23 - Antiprotozoals & Malaria

Question 1

Distributional selectivity

Answer 1

A drug equally toxic to host and parasite is useful if parasiting cell is exposed to a higher concentration than the host cell

Question 2

Distributional selectivity can be achieved by…

Answer 2

• Selective distribution
• Selective accumulation by the parasite
• Selective administration

Question 3

4 types of protozoal infections

Answer 3

Sporozoa, flagellates, ciliates and amoeba

Question 4

The most common protozoal infections are _______, such as ________.

Answer 4

The most common protozoal infections are sporozoa, such as malaria.

Question 5

Leishmania is caused by which class of protozoa?

Answer 5

Flagellates

Question 6

Malaria is a sporozoa parasite of which genus?

Answer 6

Plasmodium

Question 7

Symptoms of malaria include…

Answer 7

Fever, pain, convulsions (which can lead to coma and death)

Question 8

Name the 4 types of malaria and state their severity…

Answer 8

• P. falciparum - severe
• P. vivax - mild to severe
• P. ovale - mild
• P. malarie - mild

Question 9

Which types of malaria can lie dormant?

a) falciparum
b) vivax and falciparum
c) ovale and vivax
d) malarie
e) all four types

Answer 9

Which types of malaria can lie dormant?

a) falciparum
b) vivax and falciparum

c) ovale and vivax

d) malarie
e) all four types

Question 10

P. vivax and P. ovale malaria can lie dormant with possibility of relapse. This dormant state is also known as…

Answer 10

hypnozoite

Question 11

The lifecycle of the malaria parasite corresponds to the cycle of…

Answer 11

Symptoms

Question 12

Outline the lifecycle of the malarial parasite (Plasmodium) (8)…

Answer 12

1. Sporozoites enter capillary via female mosquito
2. Liver cell entry
3. Liver cell rupture, release of merozoites
4. RBC penetration
5. Asexual reproduction
6. Rupture of RBCs
7. Development into gametocytes
8. Uptake by mosquito during blood meal

Question 13

Malarial parasites require treatment with a drug with very high activity because of their…

Answer 13

High replication rate

Question 14

A drug with 94% activity against plasmodium results in:

a) slight decrease in numbers
b) significant decrease in numbers
c) stasis in numbers
d) slower increase in numbers

Answer 14

A drug with 94% activity against plasmodium results in:

a) slight decrease in numbers
b) significant decrease in numbers

c) stasis in numbers

d) slower increase in numbers

So to eliminate plasmodium, drug activity >>94% required

Question 15

Treatment for malaria can be divided into prevention and drug therapies. Describe 3 methods of prevention…

Answer 15

• Insect repellent
• Mosquito nets
• Covering skin

Question 16

Drug cures for malaria can be divided into 3 categories…

Answer 16

• Clinical cures (no significant symptoms)
• Radical cures (complete)
• Prophylaxis (preventative)

Question 17

Name the 5 classes of antimalarial drugs…

Answer 17

1. 4-Aminoquinolones
2. Quinoline-methanols
3. 8-Aminoquinolones
4. Antifolates
5. Hydroxynaphthonquinone

Question 18

An example of a 4-aminoquinolone is chloroquine…

Answer 18

• Accumulates in parasite lysosomes
• Inhibits digestion of Hb/ free haem conversion
• Oral administration
• Well absorbed with few side effects
• BUT resistance issues (must be combined w/ other drugs)

Question 19

Examples of quinoline-methanosl are quinine and mefloquine…

Answer 19

• may intercalate with malarial DNA
• works against erythrocytic forms
• Oral administration w/ rapid metabolism
• 30 day t1/2
• Quinine has higher side effects

Question 20

An example of an 8-aminoquinoline is primaquine…

Answer 20

• Radical cure for exoerythrocytic forms
• Kills gametocytes
• Metabolised by liver to quinoline (quinine derivative cytoxic to host and parasite)
• Used after curing clinical symptoms
• Causes haemolytic anaemia in patients with G6PDH deficiency :-(

Question 21

An example of an antifolate is proguanil…

Answer 21

• Dihydrofolate reductase inhibitor
  
  • Inhibits DNA synthesis
• Resistance issues
  
  • Co-administered with atovaquone

Question 22

An example of a hydroxynaphthoquinone is atovaquone…

Answer 22

• Inhibits mitochondrial electron transport chain in parasites
• Co-administered with proguanil (antifolate)
• Used for prophylaxis in areas with resistant strains

Question 23

A new treatment for malaria is ACT, which stands for…

Answer 23

Artemisinin-based Combination Therapy

Question 24

Malarial resistance is the result of…

Answer 24

Monotherapy drug use

Question 25

Key targets of malarial resistance…

Answer 25

• Plasmodial (Pf) transporter gene
  
  • Chloroquine resistance (CR)
  • Multidrug resistance (mdr1)
• P. falciparium Na+/H+ exchanger
• Folate biosythesis
• Cytochrome bc1 complex

Question 26

Mutation in which malarial gene is responsible for chloroquine resistance?

Answer 26

Plasmodial (Pf) transporter gene

Question 27

Name 3 antigens present on the malarial parasite (there are many more)…

Answer 27

• Histidine-rich protein 2 (HRP-2)
• Plasmodium lactate dehydrogenase (pLDH)
• Aldolase

Antibodies to these proteins key to aquired immunity, corresponding to high serum prevalence of IgG

Question 28

Which method of early detection is more cost and time effective than microscopy lateral flow ‘immuno-chromatographic’ antigen-detection tests…

Answer 28

Rapid diagnostic tests (RDTs)