Human African trypanosomiasis and Leishmaniasis Flashcards
Kinetoplastida (the order)
-parasitic protozoa
-named after the “kinetoplast” a network of circular DNA molecules within the single mitochondrion
-genera which infect man include:
-leishmania spp
-trypanosoma spp
-
Human African trypanosomiasis (HAT)
- man and animals
- trypanosoma brucei gambiense and T.b rhodesiense cause disease in man
Sleeping sickness facts:
vector= tsetse fly (moist savanna and woodlands)
natural host=
ungulates &other mammals (rhodesinse)
mainly man only (gambiense)
genus= Glossina
Who first recognised that trypanosomes caused sleeping sickness?
Sir David Bruce (Edinburgh)
Muriel Robertson
-life cycle of the trypanosome, cycling between humans and tsetse flies
Transmission of trypanosomes:
Via bite of tsetse fly
- Inoculation of parasites in saliva
- ingestion of parasites with blood meal
Trypanosoma brucei gambiense
- causes chronic form of the disease
- this form = endemic in West and Central Africa
Trypanosoma brucei rhodesiense
- causes acute form of the disease (just weeks between infection and death)
- East and Southern Africa
Stages:
- parasites injected by tsetse fly invade the blood and lymphatic systems
- they later invade the CNS and brain
- brain disorders in late stage include sleep wake patterns (hence sleeping sickness)
Weeks after infection
successive waves of parasitaemia
- due to timing of immune reaction
- parasites grow for about a week before immune system mounts fatal antibody response
- a small number of parasites change their coat and can now grow while immune system needs to check their foreign status again
Structure of trypanosome:
-surface is covered in densely packed “VARIANT SURFACE GLYCOPROTEIN” (Vsg) coat
Structure of trypanosome: (ii)
- single coat protein expressed at one time
- proteins form homodimers
- they anchor to the membrane via a glycosyl phosphatidyl inositol (gpi) anchor
- coat prevents complement proteins fixing at the trypanosomes plasma membrane
Structure of trypanosome: (iii)
- they have potential to express over 1000 VSGs, but express only one at a time
- complex gene expression regulation
Process of antigenic variation in trypanosomes
-affects ability to produce vaccine against African trypanosomiasis
Chemotherapy of human African trypanosomiasis (HAT)
- 5 drugs
- Suramin and pentamidine useful against early stage disease (before invasion of the CNS)
- melarsoprol and eflornithine useful against late stage of disease (after CNS invasion)
5 DRUGS useful in chemotherapy of HAT
- Suramin
- Pentamidine
- Melarsoprol
- Eflornithine
- Nifurtimox
Vector control:
- insecticide spraying
- tsetse trapping
- sterile male release
The Leishmaniases:
- parasites of different species affect different parts of the body - They invade macrophages
- after macrophage invasion they become amastigote forms proliferating inside the macrophages
Vector for Leishmania parasites:
-sandflies
Who first described Leishmania parasites? in 1900
William Leishman (Glasgow uni)
New world Leishmaniasis:
L. mexicana (cutaneous)
L. braziliensis (mucocutaneous)
L. infantum (visceral)
Leishmaniasis = zoonotic
dogs represent key reservoir host
Sandfly/human stages (LEISH)
- sandfly takes blood meal (and injects promastigote stage into skin of human)
- Promastigotes are phagocytized by macrophages
- Promastigotes transform into amastigotes inside macrophages
- Amastigotes multiply in cells of various tissues
- Sandfly takes a blood meal (and ingests macrophages infected with amastigotes)
- Ingestion of parasitized cell
- Amastigotes transform into promastigote stage in midgut
- Divide in midgut and migrate to proboscis
Amastigotes
inside macrophage
