RESUMEN
Like other pathogens, parasitic helminths can rapidly evolve resistance to drug treatment. Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to tracking its spread and improving the efficacy and sustainability of parasite control. Here, we use an in vivo genetic cross between drug-susceptible and multi-drug-resistant strains of Haemonchus contortus in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies new alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor cky-1 in ivermectin resistance. This gene is within a locus under selection in ivermectin-resistant populations worldwide; expression analyses and functional validation using knockdown experiments support that cky-1 is associated with ivermectin survival. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode and identifies variants for the development of molecular diagnostics to combat drug resistance in the field.
Asunto(s)
Antihelmínticos , Ivermectina , Ivermectina/farmacología , Levamisol , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Resistencia a Medicamentos/genética , Bencimidazoles , Genómica , Factores de TranscripciónRESUMEN
Haemonchus contortus is a haematophagous parasitic nematode that infects small ruminants and causes significant animal health concerns and economic losses within the livestock industry on a global scale. Treatment primarily depends on broad-spectrum anthelmintics, however, resistance is established or rapidly emerging against all major drug classes. Levamisole (LEV) remains an important treatment option for parasite control, as resistance to LEV is less prevalent than to members of other major classes of anthelmintics. LEV is an acetylcholine receptor (AChR) agonist that, when bound, results in paralysis of the worm. Numerous studies implicated the AChR sub-unit, ACR-8, in LEV sensitivity and in particular, the presence of a truncated acr-8 transcript or a deletion in the acr-8 locus in some resistant isolates. Recently, a single non-synonymous SNP in acr-8 conferring a serine-to-threonine substitution (S168T) was identified that was strongly associated with LEV resistance. Here, we investigate the role of genetic variation at the acr-8 locus in a controlled genetic cross between the LEV susceptible MHco3(ISE) and LEV resistant MHco18(UGA2004) isolates of H. contortus. Using single worm PCR assays, we found that the presence of S168T was strongly associated with LEV resistance in the parental isolates and F3 progeny of the genetic cross surviving LEV treatment. We developed and optimised an allele-specific PCR assay for the detection of S168T and validated the assay using laboratory isolates and field samples that were phenotyped for LEV resistance. In the LEV-resistant field population, a high proportion (>75%) of L3 encoded the S168T variant, whereas the variant was absent in the susceptible isolates studied. These data further support the potential role of acr-8 S168T in LEV resistance, with the allele-specific PCR providing an important step towards establishing a sensitive molecular diagnostic test for LEV resistance.
Asunto(s)
Antihelmínticos , Hemoncosis , Haemonchus , Animales , Levamisol/farmacología , Resistencia a Medicamentos/genética , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Receptores Colinérgicos/genética , Hemoncosis/tratamiento farmacológico , Hemoncosis/veterinaria , Hemoncosis/parasitologíaRESUMEN
A population of Haemonchus contortus that was highly resistant to benzimidazoles and avermectin/milbemycins with a subpopulation that was resistant to levamisole, was replaced with a susceptible laboratory isolate of H. contortus in a flock of sheep. The anthelmintic susceptibility and population genetics of the newly established population were evaluated for 3.5 years using in vivo, in vitro, and molecular methods. Successful replacement of the resistant population with a susceptible population was confirmed using phenotypic and genotypic measurements; larval development assay indicated full anthelmintic susceptibility; albendazole treatment yielded 98.7% fecal egg count reduction; pyrosequence genotyping of single nucleotide polymorphisms in positions 167 and 200 of the isotype-1 beta tubulin gene were present at 0.0 and 1.7%, respectively; microsatellite genotyping indicated the background haplotype was similar to the susceptible isolate; and haplotypes of the isotype-1 beta tubulin gene were similar to the susceptible isolate. To sustain the susceptibility of the new population, targeted selective treatment was implemented using albendazole. Surprisingly, within 1.5 years post-replacement, the population reverted to a resistant phenotype. Resistance to albendazole, ivermectin, and moxidectin was confirmed via fecal egg count reduction test, larval development assay, and pyrosequencing-based genotyping. Targeted selective treatment was then carried out using levamisole. However, within one year, resistance was detected to levamisole. Population genetics demonstrated a gradual change in the genetic structure of the population until the final population was similar to the initial resistant population. Genetic analyses showed a lack of diversity in the susceptible isolate, suggesting the susceptible isolate had reduced environmental fitness compared to the resistant population, providing a possible explanation for the rapid reversion to resistance. This work demonstrates the power of combining molecular, in vitro, and in vivo assays to study phenotypic and genotypic changes in a field population of nematodes, enabling improved insights into the epidemiology of anthelmintic resistance.
Asunto(s)
Antihelmínticos , Hemoncosis , Haemonchus , Preparaciones Farmacéuticas , Enfermedades de las Ovejas , Animales , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Resistencia a Medicamentos/genética , Granjas , Estructuras Genéticas , Hemoncosis/tratamiento farmacológico , Hemoncosis/veterinaria , Haemonchus/genética , Recuento de Huevos de Parásitos/veterinaria , Ovinos , Enfermedades de las Ovejas/tratamiento farmacológico , Enfermedades de las Ovejas/epidemiologíaRESUMEN
BACKGROUND: The canine hookworm, Ancylostoma caninum is the most prevalent and important intestinal nematode parasite of dogs in the USA. Hookworms are typically well controlled by treatment with all commonly used anthelmintics that are approved for this use in dogs. However, in the past few years, cases of recurrent/persistent canine hookworm infections appear to have dramatically increased, suggesting that anthelmintic resistance (AR) may have evolved in this parasite. These cases are highly overrepresented by greyhounds, but multiple other breeds are also represented. The aim of this study was to characterize several of these suspected resistant isolates using in vitro, genetic and clinical testing to determine if these cases represent true anthelmintic resistance in A. caninum. METHODS: Fecal samples containing hookworm eggs from three cases of persistent hookworm infections; one from a greyhound, one from a miniature schnauzer and one from a hound-mix, were received by our laboratory. These were then used to establish infections in laboratory dogs and to perform egg hatch assays (EHA) and larval development assays (LDA) for detecting resistance to benzimidazoles and macrocyclic lactones, respectively. Additional EHA and LDA were performed on eggs recovered from the laboratory-induced infections. Fecal egg count reduction tests were performed to detect resistance to pyrantel. Deep amplicon sequencing assays were developed to measure the frequency of non-synonymous single nucleotide polymorphisms (SNP) at codons 167, 198 and 200 of the A. caninum isotype-1 ß-tubulin gene. RESULTS: Resistance ratios for the three A. caninum isolates tested ranged from 6.0 to > 100 and 5.5 to 69.8 for the EHA and LDA, respectively. Following treatment with pyrantel, reduction in faecal egg counts was negative or 0%. Deep amplicon sequencing of the isotype-1 ß-tubulin gene identified a high frequency of resistance-associated SNPs at codon 167 in all three resistant isolates and in two additional clinical cases. CONCLUSIONS: These data conclusively demonstrate multiple anthelmintic resistance in multiple independent isolates of A. caninum, strongly suggesting that this is an emerging problem in the USA. Furthermore, evidence suggest that these resistant hookworms originate from racing greyhound farms and kennels, though additional research is needed to confirm this.
Asunto(s)
Ancylostoma/efectos de los fármacos , Ancylostoma/genética , Anquilostomiasis/veterinaria , Antihelmínticos/farmacología , Resistencia a Múltiples Medicamentos/genética , Recuento de Huevos de Parásitos/veterinaria , Anquilostomiasis/parasitología , Animales , Cruzamiento , Enfermedades de los Perros , Perros , Heces/parasitología , Polimorfismo de Nucleótido Simple , Pirantel/farmacología , Estados UnidosRESUMEN
Anthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, management strategies increasingly aim to preserve a proportion of the parasite population in 'refugia', unexposed to treatment. While persuasive in its logic, and widely advocated as best practice, evidence for the ability of refugia-based approaches to slow the development of drug resistance in parasitic helminths is currently limited. Moreover, the conditions needed for refugia to work, or how transferable those are between parasite-host systems, are not known. This review, born of an international workshop, seeks to deconstruct the concept of refugia and examine its assumptions and applicability in different situations. We conclude that factors potentially important to refugia, such as the fitness cost of drug resistance, the degree of mixing between parasite sub-populations selected through treatment or not, and the impact of parasite life-history, genetics and environment on the population dynamics of resistance, vary widely between systems. The success of attempts to generate refugia to limit anthelmintic drug resistance are therefore likely to be highly dependent on the system in hand. Additional research is needed on the concept of refugia and the underlying principles for its application across systems, as well as empirical studies within systems that prove and optimise its usefulness.
Asunto(s)
Antihelmínticos/farmacología , Resistencia a Medicamentos , Helmintos/efectos de los fármacos , Animales , Helmintiasis/parasitología , Helmintos/genética , Helmintos/crecimiento & desarrollo , Humanos , Refugio de FaunaRESUMEN
Motility is a commonly used in vitro phenotype for assessing anthelmintic activity of candidate compounds, and for detecting anthelmintic resistance in nematodes. Third-stage larvae (L3) of parasitic nematodes are commonly used in motility-based assays because L3 are simple to obtain and can remain viable in storage for extended periods. To improve the measurement of motility of microscopic stages of nematodes, our laboratory developed the Worminator, which quantitatively measures motility of parasites. Using the Worminator, we compared the dose-response characteristics of several avermectin/milbemycin (AM) compounds using L3 from both AM-susceptible and AM-resistant Cooperia spp. (abamectin, doramectin, eprinomectin, ivermectin, moxidectin) and Haemonchus contortus (eprinomectin, ivermectin, moxidectin). Concentrations tested with the Worminator ranged from 0.156 to 40⯵M. Differences in EC50 between AM-susceptible and AM-resistant isolates of Cooperia spp. and Haemonchus contortus were small, with resistance ratios ranging from 1.00 to 1.34 for Cooperia spp., 0.99 to 1.65 for Haemonchus contortus. Larval migration inhibition assays were conducted using the same isolates and were equally ineffective for detection of resistance with resistance ratios less than 2.0. These results contrast with those of the Larval Development Assay where we obtained a resistance ratio of 16.48 using the same isolates of Haemonchus contortus. Moreover, even at the highest concentration tested (40 µM), 100% inhibition of motility was never achieved and EC50 for Worminator assays were more than 100× higher than peak plasma levels achieved in vivo following treatment. These data demonstrate that dose-response characteristics for inhibition of motility in L3 of gastrointestinal nematodes of livestock do not significantly differ for AM-susceptible and AM-resistant isolates. These data challenge the suitability of motility as a phenotype for detecting and measuring resistance to AM drugs in gastrointestinal nematodes of livestock.
Asunto(s)
Resistencia a Múltiples Medicamentos , Ivermectina/análogos & derivados , Larva/efectos de los fármacos , Ganado/parasitología , Macrólidos/farmacología , Fenotipo , Animales , Antihelmínticos/farmacología , Tracto Gastrointestinal/parasitología , Haemonchus/efectos de los fármacos , Ivermectina/farmacología , Larva/fisiología , Larva/ultraestructura , Movimiento/efectos de los fármacos , Nematodos/efectos de los fármacos , Nematodos/fisiología , Nematodos/ultraestructura , Ovinos , Enfermedades de las Ovejas/tratamiento farmacológico , Enfermedades de las Ovejas/parasitología , Trichostrongyloidea/efectos de los fármacosRESUMEN
Haemonchus contortus resistant to multiple anthelmintics threaten the viability of the small ruminant industry in areas where this parasite is prevalent. In response to this situation, the FAMACHA© system was developed and validated for use with small ruminants as a way to detect clinical anemia associated with haemonchosis. Given that H. contortus and multiple anthelmintic resistance is a similar problem in camelids, the FAMACHA© system might also provide the same benefits. To address this need, a validation study of the FAMACHA© system was conducted on 21 alpaca and llama farms over a 2-year period. H. contortus was the predominant nematode parasite on 17 of the 21 farms (10 alpaca and 7 llama farms) enrolled in the study, based on fecal culture results. The FAMACHA© card was used to score the color of the lower palpebral (lower eye lid) conjunctiva on a 1-5 scale. Packed cell volume (PCV) values were measured and compared to FAMACHA© scores using FAMACHA© score cutoffs of ≥3 or ≥4 and with anemia defined as a PCV ≤15%, ≤17%, or≤20%. PCV was significantly associated with FAMACHA© score, fecal egg count (FEC), and body condition score (BCS), regardless of the FAMACHA© cutoff score or the PCV% chosen to define clinical anemia (p<0.01 in all cases). The use of FAMACHA© scores ≥3 and PCV ≥ 15% indicating anemia provided the best sensitivity (96.4% vs 92.9% for FAMACHA© ≥4), whereas FAMACHA scores ≥ 4 and PCV ≤20% provided the best specificity (94.2% vs 69.1% for FAMACHA© ≥3). The data from this study support the FAMACHA© system as a useful tool for detecting clinical anemia in camelids suffering from haemonchosis. Parameters for making treatment decisions based on FAMACHA© score in camelids should mirror those established for small ruminants.
Asunto(s)
Antihelmínticos/farmacología , Camélidos del Nuevo Mundo , Hemoncosis/veterinaria , Haemonchus/aislamiento & purificación , Anemia/diagnóstico , Anemia/veterinaria , Animales , Resistencia a Medicamentos , Heces/parasitología , Hemoncosis/diagnóstico , Hemoncosis/parasitología , Haemonchus/efectos de los fármacos , Sensibilidad y EspecificidadRESUMEN
Recent reports indicate that anthelmintic resistance in gastrointestinal nematodes of cattle is becoming increasingly prevalent worldwide. Presently, the fecal egg count reduction test (FECRT) is the only means available for detection of resistance to anthelmintics in cattle herds at the farm level. However, the FECRT is labor and cost intensive, and consequently is only rarely performed on cattle farms unless for research purposes. If costs could be reduced, cattle producers might be more likely to pursue drug resistance testing on their farms. One approach to reducing the cost of the FECRT, is the use of composite fecal samples for performing fecal egg counts (FEC), rather than conducting FEC on fecal samples from 15 to 20 individual animals. In this study FECRT were performed on 14 groups of cattle using both individual and composite FEC methods To measure how well the results of composite sampling reproduce those of individual sampling, Lin's Concordance Correlation Coefficient was utilized to describe both the linear relationship between methods and the slope and y-intercept of the line relating the data sets. There was little difference between the approaches with 98% agreement in mean FEC found between methods Mean FEC based on individual counts ranged between 0 and 670.6 eggs per gram of feces, indicating that the results of this study are applicable to a wide range of FEC levels. Standard error of the mean FEC and range of FEC are reported for each group prior to and following treatment to describe the variability of the data set. There was greater than 95% agreement in drug efficacy between individual and composite sampling methods, demonstrating composite sampling is appropriate to evaluate drug efficacy. Notably, for all groups tested the efficacy calculated by composite sampling was within the 95% confidence interval for efficacy calculated using individual sampling. The use of composite samples was shown to reduce the number of FEC required by 79%. These data demonstrate that pooling fecal samples from a group of cattle and then performing repeated FEC on that composite sample yields results very similar to performing individual FEC on those same animals, while substantially reducing the cost of performing a FECRT as compared to individual fecal samples. Furthermore, we have developed suggested methods for using composite samples in a FECRT, provided a cost comparison for this methodology, and described potential issues associated with the use of composite samples that must be considered.
Asunto(s)
Antihelmínticos/farmacología , Enfermedades de los Bovinos/parasitología , Resistencia a Medicamentos , Heces/parasitología , Enfermedades Gastrointestinales/veterinaria , Manejo de Especímenes/veterinaria , Animales , Bovinos , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/parasitología , Recuento de Huevos de Parásitos , Manejo de Especímenes/métodosRESUMEN
A sheep farm experiencing high lamb mortality and poor body conditions of ewes due to haemonchosis was tested for the presence of anthelmintic-resistant nematodes in August 2014. A fecal egg count reduction test was performed in Colombia on this farm and a DrenchRite® Larval development Assay (LDA) was shipped to the University of Georgia in the United States for resistance testing. The fecal egg count reduction test (FECRT) was conducted on 70 out of 500 animals allocated into five groups of 14 animals each: untreated control, albendazole (ABZ; 3.5mg/kg sc), ivermectin (IVM; 0.2mg/kg sc), moxidectin (MOX; 0.2mg/kg sc) and levamisole (LEV; 5mg/kg sc) plus triclabendazol/ivermectin (TBZ; 10mg/kg and IVM; 0.2mg/kg po). Individual fecal egg counts (FEC) using the modified McMaster technique and pooled larval cultures were performed 10days after anthelmintic treatment. Following 10days the initial results from the ABZ and IVM groups, 24 animals were treated twice with trichlorfon (TCF; 50mg/kg po) on days 0 and 6, and then checked for FEC on day 10. Mean differences in FEC before and after treatment were negligible (3 to 8% change) for the control, ABZ, LEV-TBZ and IVM groups. The MOX treatment resulted a mean FEC reduction of 76.7%, which was not-significant by t-test (p=0.08). The TCF treatment showed a mean FEC reduction of 42.3%, which was also not-significant (p=0.1). The DrenchRite® LDA was used to evaluate the resistance status to benzimidazole, levamisole, ivermectin and moxidectin on this farm. Coprocultures indicated that the predominant worm species was Haemonchus contortus (Colombia 94-100%) (UGA 77% H. contortus and 23% Trichostrongylus colubriformis). Resistance was evaluated for both H. contortus and T. colubriformis. The LDA results indicated high resistance to all 4 anthelmintics for both parasite species. The current study, together with similar surveys in 4 other Antioquian goat and sheep farms, confirms the presence of multi-drug resistant H. contortus to all three classes of anthelmintics in this region of Colombia.
Asunto(s)
Antihelmínticos/farmacología , Hemoncosis/veterinaria , Haemonchus/efectos de los fármacos , Enfermedades de las Ovejas/parasitología , Animales , Colombia/epidemiología , Resistencia a Múltiples Medicamentos , Heces/parasitología , Hemoncosis/epidemiología , Hemoncosis/parasitología , Recuento de Huevos de Parásitos/veterinaria , Ovinos , Enfermedades de las Ovejas/epidemiologíaRESUMEN
A major hindrance to evaluating nematode populations for anthelmintic resistance, as well as for screening existing drugs, new compounds, or bioactive plant extracts for anthelmintic properties, is the lack of an efficient, objective, and reproducible in vitro assay that is adaptable to multiple life stages and parasite genera. To address this need we have developed the "Worminator" system, which objectively and quantitatively measures the motility of microscopic stages of parasitic nematodes. The system is built around the computer application "WormAssay", developed at the Center for Discovery and Innovation in Parasitic Diseases at the University of California, San Francisco. WormAssay was designed to assess motility of macroscopic parasites for the purpose of high throughput screening of potential anthelmintic compounds, utilizing high definition video as an input to assess motion of adult stage (macroscopic) parasites (e.g. Brugia malayi). We adapted this assay for use with microscopic parasites by modifying the software to support a full frame analysis mode that applies the motion algorithm to the entire video frame. Thus, the motility of all parasites in a given well are recorded and measured simultaneously. Assays performed on third-stage larvae (L3) of the bovine intestinal nematode Cooperia spp., as well as microfilariae (mf) of the filarioid nematodes B. malayi and Dirofilaria immitis, yielded reproducible dose responses using the macrocyclic lactones ivermectin, doramectin, and moxidectin, as well as the nicotinic agonists, pyrantel, oxantel, morantel, and tribendimidine. This new computer based-assay is simple to use, requires minimal new investment in equipment, is robust across nematode genera and developmental stage, and does not require subjective scoring of motility by an observer. Thus, the "Worminator" provides a relatively low-cost platform for developing genera- and stage-specific assays with high efficiency and reproducibility, low labor input, and yields objective motility data that is not subject to scorer bias.
RESUMEN
An isolate of Haemonchus contortus, UGA/2004, highly resistant to benzimidazoles, levamisole, and ivermectin was isolated from sheep at the University of Georgia, and passaged through experimentally infected goats. We measured the expression of twenty-nine mRNAs encoding drug targets and P-glycoproteins (P-gps), comparing the results to a fully susceptible laboratory passaged isolate. Expression levels of some nicotinic acetylcholine receptor mRNAs were markedly different in UGA/2004. Levels of the Hco-acr-8b mRNA, encoding a truncated subunit, were very high in resistant L3, but undetectable in susceptible larvae, with expression of the full-length Hco-acr-8a mRNA also significant increased. Expression of Hco-unc-63 and Hco-unc-29.3 mRNAs was significantly reduced in the resistant larvae. Expression of the Hco-glc-3 and Hco-glc-5 mRNAs, encoding glutamate-gated chloride channel subunits, were slightly reduced in resistant larvae. We observed significant increases in the expression of the Hco-pgp-2 and Hco-pgp-9 mRNAs in the UGA/2004 larvae, consistent with previous reports; we also saw a decrease in the levels of Hco-pgp-1 mRNA. Treatment of the larvae with ivermectin and moxidectin in vitro produced variable and inconsistent changes in P-gp mRNA levels. The sequences of the ß-tubulin isotype 1 mRNAs showed that the resistant larvae had a resistance-associated allele frequency of >95% at codon 200 and â¼40% and codon 167. No changes at codon 198 were present. The presence of the truncated acr-8b mRNA may be a reliable indicator of levamisole resistance, but complex changes in gene expression associated with macrocyclic lactone resistance make the identification of a single genetic marker for this resistance difficult.
Asunto(s)
Antihelmínticos/farmacología , Resistencia a Medicamentos , Hemoncosis/veterinaria , Haemonchus/efectos de los fármacos , Haemonchus/genética , Proteínas del Helminto/genética , Polimorfismo Genético , Enfermedades de las Ovejas/parasitología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Secuencia de Bases , Bencimidazoles/farmacología , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Cabras , Hemoncosis/parasitología , Haemonchus/aislamiento & purificación , Haemonchus/metabolismo , Proteínas del Helminto/metabolismo , Datos de Secuencia Molecular , OvinosRESUMEN
OBJECTIVE: To determine prevalence of anthelmintic resistance on sheep and goat farms in the southeastern United States. DESIGN: Cross-sectional study. ANIMALS: Sheep and goats from 46 farms in 8 southern states, Puerto Rico, and St Croix in the US Virgin Islands. PROCEDURES: Parasite eggs were isolated from fecal samples, and susceptibility to benzimidazole, imidathiazole, and avermectin-milbemycin anthelmintics was evaluated with a commercial larval development assay. RESULTS: Haemonchus contortus was the most common parasite on 44 of 46 farms; Trichostrongylus colubriformis was the second most commonly identified parasite. Haemonchus contortus from 45 (98%), 25 (54%), 35 (76%), and 11 (24%) farms were resistant to benzimidazole, levamisole, ivermectin, and moxidectin, respectively. Resistance to all 3 classes of anthelmintics was detected on 22 (48%) farms, and resistance to all 3 classes plus moxidectin was detected on 8 farms (17%). CONCLUSIONS AND CLINICAL RELEVANCE: Findings provided strong evidence that anthelmintic resistance is a serious problem on small ruminant farms throughout the southeastern United States. Owing to the frequent movement of animals among regions, the prevalence of resistance in other regions of the United States is likely to also be high. Consequently, testing of parasite eggs for anthelmintic resistance should be a routine part of parasite management on small ruminant farms.
Asunto(s)
Antihelmínticos/farmacología , Resistencia a Medicamentos , Enfermedades de las Cabras/tratamiento farmacológico , Helmintiasis Animal/tratamiento farmacológico , Enfermedades de las Ovejas/tratamiento farmacológico , Animales , Estudios Transversales , Relación Dosis-Respuesta a Droga , Heces/parasitología , Femenino , Enfermedades de las Cabras/parasitología , Cabras , Haemonchus/efectos de los fármacos , Helmintiasis Animal/parasitología , Masculino , Recuento de Huevos de Parásitos/veterinaria , Pruebas de Sensibilidad Parasitaria/veterinaria , Ovinos , Enfermedades de las Ovejas/parasitología , Sudeste de Estados Unidos , Strongylus/efectos de los fármacos , Resultado del TratamientoRESUMEN
Three experiments were conducted to test whether a pair of tufted capuchin monkeys (Cebus apella) could generalize their ability to exchange tokens and tool objects with a human experimenter to similar exchanges with a conspecific partner. Monkeys were tested in side-by-side enclosures, one enclosure containing a tool-use apparatus and one or more token(s), and the other enclosure containing one or more tool object(s). The monkeys willingly transferred tokens and tools to a conspecific with little practice. Following a small amount of training, we also found that the monkeys would select situation-appropriate tokens to exchange for specific tools, but did not select appropriate tool objects in response to another monkey's token transfers. Implications regarding role reversal are discussed.
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Comunicación Animal , Aprendizaje por Asociación , Cebus/psicología , Generalización Psicológica , Comportamiento del Uso de la Herramienta , Animales , Humanos , MasculinoRESUMEN
Several studies have demonstrated that nonhuman primate males with low cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) exhibit antisocial behavior patterns. Included in these deleterious patterns are impulse control deficits associated with violence and premature death. No studies to date have longitudinally studied the long-term outcome of young subjects with low CSF 5-HIAA concentrations as they mature into adults. In this study we examined longitudinal relations among serotonergic and dopaminergic functioning, as reflected in CSF metabolite concentrations, aggression, age at emigration, dominance rank, and mortality in free-ranging rhesus macaque (Macaca mulatta) males. Our results indicate long-term consistency of individual differences in levels of 5-HIAA in CSF in the subject population from the juvenile period of development through adulthood. We found a significant negative correlation between 5-HIAA concentrations measured in juveniles and rates of high-intensity aggression in the same animals as adults. Further, CSF 5-HIAA concentrations were lower in juveniles that died than in animals that survived. For the young animals that migrated there was a positive correlation between CSF 5-HIAA concentration and age at emigration, whereas for the animals that remained in their troop until later in sexual maturity there was a negative correlation between CSF 5-HIAA concentration and age of emigration. After animals emigrated to a new troop, social dominance rank in the new troop was positively correlated with early family social dominance rank, but inversely correlated with juvenile CSF 5-HIAA concentrations. Taken together, our findings suggest that males with low central serotonin levels early in life delay migration and show high levels of violence and premature death, but the males that survive achieve high rank. These findings indicate that longitudinal measures of serotonergic and dopaminergic functioning are predictive of major life-history outcomes in nonhuman primate males. Low concentrations of CSF 5-HIAA are associated with negative life-history patterns characterized by social instability and excessive aggression, and positive life-history patterns characterized by higher dominance rank.
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Ácido Hidroxiindolacético/líquido cefalorraquídeo , Macaca mulatta/fisiología , Predominio Social , Agresión , Animales , Ácido Homovanílico/líquido cefalorraquídeo , Macaca mulatta/metabolismo , Masculino , Metoxihidroxifenilglicol/líquido cefalorraquídeo , MortalidadRESUMEN
Is music just noise, and thus potentially harmful to laboratory animals, or can it have a beneficial effect? Research addressing this question has generated mixed results, perhaps because of the different types and styles of music used across various studies. The purpose of this study was to test the effects of 2 different types (vocal versus instrumental) and 2 genres (classical vocal versus 'easy-listening' vocal) of music on social behavior in 31 female and 26 male chimpanzees (Pan troglodytes). Results indicated that instrumental music was more effective at increasing affiliative behavior in both male and female chimpanzees, whereas vocal music was more effective at decreasing agonistic behavior. A comparison of 2 genre of vocal music indicated that easy-listening (slower tempo) vocal music was more effective at decreasing agonistic behavior in male chimpanzees than classical (faster tempo) vocal music. Agonistic behavior in females remained low (<0.5%) throughout the study and was unaffected by music. These results indicate that, like humans, captive chimpanzees react differently to various types and genres of music. The reactions varied depending on both the sex of the subject and the type of social behavior examined. Management programs should consider both type and genre when implementing a musical enrichment program for nonhuman primates.
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Conducta Animal , Música , Pan troglodytes/psicología , Conducta Social , Animales , Animales de Laboratorio , Femenino , Masculino , Factores SexualesRESUMEN
The examination of nonhuman primate (NHP) lateralized behaviors may provide insight into the evolution of hemispheric specialization. This study examined nipple preference in 64 infant macaques in order to consider the ontogeny of lateralized behavior. We used a focal animal sampling method to record nipple contact during 15, 30-min observation sessions collected across each infant's first year of life. Using a lateralized behavior index (LBI) we calculated individual and population preferences (LBI=(R-L)/(R+L); "R"=mean right nipple contact, "L"=mean left nipple contact). Strength of preference was calculated as the absolute value of this score. Infants exhibited no population preference for a particular nipple, but showed a significant strength of preference that developed after 48 hr. Interestingly, successive siblings preferred the nipple not used by the previous infant. These findings suggest that nipple preference is guided by external stimuli, and that nipple preference during infancy may not be a behavioral representation of hemispheric specialization.
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Conducta Animal/fisiología , Conducta de Elección/fisiología , Lateralidad Funcional/fisiología , Pezones , Conducta en la Lactancia/fisiología , Factores de Edad , Animales , Animales Lactantes , Femenino , Macaca mulatta , Masculino , Paridad/fisiología , Embarazo , Factores SexualesRESUMEN
Unlike monozygotic (MZ) twins, dizygotic (DZ) twins develop from separate ova. The resulting twins can have different sires if the fertilizing sperm comes from different males. Routine paternity testing of a pair of same-sexed chimpanzee twins born to a female housed with two males indicated that the twins were sired by two different males. DNA typing of 22 short-tandem repeat (STR) loci demonstrated that these twins were not MZ twins but heteropaternal DZ twins. Reproductive data from 1926-2002 at five domestic chimpanzee colonies, including 52 twins and two triplets in 1,865 maternities, were used to estimate total twinning rates and the MZ and DZ components. The average chimpanzee MZ twinning rate (0.43%) equaled the average human MZ rate (0.48%). However, the chimpanzee DZ twinning rate (2.36%) was over twice the human average, and higher than all but the fertility-enhanced human populations of Nigeria. Similarly high twinning rates among African chimpanzees indicated that these estimates were not artifacts of captivity. Log-linear analyses of maternal and paternal effects on recurrent twinning indicated that females who twinned previously had recurrence risks five times greater than average, while evidence for a paternal twinning effect was weak. Chimpanzee twinning rates appear to be elevated relative to corresponding estimated human rates, making twinning and possibly heteropaternity more important features of chimpanzee reproductive biology than previously recognized.
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Progenie de Nacimiento Múltiple/estadística & datos numéricos , Pan troglodytes/genética , Paternidad , Preñez/genética , Gemelos Dicigóticos/genética , Animales , Dermatoglifia del ADN/métodos , Femenino , Masculino , Embarazo , Recurrencia , Factores de Riesgo , Conducta Sexual AnimalRESUMEN
This study considers the use of nonsocial environmental enrichment by captive chimpanzees at the Primate Foundation of Arizona. The goal was to determine whether a relationship existed between controllability of enrichment items by captive chimpanzees and frequency of use. The study measured controllability, the ability of nonhuman animals to alter aspects of their environment by the potential destructibility of the enrichment item. This study examined additional factors that may affect enrichment use: individual age, sex, rearing history, social group composition, and availability of outdoor access. The chimpanzees in the study used destructible items--the enrichment category with the highest level of controllability--more than indestructible items across all age, sex, and rearing classes. Thus, controllability seems to be an important factor in chimpanzee enrichment. Younger individuals and groups with outdoor access used enrichment more than did older individuals and groups with indoor-only access. Individual sex, rearing history, and social group composition had minimal effects on enrichment use. These results support the importance of control to captive chimpanzees and further enable captive management to customize enrichment programs to the needs of particular animals.
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Crianza de Animales Domésticos , Pan troglodytes/psicología , Conducta Social , Animales , Animales de Zoológico , Femenino , Masculino , Medio SocialRESUMEN
Research on cross-modal performance in nonhuman primates is limited to a small number of sensory modalities and testing methods. To broaden the scope of this research, the authors tested capuchin monkeys (Cebus apella) for a seldom-studied cross-modal capacity in nonhuman primates, auditory-visual recognition. Monkeys were simultaneously played 2 video recordings of a face producing different vocalizations and a sound recording of 1 of the vocalizations. Stimulus sets varied from naturally occurring conspecific vocalizations to experimentally controlled human speech stimuli. The authors found that monkeys preferred to view face recordings that matched presented vocal stimuli. Their preference did not differ significantly across stimulus species or other stimulus features. However, the reliability of the latter set of results may have been limited by sample size. From these results, the authors concluded that capuchin monkeys exhibit auditory-visual cross-modal perception of conspecific vocalizations.