1. Plasmodium falciparum 2. Plasmodium vivax 3. Plasmodium ovale 4. Plasmodium malariae 5. Plasmodium knowlesi

Mosquito species that transmits malaria (30-40 species) Only females transmit disease (needs blood for eggs) Males only eat sugar to survive

(Section D: Other Infectious Agents) Lecture 27 Flashcards by Lucky Cat

Malaria
* Source
* Cases
* Deaths

Infected mosquitoes
~249 million cases
608,000 deaths (2012)

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What is the majority of cases malaria in?

Children under age of 5

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Plasmodium
* Motility
* Type of parasite
* Hosts

Apicomplexa
Obligate parasite
2 hosts (vertebrate and arthropod)

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What type of hosts are vertebrates and arthropods for Plasmodium?

Vertebrate: Intermediate host (asexual reproduction)
Arthropod: Definitive host (sexual reproduction)

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Plasmodium species

Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi

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Plasmodium falciparum

Deadly to humans
* 48 hour cycles of fever

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Plasmodium vivax

48 hours fever cycle
* Similar to Plasmodium ovale but differ in blood group

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Plasmodium ovale

48 hour fever cycle

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Plasmodium malariae

Long term illness
* 72 hour fever cycle

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What is the 48 hour fever cycle known as?

Tertian Cycle

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Plasmodium knowlesi

Zoonotic (comes from animals)
* 24 hour fever cycle

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Anopheles

Mosquito species that transmits malaria (30-40 species)
Only females transmit disease (needs blood for eggs)
Males only eat sugar to survive

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Anopheles
* Anatomy

(7)

Proboscis
Salivary glands and duct
Dorsal Diverticulum
Crop
Anterior midgut junction
Stomach
Malphighian tubule

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Proboscis

To pierce and bite

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What function does the saliva of mosquitoes do?

Serves to numb the bite site and anticoagulant

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Dorsal Diverticulum and Crop

Store and digest sugar

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Anterior midgut junction

Separates sugar and blood meals

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Stomach

For the blood meals

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Malpigion tubules

Serves as kidneys

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Do mosquitoes have a closed circulatory system?

No
* Hemolymph is circulatory fluid that encloses all the organs

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Plasmodium Life Cycle
* Mosquito

Biting infected organism + Getting blood meal
Fertilization + Form zygote (diploid)
Ookinete (tetraploid + motile)
Sporogony (creates sporozoites)
Cyst ruptures (sporozoites go to salivary glands via hemolymph)

Plasmodium Life Cycle (mosquito)
* What does mosquito pick up when it bites an infected host?

Gametocytes
* Male - Microgametocytes
* Female - Macrogametocytes

Plasmodium Life Cycle (mosquito)
* How does fertilization occur?

Male gametocytes undergo exflagellation (matures, release sperm)
Fertilizes female gametocytes
Forms zygotes (diploid)

Plasmodium Life Cycle (mosquito)
* What happens to ookinetes?

Forms in the stomach of the mosquito
* Moves through the epithelium to wall of stomach
* Ookinetes - Tetraploid

Plasmodium Life Cycle (mosquito) * What is sporogyny?

Asexual reproduction * Happens when oocyst form * Haploid stage (NOT TETRAPLOID) * Creates haploid sporozoites

Plasmodium Life Cycle (mosquito) * What happens when oocysts rupture?

Releases sporozoites in hemolymph * Travels to the salivary glands/ducts

Plasmodium Life Cycle * Humans

1. Infected mosquitoes bite + inject (sporozoites) 2. Infiltrates liver cells (becomes cryptozoites) 3. Asexual reproduction + Hepatocyte rupture (merozoites are released) 4. Invade RBCs (Early Trophozoite to Trophozoite) 5. Schizogony in RBCs (asexual reproduction) + Rupture (releases merozoites) 6. Some merozoites become gametocytes

Plasmodium Life Cycle (humans) * Where do sporozoites hide in the body?

In the liver cells (hepatocytes)

Plasmodium Life Cycle (humans) * Are cryptozoites infective? * What do cryptozoites do?

* No they are non-infective; they are just sporozoites in the liver cells * Divide asexually (similar to binary fission)

Plasmodium Life Cycle (humans) * What is schizogony?

A form of cell division similar to binary fission but no cytokinesis occurs (a bunch of divided cells bunched together) * Forms a **schizont**

Plasmodium Life Cycle (humans) * What is the early trophozoite form like?

Ring form

Plasmodium Life Cycle (humans) * Where do trophozoites occur?

Occur in RBCs when early trophozoites mature in the RBCs

Plasmodium Life Cycle (humans) * How do trophozoites affect RBCs?

Cytoadhesion * Make the RBCs sticky

Plasmodium Life Cycle (humans) * What cells do mosquitoes take up when they take a blood meal?

Both gametocytes and merozoites

Plasmodium Life Cycle (humans) * What do merozoites do in the mosquitoes that take them up?

Nothing, only the gametocytes will continue reproduction in mosquitoes

Signs/Symptoms of Malaria

* Flu-like symptoms * Other signs

Diploid and Haploid lifecycle stages of Plasmodium

* Haploid most of the time * Diploid/Tetraploid in mosquito for short time

Diagnosis of Malaria

* Microscopy of blood smear * PCR with different genes * Rapid testing

What forms of transmission can occur with malaria?

* Vertical transmission (mother to child) * Blood infection (through blood transplants) * Liver infections

Survival and Pathogenesis of Malaria

Host invasion * Hides * Invades (get nutrients) Immune evasion * Antigenic variation * Intracellular hiding Toxins

What is the mechanism for toxins released by malaria?

Free heme groupo is toxic to cells * Stacked heme groups are released during destruction of RBCs * Known as **hemozoins**

What are the steps of malaria treatment?

1. Identify species 2. Clinical status of patient (pregnant, HIV positive etc.) 3. Drug susceptibility 4. Previous use of antimalarials (e.x. Chemoprophylaxis)

What drugs are used for treating malaria?

1. **Artemisimin**: Creates free radicals that are toxic to Plasmodium 2. **Chloroquine**: Preventing heme groups from forming hemozoin

Which drug is malaria resistant against?

Chloroquine

Why is eradication of Plasmodium difficult?

1. Costly 2. Damages environment 3. Plasmodium is good at immune evasion

Sickle Cell Anemia * Genetics * Carrier vs. Affected * Mutation

* Autosomal recessive * Carriers are heterozygous and affected are homozygous * Point mutation (AT switch) that makes valine instead of glutamate

What does the point mutation in Sickle Cell Anemia result in?

Beta subunit mutation * When the hemoglobin is deoxygenated, forms fibers

What advantage does sickle cell anemia impart against malaria?

Prevents malaria from: 1. Invading (the fibers make invading hard) 2. Using heme (the heme structure is mutated, making it not usable) 3. Surviving long term (mutated RBCs are degraded by the body, along with the Plasmodium)

Prevention of Malaria Infection

* Vector control * Insecticide nets * Case managing * Inside residual spraying * Prophylaxis * Vaccines for children

What does malaria vaccine do?

1. Targets sporozoites 2. Prevent liver infection