Inhibitory effects of fluoroquinolone antibiotics on Babesia divergens and Babesia microti, blood parasites of veterinary and zoonotic importance

SUMMARY Babesiosis is an emerging, tick-transmitted, zoonotic disease caused by hematotropic parasites of the genus Babesia. Babesial parasites (and those of the closely related genus Theileria) are some of the most ubiquitous and widespread blood parasites in the world, second only to the trypanosomes, and consequently have considerable worldwide economic, medical, and veterinary impact. The parasites are intraerythrocytic and are commonly called piroplasms due to the pear-shaped forms found within infected red blood cells. The piroplasms are transmitted by ixodid ticks and are capable of infecting a wide variety of vertebrate hosts which are competent in maintaining the transmission cycle. Studies involving animal hosts other than humans have contributed significantly to our understanding of the disease process, including possible pathogenic mechanisms of the parasite and immunological responses of the host. To date, there are several species of Babesia that can infect humans, Babesia microti being the most prevalent. Infections with Babesia species generally follow regional distributions; cases in the United States are caused primarily by B. microti, whereas cases in Europe are usually caused by Babesia divergens. The spectrum of disease manifestation is broad, ranging from a silent infection to a fulminant, malaria-like disease, resulting in severe hemolysis and occasionally in death. Recent advances have resulted in the development of several diagnostic tests which have increased the level of sensitivity in detection, thereby facilitating diagnosis, expediting appropriate patient management, and resulting in a more accurate epidemiological description.

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Interactions between the intestinal flagellates Giardia muris and Spironucleus muris and the blood parasites Babesia microti, Plasmodium yoelii and Plasmodium berghei in mice

Parasitology ◽

10.1017/s0031182000054184 ◽

1982 ◽

Vol 85 (1) ◽

pp. 101-110 ◽

Cited By ~ 2

Author(s):

Sara J. Brett ◽

F. E. G. Cox

Keyword(s):

Small Intestine ◽

Total Duration ◽

Plasmodium Yoelii ◽

Blood Parasite ◽

Blood Parasites ◽

Babesia Microti ◽

Parasite Infections ◽

Immunological Factors ◽

Temporary Decrease ◽

Giardia Muris

SUMMARYIn mice infected with the intestinal flagellates Giardia muris or Spironucleus muris, together with the blood parasites Babesia microti or Plasmodium yoelii, there is a temporary decrease of flagellate cyst output coincident with the peak of the blood parasite infections, followed by a rapid return to normal levels. This decrease in cyst output is correlated with decreased numbers of trophozoites in the small intestine. The effect on S. muris is more marked than that on G. muris. Neither blood parasites has any effect on the total duration of the flagellate infection and the flagellates do not affect the blood parasites. In mice infected with G. muris or S. muris and P. berghei there is also a decrease in cyst output but this is less apparent than in infections with B. microti or P. yoelii because of the fatal nature of the P. berghei infection. It is suggested that the decrease in cyst output is probably due to changes in the contents of the small intestine or to non-specific immunological factors rather than to specific immunological changes.

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Blood parasites of the striped field mouse Apodemus agrarius and their morphological characteristics

Biologia ◽

10.2478/s11756-009-0195-3 ◽

2009 ◽

Vol 64 (6) ◽

Cited By ~ 4

Author(s):

Grzegorz Karbowiak ◽

Michal Stanko ◽

Jana Fričová ◽

Irena Wita ◽

Joanna Hapunik ◽

...

Keyword(s):

Seasonal Pattern ◽

Morphological Characteristics ◽

Common Species ◽

Blood Parasites ◽

Babesia Microti ◽

Infection Prevalence ◽

Field Mouse ◽

Intensity Of Infection ◽

Apodemus Agrarius ◽

Nested Analysis

AbstractBlood parasites of Apodemus agrarius were investigated in Eastern Slovakia during 1998–2005. The following parasitic species were detected: Trypanosoma grosi, Babesia microti-like piroplasms and Bartonella sp. Trypanosoma grosi was the most common species, with an infection prevalence of 12.7%. Trypanosomes were morphologically typical of the lewisi group, however, they were bigger than T. grosi described in A. flavicollis and A. sylvaticus. The differences analysed by nested analysis of variance were statistically significant. Pleomorphism was not observed. Infections with piroplasms were detected only at two sites, with an intensity of infection not exceeding 0.1%. The morphology of the piroplasms was different from those typical of B. microti. Bartonella occurred at two sites in 0.81% of the animals sampled. The prevalence of infection had a seasonal pattern throughout the study years. Trypanosomes occurred from July to November, with a peak in September, piroplasms occurred in May and June, and Bartonella sp. from May to July.

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Inhibitory effects of 19 antiprotozoal drugs and antibiotics on Babesia microti infection in BALB/c mice

The Journal of Infection in Developing Countries ◽

10.3855/jidc.5500 ◽

2015 ◽

Vol 9 (09) ◽

pp. 1004-1010 ◽

Cited By ~ 5

Author(s):

Jun-ming Yao ◽

Hao-bing Zhang ◽

Cong-shan Liu ◽

Yi Tao ◽

Meng Yin

Keyword(s):

Drug Screening ◽

Antimalarial Drugs ◽

Babesia Microti ◽

Inhibitory Effects ◽

Drug Activity ◽

Inhibitory Rate ◽

Antiparasitic Drug

Introduction: Different results have been achieved in the evaluation of antiparasitic drug activity in Mongolian jirds, hamsters, and BALB/c mice infected with Babesia microti. The aims of the present study were to find a preferable method for drug screening and to re-evaluate the activity of several drugs against B. microti. Methodology: The activity of 19 drugs on B. microti-infected BALB/c mice was evaluated. The study was built on Peters' four-day suppressive test, and the pathogenicity of the blood from the treated mice was also used as indicator. Results: The results showed that 15 of the 19 drugs had little or no in vivo effect against B. microti. The inhibitory rates of atovaquone and azithromycin were high at all doses, but the microscopy-negative blood of recovered mice was still infectious. Similar to robenidine hydrochloride at 25 and 50 mg/kg, primaquine at 100 mg/kg had a 100% inhibitory rate. Robenidine hydrochloride achieved a 100% inhibitory rate at 100 mg/kg, and the blood of recovered mice did not result in parasitemia in subpassage experiments. Parasite-negative blood from mice treated with antimalarial drugs (clinically used for babesiosis) still caused parasitemia in subpassage experiments. This suggests that these drugs cannot eradicate the parasites. Conclusions: Peters' four-day suppressive test and the pathogenicity of the blood from the treated mice are suitable methods for preliminary investigating possible drugs against B. microti. Considering that robenidine hydrochloride achieved the best activity against B. microti in BALB/c mice in our study, further studies are needed.

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Babesiosis and malaria

10.1093/med/9780198570028.003.0055 ◽

2011 ◽

Author(s):

F. E. G. Cox

Keyword(s):

Ixodes Scapularis ◽

Life Cycles ◽

Molecular Techniques ◽

Babesia Microti ◽

Babesia Divergens ◽

The World ◽

Causative Agents ◽

The Usa ◽

Human Infections ◽

Human Babesiosis

Babesiosis and malaria are rare zoonoses that, with new developments in diagnosis and the application of molecular techniques, are becoming increasingly frequently recognised. Babesia species infect millions of cattle and unknown numbers of sheep, dogs, horses, and wildlife throughout the world but human infections are very uncommon. There are two distinct forms of human babesiosis. In Europe the causative agent is Babesia divergens, a natural parasite of cattle transmitted by the tick Ixodes ricinis. B. divergens infections in humans are extremely rare and nearly all have been recorded from asplenic or otherwise immunocompromised patients. In the USA, human babesiosis is more common than in Europe, although still very rare, and is not restricted to immunocompromised individuals. The causative agents are Babesia microti and B. duncani, common parasites of rodents, transmitted by the tick Ixodes scapularis. In addition there have been sporadic reports of human babesiosis from other parts of the world but in most cases the species of Babesia involved has not been characterised. Malaria parasites and Babesia both inhabit red blood cells during part of their life cycles and these stages cause the diseases, malaria and babesiosis, which are similar in many respects. The facts that humans can occasionally acquire malaria and babesiosis from animals, that both parasites appear similar when seen in blood films and that both cause similar symptoms can cause problems in diagnosis and these rare infections are, therefore, of interest to clinicians and epidemiologists.

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Babesiosis as a disease of people and dogs. Molecular diagnostics: a review

Veterinární Medicína ◽

10.17221/1946-vetmed ◽

2008 ◽

Vol 53 (No. 5) ◽

pp. 229-235 ◽

Cited By ~ 2

Author(s):

B. Skotarczak

Keyword(s):

Clinical Symptoms ◽

Early Stage ◽

Correct Diagnosis ◽

Antibody Test ◽

Diagnostic Methods ◽

Babesia Microti ◽

Babesia Divergens ◽

Polymerase Chain ◽

Etiological Agents ◽

Selection Of

Babesia is the causative agent of babesiosis, a tick-borne zoonosis which has been increasingly described throughout the world. Babesia microti and Babesia divergens are the etiological agents of human babesiosis. Babesia canis is the principal etiological agent of canine babesiosis. Currently, the diagnostics of babesiosis is based mainly on serological methods and the immunofluorescent antibody test (IFA) is most commonly used. However, even in the acute phase of the disease, seroconversion does not always occur. Clinical symptoms, because of their unspecificity, cannot be used to make a correct diagnosis. In this situation other diagnostic methods are needed. The use of PCR (polymerase chain reaction) is the most promising of these. An advantage of this method is that it allows identification of the parasite in the early stage of disease which enables early diagnosis, implementation of therapy and avoidance of complications. However, the standardization of this technique remains to be carried out. Selection of a genetic marker for PCR is very important for the sensitivity of this technique and it is discussed in this paper.

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Novel Diamidines with Activity against Babesia divergensIn Vitroand Babesia microtiIn Vivo

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01482-10 ◽

2011 ◽

Vol 55 (7) ◽

pp. 3439-3445 ◽

Cited By ~ 9

Author(s):

Angela Nehrbass-Stuedli ◽

David Boykin ◽

Richard R. Tidwell ◽

Reto Brun

Keyword(s):

Inhibitory Concentration ◽

Chemotherapeutic Agents ◽

Babesia Microti ◽

Parasitic Diseases ◽

Significant Activity ◽

Subcutaneous Route ◽

Compound A ◽

Content Type ◽

Babesia Divergens

ABSTRACTDicationic diamidines, such as diminazene and pentamidine, are well-studied chemotherapeutic agents with significant activity against parasitic diseases. Thein vitroactivities of novel diamidine compounds against theBabesia divergensstrains 1903B and 4201 were investigated. The most potent compound, a diphenyl furan, had a 50% inhibitory concentration (IC50) of 1.5 ng/ml. In a murine model, several test compounds were effective enough to cure mice infected withBabesia microtiat a dose of 12.5 and/or 25 mg/kg of body weight given by the subcutaneous route for 4 days. The best antibabesial properties were exhibited by terphenyls, benzimidazoles, diphenyl furans, pentamidine, and pentamidine analogues.

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Assessing an Adaptation of the Universal Parasite Diagnostic Assay for Bloodborne Parasites in a US State Public Health Laboratory

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.21-0707 ◽

2021 ◽

Author(s):

Brooke Clemons ◽

Joel Barratt ◽

Meredith Lane ◽

Yvonne Qvarnstrom ◽

Allen E. Teal ◽

...

Keyword(s):

Public Health ◽

New York ◽

Parasitic Infection ◽

Rdna Locus ◽

Blood Parasites ◽

Babesia Microti ◽

Parasitic Infections ◽

Reference Laboratory ◽

Rt Pcr ◽

Next Generation Sequencing Ngs

For complex clinical cases where a parasitic infection is suspected, it can be difficult for clinicians to recommend an appropriate laboratory test. These tests are usually pathogen-specific and require a certain degree of suspicion for the precise etiology. Recently, Flaherty et al. (2021) described an assay, the universal parasite diagnostic (UPDx) that can potentially provide a diagnosis of any parasite present in a specimen. Using primers that amplify DNA from all eukaryotes, UPDx differentiates several parasitic infections in blood by amplicon-based next-generation sequencing (NGS) of the 18S rDNA locus. As the state’s public health reference laboratory, the Parasitology Laboratory at the Wadsworth Center (New York, NY) receives specimens from patients who have potentially encountered a wide variety of parasites. As such, the ability to differentiate several blood parasites using a single assay is of interest. We assessed UPDx for its ability to confirm parasitic infections for 20 specimens that were previously identified by real-time PCR (RT-PCR). This included specimens positive for Babesia microti, Trypanosoma cruzi, Leishmania tropica, various Plasmodium species, and specimens comprising mixed Plasmodium sp. infections. Results obtained using UPDx were largely concordant with the RT-PCR assays. A T. cruzi positive specimen was negative by UPDx and for two mixed Plasmodium sp. infections only one species was detected. The results obtained for other specimens were concordant. We conclude that UPDx shows promise for the detection of blood parasites in diagnostic laboratories. As NGS becomes cheaper, assays like UPDx will become increasingly amenable to use in clinical settings.

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Evaluation of the Inhibitory Effects of Coumermycin A1 on the Growth of Theileria and Babesia Parasites in vitro and in vivo

Pakistan Veterinary Journal ◽

10.29261/pakvetj/2021.064 ◽

2021 ◽

Vol 41 (04) ◽

pp. 469-474

Author(s):

Mahmoud AbouLaila

Keyword(s):

Dna Gyrase ◽

Babesia Microti ◽

Babesia Species ◽

Inhibitory Effects ◽

Theileria Equi ◽

Dna Topoisomerase ◽

Ic50 Values ◽

Gyrase A

Coumermycin A1, a coumarin antibiotic, has anticancer, antibacterial, antiviral, and antimalarial activities. We aimed to evaluate the anti-thielerial and anti-babesial activity of coumermycin A1 in mice in vivo. Coumermycin A1 efficacy was determined by the transcription of DNA gyrase, a type II DNA topoisomerase using reverse transcriptase-polymerase chain reaction (RT-PCR) transcription. Coumermycin A1 significantly inhibited the development of preliminary parasitemia (1%). Theileria equi and the Babesia species B. bigemina, B. bovis, and B. caballi were observed with IC50 values of 80, 70, 57, and 65 nM, respectively. Their development was remarkably inhibited at observed concentrations of 10, 25, 50, and 100µM for the studied organisms T. equi, and the Babesia species B. caballi, B. bovis and B. bigemina, respectively. In the subsequent viability test, parasite re-growth was suppressed at 100µM for B. bigemina and B. bovis and at 50 µM for B. caballi and T. equi. Coumermycin A1 Treatment of B. bovis cultures with Coumermycin A1 completely suppressed the transcription of the DNA gyrase subunits B and A genes. In BALB/c mice, the development of Babesia microti was inhibited by 70.73% using 5 mg/kg of Coumermycin A1.

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Babesiosis Presenting as Acute Liver Failure

Case Reports in Gastroenterology ◽

10.1159/000485373 ◽

2017 ◽

Vol 11 (3) ◽

pp. 769-773 ◽

Cited By ~ 3

Author(s):

Yousef Nassar ◽

Seth Richter

Keyword(s):

United States ◽

Liver Failure ◽

Acute Liver Failure ◽

Common Species ◽

Babesia Microti ◽

Midwestern United States ◽

Babesia Divergens ◽

Ixodes Ticks ◽

Babesia Venatorum

Babesiosis is a zoonotic, tick-borne infection caused by the protozoan Babesia. It is transmitted by the Ixodes ticks which transmit the infection to humans. Babesia microti, Babesia duncani, Babesia divergens, and Babesia venatorum are species that have been identified as being infectious to humans worldwide. The most common species causing infection to humans is B. microti which is endemic to the Northeast and Midwestern United States with most infections occurring between the months of May and October. We report a case of an elderly man with acute liver failure due to an infection with B. microti.

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