Lecture 21 Learning Objectives

Identify major regions that are endemic with malaria

Sub-Saharan Africa, South America, South Asia

Explain how vector distribution effects transmission

Some vectors no longer carry malaria, so those places don't have high malaria rates

Define vectorial capacity

Daily rate at which new infections arise from a currently infectious case

Identify vector with highest vectorial capacity

An. gambiae

Explain EIR, the factors that define it and how it relates to transmissibility

EIR (Entomologic Inoculation Rate) estimates how often people are bitten by infectious mosquitoes. It reflects transmission intensity & is closely tied to vectorial capacity.

Key factors: mosquito population density; % of female mosquitoes infected; # of infected mosquitoes feeding on a person in a unit of time

Describe the current vector control efforts used to reduce EIR

Indoor Residual Spraying (IRS): applied to walls & surfaces to kill them;

spray has some health/environmental risk;

insecticide treated nets (b/c they feed at night)

Explain the mechanism of action of pyrethroids

Insecticide that is sprayed on walls/surfaces/nets

Explain the mechanisms of pyrethroid resistance

Target site changes: pyrethroids target Na+ channels in mosquitoes; insecticide keeps the channel open, so it can kill; A.A. mutations close the channel.

Metabolic resistance: mosquitoes increase activity of detoxifying enzymes, specifically cytochrome 450; cytochrome 450 can contribute to metabolic resistance

Describe how chloroquine kills malaria parasites and explain how resistance reduced its effectiveness

Targets blood stage of parasite; chloroquine blocks the detoxification of hemazin into hemozoin. heme is produced

Heme accumulates & kills the parasite;

resistance is due to changes in transporter protein (pumps chloroquine out)

Explain the mechanism of action of artemisinin and why artemisinin-based combination therapies (ACTs) are the current standard treatment for uncomplicated P. falciparum malaria

Activated during parasite digestion of Hb inside RBCs;

rapidly reduces blood-stage parasite numbers;

rapid clearance & monotherapy is strongly discouraged

Explain why combinational therapy is more effective at preventing resistance

Artemisinin is combined w/ another drug b/c it's fast-acting but short lived. Small # of parasites could survive after artemisinin levels fall off & a 2nd longer-acting drug eliminates remaining parasites