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Babesiosis - Combination therapy cures tick-borne illness in mice

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Combination therapy cures tick-borne illness in mice
Yale News
June 6th 2016
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.

The researchers found that the combination of atovaquone and ELQ-334, at low doses, cleared the infection and prevented recurrence up to 122 days after treatment.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Research paper.

Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone.
Lauren A. Lawres, Aprajita Garg, Vidya Kumar, Igor Bruzual, Isaac P. Forquer, Isaline Renard, Azan Z. Virji, Pierre Boulard, Eduardo X. Rodriguez, Alexander J. Allen, Sovitj Pou, Keith W. Wegmann, Rolf W. Winter, Aaron Nilsen, Jialing Mao, Douglas A. Preston, Alexia A. Belperron, Linda K. Bockenstedt, David J. Hinrichs, Michael K. Riscoe, J. Stone Doggett, and Choukri Ben Mamoun.
http://jem.rupress.org/content/early/2016/06/06/jem.20151519.abstract

ABSTRACT
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.
 

msf

Senior Member
Messages
3,650
Interesting stuff - looks like combination therapy is not just needed for chronic Lyme but for its co-infections too.
 

barbc56

Senior Member
Messages
3,657
Out of curiosity, why do they test this treatment on mice with immunodeficiency? Is this normal protocol?

What about testing in both immunodeficient mice and mice with normal immune systems? It might be related to the subset of me/cfs patients who are immunodeficient. Or not?
 
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Vasha

Senior Member
Messages
119
Out of curiosity, why do they test this treatment on mice with immunodeficiency? Is this normal protocol?

What about testing in both immunodeficient and mice with normal immune systems? It might be related to the subset of me/cfs patients who are immunodeficient. Or not?

Hi @barbc56 -

This is a guess as to why they picked immunodeficient mice, but babesiosis can be very serious, including causing death, for people who are immunodeficient. (E.g. on cancer therapy, on strong immunosuppressants, etc. rather than the less acute immunodeficiency seen in ME).

-Vasha
 

duncan

Senior Member
Messages
2,240
Linda Bockenstedt is one of the authors. Many Lyme patients take issue with some of her stances.

Babesia used to be Peter Krauses territory (one of the IDSA Guidelines forces), but I think he has been spending a lot of time trying to nail down Miyamotoi. Maybe Bockenstedt is assuming more of the babesia efforts.

They all pretty much share the same watering hole anyway.
 

barbc56

Senior Member
Messages
3,657
Hi @barbc56 -

This is a guess as to why they picked immunodeficient mice, but babesiosis can be very serious, including causing death, for people who are immunodeficient. (E.g. on cancer therapy, on strong immunosuppressants, etc. rather than the less acute immunodeficiency seen in ME).

-Vasha
I edited my post as I left out a word. I meant to say to mice with and without immunodeficiency and not human subjects. As you say, that would be disastrous for patients!
 

Vasha

Senior Member
Messages
119
I edited my post as I left out a word. I meant to say to mice with and without immunodeficiency and not human subjects. As you say, that would be disastrous for patients!

Oh, ha ha (not the disaster for patients but the misunderstanding. :) )

No, I understood what you meant @barbc56 - I was trying to say that maybe they picked immunodeficient mice rather than regular mice as a better model for immunodeficient people . . . since babesiosis in immunodeficient people is a big concern.

As to why not test both immunodeficient mice and normal mice . . . maybe cost. Knock-out/model lab animals are expensive.

All speculation, regardless. :)

-Vasha
 

msf

Senior Member
Messages
3,650
Out of curiosity, why do they test this treatment on mice with immunodeficiency? Is this normal protocol?

What about testing in both immunodeficient mice and mice with normal immune systems? It might be related to the subset of me/cfs patients who are immunodeficient. Or not?

They may have chosen immunodeficient mice because immunocompetent mice might clear the infection straightaway, giving them nothing to study.
 

barbc56

Senior Member
Messages
3,657
They may have chosen immunodeficient mice because immunocompetent mice might clear the infection straightaway, giving them nothing to study.

That sounds logical. I wonder if the mice who are not immunodeficient are injected with lyme vs. those who are to see if there is more of a long term effect with the mice who are immunodeficient.But that would be more about contacting lyme. I guess this could eventually study treatment based on these results.

Take this with a grain of salt. I get confused when it comes to the immune system. If anyone has a good but short summary, I would appreciate it!

Thanks!

Btw, if you haven't seen this, the whole issue of using mice for experiences is a conspiracy. By the mice. There's nothing about tooting your own horn. It was pure coincidence that I found the site as I wasn't looking for related information. I looked at my computer history and still can't figure out how I found it!

http://forums.phoenixrising.me/inde...s-a-front-for-psychosocial-experiments.45132/

Also, Paul McCartney has been dead since 1966! It must be true as I read it on the Internet!
 
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