==病原体=Malaria in Yaeyama, Okinawa, Japan===*[https://storymaps.arcgis.com/collections/b8f0dcc7c52746e8837e9aecb1833db0 Malaria History in Yaeyama War Malaria & Malaria Elimination (in 4 languages)]*[https://www.amazon.co.jp/gp/product/4901427261/ マラリア撲滅への挑戦者たち (やいま文庫13) 南風原 英育] ==Pathogen and life cycle==
*[https://www.youtube.com/watch?v=1v55yg0RfoY YouTube: Malaria Lifecycle Part 1]
*[https://www.youtube.com/watch?v=MxiWp8vkRFI YouTube: Malaria Lifecycle Part 2]
##hypnozoite only by ''P. vivax'' and ''P. ovale''
*===Human blood stage===
#merozoite
#trophozoite
##gametocyte
###male/female
*===Mosquito stage===
#gametocyte
#macrogametocyte
**Genetically sub-Saharan people highly lack Duffy antigen, which consists the reason why ''P. vivax'' is not endemic in sub-Sahara
==疫学Epidemiology==
in 2017
*219mil. per year ←500mil. in 2005
**琵琶湖南岸の水田と湖へ注ぐ小川でハマダラカが繁殖
*最後の患者は1961年沖縄
===China is certified as malaria-free by WHO in 2021===
*[https://www.who.int/news/item/30-06-2021-from-30-million-cases-to-zero-china-is-certified-malaria-free-by-who From 30 million cases to zero: China is certified malaria-free by WHO]
==Vector==
*economical development
==症状Prophylaxis==*ABCD of malaria prophylaxis**Awareness**Bite protection**Chemoprophylaxis**Diagnosis and treatment *atovaquone/proguanil**effective for both of liver stage and blood stage**needs 1 week continuation after leaving endemic area*mefloquine, doxycycline**effective only in blood stage**needs 4 weeks continuation after leaving endemic area ==Malaria immunology=====Reasons why immunity against ''Plasmodium'' needs repetitive infections===*Genetic heterogeneity of ''Plasmodium''*Modulation of host immune responses by ''Plasmodium'' ===Candidate antigens for malaria vaccine===*Radiation-attenuated sporozoite (RAS)*Genetically-attenuated sporozoite (GAS)**Sap 1: early arresting**Fabb/f: late arresting*Circumsporozoite protein (CSP) [https://www.niid.go.jp/niid/ja/typhi-m/iasr-reference/2566-related-articles/related-articles-508/11207-508r08.html IASR 2022年6月] ===Proteins on RBC knobs===*Surface proteins on trophozoite-infected RBC**PfEMP-1***binds adhesion molecules on brain endotherial cells = sequestration****ICAM-1, VCAM-1, CD36***only in ring form in blood**RIFINs**STAVOR ==Vaccine==*Successful passive immunization**Injection of malaria-immune IgG**Cohen, Nature 12:733, 1961 *Successful live attenuated vaccine**Radiation-attenuated sporozoite (RAS) vaccine**sporozoite was deleted for propagation ability in human liver**Hoffman, 2002, JID 185:1155 {|class="wikitable"|-!human liver|*pre-erythrocytic vaccine*anti-infection|*RTS, S/AS01|-!human RBC|*asexual blood-stage vaccine*anti-disease|*BK-SE36*Rh5*PfRipr*MSP1-withdrawn*AMA1-withdrawn*MSP3-withdrawn*GLURP-withdrawn|-!mosquito mid-gut|*transmission-blocking vaccine*anti-transmission|*Pfs25/Pvs25*Pfs230|} ===RTS, S/AS01===*antigen: circumsporozoite protein (CSP)*adjuvant: AS01*4 doses*phase 3**efficacy: infant 26%, children 36%**Lancet. 2015;386(9988):31-45*WHO Malaria Vaccine Implementation Programme (MVIP) is ongoing**Kenya, Ghana, Malawi*efficacy wanes in time**anti-CSP Ab titers wane**White, Lancet Inf. Dis., 2015;15(12)1450-8 ===AMA1-withdrawn===*no efficacy for overall*ad hoc analysis: 64.3% efficacy against a specific ''Plasmodium'' polymorphism, AMA1 3D7 DNA sequence**clinically meaningless because of many polymorphism ===Pvs25-withdrawn===*antigen: Pvs25H expressed in ''S. cerevisiae''*adjuvant: alhydrogel, ISA51**not enough antibody induction or serious side effects at phase 1 ==='''W'''heat '''G'''erm '''C'''ell-'''F'''ree Protein Synthesis '''S'''ystem (WGCFS)===*to extract ribosome, tRNA, TFs from germ (胚芽) of wheat**WGCFS is optimal recombinant protein synthesis system for ''Plasmodium'' proteins, much better than utilization of ''E. coli''*Immunoscreening against ''Plasmodium'' and recombinant target protein as antigen ===Potential of transmission-blocking vaccine===*被接種者個人の感染は予防されないため,TBV単独でのphase 3は原理的に困難.やるとしたら複数の村をincorporateしての大規模なcluster-randomizationを行い,村間に蚊が飛んでいかない程度の境界域も設けて,数年~10年単位で疫学的に観察する必要があり,およそ現実的ではない.*よってTBVはphase 2までが現実的で,その後は他の直接的な感染防止策が確立された時点でcombine methodとして地域単位で接種してtransmissionの減少を観察するという phase 4 が必要. ==Clinical feature=====severe malaria===*cerebral malaria*AKI, acute renal failure**"black water fever", mechanism unknown***treatment with quinine is associated with black water fever*jaundice*acidosis*ARDS*DIC, less common*purpura fulminans, due to coagulation abnormality; rare condition *mortality due to falciparum increases according to age ==Diagnosis==*increase likelihood in imported cases**fever>39℃**splenomegaly**low platelet count***decrease likelihood in imported cases** ===suspected cerebral malaria===*first check blood glucose**''Plasmodium'' consume blood glucose and quinine induce insulin secretion*there is no definitive diagnosis for cerebral malaria, only clinical diagnosis*pathogenesis of cerebral malaria is still unknown ===microscopy===*[https://www.mcdinternational.org/trainings/malaria/english/DPDx5/HTML/Frames/M-R/Malaria/body_Malariadiagfind2 Comparison of Plasmodium Species Which Cause Malaria in Humans] ==Treatment==*Quinine [ku-'''wai'''-na-in] ===arteminisin-based combination therapy===*to reduce parasites by rapid-acting arteminisin*to prevent recrudescence and drug resistance by lumefantrine or others *arteminisin resistant around Thailand-Myanmar border and Thailand-Cambodia border *IV forumulations for severe malarial patients who have difficulty in PO administration**IV artesunate is more effective than IV quinine***IV artesunate is unavailable in Japan
==検査=clinical classification of malaria==={|class="wikitable"|-!rowspan="3"|malaria|colspan="2"|severe|-|rowspan="2"|uncomplicated|falciparum|-|non-falciparum|}
==治療==*no specific additional treatment for cerebral malaria other than usual malaria treatment, nothing proved effective