The treatment strategies for either human or animal babesiosis have been established and used for many years. With the rising indications of drug resistance and adverse side effects, finding effective and alternative therapies is urgently needed. Sitamaquine (SQ) is an 8-aminoquinoline that was first synthesized as a part of the collaborative anti-malarial program that led to primaquine. In this study, we evaluated the inhibitory effects of SQ on Babesia spp. in vitro and in vivo. The half-maximal inhibitory concentration (IC50) on in vitro cultured Babesia gibsoni was 8.04 ± 1.34 μM. Babesia gibsoni parasites showed degenerative morphological changes following SQ treatment. The in vivo growth inhibitory effects of SQ were evaluated in BALB/c mice infected with B. microti and atovaquone (ATV)-resistant B. microti strain. Oral administration of SQ at a dose of 20 mg/kg significantly inhibited the growth of B. microti and ATV-resistant B. microti. Meanwhile, SQ also showed inhibitory effects on the growth of B. rodhaini, a lethal rodent Babesia species. All mice infected with B. rodhaini treated with SQ survived, whereas the mice in the control group succumbed to the disease. The results obtained in this study indicate that SQ has potent inhibition effects against Babesia spp., which support SQ as a prospective alternative candidate for babesiosis treatment.

Piroplasmosis, a tick-borne disease affecting livestock, including camels, is caused by intracellular apicomplexan parasites belonging to the order Piroplasmida. Despite its importance, there\'s limited research on piroplasmosis among Egyptian camels. This study aimed to fill this gap by investigating tick-borne piroplasmids in camels from Cairo and Giza Governorates. Out of 181 blood samples collected between October 2021 and March 2022 from apparently healthy one-humped camels (Camelus dromedarius), PCR assays revealed a 41.4 % infection rate with various piroplasmids. Detected species included B. bovis (17.7 %), B. bigemina (12.2 %), B. caballi (8.3 %), B. naoakii (11.6 %), B. microti (1.7 %), T. equi (4.4 %), and Theileria spp. (28.7 %). Phylogenetic analysis revealed the first detection of T. equi genotype E in Egypt and identified a novel B. caballi genotype. Additionally, B. microti isolates were identified as the US-type. These findings shed lights on piroplasmosis among Egyptian camels, and provide valuable information for devising effective control strategies, especially B. microti, a pathogen with potential human health risks.

Endochin-like quinolones (ELQs) define a class of small molecule antimicrobials that target the mitochondrial electron transport chain of various human parasites by inhibiting their cytochrome bc1 complexes. The compounds have shown potent activity against a wide range of protozoan parasites, including the intraerythrocytic parasites Plasmodium and Babesia, the agents of human malaria and babesiosis, respectively. First-generation ELQ compounds were previously found to reduce infection by Babesia microti and Babesia duncani in animal models of human babesiosis but achieved a radical cure only in combination with atovaquone and required further optimization to address pharmacological limitations. Here, we report the identification of two second-generation 3-biaryl ELQ compounds, ELQ-596 and ELQ-650, with potent antibabesial activity in vitro and favorable pharmacological properties. In particular, ELQ-598, a prodrug of ELQ-596, demonstrated high efficacy as an orally administered monotherapy at 10 mg/kg. The compound achieved radical cure in both the chronic model of B. microti-induced babesiosis in immunocompromised mice and the lethal infection model induced by B. duncani in immunocompetent mice. Given its high potency, favorable physicochemical properties, and low toxicity profile, ELQ-596 represents a promising drug for the treatment of human babesiosis.

Babesiosis is perceived mainly an animal disease; however, awareness that Babesia spp. parasites that can cause diseases in humans is increasing significantly. Babesiosis is spread by the bite of an infected tick (Ixodes spp.), but it can also be transmitted by transfusion of infected blood and from an infected mother to her child during pregnancy or childbirth. The parasites multiply in the bloodstream and destroy red blood cells. This study aimed to assess the influence of Babesia microti on the histological structure of the placenta. Histopathological material collected from pregnant rats infected with Babesia microti was used in the experiment. Microscopic images of the placentas were assessed by Mallory staining and by using methylene blue-stained semi-thin sections. In addition, FISH was used to detect parasite DNA. The presence of piroplasms in both maternal and fetal vessels was demonstrated. Babesia microti infection caused vacuolization of syncytioblasts and cytotrophoblasts, accumulation of collagen fibers in placental villi, and increased adhesion of erythrocytes to the vascular walls. These results indicate that Babesia may influence the course of pregnancy and invite further research on the mechanism of piroplasm penetration into cells.

Diminazene aceturate (DA), imidocarb dipropionate (ID), atovaquone (ATO), azithromycin (AZI), clindamycin, and quinine have been used to treat animal and human babesiosis for many years, despite their negative effects and rising indications of resistance. Thus, finding anti-babesial compounds that can either treat the infection or lower the dose of drugs given has been a primary objective. Quinazolines are one of the most important nitrogen heterocycles, with a wide range of pharmacological activities including analgesic, anti-inflammatory, sedative-hypnotic, anti-histaminic, anti-cancer, and anti-protozoan properties. The present study investigated the anti-babesial activities of twenty 6,7-dimethoxyquinazoline-2,4-diamines on Babesia spp. One candidate, 6,7-dimethoxy-N4-ethylisopropyl-N2-ethyl(pyridin-4-yl)quinazoline-2,4-diamine (SHG02), showed potent inhibition on Babesia gibsoni in vitro, as well as on B. microti and B. rodhaini in mice. Our findings indicate that the candidate compound SHG02 is promising for further development of anti-babesial drugs and provides a new structure to be explored for developing anti-Babesia therapeutics.

Tick-borne Babesiosis is a parasitic infection caused by Babesia microti that can infect both animals and humans and may spread by tick, blood transfusions, and organ transplantation. The current therapeutic options for B. microti are limited, and drug resistance is a concern. This study proposes using computational drug design approaches to find and design an effective drug against B. microti. The study investigated the potentiality of nine natural compounds against the pathogenic human B. microti parasite and identified Vasicinone and Evodiamine as the most promising drugs. The ligand structures were optimized using density functional theory, molecular docking, molecular dynamics simulations, quantum mechanics such as HOMO-LUMO, drug-likeness and theoretical absorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacokinetics characteristics performed. The results showed that Vasicinone (-8.6 kcal/mol and -7.8 kcal/mol) and Evodiamine (-8.7 kcal/mol and -8.5 kcal/mol) had the highest binding energy and anti-parasitic activity against B. microti lactate dehydrogenase and B. microti lactate dehydrogenase apo form. The strongest binding energy was reported by Vasicinone and Evodiamine; the compounds were evaluated through molecular dynamics simulation at 100 ns, and their stability when they form complexes with the targeted receptors was determined. Finally, the pkCSM web server is employed to predict the ADMET qualities of specific molecules, which can help prevent negative effects that arise from taking the treatment. The SwissADME web server is used to assess the Lipinski rule of five and drug-likeness properties including topological polar surface area and bioavailability. The Lipinski rule is used to estimate significant drug-likeness. The theoretical pharmacokinetics analysis and drug-likeness of the selected compounds are confirmed to be accepted by the Lipinski rule and have better ADMET features. Thus, to confirm their experimental value, these mentioned molecules should be suggested to carry out in wet lab, pre-clinical, and clinical levels.

Being one of the widespread parasitic infections in particular parts of the United States, babesiosis may present with varying severity of clinical manifestations. Depending on the severity and degree of hemolysis, some patients may need a more aggressive approach, such as repeated red blood cell (RBC) transfusions, while in others, symptoms may be well-controlled with conservative therapy only using a disease-specific approach. We are presenting two cases with a significant difference in severity and medical therapy.

Human babesiosis is a zoonotic disease caused by protozoan parasites of the Babesia genus, primarily in the Northeastern and Midwest United States due to B. microti, and Western Europe due to B. divergens. Parasites are transmitted by the bite of the ixodid tick when the vector takes a blood meal from the vertebrate host, and the economic importance of bovine babesiosis is well understood. The pathology of human disease is a direct result of the parasite\'s ability to invade host\'s red blood cells. The current understanding of human babesiosis epidemiology is that many infections remain asymptomatic, especially in younger or immune competent individuals, and the burden of severe pathology resides within older or immunocompromised individuals. However, transfusion-transmitted babesiosis is an emerging threat to public health as asymptomatic carriers donate blood and there are as yet no licensed or regulated tests to screen blood products for this pathogen. Reports of tick-borne cases within new geographical regions such as the Pacific Northwest of the US, through Eastern Europe, and into China are also on the rise. Further, new Babesia spp. have been identified globally as agents of severe human babesiosis, suggesting that the epidemiology of this disease is rapidly changing, and it is clear that human babesiosis is a serious public health concern that requires close monitoring and effective intervention measure.

Babesiosis is an emerging tick-transmitted zoonosis in large parts of the world. In Sweden, the occurrence and diversity of Babesia species is largely unknown. In order to estimate the exposure to Babesia from infected ticks, we collected questing Ixodes ricinus from several sites across southern Sweden during two consecutive field seasons and investigated the occurrence of Babesia species. We report for the first time the occurrence of the zoonotic species Babesia venatorum in Swedish ticks, with a prevalence of 1%. We also detected B. microti (prevalence 3.2%) and B. divergens (prevalence 0.2%). The incidence of Babesia in questing ticks is substantially lower than that of several other tick-borne diseases in Sweden. Nevertheless, babesiosis should not be neglected as a possible diagnosis following tick bites in humans and animals in Sweden.

Babesia microti is a tick-transmitted zoonotic hemoprotozoan parasite. In the present study, we investigated B. microti infection in questing ticks in Mongolia. A total of 219 questing ticks were collected from three different Mongolian provinces (Bayan-Olgii, Khovsgol, and Selenge). Of these, 63 from Selenge were identified as Ixodes persulcatus, while the remaining 156 (from all three provinces) were identified as Dermacentor nuttalli. When the tick DNA samples were screened using a B. microti-specific nested PCR, 19 (30.2%) of the 63 I. persulcatus ticks were found to be B. microti-positive. The parasite was not detected in D. nuttalli. Subsequently, the 18S rRNA, cox1, and tufA sequences of B. microti were amplified, sequenced, and subjected to phylogenetic analyses. Sequencing analyses showed that the Mongolian 18S rRNA, cox1, and tufA sequences were 99.6-100%, 96.7-97.2%, and 94.7-95.3% homologous, respectively, with B. microti R1 strain US-type sequences from humans. In the phylogenetic analyses, the Mongolian cox1 and tufA sequences were found to be separate lineages, which formed sister-clades to the R1 strain sequences, while all of the Mongolian B. microti 18S rRNA sequences were clustered within US-type clade containing several other sequences of human origin. In conclusion, in addition to reporting the presence of B. microti for the first time in questing ticks in Mongolia, the present study found that Mongolian I. persulcatus ticks were infected with US-type B. microti. These findings warrant large-scale studies to detect and characterize B. microti in ticks, small mammals, and humans. Such studies should provide us with a better understanding of zoonotic Babesia epidemiology in Mongolia.