Biogents – Science for Your Protection –

Malaria

Dashboard:

  • Annual Infections: estimated 228 million people in 2018
  • Annual deaths: 405,000 in 2018
  • Distribution: subtropics and tropics

Introduction

There are probably very few people who have never heard the term malaria. But what do you actually know about malaria?

Malaria is not caused by a virus or a bacterium, but by protozoan blood parasites in the genus Plasmodium. The European Centre for Disease Prevention and Control (ECDC) lists four species from the genus Plasmodium that are responsible for malaria in humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae. The World Health Organization (WHO) and the US Center for Disease Control and Prevention (CDC) list one more pathogen, Plasmodium knowlesi, which most often causes malaria in macaque monkeys but occasionally also in humans. Of the 5 types of human malaria, P. falciparum and P. vivax are responsible for almost 95% of all infections worldwide (1; 2)

Malaria is one of the three most common infectious diseases, together with HIV/AIDS and tuberculosis. It is the only one of these three diseases that is transmitted by mosquitoes (mosquitoes of the genus Anopheles) and often poses a major economic and health challenge in the regions where it is present.

Between 200 and 250 million people become infected with the disease every year. The WHO estimates that 405,000 died from malaria in 2018. According to the 2019 WHO World Malaria Report, 50% of global cases (about 228 million) were attributable to only 6 countries:

Nigeria (25%), the Democratic Republic of the Congo (12%), Uganda (5%) as well as Côte d’Ivoire, Mozambique and Niger with 4% each.

About 67% of the deaths were children. The most severely affected countries in the world are often also the poorest countries in the world. The CDC speaks of a “vicious circle of poverty and disease”. While the WHO Africa region accounts for 93% of all reported cases and 94% of all deaths, Plasmodium parasites are found today in about 91 countries in the world. This widespread distribution leaves about 50% of the world’s population potentially at risk for malaria. (1; 2; 3; 4; 5)

The transmission route of malaria

Malaria is caused by protozoan parasites of the genus Plasmodium and are transmitted by Anopheles mosquitoes.

Transmission cycle

  1. Humans become infected through the bite of an infected Anopheles mosquito. During the feeding process, infectious sporozoites are release from the mosquito’s salivary glands and enter the bloodstream
  2. Sporozoites make their way to the liver where they invade liver cells. Within the liver cells the parasite multiples and transforms to a stage called merozoites. Infected cells eventually rupture releasing merozoites into the blood where the enter red blood cells.
  3. In the red blood cells, the parasites grow, eventually destroying the blood cells and the cycle of invasion and destruction continues.
  4. Reproductive stages of the parasite, male and female gametocytes, occur in some blood cells. When ingested by a biting mosquito, they mate in the gut of the mosquito forming an oocyst.
  5. Within the oocyst, sporozoites develop and eventually make their way to the salivary glands where the whole cycle repeats with the transfer of infectious sporozoites to a human during a mosquito bite
Malaria transmission cycle

According to current knowledge, human Plasmodium parasites are transmitted exclusively by mosquitoes (Culicidae) of the genus Anopheles. Anopheles is a genus of mosquitoes with a worldwide distribution world that are commonly referred to as “malaria mosquitoes“. These and other mosquitoes that are able to transmit diseases are called vectors. Currently, 493 species are ascribed to the genus Anopheles, but not all of them can transmit the pathogen. According to the ECDC, about 60 to 100 Anopheles mosquito species are capable of spreading the pathogen, sometimes with very different efficacy. The efficiency of transmission is referred to as the vector competence of the respective species. (6) According to the CDC, only about 30 to 40 species are routinely associated with actual transmission in the wild. (1, 2)

Distribution map of malaria

Malaria distribution map from 2019 WHO World Malaria ReportSource: World Malaria Report 2019

However, the risk of malaria transmission by mosquitoes should not be underestimated in other regions of the world that are not currently affected by the disease but where Anopheles mosquitoes are distributed. The “Malaria Atlas Project” of the WHO and Oxford University has defined so-called “Dominant Vector Species”. These 41 Anopheles species are characterized by the fact that they have the most efficient vectors in the geographic regions where they are found. In areas where malaria has been eliminated, but the vectors persist, there is, a potential risk for transmission should the pathogen be introduced. (7)

Since human Plasmodium are blood parasites, transmission by vectors is not the only way to become infected. Blood transfusions, donor organs or contaminated syringes also pose a risk. Transmission from a mother to her child is also possible during pregnancy and delivery. (8)

The disease

While there is no typical course of malaria, commonly a patient will report a combination of the symptoms below:

  • Fever
  • Chills
  • Sweats
  • Headaches
  • Nausea and vomiting
  • Body aches
  • General malaise

The course of the disease differs depending on the causative pathogen.

The most common, but also the most severe form of the disease is caused by P. falciparum.  The incubation period is between 7 to 15 days after infection. The initial symptoms are often accompanied by vomiting, cough, diarrhea and abdominal pain. In severe cases, symptoms related to organ failure may develop, such as acute renal failure, pulmonary edema and circulatory collapse. Cerebral malaria can occur when the disease attacks the central nervous system and the brain causing seizures, clouding of consciousness, coma and potentially, death. Falciparum malaria may be fatal if treatment is delayed beyond 24 h after the onset of clinical symptoms. Travelers to P. falciparum endemic areas should always consider malaria a possibility if a fever occurs around 7 days after return.

The second most common form of the disease is caused by P. vivax. The incubation period is about 12 to 18 days. After the initially general and unspecific symptoms, a typical alternating fever sets in and every 48 hours, the patient experiences violent fever spikes lasting 3 to 4 hours. The body temperature can rise extremely quickly to around 40°C and then fall again just as quickly, accompanied by outbreaks of sweating. The disease is well treatable today and is very rarely fatal.

Malaria caused by P. ovale and P. malariae are much less common and also easily treatable.

A fifth species that can occasionally infect humans is P. knowlesi, which is usually associated with monkeys. Human cases have been reported from Malaysia, Indonesia, and other SE Asian countries. (10)

Diagnosis
Malaria is typically diagnosed by identification of the parasites in a blood smear with microscopy. Rapid diagnostic tests (RDTs) are also available that can detect malaria antigens in the blood in about 15 minutes. These tests do not replace microscopy, but can be useful when a trained microscopist is unavailable.

Brief history of malaria

Malaria has been around for as long as humans have existed and so it has accompanied almost every episode of human history. The first written records of the disease can be found in Chinese documents as early as 2700 BC, in 2000 BC on Mesopotamian clay tablets or in 1570 BC on Egyptian papyrus. Almost 700 years later, an ancient Indian text even calls it the “king of diseases”. Malaria is mentioned in Homer’s Iliad in 850 BC as well as in the natural philosophy texts of Empedocles around 550 BC and Hippocrates around 400 BC. Around the same time, Aristotle, Plato and Sophocles are said to have written about it. Although the exact circumstances of his death are unclear, malaria is often discussed as a contributing factor in the death Alexander the Great in Babylon at the age of 32.  About 200 years later, the Romans presumably brought the pathogen from Egypt and carried it as far north as England and Denmark. Malaria was a permanent feature of early European settlements. Around 1900, the pathogen had its largest distribution worldwide and was found in the tropics, subtropics and temperate latitudes of all continents, from Sweden, Russia and the USA in the north to Argentina, South Africa and Australia in the south. (11; 12; 13; 14)

Europe

Due to strict public health measures instituted in the 20th century, it is extremely unlikely to get malaria in Europe today. In 2018, the ECDC registered 8349 cases. By far the most of these cases were travel related. However, 14 cases were autochthonous, which means that the patients were infected in Europe. In Greece, multiple small outbreaks of malaria have been documented since 2009 with about a dozen locally transmitted cases per year. In 2018, 10 of the 14 autochthonous cases recorded in Europe originated in Greece. Two were detected in Spain and one each in Italy and France. In Germany, 896 cases were reported, all of which could be attributed to travel to malaria endemic areas.

The data for Germany from 2018 are in line with the long-term average. Over the past 20 years, the Robert Koch Institute (RKI) has reported between 500-1000 imported malaria cases every year. Although the risk of autochthonous transmission in Germany is very low, Anopheles vectors of the 20th century are still common and widespread in the country today. (15; 16; 17)

North America

It was not until the 1930s that the USA began to take targeted, large-scale action against malaria. One of these measures was the foundation of the Office of National Defense Malaria Control Activities, today’s CDC, in 1946. (11; 18)

Since 1951, malaria has also been considered as eradicated in North America. However, it is still a major problem in Latin America. Every year, the CDC registers between 1500 to 2000 cases of malaria, about 5 of which are fatal. These infections are acquired, almost exclusively,  during a visit to countries where the disease is endemic. (19)

What can you do to protect yourself?

According to the WHO, about 2.7 billion US dollars are invested every year to further reduce malaria. Every year the list of malaria-free countries grows. In 2018, the WHO declared Paraguay and Uzbekistan malaria-free, and in 2019 Algeria and Argentina were added. The countries on the Mekong River (China, Laos, Myanmar, Thailand, Cambodia and Vietnam), once one of the most severely affected regions in the world, were able to reduce the number of infections by 76% between 2010 and 2018, and the number of deaths fell by 95%. Extensive multinational projects such as the “Malaria Atlas Project” are supporting local governments as well as scientists worldwide to further reduce the disease.

As a private person, whether at home or in your own garden, you can help to defeat malaria. The easiest way to do this is to protect yourself and thus not contribute to the spread of the disease. If you are travelling in an endemic area, you should always make sure that you are well protected against mosquito bites. It is best to have an insect spray with you that contains the proven active ingredients such as DEET, Picaridin or oil of lemon eucalyptus. These substances have shown effective protection against mosquitoes and other insects in numerous laboratory tests, also in our own Biogents laboratory. However, since it is not always possible to be one hundred percent sure that a mosquito won’t bite you, you should talk to your family doctor about chemoprophylaxis in malaria areas. These are drugs that protect you from infection by the parasite in case of a bite. In your local accommodations, you should provide nets for the doors and windows and beds. If you want to protect yourself at home against mosquitoes and the diseases they transmit, an effective, long-term as well as eco-friendly measure is using mosquito traps such as the BG-Mosquitaire CO2. (1; 2; 20)

Sources:
1) https://www.ecdc.europa.eu/en/malaria/facts/factsheet
2) https://www.cdc.gov/malaria/about/biology/index.html
3) https://www.bundestag.de/resource/blob/410842/9b3adbca930e6a628e70e76fe0a2f88d/weltweit-infektionskrankheiten-data.pdf
4) https://www.who.int/en/news-room/fact-sheets/detail/malaria
5) https://www.cdc.gov/malaria/malaria_worldwide/impact.html#:~:text=Nearly%20half%20the%20world’s%20population,clinical%20episodes%2C%20and%20445%2C000%20deaths.
6) https://www.rki.de/DE/Content/InfAZ/V/VektorInf/Bundesgesundheitsblatt_Mai_2014_Frank_et_al.pdf?__blob=publicationFile
7) https://malariaatlas.org/
8) https://www.cdc.gov/malaria/about/faqs.html#transmission
9) https://www.dimdi.de/static/de/klassifikationen/icd/icd-10-gm/kode-suche/htmlgm2018/block-b50-b64.htm
10) https://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Malaria.html
11) https://www.ncbi.nlm.nih.gov/books/NBK215624/pdf/Bookshelf_NBK215624.pdf
12) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617065/#B14-microorganisms-07-00179
13) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825508/
14) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145123/
15) https://www.ecdc.europa.eu/sites/default/files/media/en/publications/Publications/Joint-ECDC-WHO%20mission-malaria-Greece-2012.pdf
16) https://www.ecdc.europa.eu/sites/default/files/documents/malaria-annual-epidemiological-report-2018.pdf
17) https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2018/Ausgaben/44_18.pdf?__blob=publicationFile
18) http://medcraveonline.com/MOJAP/MOJAP-02-00048.pdf
19) https://www.cdc.gov/malaria/resources/pdf/fsp/cdc_malaria_domestic_unit.pdf?source=post_page—————————
20) https://www.who.int/news-room/feature-stories/detail/world-malaria-report-2019