Treatment of Human Babesiosis: Then and Now

Renard, Isaline; Mamoun, Choukri Ben

doi:10.3390/pathogens10091120

Cited by 43 publications

(62 citation statements)

References 132 publications

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“…Eighty-eight percent of these cases were residents of 7 states where tickborne transmission is well established: Connecticut, Massachusetts, Minnesota, New Jersey, New York, Rhode Island, and Wisconsin. Although transmission through transfusion, organ transplant, and placenta is possible and has been reported, history of travel to areas with established local transmission has been documented for many of the cases from those states that lack an established local transmission [2 , 3] . It is speculated that the thoroughness of reported statistics might have been affected by the COVID-19 pandemic and its inevitable challenges in 2019 [2] .…”

Section: Introductionmentioning

confidence: 99%

Splenic artery embolization for spontaneous splenic rupture due to Babesiosis: a case report

Khazai

Homsi

Anendaga

et al. 2022

Radiology Case Reports

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Section: Introductionmentioning

confidence: 99%

Splenic artery embolization for spontaneous splenic rupture due to Babesiosis: a case report

Khazai

Homsi

Anendaga

et al. 2022

Radiology Case Reports

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“…Babesia parasites are phylogenetically closely related to Plasmodium species and cause a malaria-like illness, which in susceptible individuals can lead to hemolytic anemia, acute respiratory distress syndrome, hepatosplenomegaly, multiorgan failure and possibly death [12]. Human babesiosis is an emerging tick-borne disease and is spreading rapidly mostly due to changes in the geographic distribution of the vector, anthropogenic factors and global warming [1, 12, 13]. Several species of Babesia, including B. microti , B. duncani and B. divergens , are known to cause infection in humans [1].…”

Section: Introductionmentioning

confidence: 99%

“…Human babesiosis is an emerging tick-borne disease and is spreading rapidly mostly due to changes in the geographic distribution of the vector, anthropogenic factors and global warming [1, 12, 13]. Several species of Babesia, including B. microti , B. duncani and B. divergens , are known to cause infection in humans [1]. B. microti , the most commonly reported Babesia pathogen, can be propagated in immunocompetent and immunocompromised mice but has not yet been successfully maintained continuously in vitro in human red blood cells [1].…”

Section: Introductionmentioning

confidence: 99%

Babesia duncani as a model organism to study the development, virulence and drug susceptibility of intraerythrocytic parasites in vitro and in vivo

Mamoun

Pal

Renard

et al. 2021

Preprint

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Hematozoa are a subclass of protozoan parasites that invade and develop within vertebrate red blood cells to cause the pathological symptoms associated with diseases of both medical and veterinary importance such as malaria and babesiosis. A major limitation in the study of the most prominent hematozoa, Plasmodium spp, the causative agents of malaria, is the lack of a broadly accessible mouse model to evaluate parasite infection in vivo as is the case for P. falciparum or altogether the lack of an in vitro culture and mouse models as is the case for P. vivax, P. malariae and P. ovale. Similarly, no in vitro culture system exists for Babesia microti, the predominant agent of human babesiosis. In this study, we show that human red blood cells infected with the human pathogen Babesia duncani continuously propagated in culture, as well as merozoites purified from parasite cultures, can cause lethal infection in immunocompetent C3H/HeJ mice. Furthermore, highly reproducible parasitemia and survival outcomes were established using specific parasite loads and different mouse genetic backgrounds. Using the combined in culture-in mouse (ICIM) model of B. duncani infection, we demonstrate that current recommended combination therapies for the treatment of human babesiosis, while synergistic in cell culture, have weak potency in vitro and failed to clear infection or prevent death in mice. Interestingly, using the ICIM model, we identified two new endochin-like quinolone prodrugs, ELQ-331 and ELQ-468, that alone or in combination with atovaquone are highly efficacious against B. duncani and B. microti. The novelty, ease of use and scalability of the B. duncani ICIM dual model make it an ideal system to study intraerythrocytic parasitism by protozoa, unravel the molecular mechanisms underlying parasite virulence and pathogenesis, and accelerate the development of innovative therapeutic strategies that could be translated to unculturable parasites and important pathogens for which an animal model is lacking.Author SummaryUse of model organisms is vital to the understanding of virulence and pathogenesis of a large number of human and animal pathogens. In case of hematozoan parasites that invade and develop within vertebrate erythrocytes, the studies are challenging because of the dearth of small animal model systems and the lack of continuous parasite growth in in vitro culture conditions. Here, we report a small animal model of lethal infection of Babesia duncani, one of the causative agents of human babesiosis. We show that in vitro cultured parasites and as well as parasites propagated in vivo can establish highly reproducible parasitemia which is dependent on the parasite load and also defined by different mouse genetic backgrounds. We further use this combined in culture-in mouse (ICIM) model of B. duncani infection to demonstrate the anti-babesial efficacy of two novel endochin like quinoline compounds. We propose that this ICIM dual model of B. duncani is an ideal system to get insights into protozoan intraerythrocytic parasitism, virulence, pathogenesis, and therapeutics and will open the vista to other important pathogens which are unculturable or lack an animal model.

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Section: Introductionmentioning

confidence: 99%

“…Currently, there is no specific therapy for B. microti human babesiosis [7]. The recommended therapeutic drugs to treat B. microti infections are azithromycin plus atovaquone as the first choice or a combination of clindamycin and quinine as an alternative [7,8]. However, the reported appearance of B. microti parasites resistant to the first two drugs in chronically infected patients and the negative side effects of the latter two call for the development of alternative therapeutic strategies and increased investments in this field [2,[7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

In Silico Survey and Characterization of Babesia microti Functional and Non-Functional Proteases

et al. 2021

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Human babesiosis caused by the intraerythrocytic apicomplexan Babesia microti is an expanding tick-borne zoonotic disease that may cause severe symptoms and death in elderly or immunocompromised individuals. In light of an increasing resistance of B. microti to drugs, there is a lack of therapeutic alternatives. Species-specific proteases are essential for parasite survival and possible chemotherapeutic targets. However, the repertoire of proteases in B. microti remains poorly investigated. Herein, we employed several combined bioinformatics tools and strategies to organize and identify genes encoding for the full repertoire of proteases in the B. microti genome. We identified 64 active proteases and 25 nonactive protease homologs. These proteases can be classified into cysteine (n = 28), serine (n = 21), threonine (n = 14), asparagine (n = 7), and metallopeptidases (n = 19), which, in turn, are assigned to a total of 38 peptidase families. Comparative studies between the repertoire of B. bovis and B. microti proteases revealed differences among sensu stricto and sensu lato Babesia parasites that reflect their distinct evolutionary history. Overall, this data may help direct future research towards our understanding of the biology and pathogenicity of Babesia parasites and to explore proteases as targets for developing novel therapeutic interventions.

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Treatment of Human Babesiosis: Then and Now

Cited by 43 publications

References 132 publications

Splenic artery embolization for spontaneous splenic rupture due to Babesiosis: a case report

Splenic artery embolization for spontaneous splenic rupture due to Babesiosis: a case report

Babesia duncani as a model organism to study the development, virulence and drug susceptibility of intraerythrocytic parasites in vitro and in vivo

In Silico Survey and Characterization of Babesia microti Functional and Non-Functional Proteases

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