Protists in humans

• malaria

  • Malaria caused by the protozoa Plasmodium species
  • Transmitted by the female anopheles mosquito
  • Infects red blood cells causing cycles of fever
  • Severe disease includes anaemia and small capillaries can become blocked by infected red blood cells in the brain (cerebral malaria), lungs and placenta
  • Kills approximately 1,200 children per day in sub-Saharan Africa
• apicomplexans

  • Contain an apical complex (api – complex) that facilitates host invasion
  • Often have complex life cycles with multiple hosts
  • Key examples
  • Plasmodium sp. – malaria
  • Toxoplasma – toxoplasmosis
  • Cryptosporidium - coccoidosis
• Plasmodium falciparum 

  • 90% cases in Africa, 50% in South east asia
  • causes majority of deaths globally
  • main cause of cerebral malaria
• Plasmodium vivax 

  • 90% of cases in Asia and South America, 50% of cases in South East Asia
  • immunity for people with the Duffy antigen
  • can cause severe malaria in 1/5 cases
  • dormant liver stage
• epidemiology of malaria

  • Global deaths from malaria in 2022 estimated to be 608,000
  • More than 50% of deaths occurred just 4 countries
  • Most victims (55%) are sub-Saharan children infected with P. falciparum (cerebral malaria)
• life cycle of malaria

  1. skin infection
  2. liver stage dependant
  3. blood stage development
  4. mosquito stage development
• skin infection

  sporozoites residing within the mosquito salivary gland are injected into the skin 
• liver stage

  • sporozoites invade liver cells within 30-60 minutes engulfed by a modified host cell membrane.
  • divide asexually within hepatocytes forming schizonts after 6-7 days
  • plasmodium vivax can form a non-replicating hypnozoite
  • enables long-term survival of parasite leading to relapses of disease years after initial infection
  • each schizont gives rise to thousands of merozoites released into the blood from ruptured hepatocytes
  • merozoites actively invade red blood cells
• blood stage

  • merozoites bind receptors on red blood cells and are internalised
  • differentiate into trophozoites and ingest cytoplasm of the red blood cell
  • malaria paroxysm
  • Rupture of haemocyte schizont in the blood releases malaria endotoxin (haemozoin and parasite DNA)
  • Induces host to produce high levels of pro-inflammatory cytokines TNF-α inducing fever like symptoms
  • Can lead to severe anaemia
  • P. falciparum proteins are expressed on the surface of infected red blood cells enabling attachment to the endothelium and can cause rosetting and capillary obstruction
  • Asexual reproduction in host red blood cells results in either many merozoites or some commit to a sexual cycle and produce gametocytes (male or female)
• mosquito stage

  • Female Anopheles mosquito pick up gametocytes from the host blood
  • Male and female gametocytes undergo gametocytogenesis within the mid gut of the mosquito forming a zygoteand motile ookinete
  • Cross midgut to form oocyst releasing thousands of sporozites which migrate to the salivary gland
• immunity of malaria

  • Immune system produces antibodies to malarial proteins expressed on the surface of red blood cells
  • Main antigen is PfEMP1 in P. falciparum
  • PfEMP1 undergoes antigenic variation to evade the immune system
• vaccination of malaria

  • RTS,S,
  • The world's first licensed malaria vaccine, which has been recommended for use by the WHO since 2021.
  • The vaccine is undergoing pilot trials in select countries and it is hoped to protect against the parasite in the future.
  • R21/Matrix-M vaccine
  • Since then, another malaria vaccine has also been developed which has been recommended for use since 2023.
• trypanosomes

  • Chagas disease and sleeping sickness
  • Kinetoplastids
• life cycle of chagas disease

  • Trypanosoma cruzi
  • Triatomine bug
  • Latin America (6-7 million people)
  • Acute - fever, fatigue, headache, rash
  • Chronic - severe cardiac and intestinal lesions
  • Intra-cellular stage in smooth muscle
• life cycle of Trypanosomiasis

  • Trypanosoma brucei
  • Tsetse fly
  • Sub-Saharan Africa (currently <1000 cases)
  • Skin lesion – migrates to central nervous system – severe sleep disturbance leading to coma/death
  • Inter-cellular stage in CNS
• immune invasion in chagas disease

  • Intracellular growth in macrophages
  • Differentiation - amastigote
• immune invasion in Trypanosomiasis

  • Antigenic variation
  • Variable Surface Glycoproteins (VSGs)
  • 2000 VSG-encoding genes – only one expressed at a time
• diarrhoea

  increase in stool frequency and loose or watery stool
• gastroenteritis

  a condition that causes nausea, vomiting diarrhoea & abdominal distress
• dysentry

  involves blood and mucus in stool – general resulting from damage to the large intestine
• how many children die a year from diarrheoal diseases

  580,000
• giardia

  • Most common protozoal parasite isolated from human stools
  • Often asymptomatic and not fatal in developed countries
  • Adhered to the intestine via adhesive disc – cytoskeleton and contractile proteins
  • Exhibits antigenic variation via Single variant surface protein (VSP)
  • Expression switching occurs once every 10 generations
• cryptospordium

  • First recorded case in 1976
  • Two main pathogens: C. hominis and C. parvum
  • Outbreaks common – disease can be fatal to the immunocompromised
• cyptospordium pathology

  • Inflammation around intestinal epithelial cells
  • Impacts normal nutrient and ion adsorption leading to diarrhoea
  • Prolonged infection in children – malnutrition and death in very young (<5 years old)
  • Healthy adults – infection lasts 1 – 2 weeks and usually self-limiting – can be fatal in the immunocompromised
• prevention and treatment of cryptospordium

  • Oocysts resistant to chlorine – removal from water by filtration
  • Most diarrhoeal disease can be prevented by good sanitation and access to clean water
  • Disease usually self-limiting and can be treated with low-osmolarity oral rehydration salts (ORS) and zinc tablets