RESUMO
A dog that shared habitat with domestic animals in a cattle farm and that was exposed to wildlife was taken to a private practitioner for clinical examination. The analyses conducted on the patient revealed the presence of Babesia bigemina by a molecular test. Clinical signs such as lethargy, anorexia and hyperthermia > 39 °C, pale mucous membranes and blood urine were observed in the patient. The animal was treated with imidocarb dipropionate (two doses each 0.5 ml/10 kg b.w. at an interval of 14 days). On treatment day 7, the clinical signs were mostly reduced. On day 30, PCR was carried out to assess the efficacy of the treatment, with a negative result. This case represents the first report of babesiosis due to B. bigemina in a dog living on a cattle farm in Mexico. It indicates the lower host specify of these pathogens and that dogs can play a role as sentinels of vector-borne parasites in livestock animals.(AU)
Um cão que compartilhava hábitat com animais domésticos em uma fazenda de gado e que foi exposto à vida selvagem foi levado a um clínico particular para que fosse examinado. As análises realizadas no paciente revelaram a presença de Babesia bigemina por um teste molecular. Sinais clínicos, como letargia, anorexia e hipertermia > 39°C, mucosas pálidas e sangue na urina foram observados no paciente. O animal foi tratado com dipropionato de imidocarb (duas doses cada 0,5 ml/10 kg de peso corporal em um intervalo de 14 dias). No dia de tratamento 7, os sinais clínicos foram reduzidos. No dia 30, foi realizada PCR para avaliar a eficácia do tratamento, com resultado negativo. Esse caso representa o primeiro relato de babesiose por B. bigemina em um cão que vive em uma fazenda de gado no México. Isso indica que o hospedeiro inferior especifica esses patógenos, e que os cães podem desempenhar um papel como sentinelas de parasitas transmitidos por vetores em animais de criação.(AU)
Assuntos
Animais , Babesia/efeitos dos fármacos , Babesiose/diagnóstico , Cães/parasitologia , Antiprotozoários/administração & dosagem , Filogenia , Zona Rural , Reação em Cadeia da Polimerase/veterinária , Técnicas de Diagnóstico Molecular/veterinária , Imidocarbo/análogos & derivados , MéxicoRESUMO
Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.
Assuntos
Amino Álcoois/farmacologia , Antiprotozoários/farmacologia , Amino Álcoois/síntese química , Amino Álcoois/química , Animais , Antiprotozoários/síntese química , Antiprotozoários/química , Babesia/efeitos dos fármacos , Babesia/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Modelos Animais de Doenças , Leishmania/efeitos dos fármacos , Leishmania/crescimento & desenvolvimento , Estágios do Ciclo de Vida/efeitos dos fármacos , Camundongos , Plasmodium/efeitos dos fármacos , Plasmodium/crescimento & desenvolvimento , Infecções por Protozoários/tratamento farmacológico , Infecções por Protozoários/parasitologia , Resultado do Tratamento , Trypanosoma/efeitos dos fármacos , Trypanosoma/crescimento & desenvolvimento , Células VeroAssuntos
Babesia/efeitos dos fármacos , Insulina/fisiologia , Putrescina/farmacologia , Ácido Selenioso/farmacologia , Transferrina/farmacologia , Animais , Babesia/crescimento & desenvolvimento , Babesia/fisiologia , Babesiose/parasitologia , Reatores Biológicos/parasitologia , Bovinos , Meios de Cultura Livres de Soro , Eritrócitos/parasitologia , Técnicas In VitroRESUMO
Imidocarb dipropionate (IMD) is a chemotherapeutic agent prescribed for the treatment and control of babesiosis; it is known to be a nucleic acid synthesis inhibitor. Although it is an effective babesicide, there are reports of persistent IMD residues retained at high levels in edible tissues of cattle, swine and sheep, raising concerns about potential effects on humans. Since the carcinogenic potential of a chemical compound can be assessed through its effect on the homologous recombination, we investigated whether IMD is recombinogenic in Aspergillus nidulans diploid cells and whether it is capable of inducing homozygosis in genes that were previously heterozygous. This analysis was done with a homozygotization assay applied to a heterozygous diploid strain of A. nidulans. IMD used at non-toxic concentrations (2.5 to 10.0 µM) was recombinogenic, demonstrated by homozygotization indices higher than 2.0 for diploid markers. A diploid homozygous for genetic markers from chromosomes I and II was also produced. Since DNA replication blockers that induce DNA strand breaks have been classified as potent inducers of homologous recombination, the recombinogenic potential of IMD may be due to induction of recombinational repair.
Assuntos
Antiprotozoários/farmacologia , Aspergillus nidulans/citologia , Aspergillus nidulans/genética , Diploide , Imidocarbo/análogos & derivados , Mitose/efeitos dos fármacos , Recombinação Genética/efeitos dos fármacos , Animais , Aspergillus nidulans/efeitos dos fármacos , Babesia/efeitos dos fármacos , Bovinos , Cromossomos Fúngicos/genética , Troca Genética/efeitos dos fármacos , Genótipo , Imidocarbo/farmacologiaRESUMO
It is proposed that the chronic asymptomatic carrier state produced by Babesia canis infection could make dogs more resistant against subsequent infections. This suggests that treatment with imidocarb dipropionate, which removes the organism, can make dogs more susceptible to reinfection in a short period of time. Ten male and female dogs of approximately 4-5 months of age were inoculated with B. canis. Half of them received treatment with imidocarb dipropionate (7 mg/kg) on days 15 and 27 post-infection and the other half were untreated. All the animals were examined using clinical and laboratory methods (CBC, platelet counts and serological study by indirect immunofluorescence test) for a 6-month period. Antibodies were first detected on day 7 post-injection and remained at high levels (1:2560) over the period in the non-treated group. This result was significantly different (P<0.001) from the treated group in which antibodies titers declined after day 34 post-infection. Six months later, after a homologous challenge infection only the dogs of treated group showed parasitaemia, thrombocytopenia and splenomegaly, which was significantly different (P<0.05) from the non-treated group. The sterilizing treatment with imidocarb dipropionate was effective in clearing the infection, but inhibited the maintenance of protective antibodies, making the animals more susceptible to reinfection.
Assuntos
Antiprotozoários/uso terapêutico , Babesia/imunologia , Babesiose/veterinária , Doenças do Cão/imunologia , Imidocarbo/análogos & derivados , Imidocarbo/uso terapêutico , Animais , Anticorpos Antiprotozoários/sangue , Antiprotozoários/farmacologia , Babesia/efeitos dos fármacos , Babesiose/tratamento farmacológico , Babesiose/imunologia , Portador Sadio/tratamento farmacológico , Portador Sadio/imunologia , Portador Sadio/veterinária , Suscetibilidade a Doenças/veterinária , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Imidocarbo/farmacologia , Masculino , Parasitemia/imunologia , Parasitemia/veterinária , Distribuição Aleatória , Organismos Livres de Patógenos Específicos , Esplenomegalia/imunologia , Esplenomegalia/veterinária , Trombocitopenia/imunologia , Trombocitopenia/veterináriaAssuntos
Babesia/crescimento & desenvolvimento , Meios de Cultura Livres de Soro/farmacologia , Lipoproteínas HDL/farmacologia , Parasitologia/métodos , Plasmodium falciparum/crescimento & desenvolvimento , Animais , Babesia/efeitos dos fármacos , Babesia/metabolismo , Eritrócitos/parasitologia , Humanos , Metabolismo dos Lipídeos , Lipoproteínas LDL/farmacologia , Lipoproteínas VLDL/farmacologia , Fosfatidilcolinas/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/metabolismoRESUMO
Babesia argentina was repeatedly exposed to imidocarb by transmitting parasites from infected ticks in a series of 4 groups of nonsplenectomised calves that had been treated prophylactically at 2 mg/kg. As the number of exposures to imidocarb increased, the parasites more readily infected the treated calves, indicating increased tolerance to the drug. Tests comparing parasites not previously exposed to imidocarb with those exposed 4 times showed that a dose of 3 mg/kg imidocarb completely cured subclinical infections with non-exposed, but not exposed, parasites; a dose of 1 mg/kg controlled acute infections with either nonexposed or exposed parasites; and the virulence of the parasite was apparently unaffected by the exposures.