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      Malaria

      Latest update: - Authors: Ula Maniewski, Nele Alders

      Malaria is a life- threatening disease caused by Plasmodium parasites transmitted by mosquitoes. There are five parasite species that can infect humans: 

      • Plasmodium falciparum
      • Plasmodium vivax
      • Plasmodium ovale
      • Plasmodium malariae
      • Plasmodium knowlesi

      Plasmodium falciparum is the deadliest amongst the species and the most prevalent on the African continent. Plasmodium vivax is the dominant malaria parasite in most countries outside of sub-Saharan Africa. Plasmodium malariae is uncommon but is found in most malaria endemic areas. Plasmodium ovale is relatively unusual outside of sub-Saharan Africa and comprises less than one percent of isolates. Plasmodium knowlesi is very rare and has been identified in southeast Asia. It's natural reservoir are macaques. It was initially discovered in Malaysia, but human cases have been reported from several neighbouring countries.

      Transmission

      Vector

      Infectious female Anopheles mosquitoes who only bite in the evening and night. They often go unnoticed because they are small and almost make no sound. 

      Life cycle

      After a bite by an infectious mosquito, people are inoculated with sporozoites. These will enter the hepatocytes within minutes where they start to multiply quickly. After an incubation period of minimally one week, the malaria parasites will appear in the blood, where they will infect the red blood cells and start to multiply (trophozoites). After one (P. knowlesi), two (P. falciparum, P. vivax, P. ovale) or three (P. malariae) days, the reds blood cells start to burst. The released parasites will infect other red blood cells. This cycle will be repeated multiple times. Blood stage parasites are responsible for the clinical manifestations of the disease. After a few cycles, gametocytes (male microgametocytes and female macrogametocytes) will appear. If ingested by an Anopheles mosquito during a blood meal, the parasites can continue its lifecycle in the Anopheles mosquito.

      Incubation period

      The time between a bite by an infectious mosquito and the development of first symptoms can range from seven days to months and sometimes more than a year.

      Symptoms

      Travellers should be aware that malaria is a life-threatening disease that can be fatal within days of onset. They must be informed that medical advice must be sought immediately in the event of fever or other flulike symptoms, until at least 3 months after their return. Malaria can be treated effectively, but without treatment this disease can quickly cause complications and become fatal. The disease appears very similar to influenza - particularly during the first few days - with fever, headache, muscle pain and sometimes diarrhea or a cough.

      Plasmodium falciparum is the most common species and results in the most severe symptoms. Plasmodium falciparum-infected erythrocytes adhere to the vascular endothelium of blood vessel walls and do not freely circulate in the blood. When this sequestration of infected erythrocytes occurs in the vessels of the brain, it is believed to be a factor in causing the severe disease syndrome known as cerebral malaria, which is associated with high mortality. 

      The other three species (P. vivax, P. ovale, P. malariae) can give significant symptoms but are normally not deadly. If mortality occurs, it is usually due to the rupture of the spleen but in rare cases severe malaria with organ failure can develop. Late-onset P. vivax and P. ovale malaria may occur despite effective prophylaxis because these parasites cause relapses that cannot be prevented with medicines that are currently recommended for chemoprophylaxis.

      Plasmodium knowlesi is primarily seen by macaques in forested areas of South East Asia, but can cause severe malaria (similar to P. Falciparum) in humans too.

      Still every year a few people die in Belgium due to malaria. These are mainly people who didn’t adhere to preventive malaria medication or where there was a delay in seeking medical attention, establishing a diagnoses or involving expert care. 

      The diagnosis of malaria can be established with a simple blood analysis (EDTA- tube) by a reliable laboratory within a few hours.

      Risk areas

      Malaria occurs only in certain tropical and subtropical areas in South America, Central America, Africa and Asia. From 1500 to 3000 m there are less or no Anopheles mosquitos. The risk of infection may also vary according to the season, being highest at the end (or soon after) the rainy season.

      The malaria world map shows malaria risk areas of all the countries of the world. More information on the creation of the malaria maps can be found on Malaria maps- background. 

      View the map

      Prevention

      Introduction

      Malaria prevention is always a combination of several measures, abbreviated by the World Health Organization (WHO) as ABCDE:

      • Awareness: Be aware of the risk according to the area, the incubation period, the possibility of delayed onset and the main symptoms.
      • Bite prevention: Protect yourself from dusk till dawn.
      • Chemoprophylaxis: Use preventive medication if indicated.
      • Diagnosis: Immediately seek diagnosis and treatment if a fever develops one week or more after entering an area where there is a malaria risk and up to three months after return.
      • Environment: Avoid outdoor activities in environments that are mosquito breeding places.

      Preventive measures

      Travellers at risk for malaria should be advised on:

      • Mosquito bite prevention: which consists of a combination of mosquito-repellent measures especially from dusk through to sunrise. These measures are also necessary when taking chemoprophylaxis, as the tablets never guarantee 100% protection.
      • Chemoprophylaxis: whether preventive malaria medication should be added to the other measures depends on how high the risk is:
        • Low risk area (pink areas): Chemoprophylaxis is not needed.
        • Moderate risk area (orange areas): Usually mosquito bite prevention and awareness are recommended. In case of higher risk of contracting malaria or severe complications, or when mosquito bite prevention is not possible, chemoprophylaxis is recommended.
        • Seasonal risk (purple areas): Chemoprophylaxis is indicated during the rainy season, but not during dry season.
        • High risk (red areas): Chemoprophylaxis is recommended for all.
      • Emergency treatment: in certain cases emergency treatment is advised.
      • Prolonged or frequent stays: a modified malaria advise applies for long or frequent stays in a malaria endemic area.

      Malaria vaccine

      Malaria vaccines have been in development since 1960’s but only in 2021 a first malaria vaccine RTS,S/AS01 (Mosquirix®)  is far enough in its development to be recommended by WHO for broad use among children living in regions with moderate to high P. falciparum malaria transmission. In 2023 a second malaria vaccine R21 (Matrix-M®) is prequalified by WHO. 

      Both vaccines work on the ‘pre-erythrocyte’ stage by targeting sporozoites through the circumsporozoite protein (CSP), which blocks the parasite from entering the liver. Both vaccines are adjuvanted recombinant virus-like particles with sequences of CSP fused to the hepatitis B surface antigen (HBsAg).

      Both vaccines are administered in a primary series of three doses with one month interval and a fourth booster dose.  It is not clear yet whether more boosters are useful and whether the vaccines are interchangeable.

      The vaccines are most effective when used in combination with other preventive measures.
      Due to their limited efficacy and rapidly weaning immunity, it is currently not advised for the use in travellers in the prevention of malaria. They can be exceptionally considered in expat children living in remote areas with a high malaria risk in combination with other malaria prevention strategies, in countries where vaccination against malaria is implemented. 

      RTS,S/AS01 (Mosquirix®)  

      RTS,S/AS01 (Mosquirix ®) has been licensed by the European Medicines Agency for the use outside of the European Union in children aged 6 weeks to 17 months. A fourth dose (booster dose) is recommended 18 months after the third dose.

      The vaccine has been shown to significantly reduce malaria and deadly severe malaria among young children in low-resource settings. In children aged 5-17 months, the vaccine efficacy against the first or only episode of clinical malaria over 12 months of follow-up was 56%. Protection against P. falciparum malaria wanes over time and vaccination may delay the acquisition of natural immunity. The vaccines also offers protection against hepatitis B infections virus but should not be used only for this purpose. 

      R21/Matrix-M®  

      R21/Matrix-M® malaria vaccine is prequalified by WHO in children aged between 5 and 36 months old.  

      In this vaccine, the virus-like particles are covered with more CSP antigens and contains no or almost no HBsAg not fused with CSP. It also uses a different adjuvant, derived from saponin, which is called Matrix-M®. Its efficacy is similar to RTS,S/AS01 (Mosquirix ®). A fourth booster doses is recommended 12 months after the third dose. 

      Malaria rapid diagnostic test

      A rapid antigen test for malaria is used in conjunction with a thick and thin smear in established laboratories. Theoretically this could be an interesting tool, but the use has not been validated in travellers and therefore can’t be sold as a diagnostic test for personal use. 

      It is available for purchase on the internet, but the use is discouraged because of the variable quality of the test, the frequent issues with the diluent and the lack of ability to perform and interpret the test correctly as a non-trained person. Due the limitations it’s not advised for use in travellers and unreliable to diagnose malaria and decide on the need of treatment. 

      Additional information

      References

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