African Trypanosomiasis - Research

Research

The genome of the parasite has been sequenced and several proteins have been identified as potential targets for drug treatment. Analysis of the genome also revealed the reason why generating a vaccine for this disease has been so difficult. T. brucei has over 800 genes that make proteins the parasite "mixes and matches" to evade immune system detection.

Recent findings indicate the parasite is unable to survive in the bloodstream without its flagellum. This insight gives researchers a new angle with which to attack the parasite.

A new treatment based on a truncated version of the apolipoprotein L-1 of high density lipoprotein and a single-domain antibody has recently been found to work in mice, but has not been tested in humans.

The cover story of the August 25, 2006 issue of the journal Cell describes an advance in understanding how Trypanosomes escape the immune system. Dr. Lee Soo Hee and colleagues, working at Johns Hopkins investigated the pathway by which trypanosomes make myristate, a 14-carbon length fatty acid. Myristate is a component of the variant surface glycoprotein (VSG), the molecule that makes up the trypanosome's outer layer. This outer surface coat of VSG is vital to the trypanosome's ability to avoid destruction by the host's immune system. Dr. Lee and colleagues discovered trypanosomes use a novel fatty acid synthesis pathway involving fatty acid elongases to make myristate and other fatty acids.

An international research team working in the Democratic Republic of the Congo, Southern Sudan, and Angola involving Immtech International and University of North Carolina at Chapel Hill have completed a Phase IIb clinical trial and began a Phase III trial in 2005 testing the efficacy of the first oral treatment for sleeping sickness, pafuramidine (DB289). Trypanosomiasis vaccines are undergoing research.

Two independent variants of the APOL1 gene found in African haplotypes carrying signatures of natural selection have been shown to confer protection against the acute version of sleeping sickness caused by T. b. rhodesiense, while at the same time increasing risk of kidney disease when inherited from both parents.

Synthetic and computer-based approaches are used for the development of newer antitrypanosomal analogues with improved efficacy and oral bioavailability.

The Dempster-Shafer theory for detecting African trypanosomiasis displays the result of detection process.

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