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Lecture notes

Malaria (MCB3024S) notes
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  • Module
  • Defence and Disease (MCB3024S)
  • Institution
  • University Of Cape Town (UCT)

Comprehensive lecture notes for the Malaria: Molecular biology module covered in MCB3024S. These notes cover all content taught in lectures as well as additional materials (powerpoints, textbooks) required to succeed. These notes were created by a student who achieved a distinction in this course.

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Document information

  • February 8, 2024
  • 29
  • 2022/2023
  • Lecture notes
  • Thomas oeleschlager
  • All classes

Subjects

  • biochemistry

Written for

  • University of Cape Town (UCT)
  • Defence and Disease (MCB3024S)
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MCB3024S

Molecular biology of Plasmodium falciparum

Malaria is caused by Plasmodium infection
- single celled eukaryotic organisms
- they are obligate protozoan parasites (cannot exist outside a host)
- have two hosts, being vertebrate host (humans) and insect hosts (mosquitos)
- they are characterized by containing an apicoplast (phylum Apicomplexa)
- there are four species that cause malaria in humans: Plasmodium ovale, Plasmodium malariae, Plasmodium vivas (Asia,
Latin America and Africa) and Plasmodium falciparum (sub Saharan Africa)

Plasmodium falciparum
- severe malaria
- is responsible for most malaria-related deaths globally
- prevalent malaria parasite in sub-Saharan Africa
- vivax is characterized by relapses
- falciparum is the most deadly and severe form of malaria

Plasmodium vivax
- moderate to severe illness
- complications are rare and relapses are characteristic of this species
- prevalent in southeast Asia, Latin America and eastern Mediterranean

Timeline of malaria discovery




Global distribution of malaria
- malaria was prevalent in most parts of the world in 1900 and over time,
malaria was gradually eradicated and still persists mostly in the tropical areas

Strategies to control and eliminate malaria
Vector control
- DDT insecticide worked well but is harmful to humans and the environment so has been largely abandoned
- today, use insecticides in a targeted away such as insecticide-treated mosquito nets (ITNs) and Indoor residual spraying
(IRS)

Case treatment
- malaria is a treatable disease, drugs can be used as a preventative measure and to treat the disease
- artemisinin based combination therapy (ACT)

Chemoprevention
- intermittent preventative treatment in pregnancy (IPTp), 2nd, 3rd trimester
- seasonal malaria chemoprevention (SMC), children 3-59 months

WHO malaria report 2021
- map shows the countries in red that have reported malaria cases
- the green, blue and pink counties are countries that have not had cases
for some time (malaria free for a few years)
- the disease still persists in the tropical areas
- about 85 countries are still in danger of malaria and it affects several
billion people world-wide who are at risk to contract the disease
- 241 million cases in 2020, resulting in 627,000 deaths
- WHO African Region accounted for 228 million cases (95%) and
602,000 deaths (96%)

,Malaria incidence 2020
- malaria incidence if the number of new cases of malaria in a year per 1000
population at risk
- map shows the malaria incidence
- the darker the colour, the higher the incidence rate
- holoendemic area is when essentially every person gets infected once a year

Number of deaths from malaria 2019
- map coincides with the number of deaths from malaria
- Nigeria and Congo are the worst affected area

Deaths from malaria by age 1990 to 2019
- map shows the age distribution of death by malaria
- majority of death us under 5




The global technical strategy for malaria 2016-2030
- WHO over the last decade has announced new strategies to eliminate
the disease
- vision to get a world free of malaria

Global trends in malaria case incidence and mortality rate
- graph shows the global trend over the last 20 years, showing case incidence and case mortality in blue and red
- the goals are clearly not reached, for both cases and death




The number of deaths from malaria by world region, 1990 to 2019
- for the African region, can see that over the years, there has not been much
change overall
- has been much progress in the eastern region and south Asian regions
- includes deaths at any age and of both sexes
- problem with delivering and prevention and diagnoses equipment

Plasmodium falciparum life cycle
- is transmitted by the mosquito
- they undergo several developmental stages
- the blood stage is when the parasite can be discovered and when
symptoms show
- from the blood stage, gametocytes are produced and get taken by
mosquitoes that feed on people and another life cycle happens inside the
mosquito

, Transmission
- the mosquito bites, and it inserts a needle into the skin, many times
- while doing so, it deposits the malaria parasite in the form of sporozoites
- it is an elongated form and they are motile, able to move around
- plasmodium sporozoites (green) are deposited under the skin of the vertebrate host
through the bite of an infected female Anopheles mosquito

Major structures in Plasmodium sporozoites




- body plan of the parasites
- do not need to memorize this
- note that all invasive parasite stages have a polarity (apical end which is the end where you find the machinery involved in
the cellular invasion of the parasites)
- sporozoites are elongated, slightly curved cells of about 10 um
- glide in shallow curves on flat surfaces
- apical end contains invasive proteins, such as adhesins such as the circumsporozoite protein (CSP)

Plasmodium berghei sporozoites 10 min after intradermal inoculation together with CD31 – labeled
vascular endothelia
- movie shows the sporozoites containing green fluorescent protein to be seen
- purple shows the blood vessels
- when they find a blood vessel, they disappear into the vessel and spread around the body

Plasmodium liver stages
- they sporozoites infect liver cells (hepatocytes) in less than 1 hour
- in the liver cells, the parasite changes form and undergoes
differentiation stages
- it then multiplies by undergoing a process called schizogony which is a
form of asexual reproduction where you replicate the genome many
times and package the genome into individual cells

Key events of the Plasmodium liver stage developmental program
1) Sporozoites (>10 < 200) are injected with mosquito saliva and are transported to the liver by the blood stream
2) Sporozoites invade hepatocytes within 30-60 min and form a parasitophorous vacuole (PV)
3) After dedifferentiation, extensive replication of the genome and organelles and segregation by schizogony produces up to
tens of thousands of merozoites
4) After 5-7 days, the PV breaks down, merozoites enclosed in vesicles (merosomes) formed from the host cells plasma
membrane are released into the liver sinusoids and enter circulation; merosomes eventually burst in the lung
microvasculature to release individual merozoites

- dedifferentiation means that you go through the differentiation pathway and can go back to differentiate into something
different
- the identity of the cell is a sporozoite for example, it can then lose this identity and completely change its identity
- bursting of the mesosomas is the start of the blood stage

Hypnozoites
- only Plasmodium vivas/ovale
- may remain dormant for months or years
- relapses caused by hypnozoites may contribute up to 80% of all P. vivax blood-
stage infections
- treatment with primaquine to clear hypnozoites can cause severe hemolysis in
people with G6PD deficiency

- do not undergo asexual reproduction but undergo a different differentiation pathway
- this is a dormant form of the parasite that can remain undetected in the liver cell for a long time
- based on a trigger, this can undergo asexual reproduction and develop the disease without being bitten by the mosquito
(called a relapse)

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