Malaria: Difference between revisions

Simple or uncomplicated malaria may be treated with oral medications. Artemisinin drugs are effective and safe in treating uncomplicated malaria.<ref>{{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 }}</ref> Artemisinin in combination with other antimalarials (known as [[artemisinin-combination therapy]], or ACT) is about 90% effective when used to treat uncomplicated malaria.<ref name="Howitt 2012" /> The most effective treatment for ''P.&nbsp;falciparum'' infection is the use of ACT, which decreases resistance to any single drug component.<ref>{{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 }}</ref><ref name="Kokwaro 2009" /> 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.<ref>{{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 }}</ref><ref>{{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 }}</ref> Another recommended combination is [[dihydroartemisinin]] and [[piperaquine]].<ref>{{harvnb|WHO|2010|p=21}}</ref><ref name="Keating 2012" /><ref>{{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 }}</ref> Artemisinin-naphthoquine combination therapy showed promising results in treating falciparum malaria.<ref>{{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 }}</ref> However,but more research is needed to establish its efficacy as a reliable treatment.<ref>{{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 }}</ref> Artesunate plus mefloquine performs better than mefloquine alone in treating uncomplicated falciparum malaria in low transmission settings.<ref>{{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 }}</ref> Atovaquone-proguanil is effective against uncomplicated falciparum with a possible failure rate of 5% to 10%; the addition of artesunate may reduce failure rate.<ref>{{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 }}</ref> Azithromycin monotherapy or combination therapy has not shown effectiveness in treating plasmodium''Plasmodium falciparum'' or ''Plasmodium vivax'' malaria.<ref>{{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 }}</ref> Amodiaquine plus sulfadoxine-pyrimethamine may achieve less treatment failures when compared to sulfadoxine-pyrimethamine alone in uncomplicated falciparum malaria.<ref>{{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 }}</ref> There is insufficient data on chlorproguanil-dapsone in treating uncomplicated falciparum malaria.<ref>{{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 }}</ref><ref>{{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 }}</ref> The addition of primaquine with artemisinin-based combination therapy for falciparum malaria reduces its transmission at day 3-4 and day 8 of infection.<ref>{{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 }}</ref> 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.<ref>{{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 }}</ref>

Infection with ''P.&nbsp;vivax'', ''P.&nbsp;ovale'' or ''P.&nbsp;malariae'' usually does not require hospitalisation. Treatment of ''P.&nbsp;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]].<ref name="Waters 2012" /><ref>{{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 }}</ref> These two drugs act against blood stages as well, the extent to which they do so still being under investigation.<ref>{{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 }}</ref>

Cases of severe and complicated malaria are almost always caused by infection with ''P. falciparum''. The other species usually cause only febrile disease.<ref>{{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 }}</ref> Severe and complicated malaria cases are medical emergencies since mortality rates are high (10% to 50%).<ref>{{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 }}</ref>

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.<ref>{{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}}</ref><ref name="Sinclair 2012" /> In another systematic review, artemisinin derivatives (artemether and arteether) were as efficacious as quinine in the treatment of cerebral malaria in children.<ref>{{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 }}</ref> 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]].<ref name="Sarkar 2009" /> Artemisinin derivatives have the same or better efficacy than quinolones in preventing deaths in severe or complicated malaria.<ref>{{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 }}</ref> Quinine [[loading dose]] helps to shorten the duration of fever and increases parasite clearance from the body.<ref>{{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 }}</ref> There is no difference in effectiveness when using intrarectal quinine compared to intravenous or intramuscular quinine in treating uncomplicated/complicated falciparum malaria.<ref>{{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 }}</ref> There is insufficient evidence for intramuscular arteether to treat severe malaria.<ref>{{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 }}</ref> The provision of rectal artesunate before transfer to hospital may reduce the rate of death for children with severe malaria.<ref>{{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 }}</ref> 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.<ref>{{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 }}</ref>

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.<ref name="NB_2022_40_9">{{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}}</ref>

[[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<ref name="Tatem2017">{{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 }}</ref>]]

The WHO estimates that in 2021 there were 247 million new cases of malaria resulting in 619,000 deaths.<ref name="who2022"/> Children under 5 years old are the most affected, accounting for 67% of malaria deaths worldwide in 2019.<ref name="who2020">{{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}}</ref> 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.<ref name="Hartman 2010" /> Since 2015, the WHO European Region has been free of malaria. The last country to report an indigenous malaria case was Tajikistan in 2014.<ref name="who2022" /> There are about 1300–1500 malaria cases per year in the United States.<ref name="Taylor 2012" /> The United States eradicated malaria as a major public health concern in 1951,<ref>{{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}}</ref> though small outbreaks persist.<ref>{{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}}</ref> 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.<ref>{{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}}</ref> About 900 people died from the disease in Europe between 1993 and 2003.<ref name="Kajfasz 2009" /> 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%<ref name="UNICEF2015">{{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}}</ref> from a 2000 estimate of 985,000, largely due to the widespread use of insecticide-treated nets and artemisinin-based combination therapies.<ref name="Howitt 2012" /> Efforts at decreasing the disease in Africa since 2000 have been partially effective, with rates of the disease dropping by an estimated forty percent on the continent.<ref>{{cite journal | vauthors = Bhatt S, Weiss DJ, Cameron E, Bisanzio D, Mappin B, Dalrymple U, Battle K, Moyes CL, Henry A, Eckhoff PA, Wenger EA, Briët O, Penny MA, Smith TA, Bennett A, Yukich J, Eisele TP, Griffin JT, Fergus CA, Lynch M, Lindgren F, Cohen JM, Murray CL, Smith DL, Hay SI, Cibulskis RE, Gething PW | display-authors = 6 | title = The effect of malaria control on ''Plasmodium falciparum'' in Africa between 2000 and 2015 | journal = Nature | volume = 526 | issue = 7572 | pages = 207–211 | date = October 2015 | pmid = 26375008 | pmc = 4820050 | doi = 10.1038/nature15535 | bibcode = 2015Natur.526..207B }}</ref>

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.<ref name="Layne 2006" /> 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).<ref name="Provost 2011" /> A 2010 estimate indicated the deadliest countries per population were Burkina Faso, [[Mozambique]] and [[Mali]].<ref name="lancet-glob-mal-mort" /> 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]].<ref name="Guerra 2007" /><ref name="Hay 2010" /> This effort led to the publication of a map of ''P.&nbsp;falciparum'' endemicity in 2010 and an update in 2019.<ref name="Gething 2011" /><ref>{{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 }}</ref><ref>{{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 }}</ref> As of 2021, 84 countries have endemic malaria.<ref name="who2022"/>

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.<ref>{{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 }}</ref> European settlers and the West Africans they [[Atlantic slave trade|enslaved]] likely brought malaria to the Americas starting in the 16th century.<ref>{{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}}</ref><ref>{{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 }}</ref>

| congenital malaria || various [[Plasmodium|plasmodia]] || plasmodium''Plasmodium'' [[vertically transmitted infection|introduced from the mother]] via the [[fetal circulation]]

| transfusion malaria || various [[Plasmodium|plasmodia]] || plasmodium''Plasmodium'' introduced by [[blood transfusion]], [[needle sharing]], or [[needlestick injury]]

Target 6C of the [[Millennium Development Goals]] included reversal of the global increase in malaria incidence by 2015, with specific targets for children under 5 years old.<ref name="doi.org">{{cite journal | vauthors = Sato S |title=Plasmodium—a''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 |url=https://doi.org/10.1186/s40101-020-00251-9 |access-date=17 August 2021}}</ref> 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.<ref>{{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}}</ref> 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.

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.<ref name="Stanway2019">{{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 }}</ref>

In a research conducted in 2019, using experimental analysis with knockout (KO) mutants of ''Plasmodium bergueiberghei'', 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.<ref name="Stanway2019"/>

In 2017 a strain of the bacteria genus [[Serratia]] was genetically modified to prevent malaria in mosquitos<ref>{{Cite journal |last=Wang |first=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 |url=https://www.science.org/doi/10.1126/science.aan5478 |journal=Science |language=en |volume=357 |issue=6358 |pages=1399–1402 |doi=10.1126/science.aan5478 |issn=0036-8075 |pmc=9793889 |pmid=28963255}}</ref><ref>{{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}}</ref> and in 2023 it has been reported that the bacteria [[Delftia tsuruhatensis]] naturally prevents the development of malaria by secreting a molecule called [[Harmane]].<ref>{{Cite journal |last=Huang |first=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 |issn=0036-8075}}</ref><ref>{{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}}</ref><ref>{{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}}</ref>

<ref name="Ashley 2014">{{cite journal |vauthors = Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han KT, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, Mayxay M, Khanthavong M, Hongvanthong B, Newton PN, Onyamboko MA, Fanello CI, Tshefu AK, Mishra N, Valecha N, Phyo AP, Nosten F, Yi P, Tripura R, Borrmann S, Bashraheil M, Peshu J, Faiz MA, Ghose A, Hossain MA, Samad R, Rahman MR, Hasan MM, Islam A, Miotto O, Amato R, MacInnis B, Stalker J, Kwiatkowski DP, Bozdech Z, Jeeyapant A, Cheah PY, Sakulthaew T, Chalk J, Intharabut B, Silamut K, Lee SJ, Vihokhern B, Kunasol C, Imwong M, Tarning J, Taylor WJ, Yeung S, Woodrow CJ, Flegg JA, Das D, Smith J, Venkatesan M, Plowe CV, Stepniewska K, Guerin PJ, Dondorp AM, Day NP, White NJ | display-authors = 6 | title = Spread of artemisinin resistance in ''Plasmodium falciparum'' malaria | journal = The New England Journal of Medicine | volume = 371 | issue = 5 | pages = 411–23 | date = July 2014 | pmid = 25075834 | pmc = 4143591 | doi = 10.1056/NEJMoa1314981 }}</ref>

[[Category:''Plasmodium''|*Malaria]]