Use of atovaquone (Mepron) in patients coinfected with Borrelia burgdorferi and Babesia microti with symptoms refractory to antibiotics and cholestyramine
Reports of successful treatment of Borrelia
burgdorferi infections, occurring concomitantly with infection with Babesia
microti in 10% of patients, have shown benefit of short-term use of atovaquone
in combination with azithromycin. Two
recent studies involving 341 patients with Lyme Disease who had symptoms
refractory to antibiotics (Post-Lyme Syndrome, PLS) have shown benefit from a
treatment protocol using pioglitazone and cholestyramine (CSM), resulting in
reduction of symptoms and improvement in visual contrast sensitivity (VCS)
scores. These improvements parallel those seen in patients with symptoms
following exposure to biotoxin-forming organisms, including dinoflagellates and
fungal species. In the PLS studies,
6% of patients did not respond to the toxin binding protocol. In this group, patients with coinfection
with Babesia were disproportionately represented.
25 patients with serologic evidence of
exposure to Babesia microti and Borrelia burgdorferi with persistent, long term
symptoms despite courses of antibiotics, including atovaquone and azithromycin
and despite use of the pioglitazone-CSM protocol were enrolled in a double-blinded,
placebo-controlled, prospective, crossover clinical trial that received FDA and
IRB approval. Patients were given
either atovaquone or placebo for 3 weeks in combination with cholestyramine and
then crossed over to the other arm of the double-blinded trial. Treatment for 6 additional weeks of
atovaquone and cholestyramine, provided on an open label basis, followed.
Symptoms and VCS scores were recorded.
22 patients completed the trial. 3 dropped out; 1 for non-study related
reasons and 2 because of intolerance to CSM.
1 patient stopped treatment at 9 weeks, feeling no improvement. Not all patients provided all interim VCS
data, but all provided exit information.
5 patients had complete resolution of their longstanding
symptoms. 16 had significant reduction
in number and/or severity of symptoms.
There were no adverse effects noted other than mild worsening of
symptoms experienced by patients during the first few weeks of atovaquone
therapy. Patients noticed clinical
improvement near the end of the second 3-week course of atovaquone, with
continued improvement noted during the third course of atovaquone in
combination with CSM.
This study supports the concept that some persistent symptoms in Lyme disease patients with Babesia are possibly related to the slow release over time of a neurotoxin made by both the Borrelia and by the Babesia organisms. Resolution of symptoms in these patients is not accomplished by short-term use of antibiotics. Neurotoxin binding protocols employing CSM have a significant adjuvant role in treating patients with chronic symptoms in Lyme patients coinfected with Babesia, but atovaquone must be continued in these patients for a prolonged period of time. Additional studies in coinfected patients are indicated as coinfection rates now exceed 10% in endemic areas. Areas of particular interest include the role of pro-inflammatory cytokines in coinfection, possible extravascular sequestration of viable Babesia organisms and the role of the extrachromosomal 35 kb plastid DNA, homologous to DNA of Euglena, in maintaining viable Babesia organisms, despite reportedly curative courses of antibiotics, in symptomatic coinfected patients.