Babesia microtiVariant With Multiple Resistance Mutations Detected in an Immunocompromised Patient Receiving Atovaquone Prophylaxis

Abstract

We report Babesia microti genomic sequences with multiple mutations in the atovaquone-target region of cytochrome b, including a newly identified Y272S mutation, plus one mutation of undetermined significance in the azithromycin-associated ribosomal protein L4. The parasite was sequenced from an immunocompromised patient on prophylactic atovaquone for Pneumocystis pneumonia prior to diagnosis of babesiosis.

Relapsing Babesiosis With Molecular Evidence of Resistance to Certain Antimicrobials Commonly Used to Treat Babesia microti Infections

“…Being immunocompromised likely negatively impacted clearance of the parasitemia, allowing the opportunity for the development of mutations in the genes associated with the atovaquone- and azithromycin-targeted proteins in the CYTb and the 50S ribosomal subunit of the parasite, respectively. In addition to these 9 patients, an additional immunocompromised patient has been reported (but not included in Table 1 because the patient was not reported to have relapsing babesiosis) [ 21 ], who developed B microti infection while receiving atovaquone as prophylaxis to prevent Pneumocystis jirovecii infection. This patient was found to have 4 different amino acid changes in CYTb, thought to reduce susceptibility to atovaquone (Y272S, V141A, M134I, and M134 T).…”

Plasma Blood Levels of Tafenoquine following a Single Oral Dosage in BALBc Mice with Acute Babesia microti Infection That Resulted in Rapid Clearance of Microscopically Detectable Parasitemia

“…The current study is the first to examine plasma levels of tafenoquine associated with a rapid reduction of B. microti parasitemia. Further studies that combine tafenoquine blood and plasma pharmacokinetic analysis with parasite reduction and clearance are necessary to establish therapeutic tafenoquine doses, not only for B. microti species, including those resistant to current treatments such as atovaquone and azithromycin but also for other Babesia that cause human babesiosis including B. duncani , which appears to be more resistant than B. microti to at least some treatments [ 5 , 17 , 19 , 31 , 37 , 38 ]. These studies are needed to establish the blood/plasma levels of tafenoquine necessary to kill parasites, as well as to determine how long the effective blood/plasma levels need to be maintained.…”

“…Immunocompromised individuals often have severe and prolonged bouts of Babesia infection, even with the most effective current treatments. In addition, Babesia parasites that are resistant to atovaquone alone or atovaquone and azithromycin may emerge [ 17 , 18 , 19 ]. More effective treatment options for babesiosis, particularly for immunocompromised individuals or for those with babesiosis refractory to current therapies, need to be developed.…”

Efficacy and mechanism of actions of cipargamin as an antibabesial drug candidate

“…Currently, the most common drugs for the treatment of human babesiosis include a combination of atovaquone (ATQ) plus azithromycin (AZM) or clindamycin plus quinine (Holbrook et al, 2023). Still, these recommended treatments often result in various problems.…”

“…For instance, multiple mutations in the B. microti cytochrome b, which was associated with the atovaquone-target region, were discovered in an atovaquone-treated relapse patient (Holbrook et al, 2023). The combination of clindamycin and quinine is the last resort for patients with severe symptoms.…”