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Infection and Immunity > Malaria > Flashcards

Malaria Flashcards

1
Q

How many cases of malaria are in the world?

A

300-500 million cases per year

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2
Q

How much of the population is exposed to malaria?

A

40% of the global population

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3
Q

How many deaths are caused by malaria?

A

1.5-2.4 million deaths per year, 90% of them in Africa

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4
Q

What age group are most fatalities for malaria?

A

85% occur in children less than 5 years

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5
Q

How many cases of malaria is there in the UK?

A

Approx 2,000 cases per year

About 7 deaths

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6
Q

How many children are affected by malaria in Africa?

A

20% all childhood deaths in Africa are due to malaria

An African child has on average between 1.6 and 5.4 episodes of malaria fever each

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7
Q

Which species causes malaria?

A

Female mosquitos

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8
Q

Where are the current risk areas for contracting malaria?

A

Geographically

  • Tropics
  • Sub-tropics
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9
Q

What is the most dangerous form of malaria?

A

P.vivax

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10
Q

What are the types of infective malaria?

A

Human
Chimpanzee
Gorilla

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11
Q

What are the stages of the human malaria cycle?

A

Sporozoites infect liver cells
Sporozoites mature into schizonts , which rupture and release merozoites .
After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ).
Merozoites infect red blood cells .
The ring stage trophozoites mature into schizonts, which rupture releasing merozoites .
Some parasites differentiate into sexual erythrocytic stages (gametocytes)

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12
Q

What is the blood stage in malaria responsible for?

A

Clinical manifestations of the disease

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13
Q

What is the mosquito stages of malaria?

A

The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal .
The parasites’ multiplication in the mosquito is known as the sporogonic cycle .
While in the mosquito’s stomach, the microgametes penetrate the macrogametes generating zygotes .
The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts .
The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito’s salivary glands. Inoculation of the sporozoite

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14
Q

What are the characteristic symptoms of malaria?

A

Characteristic high fever

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15
Q

How is the fever in malaria caused?

A

Red blood cell full of haemoglobin- haem is toxic, parasites packs that haem in toxin, this is called haemozoin
Malaria pigment- haemozoin- haem and histidine-rich protein

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16
Q

What parasite causes cerebral malaria?

A

Plasmodium falciparum

17
Q

What does cerebral malaria do?

A

Sequestration of infected red cells in brain

Coma –> Death

18
Q

What are the main species of parasites causing malaria?

A 
Plasmodium vivax
Plasmodium ovale
Plasmodium falciparum
Plasmodium malariae
Plasmodium knowlsi
Malignant tertian malaria
Benign tertian malaria
Benign quartan malaria
19
Q

What is the rate of change in P. falciparum?

A

Roughly 1-2% per division

20
Q

How many variants of P.falciparum is there?

A

40-50 variant genes per clone of the parasite

>1,000 parasite population

21
Q

What are VAR genes?

A

Pfemp1 family of proteins inserted into surface of red blood cells

22
Q

What are VAR genes for?

A

Double function

Variant antigen for immune evasion and adhesion to endothelial cells of capillaries

23
Q

Are brain Pfemp1 proteins specific?

A

Most pfemp1 proteins are specific in the brain

24
Q

Are placenta Pfemp1 proteins specific?

A

Only 1 or 2

25
Q

What do brain Pfemp1 proteins bind to?

A

ICAM-1
VCAM-1
CD36
Thrombospondin

26
Q

What does placenta Pfemp1 proteins bind to?

A

Chondroitin sulphate

Hyaluronis acid on syncytiotrophoblast

27
Q

What are Pfemp1 antigens placenta threatening for?

A

Immunologically cross-reactive

First pregnancy is threatened

28
Q

What are mutations in haemoglobin genes?

A

Haemoglobinopathies

29
Q

What can happen in the placenta with individuals with malaria?

A

Infected red cells can sequester in the venules of the placenta as well as the brain. Stillbirth
Ultrasound scans- the diameter of the average foetus’s head is significantly smaller when malaria infection occurs in the first half of pregnancy
Even a single infection (detected and treated) of P. falciparum or P. vivax malaria is associated with reduced fetal head diameter, irrespective of whether the woman had shown symptoms
If the infection is well-treated, then the effect is not seen at birth
So, early treatment with effective drugs might allow growth to recover later in pregnancy

30
Q

What are ways to control malaria?

A

Vector control
Bednets
Prophlactic drugs- take before going to a malaria infected country
Vaccines?

31
Q

What are malaria vaccines?

A

Confounded by antigenic variation. Most effective type is irradiated sporozoites, but supply and ethical problems in development and implementation

32
Q

What are anti-malarial drugs?

A 
Quinine
Chloroquine
Proguanil
Mefloquine- Lariam
Artemesinin
33
Q

What is Artemesinin?

A

Chinese herb (Qinghaosu)- treatment for fevers predates the use of Quinine. Artemisia annua- first documented successful therapeutic agent for malaria in 340 AD. Active agent isolated 1972. Many derivatives. Kills the ring stage, so before merezoites sequester in the brain. Very rapid parasite clearance. Anti-nematode drug Ivermectin also kills mosquitoes feeding on patients’ blood

34
Q

What are the dangers of anti-malarial drugs?

A

widespread drug resistance- enhanced by unregulated use of anti-malarials and in areas of social disruption and military activity, combined with international travel. Artemesinin resistance spreading from SE Asia

35
Q

What insecticides are mainly used for control of malaria?

A

Pyrethroids
Safe, cheap, effective and long-lasting
Only insectide approved by the WHO

36
Q

What can be used instead of pyrethroids?

A

Organophosphates and carbamates are available for indoor spraying, although they cost more and are less effective

37
Q

What types of vaccines are being developed for malaria?

A

Antigen-encoding DNA inserted into adenovirus and then boosted with antigen in Vaccinia Ankara virus (excellent for cytotoxic T cells)
May even go back to whole attenuated parasites that are genetically modified to be replicated deficient/disabled

Infection and Immunity (20 decks)

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