Protozoan Parasites (7-8) Flashcards
What are ampicomplexan parasites?
→ eukaryotic obligate parasites (one or multiple hosts depending on species)
→ disease agents: malaria parasites (Plasmodia), coccidia (inc. cryptosporidium), piroplasms (babesia)
What is apicomplexan’s evolutionary journey?
2 endosymbiosis events → ancestral cell consumed red algae, then underwent secondary endosymbiosis
→ endosymbiotic gene transfer, loss of nucleus and mitochondria of symbiont
→ loss of photosynthetic ability and loss of organelles lead to apicomplexans e.g. Cryptosporidium
→ relevant for development of treatment e.g. herbicides could target apicomplexa and not their host
What is the apical complex of apicomplexans?
Distinctive structure at apical end to amicomplexans
→ key cellular machinery for host cell invasion (amicoplexans must invade host cells)
→ essential for movement
→ includes secretory organelles: micronemes, rhoptries, polar rings (composed of micro tubules), conoid (very tip - pokes out in response to Ca)
→ subpellicular membranes enable parasite feeding from host
What is involved in host cell invasion of amicoplexans?
Conoids → protrude into host cells in response to calcium
Rhoptries → secretory organelles releasing rhoptry proteins into host during invasion
Micronemes → secrete proteins into host cell enabling entry
A parasitophorus vacuole is formed → parasite moved into this vacuole
Polar ring → microtubule organising centre
What is the amicoplexan life cycle?
Can involve one or more hosts
Sexual → gametes fuse to form zygote
Asexual → sporozoites differentiate to form merozoites
Merozoites undergo multiple rounds of replication → don’t differentiate again just multiply by merogony
→ some differentiate into gamonts to invade
Gamonts differentiate into gametes (sporozoites are typically invasive part)
What is malaria?
A life-threatening disease → caused by plasmodian amicoplexan parasites
Mosquito vectors are necessary for disease transmission
Half of the world’s population is at risk → mainly in tropical areas, 247 million cases in 2021 (huge no.), 619000 deaths
Disease can cause considerable morbidity and mortality
WHO Africa region carries disproportionately high share of global burden (95%) → 80% of deaths were children under 5
Where is malaria distributed globally?
Band across the tropics where malaria is dominant
What does malaria impact on?
Impact on → individuals, families, communities, countries, regions
Multiple interconnected impacts → health, productivity, economic, education, health services
What are the causative agents of malaria?
Plasmodium falciparum - most virulent species
Plasmodium vivax - concurrent infection is not uncommon
Plasmodium malariae
Plasmodium ovale
Plasmodium knowlesi - emergent zoonotic (crossing from monkeys to humans)
→ top two cause majority of mortality and morbidity
Vector: female (only ones that take blood meals) Anopheles mosquito
What is involved in plasmodium life cycles?
Always involves mammal and a female mosquito as hosts
In insects: gametes fuse to form zygote which forms oocyst
In humans: sporozoites differentiate to form merozoites, - undergo multiple rounds of replication, some differentiate into gamonts - differentiate into gametes
Has human liver and blood stages
Multiple rounds of merogony occurs in RBC → burst into blood, causes disease symptoms, synchronous RBC bursting causes spike in symptoms
What is the disease presentation of malaria?
Asymptomatic malaria → circulating parasites but not symptoms (may have level of immunity)
Uncomplicated malaria → nonspecific symptoms: fever, shaking chills, profuse sweating, headache, nausea, vomiting, diarrhoea, anaemia (RBC bursting)
Complicated malaria → as above with additional organ damage and anaemia, associated with higher levels of parasetemia and increased mortality
→ impaired consciousness, multiple convulsions, difficulty breathing, dark or bloody urine, jaundice, abnormal bleeding
What causes malaria disease symptoms?
Blood stage parasites → undergo synchronous schizogony, organ damage and anaemia due to ruptured erythrocytes
→ the simultaneous rupture of the infected erythrocytes and release of antigens and waste products accounts for the intermittent fever associated with malaria occurring either 48 or 72h intervals
Pathology and clinical manifestations associated with malaria are almost exclusively due to the asexual erthrocytic stage parasites (tissue schizonts cause little pathology)
Disease has a tendency to relapse or precedence over months or years - dormant phase in liver
Most susceptible → children, pregnant women, unborn children, those living with HIV/AIDS
Long term impact on health life chances and economics
What are the specific complications with Plasmodium falciparum?
Cerebral malaria → often fatal, extremely high temp associated with convulsions and coma
→ infected erythrocytes adhere to capillary endothelial cells become blocked - become knobbly as a result of parasite proteins exported to the membrane, bind to ligands on host cells
Backwater fever → massive lysis or erythrocytes causes high levels of free haemoglobin in the blood and renal failure, the presence of haemoglobin in the urine gives the condition its name
What adaptations of plasmodia and humans has the co-evolution lead to?
Plasmodia → array of hypervariable membrane proteins to switch between and evade immune system
→ P.falciparum genome contains large family of 60 var genes that encode hypervariable erythrocyte membrane protein 1 (PfEMP1) - during erythrocytic stage each parasite expresses one of its var genes, switching enables it to evade destruction by host immune system
Humans → higher proportions of people lacking Duffy blood group receptor in endemic areas of P.vivax which cannot bind to receptors and invade cells
→ several inherited erythrocyte disorders in endemic areas offering protection against infection e.g. sickle cell anaemia - having heterozygous alleles offers protection - a glutamic acid residue is replaced by a valine which reduces oxygen carrying capacity (homozygous often die before 30)
How is malaria diagnosed?
WHO criteria: fever and presence of parasites
Light microscopic examination of blood smear and rapid diagnostic tests
What are the treatment recommendations for malaria?
P.falciparum → artemisinin combination therapy (ACT) - artemisinin derivative plus quinine derivation
P.vivax and P.ovale → chloroquine (cheaper) unless drug resistance issue in area then ACT
→ drug resistance is a major concern so combination therapy sometimes used
What are the vector control methods for malaria?
Widespread insecticide/larvicide (spray walls)
Destruction of breeding grounds
Indoor residual spraying (IRS)
Long-acting insecticide treated bednets (ITN)
Experimental methods in pipeline
→ take organisational, economic and political drive
How do insecticide treated bed nets help control malaria?
Have been shown to reduce severe disease and mortality due to malaria in endemic regions
→ reduce all-cause mortality by about 20%
→ currently only pyrethroid insecticides approved - very low mammalian toxicity, highly toxic to insects and have a rapid knock-down effect even at low doses - have a high residual effect: don’t rapidly break down unless washed or exposed to sunlight
→ need for frequent retreatments (6-12 months) - barrier for full implementation in endemic counties
Long lasting insecticidal nets are the preferred form for public health programmes
How is malaria controlled on the human level?
Chemoprotection → prophylactic dose to travellers to endemic areas
Chemoprevention → full treatment dose to children and pregnant women, seasonal (rainy season), mass drug administration
Vaccine → possibility
Treatment of disease → rapid diagnosis + treatment prevents transfer
How can the drugs used to treat malaria work?
Kill parasites in the liver → causal prophylaxis
Kill asexual parasites in RBC → suppressive prophylaxis
Kill sexual parasites (gametocytes) in RBC → gametocytocidal prophylaxis
