Parasitic infection treatment and interventions Flashcards
Why is development of vaccines against parasites difficult (+ what vaccines have been developed)
Parasites are complex, long lived and require time to complete their complex lifecycles
Have developed sophisticated ways to manipulate and evade host immune response
Transition through many developmental stages, adopting different morphologies and rely on stage-specific biological parameters
Occupy different niches across lifecycles, both internal and external to hosts
Many are not lab-adaptable so cannot grow and study in detail
Vaccines developed against malaria, leishmaniasis, schistosomiasis and hookworm, varying degrees of success, with malaria vaccines most advanced
Malaria vaccine development
Targets 3 stages: sporozoite (injected into host by infected mosquito), merozoite (bursts from RBCs during blood stage) and mosquito stages (gametocytes, gametes, ookinetes) that develop in mosquito midgut following gametocyte uptake in blood meal
Most advanced vaccine is RTS,S, a pre-erythrocytic stage vaccine. Consists of a virus-like particle (VLP) displaying hepatitis B surface antigen alone (S) and fused with P. falciparum circumsporozoite protein fragment containing its central repeats and T cell epitopes (RTS). Efficacy of 51.3% against clinical malaria in children over 12 months after 3 doses of vaccine. Reduces clinical disease, but has no effect on transmission or parasite control
Transmission blocking vaccines use antigens expressed during mosquito parasite stages to induce functional antibodies that attack parisite in mosquito and impair its viability, inhibit development, or impede interaction with mosquito midgut. Hope is to reduce number of circulating infectious mosquitos below a threshold of transmission to achieve natural population bottleneck
Chemotherapy
a) against helminths
b) against malaria (and problems)
a) Ivermectin - widely used in vet medicine to treat lung and stomach worms in cattle, scabies in pigs, heartworm in dogs. AlsoO. volvulus in humans (causes river blindness)
Praziquantel - treat schistosomiasis
Albendazole - treat intestinal parasites (annual deworming programs)
Usually administered annually, very effective in reducing worm-related morbidity in children. But not given frequently enough to interrupt transmission/eliminate. Giving too often to farm animals can drive resistance
b) Artemisinin - part of combination therapies to treat malaria
P. falciparum has developed resistance to most antimalarial drugs. Current treatment is using artemisinin-combination therapies (ACTs) as multiple drugs are more difficult for parasites to develop resistance against. However, resistance to ACTs is prevalent, concerning as currently no alternative therapies
Vector control for malaria
Eradication of malaria is a major global public health objective. Reducing number of cases through vector control has proven this is critical to interrupting transmission. Widespread use of DDT compound has targeted mosquito populations and eradicated malaria from some areas. Pyrethroid-impregnated bednets, DDT indoor residual spraying and ACTs has measurably reduced P. falciparum malaria in sub-Saharan Africa
