Plasmodium
Malaria is the most important of all the tropical diseases in terms
of morbidity and mortality.
Malaria parasites belong to the genus plasmodium. Four species
of malaria parasites infecting human are:
Plasmodium falciparum (Pf) malignant tertian malaria
confined to some province in South
Plasmodium vivax (Pv)
benign tertian malaria
world-wide distribution
Plasmodium malariae (Pm)
Quartan malaria
sporadic distribution
Plasmodium ovala (Po)
Ovala malaria
confined in some places
common in West Africa
形态
P.v
P.m
P.f
环形体
较大，占Rbc1/3, 同P.v
核一个
小，占Rbc的1/6，
时有两个或两个以
上的虫体Rb中
阿米巴样滋养体
不规则，有伪足、带状或卵圆形
空泡
裂殖体
裂殖子6-12个，
成熟裂殖体有
12-24个裂殖子， 呈菊花样排列
排列不规则
雄配子体
小，圆形，核大 与P.v相似
疏松，核位于中
央
腊肠形，两端钝圆，
核大，疏松位于中
央
雌配子体
大，圆形，核小 与P.v相似
致密，核偏位
新月形，两端尖细，
核小致密，居中
红细胞变化
Rbc胀大，褪色， Rbc大小正常， 色泽正常，变形力
薛氏小点
有齐氏小点
下降，有茂氏小点
Two host are required to complete the life cycle of Plasmodium
Human are only the intermediate host in which the asexual phase
of parasite occurs, the female anopheline mosquito acts as the
definitive host, in which the sexual phase occurs.
Intracellular parasites (liver cell, RBC)
Obligate parasites, reproduce in alternating sexual and
asexual cycle
asexual cycle: in man schizogony occurs & beginning
of gametocytogenesis
sexual cycle: process beginning in man, completing in
the mosquito ( gametogony, sporogony)
The infection starts with the bite of an infected mosquito,
when the sporozoite ( infective form) is inoculated by
skin into the blood stream & subsequently
invades a hepatocyte.
Within the hepatocyte, the parasite undergoes a period of
differentiation and multiplication to produce the extra
-erythrocytic schizont, contained a few thousand merozoites
The merozoite, when released from the hepatocyte,
enters the blood stream & invades an erythrocytes
to start a periodic phase of differentiation & asexual
multiplication leading to the erythrocytic schizonts.
This process, known as erythrocytic stage within a period of
36-72 hours depending
on the species:
Pv, Po—44-48 hrs
Pf—36 –48 hrs
Pm—72 hro
At the end of the schizogonic cycle, the infected erythrocyte
rupture, liberating merozoites, which in turn infected new
erythrocyte.
The products
of schizont rupture may
stimulate the release of tumor
necrosis necrosis factor (TNF)
and other cytokines from host,
causing malarial paroxysms
(primary attack of malaria)
At same stage, a proportion of merozoites undergo sexual
differentiation forming male and female gametocytes.
Gametocytes continues to
circulate in the blood stream
for some time & if ingested by
a mosquito anopheles,
undergo transformation to
gametes which fertilize
to from first a zygote,
then an ookinete and final oocyst.
The oocyst produces by sporogony
thousands of sporozoites which
migrate to the salivary gland
of the moaquito, where they
stay until the next bite, thus
completing the cycle.
生活史特点：
1.细胞内寄生，有宿主转换和世代交替的现象。
2.在人体内行裂体增殖及配子生殖的开始，在蚊体内
完成有性生殖。
(一)人体内发育
1.红细胞外期
子孢子(sporozoite)侵入肝细胞
红外裂殖体
红外裂殖子
速发型：短潜伏期
迟发型：长潜伏期发作
复发
部分被巨噬细胞消灭
部分侵入红细胞
红细胞内期
早期滋养体(环形体，ringform)
晚期滋养体(阿米巴形滋养体，amoeboid form)
裂殖体(schizont)早期→成熟→(裂体增殖)
被M吞噬
裂殖子(merozoite)
侵入RBC→
配子体形成
雄(小)配子体(microgametocyte)
雌(大)配子体(macrogametocyte)
蚊吸入
(二)蚊体内发育
雌配子(染色体减数分裂)
雄配子(4-8 个细丝)
交配→合子→动合子→囊合子→子孢子
oocyst
In all of four species, asexual multiplication take place within
the liver cells,
P.vivax & P. ovale a proportion of the infecting sporozoites
enter a resting stage before undergoingasexual multiplication,
white order undergo this multiplication without delay.
The resting stage of the parasite of know as a hypnozoite.
After a period of weeks months or year.
Reactivation of the hypnozoite initiates asexual division.
The hypnozoite have not been observed in the liver cell, infected
by sporozoites of P. falciparum & P. malariae.
Relationship between the life cycle & relapse
or recrudescence
Relapse is a recurrence that taken place after complete
initial clearing of the erythrocytic infection & implies reinvasion
of the blood stream by merozites from activated hypozoites
in liver.
Recrudescence is a recurrence of symptoms in a patient
whose blood stream infection has previously been at such a
low level as not to be clinically demonstrable or cause
symptoms.
Exoerythrocytic stage
Sprozoites inoculated when mosquito sucks bleed
Sprozoites circulate with blood stream then invade liver cells
where schizont occurs
Two kind of sprozoites, one develop rapidly, another one slowly
the latter called hypnozoite
Rupture of infected cells release thousands of merozoites
Sprozoites
EE schizont
EE merozoites
Merozoites penetrate circulating RBC, continued cycles of
schizogony within RBC responsible for clinical illness
Schizont from hypnozoite develop slowly, released merozoites
responsible for the relapse
No malarial pigment observed in EE stage
Erythrocytic stage
Merozoites invade to the RBC, through ring form,
growing amoebid form, presegmenting schizont,
mature schizont, then penetrate fresh RBC again
Merozoites penetrate fresh RBC develop to ring form
again or develop in gametocytes
Pigment occurs in this stage
The proportion of macrogametocyte and microgametocyte
have to be 8:1
Mosquito phase of cycle
Mosquito infected when sucking blood
Gametogenesis gametocytes
midgut
macrogametocytes
macrogamete
zygote
microgametocytes
Zygote
ookinete
microgamete
oocyst
sporozoites (salivary gland)
四种疟原虫的发育过程的比较
P.v
P.m
P.f
P.o
红外期迟发型子孢子
有
无
无
有
红外期裂殖体大小
42-60μ
48μ
60μ
70x50μ
红外期裂殖体数目
12000个
15000个
40000个
15400个
红外期(速发型)发育时间
红外期特点
1.来自子孢子 2.在肝细胞无疟色素 3.无症状
红内期发育周期
48h
红内期裂殖子数目
36-48h
48h
12-24 个 (16) 6-12个
8-36个
6-12个
红内期发育场所
外周血液
环、配在外 外周血液
周其他在皮
下脂肪及内
脏毛细管
红内期特点
1.来自红外裂殖子或红内期裂殖子
2.在红细胞内有疟色素
3.有症状
在 蚊 体 内 发 育 成 熟 时 间 10-11d
(25℃)
72h
外周血液
16d
12d
-
生理
(一) 营养
分解
Hb→珠蛋白+血红素
酶 作用
氨基酸
葡萄糖消耗量比正常大100倍
脂肪类耗量也增加4-5倍
(二)与红细胞的关系
1.对红细胞的选择性
疟色素
提供虫体合成蛋白
P.v侵入幼稚Rbc和网织Rbc
感染度不超过1%
P.m侵入衰老的Rbc
感染度小于1/500
P.f对各期Rbc无选择性
感染度达10%以上
2.寄生红细胞的变化
P.v寄生的红细胞可胀大，色泽变淡，并出现薛氏小点
P.f可出现:
(1) 小突起出现，使Rbc粘附力增大粘于血管内皮上。
(2) Rbc可塑性下降，不能通过5μ的微血管。
3.裂殖子的释出和侵入红细胞
裂殖体
成熟
裂殖子
活动
红细胞变形
泡状隆起
侵入则分成 附着→入胞→封口三个过程
红细胞胀大
破裂
释出
Physiology
Nourishment & metabolism
Intake of food through the cytostome
hemoglobin
hematin + globin
hemazoin
(malarial pigment)
resynthesized
parasite protein
Aerobic metabolism
amount of oxygen consumed by the infected
about 100 times larger than that of the normal RBC
protein, fat, enzyme required,
Relationship with the RBC
Pv– invade young RBC
Pm—invade old RBC
Pf—invade all stages of RBC
Change of infected RBC
Pv—enlarged, pale, Schuffner’s dots
Pf—RBC develop excrescence, so RBC’s sticky & adherence to
the capillary in internal organs
Rupture of schizont & invasion of merozoite into RBC, the pellicle
of merozoite surround by surface coat
Invasion of merozoite:
Apical end adherence to the RBC’s membrane
Deform & invasion of RBC’s membrane
Invasion of merozoite into RBC form of parasitophorous vacucle
致病
(一)潜伏期
即从病原体侵入机体到出现症状的时间
短 11-25d
P.v
长 6-12m
P.m 18-25d
P.f 7-27d
（二）发作
1. 原因 红内期裂殖体成熟，裂殖子胀破红细胞后疟原虫
代谢产物残余，变性的血红蛋白和红细胞碎片进入血
液， 刺激M产生内源性致热源，作用于下丘脑体温中
枢
引起疟疾发作所需要的最低原虫血症
P.v 10-500/mm3 P.m 140/mm3
P.f 500-1300/mm3
2. 临床表现
周期性发作的冷、热、汗是疟疾的典型症状
但也可因为是初发或重复感染或混合感染而使周期性不明显
(三)贫血
原因：1.大量破坏
2.脾功能亢进
3.免疫反应(自身抗体和免疫复合物形成)
4.骨髓抑制
(四)脾肿大
热带巨脾综合症：巨脾、肝肿大、血IgM升高，抗疟药有效
(五)疟性肾病
由P.m引起多见，可致低蛋白血症、水肿蛋白尿、高血压
(六)黑尿热
恶性疟患者多见，
病人有高热、贫血、腰痛、血红蛋白尿、 衰竭
(七)凶险性疟疾
脑型、胃肠型、厥冷型、出血型等。
机理：机械性阻塞学说：内皮细胞表达粘附受体,增强
内皮细胞的粘附性, 脑微血管阻塞、缺O2、
养料耗竭
(八)再燃和复发
1.再燃(recrudescense)
初发后，由于残存的极少量红内期原虫，在一定条件下，
疟原虫大量增殖或又出现症状的情况，即称再燃。
2.复发(relapse)
急性疟患者在发作数次后或用杀裂殖体药物治疗后，可
以停止发作，血中原虫被彻底肃清，并经血液转种也不
能使受血者发病，经一段时间后，在无重复感染情况下，
出现原虫血症或症状，称复发，为红外期迟发型子孢子
(休眠子)引起。
(九)先天性疟疾和儿童疟疾
先天性疟疾的疟原虫来自母体，经胎盘传播，新生儿出生
后4 -12周开始发病。
先天性疟疾还可致早产、流产、死胎、低出生体重儿等。
儿童疟疾主要发生在热带的疟疾流行区，出生一个月后多见，
死亡率高。
(十)生活史与致病的关系
潜伏期
发作
再燃
复发
Pathogenesis
The pathogenic effects of a malarial infection have been considered
to be directly related to hemolysis of infected & uninfected
erythrocytes, liberation of the metabolites & antigens or toxin of
the parasite & the immunologic response of the host to antigenic
material.
In falciparum malaria the phenomenon of cytoadherence is basic
to the locally diminished tissue profession seen in its more sever
complication.
1. Primary attack
Recrudescence
Relapse
Incubation period
Pv—11-25 d ( 6-12 m)
Pf—7-27 d
Pm—18-35 d
typical clinical manifestation of malarial paroxysm
chill ( 20 min-1 hr) fever (1-4 hrs)
sweating (2-3 hrs)
Definite amount of parasites required for paroxysm
Pv 10-500/mm3
Pf 500-1300/ mm3
Pm 140/mm3
Periodicity of paroxysm coincides with time of
release of merozoites
Pv: 48 hrs
Pf: 72 hrs
Pm: 36-48 hrs
2. Anemia
3. Splenomegaly
4. Pernicious malaria
cerebral type, gastrointestinal type, algid type and so on
Parasite develop in RBC
Pf
Surface change in
RBC
Metabolism of hemoglobin
hemozoin formation
Adherence to
endothelium
Fe store depletion
lysis of cells infected
stroma
hemoglobin
antigen
splenomegaly
fever
hemoglobinemia
disseminated
intravascular
coagulation
autoAb
destruction
normal RBC
antibody bind
Pv
hemoglobinuria
nephritis
Localized decreased
microirculation
anemia
tissue anoxia
adrenal
cerebral
bacterial
sepsis
shock hyperpyrexia
coma
gastrointestinal
dysentery
hepalic
jaundice
pulmonary
edema
renal
auuria
免疫
(一)先天性免疫
1.Duffy氏血型阴性，对间日疟原虫有完全的不感受性。
2.镰状红细胞症患者，恶性疟症状轻。G6PD
(二)获得性免疫
带虫免疫：疟疾急性发作停止后，患者血中或组织中仍
有少量原虫未被清除，但对新的感染有免疫
力，即机体免疫力与原虫保持着相对稳定。
一旦原虫被消灭，免疫力也随之消失，即是
带虫免疫(premunition)
免疫逃避(immune evasion): 疟原虫逃避免疫效应，在宿主
体内长期存在，与机体的保护性
免疫抗体共存，即为免疫逃避。
可能是通过抗原变异，抗原抗体复
合物或胞内寄生阻断T细胞的作用。
Immunity
An important distinction must be make between conditions that
confer resistance to malaria & acquired immunity, which develop
after infection or after immunization
Insusceptibility of most blacks to P.vivax malaria because of the
absence of the merozoite receptor associated with the Duffy factor
on red cells
The presence of the sickle hemoglobin trait confers another form
of resistance to P.falciparum, which does not prevent infection
but limit high degrees of parasitemia that might be fatal. In some
parts of the world G-6-PD deficiency of red cells also appears to
limit parasitemia
Premunition & evasion of host immunity
Protective immunity against malaria parasites is slow to develop
and non-sterile. This protective immunity persists, while the
malaria parasites are still in the host, this kind of immunity
called PREMUNITION in malariology. It may be explained
by both the extreme antigenic diversity at the parasite & the
existence of Evasion of immunity
By the poor immunogenicity of its antigens because of their
analogy to host molecules, or by sequestration, (The ability
of parasite to remain sequestered by cytoadherence the
to the capillary lining of certain tissues & thus avoiding
exposure to immune effector mechanisms), or by antigenic
variation
诊断
(一)病原检查
1.薄血片检查
2.厚血片检查
3.骨髓检查
QBC(quantitative buffy coat)
(二)免疫学检查
IFA、IHA、ELISA、McAb
(三)DNA probe、PCR方法
Diagnosis
Despite the wide range of immunological & molecular
techniques currently available, the only certain means of
diagnosing all 4 species of human malaria is the
detection of the plasmodium by microscopic examination
of the blood
Both thick & thin blood film should be prepared. The
thick film method, which concentrates layers of red
blood cells on a small surface, is the most sensitive
for clinical use. The thin film is useful for species
identification in case of doubt. Giemsa is the most
commonly used of stains for routine diagnosis
the bone marrow
Immunological methods provide the means for detecting
either the parasite antigens or the host antibodies.
The detection of antigens may be an acceptable alternative
to parasite detection, if the assay is easy to use & dose not
require a microscope, but the detection of antibodies merely
provides information on past malaria experience & is of
limited use for individual diagnosis
IFA、IHA、ELISA、McAb
The presence of parasite in the blood means that there is
parasite DNA & RNA present and the application of DNA
or RNA hybridization to detect these molecules.
PCR, DNA probe
流行情况
(一)分布
(二)流行环节
1.传染源：现症病人和血液中带配子体的带虫者#
2.传播媒介：(1)中华按蚊：平原地区
(2)嗜人按蚊：丘陵地区
(3)微小按蚊：南方地区
(4)大劣按蚊：主要在海南岛
传播方式
(1)经蚊媒传播
(2)经输血传播
(3)经胎盘传播
(4)经伤口传播
3.易感人群
(三)影响传播的因素
1.自然因素
2.社会因素
防治原则
(一)治疗病人和带虫者，以消灭传染源
控制症状——杀灭裂殖体——氯喹
防止复发——杀灭红外裂殖体——伯喹
(二)防蚊灭蚊以切断传播途径
(三)保护易感者
1.防蚊
2.预防性服药
3.预防输血传播
4.疫苗的研制
Prophylaxis & chemotherapy
Endemicity of human malaria is usually determined by the geographic
distribution of its vector female anopheline mosquito
Anopheles sinensis
A. minimus
Three basic elements of prevention as follow:
Control of the source of infection-----elimination of gametocytes by
chemotherapy of human gametocyte carrier
Control of transmission route-----elimination of adult vector by
residual insecticides and destruction of aquatic stage of vector by
larvicides and modification of breeding place
Protection of susceptible population by chemoprophylaxis,
vaccination, and impregnated bed-nets
New vaccine approaches