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BIOL3027 - Selective Toxicity > VJ - Antimalarials I > Flashcards

VJ - Antimalarials I Flashcards

1
Q
A
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2
Q

What is Malaria? (3)

A
  • Derived from Old Italian “mal aria” (bad air)
  • Caused by Plasmodium spp. via Anopheles mosquitoes
  • One of the “big three” killers (with HIV & TB)
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3
Q

What are the primary regions where malaria is endemic? (3)

A
  • Most of Africa
  • Half of South America
  • Parts of Southeast Asia
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4
Q

Why have malaria case reductions slowed since 2000? (3)

A
  • Funding and resource limitations
  • Resistance (mosquito and Plasmodium)
  • Impact of COVID-19
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5
Q

What is the name of the mosquito vector and how is it distributed?

A

Vector: Plasmodium transmitted by female Anopheles mosquitoes (~40 species linked to malaria).

Distribution: Widespread globally, especially in tropical/sub-tropical areas; common near stagnant water (mosquito breeding sites).

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6
Q

What is the transmission cycle of malaria? (3)

A
  1. Mosquito ingests parasite by feeding on an infected host.
  2. Parasite grows and replicates in the mosquito’s gut.
  3. Passed to new hosts (8-15 sporozoites) via subsequent bites.
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7
Q

What are 2 other transmission routes of malaria?

A
  • Blood transfusions, contaminated needles (rare).
  • Intra-uterine (mother to baby)
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8
Q

What are the five Plasmodium species that cause malaria?

A
  • P. falciparum (most severe, 90% of deaths)
  • P. vivax, P. ovale, P. malariae (milder forms)
  • P. knowlesi (zoonotic, affects monkeys and humans)
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9
Q

What are the main methods for malaria diagnosis? (3)

A
  • Microscopic examination with Giemsa/Wright stain
  • Antigen-capture (RDT)
  • PCR (LAMP) for strain detectiona
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10
Q

What factors influence susceptibility to malaria? (2)

A

Protection:

  • Genetic traits: Sickle Cell Disease (HbS), β-thalassemia, glucose-6-phosphate dehydrogenase deficiency
  • Lack of Duffy antigens on red blood cells (blocks Plasmodium entry)

Risk:

  • Pregnancy
  • Co-infections (e.g., HIV, helminths, COVID-19)
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11
Q

What is the life cycle of malaria? (7)

A
  1. Sporozoite Injection: Mosquito injects sporozoites into the bloodstream.
  2. Liver Stage: Sporozoites enter liver, where they reproduce asexually (~10 days, asymptomatic).
  3. Blood Stage: Merozoites are released into the blood, invade RBCs, reproduce asexually, and cause cells to burst—resulting in cyclic fever.
  4. Gametocyte Formation: Some merozoites become gametocytes, circulating in the blood.
  5. Mosquito Stage: Another mosquito ingests gametocytes, which mature into gametes and reproduce sexually.
  6. Oocyst Development: Form ookinetes that burrow into the mosquito gut wall, forming oocysts.
  7. Transmission Cycle: Oocysts burst, releasing sporozoites to the mosquito’s salivary glands, ready to infect a new host.
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12
Q

What is schizogony in the malaria parasite’s life cycle? (2)

A

Schizogony: Rapid asexual reproduction; a single P. vivax parasite can produce 250 million merozoites in 14 days

  • Drug Challenge: Antimalarial drugs must destroy at least 94% of parasites every 48 hours just to maintain equilibrium, as the parasite multiplies so quickly.
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13
Q

What are the main strategies to stop malaria? (7)

A
  1. Vector Control: Targeting mosquitoes through larvicides, insecticides, and nets.
  2. Genetics: Releasing genetically modified mosquitoes to reduce population.
  3. Transmission Prevention: Drugs that block the spread from infected individuals.
  4. Vaccination: Developing vaccines to prevent infection.
  5. Acute Treatment: Drugs to treat active infections.
  6. Radical Cure: Drugs to eliminate dormant liver forms (prevent relapse).
  7. Prophylaxis: Drugs to prevent infection in at-risk individuals.
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14
Q

What are vector control methods for malaria prevention? (4)

A

1) Targeting Larvae:

  • Use larvicides like Methoprene (hormone analogue) to prevent maturation.
  • Remove/cover standing water (e.g., drain swamps, use oil films) to eliminate breeding sites.

2) Targeting Adult Mosquitoes:

  • Apply insecticides and repellents.
  • Use long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS).

3) Sterile Insect Technique (SIT):

  • Release sterilized male mosquitoes to reduce population.

4) Incompatible Insect Technique (IIT):

  • Release males infected with Wolbachia bacteria to produce infertile offspring.
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15
Q

What are the pros and cons of using DDT and Pyrethrins for malaria control?

A

DDT:

  • Opens voltage-gated Na+ channels in insects, highly selective for mosquitoes.
  • Cons: Bio-accumulates in animals (t½ = 6-10 years), causing issues like eggshell thinning in predators (e.g., bald eagles). Restricted to vector control (Stockholm Convention 2004).

Pyrethrins:

  • Shorter half-life, safer alternative to DDT.
  • Cons: More costly than DDT.
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16
Q

How have mosquitoes developed resistance to insecticides (3), and what is a potential solution?

A

Resistance Issues: Mosquitoes have developed resistance via:

  • Enzyme upregulation (CYP450, GSTe2) to detoxify insecticides.
  • Mutations making sodium channels insensitive.
  • Thickened leg cuticle reducing insecticide uptake.

Solution: Combining CYP450 inhibitors with LLINs to enhance efficacy.

17
Q

What are the issues with current insecticides (2), and is there potential for better options?

A

Current Issues:

  • Resistance: Mosquitoes have developed resistance to many insecticide classes (e.g., neonicotinoids, carbamates, organophosphates).
  • Environmental Impact: Non-selective toxicity harms beneficial insects like pollinators (e.g., honeybees) and other animals.

Future Potential: Research aims to develop more selective and environmentally friendly insecticides to reduce resistance and minimize ecological damage.

18
Q

What are the steps involved in the Sterile Insect Technique (SIT)? (5)

A
  1. Mass Rearing: Mosquitoes are bred in special facilities.
  2. Separation and Sterilization: Male and female mosquitoes are separated, and ionizing radiation is used to sterilize the males.
  3. Release: Sterile male mosquitoes are released into towns or cities.
  4. Mating Competition: Released sterile males compete with wild males to mate with females.
  5. Infertile Eggs: Females that mate with sterile males lay infertile eggs, leading to a reduction in the mosquito population and decreased disease transmission.
19
Q

What is the Incompatible Insect Technique (IIT) and how does it work? (3)

A

IIT Overview: Males are infected with Wolbachia, a maternally inherited endosymbiotic bacteria.

Mechanism: When these Wolbachia-infected males mate with wild females that lack the same Wolbachia strain, the eggs are rendered infertile due to cytoplasmic incompatibility.

Combination with SIT: Trials combining SIT and IIT have shown success in eliminating mosquito populations

20
Q

What are genetic approaches to controlling mosquito populations (3), and what concerns do they raise?

A

Gene Drive Introduction:

  • Modified male mosquitoes are released with a gene drive that increases the likelihood of gene inheritance to 99%, rather than the typical 50/50.

CRISPR-Cas9 Utilization:

  • This technology is used to insert a defective doublesex gene in offspring, resulting in either infertile females or a population composed solely of males.

Field Trial Effectiveness:

  • These methods have shown promise in field trials for reducing mosquito populations.

Ethical Concerns:

  • The potential ecological impacts and ethical implications of releasing genetically modified organisms into the wild raise important questions about their use.
21
Q

What are the challenges in developing a malarial vaccine? (4)

A
  1. Species Specificity: It is unlikely that a single vaccine will be effective against all Plasmodium species.
  2. High Parasite Multiplication: A single parasite can multiply exponentially (10,000 to 40,000 times), making it difficult to generate enough antibodies to eliminate every sporozoite before they reach the liver.
  3. Immune Evasion: Parasites can hide within host cells, complicating the immune response.
  4. Lack of Investment: Malaria is often not a priority for Western pharmaceutical companies, affecting research and development.
22
Q

What are the pharmacological targets in malaria treatment? (4)

A

Sporozoites: Target the initial infective stage introduced by the mosquito.

Liver Forms: Address the hepatic stage where parasites multiply asymptomatically.

Blood Forms: Focus on the asexual reproduction phase occurring within red blood cells.

Gametocytes: Target the sexual stage to prevent transmission to mosquitoes and break the cycle.

23
Q

What are most vaccine efforts aimed at targeting?

A

Most vaccine efforts are aimed at targeting the infectious stage—specifically, the sporozoites introduced into the body by mosquito bites.

BIOL3027 - Selective Toxicity (17 decks)

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