21) Case Study : Malaria

Question 1

What are the 2 approaches to find medicinal plants

Answer 1

1) Random search = plants from a specific region are collected and screened, this method has consistently low success rates.
2) Targeted search = plants are selected using specific scientific clues, so success is usually higher.

Question 2

What are the 3 types of targeted searches

Answer 2

•Phylogenetic surveys = collect plants closely related to species already known to produce useful compounds
•Ecological surveys = select plants from specific habitats or with useful traits e.g. plants resistant to insect predation may produce defensive chemicals with medicinal value
• Ethnobotanical surveys = study plants used in traditional medicine by indigenous peoples, especially for specific diseases, often gives positive results

Question 3

What’s the name of the most common & dangerous species responsible for malaria

Answer 3

Plasmodium falciparum

Question 4

Describe the malaria life cycle

Answer 4

1) Mosquito → human (infective stage). An infected female Anopheles mosquito bites a human, It injects sporozoites in its saliva, Sporozoites travel quickly to the liver.
2) Liver stage - Sporozoites enter hepatocytes, They multiply and form schizonts. Liver cells rupture and release merozoites into the blood
3) Blood stage (causes symptoms) - Merozoites infect red blood cells, the RBCs eventually burst and release more merozoites. This repeating cycle causes the periodic fever attacks of malaria

Question 5

What’s the basic pathogenesis of cerebral falciparum malaria

Answer 5

•In Malaria caused by P. falciparum, infected red blood cells become sticky
•They stick inside the small blood vessels of the brain = This blocks blood flow = Less oxygen and glucose reach brain tissue = Brain cells become damaged
•This causes: severe headache, confusion, seizures & coma
The blockage and lack of oxygen make it very dangerous and can quickly become fatal.

Question 6

What drug was initially used to treat malaria and what was used after that & why

Answer 6

Initially quinine ( + chloroquine) but this quickly developed resistance and stopped being effective so during the Chinese war the Chinese discovered Artemisinin

Question 7

How does artemisinin kills the malaria parasite (Mode of action)

Answer 7

Artemisinin contains a special endoperoxide bridge (an O–O bond), which is essential for activity. Inside the malaria parasite, hemoglobin is broken down, releasing heme iron (Fe²⁺). This iron reacts with artemisinin and breaks the peroxide bridge, activating the drug = forms highly reactive carbon-centred free radicals. These radicals then covalently bind (alkylate) important parasite proteins, lipids, and sometimes heme itself, damaging vital cell functions such as metabolism and protein synthesis. Because these proteins stop working = the parasite quickly dies.

Question 8

Can artemisinin be used as monotherapy

Answer 8

Artemisinin monotherapy is avoided because its short half-life may allow surviving Plasmodium falciparum parasites to regrow, causing recrudescence; therefore it is combined with a longer-acting partner drug in ACTs (artemisinin-based combination therapy)

Question 9

What makes monotherapy of artemisinin dangerous

Answer 9

Artemisinin resistance in P. falciparum is linked to mutations in the pfkelch13 (K13) propeller gene. These mutations cause delayed parasite clearance, meaning the parasites are killed more slowly after treatment. Because artemisinin is cleared from plasma very quickly, using it alone means resistant parasites can survive once drug levels drop, leading to recrudescence and treatment failure. So resistance is the main reason monotherapy is dangerous.

Question 10

What’s ACT

Answer 10

ACT = Artemisinin-based Combination Therapy, The “C” = Combination. It means:
• a fast-acting artemisinin derivative
• plus a long-acting companion drug from a different class
The artemisinin kills parasites rapidly at the start, while the companion drug stays in the blood much longer and kills the remaining parasites. That long tail of drug exposure is what helps prevent recrudescence and slows resistance development.

Question 11

ACT examples

Answer 11

Artemisinin part, These are the fast killers:
• artemether → lipophilic
• artesunate → hydrophilic
• dihydroartemisinin → active metabolite
Companion drugs= these are the long-acting partners that remain to kill the leftover parasite after artemisinin is cleared
• lumefantrine
• mefloquine
• amodiaquine

Question 12

What is a co-formulated tablet & why is it necessary

Answer 12

A co-formulated tablet means both drugs are in one tablet.
This is important because patients are forced to take both drugs together, reducing the chance of accidentally taking only artemisinin and promoting resistance.