Download P. falciparum

Plasmodium (疟原虫)
History
 Malaria is an old infectious disease. The first
documentation about it is at 1500BC.
 Until the end of the 19th century, it was commonly
thought that malaria was caused by breathing bad air
(mal-aria) and was associated with swamps
History
Important application of the knowledge
about malaria: W. Gorgas successfully
implemented control strategies for malaria
and yellow fever during the construction of
Panama Canal
Global distribution
Plasmodium that infect human
Malaria current status
Morphology
•
Plasmodium is the one-cell parasite, so the basic
morphology is a nucleus (chromatin), cytoplasma
and cell membrane
•
Wright or Giemsa stain gives the Cytoplasm –
bluish; Chromatin - red to red-purple while the
malarial pigments are yellow-brown
•
There are three stages and six main forms of
plasmodium in RBC
Plasmodium in RBC
Trophozoites (滋养体期)：ring form and developing
trophozoites
Schizonts (裂殖体期)：immature and mature -merozoites
Gametocyte (配子体期)： Microgametocytes and
macrogametocytes
Trophozoites
• Fig. 1: normal red cell; Figs. 2-5: ring stage
parasites (young trophozoites)
Ring form trophozoites
Thin blood film (Giemsa stained)
• Ring like plasma with one nucleus at one side
Mature trophozoites (amoeboid form)
• The plasmodium grow with pseudopods, more cytoplasma
and malarial pigment presented in the plasma
• Red blood cell enlarged and became pale with
Schüffner‘s dots(薛氏小点)
Schizonts
• Figs.： increasingly mature schizonts
Macrogametocyte (female gametocyte)
of P.v
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Giemsa staining
compact nucleus, usually at edge of the parasite
scattered pigment granules
The gametocyte is completely filling its host cell
Microgametocyte (male gametocyte) of P.v
• Giemsa staining
• large nucleus at the center of the cell
• scattered pigment granules
Macrogametocyte of P. f
• The crescent-shaped gametocytes of P.
falciparum are very distinctive, but
tend to only appear late in the
infection
• Compact nucleus, red, usually at the
center of the cell
• Malarial pigments around the nucleus
Microgametocyte of P. f
• Sausage-shaped with two
blunt end
• Large nucleus at the center
• Sometimes hard to
distinguish from the female
gametocytes
exo-erythrocytic stage—
merozoites in liver cells
The vector – female Anopheles
Development in the vector
Gametocytes
zygote
oocyst
sporozoites
Life Cycle
Life cycle
• Infective stage：sporozoites
• Transmission
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female Anopheles mosquito
transfusion
transplacental
needle stick
• Pathogenic stages：erythrocytic stage
• Diagnositic stages：erythrocytic stage
Pathogenesis
Clinical features
Incubation period （潜伏期）
• Time interval between the mosquito bite and the onset
of the clinical symptoms
• Time for the sporozoite reaching liver and entering
• Duration of the development in the liver
• Time of development in the RBC to produce sufficient
erythrocytic merozoites to cause clinical symptoms
– P. falciparum 7 to 27 days
– P. vivax 8 to 31 days
– P. malarie 18 to 40 days
– P. ovale 16 to 18 days
Clinical features
Typical malaria paroxysm（发作）

Malarial paroxysm -symptom for erythrocytic phase
– RBCs rupture releasing merozoites, malarial metabolites,
endotoxin in blood
– shaking chill（寒战） followed by fever （高热）(2-20
hrs)
– profuse sweating when fever breaks（出汗退热）
– repeated characteristic cycle for each species
P. falciparum 36-48hrs
P. vivax 48hrs
P. malariae 72hrs
P. ovale 48hrs
Recrudescence versus relapse
• Recrudescence （再燃） is the return of the
symptom of malaria after apparent cure, which is
due to a sudden increase in what was a persistent,
low-level parasite population in the blood.
– The periodic increase in numbers of parasites results
from a residual population persisting at very low levels
in the blood after inadequate or incomplete treatment
of the initial infection.
– The asymptomatic situation may last for as long as 53
years.
Recrudescence versus relapse
• Victims may suffer relapse （复发）after apparent
recovery of malaria. This is caused by the long prepatent
sporozoites (LPPs) or hypnozoites which remain dormant
in the hepatocytes for an indefinite period.
– P. vivax and P. ovale will develop hypnozoites in the liver
responsible for relapse while patients infected with P. falciparum
and P. malariae have no phenomenon of relapse
• All four types of plasmodium can maintain low level of
parasitemia and account for the recrudescence of the
disease
Clinical features
• liver & spleen damage of long-term
• complications from P. falciparum
– Anemia
– tropical splenomegaly syndrome
– cerebral malaria - 50% of deaths
• coma and renal failure due to tubular
necrosis
tropical splenomegaly syndrome
Cerebral malaria
Diagnosis
• Travel history to endemic area & presence of
symptoms, e.g., fever and chills
• Thick smears - hard to read
• Thin smears - see RBC morphology and parasite
characteristics
• serology - helps rule out fever of unknown origin
• DNA probes- too slow & costly esp. in field
Diagnosis
Thick blood smear
Thin blood smear
Indirect fluorescent antibody test
（IFA）
Treatment
• Quinidine( 奎 尼 丁 ), chloroquine( 氯 喹 ),
primaquine(伯氨喹), pyrimethamine(乙胺嘧
啶), artemisinin(青蒿素), sulfadoxine(磺胺),
mefloquine( 甲 氟 喹 ), tetracycline( 四 环 素 ),
proguanil(氯胍)
• affect parasite in different ways depending on
stage when administered
• different species react differently
• emergence of drug-resistant malaria
Prevention and control
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Personal protection- netting, repellents, etc.
mosquito control or eradication - not easy
avoid sharing needles
develop vaccines - not currently available
select proper treatment for species and
morphological forms
summary
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Relapse
Recrudescence
Typical malaria paroxysm
How to reduce the morbidity and mortality
of malaria?