Plasmodium Flashcards
Apicomplexa
Organism that has a small nose (polar ring) that it uses for host attachment.
What are the 4 species that cause malaria in humans?
- P. vivax
- P. ovale
- P. malariae
- P. falciparum
What organism causes the worst malaria in humans?
P. falciparum
What vector spreads malaria?
Anopholese gambesi (mosquitoe)
Describe the Malaria lifecycle.
- Mosquitoe takes blood meal and ingects sporozoites into host
- The sporozoites in the exo-erythrocytic cycle willtravel to liver cells and infect them. There they will create a schizont (infected cell filled with merozoites) which will then reupture releasing the merozoites.
- These merozoites released in the schizont can enter the erythrocytic cycle and infect RBCs. In the RBC can matue to a immature trophozoite, then a mature trophozoite and form a shizont filled with merozoites. The rupturing of the shizont can lead to the reinfection of RBCs.
- The immature trophozoite can mature into a gametocyte which can then be ingested by a mosquitoe during a blood meal starting the sporogonic cycle.
- Some of the gametocytes can mature into extraflagellated microgametocytes while others mature into macrogametcytes. The microgametocyte enters the macrogametocyte to make a ookinete which them matures into a oocyst.
- The oocyst ruptures and releases sporozoites in the salavary glands of the mosquitoe and the cycle repeats with a blood meal.
General smptoms of malaria.
- headache, nausea, chills, diarrhea, and fever (up to 41 degrees)
- anemia (lack of hemoglobin to carry oxygen) w=hich is a consequence of the RBC ruptue
- splenomegaly (enlarged spleen) due to the increase # of damaged cells leading to a full spleen
What is the incubation period of Plasmodium?
10-15 days
Lab Diagnostics for Malaria.
Microscopic diagnosis via blood smear (thick film and thin film) : most common practice for diagnosis
Rapid Diagnostic tests detect antigens of Plasmodium but most tests only detect one species. The rapid tests can detects HRP2 (only P. falciparum), different subtypes of pLDH (can just be for P. falciparum or for all species depending on the subtypes), and Aldolase (all species)
What is the geographical distrabution of malaria?
Mainly tropical and subtropical areas
What are the most widespread species of Plasmodium?
P.vivax and P. falciparum
Which species of Plasmodium cause hypnozoites and describe what they are?
P. vivax and P. ovale
Hypnozoites are infected liver cells that remain latent in the liver
What forms of Plasmodiumremain “benign”?
P. malariae (can remain infected up to 40+ years before causing harm)
P. knowlesi (primarily benign course)
Plasmodium falciparum
- recodnized as the most deadly form of malaria
- infects all ages of RBCs (increase the % of infected cells/ paracitemia)
- leads to complications such as cerebral malria, blackwater fever, and severe anemia)
Cerebral malaria
- metabolic encephalopathy (cerebral anoxia associated with increased glucose catabolism and lactate production by infected sticky RBC clumps)
The P. falciparum bind endothelium in the cerebral vasculature causing sequestration of RBCs - Clinically these patients will have altered states of conciousness, confusion, hallucinations, seizures, motor abnomalities, and comas (can be fatal)
Blackwater fever
- caused by P. falciparum
- characterized by hemoglobinuria secondary to massive hemolysis
- sometimes due to hypersensetivity o drugs
- hepatic, renal, adrenal, and pulmonary complications can also be seen with severe infections
How and why do parasites differenciate into gametocyte form?
- suspected the parasites can communicate with other parasites and let them know when they need to differeciate
Extracellular vesicles, exosomes that contain plasmids for differenciation, are secreted by P. falciparum infect RBCs and act as intracellular communication mediators
Describe P. falciparums pathogenesis.
They are able to sequester themselves into deep vasculature due to the adherance of infected RBCs to endothelial cells (increased RBC stiffness) which results in the accumulation of parasites in organs throughout the body
Decreased bloodflow= decreased immune cells to area
PfemP1
P. falciparum erythrocyte membrane protein 1
Expressed on the surface of mature RBCs infected with P. falciparum. They undergo clonal antigenic variation allowing it to bind to several different cell receptors
This is important for the sequestaration of infected cells to evade spleen-dependent killing and antigenic variation for evading antibody-dependent killing
It also increases the poduction of inflammatory cytokines like TNF-alpha which leads to upreguation of ICAM-1 and further sequestration and eventually glucose and oxygen avalibility will decrease (can lead to cerebral malaria)
What does PfEMP1 bind to?
- Complement receptor CR1
- Blood group antigen A
- CD36 on endothelial cells, monocytes, and platletes in systemetic vasculature
- ICAM-1 in the brain
- Chondroitin sulfate A (CSA) in the placenta
- Can bind to and down regulate dendritic cell function (which decreases parasitic detection by immune system)
Anemia
Lysis of RBC and increased splenic removal of unifected RBC (rosetting). The release of TNF-alpha (proinflammatory cytokine) can decrease erythropoietin which stimulated RBC production
What drugs are used to treat malaria?
- Quinine was the ealiest antimalarial
- Chloroquine is a synthetic antimalarial which can form complexs with our heme and makes it toxic for plasmodium but there has been drug resistance seen since 1950
- we now do a artemisinin based combination therapy or ACT
Malaria Vaccine
- difficukt to develop due to the many lifestyle stages
- The RTS.S/A01 vaccine is somewhat effective in babies (affects the sporozoites stage) but there is no reduction in transmission but there is increased survival from infection
What is the most effective prevantative method of malaria?
Bed nets soaked with insecticide
