Acaricide resistance has become widespread in countries where cattle ticks, Rhipicephalus (Boophilus) microplus, are a problem. Resistance arises through genetic changes in a cattle tick population that causes modifications to the target site, increased metabolism or sequestration of the acaricide, or reduced ability of the acaricide to penetrate through the outer protective layers of the tick's body. We review the molecular and biochemical mechanisms of acaricide resistance that have been shown to be functional in R. (B.) microplus. From a mechanistic point of view, resistance to pyrethroids has been characterized to a greater degree than any other acaricide class. Although a great deal of research has gone into discovery of the mechanisms that cause organophosphate resistance, very little is defined at the molecular level and organophosphate resistance seems to be maintained through a complex and multifactorial process. The resistance mechanisms for other acaricides are less well understood. The target sites of fipronil and the macrocyclic lactones are known and resistance mechanism studies are in the early stages. The target site of amitraz has not been definitively identified and this is hampering mechanistic studies on this acaricide.Keywords: Cattle tick, resistance mechanisms, target site mutation, metabolism. ResumoA resistência aos acaricidas tornou-se amplamente difundida nos países onde os carrapatos bovinos, Rhipicephalus (Boophilus) microplus, são um problema. A resistência surge por meio de alterações genéticas em uma população de carrapatos que causam modificações no local de ação, aumento do metabolismo ou sequestro do acaricida, ou ainda redução na capacidade do acaricida em penetrar através das camadas protetoras do corpo do carrapato. Neste artigo, foram revisados os mecanismos moleculares e bioquímicos da resistência aos acaricidas que ocorrem em R. (B.) microplus. A partir de um ponto de vista dos mecanismos envolvidos, a resistência aos piretróides tem sido caracterizada em maior grau do que em qualquer outra classe de acaricida. Embora uma grande quantidade de pesquisas têm sido direcionada para a descoberta de mecanismos que causam resistência aos organofosforados, muito pouco é conhecido ao nível molecular, e essa resistência parece ser mantida por intermédio de um processo multifatorial e complexo. Os mecanismos de resistência para os demais acaricidas são bem menos compreendidos. Os alvos de ação do fipronil e das lactonas macrocíclicas são conhecidos, e os estudos dos mecanismos de ação envolvidos estão ainda em estágios iniciais. O alvo de ação do amitraz ainda não foi definitivamente identificado, e isso é limitante aos estudos dos mecanismos envolvidos na resistência a esse acaricida.Palavras-chave: Carrapato bovino, mecanismos de resistência, mutação no local de ação, metabolismo.

Opisthorchiasis is a major public health problem in

BackgroundSchistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ) is the drug of choice for morbidity control but few dose comparisons have been made.MethodologyNinety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz) before and 28–30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45) or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45). Adverse events were assessed at 3 and 24 hours posttreatment.Principal FindingsBaseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI): 56.6–88.5%) and 80.8% (95% CI: 60.6–93.4%) for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60). O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4–84.4%) and 96.6% (95% CI: not defined), respectively (P = 0.009). Egg reduction rates (ERRs) against O. viverrini were very high for both doses (>99%), but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1%) and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment). Adverse events were common (96%), mainly mild with no significant differences between the two treatment groups.Conclusions/SignificanceCure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses.Trial RegistrationControlled-Trials.com ISRCTN57714676

Infestations with ticks have an important economic impact on the cattle industry worldwide and resistance to acaricides has become a widespread phenomenon. To optimize their treatment strategy, farmers need to know if and against which classes potential acaricide-resistance does occur. Bioassays are used to assess the resistance level and pattern of Rhipicephalus (Boophilus) microplus populations. The objective of the current study was to assess the susceptibility of Þeld populations originating from Argentina (8), South Africa (3), and Australia (2) using the Larval Tarsal Test. Nine acaricidal compounds from Þve major classes were tested: organosphosphates, synthetic pyrethroids (SP), macrocyclic lactones, phenylpyrazols, and amidines. The resistance ratios at concentrations inducing 50 and 90% mortality were used to detect established and emerging resistance. This study conÞrmed the newly reported presence of amitraz resistance in populations from Argentina. In addition, resistance to SP appeared to be widespread (88%) in the Argentinean farms, which had been selected based on the observation of lack of treatment efÞcacy by farmers. In South Africa one of the three populations was found to be resistant to SP and to a phenylpyrazol compound (pyriprol). Furthermore, resistance to organosphosphates and SP was observed in Australia. Finally, the Larval Tarsal Test proved to be a suitable test to evaluate the susceptibility of R. microplus Þeld populations to the most relevant acaricidal classes.RESUMEN Las infestaciones por garrapatas tienen un importante impacto económico en la industria del ganado de todo el mundo y la resistencia a los acaricidas se ha convertido en un fenómeno generalizado. Con el Þn de optimizar la estrategia de los tratamientos, los ganaderos necesitan saber en contra de cuáles clases de acaricidas ocurre esa potencial resistencia. Se utilizan bioensayos para evaluar el patrón y nivel de resistencia de Rhipicephalus (Boophilus) microplus. El objetivo del presente estudio fue evaluar la susceptibilidad de poblaciones de campo procedentes de Argentina (8), Sudáfrica (3) y Australia (2) usando la prueba del tarso de las larvas (LTT). Nueve compuestos acaricidas de cinco clases principales: organofosforados (OP), piretroides sintéticos (SP), lactonas macrocṍclicas (ML), fenilpirazoles (PYZ) y amidinas. Para detectar resistencia establecida y emergente, se calcularon niveles de resistencia basados en concentraciones que inducen mortalidad a 50% y 90%. Este estudio conÞrma la nueva denuncia de la presencia de resistencia al amitraz en las poblaciones de garrapatas de Argentina. Además, la resistencia a SP parece estar muy difundida (88%) en los establecimientos argentinos, seleccionados sobre la base de la observación de los ganaderos, de la falta de eÞcacia de los tratamientos. En Sudáfrica, en una de las tres poblaciones, se encontró que era resistente a SP y a un compuesto PYZ (pyriprol). Además, resistencia a OP y SP fue observada en Australia. Finalmente, la LTT ha demostrado ser un...

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Resistance to synthetic pyrethroids (SP) in the cattle tick Rhipicephalus (Boophilus) microplus is widespread throughout its distribution area. Three single nucleotide substitutions identified in Domains II and III of the sodium channel gene of R. (B.) microplus are known to be associated with target site pyrethroid resistance. We developed a multiplex PCR using allele-specific primers to amplify wild type or mutated genotypes of the three mutations simultaneously. This assay was used to screen tick samples originating from Brazil, Argentina, Mexico, South Africa and Australia whose phenotype to flumethrin and cypermethrin had been determined by the use of the Larval Tarsal test (LTT) or the Larval Packet Test (LPT). These mutations were found to have distinct geographical distributions and result in different resistance phenotypes. The L64I Domain II mutation conferring resistance to several SP compounds was found in all the Brazilian, Argentinean and Australian populations and in one South African population, with frequencies between 38% and 100% in flumethrin and cypermethrin resistant populations. In contrast, this mutation was not found in samples from Mexico, while the Domain III mutation was found exclusively in this country. The G72V Domain II flumethrin-specific mutation was found in a single Australian population, with a very low resistant allele frequency (3%). The homozygous resistant RR genotype of the L64I Domain II mutation correlated significantly with the survival rates at the discriminating doses of flumethrin and cypermethrin. This survey shows the widespread distribution of the L64I Domain II mutation and provides evidence of its geographic separation from the Domain III mutation.

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