16 Treatment for malaria

Question 1

Treatment guides

Answer 1

Plasmodium species: progression and severity of symptoms, treatment for dormant hypnozoites
Patient status: oral treatment (uncomplicated malaria), parenteral treatment (severe malaria)
Drug susceptibility

Question 2

Heme accumulation MOA

Answer 2

Accumulation of toxic heme in infected erythrocyte
Toxic heme is normally converted by plasmodium into non-toxic hemozoin
Anti-malarial activity: prevent fusion of interaction between food vacuole with heme

Stage: early to middle stages of erythrocytic cycle (young trophozoite stage/ring stage)

Question 3

H2O2/free radical formation MOA

Answer 3

Direct killing of plasmodium via production of H2O2/free radicals in cytoplasm

Question 4

Blocking of protein/folic acid synthesis MOA

Answer 4

Inhibits protein/folic acid synthesis for cell division (S/M phases)

Stage: late stages of erythrocytic cycle (schizont)

Question 5

Interference of the ETC MOA

Answer 5

Not understood

Question 6

Main targets

Answer 6

Hyponozoites: liver stages of P vivax and P ovale, can be dormant for 3-45 weeks
Ring stage: early trophozoite stage, before malaria is evident
Trophozoite: mid-trophozoite stage, parasite growing within host RBC from ring stage to before nuclear division
Schizont: late trophozoite stage (mature malaria parasite in host liver cells/RBC undergoing nuclear division)
Gametocyte: sexual stages

Question 7

Mechanisms of action

Answer 7

Quines: heme accumulation (except primaquine [H2O2 formation])
Artemisinin: free radical formation
Atovaquone-proguanil: interference of ETC
Antibiotics: blocks protein synthesis/folic acid synthesis

Question 8

Target life cycle stages

Answer 8

Quines: RT(g) = ring and trophozoite stages, gametocytes = secondary (except mefloquine)
Primaquine: HGb = hypnozoites, gametocytes, blood stages (ring, trophozoite, schizont)
Artemisinins: RSgt = (blood stages) ring, schizont, gametocytes, trophozoites
Antibiotics: TS = schizont, trophozoite

Question 9

Indications for uncomplicated malaria

Answer 9

First line drug: chloroquine (resistant) -> artemether-lumefantrine combination
Artemisinin-based combination therapy

Question 10

Indications for severe malaria

Answer 10

Quinine via IV/IM

Question 11

Indications for prophylaxis

Answer 11

1 Doxycycline: 1 week before and 4 weeks after
Mefloquine: 1 week before and 2-3 weeks after
Atovaquone-proguanil
Chloroquine

Question 12

Side effects and contradicitons

Answer 12

Hypersensitivity (allergy)
heart problems (quinine = QT prolongation)
G6PD deficiency (quine drugs)