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BACKGROUND: Fungicide resistance in Pyrenophora teres f. maculata and P. teres f. teres has become an important disease management issue. Control of the associated barley foliar diseases, spot form and net form net blotch, respectively, relies on three major groups of fungicides, demethylation inhibitors (DMIs), succinate dehydrogenase inhibitors (SDHIs) and quinone outside inhibitors (QoIs). However, resistance has been reported for the DMI and SDHI fungicides in Australia. To enhance detection of different resistance levels, phenotyping and genotyping workflows were designed. RESULTS: The phenotyping workflow generated cultures directly from lesions and compared growth on discriminatory doses of tebuconazole (DMI) and fluxapyroxad (SDHI). Genotyping real‐time polymerase chain reaction (PCR) assays were based on alleles associated with sensitivity or resistance to the DMI and SDHI fungicides. These workflows were applied to spot form and net form net blotch collections from 2019 consisting predominantly of P. teres f. teres from South Australia and P. teres f. maculata from Western Australia. For South Australia the Cyp51A L489‐3 and SdhC‐R134 alleles, associated with resistance to tebuconazole and fluxapyroxad, respectively, were the most prevalent. These alleles were frequently found in single isolates with dual resistance. This study also reports the first detection of a 134 base pair insertion located at position‐66 (PtTi‐6) in the Cyp51A promoter of P. teres f. maculata from South Australia. For Western Australia, the PtTi‐1 insertion was the most common allele associated with resistance to tebuconazole. CONCLUSION: The workflow and PCR assays designed in this study have been demonstrated to efficiently screen P. teres collections for both phenotypic and genetic resistance to DMI and SDHI fungicides. The distribution of reduced sensitivity and resistance to DMI and SDHI fungicides varied between regions in south‐western Australia, suggesting the emergence of resistance was impacted by both local pathogen populations and disease management programmes. The knowledge of fungicide resistance in regional P. teres collections will be important for informing appropriate management strategies. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Artemisinin-based combination therapies (ACTs) were introduced as the standard of care for uncomplicated malaria in Africa almost two decades ago. Recent studies in East Africa have reported a gradual increase in kelch13 ( k13 ) mutant parasites associated with reduced artesunate efficacy. As part of the Community Access to Rectal Artesunate for Malaria project, we collected blood samples from 697 children with signs of severe malaria in northern Uganda between 2018 and 2020, before and after the introduction of rectal artesunate (RAS) in 2019. K13 polymorphisms were assessed, and parasite editing and phenotyping were performed to assess the impact of mutations on parasite resistance. Whole-genome sequencing was performed, and haplotype networks were constructed to determine the geographic origin of k13 mutations. Of the 697 children, 540 were positive for Plasmodium falciparum malaria by PCR and were treated with either RAS or injectable artesunate monotherapy followed in most cases by ACT. The most common k13 mutation was C469Y (6.7%), which was detected more frequently in samples collected after RAS introduction. Genome editing confirmed reduced in vitro susceptibility to artemisinin in C469Y-harboring parasites compared to wild-type controls ( P < 0.001). The haplotypic network showed that flanking regions of the C469Y mutation shared the same African genetic background, suggesting a single and indigenous origin of the mutation. Our data provide evidence of selection for the artemisinin-resistant C469Y mutation. The realistic threat of multiresistant parasites emerging in Africa should encourage careful monitoring of the efficacy of artemisinin derivatives and strict adherence to ACT treatment regimens., Competing Interests: The authors declare no conflict of interest.

Background: Cambodia targets P. falciparum malaria elimination by 2023 and all human malaria species by 2025, aligning with WHO's Mekong Malaria Elimination program. The Intermittent Preventive Treatment for Forest Goers (IPTf) project aimed at forest-specific malaria elimination. The study aims to pinpoint the main factors driving malaria transmission in Cambodian forests and evaluate the initial implementation and effectiveness of IPTf in accelerating the elimination of malaria by treating and preventing infections among at-risk populations in these areas., Methods: From March 11, 2019, to January 30, 2021, a malaria intervention program took place in isolated forests in Northeast Cambodia. The first phase focused on observing forest goers (FGs) within the forests, documenting their malaria risk. In the second phase, a monthly artesunate-mefloquine IPTf was implemented by trained forest malaria workers who were former FGs conducting interviews, blood collection, and IPTf administration., Findings: Throughout the two-year period, 2198 FGs were involved in 3579 interviews, with 284 in both the observation and intervention phases. Following IPTf implementation, PCR-confirmed malaria prevalence significantly decreased from 2.9% to 0.5% for P. falciparum and from 21.0% to 4.7% for P. vivax . Among the 284 participants tracked through both phases, malaria prevalence fell from 2.5% to 0.3% for P. falciparum and from 22.5% to 3.7% for P. vivax . The intervention phase demonstrated a rapid decline in P. falciparum prevalence among mobile and previously inaccessible populations, while also revealing a higher P. falciparum infection risk associated with activities inaccurately labelled as farming, underscoring the need for customized interventions., Interpretation: The successful implementation of IPTf in Cambodia's remote forests has markedly decreased malaria prevalence among high-risk groups. Cambodia's National Malaria Program has acknowledged this strategy as essential for malaria elimination intervention, endorsing forest-specific approaches to meet the 2025 goal of eradicating all human malaria species in Cambodia., Funding: The study received funding from the French 5% Initiative (Initiative Canal 2-17SANIN205)., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Background: In early 2016, in Preah Vihear, Northern Cambodia, artesunate/mefloquine was used to cope with dihydroartemisinin/piperaquine-resistant Plasmodium falciparum parasites. Following this policy, P. falciparum strains harbouring molecular markers associated with artemisinin, piperaquine and mefloquine resistance have emerged. However, the lack of a viable alternative led Cambodia to adopt artesunate/mefloquine countrywide, raising concerns about a surge of triple-resistant P. falciparum strains., Objectives: To assess the prevalence of triple-resistant parasites after artesunate/mefloquine implementation countrywide in Cambodia and to characterize their phenotype., Methods: For this multicentric study, 846 samples were collected from 2016 to 2019. Genotyping of molecular markers associated with artemisinin, piperaquine and mefloquine resistance was coupled with phenotypic analyses., Results: Only four triple-resistant P. falciparum isolates (0.47%) were identified during the study period. These parasites combined the pfk13 polymorphism with pfmdr1 amplification, pfpm2 amplification and/or pfcrt mutations. They showed significantly higher tolerance to artemisinin, piperaquine and mefloquine and also to the mefloquine and piperaquine combination., Conclusions: The use of artesunate/mefloquine countrywide in Cambodia has not led to a massive increase of triple-resistant P. falciparum parasites. However, these parasites circulate in the population, and exhibit clear resistance to piperaquine, mefloquine and their combination in vitro. This study demonstrates that P. falciparum can adapt to more complex drug associations, which should be considered in future therapeutic designs., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Introduction: Several markers have been investigated to predict the prognosis of lung cancer. In the present study, the prognostic values of epithelial growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, and p120 catenin expression were investigated by immunohistochemistry in patients with a surgically resected non-small cell lung carcinoma (NSCLC)., Patients and Method: EGFR, VEGF, E-cadherin, and p120 catenin expression were prospectively determined in resected specimens from patients with NSCLC who had undergone surgery between 2003 and 2007. Patients' and disease-related general characteristics and survival rate were recorded., Results: One hundred seventeen patients with a mean age of 61.3 years were included in the study. After a mean follow-up of 27.5 months, the median survival was determined to be 44.0 months and the 5-year survival was 46.2%. The 5-year survival in negative and positive staining groups were as follows; 32% and 66.7% for EGFR (p = 0.02), 37.8% and 50.7% for VEGF (p = 0.5), 41% and 66% for E-cadherin (p = 0.19), 46% and 50% for p120 catenin (p = 0.27). The differentiation, N status, stage and EGFR staining were variables significantly affecting survival (p = 0.001, 0.006, 0.03 and 0.02 respectively). In multivariate Cox analysis, the EGFR staining level and N status were variables those significantly affecting survival (p = 0.021 and p = 0.010)., Conclusions: While negative staining of EGFR was related with poor survival, staining of VEGF, E-cadherin, and p120 catenin were not related with survival in patients with resected NSCLC., (Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.)

Primary hydatid cysts very rarely form in intrathoracic yet extrapulmonary sites. Accurate preoperative diagnosis in such cases is difficult, and corrective surgical procedures necessarily differ from those that are used to treat the far more typical pulmonary or hepatic hydatid cysts. We retrospectively evaluated the diagnostic and operative characteristics of intrathoracic extrapulmonary hydatid cysts, and we examined the outcome of aggressive surgical interventions that went beyond conventional parenchymal-sparing procedures.From 2003 through 2007, 14 patients (mean age, 39.14 +/- 16.8 yr) underwent surgical treatment in our hospital for primary intrathoracic extrapulmonary hydatid cysts. These cysts were variously in the diaphragm, chest wall, mediastinum, pleura, and pericardial cavity. All patients underwent cystectomy, decortication, resection, and repair of the adjacent structure. No complication, recurrence, or death occurred in the follow-up period of 15 +/- 18.1 months (range, 2-52 mo).In order to achieve complete resection and to avoid recurrence of disease from intrathoracic extrapulmonary hydatid cysts, the thoracic surgeon should forgo cystotomy and capitonnage in favor of cystectomy with a wide resection and reconstruction of surrounding tissues. Postoperatively, patients should adhere to a regimen of anthelmintic therapy.