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*===Human liver stage===#schizontsprozoite→schizont
*===Human blood stage===
*===Mosquito stage===
==症状==*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
==治療==Quinine ku-'''wai'''-na-in キニーネ*no specific additional treatment for cerebral malaria other than usual malaria treatment, nothing proved effective
→Vaccine
{{TM menu}} ==歴史History of malaria==
*2700BCのNei Ching（內經＝黃帝內經）に記述あり
*ヒポクラテスも記述
*1948年 P.C.C. Graham が初めてヒト肝細胞への感染を発見
==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]
===etymology===
*''sporo-''
**
*''mero-''
**[Gr] part
*''tropho-''
**
*''hypno-''
**
*''-zoite'', ''-zont''
**
*''gameto-''
**
*''oo-''
**
*''-kinate''
**
*''-cyst''
**
*sporozoite
*merozoite
*trophozoite
*schizont
*hypnozoite
*gametocyte
*ookinate
*oocyst
##hypnozoite only by ''P. vivax'' and ''P. ovale''
#merozoite
#trophozoite
##gametocyte
###male/female
#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==
*treatment
*economical development
==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
==検査=clinical classification of malaria==={|class="wikitable"|-!rowspan="3"|malaria|colspan="2"|severe|-|rowspan="2"|uncomplicated|falciparum|-|non-falciparum|}
==予後Prognosis==
