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1.
Exp Parasitol ; 210: 107831, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926147

RESUMO

Babesia (B.) bovis is one of the main etiological agents of bovine babesiosis, causes serious economic losses to the cattle industry. Control of bovine babesiosis has been hindered by the limited treatment selection for B. bovis, thus, new options are urgently needed. We explored the drug library and unbiasedly screened 640 food and drug administration (FDA) approved drug compounds for their inhibitory activities against B. bovis in vitro. The initial screening identified 13 potentially effective compounds. Four potent compounds, namely mycophenolic acid (MPA), pentamidine (PTD), doxorubicin hydrochloride (DBH) and vorinostat (SAHA) exhibited the lowest IC50 and then selected for further evaluation of their in vitro efficacies using viability, combination inhibitory and cytotoxicity assays. The half-maximal inhibitory concentration (IC50) values of MPA, PTD, DBH, SAHA were 11.38 ± 1.66, 13.12 ± 4.29, 1.79 ± 0.15 and 45.18 ± 7.37 µM, respectively. Of note, DBH exhibited IC50 lower than that calculated for the commonly used antibabesial drug, diminazene aceturate (DA). The viability result revealed the ability of MPA, PTD, DBH, SAHA to prevent the regrowth of treated parasite at 4 × and 2 × of IC50. Antagonistic interactions against B. bovis were observed after treatment with either MPA, PTD, DBH or SAHA in combination with DA. Our findings indicate the richness of FDA approved compounds by novel potent antibabesial candidates and the identified potent compounds especially DBH might be used for the treatment of animal babesiosis caused by B. bovis.


Assuntos
Antiprotozoários/farmacologia , Babesia bovis/efeitos dos fármacos , Animais , Antiprotozoários/toxicidade , Babesia bovis/crescimento & desenvolvimento , Babesiose/tratamento farmacológico , Babesiose/parasitologia , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/parasitologia , Cães , Doxorrubicina/farmacologia , Doxorrubicina/toxicidade , Aprovação de Drogas , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala , Concentração Inibidora 50 , Células Madin Darby de Rim Canino/efeitos dos fármacos , Ácido Micofenólico/farmacologia , Ácido Micofenólico/toxicidade , Pentamidina/farmacologia , Pentamidina/toxicidade , Bibliotecas de Moléculas Pequenas , Espectrometria de Fluorescência , Vorinostat/farmacologia , Vorinostat/toxicidade
2.
Pediatrics ; 144(6)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31776195

RESUMO

Neonatal tick bites place infants at risk for acquiring infections that have rarely or never been documented in this age group. We describe 2 rare cases of tickborne infection in neonates. The first patient presented with multiple erythema migrans and fever, leading to a diagnosis of early disseminated Lyme disease. The second patient presented with irritability, fever, and worsening anemia due to babesiosis. Both infants had been bitten by arthropods fitting the description of ticks before the onset of symptoms. Our cases demonstrate the clinical course of 2 common tickborne infections occurring at an atypical age, opening the door to new, complex questions for which little guiding data exists. As tickborne infections become more prevalent, we expect other clinicians will be faced with similarly challenging neonatal cases. Providers must use past experience and a keen eye to identify neonates with tickborne infections and sort through their optimal diagnosis and management. In this article, we raise some of the questions we faced and discuss our conclusions.


Assuntos
Babesiose/diagnóstico , Eritema Migrans Crônico/diagnóstico , Parasitemia/diagnóstico , Animais , Antibacterianos/uso terapêutico , Antiprotozoários/uso terapêutico , Atovaquona/uso terapêutico , Azitromicina/uso terapêutico , Babesiose/tratamento farmacológico , Ceftriaxona/uso terapêutico , Eritema Migrans Crônico/tratamento farmacológico , Exantema/microbiologia , Feminino , Humanos , Recém-Nascido , Parasitemia/tratamento farmacológico , Picadas de Carrapatos/complicações
3.
Parasit Vectors ; 12(1): 482, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610802

RESUMO

BACKGROUND: A century ago, pantheras were abundant across Asia. Illegal hunting and trading along with loss of habitat have resulted in the designation of Panthera as a genus of endangered species. In addition to the onslaught from humans, pantheras are also susceptible to outbreaks of several infectious diseases, including babesiosis. The latter is a hemoprotozoan disease whose causative agents are the eukaryotic parasites of the apicomplexan genus Babesia. Babesiosis affects a varied range of animals including humans (Homo sapiens), bovines (e.g. Bos taurus), pantheras (e.g. Panthera tigris, P. leo, P. pardus) and equines. Babesia spp. are transmitted by the tick vector Ixodes scapularis or ticks of domestic animals, namely Rhipicephalus (Boophilus) microplus and R. (B.) decoloratus. At the level of protein translation within these organisms, the conserved aminoacyl tRNA synthetase (aaRS) family offers an opportunity to identify the sequence and structural differences in the host (Panthera) and parasites (Babesia spp.) in order to exploit these for drug targeting Babesia spp. METHODS: Using computational tools we investigated the genomes of Babesia spp. and Panthera tigris so as to annotate their aaRSs. The sequences were analysed and their subcellular localizations were predicted using Target P1.1, SignalP 3.0, TMHMM v.2.0 and Deeploc 1.0 web servers. Structure-based analysis of the aaRSs from P. tigris and its protozoan pathogens Babesia spp. was performed using Phyre2 and chimera. RESULTS: We identified 33 (B. bovis), 34 (B. microti), 33 (B. bigemina) and 33 (P. tigris) aaRSs in these respective organisms. Poor sequence identity (~ 20-50%) between aaRSs from Babesia spp. and P. tigris was observed and this merits future experiments to validate new drug targets against Babesia spp. CONCLUSIONS: Overall this work provides a foundation for experimental investigation of druggable aaRSs from Babesia sp. in an effort to control Babesiosis in Panthera.


Assuntos
Aminoacil-tRNA Sintetases/efeitos dos fármacos , Babesia/enzimologia , Babesiose/tratamento farmacológico , Panthera/parasitologia , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/genética , Animais , Babesia/classificação , Babesia/genética , Babesiose/transmissão , Domínio Catalítico , Biologia Computacional , Sistemas de Liberação de Medicamentos/veterinária , Espécies em Perigo de Extinção , Inibidores Enzimáticos/metabolismo , Genoma de Protozoário , Isocumarinas/metabolismo , Cadeias de Markov , Anotação de Sequência Molecular , Fases de Leitura Aberta , Panthera/genética , Panthera/metabolismo , Alinhamento de Sequência/veterinária
4.
BMC Vet Res ; 15(1): 314, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477120

RESUMO

BACKGROUND: Malarone® is a drug used for the treatment of malaria in humans. This drug is also particularly effective in the treatment of canine Babesia gibsoni infections. Malarone® is rarely used in dogs, and its adverse effects have not been widely reported. Its mechanism of action is related to the inhibition of cytochrome b and electron transport in the cell. This is the first known report of the development of acute pancreatitis and alopecia in a dog following the administration of Malarone®. CASE PRESENTATION: A 3-year-old, intact, female Maltese was referred to our clinic with intermittent vomiting and sudden, generalized alopecia. Two months previously, the dog had been prescribed Malarone® for the treatment of a suspected B. gibsoni infection. The dog was evaluated using hematology, radiography, ultrasonography, a PCR for Babesia detection, and a canine pancreatic lipase immunoreactivity (cPLI) assay. The result of the PCR test was negative, whereas the cPLI assay yielded a positive result. Dermatologic examination revealed bacterial infection with hair cycle arrest. CONCLUSIONS: Based on these findings, drug-induced acute pancreatitis and alopecia with superficial pyoderma were diagnosed. Malarone® may induce severe adverse reactions in dogs. Therefore, careful monitoring for adverse effects is required when using Malarone® in dogs.


Assuntos
Alopecia/veterinária , Antimaláricos/efeitos adversos , Atovaquona/efeitos adversos , Doenças do Cão/induzido quimicamente , Pancreatite/veterinária , Proguanil/efeitos adversos , Alopecia/induzido quimicamente , Animais , Antimaláricos/uso terapêutico , Atovaquona/uso terapêutico , Babesiose/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Cães , Combinação de Medicamentos , Feminino , Pancreatite/induzido quimicamente , Proguanil/uso terapêutico
5.
Transfus Apher Sci ; 58(4): 439-441, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31307834

RESUMO

Babesiosis is a tick-borne infectious disease caused by the protozoa Babesia but transplacental, and transfusion transmission may occur. While most infections are asymptomatic, rarely, it can present with a severe, life-threatening illness. Treatment is primarily with antibiotics, but red cell exchange (RCE) has been used in more severe cases which are characterized by high-grade parasitemia, evidence of severe hemolysis and or multi-organ failure. A threshold parasite level of 10% has arbitrarily been applied as an indication for RCE; however, this threshold is not evidence-based. We report on three cases of severe babesiosis in which we considered the use of RCE on the basis of a parasite level greater than 10%, but the procedure was not performed. We deferred RCE on account of the good clinical state of the patient and the absence of end-organ failure. All patients were followed daily until discharge. Two of these patients had been splenectomized, and each received a single unit of red blood cells during the hospitalization. The third patient had a long history of refractory lymphoma and was pancytopenic requiring multiple transfusions during the years before the diagnosis of babesiosis. She had transfusion-transmitted babesiosis from a red blood cell transfused 46 days prior to diagnosis. All three patients responded well to antibiotics, and none expired. This small case series suggests that requests for RCE solely on the basis of an arbitrary level of parasitemia should be questioned and the clinical state and evidence of end-organ failure considered in the decision to perform RCE.


Assuntos
Antibacterianos/administração & dosagem , Babesiose/tratamento farmacológico , Parasitemia/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Babesiose/sangue , Transfusão de Eritrócitos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Parasitemia/sangue , Estudos Retrospectivos
6.
Artigo em Inglês | MEDLINE | ID: mdl-31254719

RESUMO

Diminazene aceturate (DA) and imidocarb dipropionate are commonly used in livestock as antipiroplasm agents. However, toxic side effects are common in animals treated with these two drugs. Therefore, evaluations of novel therapeutic agents with high efficacy against piroplasm parasites and low toxicity to host animals are of paramount importance. In this study, the 400 compounds in the Pathogen Box provided by the Medicines for Malaria Venture foundation were screened against Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi. A fluorescence-based method using SYBR Green 1 stain was used for initial in vitro screening and determination of the half maximal inhibitory concentration (IC50). The initial in vitro screening performed using a 1 µM concentration as baseline revealed nine effective compounds against four tested parasites. Two "hit" compounds, namely MMV021057 and MMV675968, that showed IC50 < 0.3 µM and a selectivity index (SI)> 100 were selected. The IC50s of MMV021057 and MMV675968 against B. bovis, B. bigemina, T. equi and B. caballi were 23, 39, 229, and 146 nM, and 2.9, 3, 25.7, and 2.9 nM, respectively. In addition, a combination of MMV021057 and DA showed additive or synergistic effects against four tested parasites, while combinations of MMV021057 with MMV675968 and of MMV675968 with DA showed antagonistic effects. In mice, treated with 50 mg/kg MMV021057 and 25 mg/kg MMV675968 inhibited the growth of Babesia microti by 54 and 64%, respectively, as compared to the untreated group on day 8. Interestingly, a combination treatment with 6.25 mg/kg DA and 25 mg/kg MMV021057 inhibited B. microti by 91.6%, which was a stronger inhibition than that by single treatments with 50 mg/kg MMV021057 and 25 mg/kg DA, which showed 54 and 83% inhibition, respectively. Our findings indicated that MMV021057, MMV675968, and the combination treatment with MMV021057 and DA are prospects for further development of antipiroplasm drugs.


Assuntos
Antipruriginosos/administração & dosagem , Babesia/efeitos dos fármacos , Babesiose/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/parasitologia , Theileria/efeitos dos fármacos , Theileriose/tratamento farmacológico , Animais , Babesia/fisiologia , Babesiose/sangue , Babesiose/parasitologia , Bovinos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Theileria/fisiologia , Theileriose/sangue , Theileriose/parasitologia
7.
J Infect Dis ; 220(3): 442-447, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31099380

RESUMO

BACKGROUND: Tafenoquine (TQ) was recently approved by the US Food and Drug Administration for prophylaxis of malaria and, in addition, for eradication of the hepatic phase of the relevant Plasmodium species. In this study, we evaluated the efficacy of TQ for treatment of Babesia microti infection in mice with severe combined immunodeficiency (SCID). METHODS: SCID mice were infected with 1.1-1.5 × 108 B. microti-infected red blood cells by intraperitoneal injection. On day 3 or 4 postinfection, when parasitemia levels typically exceeded 10%, mice were treated with TQ vs vehicle alone, both administered by oral gavage. RESULTS: A single dose of TQ completely eliminated detectable parasites, with a >90% reduction in the level of parasitemia within just 4 days. Before elimination, a conspicuous phenotypic change in the parasite was observed. Although parasitologic cure was not achieved, there was no evidence for the development of drug resistance. CONCLUSIONS: This study suggests that TQ may be a highly useful drug to treat B. microti infection in patients. If further animal studies establish that a marked reduction in B. microti parasitemia can be reliably achieved with peak blood levels of TQ known to be well tolerated in humans, a clinical trial in patients should be considered.


Assuntos
Aminoquinolinas/farmacologia , Babesia microti/efeitos dos fármacos , Babesiose/tratamento farmacológico , Animais , Babesiose/parasitologia , Feminino , Malária/tratamento farmacológico , Camundongos , Camundongos SCID , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Plasmodium/efeitos dos fármacos
8.
Parasit Vectors ; 12(1): 269, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138282

RESUMO

BACKGROUND: There are no effective vaccines against Babesia and Theileria parasites; therefore, therapy depends heavily on antiprotozoal drugs. Treatment options for piroplasmosis are limited; thus, the need for new antiprotozoal agents is becoming increasingly urgent. Ellagic acid (EA) is a polyphenol found in various plant products and has antioxidant, antibacterial and effective antimalarial activity in vitro and in vivo without toxicity. The present study documents the efficacy of EA and EA-loaded nanoparticles (EA-NPs) on the growth of Babesia and Theileria. METHODS: In this study, the inhibitory effect of EA, ß-cyclodextrin ellagic acid (ß-CD EA) and antisolvent precipitation with a syringe pump prepared ellagic acid (APSP EA) was evaluated on four Babesia species and Theileria equi in vitro, and on the multiplication of B. microti in mice. The cytotoxicity assay was tested on Madin-Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3) and human foreskin fibroblast (HFF) cell lines. RESULTS: The half-maximal inhibitory concentration (IC50) values of EA and ß-CD EA on B. bovis, B. bigemina, B. divergens, B. caballi and T. equi were 9.58 ± 1.47, 7.87 ± 5.8, 5.41 ± 2.8, 3.29 ± 0.42 and 7.46 ± 0.6 µM and 8.8 ± 0.53, 18.9 ± 0.025, 11 ± 0.37, 4.4 ± 0.6 and 9.1 ± 1.72 µM, respectively. The IC50 values of APSP EA on B. bovis, B. bigemina, B. divergens, B. caballi and T. equi were 4.2 ± 0.42, 9.6 ± 0.6, 2.6 ± 1.47, 0.92 ± 5.8 and 7.3 ± 0.54 µM, respectively. A toxicity assay showed that EA, ß-CD EA and APSP EA affected the viability of cells with a half-maximal effective concentration (EC50) higher than 800 µM. In the experiments on mice, APSP EA at a concentration of 70 mg/kg reduced the peak parasitemia of B. microti by 68.1%. Furthermore, the APSP EA-atovaquone (AQ) combination showed a higher chemotherapeutic effect than that of APSP EA monotherapy. CONCLUSIONS: To our knowledge, this is the first study to demonstrate the in vitro and in vivo antibabesial action of EA-NPs and thus supports the use of nanoparticles as an alternative antiparasitic agent.


Assuntos
Antiprotozoários/farmacologia , Babesia microti/efeitos dos fármacos , Babesia/efeitos dos fármacos , Ácido Elágico/farmacologia , Theileria/efeitos dos fármacos , Animais , Babesia/crescimento & desenvolvimento , Babesiose/tratamento farmacológico , Bovinos , Linhagem Celular , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/parasitologia , Humanos , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Extratos Vegetais/farmacologia , Theileria/crescimento & desenvolvimento , Theileriose/tratamento farmacológico
9.
PLoS Negl Trop Dis ; 13(5): e0007030, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31125333

RESUMO

BACKGROUND: Chemotherapy is a principle tool for the control and prevention of piroplasmosis. The search for a new chemotherapy against Babesia and Theileria parasites has become increasingly urgent due to the toxic side effects of and developed resistance to the current drugs. Chalcones have attracted much attention due to their diverse biological activities. With the aim to discover new drugs and drug targets, in vitro and in vivo antibabesial activity of trans-chalcone (TC) and chalcone 4 hydrate (CH) alone and combined with diminazene aceturate (DA), clofazimine (CF) and atovaquone (AQ) were investigated. METHODOLOGY/PRINCIPAL FINDINGS: The fluorescence-based assay was used for evaluating the inhibitory effect of TC and CH on four Babesia species, including B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi, the combination with DA, CF, and AQ on in vitro cultures, and on the multiplication of a B. microti-infected mouse model. The cytotoxicity of compounds was tested on Madin-Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3), and human foreskin fibroblast (HFF) cell lines. The half maximal inhibitory concentration (IC50) values of TC and CH against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi were 69.6 ± 2.3, 33.3 ± 1.2, 64.8 ± 2.5, 18.9 ± 1.7, and 14.3 ± 1.6 µM and 138.4 ± 4.4, 60.9 ± 1.1, 82.3 ± 2.3, 27.9 ± 1.2, and 19.2 ± 1.5 µM, respectively. In toxicity assays, TC and CH affected the viability of MDBK, NIH/3T3, and HFF cell lines the with half maximum effective concentration (EC50) values of 293.9 ± 2.9, 434.4 ± 2.7, and 498 ± 3.1 µM and 252.7 ± 1.7, 406.3 ± 9.7, and 466 ± 5.7 µM, respectively. In the mouse experiment, TC reduced the peak parasitemia of B. microti by 71.8% when administered intraperitoneally at 25 mg/kg. Combination therapies of TC-DA and TC-CF were more potent against B. microti infection in mice than their monotherapies. CONCLUSIONS/SIGNIFICANCE: In conclusion, both TC and CH inhibited the growth of Babesia and Theileria in vitro, and TC inhibited the growth of B. microti in vivo. Therefore, TC and CH could be candidates for the treatment of piroplasmosis after further studies.


Assuntos
Antiprotozoários/administração & dosagem , Babesia/efeitos dos fármacos , Babesia/crescimento & desenvolvimento , Babesiose/tratamento farmacológico , Chalconas/administração & dosagem , Theileria/efeitos dos fármacos , Theileria/crescimento & desenvolvimento , Theileriose/tratamento farmacológico , Animais , Antiprotozoários/química , Babesia/genética , Babesiose/parasitologia , Linhagem Celular , Chalconas/química , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Concentração Inibidora 50 , Camundongos Endogâmicos BALB C , Theileria/genética , Theileriose/parasitologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-31100920

RESUMO

Equine Piroplasmosis (EP) is a tick-borne disease caused by apicomplexan protozoan parasites, Babesia caballi and Theileria equi. The disease is responsible for serious economic losses to the equine industry. It principally affects donkeys, horses, mules, and zebra but DNA of the parasites has also been detected in dogs and camels raising doubt about their host specificity. The disease is endemic in tropical and temperate regions of the world where the competent tick vectors are prevalent. Infected equids remain carrier for life with T. equi infection, whilst, infection with B. caballi is cleared within a few years. This review focuses on all aspects of the disease from the historical overview, biology of the parasite, epidemiology of the disease (specifically highlighting other non-equine hosts, such as dogs and camels), vector, clinical manifestations, risk factors, immunology, genetic diversity, diagnosis, treatment, and prevention.


Assuntos
Babesiose/epidemiologia , Doenças dos Cavalos/epidemiologia , Theileriose/epidemiologia , Animais , Babesia/fisiologia , Babesiose/diagnóstico , Babesiose/tratamento farmacológico , Babesiose/imunologia , Vetores de Doenças , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/imunologia , Cavalos , Fatores de Risco , Theileria/fisiologia , Theileriose/diagnóstico , Theileriose/tratamento farmacológico , Theileriose/imunologia , Carrapatos
11.
Parasitol Res ; 118(4): 1103-1112, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30770979

RESUMO

Human babesiosis, a worldwide emerging tick-borne disease, is caused by the intraerythrocytic apicomplexan parasite, babesia. In recent years, the number of infected patients globally has continued to rise, and thus human babesiosis poses a significant public health threat. Therefore, stronger initiatives should be undertaken to prevent further spread and development of this disease. In the present review, we summarize the epidemiology of reported human babesiosis cases in China from 1993 until now. The data show that Babesia microti is the dominant species causing human babesiosis in China and has led to more than 100 human infections thus far, where Babesia crassa-like is the second-most common. Moreover, Guangxi province is the second-most infected area after the Heilongjiang province. We also review the babesia life cycle, manifestation, diagnosis, and treatment. Additionally, we discuss babesiosis prevention strategies to raise public awareness, and also provide suggestions for improved babesiosis control.


Assuntos
Babesia microti/isolamento & purificação , Babesiose , Doenças Transmitidas por Carrapatos/epidemiologia , Animais , Babesiose/diagnóstico , Babesiose/tratamento farmacológico , Babesiose/epidemiologia , Babesiose/prevenção & controle , China/epidemiologia , Geografia , Humanos , Estágios do Ciclo de Vida , Camundongos , Doenças Transmitidas por Carrapatos/parasitologia , Carrapatos/parasitologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-30785049

RESUMO

Diminazene aceturate (DA) is commonly used in the treatment of bovine babesiosis caused by Babesia bovis. In this study, we attempted to develop resistance in B. bovis in vitro to DA and clofazimine (CF, a novel antibabesial agent) using short- and long-term drug pressures. In the short term, we found that 6.7 ±â€¯2 (0.54 ±â€¯0.16 µM)-, 12.9 ±â€¯8.6 (1.05 ±â€¯0.7 µM)-, and 14 ±â€¯5.9 (1.14 ±â€¯0.48 µM)-fold increases in the half-maximal inhibitory concentration (IC50) of DA were demonstrated on B. bovis cultivated with 0.04 µM of DA pressure for 4, 8, and 12 days, respectively, as compared to that on parental culture (0.08 ±â€¯0.0065 µM) before drug pressure was initiated. However, in B. bovis cultivated with 0.04 µM of DA pressure after 16 days, the parasites could not tolerate 0.8 µM of DA. In the long term, 7.6 ±â€¯3.5-, 20.5 ±â€¯0.1-, and 26.8 ±â€¯5.5-fold increases in the IC50 of DA were demonstrated on parasites from subcultures at days 8, 3, and 5 post-cultivation, respectively, in a drug-free medium, where these subcultures were obtained from B. bovis cultivated with DA pressure with changing doses for 30, 60, and 90 days, respectively. However, the second and third times, no increase was demonstrated on B. bovis from these subcultures at days 15 and 30 post-cultivation in a drug-free medium. In addition, in B. bovis cultivated with drug pressure after 90 days, the parasites tolerate up to 0.64 µM DA. All findings demonstrated that DA resistance in B. bovis is unstable and lost within 15 days of drug withdrawal. However, treatment with subtherapeutic doses of DA in cattle might result in the development of resistance in B. bovis, which may not even respond to subsequent treatments with high doses of DA. Thus, if the bovine babesiosis caused by B. bovis is unresponsive to DA, treatment with other antibabesial agents might be recommended.


Assuntos
Antiprotozoários/farmacologia , Babesia bovis/efeitos dos fármacos , Diminazena/análogos & derivados , Resistência a Medicamentos , Animais , Babesiose/tratamento farmacológico , Bovinos , Diminazena/farmacologia , Eritrócitos/parasitologia , Concentração Inibidora 50
13.
Parasit Vectors ; 12(1): 37, 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30651142

RESUMO

BACKGROUND: Developing new antibabesial drugs with a low toxic effect to the animal and with no resistance from Babesia parasites is in urgent demand. In this concern, the antimalarial, anticancer and antioxidant effect of thymoquinone (TQ), a phytochemical compound found in the plant Nigella sativa, has been reported. Therefore, in the present study, the antibabesial effect of this compound was evaluated on the growth of piroplasm parasites. RESULTS: Significant inhibition (P < 0.05) of the in vitro growth of piroplasm parasites were observed after treatment by TQ with IC50 values of 35.41 ± 3.60, 7.35 ± 0.17, 0.28 ± 0.016, 74.05 ± 4.55 and 67.33 ± 0.94 µM for Babesia bovis, Babesia bigemina, Babesia divergens, Theileria equi and Babesia caballi, respectively. The in vitro inhibitory effect of TQ was significantly enhanced (P < 0.05) when used in combination with either diminazene aceturate on bovine Babesia and equine Babesia and Theileria cultures. In B. microti-infected mice, oral and intraperitoneal administrations of TQ showed significant (P < 0.05) inhibition of parasite growth at a dose of 70 mg/kg and 50 mg/kg, respectively, compared to the control group. CONCLUSIONS: The obtained results indicate that thymoquinone might be a promising medicinal compound for use in the treatment of animal piroplasmosis.


Assuntos
Babesia/efeitos dos fármacos , Babesiose/tratamento farmacológico , Benzoquinonas/administração & dosagem , Benzoquinonas/farmacologia , Administração Oral , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Babesia/crescimento & desenvolvimento , Babesiose/parasitologia , Benzoquinonas/uso terapêutico , Diminazena/administração & dosagem , Diminazena/análogos & derivados , Diminazena/uso terapêutico , Modelos Animais de Doenças , Feminino , Concentração Inibidora 50 , Camundongos , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Theileria/efeitos dos fármacos , Theileriose/tratamento farmacológico
14.
Int J Parasitol ; 49(2): 165-174, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30690090

RESUMO

Babesiosis is a worldwide emerging tick-borne disease that is increasing in frequency and geographic range. It imposes a significant health burden, especially on those who are immunocompromised and those who acquire the infection through blood transfusion. Death from babesiosis occurs in up to 20 percent of these groups. Diagnosis is confirmed with identification of typical intraerythrocytic parasites on a thin blood smear or Babesia DNA using PCR. Treatment consists of atovaquone and azithromycin or clindamycin and quinine, and exchange transfusion in severe cases. Personal and communal protective measures can limit the burden of infection but it is important to recognize that none of these measures are likely to prevent the continued expansion of Babesia into non-endemic areas.


Assuntos
Antiprotozoários/uso terapêutico , Babesiose/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Testes Diagnósticos de Rotina/métodos , Gerenciamento Clínico , Babesiose/diagnóstico , Babesiose/tratamento farmacológico , Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/tratamento farmacológico , Efeitos Psicossociais da Doença , Transfusão Total , Saúde Global , Humanos
16.
Ticks Tick Borne Dis ; 10(1): 124-126, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30245087

RESUMO

A possible novel Babesia species infection of a maned wolf (Chrysocyon brachyurus) was first reported in 2012. The current case details a confirmed report of a maned wolf with infection by an undetermined species of Babesia. As the mortality and morbidity of babesiosis is high, this may become a significant concern to captive maned wolves, which are considered a near-threatened species by the World Association of Zoos and Aquariums. The aim of this study is to report the clinical, morphological and molecular characterization of this Babesia species. A 2.5-year-old, intact female maned wolf was found laterally recumbent with pale mucous membranes and jaundice the morning of presentation. Hematological and serum biochemical data were consistent with babesiosis and showed a regenerative severe anemia, leukocytosis, thrombocytopenia, hyperbilirubinemia, azotemia, increased creatine phosphokinase and increase alanine aminotransferase. On blood film review, inclusion bodies were seen in the red blood cells with cytomorphological features that were most consistent with a small form Babesia species. A blood sample was sent for polymerase chain reaction (PCR) testing and multi-locus sequence analyses. These findings suggested a unique Babesia species that is most closely related to a Babesia species (Babesia sp. AJB-2006) that has been found to infect raccoons (Procyon lotor) in North America. Although the cytomorphological features of the piroplasms and the clinical presentation were similar in both the current and 2012 case, when comparing the 18S melt curve temperature of the two Babesia isolates, the peak temperature was different. Unfortunately, genetic material from the 2012 case was not available so comparison of multi-locus gene sequences could not be performed, excluding the possibility to definitively state if the Babesia spp. from both cases were distinct from each other. The maned wolf was treated with a whole blood transfusion, dexamethazone (0.28 mg/kg IM), azithromycin (10 mg/kg in NaCl SC), atavaquone (1.5 cc PO), and 2 imidocarb (6.6 mg/kg IM) injections, and clinically improved. These findings demonstrate the need to further characterize the molecular and epidemiological differences of the Babesia species in this case report and the Babesia species known to infect raccoons.


Assuntos
Anti-Infecciosos/uso terapêutico , Babesia/classificação , Babesia/isolamento & purificação , Babesiose/tratamento farmacológico , Canidae , Animais , Animais de Zoológico , Babesia/citologia , Babesia/genética , Babesiose/microbiologia , Feminino , Resultado do Tratamento
17.
J Biol Chem ; 293(52): 19974-19981, 2018 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-30463941

RESUMO

Human babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia Clinical cases caused by Babesia duncani have been associated with high parasite burden, severe pathology, and death. In both mice and hamsters, the parasite causes uncontrolled fulminant infections, which ultimately lead to death. Resolving these infections requires knowledge of B. duncani biology, virulence, and susceptibility to anti-infectives, but little is known and further research is hindered by a lack of relevant model systems. Here, we report the first continuous in vitro culture of B. duncani in human red blood cells. We show that during its asexual cycle within human erythrocytes, B. duncani develops and divides to form four daughter parasites with parasitemia doubling every ∼22 h. Using this in vitro culture assay, we found that B. duncani has low susceptibility to the four drugs recommended for treatment of human babesiosis, atovaquone, azithromycin, clindamycin, and quinine, with IC50 values ranging between 500 nm and 20 µm These data suggest that current practices are of limited effect in treating the disease. We anticipate this new disease model will set the stage for a better understanding of the biology of this parasite and will help guide better therapeutic strategies to treat B. duncani-associated babesiosis.


Assuntos
Antiparasitários/farmacologia , Babesia/efeitos dos fármacos , Babesiose/tratamento farmacológico , Babesiose/parasitologia , Eritrócitos/parasitologia , Testes de Sensibilidade Parasitária/métodos , Atovaquona/farmacologia , Azitromicina/farmacologia , Babesia/crescimento & desenvolvimento , Técnicas de Cultura de Células/métodos , Clindamicina/farmacologia , Humanos , Quinina/farmacologia
18.
Nurse Pract ; 43(10): 48-54, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30234826

RESUMO

Human babesiosis continues to spread in multiple regions of the US. It is transmitted by Ixodes species ticks, as are Lyme disease and anaplasmosis. Its variable clinical presentations, together with serologic detection limitations, require that a high index of clinical suspicion be present for prompt diagnosis. This article discusses case examples showing the wide range of symptoms and presentations that are possible with babesiosis.


Assuntos
Anti-Infecciosos/uso terapêutico , Babesiose/diagnóstico , Babesiose/tratamento farmacológico , Animais , Atovaquona/uso terapêutico , Azitromicina/uso terapêutico , Babesiose/epidemiologia , Clindamicina/uso terapêutico , Quimioterapia Combinada , Humanos , Quinina/uso terapêutico
19.
BMJ Case Rep ; 20182018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262525

RESUMO

A 67-year-old woman presented with 5 days of myalgias and fevers on completion of a 21-day course of amoxicillin for Lyme disease (Borrelia burgdorferi infection). She was found to have profound thrombocytopenia, as well as new anaemia and leucopenia. Workup revealed Babesia microti as the causative agent of her symptoms. The patient quickly improved after appropriate antimicrobial therapy directed against babesiosis was started. This case illustrates the importance of basic microbiology, including epidemiology and common vectors, when creating a differential diagnosis. Because the Ixodes scapularis tick can harbour and transmit multiple parasites simultaneously, the possibility of coinfection should be considered in any patient not responding to appropriate initial medical therapy.


Assuntos
Babesiose/complicações , Coinfecção/diagnóstico , Doença de Lyme/complicações , Idoso , Animais , Antibacterianos/uso terapêutico , Atovaquona/uso terapêutico , Azitromicina/uso terapêutico , Babesia microti/isolamento & purificação , Babesiose/diagnóstico , Babesiose/tratamento farmacológico , Babesiose/genética , Coinfecção/tratamento farmacológico , Feminino , Humanos , Ixodes/parasitologia
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