Stromal p16 and SATB2 Expression Does Not Distinguish Atypical Polypoid Adenomyoma (APA) From its Benign Mimics.

Atypical polypoid adenomyoma (APA) is a polypoid biphasic lesion of low malignant potential that arises in the lower uterine segment and uterine corpus. The diagnosis of APA is often challenging on biopsy and curettage specimens, and both benign and malignant processes need to be considered in the differential. Stromal expression of p16 and SATB2 have recently been shown to distinguish APA from myoinvasive endometrioid carcinoma. The authors hypothesized that p16 and SATB2 immunohistochemistry could also aid in the distinction of APA from benign adenomyomatous polyp and endometrioid adenomyoma. The study comprised 10 APAs, 7 adenomyomatous polyps, 11 endometrioid adenomyomas, and 10 myoinvasive endometrioid carcinomas. The majority of APAs showed moderate to strong, diffuse p16 and stromal expression. However, most adenomyomatous polyps and endometrioid adenomyomas also exhibited moderate to strong, focal to diffuse p16 stromal expression. SATB2 showed weak to moderate, focal to diffuse expression in the majority of APAs, adenomyomatous polyps and endometrioid adenomyomas. In contrast, p16 and SATB2 were negative to weak and focal in 90% of myoinvasive endometrioid carcinomas. Our findings demonstrate that p16 and SATB2 may be helpful in the differential diagnosis of myoinvasive endometrioid carcinoma and APA while not useful in separating APA from adenomyomatous polyp and endometrioid adenomyoma.

PD-L1 Expression in HPV-associated Versus HPV-independent Invasive Vulvar Squamous Cell Carcinoma.

Two etiological pathways have been implicated in the pathogenesis of vulvar squamous cell carcinoma (VSCC): a high-risk human papillomavirus (HPV)-associated route and an HPV-independent pathway characterized by TP53 mutations. Programmed cell death ligand 1 (PD-L1) has become increasingly useful in predicting the response to checkpoint inhibitor therapy in squamous cell carcinomas at various anatomical sites. This study aimed to assess the association between PD-L1 expression and the VSCC subtype to evaluate the utility of PD-L1 in prognostication and therapeutic selection based on HPV status. PD-L1 status was assessed using 3 separate metrics for the extent of PD-L1 staining in various cell types: immune cell score, tumor proportion score (TPS), and combined positive score. The study group consisted of 25 HPV-associated and 28 HPV-independent VSCCs. PD-L1 expression was positive in the majority of VSCCs according to all 3 scoring metrics (84.9% by immune cell score, 77.3% by TPS, and 90.6% by combined positive score). PD-L1 expression was observed in the majority of cases in both groups (60%-96.4%). PD-L1 expression using the TPS method was greater in HPV-independent tumors than in HPV-associated tumors ( P = 0.004), and high PD-L1 expression was also more common in the HPV-independent subtype ( P = 0.016 using the TPS method and P = 0.013 using the combined positive score method). Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.

Rolling epidemic of Legionnaires' disease outbreaks in small geographic areas.

Legionnaires' disease (LD) is reported from many parts of the world, mostly linked to drinking water sources or cooling towers. We reviewed two unusual rolling outbreaks in Sydney and New York, each clustered in time and space. Data on these outbreaks were collected from public sources and compared to previous outbreaks in Australia and the US. While recurrent outbreaks of LD over time linked to an identified single source have been described, multiple unrelated outbreaks clustered in time and geography have not been previously described. We describe unusual geographic and temporal clustering of Legionella outbreaks in two cities, each of which experienced multiple different outbreaks within a small geographic area and within a short timeframe. The explanation for this temporal and spatial clustering of LD outbreaks in two cities is not clear, but climate variation and deteriorating water sanitation are two possible explanations. There is a need to critically analyse LD outbreaks and better understand changing trends to effectively prevent disease.

Adherence to anti-vectorial prevention measures among travellers with chikungunya and malaria returning to Australia: comparative epidemiology.

OBJECTIVE: Compare the adoption and adherence to health protection behaviours prior to and during travel among international Australian travellers who return to Australia with notified chikungunya or malaria infection. This information could inform targeted health promotion and intervention strategies to limit the establishment of these diseases within Australia. RESULTS: Seeking travel advice prior to departure was moderate (46%, N = 21/46) yet compliance with a range of recommended anti-vectorial prevention measures was low among both chikungunya and malaria infected groups (16%, N = 7/45). Reasons for not seeking advice between groups was similar and included 'previous overseas travel with no problems' (45%, N = 9/20) and 'no perceived risk of disease' (20%, N = 4/20). Most chikungunya cases (65%, N = 13/20) travelled to Indonesia and a further 25% (N = 5/20) visited India, however most malaria cases (62%, N = 16/26) travelled to continental Africa with only 12% (N = 3/26) travelling to India. The majority (50%, N = 10/20) of chikungunya cases reported 'holiday' as their primary purpose of travel, compared to malaria cases who most frequently reported travel to visit friends and family (VFR; 42%, N = 11/26). These results provide import data that may be used to support distinct public health promotion and intervention strategies of two important vector-borne infectious diseases of concern for Australia.

Pandemics, public health emergencies and antimicrobial resistance - putting the threat in an epidemiologic and risk analysis context.

Public health messaging about antimicrobial resistance (AMR) sometimes conveys the problem as an epidemic. We outline why AMR is a serious endemic problem manifested in hospital and community-acquired infections. AMR is not an epidemic condition, but may complicate epidemics, which are characterised by sudden societal impact due to rapid rise in cases over a short timescale. Influenza, which causes direct viral effects, or secondary bacterial complications is the most likely cause of an epidemic or pandemic where AMR may be a problem. We discuss other possible causes of a pandemic with AMR, and present a risk assessment formula to estimate the impact of AMR during a pandemic. Finally, we flag the potential impact of genetic engineering of pathogens on global risk and how this could radically change the epidemiology of AMR as we know it. Understanding the epidemiology of AMR is key to successfully addressing the problem. AMR is an endemic condition but can play a role in epidemics or pandemics, and we present a risk analysis method for assessing the impact of AMR in a pandemic.

Influenza A H5N1 and H7N9 in China: A spatial risk analysis.

BACKGROUND: Zoonotic avian influenza poses a major risk to China, and other parts of the world. H5N1 has remained endemic in China and globally for nearly two decades, and in 2013, a novel zoonotic influenza A subtype H7N9 emerged in China. This study aimed to improve upon our current understanding of the spreading mechanisms of H7N9 and H5N1 by generating spatial risk profiles for each of the two virus subtypes across mainland China. METHODS AND FINDINGS: In this study, we (i) developed a refined data set of H5N1 and H7N9 locations with consideration of animal/animal environment case data, as well as spatial accuracy and precision; (ii) used this data set along with environmental variables to build species distribution models (SDMs) for each virus subtype in high resolution spatial units of 1km2 cells using Maxent; (iii) developed a risk modelling framework which integrated the results from the SDMs with human and chicken population variables, which was done to quantify the risk of zoonotic transmission; and (iv) identified areas at high risk of H5N1 and H7N9 transmission. We produced high performing SDMs (6 of 8 models with AUC > 0.9) for both H5N1 and H7N9. In all our SDMs, H7N9 consistently showed higher AUC results compared to H5N1, suggesting H7N9 suitability could be better explained by environmental variables. For both subtypes, high risk areas were primarily located in south-eastern China, with H5N1 distributions found to be more diffuse and extending more inland compared to H7N9. CONCLUSIONS: We provide projections of our risk models to public health policy makers so that specific high risk areas can be targeted for control measures. We recommend comparing H5N1 and H7N9 prevalence rates and survivability in the natural environment to better understand the role of animal and environmental transmission in human infections.

Correction: Influenza A H5N1 and H7N9 in China: A spatial risk analysis.

[This corrects the article DOI: 10.1371/journal.pone.0174980.].

Publicly available software tools for decision-makers during an emergent epidemic-Systematic evaluation of utility and usability.

Epidemics and emerging infectious diseases are becoming an increasing threat to global populations-challenging public health practitioners, decision makers and researchers to plan, prepare, identify and respond to outbreaks in near real-timeframes. The aim of this research is to evaluate the range of public domain and freely available software epidemic modelling tools. Twenty freely utilisable software tools underwent assessment of software usability, utility and key functionalities. Stochastic and agent based tools were found to be highly flexible, adaptable, had high utility and many features, but low usability. Deterministic tools were highly usable with average to good levels of utility.

An overview of the epidemiology and emergence of influenza A infection in humans over time.

In recent years multiple novel influenza A strains have emerged in humans. We reviewed publically available data to summarise epidemiological characteristics of distinct avian influenza viruses known to cause human infection and describe changes over time. Most recently identified zoonotic strains have emerged in China (H7N9, H5N6, H10N8) - these strains have occurred mostly in association with visiting a live bird market. Most zoonotic AIVs and swine influenza variants typically cause mild infections in humans however severe illness and fatalities are associated with zoonotic H5N6, H10N8, H7N9 and H5N1 serotypes, and the H1N1 1918 Spanish Influenza. The changing landscape of avian influenza globally indicates a need to reassess the risk of a pandemic influenza outbreak of zoonotic origin.