Histamine-mediated signalling: a new pharmaceutical target to control malaria relapses?

Malaria, a disease affecting humans but also many other vertebrate animals, is caused by a vector-borne pathogen, Plasmodium. The dynamic of malaria infection within the vertebrate host is characterized by drastic temporal changes in the intensity of infection. After an initial acute phase, characterized by a very high parasite burden in the blood, the infection reaches a chronic phase where the parasite burden stabilizes at low level for several months or years. The chronic phase of infection may be interrupted by relapses during which Plasmodium go through intense, but short, episodes of replication leading to temporarily increased parasite burden. Malaria relapses seem to be induced by several environmental cues (e.g. photoperiod, hormone level) but also by bites of the mosquito vector. Some Plasmodium species respond to mosquito bites by enhancing their replication rate in the vertebrate host. Although the mechanisms by which mosquito probing can induce an increase in Plasmodium replication, and ultimately a relapse, are not known, the physiological response of the vertebrate host to mosquito saliva could be the triggering mechanism. The injection of mosquito saliva induces an allergic inflammatory response mediated by increases in histamine concentration. It has been suggested that the biological effects of histamine, such as immunosuppression, vasodilatation, modification of the endothelial permeability, might be exploited by Plasmodium. In addition, the existence of a Plasmodium protein that stimulates histamine release in the blood of infected hosts supports the hypothesis that the presence of histamine is advantageous to the pathogen. Targeting this metabolic pathway may provide novel therapeutic approaches to control the replication of Plasmodium in the vertebrate host. 

Project details

Basic Science

Feb 2020 — Jan 2021

$95,570

Switzerland