Mosquitoes (Malaria)

Question 1

Types of plasmodium which cause malaria in humans:

Answer 1

P. falciparum 
P. vivax
P. malariae
P. ovale
P. knowlesi

Question 2

Infective stage of plasmodium parasite (for humans)

Answer 2

Sporozoite

Question 3

Why is P.vivax not present in West Africa?

Answer 3

High % (95) population are negative for erthyrocytic receptors called Duffy Antigen. Duffy antigen is proinflammatory chemokine receptor used by P. vivax (Langhi and Bordin, 2006).

Question 4

Diseases that confer malaria resistance

Answer 4

Sickle cell anaemia
Thalassemia
G6PD deficiency
- RBC more liley to die from oxidative stress when infected

Question 5

What happens in the first 1-2 weeks of infection by P. falciparum, P. malariae and P. knowlesi?

Answer 5

Multiply asexually and mature from sporozoites to merozoites in the liver.

Question 6

Where do the malaria parasite first go when they infect a human?

Answer 6

Hepatic sclerenchymal cells

Question 7

Does the liver stage have any outward symptoms?

Answer 7

No, asymptomatic.

Question 8

What happens in the months and years of initial infection by P. vivax and P. ovale?

Answer 8

Dormant hepatic stage = hypnozoites (don’t divide)

Wait then turn into merozoites.

Question 9

Preferred RBC targets for P. falciparum and P. ovale

Answer 9

red blood cells of all ages

Question 10

Preferred RBC targets for P. vivax

Answer 10

reticulocytes ( young and immature red blood cells)

Question 11

Preferred RBC targets for P. malariae and P. knowlesi

Answer 11

older red blood cells

Question 12

Stages of th erythrocytic phase

Answer 12

Early trophozoite (ring)
Late trophozoite
Shizont (merozoites inside)
Rupture schizont (releases merozoites)

Question 13

What does the rupturing of the shizont cause?

Answer 13

Release of inflammatory cytokines
-> temperature spikes (fevers)
Extreme fatigue 
Headaches
Jaundice 
Abnormally enlarged spleen (splenomegaly)

Question 14

Sexual reproduction stages

Answer 14

Human
Early trophozoite -> gametogony
Taken up by mosquito in blood meal
Travel to gut - mature and fuse into zygote
Ookinete
Oocyst - ruptures and releases sporozoites

Question 15

What are fever paroxyms?

Answer 15

The pattern of fever occurrence, e.g. every 24hrs.

Question 16

What are the different fever paroxysms of the species of malaria that infect humans?

Answer 16

P. malariae = 72hrs
P. vivax ad P. ovale = 48hrs
P. knowlesi = 24hrs
P. falciparum = variable (24/48 hrs)

Question 17

How do malaria parasites get into the mosquito gut?

Answer 17

Uses chitinases to burst into gut

Question 18

How can mosquitos defend agains plasmodium?

Answer 18

Encapsulate oocysts

Question 19

Why do wild-type mosquitoes not encapsulate?

Answer 19

The energetic expense of encapsulating oocysts is greater than the fitness cost of being infected.

Question 20

What is the time bomb theory?

Answer 20

Parasite is too fast for mosquito immune system.

Question 21

What does Plasmodium use to travel through cells quickly?

Answer 21

subtilisin2 (protease)

Question 22

What is the formula for the Ross-MacDonald model for malaria transmission?

Answer 22

Ro = (m.a^2.p^n.b)/(-rln(p))

Question 23

What do the letters stands for in this formula: Ro = (m.a^2.p^n.b)/(-rln(p))?

Answer 23

m = bites per person per night 
a = probability of mosquito to take human meal
p = daily mosquito survival rate
n = Number of days to complete mosquito lifecycle
b = susceptibility to infection human/mosquito
r = rate of recovery of infected humans

Question 24

What are the assumptions of the Ross-MacDonald model for malaria transmission?

Answer 24

no host immunity (humans)
mosquitoes bite at random
humans and mosquito populations homogenous

Question 25

Ways to sample mosquitoes (7)

Answer 25

``` Tent trap Biting catch Plant catch Light trap Resting catch Exit catch Spray catch ```

Question 26

What is exflagellation?

Answer 26

Gametocyte bursts to release microgametocytes.

Question 27

What triggers exflagellation?

Answer 27

Drop in temperature Drop in [CO2] Increase in pH Presence of xanthurenic acid (broaden pH range exflagellation will occur in)

Question 28

Why does P. falciparum cause the worst infections? | short answer

Answer 28

Puts sticky protein coat on infected blood cells - > clumping of RBCs - > blocking of blood vessels

Question 29

What are the complications of P. falciparum?

Answer 29

haemolytic anaemia + ischemic damage ``` Cerebral malaria Bilious malaria (liver) Lungs + Kidneys + Spleen = sepsis-like symptoms ```

Question 30

What can cerebral malaria cause?

Answer 30

Seizures Coma Altered mental state

Question 31

What can bilious malaria cause?

Answer 31

diarrhoea vomitting jaundic liver failure

Question 32

Diagnosis of malaria

Answer 32

``` Blood smear Low platelet count Elevated lactate dehydrogenase Normochromic and normocytic anaemia PCR Fever pattern (paroxysms) ```

Question 33

What are the two types of blood smear and what do they show?

Answer 33

Thick blood smear - % of infection (parasite in RBCs) | Thin blood cells - species identification

Question 34

What is normochromic and normocytic anaemia?

Answer 34

Normal colour, normal size, low red blood cells

Question 35

What causes elevated lactate dehydrogenase in malaria sufferers?

Answer 35

Haemolysis (RBCs)

Question 36

Types of recurrent malaria

Answer 36

Recrudescence Relapse Reinfection

Question 37

What is recrudescence?

Answer 37

The recurrence of malaria in an individual due to ineffective treatment.

Question 38

What is relapse (in terms of malaria infection)?

Answer 38

The recurrence of malaria in an individual due to treatment killing merozoites, but live hypnozoites remaining in the liver.

Question 39

What is reinfection?

Answer 39

The recurrence of malaria in an individual after effective treatment due to a new infection (no immunity).

Question 40

Methods for prevention of infection (mosquito focus)

Answer 40

Full body clothing Insecticide-covered mosquito nets Indoor insecticide spray Empty stagnant water

Question 41

Why does P. falciparum cause RBCs to clump? (survival)

Answer 41

With other species, the spleen destroys most infected RBCs. By clumping and blocking blood vessels, it prevents infected cells from going to the spleen.

Question 42

Two scientific options for malaria control

Answer 42

Monoclonal anitbodies | Knocking out genes (in mosquito)

Question 43

Current available malaria treatment (humans)

Answer 43

Suppressive treatment/chemo prophylaxis Radical treatment Therapeutic treatment

Question 44

What is the name of the protein which makes read blood cells sticky in P. falciparum infection?

Answer 44

PfEMP1 (Plasmdium falciparum erythrocyte membrane protein 1) - blood group O only RIFINs to form rosettes with group A RBCs?? (Goel et al., 2015)

Question 45

How does P. falciparum avoid antibodies?

Answer 45

Changes sticky membrane protein on outside of infected cells (e.g. PfEMP1 - blood group O only (Goel et al., 2015))

Question 46

What is red blood cell rosetting?

Answer 46

the formation of clusters in which uninfected red blood cells (RBCs) aggregate around a central Plasmodium falciparum-infected RBC (iRBC) - because of stickiness?

Question 47

Possible targets for future treatment research

Answer 47

Merozoite surface protein 1 Enzymes for entry of gametcytes into mosquito gut - allosamidin (inibits chitinases) Adhesion to midgut of mosquito (basal lamina) Enzyme for cutting through cells rapidly (subtilisin2 (protease))