Izvorni kod stranice Malarija

{{Infobox disease
 | Name           = Malarija
 | ICD10          = {{ICD10|B|50||b|50}}-{{ICD10|B|54||b|54}}
 | ICD9           = {{ICD9|084}}
 | Image          = Malaria.jpg
 | Caption        = ''Plasmodijum'' iz pljuvačke ženke komarca se kreće duž tela komarca
 | DiseasesDB     = 7728
 | MedlinePlus    = 000621
 | OMIM           = 248310
 | eMedicineSubj  = med
 | eMedicineTopic = 1385
 | eMedicine_mult = {{eMedicine2|emerg|305}} {{eMedicine2|ped|1357}}
 | MeshName       = Malaria
 | MeshNumber     = C03.752.250.552
 }}
[[Datoteka:P vivax trophozoite4.jpg|mini|[[Crvena krvna zrnca]] inficirana sa ''P. vivax'']]
'''Malarija''' je infektivna bolest koju izaziva sićušni [[parazit]] ''[[Plasmodium]]'' i to bilo koja od četiri vrste, koliko ih i postoji. Svaka od ovih vrsti ima svoje specifičnosti, bilo prema reakciji na [[medikamenti|medikamente]] ili prema lokaciji u organizmu nakon [[infekcija|infekcije]], ali i prema efektima koje ima po zdravlje čoveka.

'''''Plasmodium falciparum''''' je vrsta koja se geografski prostire u tropskim i suptropskim područjima, dakle oko [[Ekvator]]a. Infekcija ovim parazitom može ugroziti život obolelog u toku par dana od ulaska parazita u organizam, a kod parazita postoji rezistencija na većinu dostupnih medikamenata, tako da terapija mora biti kombinovana.

'''''Plasmodium vivax, P. malariae i P. ovale''''' su preostale vrste, koje nisu tako opasne po čoveka. Postoje primjeri uspešnog oporavka nakon mesec dana, čak i bez lečenja priznatim medikamentima. Nalaze se u svim tropskim krajevima sveta, izuzev '''Plasmodium ovale ''' koji je nađen samo u zapadnoj [[Afrika|Africi]].<ref name="Abeku 2007"/> ''Plasmodium vivax '' i ''P malariae'' se mogu nastaniti u [[jetra|jetri]] čoveka, što može izazvati dodatne komplikacije i zahtevati dodatni medicinski tretman.<ref name="Arnott 2012"/><ref name="Baird 2013"/><ref name="White 2011"/>

Prenosnik ovog parazita, a i same bolesti, je jedna vrsta tropskog roda [[komarac]]a ''Anopheles'', koji ubodom unosi istog u čoveka. Pošto se [[larva|larve]] komarca sve do izlaska iz ljušture nalaze pod [[voda|vodom]], uglavnom u [[močvara|močvarnom]] područjima malarija je najrasprostranjenija u močvarnim područjima.

U svijetu se svake godine malarijom zarazi 300-350 miliona ljudi, od čega 1,3 miliona umiru. Većina slučajeva se događa u tropskim krajevima, a većina smrti u [[subsaharska Afrika|subsaharskoj Africi]].

Francuski vojni liječnik [[Charles Louis Alphonse Laveran]] je godine [[1907]]. dobio [[Nobelova nagrada za medicinu|Nobelovu nagradu za medicinu i fiziologiju]] zahvaljujući svom otkriću uzročnika malarije. Godine [[1902]]. istu je nagradu dobio britanski liječnik [[Sir Ronald Ross]] za svoj opis životnog ciklusa plazmodija.

Poznati biolog Robert Koch otkrio je da se malarija može uspješno sprječiti isušivanjem močvara, prirodnog staništa muhe prijenosnika malarije, te je na taj način uspješno liječio malariju u Brijunskom arhipelagu, nakon čega su istom metodom njemački liječnici nastavili iskorijenivati malariju u Istri.

== Opis ==
Plasmodium falciparum je vrsta koja se geografski prostire u tropskim i subtropskim područjima, dakle oko Ekvatora. Infekcija ovim parazitom može ugroziti život obolelog u toku par dana od ulaska parazita u organizam, a kod parazita postoji rezistencija na većinu dostupnih medikamenata, tako da terapija mora biti kombinovana.

Plasmodium vivax, P. malariae i P. ovale su preostale vrste, koje nisu tako opasne po čoveka. Postoje primjeri uspešnog oporavka nakon mesec dana, čak i bez lečenja priznatim medikamentima. Nalaze se u svim tropskim krajevima sveta, izuzev Plasmodium ovale koji je nađen samo u zapadnoj Africi. Plasmodium vivax i P malariae se mogu nastaniti u jetri čoveka, što može izazvati dodatne komplikacije i zahtevati dodatni medicinski tretman.

Prenosnik ovog parazita, a i same bolesti, je jedna vrsta tropskog roda komaraca Anopheles, koji ubodom unosi istog u čoveka. Pošto se larve komarca sve do izlaska iz ljušture nalaze pod vodom, uglavnom u močvarnom područjima malarija je najrasprostranjenija u močvarnim područjima.

Prijenos ovog jako malog parazita je jedino moguć preko Anopheles, jer se jedan dio životnog ciklusa odvija unutar komarca, a kako se nalaze najčešće u pljuvačnim žlijezdama komarca, paraziti se ubodom prenose direktno u krv, tačnije u crvena krvna zrnca. Njihov put je najčešće prema jetri gdje se generiše veliki broj parazita koji zaposjedaju sve veći broj eritrocita, koje svojom reprodukcijom uništavaju u velikom broju.

=== Simptomi ===
Zavisno od vrste parazita iz roda Plasmodium i vremena inkubacije, prvi simptomi se mogu javiti 7-14 dana ili čak i 8-10 meseci nakon unošenja parazita. Dosta toga zavisi i od imuniteta, pa se tako mogu zabeležiti slučajevi potpunog imuniteta, koji je stečen vremenom.

Simptomi malarije, pogotovo u prvih nekoliko dana, ne izgledaju ništa drugačije od uobičajenih simptoma koje imaju neke druge bolesti koje uzrokuju bakterije, virusi ili paraziti. To otprilike uključuje povećanu telesnu temperaturu, glavobolju, umor, pojačano znojenje, povraćanje, ali mogu se javiti i nešto drugačiji znaci kao suv kašalj, bolovi u mišićima, povećanje jetre, ili čak nervne disfunkcije i gubitak svesti.

== Uzročnik ==
Malarija je uzrokovana protozoanskim [[parazit]]om iz roda ''Plasmodium'', kojeg prenosi [[komarac]] ''Anopheles''. Kod čovjek malariju uzrokuju ''[[Plasmodium falciparum|P. falciparum]]'', ''[[Plasmodium malariae|P. malariae]]'', ''[[Plasmodium ovale|P. ovale]]'', ''[[Plasmodium vivax|P. vivax]]'' i ''[[Plasmodium knowlesi|P. knowlesi]]''. ''Plasmodium falciparum'' je najčešći uzročnik i najčešće uzrokuje smrt.

=== Životni ciklus ===
Komarci roda ''Anopheles'' su primarni domaćini uzročnika, te imaju ulogu vektora (prijenosnika zaraze) na ljude i druge kralježnjake, sekundarne domaćine. Mladi komarci hraneći se krvlju zaraženih kralježnjaka probavljaju gametocite uzročnika. U probavnom sustavu komarca gamete se difereciraju u muške i ženske te se spajaju ookinete, koje se probijaju iz probavnog sustava komarca te formiraju oociste u stijenci probavnog sustava. Kada oociste rupturira iz nje izlaze sporozite i kroz komarčevo tijelo migriraju u žlijezde slinovnice komaraca. Prilikom sljedećeg hranjenja komarca, sporozoite, zajedno sa slinom uzlaze u krvotok. Uzročnici se mogu prenesti i transfuzijom krvi, što je vrlo rijetko.

=== Rekurentna malarija ===
Malarija nakon liječenja se javlja zbog tri razloga. Do ponovnog javljanja bolesti može doći zbog neadekvatnog liječenja, zbog reinfekcije novim ugrizom komarca. Relaps bolesti karakterizira ''P. vivax'' i ''P. ovale'', koji se nakon nestanka iz krvi, ponovno pojave iz latentnih parazita u jetri.

== Patogeneza ==
Infekcija malarijom odvija se u dvije faze. Prva jetrena egzoeritrocitna faza, te eritrocitna faza. Kada sporozoiti uzročnika malarije dospiju u krvotok, dospiju do [[jetra|jetre]], gdje ulaze u hepatocite i u njima se aseksulano razmnožavaju. Bolest je kroz tih 8-30 dana najčešće asimptomatska. Kod ''P. vivax'' i ''P. ovale'' jetrena faza može latentno trajati i do 1,5-3 godine. Kod ''P. vivax'' merozoite prelaze u hipnozoite koje u hepatocitima miruju nekoliko mjeseci (6-12 tipično) pa do tri godine. U jetrenim stanicama nastaju brojne merozoite koje nakon raspadanja stanica jetre ulaze u [[eritrocit]]e. U eritrocitima paraziti se ponovno aseksulano razmnožavaju. Poprimaju oblik prstena, zatim rastu u ameboidni oblik iz kojeg nastaju shizonti sa 8 fo 24 merozoita svaki. Oni ponovno izlaze iz stanica te ulaze u nove eritrocite. Takvim valovima periodične masovne invazije novih eritrocita, značjano se povećava količina uzročnika, dok se klinički prati porast tjelesne temperature. Dio parazita u eritrocitima prelazi u spolne gametocite koji nakon što komarac popije krv, u komarčevom probavnom sustavu započinju novi ciklus.
U stanicama jetre i eritrocitima parazit je dobro zaštićen od imunološkog odgovora. Zaražene eritrocite ipak uklanja [[slezena]]. ''P. falciparum'' na eritrocitima izražava adhezivne proteine zbog čega se lijepi na malim krvnim žilama i uzrokuje začepljenje mikrovaskulature.

Oštečenje jetre uzrokovano malarijom je rijetko i obično posljedica već postojeće bolesti jetre (nrp. virusni hepatitis, alkoholna bolest jetre).

== Dijagnoza ==
Na bolest se uglavnom posumnja na temelju epidemiološke anamneze (boravak u krajevima gdje je prisutna bolest), simptoma bolest. Za dijagnozu bolesti koristi se mikroskopski pregled krvi (razma periferne krvi ili gusta kap). Razvijeni su i brzi dijagnostički testovi na bazi antigena.<ref name="Abba 2011"/><ref name="Ameri 2010"/>

Malarija se prema [[Svjetska zdravstvena organizacija|SZO]] klasificira kao nekomplicirana ili kao teška. U slučaju da je prisutan jedan od sljedećih kriterija bolest je teška, a ako nije onda je nekomplicirana:<ref>Guidelines for the Treatment of Malaria http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf {{Webarchive|url=https://web.archive.org/web/20150422004034/http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf |date=2015-04-22 }}</ref>
*Kliničke značajke:
** promjena stanja svijesti
** prostracije - značajna opća slabost (osobe ne može hodati, sjediti)
** nemogućnost hranjenja
** višestruke konvulzije - dva ili više napada 
** duboko disanje (acidotično disanje)
** cirkulatorni kolaps ili šok, niski art. krvni tlak (hipotenzija) - manje od 70mmHg kod odraslih ili manje od 50mmHg kod djece
** [[žutica]] uz dokaz disfunkcije nekog drugog vitalnog organa
** [[hemoglobinurija]]
** spontano krvarenje
** [[plućni edem]] (radiološki)
*Laboratorijske značajke:
** [[hipoglikemija]] (glukoza u krvi manje od 2,2&nbsp;mmol/L)
** [[metabolička acidoza]] (bikarbonati u plazmi < 15&nbsp;mmol/L)
** teška normocitna [[anemija]] (Hb < 5 g/dl)
** [[hemoglobinurija]]
** hiperparazitemija (> 2%/100 000/μL
** [[hiperlaktatemija]] (laktati u krvi > 5&nbsp;mmol/L)
** oštećenje bubrega (serumski [[kreatinin]] > 265 μmol/L

== Liječenje ==
[[Datoteka:Malaria map.PNG|mini|250px|Države u kojima postoji mogućnost od izbijanja malarije obojene su u crveno]]
Tretiranje ove bolesti odgovarajućim lekovima zavisi od vrste Plasmodium koja je prisutna u organizmu čoveka, koncentracije samog parazita u krvi kao i otpornisti parazita na neke od lekova. Pravilna terapija lekovima protiv malarije nakon 48 sati uklanja sve simptome bolesti, a već nakon 3-4 dana parazit je uklonjen iz krvotoka.

Postoji niz najrazličitijih lekova koji se koriste kako za sprečavanje, tako i za tretman bolesti (najpoznatiji je svakako kinin), a među njima najefikasniji i najpoznatiji su Chloroquine, Mefloquine, Doxycycline, Primaquine, Malarone, najčešće korišteni u preventivne svrhe.

Da bi se sprečile ponovne pojave ove bolesti (rekurence), u terapiju se uključuje i Primaquine, koji sprečava ponovni razvoj parazita, naročito vrsta P. ovale i P. vivax.

=== Prevencija ===
Metode za prevenciju malarije uključuju lijekove (profilaksa), eradikaciju komaraca i prevenciju uboda komaraca. Prisutnost malarije u određenom području zahtjeva kombinaciju nekoliko faktora, guste naseljenosti čovjeka, brojne populacije komaraca i visokog stupnja prijenosa sa komaraca na ljude i sa ljudi na komarce. Slabljenje jedne od karika dovodi do nestanka bolesti.

Uklanjanje prijenosnika bolesti postiglo se je isušivanjem močvarnih područja, boljim sanitarnim uvjetima, te insekticidima. Mjere su bile uspješne uz značajan ekološki učinak. Određeni učinak postiže se i mrežama protiv komaraca na krevetima, kako se komarci roda ''Anopheles'' hrane noću.

Profilaksa lijekovima (kemoprofilaksa) mjera je koja se odnosi na osobe koji putuju u endemska područja malarije. Obično se lijekovi (klorokin, meflokin) uzimaju dva tjedna prije odlaska, te se nastavljaju do šest tjedana po povratku iz ugroženog područja.

=== Lijekovi ===
Medikamentozno liječenje ovisi o težini bolesti. Nekomplicirana malarija liječi se peroralnim uzimanjem kombinacije dva ili više antimalarijska lijeka ([[antimalarici]] - npr. kinin, sulfadoksin-pirimetamin, doksiciklin, klindamicin).<ref name="Achan 2011"/> Najučinkovitije su kombinacije sa [[artemizinin]]om.

Teška malarija se liječi parenteralnim pripravcima antimalarika uz suportivne mjere u jednicima intenzivnog liječenja, zbog potrebe nadzora vitalnih funkcija.

Većina oboljelih ako se adekvatno liječi potpuno se oporavi. Teška malarija može brzo napredovati i uzrokovati smrt u nekoliko sata ili dana. Najteži oblici bolesti, liječeni u najboljim centrima imaju smrtnost do 20%.

== Povijest ==
Malarija je prisutna kod ljudi preko 50 000 godina. Prvi zapisi o povremenim epidemijama groznice potječu iz drevne Kine 2700 godina prije nove ere.<ref>Cox F (2002). "History of human parasitology". Clinical Microbiology Reviews 15 (4): 595–612. {{DOI|10.1128/CMR.15.4.595-612.2002}}. {{PMC|126866}}. {{PMID|12364371}}</ref> Smatra se da je malarija zaslužna i za pad moći [[Rimsko carstvo|rimskog carstva]],<ref>{{Cite web |title=DNA clues to malaria in ancient Rome |date=February 20, 2001 |work=BBC News |url=http://news.bbc.co.uk/2/hi/science/nature/1180469.stm}}, in reference to {{cite journal |journal=Ancient Biomolecules |title=Biomolecular archaeology of malaria |author=Sallares R, Gomzi S |volume=3 |issue=3 |year= 2001 |pages=195–213 |oclc=538284457}}</ref> gdje je znana kao rimska groznica. Močvarni dijelovi južne Italije vrlo su pogodni za širenje bolesti. U Europi i Sj. Americi bolest je bila dosta rasprostranjen do 20.st. Tijekom [[drugi svjetski rat|drugog svjetskog rata]] malarije je bila glavna zdrastvena prijetnja američkim vojnicima na pacifičkom bojištu te se smatra da je oko 500 000 zaraženo, a prema nekim izvorima 60 000 američkih vojnika na afričkom i južnopacifičkom bojištu je umrlo od bolesti.

Za svoje otkriće uzročnika malarije, francuski vojni liječnik [[Charles Louis Alphonse Laveran]] dobio je [[Nobelova nagrada|Nobelovu nagradu]] za [[fiziologija|fiziologiju]] [[1907.]] [[Velika Britanija|Britanac]] Sir [[Ronald Ross]] također je dobio Nobelovu nagradu ([[1902.]]) za opis životnih ciklusa parazita malarije koji se razvijaju unutar komaraca-prijenosnika.

Prvi učinkoviti lijek protiv malarije koristili su lokalni stanovnici u [[Peru]]u, koji su priređivali tinkturu iz kore drveta lat. ''Cinchona'' koja je sadržavala [[kinin]]. [[Isusovci]] su primjetili učinkovitost terapije, te su je tijekom 1640-ih uveli u Europu, gdje je bila ubrzo općeprihvaćena. Tek su 1820. francuski kemičari Pierre Joseph Pelletier i Joseph Bienaimé Caventou, otkrili i izolirali aktivni sastojak kinin iz kore. Tijekom 1940-ih klorokin je zamijenio kinin. Tijekom 1970-ih kineski znanstvenik Tu Youyou, otkrio je artemizinin, koji je u kombinaciji sa drugima antimalaricima,  postao preporučeni lijek.

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<ref name="Wongsrichanalai 2008">{{cite journal |author=Wongsrichanalai C, Meshnick SR |title=Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia–Thailand border |journal=Emerging Infectious Diseases |volume=14 |issue=5 |pages=716–9 |year=2008 |pmid=18439351 |pmc=2600243 |doi=10.3201/eid1405.071601 |url=http://www.cdc.gov/eid/content/14/5/716.htm}}</ref>

<ref name="World Malaria Report 2012">{{Cite report |url=http://www.who.int/malaria/publications/world_malaria_report_2012/wmr2012_no_profiles.pdf |format=PDF |title=World Malaria Report 2012 |publisher=World Health Organization}}</ref>

<ref name="Worrall 2005">{{Cite journal |author=Worrall E, Basu S, Hanson K |title=Is malaria a disease of poverty? A review of the literature |journal=Tropical Health and Medicine |year=2005 |volume=10 |issue=10 |pages=1047–59 |doi=10.1111/j.1365-3156.2005.01476.x |pmid=16185240}} {{open access}}</ref>

<ref name="WSJ 2008">{{Cite web |author=Schoofs M |title=Clinton foundation sets up malaria-drug price plan |url=http://online.wsj.com/article/SB121626447476161201.html |date=July 17, 2008 |publisher=Wall Street Journal |accessdate=2012-05-14}}</ref>

<ref name="Yangzom 2012">{{Cite journal |author=Yangzom T, Gueye CS, Namgay R, Galappaththy GN, Thimasarn K, Gosling R, Murugasampillay S, Dev V |title=Malaria control in Bhutan: Case study of a country embarking on elimination |year=2012 |volume=11 |page=9 |pmid=22230355 |pmc=3278342 |doi=10.1186/1475-2875-11-9 |journal=Malaria Journal}} {{open access}}</ref>
-->
}}

== Literatura ==
{{refbegin|2}}
* {{Cite report |author=WHO |title=Guidelines for the Treatment of Malaria |edition=2nd |year=2010 |publisher=World Health Organization |isbn=978-9-2415-4792-5 |url=http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf |format=PDF |ref=harv |access-date=2015-04-24 |archive-date=2015-04-22 |archive-url=https://web.archive.org/web/20150422004034/http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf |url-status=dead }}
* {{Cite book |author=Schlagenhauf-Lawlor P |title=Travelers' Malaria |year=2008 |publisher=PMPH-USA |isbn=978-1-55009-336-0 |url=http://books.google.com/books?id=54Dza0UHyngC |ref=harv}}
* {{Cite book |author=Packard RM |title=The Making of a Tropical Disease: A Short History of Malaria |url=http://books.google.com/books?id=B_V1Xj6wH7IC |year=2007 |publisher=JHU Press |isbn=978-0-8018-8712-3 |series=Johns Hopkins Biographies of Disease}}
* {{Cite book |author=Shah S |title=The Fever: How Malaria Has Ruled Humankind for 500,000 Years |url=http://books.google.com/books?id=4jUjPh64X9UC |year=2010 |publisher=Macmillan |isbn=978-0-374-23001-2}} [http://www.amazon.com/Fever-Malaria-Ruled-Humankind-Years/dp/0374230013/ excerpt and text search]
* {{Cite book |author=Bynum WF, Overy C |title=The Beast in the Mosquito: The Correspondence of Ronald Ross and Patrick Manson |url=http://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}}
{{refend}}

== Vanjske veze ==
{{Commonscat|Malaria}}
* {{dmoz|Health/Conditions_and_Diseases/Infectious_Diseases/Parasitic/Malaria}}
* [http://www.emro.who.int/entity/malaria-control-and-elimination/ WHO site on malaria]
* [http://www.unhco.org/malaria/ UNHCO site on malaria] {{Webarchive|url=https://web.archive.org/web/20111220220958/http://www.unhco.org/malaria/ |date=2011-12-20 }}
* [http://www.rollbackmalaria.org/gmap/ Global Malaria Action Plan] (2008)
* [http://doctorswithoutborders.org/news/issue.cfm?id=2395 Doctors Without Borders/Médecins Sans Frontières – ''Malaria''] information pages
* [http://www.wehi.edu.au/other_domains/MalDB/who.html Who/TDR Malaria Database] {{Webarchive|url=https://web.archive.org/web/20130520072620/http://www.wehi.edu.au/other_domains/MalDB/who.html |date=2013-05-20 }}
* [http://www.antimalariaomd.org/en/index.php Anti malaria and sustainable development] {{Webarchive|url=https://web.archive.org/web/20180317174946/http://www.antimalariaomd.org/en/index.php |date=2018-03-17 }}
* [http://www.wwarn.org Worldwide Antimalarial Resistance Network (WWARN)]

[[Kategorija:Malarija| ]]
[[Kategorija:Tropske bolesti]]
[[Kategorija:Protozoalne bolesti]]