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Bovine babesiosis is a tick-transmitted disease caused by intraerythrocytic protozoan parasites of the genus Babesia. Its main causative agents in the Americas are Babesia bigemina and Babesia bovis, while Babesia ovata affects cattle in Asia. All Babesia species secrete proteins stored in organelles of the apical complex, which are involved in all steps of the invasion process of vertebrate host cells. Unlike other apicomplexans, which have dense granules, babesia parasites instead have large, round intracellular organelles called spherical bodies. Evidence suggests that proteins from these organelles are released during the process of invading red blood cells, where spherical body proteins (SBPs) play an important role in cytoskeleton reorganization. In this study, we characterized the gene that encodes SBP4 in B. bigemina. This gene is transcribed and expressed in the erythrocytic stages of B. bigemina. The sbp4 gene consists of 834 nucleotides without introns that encode a protein of 277 amino acids. In silico analysis predicted a signal peptide that is cleaved at residue 20, producing a 28.88-kDa protein. The presence of a signal peptide and the absence of transmembrane domains suggest that this protein is secreted. Importantly, when cattle were immunized with recombinant B. bigemina SBP4, antibodies identified B. bigemina and B. ovata merozoites according to confocal microscopy observations and were able to neutralize parasite multiplication in vitro for both species. Four peptides with predicted B-cell epitopes were identified to be conserved in 17 different isolates from six countries. Compared with the pre-immunization sera, antibodies against these conserved peptides reduced parasite invasion in vitro by 57%, 44%, 42%, and 38% for peptides 1, 2, 3, and 4, respectively (p < 0.05). Moreover, sera from cattle infected with B. bigemina cattle contained antibodies that recognized the individual peptides. All these results support the concept of spb4 as a new gene in B. bigemina that should be considered a candidate for a vaccine to control bovine babesiosis.
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BACKGROUND: Daily more than 3,000 children are injured or killed on the road, often along the school route. Road traffic crashes and resulting injuries are preventable. More can be done to reduce injuries and save lives. Traffic Conflict Techniques (TCTs) are simple methods of collecting observational data to evaluate the effectiveness of road safety interventions through counting and analyzing traffic conflicts. A TCT Toolkit was developed and piloted to analyze pedestrian-vehicle traffic conflicts in school zones in low- and middle-income countries. METHODS: Three non-governmental organizations in Ghana, Vietnam, and Mexico applied three TCTs from the TCT Toolkit to collect traffic conflict data before (pre-intervention) and after (post-intervention) road safety intervention implementation. As the number of traffic conflicts was often less than 100, confidence intervals (CIs) based on gamma distributions were calculated for the traffic conflict rate. Using the calculated traffic conflict rate, the difference between pre- and post-intervention rates was assessed by determining overlap of the CIs. When CIs did not overlap, the difference was said to be statistically significant at the 0.05 level. RESULTS: For each method, results indicated a decrease in traffic conflicts between pre- and post-intervention data collection periods. Pre- and post-intervention traffic conflict rates with non-overlapping CIs demonstrated the results were statistically significant, providing evidence that the road safety interventions were effective. CONCLUSIONS: TCTs are relatively low-cost and simple techniques that provide an opportunity to base road safety improvement decisions on real-world data. TCTs are effective in objectively evaluating road safety interventions and can help decision-makers evaluate strategies for improving road safety, preventing injuries and saving lives.
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BACKGROUND: Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained for similarly conducted trials of a single oral dose of albendazole (ALB; 400 mg). METHODOLOGY: The efficacy of MEB, as assessed by FECR, was determined in six trials involving 5,830 school children in Brazil, Cambodia, Cameroon, Ethiopia, United Republic of Tanzania, and Vietnam. The efficacy of MEB was compared to that of ALB as previously assessed in 8,841 school children in India and all the above-mentioned study sites, using identical methodologies. PRINCIPAL FINDINGS: The estimated FECR rate [95% confidence interval] of MEB was highest for A. lumbricoides (97.6% [95.8; 99.5]), followed by hookworm (79.6% [71.0; 88.3]). For T. trichiura, the estimated FECR rate was 63.1% [51.6; 74.6]. Compared to MEB, ALB was significantly more efficacious against hookworm (96.2% [91.1; 100], p<0.001) and only marginally, although significantly, better against A. lumbricoides infections (99.9% [99.0; 100], pâ=â0.012), but equally efficacious for T. trichiura infections (64.5% [44.4; 84.7], pâ=â0.906). CONCLUSIONS/SIGNIFICANCE: A minimum FECR rate of 95% for A. lumbricoides, 70% for hookworm, and 50% for T. trichiura is expected in MEB-dependent PC programs. Lower FECR results may indicate the development of potential drug resistance.
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Antihelmínticos/farmacología , Enfermedades Endémicas , Helmintiasis/tratamiento farmacológico , Helmintos/efectos de los fármacos , Mebendazol/farmacología , Adolescente , Albendazol/farmacología , Albendazol/uso terapéutico , Animales , Antihelmínticos/uso terapéutico , Brasil , Cambodia , Camerún , Niño , Preescolar , Enfermedades Endémicas/prevención & control , Etiopía , Heces/parasitología , Femenino , Helmintiasis/prevención & control , Humanos , Masculino , Mebendazol/uso terapéutico , Recuento de Huevos de Parásitos , Suelo/parasitología , Tanzanía , Resultado del Tratamiento , VietnamRESUMEN
Elasticity estimation of thin-layered soft tissues has gained increasing interest propelled by medical applications like skin, corneal, or arterial wall shear modulus assessment. In this work, the authors propose one-dimensional transient elastography (1DTE) for the shear modulus assessment of thin-layered soft tissue. Experiments on three phantoms with different elasticities and plate thicknesses were performed. First, using 1DTE, the shear wave speed dispersion curve inside the plate was obtained and validated with finite difference simulation. No dispersive effects were observed and the shear wave speed was directly retrieved from time-of-flight measurements. Second, the supersonic shear imaging (SSI) technique (considered to be a gold standard) was performed. For the SSI technique, the propagating wave inside the plate is guided as a Lamb wave. Experimental SSI dispersion curves were compared with finite difference simulation and fitted using a generalized Lamb model to retrieve the plate bulk shear wave speed. Although they are based on totally different mechanical sources and induce completely different diffraction patterns for the shear wave propagation, the 1DTE and SSI techniques resulted in similar shear wave speed estimations. The main advantage of the 1DTE technique is that bulk shear wave speed can be directly retrieved without requiring a dispersion model.
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Módulo de Elasticidad/fisiología , Diagnóstico por Imagen de Elasticidad/instrumentación , Diagnóstico por Imagen de Elasticidad/métodos , Algoritmos , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Modelos Biológicos , Fantasmas de Imagen , Reproducibilidad de los ResultadosRESUMEN
Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.
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Predisposición Genética a la Enfermedad , Lepra/genética , Proteínas/genética , Ubiquitina-Proteína Ligasas/genética , Alelos , Brasil , Estudios de Casos y Controles , Mapeo Cromosómico , Cromosomas Humanos Par 6/genética , Perfilación de la Expresión Génica , Haplotipos , Humanos , Proteínas de Microfilamentos , Chaperonas Moleculares , Fenotipo , Polimorfismo de Nucleótido Simple/genética , ARN Mensajero/análisis , ARN Mensajero/genética , VietnamRESUMEN
Leprosy, a chronic infectious disease caused by Mycobacterium leprae, affects an estimated 700,000 persons each year. Clinically, leprosy can be categorized as paucibacillary or multibacillary disease. These clinical forms develop in persons that are intrinsically susceptible to leprosy per se, that is, leprosy independent of its specific clinical manifestation. We report here on a genome-wide search for loci controlling susceptibility to leprosy per se in a panel of 86 families including 205 siblings affected with leprosy from Southern Vietnam. Using model-free linkage analysis, we found significant evidence for a susceptibility gene on chromosome region 6q25 (maximum likelihood binomial (MLB) lod score 4.31; P = 5 x 10(-6)). We confirmed this by family-based association analysis in an independent panel of 208 Vietnamese leprosy simplex families. Of seven microsatellite markers underlying the linkage peak, alleles of two markers (D6S1035 and D6S305) showed strong evidence for association with leprosy (P = 6.7 x 10(-4) and P = 5.9 x 10(-5), respectively).
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Masculino , Femenino , Humanos , Alelos , /genética , /genética , Escala de Lod , Lepra/genética , Ligamiento Genético , Repeticiones de Microsatélite , VietnamRESUMEN
The authors studied 70 leprosy patients and 20 normal individuals, comparing the traditional sera collection method and the finger prick blood with the conservation on filter paper for specific antibodies against the native phenolic glycolipid-I (PGL-I) from Mycobacterium leprae. The finger prick blood dried on filter paper was eluated in phosphate buffer saline (PBS) containing 0.5 percent gelatin. The classical method for native PGL-I was performed for these eluates, and compared with the antibody determination for sera. It was observed that there is a straight correlation comparing these two methods; although the titles found for the eluates were lower than those obtained for serology. This blood collection method could be useful for investigation of new leprosy cases in field, specially in contacts individuals