The genetic diversity and geographic structure of the human fungal pathogen A. fumigatus have been the subject of many studies. However, most previous studies had relatively limited sample ranges and sizes and/or used genetic markers with low-level polymorphisms. In this paper, we characterize a global collection of strains of A. fumigatus using a panel of 9 highly polymorphic microsatellite markers. Using these markers, we analyze 2,026 isolates, which is ~3 times the number of isolates reported so far in previous studies. Our analyses suggest that A. fumigatus contains historically differentiated genetic populations but that its evolution is significantly impacted by contemporary forces such as widespread gene flow and local antifungal drug pressure. In the wake of a global rise in resistance to azoles in fungal pathogens, our findings should aid in developing management strategies to mitigate current increases to azole resistance.

Key Points Question Did the delivery of services within a cancer system change during the first year of the COVID-19 pandemic? Findings This population-based cohort study conducted in Ontario, Canada, found a total of 4 476 693 cancer care services during the first year of the COVID-19 pandemic, compared with 5 644 105 services in the year prior, representing a reduction of 20.7% and suggesting a backlog of 1 167 412 cancer services during the first pandemic year. Limited change was observed in systemic treatments and emergency or urgent imaging examinations and surgical procedures, while major reductions were observed in cancer screening tests, biopsies, surgical treatments, and new consultations for systemic and radiation treatment. Meaning These findings provide evidence on the deficits in cancer care that occurred during the first year of the COVID-19 pandemic that are likely to inform continued delivery of care, recovery, and future pandemic planning.

PurposeAmphotericin B (AMB) is one of the major antifungal drugs used in the management of aspergillosis and is especially recommended for treating triazole-resistant strains of Aspergillus fumigatus. However, relatively little is known about the AMB susceptibility patterns of A. fumigatus in many parts of the world. This study aims to describe the AMB susceptibility patterns in Hamilton, Ontario, Canada.MethodsThe in vitro susceptibilities of 195 environmental and clinical A. fumigatus isolates to AMB were tested by the broth microdilution method as per the Clinical and Laboratory Standards Institute’s guidelines. Catalase-generated oxygen bubbles trapped by Triton X-100 were used to quantify catalase activity in a representative group of isolates.ResultsOf the 195 isolates, 188 (96.4%) had the minimum inhibitory concentration (MIC) of AMB ≥2 mg/L, with approximately 80% and 20% of all clinical and environmental isolates having MICs of ≥ 4 mg/L. Overall, the clinical isolates were less susceptible to AMB than environmental isolates (P-value <0.001). The strain with the highest AMB MIC (16 mg/L) had one of the highest catalase activities. However, there was no correlation between AMB MIC and catalase activity in our sample.ConclusionThe widespread AMB resistance suggests that using AMB in the management of A. fumigatus infections in Hamilton would likely result in treatment failure. Although high catalase activity may have contributed to AMB resistance in some isolates, the mechanism(s) for the observed AMB resistance in Hamilton is unknown and likely complex.

Aspergillus fumigatus is a widespread opportunistic fungal pathogen causing an alarmingly high mortality rate in immunocompromised patients. Nosocomial infections by drug-resistant A. fumigatus strains are of particular concern, and there is a pressing need to understand the origin, dispersal and long-term evolution of drug resistance in this organism. The objective of this study was to investigate the diversity and putative origins of triazole resistance of A. fumigatus from India. Eighty-nine isolates, including 51 multiple triazole resistant (MTR) isolates and 38 azole-susceptible isolates, were genotyped using multilocus sequence typing (MLST), mating typing and PCR fingerprinting. MLST resolved the 51 MTR isolates into three genotypes, two of which have susceptible counterparts, suggesting that MTR isolates originated multiple times in India. The multiple-origin hypothesis was further supported by the diversity of sequences at the triazole target gene CYP51A among the MTR isolates, and by PCR fingerprints. Interestingly, there is abundant evidence for mating and recombination in natural population of A. fumigatus in India, suggesting that sexual spread of TR34 /L98H, the dominant MTR allele, is possible. Our results call for greater attention to MTR in A. fumigatus and for better management of antifungal drug use.

Aspergillus fumigatus is a saprophytic fungus that can cause lethal invasive aspergillosis in immunocompromised patients. Recent studies have shown that Eurasian and North American populations of A. fumigatus often consist of genetically diverse strains. However, very little is known about African populations of A. fumigatus. Here, we characterise the genetic diversity and triazole susceptibility of A. fumigatus in Cameroon, West Africa. A total of 495 soil samples were obtained from nine collection sites in three Cameroonian regions. Nine microsatellite markers were used to genotype all 51 identified A. fumigatus isolates. In vitro susceptibility to itraconazole and voriconazole was tested using micro broth dilution. The 51 Cameroonian A. fumigatus isolates belonged to 45 genotypes. Consistent with recombination, 32 of 36 possible pairwise loci combinations are phylogenetically incompatible. Interestingly, evidence for geographic sub-structuring was found within Cameroon and the sub-population with the most evidence of recombination was also the least susceptible sub-population to the triazole antifungals tested. Furthermore, the Cameroonian sample was significantly differentiated from those in Eurasia and North America. Overall, our results indicate the genetic uniqueness of Cameroonian A. fumigatus populations and that additional novel genetic diversity likely exist in other parts of Africa.

f Nasopharyngeal colonization by the Gram-positive bacterium Streptococcus pneumoniae is a prerequisite for pneumonia and invasive pneumococcal diseases. Colonization is asymptomatic, involving dynamic and complex interplay between commensals, the host immune system, and environmental factors. The elderly are at an increased risk of developing pneumonia, which might be due to changes in the respiratory microbiota that would impact bacterial colonization and persistence within this niche. We hypothesized that the composition of the upper respiratory tract (URT) microbiota changes with age and subsequently can contribute to sustained colonization and inefficient clearance of S. pneumoniae. To test this, we used a mouse model of pneumococcal colonization to compare the composition of the URT microbiota in young, middle-aged, and old mice in the naive state and during the course of colonization using nasal pharyngeal washes. Sequencing of variable region 3 (V3) of the 16S rRNA gene was used to identify changes occurring with age and throughout the course of S. pneumoniae colonization. We discovered that age affects the composition of the URT microbiota and that colonization with S. pneumoniae is more disruptive of preexisting communities in older mice. We have further shown that host-pathogen interactions following S. pneumoniae colonization can impact the populations of resident microbes, including Staphylococcus and Haemophilus. Together, our findings indicate alterations to the URT microbiota could be detrimental to the elderly, resulting in increased colonization of S. pneumoniae and decreased efficiency in its clearance.

Background:Despite significant efforts to understand adverse pregnancy outcome in women receiving Antiretroviral Therapy (ART), ART-related adverse birth outcomes are still poorly understood. We systematically review ART-related adverse birth outcomes among HIV-infected pregnant women; we also review the covariates associated with adverse birth outcomes in the aforementioned group.Methods:The main source for our systematic review was electronic bibliographic databases. Databases such as MEDLINE, PubMed, EMBASE and AIDSLINE were searched. Furthermore, search engines such as Google and Google Scholar were specifically searched for gray literature. Methodological quality of available literature was assessed using the Newcastle - Ottawa Quality Assessment Scale & M. Hewitt guideline. We examined a total of 1,124 papers and reviewed the studies using the PICOT criteria which stands for Patient (population), Intervention (or “Exposure”), Comparison, Outcome and Type of study. Finally, 32 methodologically fit studies were retained and included in our review.Results:Frequently observed adverse birth outcomes included low birth weight (LBW), Preterm Birth (PB), Small for Gestational Age (SGA), while still birth and congenital anomalies were infrequent. Type of regimen such as Protease Inhibitor (PI) based regimens and timing of initiation of ART are some of the factors associated with adverse pregnancy outcomes. Covariates principally included malnutrition and other co-morbidities such as malaria and HIV.Conclusions and Public Health Implications:There is growing evidence in published literature suggesting that ART might be causing adverse birth outcomes among pregnant women in developing countries. There is a need to consider regimen types for HIV-infected pregnant women. There is need to design large cohort studies.

Abstract