Mechanisms of Phosphine Toxicity

Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3), the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N) and arsenic (As), which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity

Potential for using pheromone trapping and molecular screening in phosphine resistance research: Presentation

Phosphine resistance monitoring typically involves bioassays of beetles from population samples collected from grain storage facilities. Insects are classified into susceptible or resistant phenotypes based on mortality or survival at one or more discriminating doses. Although valuable, phenotype testing has several drawbacks. First, phenotype testing needs live insects, and considerable effort is required to collect and maintain them before testing. Second, population samples may contain multiple genotypes expressing different levels of resistance that may not be distinguishable using discriminating dose bioassays. Third, collections are likely to be focussed around grain storages to maximise sampling success. Recent research shows that several key pests are actively dispersing through flight. The availability of commercial pheromone lures and recent advances in molecular screening provide an opportunity to provide information on resistance gene frequencies more broadly across the landscape. This approach is proving to be a valuable adjunct to traditional resistance testing in Australia.Phosphine resistance monitoring typically involves bioassays of beetles from population samples collected from grain storage facilities. Insects are classified into susceptible or resistant phenotypes based on mortality or survival at one or more discriminating doses. Although valuable, phenotype testing has several drawbacks. First, phenotype testing needs live insects, and considerable effort is required to collect and maintain them before testing. Second, population samples may contain multiple genotypes expressing different levels of resistance that may not be distinguishable using discriminating dose bioassays. Third, collections are likely to be focussed around grain storages to maximise sampling success. Recent research shows that several key pests are actively dispersing through flight. The availability of commercial pheromone lures and recent advances in molecular screening provide an opportunity to provide information on resistance gene frequencies more broadly across the landscape. This approach is proving to be a valuable adjunct to traditional resistance testing in Australia

Utility of biotechnology based decision making tools in postharvest grain pest management: An Australian case study

A major concern for the Australian grain industry in recent years is the constant threat of resistance to the key disinfestant phosphine in a range of stored grain pests. The need to maintain the usefulness of phosphine and to contain the development of resistance are critical to international market access for Australian grain. Strong levels of resistance have already been established in major pests including the lesser grain borer, Rhyzopertha dominica (F.), the red flour beetle, Tribolium castaneum (Herbst), and most recently in the rusty grain beetle Cryptolestes ferrugineus (Stephens). As a proactive integrated resistance management strategy, new fumigation protocols are being developed in the laboratory and verified in large-scale field trials in collaboration with industry partners. To aid this development, we have deployed advanced molecular diagnostic tools to accurately determine the strength and frequency of key phosphine resistant insect pests and their movement within a typical Australian grain value chain. For example, two major bulk storage facilities based at Brookstead and Millmerran in southeast Queensland, Australia, were selected as main nodes and several farms and feed mills located in and around these two sites at a scale of 25 to 100 km radius were selected and surveyed. We determined the type, pattern, frequency as well as the distribution of resistance alleles accurately for two major pests, R. dominica and T. castaneum. Overall, this information along with the phenotypic data, provide a basis for designing key intervention strategies in managing resistance problems in the study area.A major concern for the Australian grain industry in recent years is the constant threat of resistance to the key disinfestant phosphine in a range of stored grain pests. The need to maintain the usefulness of phosphine and to contain the development of resistance are critical to international market access for Australian grain. Strong levels of resistance have already been established in major pests including the lesser grain borer, Rhyzopertha dominica (F.), the red flour beetle, Tribolium castaneum (Herbst), and most recently in the rusty grain beetle Cryptolestes ferrugineus (Stephens). As a proactive integrated resistance management strategy, new fumigation protocols are being developed in the laboratory and verified in large-scale field trials in collaboration with industry partners. To aid this development, we have deployed advanced molecular diagnostic tools to accurately determine the strength and frequency of key phosphine resistant insect pests and their movement within a typical Australian grain value chain. For example, two major bulk storage facilities based at Brookstead and Millmerran in southeast Queensland, Australia, were selected as main nodes and several farms and feed mills located in and around these two sites at a scale of 25 to 100 km radius were selected and surveyed. We determined the type, pattern, frequency as well as the distribution of resistance alleles accurately for two major pests, R. dominica and T. castaneum. Overall, this information along with the phenotypic data, provide a basis for designing key intervention strategies in managing resistance problems in the study area

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Unique genetic variants in dihydrolipoamide dehydrogenase (dld) gene confer strong resistance to phosphine in the rusty grain beetle, Cryptolestes ferrugineus (Stephens)

The rusty grain beetle, Cryptolestes ferrugineus, a major pest of stored commodities, has developed very high levels (>1000×) of resistance to the fumigant phosphine. Resistance in this species is remarkably stronger than reported in any other stored product pests demanding the need to understand the molecular basis of this trait. Previous genetic studies in other grain insect pests identified specific variants in two major genes, rph1 and rph2 in conferring the strong resistance trait. However, in C. ferrugineus, although the gene, rph1 was identified as cytochrome-b5-fatty acid desaturase, the rph2 gene has not been reported so far. We tested the candidate gene for rph2, dihydrolipoamide dehydrogenase (dld) using the recently published transcriptome of C. ferrugineus and identified three variants, L73N and A355G + D360H, a haplotype, conferring resistance in this species. Our sequence analysis in resistant strain and phosphine selected resistant survivors indicates that these variants occur either alone as a homozygote or a mixture of heterozygotes (i.e complex heterozygotes) both conferring strong resistance. We also found that one of the three variants, possibly L73N expressing “dominant” trait at low frequency in resistant insects. Comparison of dld sequences between Australian and Chinese resistant strain of this species confirmed that the identified variants are highly conserved. Our fitness analysis indicated that resistant insects may not incur significant biological costs in the absence of phosphine selection for 19 generations. Thus, we propose that the observed high levels of resistance in C. ferrugineus could be primarily due to the characteristics of three unique variants, L73N and A355G + D360H within dld

Delaying surgery for patients with a previous SARS-CoV-2 infection

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