Editing Malaria (section)

==Cause==
[[File:Life Cycle of the Malaria Parasite.jpg|thumb|upright=1.6|The life cycle of malaria parasites: Sporozoites are introduced by a mosquito bite. When they reach the liver, they multiply into thousands of merozoites. The merozoites infect red blood cells and replicate, infecting more and more red blood cells. Some parasites form gametocytes, which are taken up by a mosquito, continuing the life cycle.]]

Malaria is caused by infection with [[parasite]]s in the genus ''[[Plasmodium]]''.<ref name="US CDC-2022">{{cite web |publisher=CDC-Centers for Disease Control and Prevention |date=2022-03-22 |title=Malaria - About Malaria - Disease |url=https://www.cdc.gov/malaria/about/disease.html |access-date=2022-04-28 |language=en-US |archive-date=2023-05-24 |archive-url=https://web.archive.org/web/20230524132501/https://www.cdc.gov/malaria/about/disease.html |url-status=live }}</ref> In humans, malaria is caused by six ''Plasmodium'' species: ''[[Plasmodium falciparum|P.&nbsp;falciparum]]'', ''[[Plasmodium malariae|P.&nbsp;malariae]]'', ''[[Plasmodium ovale curtisi|P.&nbsp;ovale curtisi]]'', ''[[Plasmodium ovale wallikeri|P.&nbsp;ovale wallikeri]]'', ''[[Plasmodium vivax|P.&nbsp;vivax]]'' and ''[[Plasmodium knowlesi|P.&nbsp;knowlesi]]''.<ref name="Ashley-2018">{{cite journal | vauthors = Ashley EA, Pyae Phyo A, Woodrow CJ | title = Malaria | journal = The Lancet | volume = 391 | issue = 10130 | pages = 1608–1621 | date = April 2018 | pmid = 29631781 | doi = 10.1016/S0140-6736(18)30324-6 | s2cid = 208791451 }}</ref> Among those infected, ''P.&nbsp;falciparum'' is the most common species identified (~75%) followed by ''P.&nbsp;vivax'' (~20%).<ref name="Nadjm-2012"/> Although ''P.&nbsp;falciparum'' traditionally accounts for the majority of deaths,<ref name="Sarkar-2009"/> recent evidence suggests that ''P.&nbsp;vivax'' malaria is associated with potentially life-threatening conditions about as often as with a diagnosis of ''P. falciparum'' infection.<ref name="Baird-2013"/> ''P.&nbsp;vivax'' proportionally is more common outside Africa.<ref name="Arnott-2012"/> Some cases have been documented of human infections with several species of ''Plasmodium'' from [[simian|higher apes]], but except for ''P.&nbsp;knowlesi''—a [[zoonosis|zoonotic]] species that causes malaria in [[macaques]]<ref name="Collins-2012"/>—these are mostly of limited public health importance.<ref name="Collins-2009"/>

The ''Anopheles'' mosquitos initially get infected by ''Plasmodium'' by taking a blood meal from a previously ''Plasmodium'' infected person or animal.<ref>{{cite web  | date=2023-06-28 |title=CDC - Malaria - FAQs |url=https://www.cdc.gov/malaria/about/faqs.html |access-date=2023-10-30 |website=www.cdc.gov |language=en-US |quote=Only Anopheles mosquitoes can transmit malaria and they must have been infected through a previous blood meal taken from an infected person. When a mosquito bites an infected person, a small amount of blood is taken in which contains microscopic malaria parasites. About 1 week later, when the mosquito takes its next blood meal, these parasites mix with the mosquito’s saliva and are injected into the person being bitten. |archive-date=2012-05-13 |archive-url=https://web.archive.org/web/20120513112631/http://www.cdc.gov/malaria/about/faqs.html |url-status=live }}</ref><ref>{{cite web  | date=2020-07-16 |title=CDC - Malaria - About Malaria - Biology |url=https://www.cdc.gov/malaria/about/biology/index.html |access-date=2023-10-30 |website=www.cdc.gov |language=en-US |quote=Thus the infected mosquito carries the disease from one human to another (acting as a “vector”), while infected humans transmit the parasite to the mosquito, In contrast to the human host, the mosquito vector does not suffer from the presence of the parasites. |archive-date=2021-01-27 |archive-url=https://web.archive.org/web/20210127071906/https://www.cdc.gov/malaria/about/biology/index.html |url-status=live }}</ref> Parasites are then typically introduced by the bite of an infected ''[[Anopheles]]'' mosquito. Some of these inoculated parasites, called "[[sporozoite]]s", probably remain in the skin,<ref>{{cite journal | vauthors = Ménard R, Tavares J, Cockburn I, Markus M, Zavala F, Amino R | title = Looking under the skin: the first steps in malarial infection and immunity | journal = Nature Reviews. Microbiology | volume = 11 | issue = 10 | pages = 701–712 | date = October 2013 | pmid = 24037451 | doi = 10.1038/nrmicro3111 | doi-access = free }}</ref> but others travel in the bloodstream to the [[liver]], where they invade [[hepatocyte]]s.<ref name="Cowman-2016">{{cite journal | vauthors = Cowman AF, Healer J, Marapana D, Marsh K | title = Malaria: Biology and Disease | journal = Cell | volume = 167 | issue = 3 | pages = 610–624 | date = October 2016 | pmid = 27768886 | doi = 10.1016/j.cell.2016.07.055 | s2cid = 2524633 | doi-access = free }}</ref> They grow and divide in the liver for 2–10 days, with each infected hepatocyte eventually harboring up to 40,000 parasites.<ref name="Cowman-2016"/> The infected hepatocytes break down, releasing these invasive ''Plasmodium'' cells, called "[[merozoite]]s", into the bloodstream. In the blood, the merozoites rapidly invade individual [[red blood cell]]s, replicating over 24–72 hours to form 16–32 new merozoites.<ref name="Cowman-2016"/><!--The Cowman ref says "48 hours" but knowlesi takes 24 and malariae takes 72, so I'll need to find a better source for that--> 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.<ref name="Cowman-2016"/> 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 "[[gametocyte]]s". 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.<ref name="Cowman-2016"/> Once inside a mosquito, the gametocytes undergo sexual reproduction, and eventually form daughter sporozoites that migrate to the mosquito's [[salivary gland]]s to be injected into a new host when the mosquito bites.<ref name="Cowman-2016"/>

The liver infection causes no symptoms; all symptoms of malaria result from the infection of red blood cells.<ref name="Ashley-2018"/> Symptoms develop once there are more than around 100,000 parasites per [[milliliter]] of blood.<ref name="Ashley-2018"/> 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.<ref name="Ashley-2018"/> The destruction of red blood cells during infection often results in anemia, exacerbated by reduced production of new red blood cells during infection.<ref name="Ashley-2018"/>

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.<ref name="Arrow-2004"/> However, in Africa, due to the extensive use of bed nets, they began to bite earlier, before bed-net time.<ref>{{cite web |vauthors=Goldman JG |title=Malaria Mosquitoes Are Biting before Bed-Net Time |url=https://www.scientificamerican.com/podcast/episode/malaria-mosquitoes-are-biting-before-bed-net-time/ |access-date=2023-05-29 |website=Scientific American |archive-date=2023-05-29 |archive-url=https://web.archive.org/web/20230529022719/https://www.scientificamerican.com/podcast/episode/malaria-mosquitoes-are-biting-before-bed-net-time/ |url-status=live }}</ref> Malaria parasites can also be transmitted by [[blood transfusion]]s, although this is rare.<ref name="Owusu-Ofori-2010"/>

===Recurrent malaria===
Symptoms of malaria can recur after varying symptom-free periods. Depending upon the cause, recurrence can be classified as either [[recrudescence]], [[relapse]], or reinfection. Recrudescence is when symptoms return after a symptom-free period due to failure to remove blood-stage parasites by adequate treatment.{{sfn|WHO|2015|p=4}} Relapse is when symptoms reappear after the parasites have been eliminated from the blood but have persisted as dormant [[Plasmodium#Life cycle|hypnozoites]]<ref>{{cite journal | vauthors = Markus MB | title = Malaria: origin of the term 'hypnozoite' | journal = Journal of the History of Biology | volume = 44 | issue = 4 | pages = 781–786 | date = 2011 | pmid = 20665090 | doi = 10.1007/s10739-010-9239-3 | s2cid = 1727294 }}</ref> in liver cells. Relapse commonly occurs between 8 and 24 weeks after the initial symptoms and is often seen in ''P.&nbsp;vivax'' and ''P.&nbsp;ovale'' infections.<ref name="Nadjm-2012"/> ''P.&nbsp;vivax'' malaria cases in [[temperate]] areas often involve [[overwintering]] by hypnozoites, with relapses beginning the year after the mosquito bite.<ref name="White-2011"/> Reinfection means that parasites were eliminated from the entire body but new parasites were then introduced. Reinfection cannot readily be distinguished from relapse and recrudescence, although recurrence of infection within two weeks of treatment ending is typically attributed to treatment failure.{{sfn|WHO|2015|p=41}} People may develop some [[premunity|immunity]] when exposed to frequent infections.<ref name="Tran-2012"/>