Molecular and Cellular Parasitology Flashcards
Define NTDs and describe problems
- Neglected Tropical Diseases - 1 billion people infected with 1 of 17 recognised NTDs - Diagnosis and treatment costs a few pence (not profitable for pharmas - Less than 1% of all registered drugs are for NTDs
What is a DALY
- Disability adjusted life years - Consequence of an infection on the productivity of an individual - Estimates the burden of a disease on the population
Describe a parasite
- Organism dependent on another organism for survival - Exo- and Endo- parasites - Direct (digestive tract) or indirect (biting insect vector) transmission routes
Important considerations when investigating parasites
- Diversity (genetic variability within species) - Life cycle in host (tissue specificity) - Active host-pathogen interactions - Antigen load - Concomitant immunity - Parasite are eukaryotes (share biology) - Most antibiotics don’t work on parasites
Pathology
A deviation from the healthy or normal state
Pathogenesis
A process based on physiological, biochemical and molecular mechanisms and which leads to harmful effects for the host
Give potential impacts of parasites on their hosts
- Impairing capacity, mechanical interference, competition for nutrients - Tissue destruction - Virulence factors - Toxins - Proteases - Immune response exhaustion - Self-damaging (immunopathology)
Virulence
A reduction in host fitness (usually measured by mortality or morbidity) as a consequence of the infection
Describe problems with studying immunopathology
- Can not study immunopathology in vitro (can study components) - Clinical immunopathology is built of snapshots - Rarely see the entire infection through to end (patients usually get treated part way through)
Describe the Leishmania life cycle
Sandfly bits and transfers metacyclic promastigotes into blood stream. MPs become attached to phagocytes and are taken up. MP transforms into intracellular amastigote and proliferates. IAs lyse the phagocyte leading to reinvasion. Cycle continues when sandfly bites again and takes up amastigotes. In sandfly midgut they proliferate as procyclic promastigotes . Transformation in to metacyclic promastigotes ready for transfer though a blood meal.
Describe the simple paradigm of intracellular control of Leishmania
-Th1 and Th2 cytokines drive polarised macrophage activation. Factors released by Th1 cells promote the production of nitric oxide (leishmanicidal) from arginine by the macrophage. Factors released by Th2 cells promote the production of polyamines from arginine which promotes the growth of Leishmania -Paradigm too simple.
What are the three sub species of African sleeping sickness and who do they infect?
Trypanasoma brucei brucei (Not human infective) - Disease in livestock T. brucei gambiense (human infective - chronic) - Months/years to progress to CNS involvement. West & Central Africa T. brucei rhodiense (human infective - acute) - Can kill in weeks/months. East & Southern Africa
Describe symptoms of ASS at the early stage
- Ulcer at the fly bite site - Swollen lymph nodes - Axillary (rhodiense) - Cervical (gambiense) - Fever, weakness, headache, joint pains, night sweats
Describe symptoms of ASS when parasite develops in lymphs/blood
- Early stage symptoms more pronounced - Anaemia due to autoagglutination of red blood cells - Cardiovascular/endocrine/kidney disorders - Oedema - Abortion - Immune response exhaustion
Describe advanced stage symptoms of ASS
- Inflammation of NS (inc. brain) - Over production of pro-inflammatory cytokines - Accumulation of lymphocytes and plasma cells at brain surface (meningo-encephalitis)
