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Medical Microbiology > Day 11: Malaria and Microscopy Malaria > Flashcards

Day 11: Malaria and Microscopy Malaria Flashcards

HC 25, 26

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1
Q

HC25: Malaria/ Plasmodium life cycle

A

Sporozoites are injected by female mosquitos with blood meal
> Sporozoites go to the liver > liver stages > parasite will adapt to form for inside human host (other environment)
> In the liver, hepatocytes are infected > formation schizonts (cells with many parasite cells in it) > rupture (exo-erythrocytic cycle)
> Iron in heme from hemoglobin is needed by malaria schizonts for development: move to blood
> Erythrocyte infected: blood stages
> Immature trophozoite made (ring stage): make clones
> In erythrocytic cycle: trophozoite develops to schizont and ruptures and re-infects other erythrocytes (no recombination, asexual)
> sometimes: maturation trophozoite of the asexual stages not chosen to become gametocyte instead of mature trophozoite
> gametocytes can are taken up by mosquito and can adapt to sexual stage

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2
Q

Mosquito stages of Plasmodium

A

Gametocytes are taken up and sexual reproduction
> microgametes and macrogametes develop
> sexual recombination between one micro- and macrogamete
> reproduction to ookinetes > development to oocyst and rupture to release sporozoites

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3
Q

Mosquito in Plasmodium is the ..

A

Final host and vector
> human is intermediate host

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4
Q

Relevance Plasmodium

A

> Children susceptible
Travelers without immunity and pregnant women susceptible
Disease and high mortality: also disability and loss of economic value

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5
Q

Plasmodium falciparum hosts

A
  • Heteroxenous: both human and Anopheles host (mosquito)
    > intermediate host: asexual reproduction: human
    > definitive host: sexual reproduction: Anopheles
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6
Q

Human malaria species

A
  • Plasmodium falciparum
  • Plasmodium vivac
  • Plasmodium malariae
  • Plasmodium ovale
  • Plasmodium knowlesi (zoonosis)
    » difference in morphology, although knowlesi hard to distinguish
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7
Q

Incubation period malaria

A

The hepatic stage, exo-erythrocytic cycle
> when schizonts mature until rupture

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8
Q

Symptoms malaria after incubation period

A

Flu like (aspecific) symptoms like fever, myalgia, headache

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9
Q

Typical malaria attacks following synchronization cycle in blood stage

A

Fever, anemia, enlarged spleen

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10
Q

Incubation period for types of malaria

A

vivax and ovale: 10-17 days, sometimes months to years
malariaeL 18-40 days, sometimes months to years
falciparum: 8-11 days
» can sometimes hide in liver and cause disease after being ‘cured’

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11
Q

Three stages of attack malaria

A
  • Cold stage, hot stage, sweating stages
    > erythrocyte ruptures, release contents and parasites, inflammation, fever peak
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12
Q

Infection P. vivax/ovale/malariae

A

Patients can be most ill but infection mostly not lethal

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13
Q

P. falciparum infection

A

Most serious disease with often lethal outcome and requires immediate treatment
> short period: organ failures
» brain, kidneys, lungs, liver, intestine

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14
Q

Most spread Plasmodium species

A

falciparum

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15
Q

P. vivax and P. ovale strategy

A

Dormancy for survival
> can make hypnozoites which can hide and survive in the liver and activate after a silent period
> after new infection with parasite (can be other malaria infection) > come into liver > old infections can re-activate
> development to more severe or milder infection (because parasite recognized earlier)
> can also re-activate without new mosquito sting

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16
Q

Diagnosis malaria

A
  • direct detection parasite
  • Microscopy: thin and thick smear, QBC
  • Indirect detection: detection of immune responses or biomarkers with PCR, rapid tests or serology
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17
Q

Minimal requirements malaria

A
  • Anopheles mosquito must be present, which are in contact with humans and in which the parasites can complete the invertebrate host part of life cycle
  • Malaria parasites must be present
  • Humans must be present, in contact with Anopheles mosquitos and in whom the parasites can complete the vertebrate host part of the life cycle
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18
Q

Prevention malaria

A

Interrupt one of their requirements, treating and vaccination

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19
Q

Quinine

A

Old treatment for malaria, derived from bark
> also a bit in tonic soda
> against severe malaria effective when no ACT available
> administration IV

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20
Q

Chloroquine

A

Malaria drug which is not used anymore
> it was very cheap, unfortunate
> resistance
> works against heme production so that nutrients are depleted for parasite

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21
Q

Sulphadoxine + Pyrimethamine

A

First combination therapy for malaria
> Long half life
> to fight antimicrobial resistance
> IPT for pregnant women > in all countries with high malaria prevalence, regular doses
> Also for prevention in children
> also resistance against this, so only used for prevention programs and not as treatment

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22
Q

Artemisinin

A

From a plant, which was used in tea in Asia
> Synthetic variants all derived from artemisinin, similar modes of action
> Artemisinins (an endoperoxide molecule) are activated by ferrous iron Fe2+ which creates free radicals by breaking endoperoxide ring
> endoperoxide activated by iron groups in heme to create free radicals > destroy a lot of proteins inside parasite
> parasite can adapt, by partly upregulating other proteins and bypassing: drug will work slower, parasite less sensitive

23
Q

Avoiding resistance against artemisinin

A

Combination therapy
> with fast acting aremisia component
> long acting partner component
> combining drugs to prevent development of resistance
> parasites now need multiple routes of resistance to become insensitive

24
Q

Drugs against P. vivax and ovale

A
  • Pamaquine: prevent recurrent episodes of malarial fever
  • And replaced by Primaquine: antimalarial with lower grade of toxicity
  • exo-erythrocytic, because hypnozoites in liver need to be attacked
25
Q

Vaccines and treatment difference

A

Treatment makes patients better who are ill
Vaccination prevents patients from becoming ill

26
Q

Types of malaria vaccies

A
  • Transmission-blocking vaccine: gametocyte development blocked or less potent
    > Less sexual development in mosquito
    > human is vaccinated, life cycle in mosquito is blocked
    > less potent gametocytes taken up by the mosquito
    > the patient does not benefit from this
  • Anti-infection vaccines
    > against pre-erythrocytic stages
    > approved ones
    > prevent disease
  • Blood stage vaccines
    > malaria reaches blood: still infection
    > Less severe disease
27
Q

Effectiveness anti-infection vaccines

A

Good in preventing very severe malaria (falciparum)
> amount of infected people does not differ
> vaccine does not act on infection, but on disease
> like RTSS, a pre-erythrocytic vaccine

28
Q

HC27: Thick smear microscopy

A

Several layers of erythrocytes on top of each other
> drop of blood on slide
> no fixation but lysis
> hard to observe concentraion
> no red blood cell structures visible

29
Q

Thin smear

A
  • Make single layer of erythrocytes and check for parasite infection malaria
    > cells are fixated
30
Q

Observations based on thick and thin smear

A
  • Thick smear: are there parasites
  • Thin smear: identification and structure analysis
31
Q

Sensitivity microscopy

A

The longer you watch, the more you see
> more sensitivity in western labs, less patients observed, more time to look

32
Q

Malaria stages in erythrocytes

A
  • Trophozoite (ring): one nucleus
  • Schizonts: division stage: multiple nuclei
  • Gametocyte: sexual stage: one nucleus
33
Q

For detection malaria in blood cell .. you need to observe

A

Cytoplasm ad nucleus

34
Q

Spots in infected erythrocytes: Mauers clefts

A

Large vacuoles outside of parasite
> can be counted, not too many
> large chunks
> only in P. falciparum

35
Q

Pigment in cytoplasm of infected erythrocyte with malaria

A

Breakdown product of hemoglobin used for division

36
Q

Schüffnerse dots

A
  • Little purple dots after staining
  • too many to count
37
Q

Form of erythrocyte per type

A

Normal: falciparum
Smaller: malariae
Enlarged: vivax
Oval: ovale
Round oval with ravels: ovale

38
Q

Number of merozoites (little parasite cytoplasm and nuclei) in mature schizont

A
  • Vivax: 8-24
  • Malariae: 8-12
  • Ovale: 8-12
  • Falciparum: 8-32 (only in peripheral blood in severe disease, usually no schizonts from falciparum observed)
39
Q

Pigment in schizonts

A
  • vivax: visible and spread out
  • malariae: centered
  • ovale: can be centered
40
Q

Young and old gametocytes in P.vivax

A

Old one has larger cytoplasm that fills almost complete erythrocyte

41
Q

P. falciparum gametocyte

A

banana shape

42
Q

P. falciparum can have … in trophozoites

A

Multiple ring phases in one erythrocyte

43
Q

Which type of malaria can have many fragments in trophozoite of rings

A

vivax

44
Q

Presence Schüffner dots per malaria

A
  • Vivax: yes, fine
  • Ovale: yes, large
  • Malariae: no
  • Falciparum: no, but can have Mauers clefts
45
Q

Size infected cells per malaria

A
  • Vivax: enlarged
  • Ovale: enlarged
  • Malariae: smaller to normal
  • Falciparum: normal
46
Q

Gametocyte in malaria type

A
  • Vivax: round or oval
  • Ovale: round
  • Malariae: round
  • Falciparum: banana-shape
47
Q

Parasitemia ratio in malaria types

A
  • Vivax: max 2%
  • Ovale: 2%
  • Malariae: <1%
  • Falciparum: can be over 5%
48
Q

Microscope slides with thin / thick smear can contain …

A

large white blood cells

49
Q

P. malariae has a characteristic schizont with

A

Flower like pigment: pigment and center and nuclei around it like a daisy

50
Q

Multiple rings in trophozoite means

A

P. falciparum

51
Q

Shape P. ovale

A

Oval, can have ravels
, has amoeboid shape, can take weird shape

52
Q

Shape p. vivax

A

has round shape but can be little wavy

53
Q

trophozoites of ovale and malariea can have

A

less of a ring shape
> malariae can have also a rectangle shape

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