Malaria Flashcards
Hypnozoite
These species have a stage of their lifecycle that can remain dormant, called a hypnozoite.
Indoor Residual Spraying
In the past, malaria was eliminated from the United States using Indoor Residual Spraying (IRS) from 1955-1969 (primarily DDT). However, its use was largely discontinued before it was eliminated elsewhere due to public concerns about environmental impacts. IRS with DDT is seeing a controlled comeback as an effective tool to reduce malaria in endemic countries.
Basic evolution of malaria, including what species came in what order, what role Duffy receptors play, and how malaria has shaped human evolution
Malaria is a protozoan parasite that existed in the presence of mosquitos for 500,000 years. It was not initially a human parasite. It took a long time to evolve to survive in humans. It could be argued that despite being in humans 10,000 or so years to date, it still kills too readily and thus isn’t that well adapted to us. Malaria exists in lots of different animals, exploiting many niches.
Plasmodium malariae was an early species that remained dormant for months or years inside humans waiting for a mosquito bite. Plasmodium vivax evolved next, and was able to actually enter blood cells by attaching to “Duffy” receptor proteins. Duffy receptors are proteins on the surface of red blood cells that participate in cell signaling. P. vivax mostly spread by Anopheles arabienses and other mosquito species (these types of mosquitoes mostly fed on animals, not humans). Duffy receptors are not essential for survival, so being “Duffy-less” began to become a dominant human genetic mutation. Now, 2/3 of Africans and their descendants are “silent” for Duffy blood group genes, so P. vivax is spread more in Asia and Europe.
Malaria evolution shifted about 2500 years ago. It was around this time that the Sahara desert formed, changing the ecology of the landscape. Human behavior changed alongside the landscape, with more people settling into farming villages. A new species of mosquito, Anopheles gambiae evolved, which specialized in biting humans. The scene was now set for a new parasite that used multiple strategies to infect red blood cells, not just the Duffy receptors. Plasmodium falciparum causes most human malaria infections now. It has antigens that vary and can be turned on and off, making it so the parasites in the blood all look different to the immune system (crazy, right?). Our immune systems can fight it off better after multiple infections. Children having their first infection are the most likely to die. Malaria has impacted human evolution greatly. About 1 of every 14 people carries a genetic mutation related to a hemoglobin disorder (thalassemia, sickle cell, ovalocytosis, hemoglobin E, and others). Hemoglobin disorders change the shape of red blood cells and confer resistance to the malaria parasite.
Malaria life cycle as drawn in class
The malaria parasite travels through 3 stages: inside the mosquito, the human liver and the human blood stream.
Malaria symptoms
Typical symptoms of malaria include fever, chills, nausea, and sweating. Symptoms occur during the human blood stream stage of the life cycle. The incubation period depends on the species, but is around ten days on average. Relapses for P. vivax and P. ovale can occur weeks to months later. This is because these species have a stage of their lifecycle that can remain dormant, called a hypnozoite.
Malaria prevention and treatment strategies
The primary reason for recent drops in mortality due to malaria (about 25%) is the use of insecticide-treated bed nets. However, resistance to the insecticides is becoming common among Anopheles gambiae.
In the past, malaria was eliminated from the United States using Indoor Residual Spraying (IRS) from 1955-1969 (primarily DDT). However, its use was largely discontinued before it was eliminated elsewhere due to public concerns about environmental impacts. IRS with DDT is seeing a controlled comeback as an effective tool to reduce malaria in endemic countries.
Drugs such as primaquine and doxycycline (different ones for different strains/locations/ travel lengths) are given as a malaria prophylaxis to those traveling to endemic countries. Vaccines are also being tested, including some that seem to have about 50% effectiveness in early trials! Time will tell if they will stay effective.
The history of quinine and artemisinin
Treatment for malaria has focused primarily on 2 drugs: quinine and artemisinin. Quinine is a class of drugs derived from the cinchona plant that were popularized in the 1600’s by a Jesuit priest in South America. They target the red blood cell phase of the parasite’s life cycle. However, resistance to quinine in many parts of the world has made it far less effective.
In the 1960’s the Chinese did a large search for plants that were effective against malaria, and found artemisinin in sweet wormwood. We aren’t sure exactly how it works, but it may target the reproductive stage of the lifecycle.
Where new malaria strains come from
Unfortunately, resistant strains to artemisinin are also becoming more common. The resistant strains develop primarily along the border of Thailand and Cambodia, for reasons that aren’t totally understood. They then spread to the rest of Asia, Africa, and Central and South America.
