section_path: Cause
section_name: Cause
paragraph_text: Cause
  
  Malaria is caused by infection with parasites in the genus Plasmodium. In humans, malaria is caused by six Plasmodium species: P. falciparum, P. malariae, P. ovale curtisi, P. ovale wallikeri, P. vivax and P. knowlesi. Among those infected, P. falciparum is the most common species identified (~75%) followed by P. vivax (~20%). Although P. falciparum traditionally accounts for the majority of deaths, recent evidence suggests that P. vivax malaria is associated with potentially life-threatening conditions about as often as with a diagnosis of P. falciparum infection. P. vivax proportionally is more common outside Africa. Some cases have been documented of human infections with several species of Plasmodium from higher apes, but except for P. knowlesi —a zoonotic species that causes malaria in macaques —these are mostly of limited public health importance.
  
  The Anopheles mosquitos initially get infected by Plasmodium by taking a blood meal from a previously Plasmodium infected person. Parasites are then typically introduced by the bite of an infected Anopheles mosquito. Some of these inoculated parasites, called " sporozoites ", probably remain in the skin, but others travel in the bloodstream to the liver, where they invade hepatocytes. They grow and divide in the liver for 2–10 days, with each infected hepatocyte eventually harboring up to 40,000 parasites. The infected hepatocytes break down, releasing these invasive Plasmodium cells, called " merozoites ", into the bloodstream. In the blood, the merozoites rapidly invade individual red blood cells, replicating over 24–72 hours to form 16–32 new merozoites. The infected red blood cell lyses, and the new merozoites infect new red blood cells, resulting in a cycle that continuously amplifies the number of parasites in an infected person. Over rounds of this infection cycle, a small portion of parasites do not replicate, but instead develop into early sexual stage parasites called male and female " gametocytes ". These gametocytes develop in the bone marrow for 11 days, then return to the blood circulation to await uptake by the bite of another mosquito. Once inside a mosquito, the gametocytes undergo sexual reproduction, and eventually form daughter sporozoites that migrate to the mosquito's salivary glands to be injected into a new host when the mosquito bites.
  
  The liver infection causes no symptoms; all symptoms of malaria result from the infection of red blood cells. Symptoms develop once there are more than around 100,000 parasites per milliliter of blood. Many of the symptoms associated with severe malaria are caused by the tendency of P. falciparum to bind to blood vessel walls, resulting in damage to the affected vessels and surrounding tissue. Parasites sequestered in the blood vessels of the lung contribute to respiratory failure. In the brain, they contribute to coma. In the placenta they contribute to low birthweight and preterm labor, and increase the risk of abortion and stillbirth. The destruction of red blood cells during infection often results in anemia, exacerbated by reduced production of new red blood cells during infection.
  
  Only female mosquitoes feed on blood; male mosquitoes feed on plant nectar and do not transmit the disease. Females of the mosquito genus Anopheles prefer to feed at night. They usually start searching for a meal at dusk, and continue through the night until they succeed. However, in Africa, due to the extensive use of bed nets, they began to bite earlier, before bed-net time. Malaria parasites can also be transmitted by blood transfusions, although this is rare.