Malaria Parasites (Plasmodium)

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Malaria Parasites (Plasmodium)

• Department of Parasitology

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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.

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• 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.
•  

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3. taxonomy

• ProtistagtProtozoagtApicomplexagtSporozoagt
• EucoccidiidagtPlasmodidaegtPlasmodium

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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

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Anopheles gambiae adult female bloodfeeding on
human skin
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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

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???

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

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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(??????)

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Morphology

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

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Morphology

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

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• 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.

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• 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)  

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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)

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

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

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

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

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• 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.

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• 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.) 

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• 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)

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????????? mature macrogametocyte (female)
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?????????
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????? Plasmodium falciparum

• ???
• Ring form

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Morphology

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

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?????

• Male gametes

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

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Sporozoites
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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.

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• 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

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?? Pathogenicity

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

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

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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.

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

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

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• 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

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

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

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?????(??)

• 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.

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

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????????????

• 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.

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• 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)

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• 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.

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• 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

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???????

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

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?????????

• 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.

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Immunology

• Premunition

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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.

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??

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

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???? Laboratory diagnosis

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

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????--???????

• ?????????,??????,?????,?????,???
• ?????????????,??,???????????????????,???????,????
  ?????

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

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Treatment

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

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?? 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)

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2. Medicines
??????????????
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???????Artemisia annua
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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

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• 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.

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Epidemiology

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

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World Distribution of Malaria
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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.

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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"

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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"

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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

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??

• 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.????????