Chemotherapy of Malaria

Question 1

malaria

Answer 1

infectious disease from protozoa of the genus plasmodium. transmitted by the bite of the female Anopheles mosquito.

Question 2

most lethal form of malaria?

Answer 2

P. falciparum. most resistance to major drugs too

Question 3

clinical signs of malaria

Answer 3

periodic episodes of chills and fever. usually enlarged spleen and liver. identified parasites in blood smears

Question 4

treatment of malaria

Answer 4

prophylaxis, treatment of acute attack, radical cure

Question 5

4 quinoline derivatives

Answer 5

quinine, chloroquine, mefloquine, primaquine

Question 6

PfCRT mutations

Answer 6

mutations in this allow the parasite to expel drugs, reducing the effect!! this is bad!!!!!!

Question 7

mechanism of quinoline drugs

Answer 7

accumulate in parasite’s food vacuoles and disrupt heme polymerization to hemozoin, causing oxidative damage to membranes and digestive proteases

Question 8

chloroguanide mechanism

Answer 8

inhibits dihydrofolate reductase

Question 9

atovaquone mechanism

Answer 9

depolarizes parasitic mitochondria and inhibits their electron transport.

Question 10

name two artemisinin compounds

Answer 10

artemether and artesunate

Question 11

artemisinin compound mechanism

Answer 11

inhibits Ca2+ ATPase (SERCA) by pretending to be thapsigargin. inhibit the SERCA of P. falciparum.

Question 12

primaquine mechanism

Answer 12

inhibits exoerythrocitic schyzogony. oxidizes schizont membranes. used for prophylaxis and prevention of relapses

Question 13

chemoprophylaxis in a chloroquine sensitive zone

Answer 13

chloroquine

Question 14

chemoprophylaxis in a chloroquine resistant zone

Answer 14

mefloquine, doxycycline, atovaquone/proguanil

Question 15

chemoprophylaxis in mefloquine resistant zone

Answer 15

doxycycline, atovaquone/proguanil

Question 16

terminal prophylaxis

Answer 16

primaquine

Question 17

mechanism for RTS,S/AS02A vaccine

Answer 17

targets pre-erythrocytic stages of P falciparum. strong humoral immune response against surface exposed sporozoite proteins. vacciine should also elicit CD8 and CD4 T cell types to get rid of infected liver cells

Question 18

treatment of severe malaria

Answer 18

IV quinidine plus antibiotic. IV artesunate followed by atovaquone, mefloquine, or doxycycline. Exhange blood transfusion

Question 19

treatment of uncomplicated malaria: chloroquine sensitive strains (falciparum, malariae, knowlesi)

Answer 19

cholorquine. alternative: hydroxychloroquine

Question 20

treatment of chloroquine sensitive strains (vivax, ovale)

Answer 20

chloroquine and primaquine. alternative: hydroxychloroquine and primaquine

Question 21

treatment of chloroquine resistant falciparum

Answer 21

atovaquone. alternatives: artemether, quinine + doxycycline (or clindomycin on kids under 8), mefloquine.

Question 22

treatment of chloroquine resistant vivax

Answer 22

quinine + doxycycline or tetracycline + primaquine. alt: atovaquone + primaquine. Mefloquine + primaquine

Question 23

radical cure!

Answer 23

for eradication of persistant exoerythrocytic parasites, use primaquine phosphate!

Question 24

new developments

Answer 24

sequencing falciparum genome. sequencing mosquito genome