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Malaria Parasites (Plasmodium)

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Title: Malaria Parasites (Plasmodium)


1
Malaria Parasites (Plasmodium)
  • Department of Parasitology

2
Introduction
  •     1. Malaria is one of the five major parasitic
  • diseases in our country.
  • Each year, more than 1,000,000 children
    die of
  • malaria in Africa.
  • 2. Four species affecting humans
  • P. vivax(P.v) causes benign tertian
    malaria.
  • P. falciparum(P.f) causes malignant
    tertian
  • malaria.
  • P. malariae(P.m) causes quartan malaria.
  • P. ovale(P.o) causes tertian malaria.

3
  • P.v and P.f are more important than P.m and P.o.
  • A few cases of P.o have been reported in China.
  •  

4
3. taxonomy
  • ProtistagtProtozoagtApicomplexagtSporozoagt
  • EucoccidiidagtPlasmodidaegtPlasmodium

5
Life Cycle In mosquito
  • 10days at 25?
  • Male and female gametocytes ? Male and female
    gametes
  • ? zygotes ? ookinetes ? oocysts ? sporozoites
  • gametogony stomach lumen gamogenesis sexual
    reproduction
  • sporogonystomach wall agamogenesis asexual
    reproduction

6
Anopheles gambiae adult female bloodfeeding on
human skin
7
In human
  • 1.       pre-erythrocytic stage
  • EE (exo-erythrocytic stage) 8 days
  •        tachy-sporozoites TS
  •        brady-sporozoites BS
  • 2.       ES (erythrocytic stage) 48h
  • schizogony EE and ES
  • result in more merozoites

8
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???
  • 1.???????2.???????????3.?????????4.??????
    ???5.???(????)6.?????????

12
Characteristic of life cycle
  • Intermediate host human
  • Final host mosquito
  • Infective stage sporozoite(???)
  • Infective mode mosquito bite skin of human
  • Parasitic position liver and red blood cells
  • Transmitted stage gametocytes(???)
  • Schizogonic cycle in red cells (?????????) 48
    hrs/P.v36-48 hrs/P. f
  • Sporozoite tachysporozite(??????) and
    bradysporozite(??????)

13
Morphology
  • P.v morphology P.f morphology
  • Ring forms (early trophozoites)
  • Late trophozoites
  • Schizonts
  • Male gametocytes Female gametocytes

14
Morphology
  • In human
  • Pre-erythrocytic stage
  • Ring forms (early trophozoites)
  • Late trophozoites
  • Schizonts
  • Male gametocytes Female gametocytes

15
  • Pre-erythrocytic schizont in liver. These mature
    in 6-14 days time liberation merozoites into the
    blood stream. Giemsa-colophonium. 400. Enlarged
    by 5.4.

16
  • Plasmodium vivax Blood Stage Parasites Thin
    Blood Smears Fig. 1 Normal red cell Figs. 2-6
    Young trophozoites (ring stage parasites) Figs.
    7-18 Trophozoites Figs. 19-27 Schizonts Figs.
    28 and 29 Macrogametocytes (female) Fig. 30
    Microgametocyte (male)  

17
P. vivax
  • Rings in 2 slightly enlarged RBCs 17 y.o. man
    with a relapse due to P. vivax (PCR confirmed), 6
    months after returning from a visit to Papua New
    Guinea (specimen contributed by Virginia SHD)

18
  • Double infection with rings, RBC enlarged and
    deformed, Schüffner's dots beginning to become
    visible 69 y.o. woman

19
  • Late ring in a RBC with Schüffner's dots 60 y.o.
    man

20
Plasmodium vivax TrophozoitesFigs. 8-18
Increasingly mature trophozoites of P. vivax
21
  • Smears from patients Increasingly mature
    trophozoites. The RBCs are enlarged and deformed,
    the parasites are ameboid, and the Schüffner's
    dots vary in intensity

22
Plasmodium vivax Trophozoites
23
Plasmodium vivax SchizontsFigs. 19-27
Increasingly mature schizonts 

24
  • P. vivax thin smear. A mature schizont about to
    rupture. A clump of malarial pigment can be seen
    in the center. Giemsa. 1000. Enlarged by 5.4.

25
  • Plasmodium vivax Schizonts Smears from patients
    Note that in these patients, the Schüffner's dots
    are not conspicuous. (This happens in many of the
    smears received it is probably related to
    variability in staining.) 

26
  • Plasmodium vivax GametocytesFig. 28 and 29
    Nearly mature and mature macrogametocyte
    (female) Fig. 30 Microgametocyte (male)
  • Plasmodium falciparum GametocytesFigs. 27, 28
    Mature macrogametocytes (female) Fig. 29, 30
    Mature microgametocytes (male)

27
????????? mature macrogametocyte (female)
28
?????????
29
????? Plasmodium falciparum
  • ???
  • Ring form

30
Morphology
  • In mosquito
  • Male and female gametes
  • ? zygotes ? ookinetes ? oocysts
  • ? sporozoites

31
?????
  • Male gametes

32
ookinetes
33
Ookinete, from the midgut of an infected
mosquito. Giemsa. 800. Enlarged by 5.4.
34
Oocysts
35
  • Oocysts of P. falciparum in midgut of an infected
    mosquito. Oocysts appear as circular bodies.
    Fresh preparation. 100. Enlarged by 5.4.

36
Sporozoites
37
Clinical Manifestation and Pathogenesis
  •  
  • 1. Incubation period P.v. 14-17 days
  • P.f.
    8-12 days
  • 2. An attack occurs because of the sudden
    liberation of merozoites, malarial pigment and
    RBC debris into the blood stream.

38
  • Three stages of each paroxysm
  • (1) The cold stage (chill) lasting for
    30min-1hr
  • (2) The hot stage(fever) lasting for 1-4hr
    (P.v. P.f. and P.o. once every other day P.m.
    once every 2 days. )
  • (3) Sweating stage 1-2hr

39
?? Pathogenicity
  • ?? Paroxysm (attack of malaria)
  • ----??????????????????????3?????????????????????
  • mechanism
  • ----???????????,?????????????,???????????????,?
    ?????????????,???????????????????????????,????????
    ??????????,????????,????????,???????????

40
  • ----???????????????,???????,????????????? p.v.
    48 hrs P.f./36 to 48 hrs P.m./72 hrs
  • Process ----to shows a succession of 3
    stages
  • ?.?? The cold stage (chill), lasting for
  • 30 min to 1 hr.
  • ?.?? The hot stage (fever), 1 to 4 hrs.
  • (3).?? Sweating stage, 1 to hrs.
  • Characteristic
  • ----(1).??? periodic
  • (2).??? repeated
  • (3).??? regular

41
3. Recrudescence and Relapse
  •        
  • Recrudescence occurs when the blood schizonticide
    does not eliminate all parasites from the blood
    stream, either because the dose was inadequate or
    because the parasite is resistant to the drug.
    Relapse occurs in P vivax and P ovale infections
    after the delayed development of liver- stage
    parasites that have not been treated adequately
    with a tissue schizonticide.
  • P.f and P.m. have only recrudescence, but, P.v.
    and P.o. both have relapse and recrudescence.

42
  • Remnant of parasites in RBC result in
    recrudescence
  • Hypnozoites in liver cause relapse

43
  • 4. Anemia splenomegaly and fatal
    malaria-cerebral malaria caused by P.f. (small
    vessels are plugged)

44
  • P.f schizogony takes place in the
    capillaries of the internal organs, the infected
    red cells tend to adhere to one other and the
    small vessels may become plugged. This may
    produce several fatal results
  • Cerebral malaria
  • Renal failure
  • Serious anemia
  • Acute respiratory distress syndrome ARDS
  • Shock

45
  • ?? anemia
  • ---- ????????????,?????????????
  • (1)????????????
  • (2)?????,???????????
  • (3)??????(???????)?
  • (4)??????????
  • ???????????????????????????,????

46
  • ??? Splenomegaly
  • ---- ????????34??,?????,??????????,????????
  • ???????????-????????

47
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51
?????(??)
  • Tropical splenomegaly syndrome. This young
    Malaysian girl had a protuberant abdomen due to a
    large spleen extending to the pelvis. She showed
    high antibody levels to P. falciparum and raised
    Ig M. It is believed that the condition results
    from repeated infection with malarial parasite
    along with an abnormal immunological response.

52
  • ????(?????)Malignant malaria
  • ----????????????????????????????????????????,???
    ??????????????
  • ????????????,??????????????????????????,????,
    ???????,??????

53
????????????
  • Section of liver from a case of P.  falciparum
    infection. The Kupffer cells (macrophages) are
    loaded with black pigment, which is malarial
    pigment (haemozoin). H and E. 400. Enlarged by
    23.4.

54
  • Brain from a case of P. falciparum infection. The
    cortex has a brownish colour and minute
    haemorrhages can be seen in the region of the
    basal ganglia. In this case death occurred due to
    haemorrhages and necrosis in the CNS (cerebral
    malaria)

55
  • Section of brain from a case of P.  falciparum
    infection. The infected cells adhere to the
    endothelial lining of the blood vessels. In small
    blood vessels this leads to occlusion and
    necrosis. H and E. 400. Enlarged by 23.4.

56
  • Same tissues observed in polarized light. The
    malarial pigment inside the red cells shines
    making it easily visible. H and E. 400. Enlarged
    by 23.4

57
???????
  • Spleen from a case of P. falciparum infection.
    The deposition of malarial pigment makes it
    almost black in colour.

58
?????????
  • Section of placenta form a case of P. falciparum
    infection. The maternal blood shows red cells
    containing parasites and pigment. The foetal
    blood shows red cells without any parasites. It
    is generally believed that congenital
    transmission of malaria does not occur and that
    malarial parasites are unable to pass the
    placental barrier H and E. 400. Enlarged by 5.4.

59
Immunology
  • Premunition

60
Diagnosis
  • A. Clinical symptoms and history
  • B. Microscopic examination of blood.
  • 1. Thin film and Thick(Giemsa's stain)
  • To master the morphology of parasites and
  • changes of infected red cells
  • 2. P.f. Only Ring forms and gametocytes can
  • be found in blood film.
  • C. Other methods Immunologic/Biochemical/Molecula
    r diagnosis.

61
??
  • 1 ????
  • ???????????
  • ???????????,??????????????malaria parasites.
  • ????
  • ???????????,?????????????????????????????????,???
    ??
  • ??????????10???,???????????

62
???? Laboratory diagnosis
  • 1.????
  • (1)?????? ??????????????????,????????
  • Thin film
  • Thick film
  • Question Which stages are there in the blood
    film of P.v. or P.f. ?
  • (2)??????????(??)

63
????--???????
  • ?????????,??????,?????,?????,???
  • ?????????????,??,???????????????????,???????,????
    ?????



64
  • 2??????(??)
  • ??????----?????????
  • ? ???????
  • ??????----???????
  • ???????????
  • 3????????
  • PCR?PROBE

65
Treatment
  • 1. Three principles
  • Control of clinical symptoms
  • Eradication of gametocytes
  • Prevent relapse

66
?? Treatment
  • Chlorquine ?quinine?artemisinin and
    artemether----anti-erythrocytic stage drugs.
    (question Which stage of plasmodium can these
    drugs kill?)
  • Primaquine and pyrimethamine ----anti-exoerythroc
    ytic stage drugs.
  • primaquine(anti-exoerythrocytic gametecyte)

67
2. Medicines
??????????????
68
???????Artemisia annua
69
Prevention
  • Chemoprophylaxis
  • -----Chloroquine / pyrimethamine
  • used for
  • prophylaxis of malaria
  • -----Chemotherapy 1 week before entry into
    the endemic area for 4 weeks after returning
    from the endemic area.
  • Malaria vaccines

70
  • Mosquito control
  • (1). Reconstruction of environment
    eradicate the breeding places of moquitoes.
  • (2). Spry insecticides DDVP and so on.
  • (3). Use mosquito nets (dipping in
    insecticide), screen, or mosquito repellents to
    protect the person from mosquito bites.

71
Epidemiology
  • A global problem Each year, 300-500
    million people become ill with malaria and
    several million died.

72
World Distribution of Malaria
73
In China
  • 1. South China-high endemic area
  • P.f. is prevalent and Mosquito vector
  • A. mimimus.
  • 2. Central China and Yantze Valley
  • P.v predominant. Mosquito vector A. listeri
  • 3. Huang Huai Region Vector A.sinensis.

74
Ronald Ross
  • Great Britain University College Liverpool,
    Great Britain 1857 1932
  • The Nobel Prize in Physiology or Medicine 1902
  • "for his work on malaria, by which he has shown
    how it enters the organism and thereby has laid
    the foundation for successful research on this
    disease and methods of combating it"

75
Charles Louis Alphonse Laveran
  • France
  • Institut Pasteur Paris, France
  • 1845 - 1922
  • The Nobel Prize in Physiology or Medicine 1907
  • "in recognition of his work on the role played by
    protozoa in causing diseases"

76
Julius Wagner-Jauregg
  • The Nobel Prize in Physiology or Medicine 1927
  • "for his discovery of the therapeutic value of
    malaria inoculation in the treatment of dementia
    paralytica
  • Austria
  • Vienna University Vienna, Austria
  • 1857 - 1940

77
??
  • 1.????????????????????????????????2.????????
    ???4?,P.v ????P.f ??,???,????3.??????-??????,???
    ??????????4.P.v????,???????????????,???????????
    P.f????5.????????????????6.??????????????????
    7.???????????????(??)????(??)?8.???????????????
    ?9.?????????????????????????,?????
  • ??PCR?????10.P.v????,P.f????
    P.f?P.f?????P.m?P.o?????11.????????
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