Malaria Flashcards
What is malaria
Malaria is a parasitic infection transmitted by the Anopheles mosquito that leads to acute life-threatening disease and poses a significant global health threat
How is malaria endemic?
Two billion people risk contracting malaria annually, including those in 90 endemic countries and 125 million travelers.
What are the current infection statistics of malaria, and how has COVID-19 affected this?
- The COVID19 pandemic has affected malaria control-> caused increases in infections
- Between 2015-19, there were approx. 224-227 million annual infections. Which was stable
- In 2020, this increased to 241 mill infections (maybe due to the burden of COVID-19 however there are other contributing factors)
What are the current death rates of malaria, and how has COVID-19 affected this?
- Between 2015-2019, there have been 0.56 million deaths (560 000 approx) (similar rate/stable)
How many malarial parasites are there, and what are the different life cycle times in the blood?
- P. falciparum which is the main killer . Takes approx. 2 days to go through the
- P. vivax-> neglected and is the 2nd most important. Doesn’t kill so many people. Has dormant liver stages. Getting rid of these dormant liver stages is very difficult
- P.ovale -48hr and dormant liver stage
- P. malariae -72hrs + no dormant liver stage
- P.knowlesi – a monkey malaria 24hrs
o There is human transmission
o You can very quick
o It kills 1% of the people it infects
What do the different life cycle timings mean?
- If there is a 48hr cycle, then youll get a fever every two days
- If there is a 72hr cycle, then you get a fever every 3 days
Describe the first part of the life cycle of the Plasmodium parasite in the host’s body.
Plasmodium is a parasite that grows intracellularly.
The life cycle of plasmodium develops in two phases: an asexual phase in the human host and a sexual phase in the carrier, the Anopheles mosquito.
- If you are bitten by a mosquito infected by the parasite, then the parasite will leave through the salivary glands of the mosquito, when it bites you
- Parasite enters through the skin and enters the bloodstream
- The parasite is in the form of sporozoites
o The Plasmodium sporozoite constitutes the first form of the malaria parasite entering the human body and, hence, provides the first and leading targets to control an infection. Only few (∼10–100) sporozoites are injected by infected mosquitoes, suggesting that they form excellent intervention targets.
Describe the middle stage of the malarial life cycle. Hint Asexual reproduction and the liver
The sporozoites transmitted during a blood meal rapidly penetrate from the blood stream into the liver parenchymal cells in which they replicate asexually
Depending on the plasmodium species, this so-called schizogony (asexual reproduction) phase lasts between 5–7 days in P. falciparum and between 6–18 days in the other species.
After schizogony is completed, the swollen liver cell ruptures and releases the mobile merozoites into the blood stream.
One single sporozoite can produce between 10,000 and more than 30,000 merozoites
Merozoites are designed specifically to infect RBCs
- This is where you start to see malaria as a disease in place of having just a malaria infection!
- When the merozoites infect RBC, another asexual reproduction occurs (16-20 times) in the process of schizogony
- This cycle continues repeatedly
- The schizogony is what causes malarial symptoms i.e.. Fevers etc…
What are hypnozoites
- In certain types of malaria, they do not go through asexual reproduction
o They sit in a dormant phase as Hypnozoites
These are the reasons why you catch malaria without being in a malaria endemic environment
The hypnozoites reactivate
Describe the end stages of malarial infection
Hint- how they reinfect another female Anopheles mosquito
A part of the merozoites differentiates within erythrocytes into sexual stages, forming macro- and microgametocytes
They sit dormant in the bloodstream, and they are waiting to be taken up by another mosquito during another blood meal.
- These gametocytes go into the mosquito guts, and they see a reduction in temperature (from 37oC to 26oC), they see Xanthurenic acid, or xanthurenate, which is a chemical shown to induce gametogenesis of Plasmodium falciparum, the parasite that causes malaria
It is found in the gut of the Anopheles mosquito.
- All of these things act on the gametocytes to activate them
Sexual reproduction in malaria
o The female= egg
o Male parasites burst from the red cell and looks for a female egg
o Sexual reproduction occurs and a zygote forms
o Zygotes morphs into a motile form called an ookinete
o This ookinete buries into the gut of a mosquito where it forms a cyst
o Primary asexual reproduction phase occurs where you produce the sporozoites, which move from the cyct to the salivary gland of the mosquito
o Then this mosquito goes onto infect another human host
What is a malarial schizont
This is the point when the parasite divides to produce daughter cells.
Parasite fills almost the entirety of the RBC. The brown bits are called hemozoin, which is a by-product of the Hb breakdown
What are global trends in malaria?
Where is the greatest incidence?
Where are the majority of global malarial deaths occurrirng?
Who does malaria majorly affect?
Globally, the malaria ASR decreased by an average 0.80% (95% confidence interval 0.58–1.02%) per year from 1990 to 2019; however, it slightly increased from 3195.32 per 100 000 in 2015 to 3247.02 per 100 000 in 2019. The incidence rate of children under 5 was higher than other age groups.
SSA has the greatest incidence of Malaria
After 2015, the ASRs in high-middle, middle and low-middle Socio-demographic Index regions began to rise and the uptrends remained in 2019. Central, Western and Eastern Sub-Saharan Africa had the highest ASRs since 1990, and traveller number in Eastern and Western Sub-Saharan Africa increased by 31.24 and 7.58%, respectively, from 2017 to 2018. Especially, most countries with ASR over 10 000 per 100 000 had increase in traveller number from 2017 to 2018, with the highest change by 89.56% in Mozambique.
What are the mechanisms in which malaria is controlled?
Drugs
Vector Control (there is a degree of drug resistance especially in vector control)
Diagnosis
Immunity/ Vaccine coverage
How would you perform vector control? In this case it would be the infected female Anopheles mosquito.
Indoor residual Spraying (IRS)
Involves the application of insecticide products to the interior surfaces (walls and ceilings) of households, public buildings, or animal dwellings in areas where individuals are considered at risk of malaria (or other vector‐borne diseases, including Chagas disease and leishmaniasis).
- Spraying twice per year
- Vectors must be susceptible to the insecticide in use
- Houses must have “sprayable” surfaces
- A high proportion of the houses in target areas must be sprayed (more than 80 percent)
- Majority of vectors (i.e., organisms that transmit malaria) must feed and rest indoors
How else would you perform vector control?
Long-lasting insecticidal nets (LLINs):
- Treated with pyrethroids
o These are insecticides - Last 3 years, even with washing
- Coverage increased from 5% in 2000 to 65% in 2020 (1 per household)
- Percentage population sleeping under a bed net increased from 2% in 2000 to 43% in 2020
- Reduce infections by 50% and deaths by 20%
Larval source management and other personal protection measures
However insecticide resistance has been identified in 88 countries
What are methods to diagnose malarial infection?
Microscopy:
- Requires skilled operatives
- Thick and thin smears, stained with Giemsa, are used
o Thick smear= determines if you are infected
o Thin smear= you can see morphology-> individual rbcs are seen. You can identify the parasite
- Allows speciation (except P. knowlesi)
- Gold-standard method
- 188 million tests in 2012
Rapid Diagnostic Tests (RDTs):
- Relatively simple to perform
- Detect specific parasite antigens (pGluDH, HRPII, pLDH)
- Single, multiple, pan species detection
- Requires drop of blood, result in 15-30 mins
- Over 419 million tests in 2020 from 0.2 million in 2005
Can you describe Malerial vaccine therapy
- Registered malaria vaccine
RTS.S is a recombinant protein-based vaccine
It is made from a region of the circumsporozoite protein (CSP) and the viral envelope protein of the hepatitis B virus (HBsAg)
If produces antibodies against CSP which when bound stop parasites for invading liver cells
Attached a Hepatitis B virus envelope protein onto the end, thus this is the vaccine that produces a response
The antibodies to the sporozoites, therefore you get protection against malaria
Reduces malaria cases in young children (5-17) by 50% and in infants (6-12 weeks) by 25%
In 2021, WHO recommended use of the vaccine for the prevention of P falciparum malaria in children living in regions with moderate to high transmission
Describe the antimalarial drugs that are utilised
Quinine
Doxycyline: Antibiotics. Doctors are more comfortable in prescribing
8-aminoquinolines: will eliminate dormant stages. Therefore, induce radical cure
- o They will kill of gametocytes (stopping transmission)
o They will kill dormant hypnozoites
o The main drug in this drug class is primaquine (must take for 14 days)
o More recent use of tafenoquine (this is taken once for radical curing)
What can malaria be classed into?
- Uncomplicated malaria
- Complicated/Severe malaria
- Treatment will depend on the infecting parasite
- Severe malaria is associated with P. falciparum
