Malaria Biology Flashcards
What is the impact that malaria has?
- Massive global impact
- Large- cases, small deaths in 2020 (Nigeria 2020: 151-275,000)
- 85 malaria endemic countries
- ~50% global population at risk
- ~241 million cases
- ~627,000 deaths
- 45-61 million DALYs (2017 data)
- 95% of malaria burden, 96% of deaths is in sub Saharan African - 80% of those deaths are children under 5. Also Pregnant women, patients with HIV/AIDS, non-immune migrants, mobile populations and travellers. 2016 ~1600 imported cased in UK.
- 5% increase in incidence between 2019-2020 due to service disruption during COVID pandemic
- 12% increase in malaria deaths between 2019-2020: 47,000 additional deaths due to service disruption during COVID pandemic – plus 22,000 through better data gathering
Tell me the origins of the protists
Origin of the protists
What are Apicomplexa and give some examples?
a large phylum of parasitic alveolates. Most of them possess a unique form of organelle that comprises a type of non-photosynthetic plastid called an apicoplast, and an apical complex structure (this is involved in invasion)
All excepting one are obligate endoparasites of animals
Includes: Babesia, Plasmodium, Cryptosporidium, Toxoplasma.
What does the tree of life only show about the genus plasmodium?
Tree only shows the best-known Plasmodium species - at least 164 other Plasmodium sp. named. Parasites of mammals, birds, reptiles, reportedly one in amphibia.
5 sp known human parasites, P. knowlesi - macaque monkey parasite in S. E Asia, but increasingly important as a human parasite.
Part of wider Apicomplexan order of blood parasites – the order haematosporida
What is plasmodium part of?
Plasmodium is part of a wider Apicomplexan order of blood parasites – the malaria parasites / order Haemosporida.
Why are the relationships within the Haemosporida historically difficult to understand?
Relationships within the Haemosporida historically difficult to understand due to limited sampling of species, absence of robust, multi locus sequence data and extreme nucleotide base composition bias in the group. P falciparum genome GC content 19%
The evolutionary history of the malaria parasite is characterised by what?
A complex series of transitions in life-history strategies and host usage
The malaria plasmodium is polyphyletic. What does this mean?
(of a group of organisms) derived from more than one common evolutionary ancestor or ancestral group and therefore not suitable for placing in the same taxon.
Who won the nobel prize in 1902 for his work on the transmission of malaria (P. vivax) by mosquitos?
Tell me about his work
Ronald Ross
- Previously thought to be a (bacterial) gastro-intestinal disease
- He fed mosquitoes on infected soldiers and then dissected them
- Giovanni Grassi - the complete life cycle of P. falciparum, vivax, malariae (1898)
- Life cycle of Taenia nana
- Life cycle of Ascaris lumbricoides (by self-experimentation!)
- Grassi’s law: there is no malaria without Anopheles
- The term malaria (from the Italian mala “bad” and aria “air”) was used by the Italians to describe the cause of intermittent fevers associated with exposure to marsh air or miasma.
- The word was introduced to English by Horace Walpole, who wrote in 1740 about a “horrid thing called mal’aria, that comes to Rome every summer and kills one.”
What are the stages of the malarial parasite life cycle?
- At stage 1, an infected female mosquito injects sporozoites when taking a blood meal
- Sporozoites migrate to the liver via the blood stream
- Sporozoites mature in liver cells and turn into schizonts
- Mature Schizonts divide (exo-erythrocytic schizogony) producing merozoites
- The liver cells rupture and release the merozoites into the blood stream. (P. vivax & P. ovale also produce hypnozoites which lay dormant and can cause relapse months or even years later)
- Merozoites penetrate the RBCs and divide asexually (erythrocytic schizogony). The RBCs rupture freeing the parasites to penetrate new RBCs. Rupture of the RBCs is synchronised every 24, 48 or 72 hrs, causing malarial fever & violent shaking.
- Some differentiate into sexual erythrocytic stages (male microgametocytes and female macrogametocytes).
- The gametocytes are ingested when a female mosquito bites and undergo a sporogonic cycle(other erythrocytic stages in the blood meal die)
- Within 30 hrs of ingestion into the mosquito’s stomach, ♂ microgametocytes penetrate the ♀macrogametes to form zygotes.
- The zygotes become motile and elongated and turn into ookinetes
- The ookinetes penetrate the gut wall and form oocysts.
- The oocysts grow, rupture and release sporozoites, which migrate to the salivary gland ready for injection into a new host
The malaria life cycle in mosquitos vs humans
What are the malaria parasites which infect humans?
P. falciparum - the cause of malignant tertian malaria
P. vivax - the most frequent cause of benign tertian malaria
P. ovale - the other, less frequent, cause of benign tertian malaria
P. malariae - the cause of benign quartan malaria
P. knowlesi - the cause of severe quotidian malaria in Southeast Asia since 1965
Plus a few other possible opportunist infections by other species identified by PCR.
What do the following mean…
Tertian malaria
Quartan malaria
Quotidian malaria
Tertian malaria – fever every other day
Quartan malaria – fever every third day
Quotidian malaria – every day!
What malaria paraistes account for nearly all human infections with plasmodium species?
P. falciparum, P. vivax, P. ovale, and P. malariae together account for nearly all human infections with Plasmodium species
What malarial parasites account for the large number of malarial deaths?
P. falciparum accounts for the overwhelming majority of malaria deaths
An increasing number of cases of severe malaria in SE Asia have been attributed to what malarial parasite?
P. knowlesi
Tell me about Plasmodium falciparum
Found worldwide in tropical and subtropical areas, and especially in Africa where this species predominates.
Can cause severe malaria because it multiples rapidly in the blood, and can thus cause severe blood loss (anaemia).
The parasite- infected erythrocytes can clog small blood vessels. When this occurs in the brain, cerebral malaria results, a complication that is fatal without treatment.
Tell me about Plasmodium vivax
Found mostly in Asia, Latin America, and in some parts of Africa
Because of the population densities especially in Asia it is probably the most prevalent human malaria parasite
Strict trophism for reticulocytes (reticulocyte-binding protein).
Historically believed to require duffy positive red blood cells
P. vivax (as well as P. ovale) has dormant liver stages (“hypnozoites”) that can activate and invade the blood (“relapse”) several months or years after the infecting mosquito bite
Duffy antigen on rbc surface historically thought to be required in P. vivax invasion, hence absence of this species from much of Africa.
Howes et al 2010 – global distribution of Duffy negative population frequency
But recent studies have identified P. vivax in duffy-negative individuals, so it isn’t the whole story, Gunalan et al 2018.
Tell me about plasmodium ovale
Found mostly in Africa (especially West Africa) and the islands of the western Pacific.
It is biologically and morphologically very similar to P. vivax.
However, unlike P. vivax, it can infect individuals who are negative for the Duffy blood group (a non-specific chemokine receptor), which is the case for many residents of sub-Saharan Africa. This explains the greater prevalence of P. ovale (rather than P. vivax) in most of Africa.
How is malaria diagnosed?
Microscopic examination of Giemsa-stained thick or thin blood (still preferred)
Antigen-based techniques:
- By detection of (host) antibodies to Plasmodium antigens (cannot distinguish between past & present infections)
- By direct detection of Plasmodium antigens (detects current infection)
PCR (not widely used due to cost and complexity but can detect low levels of parasites)
What does the anopheles vector distribution depend on?
Depends on:
Abundance – the species needs to exist in numbers high enough to ensure individuals encounter an infectious human to pick up the malaria parasite
Longevity – individual mosquitoes need to survive long enough after feeding on infected blood to allow the parasite time to develop and travel to the mosquito’s salivary glands ready to infect the next person bitten
Capacity – each mosquito needs to be able to carry enough malaria parasites in the salivary glands to ensure the parasite is transmitted to the next human
Contact with humans – the species needs to prefer to feed on humans rather than other animals, and be able to survive and breed in places close to homes, and be able to find people (usually by entering their houses
Malaria distribution
