Array ( [0] => {{Short description|Mosquito-borne infectious disease}} [1] => {{other uses}} [2] => {{Distinguish|Miliaria}} [3] => {{pp-move|small=yes}} [4] => {{Infobox medical condition (new) [5] => | name = Malaria [6] => | pronounce = {{IPAc-en|m|ə|ˈ|l|ɛər|i|ə}} [7] => | image = Malaria Parasite Connecting to Human Red Blood Cell (34034143483).jpg [8] => | caption = [[Plasmodium|Malaria parasite]] connecting to a [[red blood cell]] [9] => | field = [[Infectious disease (medical specialty)|Infectious disease]] [10] => | symptoms = Fever, vomiting, headache, [[jaundice|yellow skin]] [11] => | complications = [[Epileptic seizure|seizures]], [[coma]], [[organ failure]], [[anemia]], [[cerebral malaria]]{{cite news |publisher=Mayo Clinic |url=https://www.mayoclinic.org/diseases-conditions/malaria/symptoms-causes/syc-20351184 |title=Malaria |date= }} [12] => | onset = 10–15 days post exposure [13] => | duration = [14] => | causes = ''[[Plasmodium]]'' transmitted to humans by ''[[Anopheles]]'' [[mosquito]]es{{cite web | url=https://www.cdc.gov/malaria/about/faqs.html | title=CDC - Malaria - FAQs | date=28 June 2023 }} [15] => | risks = [16] => | diagnosis = Examination of the blood, [[malaria antigen detection tests|antigen detection tests]] [17] => | differential = [18] => | prevention = [[Mosquito net]]s, [[insect repellent]], [[mosquito control]], medications [19] => | treatment = [20] => | medication = [[Antimalarial medication]] [21] => | frequency = 247 million (2021) [22] => | deaths = 619,000 (2021) [23] => | alt = [24] => }} [25] => [26] => '''Malaria''' is a [[Mosquito-borne disease|mosquito-borne infectious disease]] that affects vertebrates.{{Cite web |title=Vector-borne diseases |url=https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases |access-date=2022-04-24 |website=www.who.int |language=en}}{{cite journal | vauthors = Dahalan FA, Churcher TS, Windbichler N, Lawniczak MK | title = The male mosquito contribution towards malaria transmission: Mating influences the Anopheles female midgut transcriptome and increases female susceptibility to human malaria parasites | journal = PLOS Pathogens | volume = 15 | issue = 11 | pages = e1008063 | date = November 2019 | pmid = 31697788 | pmc = 6837289 | doi = 10.1371/journal.ppat.1008063 | doi-access = free }} Human malaria causes [[Signs and symptoms|symptoms]] that typically include [[fever]], [[fatigue (medical)|fatigue]], [[vomiting]], and [[headache]]s.{{cite journal | vauthors = Basu S, Sahi PK | title = Malaria: An Update | journal = Indian Journal of Pediatrics | volume = 84 | issue = 7 | pages = 521–528 | date = July 2017 | pmid = 28357581 | doi = 10.1007/s12098-017-2332-2 | s2cid = 11461451 }} In severe cases, it can cause [[jaundice]], [[Epileptic seizure|seizures]], [[coma]], or [[death]]. Symptoms usually begin 10 to 15 days after being bitten by an infected ''[[Anopheles]]'' [[mosquito]].{{cite web |title=Fact sheet about malaria |url=https://www.who.int/news-room/fact-sheets/detail/malaria |website=www.who.int |access-date=28 September 2023 |language=en}} If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial [[Immunity (medical)|resistance]] disappears over months to years if the person has no continuing exposure to malaria.{{cite journal | vauthors = Caraballo H, King K | title = Emergency department management of mosquito-borne illness: malaria, dengue, and West Nile virus | journal = Emergency Medicine Practice | volume = 16 | issue = 5 | pages = 1–23; quiz 23–4 | date = May 2014 | pmid = 25207355 | s2cid = 23716674| url = http://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=405 | url-status = live | archive-url = https://web.archive.org/web/20160801202316/http://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=405 | archive-date = 2016-08-01 }} [27] => [28] => Human malaria is caused by [[protozoa|single-celled microorganisms]] of the ''[[Plasmodium]]'' group. It is spread exclusively through bites of infected female ''Anopheles'' mosquitoes.{{cite journal | vauthors = Walter K, John CC | title = Malaria | journal = JAMA | volume = 327 | issue = 6 | pages = 597 | date = February 2022 | pmid = 35133414 | doi = 10.1001/jama.2021.21468 | s2cid = 246651569 | doi-access = free }} The mosquito bite introduces the [[parasite]]s from the mosquito's [[saliva]] into a person's blood. The parasites travel to the [[liver]], where they mature and reproduce. Five species of ''Plasmodium'' commonly infect humans. The three species associated with more severe cases are ''[[Plasmodium falciparum|P. falciparum]]'' (which is responsible for the vast majority of malaria deaths), ''[[Plasmodium vivax|P. vivax]]'', and ''[[Plasmodium knowlesi|P. knowlesi]]'' (a simian malaria that spills over into thousands of people a year).{{Cite web |title=Fact sheet about malaria |url=https://www.who.int/news-room/fact-sheets/detail/malaria |access-date=2024-02-19 |website=www.who.int |language=en}}{{Cite web |last=World Health Organization |title=Global Technical Strategy for Malaria 2016-2030 |url=https://www.who.int/docs/default-source/documents/global-technical-strategy-for-malaria-2016-2030.pdf}} ''[[Plasmodium ovale|P. ovale]]'' and ''[[Plasmodium malariae|P. malariae]]'' generally cause a milder form of malaria. Malaria is typically diagnosed by the [[histology|microscopic examination]] of blood using [[blood film]]s, or with [[Malaria antigen detection tests|antigen-based]] [[rapid diagnostic test]]s. Methods that use the [[polymerase chain reaction]] to detect the parasite's [[DNA]] have been developed, but they are not widely used in areas where malaria is common, due to their cost and complexity.{{cite journal | vauthors = Nadjm B, Behrens RH | title = Malaria: an update for physicians | journal = Infectious Disease Clinics of North America | volume = 26 | issue = 2 | pages = 243–259 | date = June 2012 | pmid = 22632637 | doi = 10.1016/j.idc.2012.03.010 }} [29] => [30] => The risk of disease can be reduced by preventing mosquito bites through the use of [[mosquito net]]s and [[insect repellent]]s or with [[Mosquito control|mosquito-control measures]] such as spraying [[insecticide]]s and draining [[standing water]]. Several medications are available to [[malaria prophylaxis|prevent malaria]] for travellers in areas where the disease is common. Occasional doses of the combination medication [[sulfadoxine/pyrimethamine]] are recommended in infants and after the first trimester of pregnancy in areas with high rates of malaria. As of 2023, two malaria vaccines have been endorsed by the [[World Health Organization]].{{cite web |title=WHO recommends R21/Matrix-M vaccine for malaria prevention in updated advice on immunization |url=https://www.who.int/news/item/02-10-2023-who-recommends-r21-matrix-m-vaccine-for-malaria-prevention-in-updated-advice-on-immunization|access-date=8 December 2023 |language=en |date=2 October 2023}} The recommended treatment for malaria is a [[antimalarial medication#Artemisinin-based combination therapies (ACTs)|combination]] of [[antimalarial medication]]s that includes [[artemisinin]].{{cite journal | vauthors = Rawat A, Roy M, Jyoti A, Kaushik S, Verma K, Srivastava VK | title = Cysteine proteases: Battling pathogenic parasitic protozoans with omnipresent enzymes | journal = Microbiological Research | volume = 249 | pages = 126784 | date = August 2021 | pmid = 33989978 | doi = 10.1016/j.micres.2021.126784 | s2cid = 234597200 | doi-access = free }} The second medication may be either [[mefloquine]], [[lumefantrine]], or sulfadoxine/pyrimethamine.{{cite book |title=Guidelines for the treatment of malaria |date=2010|publisher=World Health Organization |location=Geneva |isbn=978-92-4-154792-5 |page=ix |edition=2nd}} [[Quinine]], along with [[doxycycline]], may be used if artemisinin is not available. In areas where the disease is common, malaria should be confirmed if possible before treatment is started due to concerns of increasing [[drug resistance]]. Resistance among the parasites has developed to several antimalarial medications; for example, [[chloroquine]]-resistant ''P. falciparum'' has spread to most malarial areas, and resistance to artemisinin has become a problem in some parts of Southeast Asia.{{cite web |title=Malaria Fact sheet N°94 |url=https://www.who.int/mediacentre/factsheets/fs094/en/ |website=WHO |access-date=28 August 2014 |date=March 2014 |archive-url=https://web.archive.org/web/20140903002027/http://www.who.int/mediacentre/factsheets/fs094/en/ |archive-date=3 September 2014}} [31] => [32] => The disease is widespread in the [[Tropics|tropical]] and [[subtropical]] regions that exist in a broad band around the [[equator]].{{Cite book | vauthors = Baiden F, Malm KL, Binka F |url=https://oxfordmedicine.com/view/10.1093/med/9780198816805.001.0001/med-9780198816805-chapter-73 |title=Malaria |year=2021 |publisher=Oxford University Press |isbn=978-0-19-185838-3 |language=en-US |doi=10.1093/med/9780198816805.001.0001/med-9780198816805-chapter-73|doi-broken-date=31 January 2024 }} This includes much of [[sub-Saharan Africa]], [[Asia]], and [[Latin America]]. In 2022, some 249 million cases of malaria worldwide resulted in an estimated 608000 deaths, with 80 percent being five years old or less.{{Cite web |title=World malaria report 2022 |url=https://www.who.int/publications-detail-redirect/9789240064898 |access-date=2024-01-30 |website=www.who.int |language=en}} Around 95% of the cases and deaths occurred in sub-Saharan Africa. Rates of disease decreased from 2010 to 2014, but increased from 2015 to 2021.{{cite book |last1=WHO |url=https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022|title=World Malaria Report 2022|date=2022|publisher=World Health Organization|isbn=978-92-4-006489-8|location=Switzerland}} According to UNICEF, nearly every minute, a child under five died of malaria in 2021,{{Cite web |title=Malaria in Africa |url=https://data.unicef.org/topic/child-health/malaria/ |access-date=2023-11-02 |website=UNICEF DATA |language=en-US}} and "many of these deaths are preventable and treatable".{{cite web|url=https://data.unicef.org/topic/child-health/malaria/ |title=Nearly every minute, a child under 5 dies of malaria|work=[[UNICEF]]|date=February 2023}} Malaria is commonly associated with poverty and has a significant negative effect on economic development. In Africa, it is estimated to result in losses of US$12 billion a year due to increased healthcare costs, lost ability to work, and adverse effects on tourism. [33] => [[File:En.Wikipedia-VideoWiki-Malaria.webm|thumb|thumbtime=0:02|upright=1.3|Video summary ([[Wikipedia:VideoWiki/Malaria|script]])]] [34] => {{TOC level|3}} [35] => [36] => ==Signs and symptoms== [37] => [[File:Symptoms of Malaria.png|thumb|upright=1.15|Main symptoms of malaria]] [38] => Adults with malaria tend to experience chills and fever – classically in periodic [[Paroxysmal attack|intense bouts]] lasting around six hours, followed by a period of sweating and fever relief – as well as headache, fatigue, abdominal discomfort, and [[myalgia|muscle pain]].{{cite book |url=https://parasiteswithoutborders.com/wp-content/uploads/2020/02/PD7thEditionLowResVersion5-11-2019.pdf |title=Parasitic Diseases |vauthors=Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA |date=2019 |publisher=Parasites Without Borders |edition=7 |location=New York |pages=110–115 |chapter=9. The Malarias |access-date=November 24, 2021}} Children tend to have more general symptoms: fever, cough, vomiting, and diarrhea. [39] => [40] => Initial manifestations of the disease—common to all malaria species—are similar to [[flu|flu-like symptoms]], and can resemble other conditions such as [[sepsis]], [[gastroenteritis]], and [[viral disease]]s. The presentation may include [[headache]], [[fever]], [[shivering]], [[arthralgia|joint pain]], [[vomiting]], [[hemolytic anemia]], [[jaundice]], [[hemoglobinuria|hemoglobin in the urine]], [[Retinopathy|retinal damage]], and [[convulsion]]s. [41] => [42] => The classic symptom of malaria is [[Paroxysmal attacks|paroxysm]]—a cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days ([[Fever#Types|tertian fever]]) in ''P. vivax'' and ''P. ovale'' infections, and every three days ([[Fever#Types|quartan fever]]) for ''P. malariae''. ''P. falciparum'' infection can cause recurrent fever every 36–48 hours, or a less pronounced and almost continuous fever. [43] => [44] => Symptoms typically begin 10–15 days after the initial mosquito bite, but can occur as late as several months after infection with some ''P. vivax'' strains. Travellers taking preventative malaria medications may develop symptoms once they stop taking the drugs. [45] => [46] => Severe malaria is usually caused by ''P. falciparum'' (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection. Individuals with cerebral malaria frequently exhibit [[neurological disorder|neurological]] symptoms, including [[abnormal posturing]], [[nystagmus]], [[conjugate gaze palsy]] (failure of the eyes to turn together in the same direction), [[opisthotonus]], [[seizure]]s, or [[coma]]. [47] => [48] => ===Complications=== [49] => Malaria has several serious [[Complication (medicine)|complications]], including the development of [[respiratory distress]], which occurs in up to 25% of adults and 40% of children with severe ''P. falciparum'' malaria. Possible causes include respiratory compensation of [[metabolic acidosis]], noncardiogenic [[pulmonary oedema]], concomitant [[pneumonia]], and severe [[anaemia]]. Although rare in young children with severe malaria, [[acute respiratory distress syndrome]] occurs in 5–25% of adults and up to 29% of pregnant women. [[Coinfection]] of [[HIV]] with malaria increases mortality. [[Kidney failure]] is a feature of [[blackwater fever]], where haemoglobin from [[lysis|lysed]] red blood cells leaks into the urine. [50] => [51] => Infection with ''P. falciparum'' may result in cerebral malaria, a form of severe malaria that involves [[encephalopathy]]. It is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever. An [[Splenomegaly|enlarged spleen]], [[hepatomegaly|enlarged liver]] or [[hepatosplenomegaly|both of these]], severe headache, [[hypoglycemia|low blood sugar]], and [[hemoglobinuria|haemoglobin in the urine]] with [[kidney failure]] may occur. Complications may include spontaneous bleeding, [[coagulopathy]], and [[circulatory shock|shock]].Davidson's Principles and Practice of Medicine/21st/351 [52] => [53] => [[Pregnancy-associated malaria|Malaria in pregnant women]] is an important cause of [[stillbirth]]s, [[infant mortality]], [[miscarriage]], and [[low birth weight]], particularly in ''P. falciparum'' infection, but also with ''P. vivax''. [54] => [55] => ==Cause== [56] => Malaria is caused by infection with [[parasite]]s in the genus ''[[Plasmodium]]''.{{Cite web | work = 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}} In humans, malaria is caused by six ''Plasmodium'' species: ''[[Plasmodium falciparum|P. falciparum]]'', ''[[Plasmodium malariae|P. malariae]]'', ''[[Plasmodium ovale curtisi|P. ovale curtisi]]'', ''[[Plasmodium ovale wallikeri|P. ovale wallikeri]]'', ''[[Plasmodium vivax|P. vivax]]'' and ''[[Plasmodium knowlesi|P. knowlesi]]''.{{cite journal |vauthors=Ashley EA, Pyae Phyo A, Woodrow CJ |title=Malaria |journal=Lancet |volume=391 |issue=10130 |pages=1608–1621 |date=April 2018 |pmid=29631781 |doi=10.1016/S0140-6736(18)30324-6 |s2cid=208791451 }} 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 [[simian|higher apes]], but except for ''P. knowlesi''—a [[zoonosis|zoonotic]] species that causes malaria in [[macaques]]—these are mostly of limited public health importance. [57] => [58] => [[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.]] [59] => [60] => The ''Anopheles'' mosquitos initially get infected by ''Plasmodium'' by taking a blood meal from a previously ''Plasmodium'' infected person.{{Cite web |last= |first= |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.}}{{Cite web |last= |first= |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.}} 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,{{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 }} but others travel in the bloodstream to the [[liver]], where they invade [[hepatocyte]]s.{{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 }} 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 this invasive form of ''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. 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 "[[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. 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. [61] => [62] => 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. [63] => [64] => 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.{{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 |language=en}} Malaria parasites can also be transmitted by [[blood transfusion]]s, although this is rare. [65] => [66] => ===Recurrent malaria=== [67] => 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.{{harvnb|WHO|2010|p=vi}} Relapse is when symptoms reappear after the parasites have been eliminated from the blood but have persisted as dormant [[Plasmodium#Life cycle|hypnozoites]]{{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 }} in liver cells. Relapse commonly occurs between 8 and 24 weeks after the initial symptoms and is often seen in ''P. vivax'' and ''P. ovale'' infections. ''P. vivax'' malaria cases in [[temperate]] areas often involve [[overwintering]] by hypnozoites, with relapses beginning the year after the mosquito bite. 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.{{harvnb|WHO|2010|p=17}} People may develop some [[premunity|immunity]] when exposed to frequent infections. [68] => [69] => ==Pathophysiology== [70] => {{further|Plasmodium falciparum#Pathogenesis}} [71] => [[File:Maternal malaria placenta - cropped - very high mag.jpg|thumb|right|[[Micrograph]] of a [[placenta]] from a [[stillbirth]] due to maternal malaria. [[H&E stain]]. Red blood cells are anuclear; blue/black staining in bright red structures (red blood cells) indicate foreign nuclei from the parasites.]] [72] => [[File:Red blood cells infected with malaria.jpg|thumb|Electron micrograph of a ''Plasmodium falciparum''-infected red blood cell (center), illustrating adhesion protein "knobs"]] [73] => [74] => Malaria infection develops via two phases: one that involves the [[liver]] (exoerythrocytic phase), and one that involves red blood cells, or [[erythrocyte]]s (erythrocytic phase). When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver where they infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days. [75] => [76] => After a potential dormant period in the liver, these organisms [[cellular differentiation|differentiate]] to yield thousands of merozoites, which, following rupture of their host cells, escape into the blood and infect red blood cells to begin the erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping itself in the [[cell membrane]] of the infected host liver cell. [77] => [78] => Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells. [79] => [80] => Some ''P. vivax'' sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead, produce hypnozoites that remain dormant for periods ranging from several months (7–10 months is typical) to several years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in ''P. vivax'' infections, although their existence in ''P. ovale'' is uncertain. [81] => [82] => The parasite is relatively protected from attack by the body's [[immune system]] because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the [[spleen]]. To avoid this fate, the ''P. falciparum'' parasite displays adhesive [[protein]]s on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. The blockage of the microvasculature causes symptoms such as those in placental malaria. Sequestered red blood cells can breach the [[blood–brain barrier]] and cause cerebral malaria. [83] => [84] => ===Genetic resistance=== [85] => {{Main|Human genetic resistance to malaria}} [86] => According to a 2005 review, due to the high levels of [[death|mortality]] and [[morbidity]] caused by malaria—especially the ''P. falciparum'' species—it has placed the greatest [[Selection (biology)|selective pressure]] on the [[human genome]] in recent history. Several genetic factors provide some resistance to it including [[sickle cell trait]], [[thalassaemia]] traits, [[glucose-6-phosphate dehydrogenase deficiency]], and the absence of [[Duffy antigen]]s on red blood cells.{{cite journal | vauthors = Pierron D, Heiske M, Razafindrazaka H, Pereda-Loth V, Sanchez J, Alva O, Arachiche A, Boland A, Olaso R, Deleuze JF, Ricaut FX, Rakotoarisoa JA, Radimilahy C, Stoneking M, Letellier T | display-authors = 6 | title = Strong selection during the last millennium for African ancestry in the admixed population of Madagascar | journal = Nature Communications | volume = 9 | issue = 1 | pages = 932 | date = March 2018 | pmid = 29500350 | pmc = 5834599 | doi = 10.1038/s41467-018-03342-5 | bibcode = 2018NatCo...9..932P }} [87] => [88] => The impact of sickle cell trait on malaria immunity illustrates some evolutionary trade-offs that have occurred because of endemic malaria. Sickle cell trait causes a change in the haemoglobin molecule in the blood. Normally, red blood cells have a very flexible, biconcave shape that allows them to move through narrow [[capillaries]]; however, when the modified [[hemoglobin S|haemoglobin S]] molecules are exposed to low amounts of oxygen, or crowd together due to dehydration, they can stick together forming strands that cause the cell to distort into a curved sickle shape. In these strands, the molecule is not as effective in taking or releasing oxygen, and the cell is not flexible enough to circulate freely. In the early stages of malaria, the parasite can cause infected red cells to sickle, and so they are removed from circulation sooner. This reduces the frequency with which malaria parasites complete their life cycle in the cell. Individuals who are [[homozygous]] (with two copies of the abnormal haemoglobin beta [[allele]]) have [[sickle-cell anaemia]], while those who are heterozygous (with one abnormal allele and one normal allele) experience resistance to malaria without severe anaemia. Although the shorter life expectancy for those with the homozygous condition would tend to disfavour the trait's survival, the trait is preserved in malaria-prone regions because of the [[heterozygote advantage|benefits]] provided by the heterozygous form. [89] => [90] => ===Liver dysfunction=== [91] => Liver dysfunction as a result of malaria is uncommon and usually only occurs in those with another liver condition such as [[viral hepatitis]] or [[chronic liver disease]]. The syndrome is sometimes called ''malarial hepatitis''. While it has been considered a rare occurrence, malarial hepatopathy has seen an increase, particularly in Southeast Asia and India. Liver compromise in people with malaria correlates with a greater likelihood of complications and death. [92] => [93] => ==Diagnosis== [94] => {{Main|Diagnosis of malaria}} [95] => [[File:5901 lores.jpg|thumb|The blood film is the [[gold standard (test)|gold standard]] for malaria diagnosis.]] [96] => [[File:Plasmodium.jpg|thumb|Ring-forms and [[gametocyte]]s of ''Plasmodium falciparum'' in human blood]] [97] => Due to the non-specific nature of malaria symptoms, diagnosis is typically suspected based on symptoms and travel history, then confirmed with a laboratory test to detect the presence of the parasite in the blood (parasitological test). In areas where malaria is common, the [[World Health Organization]] (WHO) recommends clinicians suspect malaria in any person who reports having fevers, or who has a current temperature above 37.5 °C without any other obvious cause.{{cite book |title=WHO Guidelines for Malaria |date=13 July 2021 |publisher=World Health Organization |chapter=5.1 Diagnosing Malaria (2015) |url=https://www.who.int/publications/i/item/guidelines-for-malaria |accessdate=28 November 2021}} Malaria should be suspected in children with signs of [[anemia]]: [[Palmar pallor|pale palms]] or a laboratory test showing [[hemoglobin]] levels below 8 [[gram]]s per [[deciliter]] of blood. In areas of the world with little to no malaria, the WHO recommends only testing people with possible exposure to malaria (typically travel to a malaria-endemic area) and unexplained fever. [98] => [99] => In sub-Saharan Africa, testing is low, with only about one in four (28%) of children with a fever receiving medical advice or a rapid diagnostic test in 2021. There was a 10-percentage point gap in testing between the richest and the poorest children (33% vs 23%). Additionally, a greater proportion of children in Eastern and Southern Africa (36%) were tested than in West and Central Africa (21%). According to UNICEF, 61% of children with a fever were taken for advice or treatment from a health facility or provider in 2021. Disparities are also observed by wealth, with an 18 percentage point difference in care-seeking behaviour between children in the richest (71%) and the poorest (53%) households. [100] => [101] => Malaria is usually confirmed by the microscopic examination of [[blood film]]s or by [[antigen]]-based [[Malaria antigen detection tests|rapid diagnostic tests]] (RDT). Microscopy – i.e. examining [[Giemsa]]-stained blood with a [[light microscope]] – is the [[Gold standard (test)|gold standard]] for malaria diagnosis. Microscopists typically examine both a "thick film" of blood, allowing them to scan many blood cells in a short time, and a "thin film" of blood, allowing them to clearly see individual parasites and identify the infecting ''Plasmodium'' species. Under typical field laboratory conditions, a microscopist can detect parasites when there are at least 100 parasites per [[microliter]] of blood, which is around the lower range of symptomatic infection. Microscopic diagnosis is relatively resource intensive, requiring trained personnel, specific equipment, electricity, and a consistent supply of [[Microscope slide|microscopy slides]] and stains. [102] => [103] => In places where microscopy is unavailable, malaria is diagnosed with RDTs, [[rapid antigen test]]s that detect parasite proteins in a [[fingerstick]] blood sample. A variety of RDTs are commercially available, targeting the parasite proteins histidine rich protein 2 (HRP2, detects ''P. falciparum'' only), [[lactate dehydrogenase]], or [[aldolase]]. The HRP2 test is widely used in Africa, where ''P. falciparum'' predominates. However, since HRP2 persists in the blood for up to five weeks after an infection is treated, an HRP2 test sometimes cannot distinguish whether someone currently has malaria or previously had it. Additionally, some ''P. falciparum'' parasites in the Amazon region lack the ''HRP2'' gene, complicating detection. RDTs are fast and easily deployed to places without full diagnostic laboratories. However they give considerably less information than microscopy, and sometimes vary in quality from producer to producer and lot to lot. [104] => [105] => [[Serological test]]s to detect antibodies against ''Plasmodium'' from the blood have been developed, but are not used for malaria diagnosis due to their relatively poor sensitivity and specificity. Highly sensitive [[nucleic acid amplification test]]s have been developed, but are not used clinically due to their relatively high cost, and poor specificity for active infections. [106] => [107] => ===Classification=== [108] => Malaria is classified into either "severe" or "uncomplicated" by the [[World Health Organization]] (WHO). It is deemed severe when ''any'' of the following criteria are present, otherwise it is considered uncomplicated.{{harvnb|WHO|2010|p=35}} [109] => * Decreased consciousness [110] => * Significant weakness such that the person is unable to walk [111] => * Inability to feed [112] => * Two or more [[convulsions]] [113] => * [[Low blood pressure]] (less than 70 [[mmHg]] in adults and 50 mmHg in children) [114] => * [[respiratory distress|Breathing problems]] [115] => * [[Circulatory shock]] [116] => * [[Kidney failure]] or [[haemoglobin|hemoglobin]] in the urine [117] => * Bleeding problems, or hemoglobin less than 50 g/L (5 g/dL) [118] => * [[Pulmonary oedema]] [119] => * [[Blood glucose]] less than 2.2 mmol/L (40 mg/dL) [120] => * [[Acidosis]] or [[lactic acid|lactate]] levels of greater than 5 mmol/L [121] => * A parasite level in the blood of greater than 100,000 per [[microlitre]] (μL) in low-intensity transmission areas, or 250,000 per μL in high-intensity transmission areas [122] => [123] => Cerebral malaria is defined as a severe ''P. falciparum''-malaria presenting with neurological symptoms, including coma (with a [[Glasgow coma scale]] less than 11, or a [[Blantyre coma scale]] less than 3), or with a coma that lasts longer than 30 minutes after a seizure.{{harvnb|WHO|2010|p=v}} [124] => [125] => ==Prevention== [126] => [127] => [[File:Anopheles stephensi.jpeg|thumb|An ''[[Anopheles stephensi]]'' mosquito shortly after obtaining blood from a human (the droplet of blood is expelled as a surplus). This mosquito is a vector of malaria, and mosquito control is an effective way of reducing its incidence.]] [128] => [129] => Methods used to prevent malaria include medications, mosquito elimination and the prevention of bites. As of 2023, there are two [[malaria vaccine]]s, approved for use in children by the WHO: [[RTS,S]] and [[Malaria vaccine#R21/Matrix-M|R21]].{{cite web |title=Fact sheet about Malaria |url=https://www.who.int/news-room/fact-sheets/detail/malaria |access-date=6 May 2020 |website=www.who.int |language=en}} The presence of malaria in an area requires a combination of high human population density, high ''[[Anopheles]]'' mosquito population density and high rates of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these is lowered sufficiently, the parasite eventually disappears from that area, as happened in North America, Europe, and parts of the Middle East. However, unless the parasite is eliminated from the whole world, it could re-establish if conditions revert to a combination that favors the parasite's reproduction. Furthermore, the cost per person of eliminating anopheles mosquitoes rises with decreasing population density, making it economically unfeasible in some areas. [130] => [131] => Prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the [[capital cost|initial costs]] required are out of reach of many of the world's poorest people. There is a wide difference in the costs of control (i.e. maintenance of low endemicity) and elimination programs between countries. For example, in China—whose government in 2010 announced a strategy to pursue malaria elimination in the [[Chinese province]]s—the required investment is a small proportion of public expenditure on health. In contrast, a similar programme in Tanzania would cost an estimated one-fifth of the public health budget. In 2021, the World Health Organization confirmed that China has eliminated malaria.{{Cite web |title=From 30 million cases to zero: China is certified malaria-free by WHO |url=https://www.who.int/news/item/30-06-2021-from-30-million-cases-to-zero-china-is-certified-malaria-free-by-who |access-date=2022-08-11 |website=www.who.int |language=en}} In 2023, the World Health Organization confirmed that Azerbaijan, Tajikistan, and Belize have eliminated Malaria.{{Cite web |title=Countries and territories certified malaria-free by WHO |url=https://www.who.int/teams/global-malaria-programme/elimination/countries-and-territories-certified-malaria-free-by-who |access-date=2024-01-30 |website=www.who.int |language=en}} [132] => [133] => In areas where malaria is common, children under five years old often have [[anaemia]], which is sometimes due to malaria. Giving children with anaemia in these areas preventive antimalarial medication improves red blood cell levels slightly but does not affect the risk of death or need for hospitalisation.{{cite journal | vauthors = Athuman M, Kabanywanyi AM, Rohwer AC | title = Intermittent preventive antimalarial treatment for children with anaemia | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD010767 | date = January 2015 | issue = 1 | pmid = 25582096 | pmc = 4447115 | doi = 10.1002/14651858.CD010767.pub2 }} [134] => [135] => ===Mosquito control=== [136] => {{further|Mosquito control}} [137] => [[File:Mansprayingkeroseneoil.jpg|thumb|left|Man spraying kerosene oil in standing water, [[Panama Canal Zone]], 1912]] [138] => [[Vector control]] refers to methods used to decrease malaria by reducing the levels of transmission by mosquitoes. For individual protection, the most effective [[insect repellent]]s are based on [[DEET]] or [[picaridin]]. However, there is insufficient evidence that mosquito repellents can prevent malaria infection.{{cite journal | vauthors = Maia MF, Kliner M, Richardson M, Lengeler C, Moore SJ | title = Mosquito repellents for malaria prevention | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 2 | pages = CD011595 | date = February 2018 | pmid = 29405263 | pmc = 5815492 | doi = 10.1002/14651858.CD011595.pub2 | collaboration = Cochrane Infectious Diseases Group }} [[Insecticide-treated net]]s (ITNs) and [[indoor residual spraying]] (IRS) are effective, have been commonly used to prevent malaria, and their use has contributed significantly to the decrease in malaria in the 21st century.{{cite journal | vauthors = Fox T, Furnival-Adams J, Chaplin M, Napier M, Olanga EA | title = House modifications for preventing malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 10 | pages = CD013398 | date = October 2022 | pmid = 36200610 | pmc = 9536247 | doi = 10.1002/14651858.CD013398.pub4 }}{{cite journal | vauthors = Pryce J, Richardson M, Lengeler C | title = Insecticide-treated nets for preventing malaria | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD000363 | date = November 2018 | pmid = 30398672 | pmc = 6418392 | doi = 10.1002/14651858.CD000363.pub3 }} ITNs and IRS may not be sufficient to eliminate the disease, as these interventions depend on how many people use nets, how many gaps in insecticide there are (low coverage areas), if people are not protected when outside of the home, and an increase in mosquitoes that are resistant to insecticides. Modifications to people's houses to prevent mosquito exposure may be an important long term prevention measure. [139] => [[File:Mosquitoes-Killedy-By-DDT-Lake-Victoria.JPG|thumb|right|Walls where indoor residual spraying of DDT has been applied. The mosquitoes remain on the wall until they fall down dead on the floor.]] [140] => [141] => ====Insecticide-treated nets==== [142] => [[File:Mosquitonet149.jpg|thumb|A mosquito net in use.]] [143] => Mosquito nets help keep mosquitoes away from people and reduce infection rates and transmission of malaria. Nets are not a perfect barrier and are often treated with an insecticide designed to kill the mosquito before it has time to find a way past the net. Insecticide-treated nets (ITNs) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net. Between 2000 and 2008, the use of ITNs saved the lives of an estimated 250,000 infants in Sub-Saharan Africa. According to UNICEF, only 36% of households had sufficient ITNs for all household members in 2019.{{Cite web |title=Malaria in Africa |url=https://data.unicef.org/topic/child-health/malaria/ |access-date=2023-10-31 |website=UNICEF DATA |language=en-US}} In 2000, 1.7 million (1.8%) African children living in areas of the world where malaria is common were protected by an ITN. That number increased to 20.3 million (18.5%) African children using ITNs in 2007, leaving 89.6 million children unprotected and to 68% African children using mosquito nets in 2015. The percentage of children sleeping under ITNs in sub-Saharan Africa increased from less than 40% in 2011 to over 50% in 2021. Most nets are impregnated with [[pyrethroid]]s, a class of insecticides with low [[toxicity]]. They are most effective when used from dusk to dawn.{{harvnb|Schlagenhauf-Lawlor|2008|p=[https://books.google.com/books?id=54Dza0UHyngC&pg=PA215 215]}} It is recommended to hang a large "bed net" above the center of a bed and either tuck the edges under the mattress or make sure it is large enough such that it touches the ground.{{cite book|title=Instructions for treatment and use of insecticide-treated mosquito nets|date=2002|publisher=World Health Organization |page=34 |url=http://whqlibdoc.who.int/hq/2002/WHO_CDS_RBM_2002.41.pdf|url-status=live|archive-url=https://web.archive.org/web/20150706081401/http://whqlibdoc.who.int/hq/2002/WHO_CDS_RBM_2002.41.pdf|archive-date=2015-07-06}} ITNs are beneficial towards pregnancy outcomes in malaria-endemic regions in Africa but more data is needed in Asia and Latin America.{{cite journal | vauthors = Gamble C, Ekwaru JP, ter Kuile FO | title = Insecticide-treated nets for preventing malaria in pregnancy | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD003755 | date = April 2006 | volume = 2006 | pmid = 16625591 | pmc = 6532581 | doi = 10.1002/14651858.CD003755.pub2 | collaboration = Cochrane Infectious Diseases Group }} [144] => [145] => In areas of high malaria resistance, piperonyl butoxide (PBO) combined with pyrethroids in mosquito netting is effective in reducing malaria infection rates.{{cite journal | vauthors = Gleave K, Lissenden N, Chaplin M, Choi L, Ranson H | title = Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 5 | pages = CD012776 | date = May 2021 | pmid = 34027998 | pmc = 8142305 | doi = 10.1002/14651858.CD012776.pub3 }} Questions remain concerning the durability of PBO on nets as the impact on mosquito mortality was not sustained after twenty washes in experimental trials. [146] => [147] => UNICEF notes that the use of insecticide-treated nets has been increased since 2000 through accelerated production, procurement and delivery, stating that "over 2.5 billion ITNs have been distributed globally since 2004, with 87% (2.2 billion) distributed in sub-Saharan Africa. In 2021, manufacturers delivered about 220 million ITNs to malaria endemic countries, a decrease of 9 million ITNs compared with 2020 and 33 million less than were delivered in 2019". As of 2021, 66% of households in sub-Saharan Africa had ITNs, with figures "ranging from 31 per cent in Angola in 2016 to approximately 97 per cent in Guinea-Bissau in 2019". Slightly more than half of the households with an ITN had enough of them to protect all members of the household, however. [148] => [149] => ====Indoor residual spraying==== [150] => Indoor residual spraying is the spraying of insecticides on the walls inside a home. After feeding, many mosquitoes rest on a nearby surface while digesting the bloodmeal, so if the walls of houses have been coated with insecticides, the resting mosquitoes can be killed before they can bite another person and transfer the malaria parasite. As of 2006, the [[World Health Organization]] recommends 12 insecticides in IRS operations, including [[DDT#Use against malaria|DDT]] and the pyrethroids [[cyfluthrin]] and [[deltamethrin]]. This public health use of small amounts of DDT is permitted under the [[Stockholm Convention]], which prohibits its agricultural use. One problem with all forms of IRS is [[insecticide resistance]]. Mosquitoes affected by IRS tend to rest and live indoors, and due to the irritation caused by spraying, their descendants tend to rest and live outdoors, meaning that they are less affected by the IRS. Communities using insecticide treated nets, in addition to indoor residual spraying with 'non-pyrethroid-like' insecticides found associated reductions in malaria.{{cite journal | vauthors = Pryce J, Medley N, Choi L | title = Indoor residual spraying for preventing malaria in communities using insecticide-treated nets | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD012688 | date = January 2022 | pmid = 35038163 | pmc = 8763033 | doi = 10.1002/14651858.CD012688.pub3 }} Additionally, the use of 'pyrethroid-like' insecticides in addition to indoor residual spraying did not result in a detectable additional benefit in communities using insecticide treated nets. [151] => [152] => ==== Housing modifications ==== [153] => Housing is a risk factor for malaria and modifying the house as a prevention measure may be a sustainable strategy that does not rely on the effectiveness of insecticides such as [[pyrethroid]]s.{{cite journal | vauthors = Tusting LS, Ippolito MM, Willey BA, Kleinschmidt I, Dorsey G, Gosling RD, Lindsay SW | title = The evidence for improving housing to reduce malaria: a systematic review and meta-analysis | journal = Malaria Journal | volume = 14 | issue = 1 | pages = 209 | date = June 2015 | pmid = 26055986 | pmc = 4460721 | doi = 10.1186/s12936-015-0724-1 | doi-access = free }} The physical environment inside and outside the home that may improve the density of mosquitoes are considerations. Examples of potential modifications include how close the home is to mosquito breeding sites, drainage and water supply near the home, availability of mosquito resting sites (vegetation around the home), the proximity to live stock and domestic animals, and physical improvements or modifications to the design of the home to prevent mosquitoes from entering, such as [[window screen]]s. [154] => [155] => '''Mass drug administration''' [156] => [157] => [[Mass drug administration]] (MDA) involves the administration of drugs to the entire population of an area regardless of disease status.{{Cite journal |last1=Webster |first1=Joanne P. |last2=Molyneux |first2=David H. |last3=Hotez |first3=Peter J. |last4=Fenwick |first4=Alan |date=2014 |title=The contribution of mass drug administration to global health: past, present and future |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=369 |issue=1645 |pages=20130434 |doi=10.1098/rstb.2013.0434 |issn=1471-2970 |pmc=4024227 |pmid=24821920}} A 2021 Cochrane review on the use of community administration of [[ivermectin]] found that, to date, low quality evidence shows no significant impact on reducing incidence of malaria transmission from the community administration of ivermectin.{{Cite journal |last1=de Souza |first1=Dziedzom K |last2=Thomas |first2=Rebecca |last3=Bradley |first3=John |last4=Leyrat |first4=Clemence |last5=Boakye |first5=Daniel A |last6=Okebe |first6=Joseph |date=2021-06-29 |editor-last=Cochrane Infectious Diseases Group |title=Ivermectin treatment in humans for reducing malaria transmission |journal=Cochrane Database of Systematic Reviews |language=en |volume=2021 |issue=6 |pages=CD013117 |doi=10.1002/14651858.CD013117.pub2 |pmc=8240090 |pmid=34184757}} [158] => [159] => ====Other mosquito control methods==== [160] => People have tried a number of other methods to reduce mosquito bites and slow the spread of malaria. Efforts to decrease mosquito larvae by decreasing the availability of open water where they develop, or by adding substances to decrease their development, are effective in some locations.{{cite journal | vauthors = Martello E, Yogeswaran G, Reithinger R, Leonardi-Bee J | title = Mosquito aquatic habitat modification and manipulation interventions to control malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 11 | pages = CD008923 | date = November 2022 | pmid = 36367444 | pmc = 9651131 | doi = 10.1002/14651858.CD008923.pub3 }} Electronic mosquito repellent devices, which make very high-frequency sounds that are supposed to keep female mosquitoes away, have no supporting evidence of effectiveness. There is a low certainty evidence that [[Fogging (insect control)|fogging]] may have an effect on malaria transmission.{{cite journal | vauthors = Pryce J, Choi L, Richardson M, Malone D | title = Insecticide space spraying for preventing malaria transmission | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD012689 | date = November 2018 | pmid = 30388303 | pmc = 6516806 | doi = 10.1002/14651858.CD012689.pub2 | collaboration = Cochrane Infectious Diseases Group }} Larviciding by hand delivery of chemical or microbial insecticides into water bodies containing low larval distribution may reduce malarial transmission.{{cite journal | vauthors = Choi L, Majambere S, Wilson AL | title = Larviciding to prevent malaria transmission | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD012736 | date = August 2019 | pmid = 31425624 | pmc = 6699674 | doi = 10.1002/14651858.CD012736.pub2 | collaboration = Cochrane Infectious Diseases Group }} There is insufficient evidence to determine whether larvivorous fish can decrease mosquito density and transmission in the area.{{cite journal | vauthors = Walshe DP, Garner P, Adeel AA, Pyke GH, Burkot TR | title = Larvivorous fish for preventing malaria transmission | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 12 | pages = CD008090 | date = December 2017 | pmid = 29226959 | pmc = 5741835 | doi = 10.1002/14651858.CD008090.pub3 | collaboration = Cochrane Infectious Diseases Group }} [161] => [162] => ===Medications=== [163] => {{Main|Malaria prophylaxis}} [164] => There are a number of medications that can help prevent or interrupt malaria in travellers to places where infection is common. Many of these medications are also used in treatment. In places where ''Plasmodium'' is resistant to one or more medications, three medications—[[mefloquine]], [[doxycycline]], or the combination of [[atovaquone/proguanil]] (''Malarone'')—are frequently used for prevention. Doxycycline and the atovaquone/proguanil are better tolerated while mefloquine is taken once a week.{{cite journal | vauthors = Tickell-Painter M, Maayan N, Saunders R, Pace C, Sinclair D | title = Mefloquine for preventing malaria during travel to endemic areas | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 10 | pages = CD006491 | date = October 2017 | pmid = 29083100 | pmc = 5686653 | doi = 10.1002/14651858.CD006491.pub4 }} Areas of the world with [[chloroquine]]-sensitive malaria are uncommon.{{cite web|title=Malaria Worldwide – How Can Malaria Cases and Deaths Be Reduced? – Drug resistance in the Malaria Endemic World|url=https://www.cdc.gov/malaria/malaria_worldwide/reduction/drug_resistance.html|website=Centers for Disease Control and Prevention|access-date=4 January 2018}} Antimalarial mass drug administration to an entire population at the same time may reduce the risk of contracting malaria in the population, however the effectiveness of mass drug administration may vary depending on the prevalence of malaria in the area.{{cite journal | vauthors = Shah MP, Hwang J, Choi L, Lindblade KA, Kachur SP, Desai M | title = Mass drug administration for malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 9 | pages = CD008846 | date = September 2021 | pmid = 34585740 | pmc = 8479726 | doi = 10.1002/14651858.CD008846.pub3 }} Other factors such as drug administration plus other protective measures such as mosquito control, the proportion of people treated in the area, and the risk of reinfection with malaria may play a role in the effectiveness of mass drug treatment approaches. [165] => [166] => The protective effect does not begin immediately, and people visiting areas where malaria exists usually start taking the drugs one to two weeks before they arrive, and continue taking them for four weeks after leaving (except for atovaquone/proguanil, which only needs to be started two days before and continued for seven days afterward). The use of preventive drugs is often not practical for those who live in areas where malaria exists, and their use is usually given only to pregnant women and short-term visitors. This is due to the cost of the drugs, [[adverse effect (medicine)|side effects]] from long-term use, and the difficulty in obtaining antimalarial drugs outside of wealthy nations. During pregnancy, medication to prevent malaria has been found to improve the weight of the baby at birth and decrease the risk of [[anaemia]] in the mother.{{cite journal | vauthors = Radeva-Petrova D, Kayentao K, ter Kuile FO, Sinclair D, Garner P | title = Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 10 | pages = CD000169 | date = October 2014 | pmid = 25300703 | pmc = 4498495 | doi = 10.1002/14651858.CD000169.pub3 }} The use of preventive drugs where malaria-bearing mosquitoes are present may encourage the development of partial resistance. [167] => [168] => Giving antimalarial drugs to infants through intermittent preventive therapy can reduce the risk of having malaria infection, hospital admission, and anaemia.{{cite journal | vauthors = Esu EB, Oringanje C, Meremikwu MM | title = Intermittent preventive treatment for malaria in infants | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 7 | pages = CD011525 | date = July 2021 | pmid = 34273901 | pmc = 8406727 | doi = 10.1002/14651858.CD011525.pub3 }} [169] => [170] => Mefloquine is more effective than sulfadoxine-pyrimethamine in preventing malaria for HIV-negative pregnant women. Cotrimoxazole is effective in preventing malaria infection and reduce the risk of getting anaemia in HIV-positive women.{{cite journal | vauthors = González R, Pons-Duran C, Piqueras M, Aponte JJ, Ter Kuile FO, Menéndez C | title = Mefloquine for preventing malaria in pregnant women | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD011444 | date = November 2018 | issue = 11 | pmid = 30480761 | pmc = 6517148 | doi = 10.1002/14651858.CD011444.pub3 | collaboration = Cochrane Infectious Diseases Group }} Giving sulfadoxine-pyrimethamine for three or more doses as intermittent preventive therapy is superior than two doses for HIV-positive women living in malaria-endemic areas.{{cite journal | vauthors = Mathanga DP, Uthman OA, Chinkhumba J | title = Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women | journal = The Cochrane Database of Systematic Reviews | issue = 10 | pages = CD006689 | date = October 2011 | volume = 2011 | pmid = 21975756 | pmc = 6532702 | doi = 10.1002/14651858.CD006689.pub2 | collaboration = Cochrane Infectious Diseases Group }} [171] => [172] => Prompt treatment of confirmed cases with artemisinin-based combination therapies (ACTs) may also reduce transmission.{{cite web|title=WHO gives indoor use of DDT a clean bill of health for controlling malaria|url=https://www.who.int/mediacentre/news/releases/2006/pr50/en/|url-status=dead|archive-url=https://web.archive.org/web/20121022215922/http://www.who.int/mediacentre/news/releases/2006/pr50/en/|archive-date=2012-10-22|publisher=WHO|vauthors=Palmer J}} [173] => [174] => === Research on malaria vaccines === [175] => {{Main|Malaria vaccine}} [176] => [[Malaria vaccine]]s have been another goal of research. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunising mice with live, radiation-[[Attenuator (genetics)|attenuated]] sporozoites, which provided significant protection to the mice upon subsequent injection with normal, viable sporozoites. Since the 1970s, there has been considerable progress in developing similar vaccination strategies for humans. [177] => [178] => In 2013, WHO and the malaria vaccine funders group set a goal to develop vaccines designed to interrupt malaria transmission with malaria eradication's long-term goal.{{cite web |title=World Malaria Report 2013 |url=https://www.who.int/entity/malaria/publications/world_malaria_report_2013/wmr2013_no_profiles.pdf?ua=1 |access-date=13 February 2014 |publisher=World Health Organization |format=PDF}} The first vaccine, called [[RTS,S]], was approved by European regulators in 2015. As of 2023, two [[malaria vaccine]] have been licensed for use. Other approaches to combat malaria may require investing more in research and greater primary health care.{{Cite web |title=Malaria eradication: benefits, future scenarios and feasibility. Executive summary of the report of the WHO Strategic Advisory Group on Malaria Eradication |url=https://www.who.int/publications-detail/strategic-advisory-group-malaria-eradication-executive-summary |url-status=dead |archive-url=https://web.archive.org/web/20190823125246/https://www.who.int/publications-detail/strategic-advisory-group-malaria-eradication-executive-summary |archive-date=August 23, 2019 |access-date=2019-08-25 |website=www.who.int |language=en}} Continuing surveillance will also be important to prevent the return of malaria in countries where the disease has been eliminated.{{cite journal |vauthors=Mendis K |date=September 2019 |title=Eliminating malaria should not be the end of vigilance |journal=Nature |volume=573 |issue=7772 |pages=7 |bibcode=2019Natur.573....7M |doi=10.1038/d41586-019-02598-1 |pmid=31485061 |doi-access=free}} [179] => [180] => As of 2019 it is undergoing pilot trials in 3 sub-Saharan African countries – Ghana, Kenya and Malawi – as part of the WHO's Malaria Vaccine Implementation Programme (MVIP).{{cite web |author=World Health Organization |date=March 2020 |title=Q&A on the malaria vaccine implementation programme (MVIP) |url=https://www.who.int/malaria/media/malaria-vaccine-implementation-qa/en/ |access-date=6 May 2020 |publisher=WHO}} [181] => [182] => Immunity (or, more accurately, [[immune tolerance|tolerance]]) to ''P. falciparum'' malaria does occur naturally, but only in response to years of repeated infection.{{cite journal |vauthors=Abuga KM, Jones-Warner W, Hafalla JC |date=February 2021 |title=Immune responses to malaria pre-erythrocytic stages: Implications for vaccine development |journal=Parasite Immunology |volume=43 |issue=2 |pages=e12795 |doi=10.1111/pim.12795 |pmc=7612353 |pmid=32981095}} An individual can be protected from a ''P. falciparum'' infection if they receive about a thousand bites from mosquitoes that carry a version of the parasite rendered non-infective by a dose of [[X-ray]] [[irradiation]]. The highly [[polymorphism (biology)|polymorphic]] nature of many ''P. falciparum'' proteins results in significant challenges to vaccine design. Vaccine candidates that target antigens on gametes, zygotes, or ookinetes in the mosquito midgut aim to block the transmission of malaria. These transmission-blocking vaccines induce [[antibodies]] in the human blood; when a mosquito takes a blood meal from a protected individual, these antibodies prevent the parasite from completing its development in the mosquito. Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have been inadequate on their own. For example, [[Manuel Elkin Patarroyo|SPf66]] was tested extensively in areas where the disease was common in the 1990s, but trials showed it to be insufficiently effective. [183] => [184] => As of 2020, the RTS,S vaccine has been shown to reduce the risk of malaria by about 40% in children in Africa.{{cite journal | vauthors = | title = Malaria vaccine: WHO position paper-January 2016 | journal = Relevé Épidémiologique Hebdomadaire | volume = 91 | issue = 4 | pages = 33–51 | date = January 2016 | pmid = 26829826 | url = https://www.who.int/wer/2016/wer9104.pdf?ua=1 | archive-url = https://web.archive.org/web/20200423102942/http://www.who.int/wer/2016/wer9104.pdf?ua=1 | archive-date = 2020-04-23 }} A preprint study of the R21 vaccine has shown 77% vaccine efficacy.{{update inline|date=June 2022}}{{cite journal |display-authors=6 |vauthors=Datoo MS, Natama MH, Somé A, Traoré O, Rouamba T, Bellamy D, Yameogo P, Valia D, Tegneri M, Ouedraogo F, Soma R, Sawadogo S, Sorgho F, Derra K, Rouamba E, Orindi B, Ramos Lopez F, Flaxman A, Cappuccini F, Kailath R, Elias S, Mukhopadhyay E, Noe A, Cairns M, Lawrie A, Roberts R, Valéa I, Sorgho H, Williams N, Glenn G, Fries L, Reimer J, Ewer KJ, Shaligram U, Hill AV, Tinto H |date=May 2021 |title=Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial |journal=Lancet |volume=397 |issue=10287 |pages=1809–1818 |doi=10.1016/S0140-6736(21)00943-0 |pmc=8121760 |pmid=33964223 |ssrn=3830681}} [185] => [186] => In 2021, researchers from the [[University of Oxford]] reported findings from a [[Phases of clinical research|Phase IIb trial]] of a candidate malaria vaccine, R21/Matrix-M, which demonstrated efficacy of 77% over 12-months of follow-up. This vaccine is the first to meet the [[World Health Organization]]'s Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy.[https://www.eurekalert.org/pub_releases/2021-04/uoo-mvb042221.php Malaria vaccine becomes first to achieve WHO-specified 75% efficacy goal], News Release 23 April 2021, [[University of Oxford]] [187] => [188] => Germany-based BioNTECH SE are developing an mRNA-based malaria vaccine BN165 {{cite web |title=Home |url=https://www.biontech.com/int/en/home.html}} which has recently initiated a Phase 1 study [clinicaltrials.gov identifier: NCT05581641] in December 2022. The vaccine, based on the circumsporozite protein (CSP) is being tested in adults aged 18–55 yrs at 3 dose levels to select a safe and tolerable dose of a 3-dose schedule. Unlike GSK's RTS,S (AS01) and Serum Institute of India's R21/MatrixM, BNT-165 is being studied in adult age groups meaning it could be developed for Western travelers as well as those living in endemic countries. For the travelers profile, a recent commercial assessment forecast potential gross revenues of BNT-165 at $479m (2030) 5-yrs post launch, POS-adjusted revenues.{{cite web |title=VacZine Analytics | Our products - MarketVIEW: Travel vaccines segment report |url=https://www.vaczine-analytics.com/products-marketviewVAMV090_travel_vaccines_segment_report.asp}} [189] => [190] => ===Others=== [191] => Community participation and [[health education]] strategies promoting awareness of malaria and the importance of control measures have been successfully used to reduce the incidence of malaria in some areas of the developing world. Recognising the disease in the early stages can prevent it from becoming fatal. Education can also inform people to cover over areas of stagnant, still water, such as water tanks that are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people. This is generally used in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas. [[Intermittent preventive therapy]] is another intervention that has been used successfully to control malaria in pregnant women and infants, and in preschool children where transmission is seasonal. [192] => [193] => ==Treatment== [194] => [[File:"British India", six stages of malaria. Wellcome L0022443.jpg|alt=Advertisement entitled "The Mosquito Danger". Includes 6 panel cartoon:#1 breadwinner has malaria, family starving; #2 wife selling ornaments; #3 doctor administers quinine; #4 patient recovers; #5 doctor indicating that quinine can be obtained from post office if needed again; #6 man who refused quinine, dead on stretcher.|thumb|An advertisement for [[quinine]] as a malaria treatment from 1927.]] [195] => [196] => Malaria is treated with [[antimalarial medication]]s; the ones used depends on the type and severity of the disease.{{cite journal | vauthors = Hanboonkunupakarn B, White NJ | title = Advances and roadblocks in the treatment of malaria | journal = British Journal of Clinical Pharmacology | volume = 88 | issue = 2 | pages = 374–382 | date = February 2022 | pmid = 32656850 | pmc = 9437935 | doi = 10.1111/bcp.14474 | s2cid = 220502723 }} While [[antipyretics|medications against fever]] are commonly used, their effects on outcomes are not clear.{{Cite web | vauthors = Greenwood B |date=1 January 2004 |title=Treatment of malaria with antimalarial |url=https://pubmed.ncbi.nlm.nih.gov |access-date=26 April 2022}} Providing free antimalarial drugs to households may reduce childhood deaths when used appropriately. Programmes which presumptively treat all causes of fever with antimalarial drugs may lead to overuse of antimalarials and undertreat other causes of fever. Nevertheless, the use of malaria rapid-diagnostic kits can help to reduce over-usage of antimalarials.{{cite journal | vauthors = Okwundu CI, Nagpal S, Musekiwa A, Sinclair D | title = Home- or community-based programmes for treating malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 5 | pages = CD009527 | date = May 2013 | pmid = 23728693 | pmc = 6532579 | doi = 10.1002/14651858.CD009527.pub2 }}{{Cite web |title=Malaria - Diagnosis and treatment - Mayo Clinic |url=https://www.mayoclinic.org/diseases-conditions/malaria/diagnosis-treatment/drc-20351190 |access-date=2022-04-25 |website=www.mayoclinic.org}} [197] => {{Further|Cotrifazid}} [198] => [199] => ===Uncomplicated malaria=== [200] => Simple or uncomplicated malaria may be treated with oral medications. Artemisinin drugs are effective and safe in treating uncomplicated malaria.{{cite journal | vauthors = McIntosh HM, Olliaro P | title = Artemisinin derivatives for treating uncomplicated malaria | journal = The Cochrane Database of Systematic Reviews | volume = 1999 | issue = 2 | pages = CD000256 | date = 1999-04-26 | pmid = 10796519 | pmc = 6532741 | doi = 10.1002/14651858.CD000256 | collaboration = Cochrane Infectious Diseases Group }} Artemisinin in combination with other antimalarials (known as [[artemisinin-combination therapy]], or ACT) is about 90% effective when used to treat uncomplicated malaria. The most effective treatment for ''P. falciparum'' infection is the use of ACT, which decreases resistance to any single drug component.{{cite journal | vauthors = Pousibet-Puerto J, Salas-Coronas J, Sánchez-Crespo A, Molina-Arrebola MA, Soriano-Pérez MJ, Giménez-López MJ, Vázquez-Villegas J, Cabezas-Fernández MT | display-authors = 6 | title = Impact of using artemisinin-based combination therapy (ACT) in the treatment of uncomplicated malaria from ''Plasmodium falciparum'' in a non-endemic zone | journal = Malaria Journal | volume = 15 | issue = 1 | pages = 339 | date = July 2016 | pmid = 27368160 | pmc = 4930579 | doi = 10.1186/s12936-016-1408-1 | s2cid = 18043747 | doi-access = free }} Artemether-lumefantrine (six-dose regimen) is more effective than the artemether-lumefantrine (four-dose regimen) or other regimens not containing artemisinin derivatives in treating falciparum malaria.{{cite journal | vauthors = Omari AA, Gamble C, Garner P | title = Artemether-lumefantrine (four-dose regimen) for treating uncomplicated falciparum malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2006 | issue = 2 | pages = CD005965 | date = April 2006 | pmid = 16625646 | pmc = 6532603 | doi = 10.1002/14651858.CD005965 | collaboration = Cochrane Infectious Diseases Group }}{{cite journal | vauthors = Omari AA, Gamble C, Garner P | title = Artemether-lumefantrine (six-dose regimen) for treating uncomplicated falciparum malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2005 | issue = 4 | pages = CD005564 | date = October 2005 | pmid = 16235412 | pmc = 6532733 | doi = 10.1002/14651858.CD005564 | collaboration = Cochrane Infectious Diseases Group }} Another recommended combination is [[dihydroartemisinin]] and [[piperaquine]].{{harvnb|WHO|2010|p=21}}{{cite journal | vauthors = Sinclair D, Zani B, Donegan S, Olliaro P, Garner P | title = Artemisinin-based combination therapy for treating uncomplicated malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2009 | issue = 3 | pages = CD007483 | date = July 2009 | pmid = 19588433 | pmc = 6532584 | doi = 10.1002/14651858.CD007483.pub2 | collaboration = Cochrane Infectious Diseases Group }} Artemisinin-naphthoquine combination therapy showed promising results in treating falciparum malaria but more research is needed to establish its efficacy as a reliable treatment.{{cite journal | vauthors = Isba R, Zani B, Gathu M, Sinclair D | title = Artemisinin-naphthoquine for treating uncomplicated ''Plasmodium falciparum'' malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 2 | pages = CD011547 | date = February 2015 | pmid = 25702785 | pmc = 4453860 | doi = 10.1002/14651858.CD011547 | collaboration = Cochrane Infectious Diseases Group }} Artesunate plus mefloquine performs better than mefloquine alone in treating uncomplicated falciparum malaria in low transmission settings.{{cite journal | vauthors = Bukirwa H, Orton L | title = Artesunate plus mefloquine versus mefloquine for treating uncomplicated malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2005 | issue = 4 | pages = CD004531 | date = October 2005 | pmid = 16235367 | pmc = 6532646 | doi = 10.1002/14651858.CD004531.pub2 | collaboration = Cochrane Infectious Diseases Group }} Atovaquone-proguanil is effective against uncomplicated falciparum with a possible failure rate of 5% to 10%; the addition of artesunate may reduce failure rate.{{cite journal | vauthors = Blanshard A, Hine P | title = Atovaquone-proguanil for treating uncomplicated ''Plasmodium falciparum'' malaria | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD004529 | date = January 2021 | pmid = 33459345 | pmc = 8094970 | doi = 10.1002/14651858.CD004529.pub3 }} Azithromycin monotherapy or combination therapy has not shown effectiveness in treating ''Plasmodium falciparum'' or ''Plasmodium vivax'' malaria.{{cite journal | vauthors = van Eijk AM, Terlouw DJ | title = Azithromycin for treating uncomplicated malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2011 | issue = 2 | pages = CD006688 | date = February 2011 | pmid = 21328286 | pmc = 6532599 | doi = 10.1002/14651858.CD006688.pub2 | collaboration = Cochrane Infectious Diseases Group }} Amodiaquine plus sulfadoxine-pyrimethamine may achieve less treatment failures when compared to sulfadoxine-pyrimethamine alone in uncomplicated falciparum malaria.{{cite journal | vauthors = McIntosh HM, Jones KL | title = Chloroquine or amodiaquine combined with sulfadoxine-pyrimethamine for treating uncomplicated malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2005 | issue = 4 | pages = CD000386 | date = October 2005 | pmid = 16235276 | pmc = 6532604 | doi = 10.1002/14651858.CD000386.pub2 | collaboration = Cochrane Infectious Diseases Group }} There is insufficient data on chlorproguanil-dapsone in treating uncomplicated falciparum malaria.{{cite journal | vauthors = Amukoye E, Winstanley PA, Watkins WM, Snow RW, Hatcher J, Mosobo M, Ngumbao E, Lowe B, Ton M, Minyiri G, Marsh K | display-authors = 6 | title = Chlorproguanil-dapsone: effective treatment for uncomplicated falciparum malaria | journal = Antimicrobial Agents and Chemotherapy | volume = 41 | issue = 10 | pages = 2261–2264 | date = October 1997 | pmid = 9333058 | pmc = 164103 | doi = 10.1128/AAC.41.10.2261 }}{{cite journal | vauthors = Bukirwa H, Garner P, Critchley J | title = Chlorproguanil-dapsone for treating uncomplicated malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2004 | issue = 4 | pages = CD004387 | date = October 2004 | pmid = 15495106 | pmc = 6532720 | doi = 10.1002/14651858.CD004387.pub2 | collaboration = Cochrane Infectious Diseases Group }} The addition of primaquine with artemisinin-based combination therapy for falciparum malaria reduces its transmission at day 3-4 and day 8 of infection.{{cite journal | vauthors = Graves PM, Choi L, Gelband H, Garner P | title = Primaquine or other 8-aminoquinolines for reducing ''Plasmodium falciparum'' transmission | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 2 | pages = CD008152 | date = February 2018 | pmid = 29393511 | pmc = 5815493 | doi = 10.1002/14651858.CD008152.pub5 | collaboration = Cochrane Infectious Diseases Group }} Sulfadoxine-pyrimethamine plus artesunate is better than sulfadoxine-pyrimethamine plus amodiaquine in controlling treatment failure at day 28. However, the latter is better than the former in reducing gametocytes in blood at day 7.{{cite journal | vauthors = Bukirwa H, Critchley J | title = Sulfadoxine-pyrimethamine plus artesunate versus sulfadoxine-pyrimethamine plus amodiaquine for treating uncomplicated malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2006 | issue = 1 | pages = CD004966 | date = January 2006 | pmid = 16437507 | pmc = 6532706 | doi = 10.1002/14651858.CD004966.pub2 | collaboration = Cochrane Infectious Diseases Group }} [201] => [202] => Infection with ''P. vivax'', ''P. ovale'' or ''P. malariae'' usually does not require hospitalisation. Treatment of ''P. vivax'' malaria requires both elimination of the parasite in the blood with chloroquine or with artemisinin-based combination therapy and clearance of parasites from the liver with an [[8-aminoquinoline]] agent such as [[primaquine]] or [[tafenoquine]].{{cite journal | vauthors = Rodrigo C, Rajapakse S, Fernando D | title = Tafenoquine for preventing relapse in people with ''Plasmodium vivax'' malaria | journal = The Cochrane Database of Systematic Reviews | volume = 9 | issue = 9 | pages = CD010458 | date = September 2020 | pmid = 32892362 | pmc = 8094590 | doi = 10.1002/14651858.CD010458.pub3 }} These two drugs act against blood stages as well, the extent to which they do so still being under investigation.{{cite journal | vauthors = Markus MB | title = Putative Contribution of 8-Aminoquinolines to Preventing Recrudescence of Malaria | journal = Tropical Medicine and Infectious Disease | volume = 8 | issue = 5 | page = 278 | date = May 2023 | pmid = 37235326 | doi = 10.3390/tropicalmed8050278 | pmc = 10223033 | doi-access = free }} [203] => [204] => To treat malaria during pregnancy, the [[World Health Organization|WHO]] recommends the use of quinine plus [[clindamycin]] early in the pregnancy (1st trimester), and ACT in later stages (2nd and 3rd trimesters).{{cite journal | vauthors = Tarning J | title = Treatment of Malaria in Pregnancy | journal = The New England Journal of Medicine | volume = 374 | issue = 10 | pages = 981–982 | date = March 2016 | pmid = 26962733 | doi = 10.1056/NEJMe1601193 | url = https://ora.ox.ac.uk/objects/uuid:e67b1397-c8ed-493f-a61e-f265d8a41c11 | doi-access = free }} There is limited safety data on the antimalarial drugs in pregnancy.{{cite journal | vauthors = Orton LC, Omari AA | title = Drugs for treating uncomplicated malaria in pregnant women | journal = The Cochrane Database of Systematic Reviews | volume = 2008 | issue = 4 | pages = CD004912 | date = October 2008 | pmid = 18843672 | pmc = 6532683 | doi = 10.1002/14651858.CD004912.pub3 | collaboration = Cochrane Infectious Diseases Group }} [205] => [206] => ===Severe and complicated malaria=== [207] => Cases of severe and complicated malaria are almost always caused by infection with ''P. falciparum''. The other species usually cause only febrile disease.{{cite journal | vauthors = Kochar DK, Saxena V, Singh N, Kochar SK, Kumar SV, Das A | title = ''Plasmodium vivax'' malaria | journal = Emerging Infectious Diseases | volume = 11 | issue = 1 | pages = 132–4 | date = January 2005 | pmid = 15705338 | pmc = 3294370 | doi = 10.3201/eid1101.040519 }} Severe and complicated malaria cases are medical emergencies since mortality rates are high (10% to 50%).{{cite journal | vauthors = Pasvol G | title = The treatment of complicated and severe malaria | journal = British Medical Bulletin | volume = 75-76 | pages = 29–47 | date = 2005 | pmid = 16495509 | doi = 10.1093/bmb/ldh059 | doi-access = free }} [208] => [209] => Recommended treatment for severe malaria is the [[parenteral administration|intravenous]] use of antimalarial drugs. For severe malaria, [[parenteral]] artesunate was superior to quinine in both children and adults.{{Cite web | work = CDC-Centers for Disease Control and Prevention |date=2022-04-11 |title=CDC - Malaria - Diagnosis & Treatment (United States) - Treatment (U.S.) - Artesunate dose 400 mg oral|url=https://www.cdc.gov/malaria/diagnosis_treatment/artesunate.html |access-date=2022-04-25 |language=en-us}} In another systematic review, artemisinin derivatives (artemether and arteether) were as efficacious as quinine in the treatment of cerebral malaria in children.{{cite journal | vauthors = Kyu HH, Fernández E | title = Artemisinin derivatives versus quinine for cerebral malaria in African children: a systematic review | journal = Bulletin of the World Health Organization | volume = 87 | issue = 12 | pages = 896–904 | date = December 2009 | pmid = 20454480 | pmc = 2789363 | doi = 10.2471/BLT.08.060327 | url = https://www.who.int/bulletin/volumes/87/12/08-060327/en/ | url-status = dead | archive-url = https://web.archive.org/web/20160304051023/http://www.who.int/bulletin/volumes/87/12/08-060327/en/ | archive-date = 2016-03-04 }} Treatment of severe malaria involves supportive measures that are best done in a [[critical care unit]]. This includes the management of [[hyperpyrexia|high fevers]] and the seizures that may result from it. It also includes monitoring for [[respiratory depression|poor breathing effort]], low blood sugar, and [[hypokalemia|low blood potassium]]. Artemisinin derivatives have the same or better efficacy than quinolones in preventing deaths in severe or complicated malaria.{{cite journal | vauthors = McIntosh HM, Olliaro P | title = Artemisinin derivatives for treating severe malaria | journal = The Cochrane Database of Systematic Reviews | volume = 1998 | issue = 2 | pages = CD000527 | date = 1998-07-27 | pmid = 10796551 | pmc = 6532607 | doi = 10.1002/14651858.CD000527 | collaboration = Cochrane Infectious Diseases Group }} Quinine [[loading dose]] helps to shorten the duration of fever and increases parasite clearance from the body.{{cite journal | vauthors = Lesi A, Meremikwu M | title = High first dose quinine regimen for treating severe malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2004 | issue = 3 | pages = CD003341 | date = 2004-07-19 | pmid = 15266481 | pmc = 6532696 | doi = 10.1002/14651858.CD003341.pub2 | collaboration = Cochrane Infectious Diseases Group }} There is no difference in effectiveness when using intrarectal quinine compared to intravenous or intramuscular quinine in treating uncomplicated/complicated falciparum malaria.{{cite journal | vauthors = Eisenhut M, Omari AA | title = Intrarectal quinine versus intravenous or intramuscular quinine for treating ''Plasmodium falciparum'' malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2009 | issue = 1 | pages = CD004009 | date = January 2009 | pmid = 19160229 | pmc = 6532585 | doi = 10.1002/14651858.CD004009.pub3 | collaboration = Cochrane Infectious Diseases Group }} There is insufficient evidence for intramuscular arteether to treat severe malaria.{{cite journal | vauthors = Afolabi BB, Okoromah CN | title = Intramuscular arteether for treating severe malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2004 | issue = 4 | pages = CD004391 | date = October 2004 | pmid = 15495107 | pmc = 6532577 | doi = 10.1002/14651858.CD004391.pub2 | collaboration = Cochrane Infectious Diseases Group }} The provision of rectal artesunate before transfer to hospital may reduce the rate of death for children with severe malaria.{{cite journal | vauthors = Okebe J, Eisenhut M | title = Pre-referral rectal artesunate for severe malaria | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 5 | pages = CD009964 | date = May 2014 | pmid = 24869943 | pmc = 4463986 | doi = 10.1002/14651858.CD009964.pub2 | collaboration = Cochrane Infectious Diseases Group }} In children with malaria and concomitant hypoglycaemia, sublingual administration of glucose appears to result in better increases in blood sugar after 20 minutes when compared to oral administration, based on very limited data.{{cite journal | vauthors = De Buck E, Borra V, Carlson JN, Zideman DA, Singletary EM, Djärv T | title = First aid glucose administration routes for symptomatic hypoglycaemia | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 4 | pages = CD013283 | date = April 2019 | pmid = 30973639 | pmc = 6459163 | doi = 10.1002/14651858.CD013283.pub2 | collaboration = Cochrane Metabolic and Endocrine Disorders Group }} [210] => [211] => Cerebral malaria is the form of severe and complicated malaria with the worst neurological symptoms.{{cite journal | vauthors = Idro R, Marsh K, John CC, Newton CR | title = Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome | journal = Pediatric Research | volume = 68 | issue = 4 | pages = 267–74 | date = October 2010 | pmid = 20606600 | pmc = 3056312 | doi = 10.1203/pdr.0b013e3181eee738 }} There is insufficient data on whether osmotic agents such as mannitol or urea are effective in treating cerebral malaria.{{cite journal | vauthors = Okoromah CA, Afolabi BB, Wall EC | title = Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD004615 | date = April 2011 | volume = 2011 | pmid = 21491391 | pmc = 4018680 | doi = 10.1002/14651858.CD004615.pub3 | collaboration = Cochrane Infectious Diseases Group }} Routine phenobarbitone in cerebral malaria is associated with fewer [[convulsion]]s but possibly more deaths.{{cite journal | vauthors = Meremikwu M, Marson AG | title = Routine anticonvulsants for treating cerebral malaria | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD002152 | date = 2002-04-22 | volume = 2002 | pmid = 12076440 | pmc = 6532751 | doi = 10.1002/14651858.CD002152 | collaboration = Cochrane Infectious Diseases Group }} There is no evidence that steroids would bring treatment benefits for cerebral malaria.{{cite journal | vauthors = Prasad K, Garner P | title = Steroids for treating cerebral malaria | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD000972 | date = 1999-07-26 | volume = 1999 | pmid = 10796562 | pmc = 6532619 | doi = 10.1002/14651858.CD000972 | collaboration = Cochrane Infectious Diseases Group }} [212] => [213] => '''Managing Cerebral Malaria''' [214] => [215] => Cerebral malaria usually makes a patient comatose. If the cause of the coma is in doubt, testing for other locally prevalent causes of encephalopathy (bacterial, viral or fungal infection) should be carried out. In areas where there is a high prevalence of malaria infection (e.g. tropical region) treatment can start without testing first. To manage the cerebral malaria when confirmed the following can be done: [216] => [217] => * Patients in coma should be given meticulous nursing care ( monitor vital signs, turn patient every 2 hours, avoid lying the patient in a wet bed etc.) [218] => * A sterile urethral catheter should be inserted to help with urinating [219] => * To aspirate stomach content, a sterile nasogastric tube should be inserted. [220] => * In the occasion of convulsions, a slow intravenous injection of benzodiazepine is administered.{{Cite book |title=A Practical Handbook (third edition) Management Of Severe Malaria |publisher=[[World Health Organization]] |year=2012 |isbn=9789241548526 |pages=43–44 |language=en}} [221] => [222] => There is insufficient evidence to show that blood transfusion is useful in either reducing deaths for children with severe anaemia or in improving their [[haematocrit]] in one month.{{cite journal | vauthors = Meremikwu M, Smith HJ | title = Blood transfusion for treating malarial anaemia | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD001475 | date = 1999-10-25 | volume = 1999 | pmid = 10796646 | pmc = 6532690 | doi = 10.1002/14651858.CD001475 | collaboration = Cochrane Infectious Diseases Group }} There is insufficient evidence that iron chelating agents such as deferoxamine and deferiprone improve outcomes of those with malaria falciparum infection.{{cite journal | vauthors = Smith HJ, Meremikwu M | title = Iron chelating agents for treating malaria | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD001474 | date = 2003-04-22 | pmid = 12804409 | pmc = 6532667 | doi = 10.1002/14651858.CD001474 | collaboration = Cochrane Infectious Diseases Group }} [223] => [224] => ===Monoclonal antibodies=== [225] => A 2022 clinical trial shows that a monoclonal antibody [[mAb L9LS]] offers protection against malaria. It binds the ''Plasmodium falciparum'' circumsporozoite protein (CSP-1), essential to disease, and makes it ineffective.{{cite journal | vauthors = | title = Lab-made antibody stops malaria| journal = Nat Biotechnol | pages = 1304 | date = September 2022| volume = 40 | issue = 9 | pmid = 36085505 | doi = 10.1038/s41587-022-01480-2| s2cid = 252181345}} [226] => [227] => ===Resistance=== [228] => [[Drug resistance]] poses a growing problem in 21st-century malaria treatment. In the 2000s (decade), malaria with partial resistance to artemisins emerged in Southeast Asia. Resistance is now common against all classes of antimalarial drugs apart from [[artemisinin]]s. Treatment of resistant strains became increasingly dependent on this class of drugs. The cost of artemisinins limits their use in the developing world. Malaria strains found on the Cambodia–Thailand border are resistant to combination therapies that include artemisinins, and may, therefore, be untreatable. Exposure of the parasite population to artemisinin monotherapies in subtherapeutic doses for over 30 years and the availability of substandard artemisinins likely drove the selection of the resistant phenotype. Resistance to artemisinin has been detected in Cambodia, Myanmar, Thailand, and Vietnam,{{cite journal|author=World Health Organization |title=Q&A on artemisinin resistance |journal=WHO Malaria Publications |year=2013 |url=https://www.who.int/malaria/media/artemisinin_resistance_qa/en/index.html |url-status=dead |archive-url=https://web.archive.org/web/20160720075407/http://www.who.int/malaria/media/artemisinin_resistance_qa/en/index.html |archive-date=2016-07-20 }} and there has been emerging resistance in Laos.{{Cite news| vauthors = Briggs H |date=2014-07-30|title=Call for 'radical action' on drug-resistant malaria|language=en-GB|work=BBC News|url=https://www.bbc.com/news/health-28569966|access-date=2023-02-23}} Resistance to the combination of artemisinin and piperaquine was first detected in 2013 in Cambodia, and by 2019 had spread across Cambodia and into [[Laos]], [[Thailand]] and [[Vietnam]] (with up to 80 percent of malaria parasites resistant in some regions).{{Cite news|url=https://www.bbc.com/news/health-49017699|title=Resistant malaria spreading in South East Asia| vauthors = Gallagher J |date=2019-07-23|access-date=2019-07-25|language=en-GB}} [229] => [230] => There is insufficient evidence in unit packaged antimalarial drugs in preventing treatment failures of malaria infection. However, if supported by training of healthcare providers and patient information, there is improvement in compliance of those receiving treatment.{{cite journal | vauthors = Orton L, Barnish G | title = Unit-dose packaged drugs for treating malaria | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD004614 | date = April 2005 | volume = 2005 | pmid = 15846723 | doi = 10.1002/14651858.CD004614.pub2 | collaboration = Cochrane Infectious Diseases Group | pmc = 6532754 }} [231] => [232] => ==Prognosis== [233] => [[File:Malaria world map - DALY - WHO2004.svg|thumb|upright=1.3|[[Disability-adjusted life year]] for malaria per 100,000 inhabitants in 2004{{div col|colwidth=10em}} [234] => {{legend|#b3b3b3| no data}} [235] => {{legend|#ffff65| <10}} [236] => {{legend|#fff200| 0–100}} [237] => {{legend|#ffdc00| 100–500}} [238] => {{legend|#ffc600| 500–1000}} [239] => {{legend|#ffb000|1000–1500}} [240] => {{legend|#ff9a00|1500–2000}} [241] => {{legend|#ff8400|2000–2500}} [242] => {{legend|#ff6e00|2500–2750}} [243] => {{legend|#ff5800|2750–3000}} [244] => {{legend|#ff4200|3000–3250}} [245] => {{legend|#ff2c00|3250–3500}} [246] => {{legend|#cb0000| ≥3500}} [247] => {{div col end}}]] [248] => When properly treated, people with malaria can usually expect a complete recovery. However, severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease, [[fatality rate]]s can reach 20%, even with intensive care and treatment. Over the longer term, developmental impairments have been documented in children who have had episodes of severe malaria. [[chronic (medicine)|Chronic]] infection without severe disease can occur in an immune-deficiency syndrome associated with a decreased responsiveness to ''[[Salmonella]]'' bacteria and the [[Epstein–Barr virus]]. [249] => [250] => During childhood, malaria causes anaemia during a period of rapid brain development, and also direct brain damage resulting from cerebral malaria. Some survivors of cerebral malaria have an increased risk of neurological and cognitive deficits, [[Emotional and behavioral disorders|behavioural disorders]], and [[epilepsy]]. Malaria prophylaxis was shown to improve cognitive function and school performance in [[clinical trial]]s when compared to [[placebo]] groups. [251] => [252] => ==Epidemiology== [253] => [[File:Malaria world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|left|Deaths due to malaria per million persons in 2012 {{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0–0}}{{legend|#ffa020|1–2}}{{legend|#ff9a20|3–54}}{{legend|#f08015|55–325}}{{legend|#e06815|326–679}}{{legend|#d85010|680–949}}{{legend|#d02010|950–1,358}}{{div col end}}]] [254] => [[File:World-map-of-past-and-current-malaria-prevalence-world-development-report-2009.png|thumb|upright=1.3|left|Past and current malaria prevalence in 2009]] [255] => [[File:Relative incidence of Plasmodium (malaria) species by country of origin for imported cases to non-endemic countries.png|thumb|upright=1.3|left|Relative incidence of ''Plasmodium'' species by country of origin for imported cases to non-endemic countries{{cite journal| vauthors = Tatem AJ, Jia P, Ordanovich D, Falkner M, Huang Z, Howes R | display-authors=etal| title=The geography of imported malaria to non-endemic countries: a meta-analysis of nationally reported statistics. | journal=Lancet Infect Dis | year= 2017 | volume= 17 | issue= 1 | pages= 98–107 | pmid=27777030 | doi=10.1016/S1473-3099(16)30326-7 | pmc=5392593 }}]] [256] => The WHO estimates that in 2021 there were 247 million new cases of malaria resulting in 619,000 deaths. Children under five years old are the most affected, accounting for 67% of malaria deaths worldwide in 2019.{{cite book |last1=WHO |url=https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021|title=World Malaria Report 2021|date=2021|publisher=World Health Organization|isbn=978-92-4-004049-6|location=Switzerland}} About 125 million pregnant women are at risk of infection each year; in [[Sub-Saharan Africa]], maternal malaria is associated with up to 200,000 estimated infant deaths yearly. Since 2015, the WHO European Region has been free of malaria. The last country to report an indigenous malaria case was Tajikistan in 2014. There are about 1300–1500 malaria cases per year in the United States. The United States eradicated malaria as a major public health concern in 1951,{{cite web | work = CDC-Centers for Disease Control and Prevention |title=CDC - Malaria - About Malaria - History - Elimination of Malaria in the United States (1947-1951) |url= https://www.cdc.gov/malaria/about/history/elimination_us.html |access-date=17 January 2020 |language=en-us |date=28 January 2019}} though small outbreaks persist.{{Cite web | work = CDC-Centers for Disease Control and Prevention|date=2019-01-28|title=CDC - Malaria - About Malaria - Malaria Transmission in the United States|url=https://www.cdc.gov/malaria/about/us_transmission.html|access-date=2021-09-03 |language=en-us}} Locally acquired mosquito-borne malaria occurred in the United States in 2003, when eight cases of locally acquired ''P. vivax'' malaria were identified in Florida, and again in May 2023, in four cases, as well as one case in Texas,{{Cite web |last=Health Alert Network (HAN) |date=2023-06-26 |title= Locally Acquired Malaria Cases Identified in the United States |url=https://emergency.cdc.gov/han/2023/han00494.asp |access-date=2023-06-27 |website=emergency.cdc.gov |language=en-us}} and in August in one case in Maryland.{{Cite news |date=2023-08-28 |title= Important Updates on Locally Acquired Malaria Cases Identified in Florida, Texas, and Maryland |language=en-us |work=Health Alert Network (HAN) - 00496 |url=https://emergency.cdc.gov/han/2023/han00496.asp |access-date=2023-08-28}} About 900 people died from the disease in Europe between 1993 and 2003. Both the global incidence of disease and resulting mortality have declined in recent years. According to the WHO and UNICEF, deaths attributable to malaria in 2015 were reduced by 60%{{cite book|title=Achieving the malaria MDG target: reversing the incidence of malaria 2000–2015|url=http://www.unicef.org/publications/files/Achieving_the_Malaria_MDG_Target.pdf|website=UNICEF|publisher=WHO|access-date=26 December 2015|date=September 2015|isbn=978-92-4-150944-2|url-status=live|archive-url=https://web.archive.org/web/20160105025916/http://www.unicef.org/publications/files/Achieving_the_Malaria_MDG_Target.pdf|archive-date=5 January 2016}} from a 2000 estimate of 985,000, largely due to the widespread use of insecticide-treated nets and artemisinin-based combination therapies. Between 2000 and 2019, malaria mortality rates among all ages halved from about 30 to 13 per 100,000 population at risk. During this period, malaria deaths among children under five also declined by nearly half (47%) from 781,000 in 2000 to 416,000 in 2019. [257] => [258] => Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; in Sub-Saharan Africa, 85–90% of malaria fatalities occur. An estimate for 2009 reported that countries with the highest death rate per 100,000 of population were [[Ivory Coast]] (86.15), [[Angola]] (56.93) and [[Burkina Faso]] (50.66). A 2010 estimate indicated the deadliest countries per population were Burkina Faso, [[Mozambique]] and [[Mali]]. The [[Malaria Atlas Project]] aims to map global [[Endemic (epidemiology)|levels of malaria]], providing a way to determine the global spatial limits of the disease and to assess [[disease burden]]. This effort led to the publication of a map of ''P. falciparum'' endemicity in 2010 and an update in 2019.{{cite journal | vauthors = Weiss DJ, Lucas TC, Nguyen M, Nandi AK, Bisanzio D, Battle KE, Cameron E, Twohig KA, Pfeffer DA, Rozier JA, Gibson HS, Rao PC, Casey D, Bertozzi-Villa A, Collins EL, Dalrymple U, Gray N, Harris JR, Howes RE, Kang SY, Keddie SH, May D, Rumisha S, Thorn MP, Barber R, Fullman N, Huynh CK, Kulikoff X, Kutz MJ, Lopez AD, Mokdad AH, Naghavi M, Nguyen G, Shackelford KA, Vos T, Wang H, Smith DL, Lim SS, Murray CJ, Bhatt S, Hay SI, Gething PW | display-authors = 6 | title = Mapping the global prevalence, incidence, and mortality of ''Plasmodium falciparum'', 2000-17: a spatial and temporal modelling study | journal = Lancet | volume = 394 | issue = 10195 | pages = 322–331 | date = July 2019 | pmid = 31229234 | pmc = 6675740 | doi = 10.1016/S0140-6736(19)31097-9 | doi-access = free }}{{cite journal | vauthors = Battle KE, Lucas TC, Nguyen M, Howes RE, Nandi AK, Twohig KA, Pfeffer DA, Cameron E, Rao PC, Casey D, Gibson HS, Rozier JA, Dalrymple U, Keddie SH, Collins EL, Harris JR, Guerra CA, Thorn MP, Bisanzio D, Fullman N, Huynh CK, Kulikoff X, Kutz MJ, Lopez AD, Mokdad AH, Naghavi M, Nguyen G, Shackelford KA, Vos T, Wang H, Lim SS, Murray CJ, Price RN, Baird JK, Smith DL, Bhatt S, Weiss DJ, Hay SI, Gething PW | display-authors = 6 | title = Mapping the global endemicity and clinical burden of ''Plasmodium vivax'', 2000-17: a spatial and temporal modelling study | journal = Lancet | volume = 394 | issue = 10195 | pages = 332–343 | date = July 2019 | pmid = 31229233 | pmc = 6675736 | doi = 10.1016/S0140-6736(19)31096-7 | doi-access = free }} As of 2021, 84 countries have endemic malaria. [259] => [260] => The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other. Malaria is prevalent in tropical and subtropical regions because of rainfall, consistent high temperatures and high humidity, along with stagnant waters where mosquito larvae readily mature, providing them with the environment they need for continuous breeding. In drier areas, outbreaks of malaria have been predicted with reasonable accuracy by mapping rainfall. Malaria is more common in rural areas than in cities. For example, several cities in the [[Greater Mekong Subregion]] of Southeast Asia are essentially malaria-free, but the disease is prevalent in many rural regions, including along international borders and forest fringes. In contrast, malaria in Africa is present in both rural and urban areas, though the risk is lower in the larger cities. [261] => [262] => ===Climate change=== [263] => {{Further|Climate change and infectious diseases#Malaria}} [264] => [265] => [[Climate change]] is likely to affect malaria transmission, but the degree of effect and the areas affected is uncertain.{{cite web|title=Climate Change And Infectious Diseases|url=https://www.who.int/globalchange/climate/en/chapter6.pdf|url-status=live|archive-url=https://web.archive.org/web/20160304063626/http://www.who.int/globalchange/climate/en/chapter6.pdf|archive-date=2016-03-04|work=Climate Change and Human Health—Risk and Responses|publisher=World Health Organization}} Greater rainfall in certain areas of India, and following an [[El Niño]] event is associated with increased mosquito numbers.{{cite web|title=Climate change and human health – risks and responses. Summary.|url=https://www.who.int/globalchange/climate/summary/en/index5.html|archive-url=https://web.archive.org/web/20031225023503/http://www.who.int/globalchange/climate/summary/en/index5.html|url-status=dead|archive-date=December 25, 2003|access-date=29 October 2018|website=www.who.int}} [266] => [267] => Since 1900 there has been substantial change in temperature and rainfall over Africa.{{Cite journal|vauthors=Hulme M, Doherty R, Ngara T, New M, Lister D|date=August 2001|title=African climate change: 1900-2100.|url=https://www.int-res.com/articles/cr/17/c017p145.pdf|journal=Climate Research|volume=17|issue=2|pages=145–68|doi=10.3354/cr017145|bibcode=2001ClRes..17..145H |doi-access=free}} However, factors that contribute to how rainfall results in water for mosquito breeding are complex, incorporating the extent to which it is absorbed into soil and vegetation for example, or rates of runoff and evaporation.{{cite journal|display-authors=6|vauthors=Smith MW, Willis T, Alfieri L, James WH, Trigg MA, Yamazaki D, Hardy AJ, Bisselink B, De Roo A, Macklin MG, Thomas CJ|date=August 2020|title=Incorporating hydrology into climate suitability models changes projections of malaria transmission in Africa|journal=Nature Communications|volume=11|issue=1|pages=4353|doi=10.1038/s41467-020-18239-5|pmc=7455692|pmid=32859908|bibcode=2020NatCo..11.4353S }} Recent research has provided a more in-depth picture of conditions across Africa, combining a malaria climatic suitability model with a continental-scale model representing real-world hydrological processes. [268] => [269] => ==History== [270] => {{Main|History of malaria|Mosquito-malaria theory}} [271] => [[File:Malaria pathogens.jpg|thumb|upright|Ancient malaria oocysts preserved in [[Dominican amber]]]] [272] => Although the parasite responsible for ''P. falciparum'' malaria has been in existence for 50,000–100,000 years, the population size of the parasite did not increase until about 10,000 years ago, concurrently with advances in agriculture and the development of human settlements. Close relatives of the human malaria parasites remain common in chimpanzees. Some evidence suggests that the ''P. falciparum'' malaria may have originated in gorillas. [273] => [274] => References to the unique periodic fevers of malaria are found throughout history. Hippocrates described periodic fevers, labelling them tertian, quartan, subtertian and quotidian.{{cite book| vauthors = Strong RP |title=Stitt's Diagnosis, Prevention and Treatment of Tropical Diseases|date=1944|publisher=The Blakiston Company|location=York, PA|page=3|edition=Seventh}} The Roman [[Columella]] associated the disease with insects from swamps. Malaria may have contributed to the decline of the [[Roman Empire]], and was so pervasive in Rome that it was known as the "[[Roman Fever (disease)|Roman fever]]". Several regions in ancient Rome were considered at-risk for the disease because of the favourable conditions present for malaria vectors. This included areas such as southern Italy, the island of [[Sardinia]], the [[Pontine Marshes]], the lower regions of coastal [[Etruria]] and the city of [[Rome]] along the [[Tiber]]. The presence of stagnant water in these places was preferred by mosquitoes for breeding grounds. Irrigated gardens, swamp-like grounds, run-off from agriculture, and drainage problems from road construction led to the increase of standing water. [275] => [276] => [[File:Ronald Ross.jpg|thumb|left|British doctor [[Ronald Ross]] received the [[Nobel Prize for Physiology or Medicine]] in 1902 for his work on malaria.]] [277] => [278] => The term malaria originates from [[Middle Ages|Mediaeval]] {{lang-it|mala aria}}—"bad air", a part of [[miasma theory]]; the disease was formerly called ''ague'' or ''marsh fever'' due to its association with swamps and marshland.{{cite journal | vauthors = Reiter P | title = From Shakespeare to Defoe: malaria in England in the Little Ice Age | journal = Emerging Infectious Diseases | volume = 6 | issue = 1 | pages = 1–11 | date = 1999 | pmid = 10653562 | pmc = 2627969 | doi = 10.3201/eid0601.000101 }} The term appeared in English at least as early as 1768.{{cite book |vauthors=Sharpe S |date=1768 |title=A view of the customs, manners, drama, &c. of Italy, as they are described in the Frusta letteraria; and in the Account of Italy in English, written by Mr. Baretti; compared with the Letters from Italy, written by Mr. Sharp |location=London |publisher=W. Nicoll }} Malaria was once common in most of Europe and North America, where it is no longer endemic, though imported cases do occur. [279] => [280] => Malaria is not referenced in the medical books of the [[Mayans]] or [[Aztecs]]. Despite this, antibodies against malaria have been detected in some South American mummies, indicating that some malaria strains in the Americas might have a pre-Columbian origin.{{cite journal | vauthors = Rodrigues PT, Valdivia HO, de Oliveira TC, Alves JM, Duarte AM, Cerutti-Junior C, Buery JC, Brito CF, de Souza JC, Hirano ZM, Bueno MG, Catão-Dias JL, Malafronte RS, Ladeia-Andrade S, Mita T, Santamaria AM, Calzada JE, Tantular IS, Kawamoto F, Raijmakers LR, Mueller I, Pacheco MA, Escalante AA, Felger I, Ferreira MU | display-authors = 6 | title = Human migration and the spread of malaria parasites to the New World | journal = Scientific Reports | volume = 8 | issue = 1 | pages = 1993 | date = January 2018 | pmid = 29386521 | pmc = 5792595 | doi = 10.1038/s41598-018-19554-0 | bibcode = 2018NatSR...8.1993R }} European settlers and the West Africans they [[Atlantic slave trade|enslaved]] likely brought malaria to the Americas starting in the 16th century.{{cite journal |vauthors=De Castro MC, Singer BH |title=Was malaria present in the Amazon before the European conquest? Available evidence and future research agenda |journal=J. Archaeol. Sci. |volume=32 |pages=337–40 |year=2005 |doi=10.1016/j.jas.2004.10.004 |issue=3|bibcode=2005JArSc..32..337D }}{{cite journal | vauthors = Yalcindag E, Elguero E, Arnathau C, Durand P, Akiana J, Anderson TJ, Aubouy A, Balloux F, Besnard P, Bogreau H, Carnevale P, D'Alessandro U, Fontenille D, Gamboa D, Jombart T, Le Mire J, Leroy E, Maestre A, Mayxay M, Ménard D, Musset L, Newton PN, Nkoghé D, Noya O, Ollomo B, Rogier C, Veron V, Wide A, Zakeri S, Carme B, Legrand E, Chevillon C, Ayala FJ, Renaud F, Prugnolle F | display-authors = 6 | title = Multiple independent introductions of ''Plasmodium falciparum'' in South America | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 2 | pages = 511–516 | date = January 2012 | pmid = 22203975 | pmc = 3258587 | doi = 10.1073/pnas.1119058109 | doi-access = free | bibcode = 2012PNAS..109..511Y }} [281] => [282] => Scientific studies on malaria made their first significant advance in 1880, when [[Charles Louis Alphonse Laveran]]—a French army doctor working in the military hospital of [[Constantine, Algeria|Constantine]] in [[Algeria]]—observed parasites inside the red blood cells of infected people for the first time.{{cite journal |title=Malarial organisms in the blood |journal=Scientific American |url=https://books.google.com/books?id=zoE9AQAAIAAJ&pg=PA37 |date=21 January 1882 |publisher=Munn & Company |pages=37–38 |volume=46 |issue=3}} He, therefore, proposed that malaria is caused by this organism, the first time a [[protist]] was identified as causing disease. For this and later discoveries, he was awarded the 1907 [[Nobel Prize for Physiology or Medicine]]. A year later, [[Carlos Finlay]], a Cuban doctor treating people with [[yellow fever]] in [[Havana]], provided strong evidence that mosquitoes were transmitting disease to and from humans. This work followed earlier suggestions by [[Josiah C. Nott]], and work by [[Sir Patrick Manson]], the "father of tropical medicine", on the transmission of [[filariasis]]. [283] => [284] => [[File:Tu Youyou 5012-1-2015.jpg|thumb|left|Chinese medical researcher [[Tu Youyou]] received the [[Nobel Prize for Physiology or Medicine]] in 2015 for her work on the antimalarial drug [[artemisinin]].]] [285] => [286] => In April 1894, a Scottish physician, [[Ronald Ross|Sir Ronald Ross]], visited Sir Patrick Manson at his house on Queen Anne Street, London. This visit was the start of four years of collaboration and fervent research that culminated in 1897 when Ross, who was working in the [[Presidency General Hospital]] in [[Kolkata|Calcutta]], proved the complete life-cycle of the malaria parasite in mosquitoes. He thus proved that the mosquito was the vector for malaria in humans by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. For this work, Ross received the 1902 Nobel Prize in Medicine. After resigning from the [[Indian Medical Service]], Ross worked at the newly established [[Liverpool School of Tropical Medicine]] and directed malaria-control efforts in [[Egypt]], [[Panama]], [[Greece]] and [[Mauritius]]. The findings of Finlay and Ross were later confirmed by a medical board headed by [[Walter Reed]] in 1900. Its recommendations were implemented by [[William C. Gorgas]] in [[Health measures during the construction of the Panama Canal|the health measures undertaken]] during construction of the [[Panama Canal]]. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against the disease. [287] => [288] => In 1896, [[Amico Bignami]] discussed the role of mosquitoes in malaria.{{cite web |title=Amico Bignami |url=https://www.whonamedit.com/doctor.cfm/2484.html |website=www.whonamedit.com |access-date=30 July 2019}} In 1898, Bignami, [[Giovanni Battista Grassi]] and [[Giuseppe Bastianelli]] succeeded in showing experimentally the transmission of malaria in humans, using infected mosquitoes to contract malaria themselves which they presented in November 1898 to the [[Accademia dei Lincei]].{{cite journal | vauthors = Cox FE | title = History of the discovery of the malaria parasites and their vectors | journal = Parasites & Vectors | volume = 3 | issue = 1 | pages = 5 | date = February 2010 | pmid = 20205846 | pmc = 2825508 | doi = 10.1186/1756-3305-3-5 | doi-access = free }} [289] => [290] => [[File:Artemisia annua West Virginia.jpg|thumb|right|''Artemisia annua'', source of the antimalarial drug [[artemisinin]]]] [291] => [292] => The first effective treatment for malaria came from the bark of [[Cinchona|cinchona tree]], which contains [[quinine]]. This tree grows on the slopes of the [[Andes]], mainly in [[Peru]]. The [[indigenous peoples of Peru]] made a [[tincture]] of cinchona to control fever. Its effectiveness against malaria was found and the [[Jesuit]]s introduced the treatment to Europe around 1640; by 1677, it was included in the [[London Pharmacopoeia]] as an antimalarial treatment. It was not until 1820 that the active ingredient, quinine, was extracted from the bark, isolated and named by the French chemists [[Pierre Joseph Pelletier]] and [[Joseph Bienaimé Caventou]]. [293] => [294] => Quinine was the predominant malarial medication until the 1920s when other medications began to appear. In the 1940s, chloroquine replaced quinine as the treatment of both uncomplicated and severe malaria until resistance supervened, first in Southeast Asia and South America in the 1950s and then globally in the 1980s. [295] => [296] => The medicinal value of ''[[Artemisia annua]]'' has been used by Chinese herbalists in [[traditional Chinese medicines]] for 2,000 years. In 1596, Li Shizhen recommended tea made from qinghao specifically to treat malaria symptoms in his "[[Compendium of Materia Medica]]", however the efficacy of tea, made with ''A. annua'', for the treatment of malaria is dubious, and is discouraged by the [[World Health Organization]] (WHO).{{cite book|publisher = World Health Organization|title = WHO monograph on good agricultural and collection practices (GACP) for ''Artemisia annua'' L.|date = 2006|url= https://www.who.int/medicines/publications/traditional/ArtemisiaMonograph.pdf}}{{cite journal| author=van der Kooy F, Sullivan SE| title=The complexity of medicinal plants: the traditional ''Artemisia annua'' formulation, current status and future perspectives. | journal=J Ethnopharmacol | year= 2013 | volume= 150 | issue= 1 | pages= 1–13 | pmid=23973523 | doi=10.1016/j.jep.2013.08.021 |type=Review }} Artemisinins, discovered by Chinese scientist [[Tu Youyou]] and colleagues in the 1970s from the plant ''Artemisia annua'', became the recommended treatment for ''P. falciparum'' malaria, administered in severe cases in combination with other antimalarials. Tu says she was influenced by a [[Chinese herbology|traditional Chinese herbal medicine]] source, ''The Handbook of Prescriptions for Emergency Treatments'', written in 340 by [[Ge Hong]].{{cite web | vauthors = Hao C |date=29 September 2011 |url=https://www.science.org/content/article/lasker-award-rekindles-debate-over-artemisinins-discovery |title=Lasker Award Rekindles Debate Over Artemisinin's Discovery |publisher=Science/AAAS |work=News: ScienceInsider |url-status=live |archive-url=https://web.archive.org/web/20140104214759/http://news.sciencemag.org/asia/2011/09/lasker-award-rekindles-debate-over-artemisinins-discovery |archive-date=4 January 2014 }} For her work on malaria, [[Tu Youyou]] received the 2015 [[Nobel Prize in Physiology or Medicine]].{{cite web |title = Nobel Prize announcement |url = https://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.pdf |website = NobelPrize.org |access-date = 5 October 2015 |url-status=live |archive-url = https://web.archive.org/web/20151006112430/http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.pdf |archive-date = 6 October 2015 }} [297] => [298] => ''Plasmodium vivax'' was used between 1917 and the 1940s for [[malariotherapy]]—deliberate injection of malaria parasites to induce a fever to combat certain diseases such as tertiary [[syphilis]]. In 1927, the inventor of this technique, [[Julius Wagner-Jauregg]], received the Nobel Prize in Physiology or Medicine for his discoveries. The technique was dangerous, killing about 15% of patients, so it is no longer in use. [299] => [300] => [[File:GuadMarinesMalaria.gif|thumb|U.S. Marines with malaria in a field hospital on [[Guadalcanal]], October 1942]] [301] => [302] => The first pesticide used for indoor residual spraying was [[DDT]]. Although it was initially used exclusively to combat malaria, its use quickly spread to [[agriculture]]. In time, pest control, rather than disease control, came to dominate DDT use, and this large-scale agricultural use led to the evolution of [[pesticide resistance|pesticide-resistant]] mosquitoes in many regions. The DDT resistance shown by ''Anopheles'' mosquitoes can be compared to [[antibiotic resistance]] shown by bacteria. During the 1960s, awareness of the negative consequences of its indiscriminate use increased, ultimately leading to bans on agricultural applications of DDT in many countries in the 1970s. Before DDT, malaria was successfully eliminated or controlled in tropical areas like Brazil and Egypt by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larval stages, for example by applying the highly toxic arsenic compound [[Paris Green]] to places with standing water. [303] => [304] => ===Names=== [305] => Various types of malaria have been called by the names below:{{Citation |title=Dorlands.com |website=dorlands.com |publisher=[[Elsevier]] |url=http://dorlands.com/ |postscript=. |access-date=2016-02-10 |archive-date=2014-01-11 |archive-url=https://web.archive.org/web/20140111192614/http://dorlands.com/ |url-status=dead }} [306] => [307] => {| class="wikitable sortable" border="1" [308] => ! Name !! Pathogen !! Notes [309] => |- [310] => | | algid malaria || ''[[Plasmodium falciparum]]'' || severe malaria affecting the [[cardiovascular system]] and causing [[chills]] and [[circulatory shock]] [311] => |- [312] => | bilious malaria || ''[[Plasmodium falciparum]]'' || severe malaria affecting the [[liver]] and causing [[vomiting]] and [[jaundice]] [313] => |- [314] => | cerebral malaria || ''[[Plasmodium falciparum]]'' || severe malaria affecting the [[cerebrum]] [315] => |- [316] => | congenital malaria || various [[Plasmodium|plasmodia]] || ''Plasmodium'' [[vertically transmitted infection|introduced from the mother]] via the [[fetal circulation]] [317] => |- [318] => | pernicious malaria || ''[[Plasmodium falciparum]]'' || severe malaria leading to grave illness [319] => |- [320] => | malignant malaria || ''[[Plasmodium falciparum]]'' || severe malaria leading to death [321] => |- [322] => | falciparum malaria, ''Plasmodium falciparum'' malaria, || ''[[Plasmodium falciparum]]'' || [323] => |- [324] => | ovale malaria, ''Plasmodium ovale'' malaria || ''[[Plasmodium ovale]]'' || [325] => |- [326] => | quartan malaria, malariae malaria, ''Plasmodium malariae'' malaria || ''[[Plasmodium malariae]]'' || paroxysms every fourth day ([[wikt:quartan#Adjective|quartan]]), counting the day of occurrence as the first day [327] => |- [328] => | quotidian malaria || ''[[Plasmodium falciparum]]'', ''[[Plasmodium vivax]]'', ''[[Plasmodium knowlesi]]'' || paroxysms daily ([[wikt:quotidian#Adjective|quotidian]]) [329] => |- [330] => | tertian malaria || ''[[Plasmodium falciparum]]'', ''[[Plasmodium ovale]]'', ''[[Plasmodium vivax]]'' || paroxysms every third day ([[wikt:tertian#Adjective|tertian]]), counting the day of occurrence as the first [331] => |- [332] => | transfusion malaria || various [[Plasmodium|plasmodia]] || ''Plasmodium'' introduced by [[blood transfusion]], [[needle sharing]], or [[needlestick injury]] [333] => |- [334] => | vivax malaria, ''Plasmodium vivax'' malaria || ''[[Plasmodium vivax]]'' || [335] => |- [336] => |} [337] => [338] => ==Eradication efforts== [339] => [[File:Members of the Malaria Commission on the Danube delta, 1929 Wellcome L0011626.jpg|thumb|Members of the Malaria Commission of the [[League of Nations]] collecting larvae on the [[Danube delta]], 1929]] [340] => [341] => Malaria has been successfully eliminated or significantly reduced in certain areas, but not globally. Malaria was once common in the United States, but the US eliminated malaria from most parts of the country in the early 20th century using vector control programs, which combined the monitoring and treatment of infected humans, draining of [[wetland]] breeding grounds for agriculture and other changes in [[water management]] practices, and advances in sanitation, including greater use of glass windows and screens in dwellings. The use of the [[pesticide]] DDT and other means eliminated malaria from the remaining pockets in southern states of the US the 1950s, as part of the [[National Malaria Eradication Program]]. Most of [[Europe]], [[North America]], [[Australia]], [[North Africa]] and the [[Caribbean]], and parts of [[South America]], [[Asia]] and [[Southern Africa]] have also eliminated malaria.{{cite web|title=Malaria Elimination Group description and list of elimination countries |access-date=2011-07-12 |url=http://www.malariaeliminationgroup.org/resources/elimination-countries |url-status=dead |archive-url=https://web.archive.org/web/20110727060254/http://www.malariaeliminationgroup.org/resources/elimination-countries |archive-date=27 July 2011 |df=dmy }} The WHO defines "elimination" (or "malaria-free") as having no domestic transmission (indigenous cases) for the past three years. They also define "pre-elimination" and "elimination" stages when a country has fewer than 5 or 1, respectively, cases per 1000 people at risk per year. In 2021, the total of international and national funding for malaria control and elimination was $3.5 billion – only half of what is estimated to be needed. According to UNICEF, to achieve the goal of a malaria-free world, annual funding would need to more than double to reach the US$6.8 billion target. [342] => [343] => In parts of the world with rising living standards, the elimination of malaria was often a collateral benefit of the introduction of window screens and improved sanitation. A variety of usually simultaneous interventions represents best practice. These include [[antimalarial drugs]] to prevent or treat infection; improvements in public health infrastructure to diagnose, sequester and treat infected individuals; [[mosquito net|bednets]] and other methods intended to keep mosquitoes from biting humans; and [[vector control]] strategies{{cite web | date = 2009 | publisher = World Health Organization | url = http://whqlibdoc.who.int/publications/2009/9789241563901_eng.pdf | title = World Malaria Report | access-date = December 17, 2009 | archive-date = January 12, 2010 | archive-url = https://web.archive.org/web/20100112144947/http://whqlibdoc.who.int/publications/2009/9789241563901_eng.pdf | url-status = live }} such as [[larvacide|larvaciding]] with insecticides, ecological controls such as draining mosquito breeding grounds or introducing fish to eat larvae and [[indoor residual spraying]] (IRS) with insecticides. [344] => [345] => ===Initial WHO program (1955–1969)=== [346] => [347] => [[File:L0074987 Malaria eradication - the world united against malaria (20675407876).jpg|thumb|right|1962 Pakistani postage stamp promoting malaria eradication program]] [348] => In 1955 the WHO launched the Global Malaria Eradication Program (GMEP).{{cite journal | vauthors = Duintjer Tebbens RJ, Thompson KM | title = Priority Shifting and the Dynamics of Managing Eradicable Infectious Diseases | journal = Management Science | volume = 55 | issue = 4 | pages = 650–663 | year = 2009 | doi = 10.1287/mnsc.1080.0965 }} The program relied largely on DDT for mosquito control and rapid diagnosis and treatment to break the transmission cycle.{{cite journal | vauthors = Mendis K, Rietveld A, Warsame M, Bosman A, Greenwood B, Wernsdorfer WH | title = From malaria control to eradication: The WHO perspective | journal = Tropical Medicine & International Health | volume = 14 | issue = 7 | pages = 802–809 | date = July 2009 | pmid = 19497083 | doi = 10.1111/j.1365-3156.2009.02287.x | s2cid = 31335358 | doi-access = free }} The program eliminated the disease in "North America, Europe, the former [[Soviet Union]]", and in "[[Taiwan]], much of the [[Caribbean]], the [[Balkans]], parts of northern Africa, the northern region of Australia, and a large swath of the South Pacific"{{cite news |last=Gladwell |first=Malcolm |author-link=Malcolm Gladwell |name-list-style=vanc |title=The Mosquito Killer |newspaper=The New Yorker |date=July 2, 2001 |url=http://gladwell.com/the-mosquito-killer/ |access-date=August 20, 2014 |archive-url=https://web.archive.org/web/20160416165010/http://gladwell.com/the-mosquito-killer/ |archive-date=April 16, 2016 |url-status=dead }} and dramatically reduced mortality in [[Sri Lanka]] and India. [349] => [350] => However, failure to sustain the program, increasing mosquito tolerance to DDT, and increasing parasite tolerance led to a resurgence. In many areas early successes partially or completely reversed, and in some cases rates of transmission increased.{{cite journal | vauthors = Chapin G, Wasserstrom R | title = Agricultural production and malaria resurgence in Central America and India | journal = Nature | volume = 293 | issue = 5829 | pages = 181–185 | year = 1981 | pmid = 7278974 | doi = 10.1038/293181a0 | bibcode = 1981Natur.293..181C | s2cid = 4346743 | doi-access = free }} Experts tie malarial resurgence to multiple factors, including poor leadership, management and funding of malaria control programs; poverty; civil unrest; and increased [[irrigation]]. The evolution of resistance to first-generation drugs (e.g. [[chloroquine]]) and to insecticides exacerbated the situation.{{cite web|url=http://www.pops.int/documents/ddt/Global%20status%20of%20DDT%20SSC%2020Oct08.pdf|title=Global status of DDT and its alternatives for use in vector control to prevent disease|last=van den Berg|first=Henk|name-list-style=vanc|date=October 23, 2008|publisher=[[Stockholm Convention on Persistent Organic Pollutants]]/[[United Nations Environment Programme]]|access-date=November 22, 2008|archive-url=https://web.archive.org/web/20101217022138/http://www.pops.int/documents/ddt/Global%20status%20of%20DDT%20SSC%2020Oct08.pdf|archive-date=December 17, 2010|url-status=dead|df=mdy-all}}{{cite journal | vauthors = Feachem RG, Sabot OJ | title = Global malaria control in the 21st century: a historic but fleeting opportunity | journal = JAMA | volume = 297 | issue = 20 | pages = 2281–2284 | date = May 2007 | pmid = 17519417 | doi = 10.1001/jama.297.20.2281 }} The program succeeded in eliminating malaria only in areas with "high socio-economic status, well-organized healthcare systems, and relatively less intensive or seasonal malaria transmission".{{cite journal | vauthors = Sadasivaiah S, Tozan Y, Breman JG | title = Dichlorodiphenyltrichloroethane (DDT) for indoor residual spraying in Africa: how can it be used for malaria control? | journal = The American Journal of Tropical Medicine and Hygiene | volume = 77 | issue = 6 Suppl | pages = 249–263 | date = December 2007 | pmid = 18165500 | doi = 10.4269/ajtmh.2007.77.249 | doi-access = free }} [351] => [352] => For example, in [[Sri Lanka]], the program reduced cases from about one million per year before spraying to just 18 in 1963{{cite book|title=The Coming Plague: Newly Emerging Diseases in a World Out of Balance|page=51|last=Garrett|first=Laurie|url=https://books.google.com/books?id=v9RY2PVOtOMC&pg=PA51|year=1994|publisher=Farrar, Straus and Giroux|isbn=978-1-4299-5327-6|access-date=August 29, 2022|archive-date=October 19, 2021|archive-url=https://web.archive.org/web/20211019223243/https://books.google.com/books?id=v9RY2PVOtOMC&pg=PA51|url-status=live}}{{cite news | url = https://www.nytimes.com/2010/12/28/health/28global.html | title = Malaria: A Disease Close to Eradication Grows, Aided by Political Tumult in Sri Lanka | first = Donald G. | last = McNeil | name-list-style = vanc | work = The New York Times | date = December 27, 2010 | access-date = February 7, 2017 | archive-date = January 4, 2017 | archive-url = https://web.archive.org/web/20170104050535/http://www.nytimes.com/2010/12/28/health/28global.html | url-status = live }} and 29 in 1964. Thereafter the program was halted to save money and malaria rebounded to 600,000 cases in 1968 and the first quarter of 1969. The country resumed DDT vector control but the mosquitoes had evolved resistance in the interim, presumably because of continued agricultural use. The program switched to [[malathion]], but despite initial successes, malaria continued its resurgence into the 1980s.{{cite book|name-list-style=vanc|title=Mosquitoes, Malaria, and Man: A History of the Hostilities Since 1880|isbn=978-0-525-16025-0|first=Gordon A.|last=Harrison|url=https://books.google.com/books?id=mfkBr2oskyEC|year=1978|publisher=Dutton|access-date=August 29, 2022|archive-date=October 19, 2021|archive-url=https://web.archive.org/web/20211019210418/https://books.google.com/books?id=mfkBr2oskyEC|url-status=live}}{{cite journal | vauthors = Karunaweera ND, Galappaththy GN, Wirth DF | title = On the road to eliminate malaria in Sri Lanka: lessons from history, challenges, gaps in knowledge and research needs | journal = Malaria Journal | volume = 13 | page = 59 | year = 2014 | pmid = 24548783 | pmc = 3943480 | doi = 10.1186/1475-2875-13-59 | doi-access = free }} [353] => [354] => Due to vector and parasite resistance and other factors, the [[Eradication of infectious diseases|feasibility of eradicating malaria]] with the strategy used at the time and resources available led to waning support for the program.{{cite journal | vauthors = Nájera JA, González-Silva M, Alonso PL | title = Some lessons for the future from the Global Malaria Eradication Programme (1955-1969) | journal = PLOS Medicine | volume = 8 | issue = 1 | pages = e1000412 | date = January 2011 | pmid = 21311585 | pmc = 3026700 | doi = 10.1371/journal.pmed.1000412 | doi-access = free }} WHO suspended the program in 1969 and attention instead focused on controlling and treating the disease. Spraying programs (especially using DDT) were curtailed due to concerns over safety and environmental effects, as well as problems in administrative, managerial and financial implementation. Efforts shifted from spraying to the use of [[Mosquito net|bednets]] impregnated with insecticides and other interventions.{{cite journal | vauthors = Rogan WJ, Chen A | title = Health risks and benefits of bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT) | journal = Lancet | volume = 366 | issue = 9487 | pages = 763–773 | year = 2005 | pmid = 16125595 | doi = 10.1016/S0140-6736(05)67182-6 | s2cid = 3762435 | url = https://zenodo.org/record/1259797 | access-date = June 13, 2019 | archive-date = October 17, 2019 | archive-url = https://web.archive.org/web/20191017205259/https://zenodo.org/record/1259797 | url-status = live }} [355] => [356] => ===Post-1969=== [357] => [358] => [[File:World-map-of-past-and-current-malaria-prevalence-world-development-report-2009.png|thumb|upright=1.3|right|Regions where malaria has been eliminated {{as of|2009|lc=y}}]] [359] => Target 6C of the [[Millennium Development Goals]] included reversal of the global increase in malaria incidence by 2015, with specific targets for children under five years old.{{cite journal | vauthors = Sato S |title=''Plasmodium''—a brief introduction to the parasites causing human malaria and their basic biology |journal=Menu Journal of Physiological Anthropology |date=29 January 2021 |volume=40 |issue=40 |page=1 |doi=10.1186/s40101-020-00251-9 |pmid=33413683 |pmc=7792015 |doi-access=free }} Since 2000, support for malaria eradication increased, although some actors in the global health community (including voices within the WHO) view malaria eradication as a premature goal and suggest that the establishment of strict deadlines for malaria eradication may be counterproductive as they are likely to be missed.{{Cite web|url=https://www.science.org/content/article/setting-deadline-eradicating-malaria-good-idea-scientists-are-divided|title=Is setting a deadline for eradicating malaria a good idea? Scientists are divided| vauthors = Enserink M |date=27 August 2019|website=Science|language=en|access-date=2019-09-30}} One of the targets of [[Sustainable Development Goal 3|Goal 3]] of the [[United Nations|UN]]'s [[Sustainable Development Goals]] is to end the malaria epidemic in all countries by 2030. [360] => [361] => In 2006, the organization [[Malaria No More]] set a public goal of eliminating malaria from Africa by 2015, and the organization claimed they planned to dissolve if that goal was accomplished. In 2007, [[World Malaria Day]] was established by the 60th session of [[World Health Assembly|the World Health Assembly]]. As of 2018, they are still functioning. [362] => [[File:Malaria Eradication- Back to the Future.webm|thumb|Video recording of a set of presentations given in 2010 about humanity's efforts towards malaria eradication]] [363] => [364] => {{As of|2012}}, [[The Global Fund to Fight AIDS, Tuberculosis and Malaria|The Global Fund to Fight AIDS, Tuberculosis, and Malaria]] has distributed 230 million insecticide-treated nets intended to stop mosquito-borne transmission of malaria. The U.S.-based [[Clinton Foundation]] has worked to manage demand and stabilize prices in the artemisinin market. Other efforts, such as the Malaria Atlas Project, focus on analysing climate and weather information required to accurately predict malaria spread based on the availability of habitat of malaria-carrying parasites. The [[Malaria Policy Advisory Committee]] (MPAC) of the [[World Health Organization]] (WHO) was formed in 2012, "to provide strategic advice and technical input to WHO on all aspects of malaria control and elimination".{{cite web|title=Executive summary and key points|url=https://www.who.int/entity/malaria/publications/world_malaria_report_2013/wmr13_summary_key_points.pdf?ua=1|work=World Malaria Report 2013|publisher=World Health Organization|access-date=13 February 2014|url-status=live|archive-url=https://web.archive.org/web/20160304091723/http://www.who.int/entity/malaria/publications/world_malaria_report_2013/wmr13_summary_key_points.pdf?ua=1|archive-date=4 March 2016}} [365] => [366] => In 2015 the WHO targeted a 90% reduction in malaria deaths by 2030, and [[Bill Gates]] said in 2016 that he thought global eradication would be possible by 2040.{{cite web |url=http://www.cfr.org/public-health-threats-and-pandemics/can-malaria-eradicated/p38243 |title=Can Malaria Be Eradicated? | vauthors = Radwick D |date=October 5, 2016 |publisher=[[Council on Foreign Relations]] |url-status=live |archive-url=https://web.archive.org/web/20161005201520/http://www.cfr.org/public-health-threats-and-pandemics/can-malaria-eradicated/p38243 |archive-date=October 5, 2016 }} According to the WHO's World Malaria Report 2015, the global mortality rate for malaria fell by 60% between 2000 and 2015. The WHO targeted a further 90% reduction between 2015 and 2030,{{cite web |url=https://www.who.int/malaria/media/world-malaria-report-2015/en/ |archive-url=https://web.archive.org/web/20151217125416/http://www.who.int/malaria/media/world-malaria-report-2015/en/ |url-status=dead |archive-date=December 17, 2015 |title=Fact Sheet: World Malaria Report 2015 |date=9 December 2015}} with a 40% reduction and eradication in 10 countries by 2020.{{Cite web|url=https://apps.who.int/iris/rest/bitstreams/1275142/retrieve|title=Malaria eradication: benefits, future scenarios & feasibility}} However, the 2020 goal was missed with a slight increase in cases compared to 2015.{{Cite web|url=https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2020|title=World Malaria Report 2020|website=www.who.int}} Additionally, UNICEF reported that the number of malaria deaths for all ages increased by 10% between 2019 and 2020, in part due to service disruptions related to the COVID-19 pandemic, before experiencing a minor decline in 2021. [367] => [368] => Before 2016, the Global Fund against HIV/AIDS, Tuberculosis and Malaria had provided 659 million ITN (insecticide treated bed nets), organise support and education to prevents malaria. The challenges are high due to the lack of funds, the fragile health structure and the remote indigenous population that could be hard to reach and educate. Most of indigenous population rely on self-diagnosis, self-treatment, healer, and traditional medicine. The WHO applied for fund to the Gates Foundation which favour the action of malaria eradication in 2007.{{cite journal | vauthors = Chandler CI, Beisel U | title = The Anthropology of Malaria: Locating the Social | journal = Medical Anthropology | volume = 36 | issue = 5 | pages = 411–421 | date = July 2017 | pmid = 28318308 | doi = 10.1080/01459740.2017.1306858 | s2cid = 34612426 | url = https://researchonline.lshtm.ac.uk/id/eprint/4328570/1/The%20Anthropology%20of%20Malaria_GREEN%20AAM.pdf }} Six countries, the United Arab Emirates, Morocco, Armenia, Turkmenistan, Kyrgyzstan, and Sri Lanka managed to have no endemic cases of malaria for three consecutive years and certified malaria-free by the WHO despite the stagnation of the funding in 2010. The funding is essential to finance the cost of medication and hospitalisation cannot be supported by the poor countries where the disease is widely spread. The goal of eradication has not been met; nevertheless, the decrease rate of the disease is considerable. [369] => [370] => While 31 out of 92 endemic countries were estimated to be on track with the WHO goals for 2020, 15 countries reported an increase of 40% or more between 2015 and 2020. Between 2000 and 30 June 2021, twelve countries were certified by the WHO as being malaria-free. Argentina and Algeria were declared free of malaria in 2019.{{Cite web|url=https://www.who.int/news/item/22-05-2019-algeria-and-argentina-certified-malaria-free-by-who|title=Algeria and Argentina certified malaria-free by WHO|website=www.who.int}} El Salvador and China were declared malaria-free in the first half of 2021.{{cite Q|Q108595589}}{{cite Q|Q108595181}}. [371] => [372] => Regional disparities were evident: [[Southeast Asia]] was on track to meet WHO's 2020 goals, while Africa, Americas, Eastern Mediterranean and West Pacific regions were off-track. The six [[Greater Mekong Subregion]] countries aim for elimination of [[Plasmodium falciparum|''P. falciparum'']] transmitted malaria by 2025 and elimination of all malaria by 2030, having achieved a 97% and 90% reduction of cases respectively since 2000. Ahead of [[World Malaria Day]], 25 April 2021, WHO named 25 countries in which it is working to eliminate malaria by 2025 as part of its E-2025 initiative.{{cite Q|Q108595714}} [373] => [374] => A major challenge to malaria elimination is the persistence of malaria in border regions, making international cooperation crucial.{{Cite web|url=http://www.bbc.com/future/story/20190925-the-race-to-stamp-out-malaria-along-the-bhutan-india-border|title=The tiny kingdom fighting an epidemic| vauthors = Ro C |date=26 September 2019|website=BBC Future|language=en|access-date=2019-09-30}} [375] => [376] => In 2018, WHO announced that Paraguay was free of malaria, after a national malaria eradication effort that began in 1950.{{cite web|url=https://www.who.int/news-room/detail/11-06-2018-who-certifies-paraguay-malaria-free|title=WHO certifies Paraguay malaria-free|date=11 June 2018|publisher=[[World Health Organization]]|access-date=17 June 2018}} [377] => [378] => As of 2019, the eradication process is ongoing, but it will be difficult to achieve a world free of malaria with the current approaches and tools. [379] => [380] => In March 2023, the WHO certified Azerbaijan and Tajikistan as malaria-free,{{Cite web |url=https://www.who.int/news/item/29-03-2023-who-certifies-azerbaijan-and-tajikistan-as-malaria-free/ |title=WHO certifies Azerbaijan and Tajikistan as malaria-free |date=2023-03-29 |accessdate=2023-06-22 |publisher=[[World Health Organization]]}} and Belize in June 2023.{{Cite web |url=https://www.who.int/news/item/21-06-2023-belize-certified-malaria-free-by-who |title=Belize certified malaria-free by WHO |date=2023-06-21 |accessdate=2023-06-22 |publisher=[[World Health Organization]]}} Cabo Verde, the latest country to eradicate Malaria, was certified in January 2024, bringing the total number of countries and territories certified malaria-free to 44.{{Cite web |url=https://www.who.int/news/item/12-01-2024-who-certifies-cabo-verde-as-malaria-free--marking-a-historic-milestone-in-the-fight-against-malaria|title=Who declares Cape Verde free of malaria |date=2024-01-12 |accessdate=2024-01-13 |publisher=[[World Health Organization]]}} [381] => [382] => ==Society and culture== [383] => {{see also|World Malaria Day}} [384] => [385] => === Economic impact === [386] => [[File:Saving Lives with SMS for Life.jpg|thumb|right|Malaria clinic in Tanzania]] [387] => [388] => Malaria is not just a disease commonly associated with [[poverty]]: some evidence suggests that it is also a cause of poverty and a major hindrance to [[economic development]]. Although [[Tropics|tropical regions]] are most affected, malaria's furthest influence reaches into some temperate zones that have extreme seasonal changes. The disease has been associated with major negative economic effects on regions where it is widespread. During the late 19th and early 20th centuries, it was a major factor in the slow economic development of the American southern states. [389] => [390] => A comparison of average per capita [[GDP]] in 1995, adjusted for [[purchasing power parity|parity of purchasing power]], between countries with malaria and countries without malaria gives a fivefold difference (US$1,526 versus US$8,268). In the period 1965 to 1990, countries where malaria was common had an average per capita GDP that increased only 0.4% per year, compared to 2.4% per year in other countries. [391] => [392] => Poverty can increase the risk of malaria since those in poverty do not have the financial capacities to prevent or treat the disease. In its entirety, the economic impact of malaria has been estimated to cost Africa US$12 billion every year. The economic impact includes costs of health care, working days lost due to sickness, days lost in education, decreased productivity due to brain damage from cerebral malaria, and loss of investment and tourism. The disease has a heavy burden in some countries, where it may be responsible for 30–50% of hospital admissions, up to 50% of [[outpatient]] visits, and up to 40% of public health spending. [393] => [394] => [[File:Malaria Patient, Nyangaton, Ethiopia (15151075077).jpg|thumb|Child with malaria in [[Ethiopia]]]] [395] => Cerebral malaria is one of the leading causes of neurological disabilities in African children. Studies comparing cognitive functions before and after treatment for severe malarial illness continued to show significantly impaired school performance and cognitive abilities even after recovery. Consequently, severe and cerebral malaria have far-reaching [[socioeconomic]] consequences that extend beyond the immediate effects of the disease. [396] => [397] => ===Counterfeit and substandard drugs=== [398] => Sophisticated [[counterfeit drugs|counterfeits]] have been found in several Asian countries such as [[Cambodia]], [[China]], [[Indonesia]], [[Laos]], [[Thailand]], and [[Vietnam]], and are a major cause of avoidable death in those countries. The WHO said that studies indicate that up to 40% of artesunate-based malaria medications are counterfeit, especially in the Greater [[Mekong]] region. They have established a rapid alert system to rapidly report information about counterfeit drugs to relevant authorities in participating countries. There is no reliable way for doctors or lay people to detect counterfeit drugs without help from a laboratory. Companies are attempting to combat the persistence of counterfeit drugs by using new technology to provide security from source to distribution. [399] => [400] => Another clinical and public health concern is the proliferation of substandard antimalarial medicines resulting from inappropriate concentration of ingredients, contamination with other drugs or toxic impurities, poor quality ingredients, poor stability and inadequate packaging. A 2012 study demonstrated that roughly one-third of antimalarial medications in Southeast Asia and Sub-Saharan Africa failed chemical analysis, packaging analysis, or were falsified. [401] => [402] => ===War=== [403] => [[File:"Don't go to Bed with Malaria Mosquito" - NARA - 514146.tif|thumb|right|World War II poster]] [404] => Throughout history, the contraction of malaria has played a prominent role in the fates of government rulers, nation-states, military personnel, and military actions. In 1910, [[Nobel Prize in Medicine]]-winner Ronald Ross (himself a malaria survivor), published a book titled ''The Prevention of Malaria'' that included a chapter titled "The Prevention of Malaria in War". The chapter's author, Colonel C. H. Melville, Professor of Hygiene at [[Royal Army Medical College]] in London, addressed the prominent role that malaria has historically played during wars: "The history of malaria in war might almost be taken to be the history of war itself, certainly the history of war in the Christian era. ... It is probably the case that many of the so-called camp fevers, and probably also a considerable proportion of the camp dysentery, of the wars of the sixteenth, seventeenth and eighteenth centuries were malarial in origin." In British-occupied India the cocktail [[Gin and tonic#History|gin and tonic]] may have come about as a way of taking quinine, known for its antimalarial properties.{{cite book | vauthors = Bryant BJ, Knights KM |title=Pharmacology for Health Professionals |date=2011 |publisher=Elsevier Australia |isbn=9780729539296 |page=895 |url=https://books.google.com/books?id=TQV6sLzYsOYC&pg=PA895 |language=en}} [405] => [406] => Malaria was the most significant health hazard encountered by U.S. troops in the South Pacific during [[World War II]], where about 500,000 men were infected. According to Joseph Patrick Byrne, "Sixty thousand American soldiers died of malaria during the African and South Pacific campaigns." [407] => [408] => Significant financial investments have been made to procure existing and create new antimalarial agents. During [[World War I]] and World War II, inconsistent supplies of the natural antimalaria drugs [[cinchona bark]] and quinine prompted substantial funding into [[research and development]] of other drugs and vaccines. American military organisations conducting such research initiatives include the Navy Medical Research Center, [[Walter Reed Army Institute of Research]], and the [[U.S. Army Medical Research Institute of Infectious Diseases]] of the US Armed Forces. [409] => [410] => Additionally, initiatives have been founded such as Malaria Control in War Areas (MCWA), established in 1942, and its successor, the Communicable Disease Center (now known as the [[Centers for Disease Control and Prevention]], or CDC) established in 1946. According to the CDC, MCWA "was established to control malaria around military training bases in the southern United States and its territories, where malaria was still problematic". [411] => [412] => ==Research== [413] => The Malaria Eradication Research Agenda (malERA) initiative was a consultative process to identify which areas of research and development (R&D) must be addressed for worldwide eradication of malaria.{{cite journal | vauthors = Hall BF, Fauci AS | title = Malaria control, elimination, and eradication: the role of the evolving biomedical research agenda | journal = The Journal of Infectious Diseases | volume = 200 | issue = 11 | pages = 1639–43 | date = December 2009 | pmid = 19877843 | doi = 10.1086/646611 | doi-access = free }}{{Cite web|url=https://www.who.int/dg/speeches/2010/malaria_20100326/en/|title=WHO {{!}} A research agenda for malaria eradication|website=www.who.int|access-date=2016-03-07|url-status=dead|archive-url=https://web.archive.org/web/20160307182232/http://www.who.int/dg/speeches/2010/malaria_20100326/en/|archive-date=2016-03-07}} [414] => [415] => ===Medications=== [416] => Malaria parasites contain [[apicoplast]]s, organelles related to the [[plastid]]s found in plants, complete with their own [[genome]]s. These apicoplasts are thought to have originated through the [[Endosymbiont|endosymbiosis]] of algae and play a crucial role in various aspects of parasite [[metabolism]], such as [[fatty acid biosynthesis]]. Over 400 proteins have been found to be produced by apicoplasts and these are now being investigated as possible targets for novel antimalarial drugs. [417] => [418] => With the onset of drug-resistant ''Plasmodium'' parasites, new strategies are being developed to combat the widespread disease. One such approach lies in the introduction of synthetic [[pyridoxal]]-amino acid [[adduct]]s, which are taken up by the parasite and ultimately interfere with its ability to create several essential [[B vitamin]]s. Antimalarial drugs using [[Organometallic chemistry|synthetic metal-based]] [[coordination complex|complexes]] are attracting research interest. [419] => * (+)-SJ733: Part of a wider class of experimental drugs called [[spiroindolone]]. It inhibits the ATP4 protein of infected red blood cells that cause the cells to shrink and become rigid like the aging cells. This triggers the immune system to eliminate the infected cells from the system as demonstrated in a mouse model. As of 2014, a [[Phases of clinical research#Phase 1|Phase 1 clinical trial]] to assess the safety profile in human is planned by the [[Howard Hughes Medical Institute]].{{cite web|url=http://www.fiercebiotechresearch.com/story/new-malaria-drug-unleashes-immune-system-assault-infected-cells/2014-12-08|title=New malaria drug unleashes an immune system assault on infected cells | vauthors = John C |publisher=fiercebiotechresearch.com|date=8 December 2014|access-date=16 December 2014|url-status=live|archive-url=https://web.archive.org/web/20160404040409/http://www.fiercebiotechresearch.com/story/new-malaria-drug-unleashes-immune-system-assault-infected-cells/2014-12-08|archive-date=4 April 2016}} [420] => * NITD246 and [[NITD609]]: Also belonged to the class of spiroindolone and target the ATP4 protein. [421] => [422] => On the basis of molecular docking outcomes, compounds 3j, 4b, 4h, 4m were exhibited selectivity towards PfLDH. The post docking analysis displayed stable dynamic behavior of all the selected compounds compared to Chloroquine. The end state thermodynamics analysis stated 3j compound as a selective and potent PfLDH inhibitor.{{cite journal | vauthors = Singh R, Bhardwaj VK, Purohit R | title = Identification of a novel binding mechanism of Quinoline based molecules with lactate dehydrogenase of ''Plasmodium falciparum'' | journal = Journal of Biomolecular Structure and Dynamics | volume = 39 | issue = 1 |date= January 2020 | pages = 348–356 | pmid = 31903852 | doi = 10.1080/07391102.2020.1711809 | s2cid = 209894772 | url = https://www.beilstein-archives.org/xiv/download/pdf/2019153-pdf }} [423] => [424] => ===New targets=== [425] => Targeting ''Plasmodium'' liver-stage parasites selectively is emerging as an alternative strategy in the face of resistance to the latest frontline combination therapies against blood stages of the parasite.{{cite journal | vauthors = Stanway RR, Bushell E, Chiappino-Pepe A, Roques M, Sanderson T, Franke-Fayard B, Caldelari R, Golomingi M, Nyonda M | title = Genome-Scale Identification of Essential Metabolic Processes for Targeting the ''Plasmodium'' Liver Stage | journal = Cell | volume = 179 | issue = 5 | pages = 1112–1128 | date = November 2019 | doi = 10.1016/j.cell.2019.10.030 | pmid = 31730853 | pmc = 6904910 | doi-access = free }} [426] => [427] => In research conducted in 2019, using experimental analysis with knockout (KO) mutants of ''Plasmodium berghei'', the authors were able to identify genes that are potentially essential in the liver stage. Moreover, they generated a computational model to analyse pre–erytrocytic development and liver–stage metabolism. Combining both methods they identified seven metabolic subsystems that become essential compared to the blood stage. Some of these metabolic pathways are fatty acid synthesis and elongation, tricarboxylic acid, amino acid and heme metabolism among others. [428] => [429] => Specifically, they studied 3 subsystems: fatty acid synthesis and elongation, and amino sugar biosynthesis. For the first two pathways they demonstrated a clear dependence of the liver stage on its own fatty acid metabolism. [430] => [431] => They proved for the first time the critical role of amino sugar biosynthesis in the liver stage of ''P. berghei''. The uptake of N–acetyl–glucosamine appears to be limited in the liver stage, being its synthesis needed for the parasite development. [432] => [433] => These findings and the computational model provide a basis for the design of antimalarial therapies targeting metabolic proteins.{{cite journal | vauthors = Roy M, Rawat A, Kaushik S, Jyoti A, Srivastava VK | title = Endogenous cysteine protease inhibitors in upmost pathogenic parasitic protozoa | journal = Microbiological Research | volume = 261 | pages = 127061 | date = August 2022 | pmid = 35605309 | doi = 10.1016/j.micres.2022.127061 | s2cid = 248741177 | doi-access = free }} [434] => [435] => ===Other=== [436] => A non-chemical vector control strategy involves genetic manipulation of malaria mosquitoes. Advances in [[genetic engineering]] technologies make it possible to introduce foreign DNA into the mosquito genome and either decrease the lifespan of the mosquito, or make it more resistant to the malaria parasite. [[Sterile insect technique]] is a genetic control method whereby large numbers of sterile male mosquitoes are reared and released. Mating with wild females reduces the wild population in the subsequent generation; repeated releases eventually eliminate the target population. [437] => [438] => [[Genomics]] is central to malaria research. With the [[whole genome sequencing|sequencing]] of ''P. falciparum'', one of its vectors ''Anopheles gambiae'', and the [[human genome]], the genetics of all three organisms in the malaria life cycle can be studied. Another new application of genetic technology is the ability to produce [[Genetically modified organism|genetically modified]] mosquitoes that do not transmit malaria, potentially allowing [[biological control]] of malaria transmission. [439] => [440] => In one study, a genetically modified strain of ''[[Anopheles stephensi]]'' was created that no longer supported malaria transmission, and this resistance was passed down to mosquito offspring.{{cite journal | vauthors = Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM, Bier E, James AA | title = Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 49 | pages = E6736-43 | date = December 2015 | pmid = 26598698 | pmc = 4679060 | doi = 10.1073/pnas.1521077112 | bibcode = 2015PNAS..112E6736G | doi-access = free }} [441] => [442] => [[Gene drive]] is a technique for changing wild populations, for instance to combat or eliminate insects so they cannot transmit diseases (in particular mosquitoes in the cases of malaria,{{cite news |url=https://www.imperial.ac.uk/news/227193/malarial-mosquitoes-suppressed-experiments-that-mimic/ |title=Malarial mosquitoes suppressed in experiments that mimic natural environments |date=28 July 2021 |access-date=21 November 2021}} [[Zika virus|zika]],{{cite news | url=https://www.bloomberg.com/view/articles/2016-02-04/fighting-zika-virus-with-genetic-engineering | title=Fighting Zika Virus With Genetic Engineering | work=Bloomberg | date=4 February 2016 | vauthors = Flam F | url-status=live | archive-url=https://web.archive.org/web/20160606220755/http://www.bloomberg.com/view/articles/2016-02-04/fighting-zika-virus-with-genetic-engineering | archive-date=6 June 2016 }} dengue and yellow fever).{{Cite news|url=https://www.telegraph.co.uk/news/0/mutant-mosquitoes-can-gene-editing-kill-malaria/ |archive-url=https://ghostarchive.org/archive/20220111/https://www.telegraph.co.uk/news/0/mutant-mosquitoes-can-gene-editing-kill-malaria/ |archive-date=2022-01-11 |url-access=subscription |url-status=live|title=Mutant mosquitoes: Can gene editing kill off malaria?| vauthors = Fletcher M |date=2018-08-11|work=The Telegraph|access-date=2018-08-12|issn=0307-1235}}{{cbignore}} [443] => [444] => In a study conducted in 2015, researchers observed a specific interaction between malaria and co-infection with the [[nematode]] Nippostrongylus brasiliensis, a pulmonary migrating [[Parasitic worm|helminth]], in mice.{{cite journal |vauthors=Griffiths EC, Fairlie-Clarke K, Allen JE, Metcalf CJ, Graham AL |date=December 2015 | veditors = Ostfeld R |title=Bottom-up regulation of malaria population dynamics in mice co-infected with lung-migratory nematodes |url=https://eprints.gla.ac.uk/113103/7/113103.pdf |journal=Ecology Letters |volume=18 |issue=12 |pages=1387–1396 |doi=10.1111/ele.12534 |pmid=26477454}} The co-infection was found to reduce the [[virulence]] of the ''Plasmodium'' parasite, the causative agent of malaria. This reduction was attributed to the nematode infection causing increased destruction of [[erythrocytes]], or red blood cells. Given that ''Plasmodium'' has a predilection for older host erythrocytes, the increased erythrocyte destruction and ensuing [[erythropoiesis]] result in a predominantly younger erythrocyte population, which in turn leads to a decrease in ''Plasmodium'' population. Notably, this effect appears to be largely independent of the host's immune control of ''Plasmodium''. [445] => [446] => Finally, a review article published in December 2020 noted a correlation between malaria-endemic regions and [[COVID-19]] case fatality rates.{{cite journal |vauthors=Arshad AR, Bashir I, Ijaz F, Loh N, Shukla S, Rehman UU, Aftab RK |date=December 2020 |title=Is COVID-19 Fatality Rate Associated with Malaria Endemicity? |journal=Discoveries |volume=8 |issue=4 |pages=e120 |doi=10.15190/d.2020.17 |pmc=7749783 |pmid=33365386 |doi-access=free}} The study found that, on average, regions where malaria is endemic reported lower COVID-19 case fatality rates compared to regions without endemic malaria. [447] => [448] => In 2017, a bacterial strain of the genus [[Serratia]] was genetically modified to prevent malaria in mosquitos{{Cite journal |last1=Wang |first1=Sibao |last2=Dos-Santos |first2=André L. A. |last3=Huang |first3=Wei |last4=Liu |first4=Kun Connie |last5=Oshaghi |first5=Mohammad Ali |last6=Wei |first6=Ge |last7=Agre |first7=Peter |last8=Jacobs-Lorena |first8=Marcelo |date=2017-09-29 |title=Driving mosquito refractoriness to ''Plasmodium falciparum'' with engineered symbiotic bacteria |journal=Science |language=en |volume=357 |issue=6358 |pages=1399–1402 |doi=10.1126/science.aan5478 |issn=0036-8075 |pmc=9793889 |pmid=28963255|bibcode=2017Sci...357.1399W }}{{Cite journal |last=Servick |first=Kelly |date=2017-09-28 |title=The microbes in a mosquito's gut may help fight malaria |url=http://www.sciencemag.org/news/2017/09/microbes-mosquito-s-gut-may-help-fight-malaria |journal=Science |doi=10.1126/science.aaq0811 |issn=0036-8075}} and in 2023, it has been reported that the bacterium [[Delftia tsuruhatensis]] naturally prevents the development of malaria by secreting a molecule called [[Harmane]].{{Cite journal |last1=Huang |first1=Wei |last2=Rodrigues |first2=Janneth |last3=Bilgo |first3=Etienne |last4=Tormo |first4=José R. |last5=Challenger |first5=Joseph D. |last6=De Cozar-Gallardo |first6=Cristina |last7=Pérez-Victoria |first7=Ignacio |last8=Reyes |first8=Fernando |last9=Castañeda-Casado |first9=Pablo |last10=Gnambani |first10=Edounou Jacques |last11=Hien |first11=Domonbabele François de Sales |last12=Konkobo |first12=Maurice |last13=Urones |first13=Beatriz |last14=Coppens |first14=Isabelle |last15=Mendoza-Losana |first15=Alfonso |date=2023-08-04 |title=Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes |url=https://www.science.org/doi/10.1126/science.adf8141 |journal=Science |language=en |volume=381 |issue=6657 |pages=533–540 |doi=10.1126/science.adf8141 |pmid=37535741 |bibcode=2023Sci...381..533H |hdl=10044/1/105278 |s2cid=260440907 |issn=0036-8075|hdl-access=free }}{{Cite news |last=Offord |first=Catherine |date=3 August 2023 |title=Microbe stops mosquitoes from harboring malaria parasite |work=[[Science (journal)|Science]] |url=https://www.science.org/content/article/microbe-stops-mosquitoes-harboring-malaria-parasite}}{{Cite news |date=2023-08-04 |title=Chance discovery helps fight against malaria |language=en-GB |work=BBC News |url=https://www.bbc.com/news/health-66394117 |access-date=2023-08-04}} [449] => [450] => ==Other animals== [451] => While none of the main four species of malaria parasite that cause human infections are known to have [[zoonosis|animal reservoirs]],{{cite web |title=Facts about malaria |url=https://www.ecdc.europa.eu/en/malaria/facts |website=European Centre for Disease Prevention and Control |date=9 June 2017 |access-date=16 July 2021 |language=en}} ''[[Plasmodium knowlesi|P. knowlesi]]'' is known to regularly infect both humans and non-human primates. Other non-human primate malarias (particularly ''P. cynomolgi'' and ''P. simium'') have also been found to have spilled over into humans.{{cite journal | vauthors = Brasil P, Zalis MG, de Pina-Costa A, Siqueira AM, Júnior CB, Silva S, Areas AL, Pelajo-Machado M, de Alvarenga DA, da Silva Santelli AC, Albuquerque HG, Cravo P, Santos de Abreu FV, Peterka CL, Zanini GM, Suárez Mutis MC, Pissinatti A, Lourenço-de-Oliveira R, de Brito CF, de Fátima Ferreira-da-Cruz M, Culleton R, Daniel-Ribeiro CT | display-authors = 6 | title = Outbreak of human malaria caused by ''Plasmodium simium'' in the Atlantic Forest in Rio de Janeiro: a molecular epidemiological investigation | journal = The Lancet. Global Health | volume = 5 | issue = 10 | pages = e1038–e1046 | date = October 2017 | pmid = 28867401 | doi = 10.1016/S2214-109X(17)30333-9 | doi-access = free }} Nearly 200 ''Plasmodium'' species have been identified that infect [[Plasmodium species infecting birds|birds]], [[Plasmodium species infecting reptiles|reptiles]], and [[Plasmodium species infecting mammals other than primates|other mammals]], and about 30 of them naturally infect non-human primates. Some malaria parasites of non-human primates (NHP) serve as [[model organism]]s for human malarial parasites, such as ''[[Plasmodium coatneyi|P. coatneyi]]'' (a model for ''P. falciparum'') and ''[[Plasmodium cynomolgi|P. cynomolgi]]'' (a model for ''P. vivax''). Diagnostic techniques used to detect parasites in NHP are similar to those employed for humans. Malaria parasites that infect rodents are widely used as models in research, such as ''[[Plasmodium berghei|P. berghei]]''. [[Avian malaria]] primarily affects species of the order [[Passeriformes]], and poses a substantial threat to birds of [[Hawaii]], the [[Galapagos]], and other [[archipelago]]es. The parasite ''[[Plasmodium relictum|P. relictum]]'' is known to play a role in limiting the distribution and abundance of [[endemic birds of Hawaii|endemic Hawaiian birds]]. [[Global warming]] is expected to increase the prevalence and global distribution of [[avian malaria]], as elevated temperatures provide optimal conditions for parasite reproduction. 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A review of the literature |journal = Tropical Medicine & International Health |year=2005 |volume=10 |issue=10 |pages=1047–59 |doi=10.1111/j.1365-3156.2005.01476.x |pmid=16185240 |doi-access=free }} [751] => [752] => {{cite news |vauthors = Schoofs M |title = Clinton foundation sets up malaria-drug price plan |url = https://www.wsj.com/articles/SB121626447476161201 |date=July 17, 2008 |newspaper=Wall Street Journal |access-date=2012-05-14 |url-status=live |archive-url = https://web.archive.org/web/20160119132836/http://www.wsj.com/articles/SB121626447476161201 |archive-date=January 19, 2016 }} [753] => }} [754] => [755] => === Sources === [756] => {{refbegin}} [757] => * {{cite report |author=WHO |title = Guidelines for the Treatment of Malaria |edition=2nd |year=2010 |publisher=World Health Organization |isbn=978-92-4-154792-5 |url = http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf |archive-url = https://web.archive.org/web/20100311024041/http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf |url-status = dead |archive-date = March 11, 2010 }} [758] => * {{cite book |vauthors=Schlagenhauf-Lawlor P |title = Travelers' Malaria |year=2008 |publisher=PMPH-USA |isbn=978-1-55009-336-0 |url = https://books.google.com/books?id=54Dza0UHyngC }} [759] => {{refend}} [760] => [761] => ==Further reading== [762] => {{refbegin}} [763] => * {{Cite book | veditors = Bynum WF, Overy C | editor-link1 = W. F. Bynum |title=The Beast in the Mosquito: The Correspondence of Ronald Ross and Patrick Manson |url=https://books.google.com/books?id=5BXbsSJLaToC |year=1998 |publisher=Rodopi |isbn=978-90-420-0721-5 |series=Wellcome Institute Series in The History of Medicine}} [764] => * {{cite book|title=Guidelines for the treatment of malaria|date=2015|publisher=World Health Organization|isbn=978-92-4-154912-7|edition=3rd |url=https://www.who.int/malaria/publications/atoz/9789241549127/en/|archive-url=https://web.archive.org/web/20150425070556/http://www.who.int/malaria/publications/atoz/9789241549127/en/|url-status=dead|archive-date=April 25, 2015}} [765] => * {{cite magazine | vauthors = Jarvis B |title=How Mosquitoes Changed Everything |magazine=[[The New Yorker]] |url=https://www.newyorker.com/magazine/2019/08/05/how-mosquitoes-changed-everything |access-date=8 August 2019 |language=en |date=29 July 2019}} [766] => *{{Cite journal | date=28 March 2019|title=Tightening the handle on malaria|journal=Nature Methods|type=Editorial|volume=16|issue=4|pages=271|doi=10.1038/s41592-019-0390-2|pmid=30923375|quote=A day dedicated to raising awareness of the disease is a good opportunity to ask how far malaria research has come and which methods are needed for further breakthroughs.|doi-access=free}} [767] => {{refend}} [768] => [769] => ==External links== [770] => {{Sister project links |wikt=malaria |commons=Category:Malaria |n=Malaria |q=Malaria |s=Malaria |b=Malaria |voy=Malaria |v=Malaria}} [771] => {{offline|med}} [772] => * [https://www.who.int/news-room/fact-sheets/detail/malaria WHO site on malaria] [773] => * [https://www.cdc.gov/parasites/malaria/index.html CDC site on malaria] [774] => * [https://www.paho.org/en/topics/malaria PAHO site on malaria] [775] => [776] => {{Medical condition classification and resources [777] => | ICD11 = {{ICD11|1F40}}–{{ICD11|1F45}} [778] => | ICD10 = {{ICD10|B50}}–{{ICD10|B54}} [779] => | ICD9 = {{ICD9|084}} [780] => | DiseasesDB = 7728 [781] => | MedlinePlus = 000621 [782] => | OMIM = 248310 [783] => | eMedicineSubj = med [784] => | eMedicineTopic = 1385 [785] => | eMedicine_mult = {{eMedicine2|emerg|305}} {{eMedicine2|ped|1357}} [786] => | MeshName = Malaria [787] => | MeshNumber = C03.752.250.552 [788] => | Orphanet = 673 [789] => | Scholia = Q12156 [790] => }} [791] => {{portal bar |Medicine}} [792] => {{malaria}} [793] => {{Chromalveolate diseases}} [794] => {{Diseases of Poverty}} [795] => {{Eradication of infectious disease}} [796] => {{Effective altruism}} [797] => [798] => {{Authority control}} [799] => {{good article}} [800] => [801] => [[Category:Malaria| ]] [802] => [[Category:Plasmodium|*Malaria]] [803] => [[Category:Insect-borne diseases]] [804] => [[Category:Infectious diseases with eradication efforts]] [805] => [[Category:Protozoal diseases]] [806] => [[Category:Tropical diseases]] [807] => [[Category:Vaccine-preventable diseases]] [808] => [[Category:Articles containing video clips]] [] => )
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Malaria

Malaria is a mosquito-borne infectious disease that is caused by single-celled parasites of the Plasmodium group. The disease is prevalent in tropical and subtropical regions, mostly in Africa, Asia, and Latin America.

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The disease is prevalent in tropical and subtropical regions, mostly in Africa, Asia, and Latin America. Transmitted through the bite of infected Anopheles mosquitoes, malaria is characterized by symptoms like fever, fatigue, vomiting, and headaches. If not treated promptly, it can lead to severe complications and even death. This Wikipedia page on malaria provides comprehensive information about the disease, including its history, causes, transmission, symptoms, prevention, and treatment. It highlights the impact of malaria globally, emphasizing its significant burden on public health, especially in developing countries. Statistics regarding the number of cases and deaths due to malaria are included, showing the magnitude of the problem. The page also delves into the scientific aspects of malaria, elucidating the life cycle of the Plasmodium parasite, its different species, and their epidemiology. Additionally, it explains the various diagnostic techniques, such as microscopy and rapid diagnostic tests, used to detect malaria infection. The section on prevention and control measures sheds light on strategies like insecticide-treated nets, indoor residual spraying, and antimalarial drugs that have been employed to combat the disease. The effectiveness and challenges associated with these interventions are discussed, along with the role of research and development in finding new prevention methods and treatments. Furthermore, the page touches upon the social and economic impact of malaria, exploring its implications for affected communities in terms of poverty, education, and productivity. It also mentions the efforts of international organizations like the World Health Organization and the Roll Back Malaria partnership in addressing malaria and the global initiatives launched to combat the disease. Overall, this Wikipedia page serves as a comprehensive resource providing a thorough understanding of malaria, its impact, and the ongoing efforts to control and eliminate it worldwide.

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