Molecular biology of Plasmodium Falciparum (Module 5)
Lecture 1
Malaria is caused by Plasmodium infection
- Prevalent by still water
- Protozoan obligate parasites
1) Needs a host to survive
2) No repository of agent outside of the host like in dirt
- Vertebrate and insect hosts
- Apicoplast (phylum Apicomplexa)
- 4 species cause malaria in human
1) Plasmodium ovale
2) Plasmodium malariae
3) Plasmodium vivax - asia, latin america, africa
4) Plasmodium falciparum – sub-Saharan Africa
Plasmodium Falciparum
- Severe malaria
1) Responsible for most malaria related deaths globally
Plasmodium Vivax
- Moderate to severe illness, complicates rare, relapses
Global Distribution of Malaria
- Most of world except poles and very cold areas
- Mostly around equatorial belt
1) SE asia
2) Central Africa
§ Most incident cases
§ Most deaths
3) South America
- Endemic to 85 countries
- More than half a million deaths a year
- Young children <5 years old!! At risk!
Strategies to control and eliminate malaria
1. Vector control
a. Insecticide treated mosquito nets (ITNs)
b. Indoor residual spraying (IRS)
2. Chemoprevention
a. Intermittent preventative treatment in pregnancy (IPTp)
i. 2nd and 3rd trimester
b. Seasonal malaria chemoprevention (SMC)
i. Children 3-59 months
3. Case treatment
a. Artemisinin based combination therapy (ACT)
,Lecture 2: Plasmodium Falciparum Life Cycle
- Very complex lifecycle with many form changes
Transmission and liver stages
- Sporozoites (single cell organisms, elongated motile cells) are deposited under
the skin of the vertebrate host through the bite of an infected female anopheles
mosquito
1) Sporozoites = elongated, slightly curved cells
§ Glide in shallow curves on flat surfaces
§ Move to find blood vessels
• 20s for blood to circulate whole body
, - Liver = first entry point of infection after travel through blood stream after
sporozoites injected with saliva
1) Hepatocytes infected and parasitophorous vacuole (PV) and
dedi`erentiation of sporozoite into just a cell where it replicates the
genome without cell division (schizogony)
§ Extensive genome and organelle replication and segregation by
schizogony produces merozoites (tens of thousands)
- PV breaks down and merozoites are enclosed in vesicles (Merosome formation)
formed from host cell plasma membrane are released into liver sinusoids and
enter circulation
- Merosomes burst in the lung microvasculature to release individual merozoites
Hypnozoite
- Relapse à patient is infected, treated and then redevelops disease without a
bite and another infection
- Only in vivax/orale
- Dormancy can last months/years
- Relapses caused by hypnozoites can contribute to 80% of all vivax blood stage
infections
- Treatment with Primaquine to clear hypnozoites can cause severe hemolysis in
people with G6PD deficiency
, Merozoite RBC Invasion
Merozoites
- Egg shaped cells
- Non motile
- Generated by sporozoites in the liver of by
trophozoite division in red blood cells
- Begin the blood cycle:
1) Capture host cell
2) Reorientation, apical attachment +
tight junction formation
3) Formation of parasitophorous
vacuole, invasion through moving
tight junction
§ PV made of a volume between
parasite plasma membrane
and red blood cell plasma
membrane pulled over the
parasite
4) Sealing PV, discharge of dense
granules, expansion of vacuole
membrane
5) Transformation into ring stage
Blood/Erythrocytic cycle (48 hours)
Trophozoite
- Early trophozoite = ring form
- Trophic period à parasite enlarges
- Ingestion of erythrocyte cytoplasm and
proteolysis of hemoglobin
- Breakdown product of hemoglobin
(heme) converted to hemozoin (malarial
pigment)
Hemoglobin
- heterotetramer
- 95% erythrocyte protein
- 60-80% degraded during trophozoite stage
- Main source that parasite feeds on
- Has a prosthetic group called heme à has coordinated iron atom
- Allows for O2 binding
- Parasitemia = measure of infection during blood cycle
- At 20% parasitemia 110g protein are consumed in 48 hours
- Hemoglobin degradation occurs in the plasmodium food vacuole
- Releases the heme (toxic to cell in high concentrations)
Lecture 1
Malaria is caused by Plasmodium infection
- Prevalent by still water
- Protozoan obligate parasites
1) Needs a host to survive
2) No repository of agent outside of the host like in dirt
- Vertebrate and insect hosts
- Apicoplast (phylum Apicomplexa)
- 4 species cause malaria in human
1) Plasmodium ovale
2) Plasmodium malariae
3) Plasmodium vivax - asia, latin america, africa
4) Plasmodium falciparum – sub-Saharan Africa
Plasmodium Falciparum
- Severe malaria
1) Responsible for most malaria related deaths globally
Plasmodium Vivax
- Moderate to severe illness, complicates rare, relapses
Global Distribution of Malaria
- Most of world except poles and very cold areas
- Mostly around equatorial belt
1) SE asia
2) Central Africa
§ Most incident cases
§ Most deaths
3) South America
- Endemic to 85 countries
- More than half a million deaths a year
- Young children <5 years old!! At risk!
Strategies to control and eliminate malaria
1. Vector control
a. Insecticide treated mosquito nets (ITNs)
b. Indoor residual spraying (IRS)
2. Chemoprevention
a. Intermittent preventative treatment in pregnancy (IPTp)
i. 2nd and 3rd trimester
b. Seasonal malaria chemoprevention (SMC)
i. Children 3-59 months
3. Case treatment
a. Artemisinin based combination therapy (ACT)
,Lecture 2: Plasmodium Falciparum Life Cycle
- Very complex lifecycle with many form changes
Transmission and liver stages
- Sporozoites (single cell organisms, elongated motile cells) are deposited under
the skin of the vertebrate host through the bite of an infected female anopheles
mosquito
1) Sporozoites = elongated, slightly curved cells
§ Glide in shallow curves on flat surfaces
§ Move to find blood vessels
• 20s for blood to circulate whole body
, - Liver = first entry point of infection after travel through blood stream after
sporozoites injected with saliva
1) Hepatocytes infected and parasitophorous vacuole (PV) and
dedi`erentiation of sporozoite into just a cell where it replicates the
genome without cell division (schizogony)
§ Extensive genome and organelle replication and segregation by
schizogony produces merozoites (tens of thousands)
- PV breaks down and merozoites are enclosed in vesicles (Merosome formation)
formed from host cell plasma membrane are released into liver sinusoids and
enter circulation
- Merosomes burst in the lung microvasculature to release individual merozoites
Hypnozoite
- Relapse à patient is infected, treated and then redevelops disease without a
bite and another infection
- Only in vivax/orale
- Dormancy can last months/years
- Relapses caused by hypnozoites can contribute to 80% of all vivax blood stage
infections
- Treatment with Primaquine to clear hypnozoites can cause severe hemolysis in
people with G6PD deficiency
, Merozoite RBC Invasion
Merozoites
- Egg shaped cells
- Non motile
- Generated by sporozoites in the liver of by
trophozoite division in red blood cells
- Begin the blood cycle:
1) Capture host cell
2) Reorientation, apical attachment +
tight junction formation
3) Formation of parasitophorous
vacuole, invasion through moving
tight junction
§ PV made of a volume between
parasite plasma membrane
and red blood cell plasma
membrane pulled over the
parasite
4) Sealing PV, discharge of dense
granules, expansion of vacuole
membrane
5) Transformation into ring stage
Blood/Erythrocytic cycle (48 hours)
Trophozoite
- Early trophozoite = ring form
- Trophic period à parasite enlarges
- Ingestion of erythrocyte cytoplasm and
proteolysis of hemoglobin
- Breakdown product of hemoglobin
(heme) converted to hemozoin (malarial
pigment)
Hemoglobin
- heterotetramer
- 95% erythrocyte protein
- 60-80% degraded during trophozoite stage
- Main source that parasite feeds on
- Has a prosthetic group called heme à has coordinated iron atom
- Allows for O2 binding
- Parasitemia = measure of infection during blood cycle
- At 20% parasitemia 110g protein are consumed in 48 hours
- Hemoglobin degradation occurs in the plasmodium food vacuole
- Releases the heme (toxic to cell in high concentrations)
