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Look at the symptoms and recognize them bro
-Blood smear with microscope to diagnose
-ADD Andrea

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-Take drugs: chloroquine (used to be most widely used to treat and prevent), primaquine
-Can be detrimental to health of the liver
-Vaccines: RTS,S/AS01
-Mosquitoes can become resistant by changing surface proteins

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-Eradicate the vector by insecticides and sprays
-Nets to sleep under
-Repellant DEET
-Decrease effects of climate change / more ACs (mosquitoes like warmth)
-Creams
-Beware still water (breeding zones)
-Preventative pills
-Questionable home remedies: garlic, B12, tea tree oil

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- Disease caused by plasmatic protostome parasite
-Transmitted by mosquitoes onto humans
-2-3 million die of it each year
-Occur in tropical regions around equator
-Main species of plasmodium: P. (ADD LATER)
-Only female mosquitoes bite
-40 species of anopheles pose threat to humans (VIKI ADDS later)

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Malaria occurs wherever the mosquito vector Anopheles is found and there are human hosts
for the protozoan parasite Plasmodium. Where malaria is found therefore depends mainly
on climatic factors such as temperature, humidity, and rainfall. Malaria is transmitted in
tropical and subtropical areas, where Anopheles mosquitoes can survive and multiply, and
Malaria parasites can complete their growth cycle in the mosquitoes (“extrinsic incubation
period”). Temperature is particularly critical. For example, at temperatures below 20°C (68°F),
Plasmodium falciparum (which causes severe malaria) cannot complete its growth cycle in
the Anopheles mosquito, and thus cannot be transmitted. In many malaria-endemic
countries, malaria transmission does not occur in all parts of the country. Even within tropical
and subtropical areas, transmission will not occur:
• at very high altitudes;
• during colder seasons in some areas;
• in deserts (excluding the oases); and
• in some countries where transmission has been interrupted through successful
control/elimination programs.
Generally, in warmer regions closer to the equator, transmission will be more intense, and
malaria is transmitted year-round. The highest transmission is found in Africa South of the
Sahara and in parts of Oceania such as Papua New Guinea. In cooler regions, transmission
will be less intense and more seasonal. There, P. vivax might be more prevalent because it is
more tolerant of lower ambient temperatures.

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-Replicate within host
-Undergoes cellular reproduction

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Steps:
1) Mosquito bites infectious person, after it can infect other people for 2 weeks
2) Mosquitoes spread sporozoites through saliva
3) Mosquito is attracted to human by CO2 production and bodily odor
4) Human starts to feel sick within 8-30 days

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Sporozoite has neural effect on mosquito, making it refrain from biting humans when it is proliferating, and when it is ready to spread it will urge the mosquito to bite, but only for small quantities of blood. This will make the mosquito want to bite more people-> GREATER spread !!

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- Can be spread through blood donation (induced malaria)-> watch your needles people!!
- Induced malaria: not spread by a vector

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1) Mosquito introduces plasmodia sporozoites through salivary glands into human circulary system
2) Travels to parenchymal cells in liver (detoxifiers)  (takes 30 minutes from bite to liver). They use the carcass of dead liver cells to avoid immuno response
3) Go through schizogony to form merozoites which enter the bloodstream  (form hepatocellular cycle with step 2)
4) Invade red blood cells and feed on hemoglobin-> mature and reproduce
5) Red blood cell ruptures, releasing ~20 new merozoites and toxic compounds causing malaria symptoms

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Introduce malaria: imported mosquito e.g., some regions in the US
Transfusion malaria: blood transfusions from an infected donor
Mainline malaria: acquired by sharing needles (drug addicts)
Congenital malaria: from mother to fetus

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-Asexual reproduction in liver and red blood cells (mitosis)
-Gametocytes are female or male. These combine to form dizygotics

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Different plasmodial species prefer RBCs of different ages
-P. Vivax and Ovale prefers younger ones
-P. falciparum doesn't discriminate
-P. Malariae prefers older ones

-Vivax and Ovale can remain within host
-Malariae longest incubation period (can last 20 years)

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- Spleen recognizes RBCs that are older (>120 days) or rigid
- Leads to splenomegaly
-Falciparum tricks the spleen by putting parasite derived protein pfEMP-1. This protein binds to endothelial cells of venules and capillaries-> hinders bloodflow-> parasite not discovered by immune system

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Lysis of RBCs releases merozoites and toxins
GPI stimulates production of tumor necrosis factor and interleukin-1 in macrophages
Cytokines will trigger symptoms

Different fever patterns for different malaria strains. Gametocytes mature at night, when mosquitoes are feeding. Falciperum is irregular
Vivax and Ovale every 2 days
Malariae every 3 days

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Summary of the life cycle of the malaria parasite

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Summary of the life cycle of the malaria parasite

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1) Asexual stage or schizogony
a) Liver stage or exoerythrocytic cycle
i) Infected mosquito bites human
ii) Migration through bloodstream to liver of human
iii) Asexual reproduction in liver cells
iv) Hepatocytes eventually rupture, release into bloodstream
b) Blood stage or erythrocytic cycle
i) Infection new erythrocytes/RBCs
ii) Ring stage in erythrocytes/RBCs
iii) Ring stage grows and divides
iv) Erythrocytes/RBCs eventually rupture, release into bloodstream
v) Infect new erythrocytes/RBCs or develop into male and female gametocytes.
2) Sexual stage
a) Another mosquito bites infected human and ingests gametocytes
b) In mosquito’s digestive tract, gametocytes unite to form zygote
c) Resulting sporozoites migrate to salivary glands of mosquito.

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• P. falciparum occurs almost exclusively in tropical and subtropical regions. Co-infection
with human immunodeficiency virus (HIV) is common in these regions and may pose a
risk factor for severe malaria.
• P. vivax is the most prevalent of the human plasmodia, with the widest geographic
distribution, including the tropics, subtropics, and temperate regions. The overwhelming
majority (>80%) of clinical cases of vivax malaria occur in South America and Southeast
Asia. P. vivax is widely distributed because it can develop in mosquitoes at a lower
temperature. Sometimes referred to as “benign” malaria, the cycle of paroxysms
(recurrent intensifications of symptoms) occurs every 2 days, and the patients generally survive even without treatment. An important factor in the life cycle of P. vivax is that it
can remain dormant in the liver of the patient for months and even years. This bridges
the cold-weather gap in the life cycle of mosquitoes in temperate countries—providing
them with a continuing supply of infected subjects.

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-Repeated infection builds immunity (not very effective because different strains)
-Sickle cell disease can prevent malaria infection
-Glycophorin A is surface molecule falciparum. If you are Glycophorin A negative you have immunity against falciparum
-Duffy blood group antigen same principle as above, but this for Vivax
-G6PD is the deficiency reduces ability of RBCs to produce NADPH via PPP -> might cause oxidative stress-> malaria struggles to survive
-Thalassemia

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Focus on life cycle and pathogenesis > immuno response

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Antigen detection using a rapid diagnostic test (RDT) is being used both in the
field and in diagnostic laboratories as an adjunct to conventional microscopic diagnosis.
RDTs use monoclonal antibodies directed at either species-specific or pan-Plasmodium
targets. These tests are simple, rapid (results in <20 minutes), and inexpensive. Thus far, one
RDT has been approved by the U.S. Food and Drug Administration (FDA): the BinaxNOW
(Binax, Scarborough, Maine) Malaria test kit, based on the antigens HRP-2 and aldolase. The
sensitivity and specificity for this test for the detection of P. falciparum are 95% and 94%,
respectively

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P. falciparum
Thick and thin blood films are searched for the characteristic rings of P. falciparum, which
frequently occur in multiples within a single cell, as well as in the accollé position. Also
diagnostic are the distinctive
crescentic gametocytes

P. vivax
RDTs may be used as an adjunct to microscopy in the diagnosis of malaria caused by P. vivax;
however, the sensitivity is generally much lower than that for detection of P. falciparum: 69%
versus 94%, respectively.
P. knowlesi
P. knowlesi–specific polymerase chain reaction (PCR) is the only reliable means of identifying
this emerging species of Plasmodium. At present, no commercially available RDTs are
designed to specifically and reliably detect P. knowlesi.
P. ovale and P. malariae
RDTs are not recommended for the diagnosis of P. ovale infection.

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-Mosquitoes do not get sick
-Genetic modification??
-Some mosquitoes bite humans and monkeys
-Spiders can be employed to hunt mosquitoes
-There is a bird vector

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Not a lot being done that's actually doing anything :(

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Not a lot being done that's actually doing anything :(

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https://www.youtube.com/watch?v=dyprqPM1rHI