An investigation of lumbar spine magnetic resonance referrals in two Irish university teaching centres: Radiology clinical judgement versus iRefer guideline compliance.

INTRODUCTION: With the annual increase in medical imaging demand, the appropriateness of the lumbar spine magnetic resonance imaging LSMRI referrals is worldwide gaining attention. This study aims to determine the appropriateness of LSMRI referrals and compare radiology clinical decisions to iRefer compliance based solely on referral text content. METHODS: Referral text was extracted from 1021 LSMRI referrals. Two review panels were recruited: three expert radiologists and three MRI radiographers. Radiologists classified cases as indicated or not indicated for scanning based on their clinical judgement. The radiographers classified based solely on iRefer guidelines. Majority voting for each case was applied to both review panels and reviewer agreement was tested using Kappa analysis. Logistic regression models were developed to identify medical disciplines associated with high rates of indicated referrals. RESULTS: 21.7% and 11.9% of the cases were found not indicated for MRI for radiologists and radiographers, respectively. Radiology review identified 18% of the GPs referrals as not indicated and 17% in the radiographers' review. Panel agreement was fair: Kappa values of 0.23 and0.26 for the radiologists and radiographers respectively. Neurosurgery was associated with the highest rate of indicated referrals across both review panels: oncology referrals raised the highest number of open comments. CONCLUSION: The study identified a lower number of not indicated referrals compared to previous research. Findings indicate the importance of both guidelines compliance and clinical judgement to optimise practice. IMPLICATIONS FOR PRACTICE: Findings in this study found that even when strict instructions were given to the MR radiographers to vet referrals using the iRefer guidelines, ambiguity within the guidelines resulted in variations in decision-making. This suggests that detailed protocols are required to support radiographers in the vetting process to ensure a standardised approach.

Multiple insecticide resistance in Aedes aegypti (Diptera: Culicidae) from Boyeros municipality, Cuba and associated mechanisms.

In this study, insecticide resistance and the mechanisms responsible were characterized in Ae. aegypti of Boyeros municipality from Havana, Cuba. Boyeros represents a high epidemiological risk because it is located near the Havana International Airport, it is highly urbanized, and it has a large influx of people from endemic countries so that it qualifies as a sentinel site for surveillance. The larvae collected from five areas of this municipality showed resistance to temephos associated with metabolic enzymes. The adult mosquitoes displayed a deltamethrin resistance and less distinctly to other pyrethroids associated with a high frequency of sodium channel gene mutations (F1534C and V1016I), detected for the first time in a field population from Cuba. The presence in the field populations of two insecticide resistance mechanisms represents a limiting factor in the success of the control operations of this vector, so other strategies should be considered to preserve the effectiveness of the insecticides available in public health for vector control in Cuba.

Insecticide resistance in two Aedes aegypti (Diptera: Culicidae) strains from Costa Rica.

Dengue (family Flaviridae, genus Flavivirus, DENV) and dengue hemorrhagic fever (DHF) are presently important public health problems in Costa Rica. The primary strategy for disease control is based on reducing population densities of the main mosquito vector Aedes aegypti (L.) (Diptera: Culicidae). This is heavily dependent on use of chemical insecticides, thus the development of resistance is a frequent threat to control program effectiveness. The objective of this study was to determine the levels of insecticide resistance and the metabolic resistance mechanisms involved in two Ae. aegypti strains collected from two provinces (Puntarenas and Limon) in Costa Rica. Bioassays with larvae were performed according to World Health Organization guidelines and resistance in adults was measured through standard bottle assays. The activities of beta-esterases, cytochrome P450 monooxygenases, and glutathione S-transferases (GST), were assayed through synergists and biochemical tests, wherein the threshold criteria for each enzyme was established using the susceptible Rockefeller strain. The results showed higher resistance levels to the organophosphate (OP) temephos and the pyrethroid deltamethrin in larvae. The efficacy of commercial formulations of temephos in controlling Ae. aegypti populations was 100% mortality up to 11 and 12 d posttreatment with daily water replacements in test containers. Temephos and deltamethrin resistance in larvae were associated with high esterase activity, but not to cytochrome P450 monooxygenase or GST activities. Adult mosquitoes were resistant to deltamethrin, and susceptible to bendiocarb, chlorpyrifos, and cypermethrin. Because temephos and deltamethrin resistance are emerging at the studied sites, alternative insecticides should be considered. The insecticides chlorpyrifos and cypermethrin could be good candidates to use as alternatives for Ae. aegypti control.

Temephos resistance and esterase activity in the mosquito Aedes aegypti in Havana, Cuba increased dramatically between 2006 and 2008.

Aedes aegypti (L.) (Diptera: Culicidae) control programmes in Cuba rely on the application of the organophosphate temephos for larval control. Hence, the monitoring of resistance to this insecticide is an essential component of such programmes. Here, 15 field populations from different municipalities of Havana City were assayed for resistance to temephos. High levels of resistance were detected in all strains and resistance ratios were highly correlated with esterase activity (P = 0.00001). Populations from three municipalities were tested in both 2006 and 2008; resistance and esterase activities both significantly increased during this 2-year period. Synergist studies demonstrated that neither glutathione transferases nor monooxygenases were associated with the increase in resistance to temephos in this period. The duration of the efficacy of commercial formulations of temephos in controlling Ae. aegypti populations in Havana City was reduced by the high level of temephos resistance observed; hence these data are of clear operational significance for the dengue control programme in Cuba. New integrated strategies to avoid further increases in temephos resistance in Cuba are necessary.

A mutation in the voltage-gated sodium channel gene associated with pyrethroid resistance in Latin American Aedes aegypti.

Pyrethroids are commonly used as mosquito adulticides and evolution of resistance to these compounds is a major threat to public health. 'Knockdown resistance' to pyrethroids (kdr) is frequently caused by nonsynonymous mutations in the voltage-gated sodium channel transmembrane protein (para) that reduce pyrethroid binding. Early detection of kdr is critical to the development of resistance management strategies in mosquitoes including Aedes aegypti, the most prevalent vector of dengue and yellow fever viruses. Brengues et al. described seven novel mutations in hydrophobic segment 6 of domain II of para in Ae. aegypti. Assays on larvae from strains bearing these mutations indicated reduced nerve sensitivity to permethrin inhibition. Two of these occurred in codons Iso1011 and Val1016 in exons 20 and 21 respectively. A transition in the third position of Iso1011 encoded a Met1011 replacement and a transversion in the second position of Val1016 encoded a Gly1016 replacement. We have screened this same region in 1318 mosquitoes in 32 additional strains; 30 from throughout Latin America. While the Gly1016 allele was never detected in Latin America, we found two new mutations in these same codons. A transition in the first position of codon 1011 encodes a Val replacement while a transition in the first position of codon 1016 encodes an Iso replacement. We developed PCR assays for these four mutations that can be read either on an agarose gel or as a melting curve. Selection experiments, one with deltamethrin on a field strain from Santiago de Cuba and another with permethrin on a strain from Isla Mujeres, Mexico rapidly increased the frequency of the Iso1016 allele. Bioassays of F(3) offspring arising from permethrin susceptible Val1016 homozygous parents and permethrin resistant Iso1016 homozygous parents show that Iso1016 segregates as a recessive allele in conferring kdr. Analysis of segregation between alleles at the 1011 and 1016 codons in the F(3) showed a high rate of recombination even though the two codons are only separated by a ~250 bp intron. The tools and information presented provide a means for early detection and characterization of kdr that is critical to the development of strategies for resistance management.

Application of the pupal/demographic-survey methodology in an area of Havana, Cuba, with low densities of Aedes aegypti (L.).

Between the April and December of 2004, an Aedes aegypti (L.) pupal/demographic survey was conducted in the Playa municipality of Havana. The aims were to identify the key types of container in the production of the adult mosquitoes (and so provide a basis for targeted control) and assess transmission risk in terms of the number of pupae/person. Pupal abundance, as measured in the survey, was compared with traditional Stegomyia indices. The immature stages of Ae. aegypti were only found in 70 of the 15,153 containers that were investigated and the pupae of this species were only seen in 52 of the containers. Ground-level water-storage tanks yielded 74.1% of all the pupae, with a further 19.0% found in miscellaneous small containers. The utility of the pupal/demographic-survey methodology in the evaluation of dengue risk in the study area, and other areas of Cuba with low densities of Ae. aegypti, is discussed.

Detection of insecticide resistance in Aedes aegypti (Diptera: Culicidae) from Cuba and Venezuela.

Four strains of Aedes aegypti (L.), one from Cuba and three from Venezuela, were bioassayed for susceptibility to eight insecticides, including the organophosphates, temephos, malathion, fenthion, pirimiphos methyl, and chlorpyrifos, and the pyrethroids, deltamethrin, lambda cyhalothrin and cypermethrin, S, S, S,-tributyl phosphorotrithioate and piperonyl butoxide were used as synergists to assess the involvement of esterases and monooxygenases in organophosphate resistance. Venezuelan strains had low levels of resistance to fenthion and malathion, and moderate to high resistance to temephos, pyrimphos methyl, and chlorpiriphos. All strains were susceptible to the pyrethroids, except the Cuban strain, which had moderate levels of resistance to cypermethrin. Organophosphate resistance in Ae. aegypti is a serious threat to control operations. Integrated strategies for Ae. aegypti control to prevent or delay pyrethroid resistance in Venezuela and Cuba are discussed.

[High esterases as mechanism of resistance to organophosphate insecticides in Aedes aegypti strains]. / Esterasas elevadas como mecanismo de resistencia a insecticidas organofosforados en cepas de Aedes aegypti.

Five strains of Aedes aegypti L. one from Cuba and 4 from Venezuela were evaluated to determine their resistance to organophosphate insecticides (temephos, chlorpiriphos and pirimiphos methyl). In the Venezuelan strains only APURE showed resistance to temephos. In TACHIRA and MIRANDA moderate resistance values were noted (FR50 5 to 10x) for chlorpiriphos and high levels of resistance (FR > 10x) to this insecticide were found in ARAGUA. All the Venezuelan strains showed high levels of resistance to pirimiphos methyl. The Cuban strain from Santiago de Cuba revealed moderate resistance to temephos and pirimiphos methyl, but high resistance to chlorpiriphos. The results of the biochemical tests proved the presence of esterase and glutathione-s-transferase at high frequency in almost every strain. By the polyacrilamide gel electrophoresis, a strongly stained band was observed in all the strains with a Rf value of 0.779; it was named esterase A4 and was not seen in the susceptible reference strain. The meaning of this esterase in the resistance to organophosphate insecticides is yet to be determined. Resistance to these insecticides in Aedes aegypti is a serious problem for the control of this species therefore integrated management strategies were proposed to prevent or delay the appearance of this species in Cuba and Venezuela.

[Adaptation of microtitration plate methods for quantification of the activity of esterases and glutathione-s-transferase in Aedes aegypti]. / Adaptación de los métodos en placas de microtitulación para la cuantificación de la actividad de esterasas y glutation-s-transferasa en Aedes aegypti.

The detection techniques for the activity of non-specific esterases and glutathione-s-transferase in Culex quinquefasciatus were modified to detect such enzymes in Aedes aegypti(L). The optimal concentration values of substrate (saturating concentration) and the optimum reading time for reaction were determined for each enzyme by using 4 Aedes aegypti strains: one from Cuba 2 from Venezuela and one susceptible reference strain. The frequency of non-specific esterases turned out to be 0.76 in MIRANDA 0.42 in ARAGUA and 1 in SANTIAGO DE CUBA in which the highest frequency value of this mechanisms was reached. The frequency of glutathione-s-transferase mechanism was 0.45 in ARAGUA 0.043 in MIRANDA and 1 in SANTIAGO DE CUBA. For the first time in Cuba a set of biochemical techniques was available for detecting the resistance mechanisms of Aedes aegypti which made it possible to create sound foundations for the easy rapid detection of the resistance of this species the main dengue vector in the Americas.

[Resistance to insecticides in Blattella germanica species strains from Santiago de Cuba]. / Resistencia a insecticidas en cepas de terreno de la especie Blattella germanica procedentes de Santiago de Cuba.

A study was conducted on the level of resistance to seven insecticides, namely, 3 organophosphate compounds (malathion, chlorpyrifos and pirimiphos-methyl), one carbamate (propoxur) and 1 pyrethroid (cypermethrin, deltamethrin and lambdacialotrine) of three field-collected strains of Blattella germanica (Linnaeus, 1767) from Santiago de Cuba. These strains showed high resistance levels to malathion, cypermethrin, deltamethrin and lambdacialotrine and low resistance to pirimiphos-methyl, and also they were susceptible to chlorpyrifos and propoxur. The levels of resistance to tested organophosphate insecticides such as malathion and pirimiphos-methyl and to pyrethroid compounds like cypermethrin, deltamethrin and lambdacialotrine may be related to the increased production of esterases as a mechanism of resistance. The value of frequency of the resistant genes for enzyme acetylcholinesterase was very low, therefore, the modified acetylcholinesterase is not involved in resistance to insecticides tested in the studied strains from Santiago de Cuba.

Insecticide resistance studies on Blattella germanica (Dictyoptera:Blattellidae) from Cuba.

We studied the levels of resistance to seven insecticides: malathion, chlorpyrifos, pirimiphos-methyl, propoxur, cypermethrin, deltamethrin, and lambda-cyhalothrin in nine strains of Blattella germanica (Linnaeus, 1717) collected from sites in Santiago de Cuba and Havana City. The strains from Santiago de Cuba, generally had high levels of resistance to malathion, cypermethrin, deltamethrin, and lambda-cyhalothrin, but only low levels of resistance to pirimiphos-methyl, chlorpyrifos, and propoxur. In the strains from Havana City we found a moderate resistance to the organophosphate insecticides, resistance to the pyrethroids (except for three strains that showed susceptibility to lambda-cyhalothrin), and susceptibility to the carbamate insecticide (propoxur).

[Course of insecticide resistance in Culex quinquefasciatus (Diptera: Culicidae) in a region of La Habana]. / Evolución de la resistencia a insecticidas en Culex quinquefasciatus (Díptera: Culicidae) en un área de La Habana.

The use of malathion to control mosquitoes in Cuba during 7 years until 1986 selected 2 resistance mechanisms: that of elevated activity of nonspecific esterases and that of altered acetylcholinesterase (Ache) in Culex quinquefasciatus (Say). In Havana, specifically in the area under study (Quibú River), malathion was replaced by cypermethrin in 1987 and cycles of treatment with cypermethrin have been intensively used since 1987 up to now when the populations of Aedes or Culex increase. In Culex quinquefasciatus (Say) from the Quibú River the resistance levels, mainly to malathion, declined significantly from 1986 to 1997. An increase of resistance to pyrethroid was observed during that period of 11 years. The mechanism of elevated esterases rose to a frequency of 1 and there was also an increase in the frequency of the mechanism of Ache. The esterase B1, responsible for the resistance to malathion, but not to pyrethroid, was selected in this population until 1986. Starting from the use of pyrethroid for the control in this area, 2 new phenotypes of esterases named A6 and B6, apparently related to pyrethroid resistance, were selected.

[Comparative analysis of resistance to insecticides in strains of Culex quinquefasciatus, from Camagüey]. / Análisis comparativo de la resistencia a insecticidas en cepas de Culex quinquefasciatus, provenientes de Camagüey.

The organophosphate, carbamate and pyrethroid resistance levels in 14 strains of Culex quinquefasciatus from Camagüey were studied by bioassays and biochemical tests in larvae with or without synergists. The use of electrophoresis in polyacrylamide gel (PAGE) allowed to identify 8 patterns of esterases, among which A3A6B6, BiB6 and B1A6B6 were the most frequent. It was observed that 6 years after the suspension of malathion, there is still resistance to this product. There was also cross resistance to propoxur. Detoxification mechanisms for deltamethryn are being developed. The most important physiological mechanisms were: elevated esterases in the resistance to malathion, modified AchE for propoxur and oxidases of multiple function for deltamethryn. In relation to the genic frequencies, the modified AchE mechanisms was more extended than that of the elevated esterases in these populations of mosquitoes of the central region of Cuba.

[Characterization of resistance to organophosphate insecticides, carbamates, and pyrethroids in Culex quinquefasciatus from the State of Miranda, Venezuela]. / Caracterización de la resistencia a insecticidas organofosforados, carbamatos y piretroides en Culex quinquefasciatus del Estado de Miranda, Venezuela.

Resistance of Culex quinquefasciatus from Miranda, Venezuela to the organophosphate insecticides malathion and chlorpirifos was higher than 30x whereas resistance to pyrethroids metylpirimifos, fention, cipametrine, deltametrine, permetrine and lambdacyalotrine and to organochlorate DDT was lower than 4x. Resistance mechanisms were analyzed with piperonyl butoxide synergist (multifunction oxidases) and S.S.S. phosphotrithiate tributyl (DEF, esterase inhibitor). Multifunction oxidases did not play a significant role in resistance to organophosphate insecticides and carbamate; however, esterases were only mechanisms of resistance to malathion and chlorpirifos. The only insecticide affected by DEF and PB was cipermetrine. Biochemical tests revealed a very low frequency of the altered acetylcholinesterase mechanism (0.13). Esterase frequencies were high (1). Electrophoresis exposed the B1, A6 and B6 esterase phenotypes.

[Levels of insecticide resistance and its mechanisms in a strain of Aedes aegypti of Santiago de Cuba]. / Niveles de resistencia a insecticidas y sus mecanismos en una cepa de Aedes aegypti de Santiago de Cuba.

As a result of the most recent dengue outbreak in Santiago de Cuba province, a strain of this vector was studied to determine the levels of sensitivity and/or resistance to organophosphate and pyrethoid insecticides. The results of bioassays showed low levels of resistance to fention, malathion and deltametrine, moderate levels of resistance to temephos, metyl-pirimifos and cipermetrine and high levels of resistance to chlorpirifios. According to the results obtained from the use of S.S.S. phosphotrithiate trybutil synergist, it was shown that esterases play an important role in resistance to temephos and chlorpirifos. Piperonyl butoxide synergist disclosed that multifunction oxidases were not involved in the resistance to any of the evaluated insecticides. Biochemical techniques were applied to detect esterase-, glutathione-S-transferase- and acetylcholineaterase-mediated resistance mechanisms of Aedes aegypti. In accordance with the high frequency values observed in each of the mechanisms, it was proved that esterases and glutathione-S-transferase were involved in the insecticide resistance but acetylcholinesterases were not. However, acetylcholinesterase gen was found in Aedes aegypti for the first time though at low frequency. The polyacrylamide-gel electrophoresis made it possible to observe a well-stained band with a relative mobility value of 0.779; this band was called A4 it was not observed in the reference strain and may be associated to organophosphate resistance which remains to be proved in future research.

Epidemiology and prophylaxis of endemic goitre in the Bwa village of Sirao (Mali).

A study was conducted in Mali, in some villages exposed to iodine deficiency disorders (IDD). To treat and, above all, prevent endemic goitre, Lipiodol UF was dispensed in two ways: by intra-muscular injection (475 mg I) or by oral administration (48 mg I to 240 mg I). In two cases, hormone levels regained normal values and thyroid hypertrophies regressed significantly. Nevertheless, the impact of the treatment on the size of the goitres seems to be in favour of injections; which is probably due to the fact that in the village which received Lipiodol UF per os, many goitres were nodular.

[The selection of a strain of Culex quinquefasciatus resistant to lambdacyhalothrin and its spectrum of cross-resistance to other insecticides]. / Selección de una cepa de Culex quinquefasciatus resistente a lambdacialotrina y su espectro de resistencia cruzada a otros insecticidas.

A field strain of Culex quinquefasciatus resistant to pyrethroid lambda-cyhalothrin insecticide was selected to be used as a reference strain in the laboratory for conducting studies of biochemistry and genetics of resistance, to evaluate the utility of this insecticide for the control of mosquitoes in Cuba, and to determine the cross resistance to organophosphate insecticides, pyrethroids and a carbamate. A high resistance to lambdacyhalothrin was obtained after 6 generations of selective pressure. Lowe or no cross resistance to other pyrethroids (deltamethrin and cypermethrin), to a carbamate (propoxur) and to the organophosphate insecticides (clorpirifos and methyl-pyrimifos) was observed. A high cross resistance to malathion (organophosphate) was detected.