Specific pathogens (parasites) Flashcards
What is malaria?
Type of unicellular plasmodium parasite.
What are 5 plasmodium that are known to infect humans?
P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi
Malaria symptoms
Most frequently fever, chills. Often cyclic, every 2-3 days. Can be accompanied by headache, myalgias, arthralgias, weakness, vomiting, and diarrhoea.
Splenomegaly, anaemia, thrombocytopenia, hypoglycaemia, pulmonary or renal dysfunction, and neurologic changes
Pathogenesis of P.falciparum
Can progress to severe potentially fatal cerebral malaria (central nervous system involvement), acute renal failure, severe anaemia and adult respiratory distress syndrome.
Pathogenesis of P.vivax
Complications tend to include splenomegaly and (rarely) splenic rupture.
Pathogenesis of P.malariae
Complications tend to include nephrotic syndrome.
What age leads to more severe malaria symptoms?
Younger ages
How is malaria infection initiated?
Injection of sporozoites into the dermis by a feeding female anopheline mosquito.
What is the vector of malaria?
Female anopheline mosquito.
What happens once sporozoites enter ECF?
Move to penetrate blood vessel by gliding motility
Where are sporozoites transported to in the blood?
Transported to the liver, where they exit the sinusoids through Kupffer or endothelial cells and enter a hepatocyte.
How do sporozoites survive inside hepatocytes?
Forming a transient vacuole (surrounded by a PVM)
What happens to sporozoites inside the PVM?
Multiply and mature into merozoites
What happens to merozoites produced in the hepatocyte?
Daughter merozoites are released in packets of merosomes into the vasculature.
There they encounter erythrocytes and begin a chronic cycle of asexual schizogony in the bloodstream
Where do merozoites replicate?
Inside red blood cells
How long is the merozoite schizogony?
1-3 days (reflects cyclic fevers)
How do mosquitos become infected?
Merozoites pre-commit to form gametocytes.
Formation of male and female gametocytes in erythrocytes leads to burst which can be ingested by female anopheles mosquito.
How is malaria diagnosed?
Blood smears
How do merozoites enter erythrocytes?
Specific ligand-receptor interaction, mediated by proteins of the EBA and PfRh family members.
What is an antimalarial drug?
Chloroquine
How does chloroquine work?
The parasite must degrade haemoglobin to acquire essential amino acids - chloroquine enters the digestive vacuole, then becomes protonated so cannot leave the vacuole. It caps hemozoin molecules to prevent further biocrystallization of heme, leading to heme buildup.
This ultimately results in cell lysis and parasite cell auto digestion
Why is chloroquine not a permanent solution?
Multiple chloroquine resistant strains have emerged.
Mutants neutralize the drug by draining chloroquine away from the schizont.
What has been shown to increase malarial sensitivity to choroquine?
Verapamil
Pathology of erythrocytes in malaria?
Increased coagulation and platelet adhesion
Increased inflammation and oxidative stress
Increased endothelial leakage
Reduced microvascular flow
Blocked blood vessels in cerebral malaria
What are malarial Var genes?
PfEMP1
What three trypanosomatid infect humans?
Leishmania spp.
Trypanosoma cruzi
Trypanosoma brucei
What causes leishmaniasis?
Leishmania spp
What causes chagas disease?
Trypanosoma cruzi
What causes sleeping sickness/ african trypanosomiasis?
Trypanosoma brucei
What is leishmania spp vector?
Sandflies
What is Trypanosoma cruzi vector?
Bugs - triatominae
What is Trypanosoma brucei vector?
Tsetse flies (glossina)
How is leishmaniasis initiated in sandfly?
Sandflies bite animals/humans that are infected and ingest the amastigotes
What happens when leishmaniasis amastigotes enter sandfly?
Amastigotes differentiate into promastigotes which multiply in the digestive tract of sandflies and migrate into the salivary glands
How is leishmaniasis infection initiated
Infected fly bites a human - the thin flagellated promastigotes are released into the host dermis along with sandfly saliva, which potentiates parasite infectivity
What happens to promastigotes of leishmaniasis inside the human?
Promastigotes are phagocytosed by macrophages - acidity of the phagolysosome induces them to transform into round amastigotes
Amastigote structure leishmaniasis
Lack flagella but contain a single mitochondrion and its DNA is massed into an organelle called the kinetoplast.
How do leishmaniasis amastigotes withstand low pH of phagolysosome?
Amastigotes resist low pH of 4.5 by expression proton transporting ATPase to maintain pH at 6.5
What happens to amastigotes inside macrophages -leishmaniasis?
Amastigotes proliferate within macrophages and dying macrophages release progeny amastigotes which can infect additional macrophages.
What cells do leishmaniasis replicate in?
Macrophages
What forms of disease does leishmaniasis cause?
Cutaneous disease, mucocutaneous disease and visceral disease involving liver spleen and bone.
How does leishmaniasis withstand complement?
Lipophosphoglycan forms a dense glycocalyx - inhibits complement action by prevention insertion of MAC as has C3b on surface to bind to MAC.
Also has Gp63, a zinc dependent protease that cleaves complement and some lysosomal antimicrobial enzymes
Where do trypanosoma brucei replicate?
Extracellular in blood
Symptoms of trypanosome disease?
Cause sustained or intermittent fevers, lymphadenopathy, splenomegaly, progressive brain dysfunction, cachexia and death.
What form are trypanosome brucei transferred to humans?
Non-dividing trypomastigotes
What causes fever in trypanosome brucei disease?
Host produces antibodies against VSG surface glycoprotein killing most organisms and causing a spike in fever.
What is a trypsomal chancre?
Painless ulcer can develop at the site of infection
How is chagas disease passed on?
Transmitted from animals to humans by triatomine bugs
Passed to host via faeces into damaged skin and mucous membranes
How does trypanosoma cruzi replicate?
Metacyclic trypomastigotes penetrate cells (mainly gut) and transform into amastigotes. Require low pH to develop into rounded amastigotes - low pH activates pore-forming proteins that disrupt the lysosomal membrane, releasing the parasite into the cell cytoplasm.
Multiply inside cells, transform into trypomastigotes and burst out of cell into blood, pass to bug or infect more cells.
What do trypanosoma cruzi require to replicate inside cells?
Low pH
