Video-assisted thoracoscopic surgery for IPA in haematology patients
Up to a third of patients die during surgery for massive haemoptysis, but the criteria for selecting asymptomatic patients for pre-emptive surgery (wedge resection, segmentectomy or lobectomy) remain controversial. A group in China (Ma et al, 2019) recently published a series of 51 haematology patients who received video-assisted thorascopic surgery (VATS), who had been selected on the basis of having a limited lesion that was resistant to antifungals. Mean blood loss was 112.35 ml and mean hospital stay was 7.75 days. No operations were converted to open surgery, and no recurrences or deaths were seen within 30 days. Postoperative complications were seen in 21.6%, most commonly excessive effusions and prolonged air leak (especially for wedge resections).
Effective plasma concentrations of itraconazole and its active metabolite for IPA
Therapeutic drug monitoring is often recommended for itraconazole but may be unavailable - for example, it is not covered by the national health insurance scheme in Japan for pulmonary aspergillosis. A recent study (Nakamura et al, 2019) measured trough plasma concentrations of itraconazole (ITZ) and its active metabolite hydroxyitraconazole (OH-ITZ) by HPLC among 34 patients taking 200 mg/day itraconazole. The variation in total ITZ+OH-ITZ concentrations was striking, ranging from 47 ng/ml to 7750 ng/ml. Concentration was clearly related to efficacy: ITZ levels were 4.8x higher among patients who improved (mean 1254 ng/ml) than those who worsened (mean 260 ng/ml), while OH-ITZ levels were 3.5x higher among patients who improved (mean 1830 ng/ml) than those who worsened (mean 530 ng/ml).
The Aspergillus fumigatus Mismatch Repair MSH2 Homolog Is Important for Virulence and Azole Resistance
Mutations in the cyp51A gene are the major mechanism for acquired azole resistance in Aspergillus, but it can also arise through defects in the DNA mismatch repair (MMR) system that lead to a genomic instability. A recent study (Fernanda dos Reis et al, 2019) looked at 62 environmental and clinical strains of A. fumigatus, of which 12 (18%) had variants in mshA, which initiates MMR. Mortality was lower for an mshA deletion mutant (30-60%) than for wild type (90%) in a mouse model of invasive aspergillosis. However, when the deletion strains were repeatedly (x10) transferred onto fresh solid agar, they began to accumulate mutations that increased virulence, and exposure to a single round of voriconazole exposure led to the appearance of mutants with 200-fold higher resistance to posaconazole than mutants evolved from the wild type strain.
Biological Control for Aflatoxin Mitigation in Farmers’ Fields in Nigeria
Aspergillus contamination of crops such as maize and peanuts can bring aflatoxins into the human food chain, leading to chronic poor health or even life-threatening liver disease and cancer, as well as economic losses. One preharvest control method used in the US for many years involves displacing the harmful mould with one or more non-toxin-producing strains. In 2014, a biocontrol product called Aflasafe was registered in Nigeria, which contains a mixture of 4 atoxigenic strains of Aspergillus flavus. A decade-long study (Bandyopadhyay et al, 2019) found that it reduced aflatoxin content by >80% compared to untreated maize, and that >95% of treated maize contained <20ppb aflatoxin.
