Plasmodium group. Plasmodium microorganisms are protoctist single-cell pathogens, also called protozoans. This group of pathogens are eukaryotic parasitic organisms that can infect humans, animals or plants. Two of the five parasitic species, Plasmodium falciparum and Plasmodium vivax, are the most dominant and therefore, the greatest threat. Plasmodium falciparum, in particular, is the deadliest malaria pathogen and the most widespread.
The other species include Plasmodium malariae, Plasmodium knowlesi and Plasmodium ovale.
Eukaryotic cells contain membrane-bound organelles, such as the nucleus.
Malaria disease is essentially caused by the asexual infective stage of the parasite when it lives within the human red blood cells. The parasite multiplies and excretes several toxic waste substances into the red blood cell, like the hemozoin pigment or GPI. These substances accumulate within the red blood cell and are eventually released into the bloodstream when the infected erythrocyte lysates. The released toxins then stimulate the immune system, creating many of the feature clinical symptoms of malaria and further influencing the pathophysiology of this disease.
The symptoms of malaria
Malaria infection can result in various symptoms, often dividing malaria into uncomplicated or severe (complicated) diseases. Following the infective mosquito bite, there is an incubation period before symptoms appear that can range from a week to a year, but, on average, it takes 10-15 days. In some aggressive cases, malaria symptom onset can occur as fast as 24 hours after the infective mosquito bite.
Shorter incubation periods are more common with the more dominant Plasmodium falciparum parasite.
The incubation period refers to the time taken for the clinical manifestations of the disease to appear after exposure to a pathogen.
Initial symptoms of malaria may be mild and unspecific, like fever, headaches, and chills, making it harder to diagnose.
The initial flu-like symptoms contribute to the misdiagnosis of this infectious disease.
Other more advanced clinical features of malaria include:
If left untreated and especially in Plasmodium falciparum infection, symptoms can quickly progress to severe illness. In the more severe forms of malaria disease caused by this parasite species, the infection is often complicated by organ failures and associated pathological manifestations like acute kidney injury or acute respiratory distress syndrome, ultimately leading to death.
Severe manifestations of malaria disease can include, for example, cerebral malaria. This condition, often associated with high mortality, has several neurological symptoms like seizures, coma and abnormal behaviour. Cerebral malaria is caused when erythrocytes infected with Plasmodium falciparum adhere to the lining of brain blood vessels instead of freely circulating in the blood.
The transmission of malaria
Malaria is typically transmitted between infected and uninfected people via the female Anopheles mosquito. This vector insect bites humans to feed on their blood to obtain the necessary proteins. If the bitten person is infected with the malaria parasite, the mosquito will also become infected while collecting the blood. The parasite will then grow and multiply inside the insect. When the mosquito feeds again, it will also release the parasite into the bloodstream of the bitten individual. Every time the mosquito feeds, it releases anticoagulants from its salivary glands into the bloodstream to facilitate blood uptake. The parasite is present in the insect’s salivary glands and is therefore released alongside the anticoagulants.
Vectors are organisms that carry the infectious disease pathogen between people or between animals and humans. The insect female Anopheles mosquito is the malaria vector and does not suffer from being infected with the parasite.
Anticoagulants are agents that prevent blood clotting, effectively ‘thinning’ the blood.
Malaria transmission, therefore, requires cyclical infection of both humans and mosquitoes. Plasmodium multiplies inside both hosts and increases the chance of infecting other mosquitoes and humans.
Plasmodium’s life cycle has two stages: a sexual stage in the mosquito and an asexual stage inside humans.
Fig. 2: Malaria transmission
Upon infection, the malaria pathogen parasite enters the bloodstream and initially targets liver cells followed by red blood cells, multiplying inside both. Most pathological manifestations result from the erythrocyte infection stage. In this step, the parasite repeatedly lyses the red blood cells it was growing inside and invades other red blood cells cyclically.
In other less common cases, malaria can also be transmitted between individuals by reusing unsterile needles during blood transfusions (transfusion-transmitted malaria) or from mother to foetus during pregnancy (congenital malaria).
In congenital malaria, the parasite is directly transmitted by infected mothers across their placenta either before or during their delivery.
The difference between yellow fever and malaria
Malaria is sometimes confused with yellow fever, another febrile mosquito-borne disease, but these are two different infectious diseases.
Despite both being common in tropical African and South American countries, malaria is far more deadly than yellow fever.
Malaria is caused by the protozoan Plasmodium pathogen transmitted via the female anopheles mosquito. Yellow fever is caused by a virus, more specifically an arbovirus of the flavivirus genus, transmitted by mosquitos of the Haemogogus and Aedes species.
A severe case of yellow fever can be mistaken for malaria as both diseases are hard to diagnose and have initial fever-like symptoms. Yellow fever, unlike malaria, however, does not have any specific drug treatment available, as no specific antiviral drugs exist to target the yellow fever viral pathogen. Despite this, most people tend to recover within of few days with supportive treatment.
Treatment for malaria
Malaria is a treatable and curable disease. Early diagnosis and treatment are important to reduce malaria incidence and deaths. The WHO guidelines recommend that malaria diagnosis be done through microscopical blood analysis for parasite detection or by using rapid diagnostic tests that rely on antigen detection.
An accurate and early diagnosis helps distinguish a malaria fever from other febrile illnesses allowing for more effective treatments and better surveillance.
Malaria treatments include the antimalarial drugs quinine and chloroquine, which prevent the parasite from growing and spreading within the body by inhibiting its protein synthesis. These drugs can also be used as prophylactics (preventive drugs) to stop an infection from occurring if a person gets bitten by an infected mosquito.
According to the WHO, the best treatment available is artemisinin-based combination therapy (ACT), especially for Plasmodium falciparum infection. ACT works by rapidly eliminating the malaria pathogen from the bloodstream, thus stopping disease progression.
Besides prophylactic drugs, two other important preventive measures play a significant role in helping the global effort to control malaria. These are vector control strategies and the malaria vaccine.
Vector control strategies include efforts to either reduce the number of malaria vector mosquitos or avoid getting bitten by them. The most important strategies in vector control are the use of insecticide-treated bed nets to protect against mosquito bites during sleep, insect-repellent spraying, or other insecticide usages that help kill infective mosquitoes.
Resistance to a drug usually occurs whenever a treatment is used extensively to kill a pathogen. Antimalarial drug resistance has emerged as a serious problem in tackling malaria.
Resistance to chloroquine, for example, has emerged, with drug-resistant Plasmodium strains appearing throughout South America and Africa.
Surveillance is paramount to detect these events and inform the treatment policy promptly. The appearance of antimalarial drug-resistant Plasmodium strains, and insecticide (DDT) resistant mosquitoes, were essentially the reason the WHO was unable to eradicate this disease throughout the past century, despite continuous efforts.
Lastly, since late 2021, the WHO has recommended using the first approved malaria vaccine RTS, S (Mosquirix), among children. This vaccine acts against Plasmodium falciparum and significantly reduces severe malaria disease in children. This new important tool will undoubtedly be very important to help meet the WHO Global Malaria program objective of reducing by at least 90% the incidence and mortality rates of malaria by 2030.
Check out our Vaccine article!
Malaria - Key Takeaways
- Malaria is a febrile infectious disease caused by protoctist Plasmodium parasites that infect and are transmitted between humans via female Anopheles mosquito bites.
- Malaria is caused by five different species of the Plasmodium group and its pathophysiology is mostly explained due to the infection and destruction of human red blood cells.
- Symptoms of malaria are often flu-like, such as fever and headaches. Severe clinical manifestations include cerebral malaria and liver enlargement.
- Malaria treatments include the antimalarial drugs quinine and chloroquine as well as artemisinin-based combination therapy (ACT).
- Vaccine administration and vector control strategies, such as bed nets are currently being used to reduce malaria incidence.
Explanations 
Exams 
Magazine 
