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Flashcards in Malaria (and Toxo) Deck (93):
1

The one exception to the "No vaccines" claim that was given in class

RTSS vaccine for malaria

 

(50% reduction in cases)

2

Malaria is caused by the genus ______

Plasmodium

3

Most severe Plasmodium?

Common in ____

falciparum

common in tropics

4

Less common plasmodium species?

Why is it less common?

Where is it found?

Vivax

Infection is limited to reticulocytes

Common in subtropics and temerate regions

5

Third and fourth common plasmodiums?

What are the types of infections they cause?

Ovale = Relapsing malaria

knowlesi = 24 hour life cycle, zoonotic infections

6

Where is plasmodium ovale found?

West africa

7

What is the fastest-replicating plasmodium species?

Knowlesi

 

It has a 24 hour lifecycle, which means it can increase the population very quickly

8

Plasmodium Life cycle:

  1. Infected mosquito injects____
  2. They go to the liver and become _____
  3. They are released and invade ___ cells
  4. Once in the cell, these become ______
  5. This multiplies, giving more ______
  6. These are released and become _____
  7. Female mosquito picks them up and _____ are formed

  1. Sporozoites
  2. Merozoites
  3. Red blood cells
  4. Trophozoites
  5. New merozoites
  6. gametocytes
  7. sporozoites

9

Which plasmodium forms hypnozoites?

How/where does this form live?

How do you treat for this?

Vivax

Lies dormant in the liver

It only responds to Primaquine

10

How does plasmodium bind to the placenta?

It binds to chondroitin sulfate A

11

Three conditions covered in malaria pathogenesis

Cerebral malaria

Severe anemia

Metabolic acidosis

12

Cerebral malaria pathogenesis

Blood brain barrier disruption (from ROS) = Edema and hemorrhage

Tissue hypoxia (from Microvascular obstruction) = Parenchymal and axonal damage

 

 

13

What causes severe anemia in malaria pathogenesis

 

Hemolysis of immature RBCs

(Rosetting)

14

What causes the metabolic acidosis in malaria?

Tissue hypoxia causes lactic acid from anaerobic glycolysis

15

Three stages of classic, uncomplicated malaria

Cold stage

hot stage

sweating stage

16

The symptoms of uncomplicated malaria are generally _______

Flu-like

 

(Chills, headache, myalgias and malaise)

 

also ANEMIA and JAUNDICE

17

5 major symptoms of severe malaria

Organ failures (renal)

Cerebral malaria

Anemia

Hemoglobinuria

Acute respiratory distress syndrome

18

What is malaria during pregnancy called?

Features?

Placental Malaria

 

Especially during first pregnancy, causes low birth weight and miscarriage

19

Antimalarials, three categories and what they target:

Tissue schizonticides = kill liver stage

Blood schizonticides = kill erythrocytic forms

Gametocytocides = kill sexual stages and block transmission

20

All antimalarial compounds are effective against ______

Asexual blood stages

21

Antimalarials that target Liver stage

Artemisinins

Primaquine

Pyrimethamine

Atovaquone

22

Antimalarials that target the hypnozoites

Primaquine

23

Antimalarials that target gametocytes

Artemisinins

Mefloquine

Amodiaquine

Primaquine

Pyrimethamine

24

Four methods of malaria prevention

Insect repellent

Insecticides

Bed nets

Chemoprophylaxis

25

5 drugs for prevention of clinical disease

Malarone (atovaquone + proguanil)

Doxycycline

Chloroquine

Mefloquine

Primaquine

26

Malarone area and preventive course

All areas

start 1-2 days before, continue one week after

27

Doxy area and preventive course of treatment

All areas

start 1-2 days before, continue 4 weeks after

28

Chloroquine areas and preventive course

Chloroquine sensitive areas

start 1-2 weeks before and continue  4 weeks after

29

Mefloquine area and Pretreatment course

Mef-sensitive areas

start more than two weeks before, continue more than four weeks after

30

Primaquine area and course of pretreatment

If >90 P. vivax in the area

Start 1-2 days before, continue one week after

31

Uncomplicated malaria (or unidentified species) can be treated with _____ agents

Examples? (area-based)

Oral

Chloroquine sensitive areas:

  •  chloroquine and hydroxychloroquine sulfate

Chloroquine resistant areas:

  • Malarone
  • Coartem (artemether + Lumefantrine)
  • Quinine Sulfate PLUS Doxy/Tetra//Clinda
  • Mefloquine

32

Treatment for uncomplicated malaria?

P. vivax/ovale (hypnozoites in liver)

**Basically add primaquine to any of the treatments of uncomplicated malaria

 

P. malariae or Knowlesi

Chloroquine or Hydroxychloroquine 

33

Tx for severe/complicated malaria

Quinidine gluconate (I.V.) PLUS Doxy/Tetracycline/Clinda

 

Cardio consult!

34

Alternative Tx for Severe/complicated malaria

Artesunate (= IV only alternative if QG not available or tolerated)

Followed by one of:

  • Malarone
  • Doxy (Clinda in pregnant women)
  • Mefloquone

35

Artemisinin type

Sesquiterpene lactone endoperoxide

 

(endoperoxide is the active group)

36

Artemisinin has low ___ but high ____

Low toxicity

High counterfeit rate

37

Artemisinin resistance has been observed in _____

SE Asia

38

Artemisinin MOA

Must be activated (via heme-iron)

Activated artemisinin forms free radicals that target parasite proteins/lipids

39

Artemisinin Mechanism of Resistance

Mutations in Kelch 13 gene 

-->Delays life cycle, alters stress response

40

Artemisinin has no effect on ___ stage

Liver

41

Artemisinin half life

1-2 hours

 

42

Artemisinin is commonly paired with ______ and ______

Mefloquone or Lumefantrine

43

Artemisinin is ______ because of the required frequency of dosing

not appropriate for chemoprophylaxis

44

Artemisinin ROA 

It is also _____ with a low ______

Oral only

insoluble with a low bioavailability

45

Semisynthetic artemisinins are available that allow...

different ROA's

(oral, IV, IM, rectal)

46

What is artesunate, what is the ROA, what does it treat?

Semisynthetic artemisinin

IM, IV, rectal

Treatment of severe malaria

47

Artemisinin antimalarial effect is associated with ___

C-max

48

Artemisinin derivatives are paired with _____

Longer half life drugs

49

3 Common combos for artemisinin

Amodiaquine

mefloquine

piperaquine

50

Artemisinin combos are standard of care for _______

uncomplicated falciparum in most areas

51

Artemisinin adverse effects

N/V/D

Dizziness

EMBRYOTOXIC in animal studies (not recommended for first trimester for uncomplicated malaria)

52

Malaria parasites ingest ____ from host cell

This is degraded into ___ and _____, which is toxic

Parasite also polymerizes it to _____,which is nontoxic

Hb

amino acids and heme

hemozoin

53

Chloroquine accumulates in _____ and inhibits _______

food vacuole

inhibits heme polymerization

54

Antimalarials generally inhibit _________

The detoxification of heme

55

4-substituted quinolines interfere with __________

 

Resistance is associated with lack of _________

Heme polymerization

 

Lack of accumulation in food vacuole

56

Hemozoin + Heme/quinoline complex -->

Capped polymer

57

Chloroquine

  • ROA?
  • Has a large_____
  • Initial/Terminal half-life?

Oral

Large volume of distribution

Initial = 3-5d

Terminal = 1-2d

58

Chloriquine (CQ) antimalarial effect is associated with...

T>MIC

59

CQ might cause ____ in pts of african descent

It is contraindicated for which 4 conditions?

prutitis

  1. psoriasis
  2. porphyria
  3. Retina/Visual field abnormalities
  4. Myopathy

60

_____ and ____ interfere with the absorption of CQ

Kaolin and antacids

61

Two possible mechanisms of CQ resistance

Primary = mutation in Pf-CRT1

(localized to food vacuole, causes reduced accumulation of CQ, no cross resistance to mefloquine or quinine)

 

Secondary = over-expression of Pf-MDR1

(drug transporter)

62

Quinine isolated from _______

bark of cinchona tree

63

Mechanism of Quinine is similar to _____

Chloroquine

64

Quinine's general catergory

Blood schizontiide

65

Quinine is the treatment of choice for...

  • Chloroquine resistant falciparum (quinine sulfate- oral)
  • Severe falciparum (IV only with concurrent cardiac monitoring)

66

Quinine dosing schedule for chemoprophylaxis?

N/A

Its short half life and higher toxicity make it an inappropriate option for chemoprophylaxis.

67

Quinine major adverse effect

Cinchonism

(tinnitus, headache, nauses, dizziness, flushing, visual disturb.)

68

Quinine may result in cell _____. Cause and Effects of this?

Cell hemolysis

-G6PD deficiency

-Blackwater fevere (hemoglobinuria)

69

Quinine DDI

May raise warfarin and digoxin levels 

Metabolized by CYP3A4

 

*** Severe HoTN***

70

Mefloquine effective against...

What's its use?

Effective against erythrocytic forms of falciparum and vivax

(Used for both prophylaxis and Rx)

71

Major Mefloquine side

Neuropsychiatric toxicity

72

Other chloroquine drugs

Lumefantrine

Piperaquine

Amodiaquine

Halofantrine

73

Primaquine metabolism

2D6 metabolism

Required for activity

74

Primaquine mechanism may involve ____

Free radicals

75

Primaquine is the drug of choice for _______

Liver stages (ACTIVELY GROWING and HYPNOZOITES)

Of Vivax and Ovale

 

*** Combo with Chloroquine

76

Primaquine is a _______ drug against ______

gametocidal

all four parasites

77

Contraindications for Primaquine

G6PD deficiency

Pregnancy/Breastfeeding

78

What compound has the same spectrum of activity and toxicity as Primaquine

Tafenoquine

79

Malarone is a combo of ______

proguanil and atavaquone

 

(atavaquone bad at monotherapy)

80

Malarone kills ______ stages, but not ______

liver and blood

NOT hypnozoites

81

Malarone is effective Tx for __________

uncomplicated malaria and chemoprophylaxis

82

Atavaquone is used to treat __________

Toxoplasma and P. jiroveci

83

Atavaquone is a _____ analog that is an inhibitor of ______

  • Ubiquitin
    • Electron acceptor for paraste dihydroorotate dehydrogenase
  • Cytochrome bc1

 

 

84

Atavaquone works synergisyically with ____

How?

Proguanil

Proguanil is converter to cycloguanil = an inhibitor of plasmodium dihydrofolate reductase-thymidylate synthetase (crucial for purine and pyrim. synthesis)

 

--> Enhances mitochondrial toxicity of atavaquone

85

Antibiotics as antimalarial drugs?

What do they target?

Tetracycline/ Doxycycline/ Clindamycin

--> Target Apicoplast

86

Doxy is paired with ___ or ____ for treatment of ________

Quinine/Quinidine

Falciparum

87

Doxy is also used for...

chemoprophylaxis in areas with high mefloquone resistance

88

Third most common food borne illness

Toxo

89

Toxo life cycle?

 

Transmission routes?

  • -sexual development in cat
  • -cysts develop in other mammals
    • Oocysts and tissue cysts --> tachyzoites --> neural/muscle --> Bradyzoites

 

Can be infected by eating raw meat (cysts) or from shedding from cats (oocysts)

90

DIagnostic stages of toxo (2)

  1. Serological diagnosis
  2. Direct ID of parasite from peripheral blood, amniotic fluid, or tissue section

91

Severe toxoplasmosis common with what diseases?

HIV/AIDS

Transplants

Chemotherapy

92

Congenital toxo occurs when?

First infection in mom

93

Drug treatment for toxo

First line = Pyrimethamine + Sulfadiazine

Alternatives: atavaquone or pentamidine