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wtorek, 7 czerwca 2016

Atovaquone - MALARONE

06-06-2016

Jest to pierwsze  radykalne lekarstwo przeciwko tym pasożytem - powiedział Choukri Ben Mamoun, profesor chorób zakaźnych."
Nowością jest terapia  , która będzie mogla zarówno zabić pasożyta oraz zapobiegać nawrotom.

Odkrycie jest istotne, ponieważ babeszioza  zarażonych jest około  19% kleszczy i  42% ssaków (myszy i innych gryzoni), które przenoszą bakterie powodujące  Borelioze.


http://news.yale.edu/2016/06/06/combination-therapy-cures-tick-borne-illness-mice

A novel combination therapy cures an emerging infectious disease, babesiosis, which is transmitted by the same ticks that transmit the agents of Lyme disease, said Yale researchers. This “radical” therapy not only clears the infection but also prevents the recurrence that often occurs with existing treatments.
The study was published online June 6 in The Journal of Experimental Medicine.
Babesiosis (bab-e-see-oh-sis) is caused by the B. microti parasite, which is most often transmitted through tick bites. It is more common in the Northeast and northern Midwestern states, and likely is on the rise as infected ticks expand geographically. Infected individuals can be asymptomatic, or develop symptoms that range from mild and flu-like to severe and life threatening. The parasite can develop resistance to existing therapies, leading to relapses after treatment.
For their study, the Yale-led team first tested in mice with diminished immune systems four drugs that are currently used in the form of two combinations to treat human babesiosis. Only one of those drugs, atovaquone, was effective in attacking a target enzyme that, when mutated, allows the parasite to develop resistance. Using the mouse model, the team observed efficacy with a fifth drug (ELQ) that involves a similar mechanism of action as atovaquone but at a different enzyme target site. They decided to test the two drugs in combination.

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09-2000
Atowakwon i azytromycyna  w leczeniu babesiozy

Results

Study Population

Of the 59 subjects who were enrolled in the study, 41 were randomly assigned to receive atovaquone and azithromycin, and 18 were randomly assigned to receive clindamycin and quinine. Forty-three of the enrolled subjects were from Nantucket, 12 were from Connecticut, and 4 were from Block Island. One of the subjects assigned to receive atovaquone and azithromycin was excluded from all analyses because he became severely ill and required assisted ventilation two days after enrollment. The subjects in the two treatment groups had similar age and sex distributions, had a similar array of symptoms, and had a similar degree of parasitemia when therapy commenced

http://www.nejm.org/doi/full/10.1056/NEJM200011163432004#t=article

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Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone

Human babesiosis is a tick-borne multisystem disease caused by Babesia species of the apicomplexan phylum. Most clinical cases and fatalities of babesiosis are caused by Babesia microti. Current treatment for human babesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin. These treatments are associated with adverse side effects and a significant rate of drug failure. Here, we provide evidence for radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone (ELQ) prodrug and atovaquone. In vivo efficacy studies in mice using ELQ-271, ELQ-316, and the ELQ-316 prodrug, ELQ-334, demonstrated excellent growth inhibitory activity against the parasite, with potency equal to that of orally administered atovaquone at 10 mg/kg. Analysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions in the Qi or Qo sites, respectively, of the cytochrome bc1 complex. Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted in complete clearance of the parasite with no recrudescence up to 122 d after discontinuation of therapy. These results will set the stage for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human babesiosis.

http://jem.rupress.org/content/early/2016/06/06/jem.20151519.abstract

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New Therapeutic Protocol for Canine Babesiosis: Acase Report



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