The AIDS Epidemic Model 2023 for Estimating HIV Trends and Transmission Dynamics in Asian Epidemic Settings.

BACKGROUND: Thirteen Asian countries use the AIDS Epidemic Model (AEM) as their HIV model of choice. This article describes AEM, its inputs, and its application to national modeling. SETTING: AEM is an incidence tool used by Spectrum for the Joint United Nations Programme on HIV/AIDS global estimates process. METHODS: AEM simulates transmission of HIV among key populations (KPs) using measured trends in risk behaviors. The inputs, structure and calculations, interface, and outputs of AEM are described. The AEM process includes (1) collating and synthesizing data on KP risk behaviors, epidemiology, and size to produce model input trends; (2) calibrating the model to observed HIV prevalence; (3) extracting outputs by KP to describe epidemic dynamics and assist in improving responses; and (4) importing AEM incidence into Spectrum for global estimates. Recent changes to better align AEM mortality with Spectrum and add preexposure prophylaxis are described. RESULTS: The application of AEM in Thailand is presented, describing the outputs and uses in-country. AEM replicated observed epidemiological trends when given observed behavioral inputs. The strengths and limitations of AEM are presented and used to inform thoughts on future directions for global models. CONCLUSIONS: AEM captures regional HIV epidemiology well and continues to evolve to meet country and global process needs. The addition of time-varying mortality and progression parameters has improved the alignment of the key population compartmental model of AEM with the age-sex-structured national model of Spectrum. Many of the features of AEM, including tracking the sources of infections over time, should be incorporated in future global efforts to build more generalizable models to guide policy and programs.

Cloning and Functional Characterization of a Double-Stranded RNA-Degrading Nuclease in the Tawny Crazy Ant (Nylanderia fulva).

RNA interference is a powerful tool that post-transcriptionally silences target genes. However, silencing efficacy varies greatly among different insect species. Recently, we attempted to knock down some housekeeping genes in the tawny crazy ant (Nylanderia fulva), a relatively new invasive species in the southern United States, but only achieved relatively low silencing efficiency when dsRNA was orally administered. Here, we detected divalent cation-dependent, dsRNA-degrading activity in the midgut fluid of worker ants in ex vivo assays. To determine whether dsRNA degradation could contribute to low effectiveness of oral RNAi in N. fulva, we cloned its sole dsRNase gene (NfdsRNase). The deduced amino acid sequence contained a signal peptide and an endonuclease domain. Sequence alignment indicated a high degree of similarity with well-characterized dsRNases, particularly the six key residues at active sites. We also identified dsRNase homologs from five other ant species and found a tight phylogenetic relationship among ant dsRNases. NfdsRNase is expressed predominantly in the abdomen of worker ants. Oral delivery of dsRNA of NfdsRNase significantly reduced the expression of NfdsRNase transcripts, and substantially suppressed dsRNA-degrading activity of worker ants' midgut fluids as well. Our data suggest that dsRNA stability in the alimentary tract is an important factor for gene silencing efficiency in N. fulva, and that blocking NfdsRNase in gut lumen could potentially improve RNAi, a novel pest management tactic in control of N. fulva and other ant species.

Comparison of gene expression in the red imported fire ant (Solenopsis invicta) under different temperature conditions.

The red imported fire ant (RIFA), Solenopsis invicta Buren is native to South America and is known as a global problematic invasive species. This study focused on the molecular response of RIFA by comparing gene expression profiles after exposing ants to low (10 °C) and high (40 °C) temperature stress and comparing them to untreated controls (30 °C). A total of 99,085 unigenes (the clustered non-redundant transcripts that are filtered from the longest assembled contigs) were obtained, of which 19,154 were annotated with gene descriptions, gene ontology terms, and metabolic pathways. 86 gene ontology (GO) functional sub-groups and 23 EggNOG terms resulted. Differentially expressed genes (DEGs) with log2FC ≥ 10 were screened and were compared at different temperatures. We found 203, 48, and 66 specific DEGs co-regulated at 10, 20, and 40 °C. Comparing transcriptome profiles for differential gene expression resulted in various DE genes, including cytochrome P450, NADH dehydrogenase subunit 1, cuticle protein and heat shock protein (HSP), which have previously been reported to be involved in cold and high temperature resistance. GO analysis revealed that antioxidant activity is up-regulated under high temperature stress. We verified the RNA-seq data by qPCR on 20 up- and down-regulated DEGs. These findings provide a basis for future understanding of the adaptation mechanisms of RIFA and the molecular mechanisms underlying the response to low and high temperatures.

The Expiry of Humira® Market Exclusivity and the Entry of Adalimumab Biosimilars in Europe: An Overview of Pricing and National Policy Measures.

Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry. Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures. Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab. Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80-90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 - €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures. Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.

The Estimation and Projection Package Age-Sex Model and the r-hybrid model: new tools for estimating HIV incidence trends in sub-Saharan Africa.

OBJECTIVES: Improve models for estimating HIV epidemic trends in sub-Saharan Africa (SSA). DESIGN: Mathematical epidemic model fit to national HIV survey and ANC sentinel surveillance (ANC-SS) data. METHODS: We modified EPP to incorporate age and sex stratification (EPP-ASM) to more accurately capture the shifting demographics of maturing HIV epidemics. Secondly, we developed a new functional form for the HIV transmission rate, termed 'r-hybrid', which combines a four-parameter logistic function for the initial epidemic growth, peak, and decline followed by a first-order random walk for recent trends after epidemic stabilization. We fitted the r-hybrid model along with previously developed r-spline and r-trend models to HIV prevalence data from household surveys and ANC-SS in 177 regions in 34 SSA countries. We used leave-one-out cross validation with household survey HIV prevalence to compare model predictions. RESULTS: The r-hybrid and r-spline models typically provided similar HIV prevalence trends, but sometimes qualitatively different assessments of recent incidence trends because of different structural assumptions about the HIV transmission rate. The r-hybrid model had the lowest average continuous ranked probability score, indicating the best model predictions. Coverage of 95% posterior predictive intervals was 91.5% for the r-hybrid model, versus 87.2 and 85.5% for r-spline and r-trend, respectively. CONCLUSION: The EPP-ASM and r-hybrid models improve consistency of EPP and Spectrum, improve the epidemiological assumptions underpinning recent HIV incidence estimates, and improve estimates and short-term projections of HIV prevalence trends. Countries that use general population survey and ANC-SS data to estimate HIV epidemic trends should consider using these tools.

Supercolonial structure of invasive populations of the tawny crazy ant Nylanderia fulva in the US.

BACKGROUND: Social insects are among the most serious invasive pests in the world, particularly successful at monopolizing environmental resources to outcompete native species and achieve ecological dominance. The invasive success of some social insects is enhanced by their unicolonial structure, under which the presence of numerous queens and the lack of aggression against non-nestmates allow high worker densities, colony growth, and survival while eliminating intra-specific competition. In this study, we investigated the population genetics, colony structure and levels of aggression in the tawny crazy ant, Nylanderia fulva, which was recently introduced into the United States from South America. RESULTS: We found that this species experienced a genetic bottleneck during its invasion lowering its genetic diversity by 60%. Our results show that the introduction of N. fulva is associated with a shift in colony structure. This species exhibits a multicolonial organization in its native range, with colonies clearly separated from one another, whereas it displays a unicolonial system with no clear boundaries among nests in its invasive range. We uncovered an absence of genetic differentiation among populations across the entire invasive range, and a lack of aggressive behaviors towards conspecifics from different nests, even ones separated by several hundreds of kilometers. CONCLUSIONS: Overall, these results suggest that across its entire invasive range in the U.S.A., this species forms a single supercolony spreading more than 2000 km. In each invasive nest, we found several, up to hundreds, of reproductive queens, each being mated with a single male. The many reproductive queens per nests, together with the free movement of individuals between nests, leads to a relatedness coefficient among nestmate workers close to zero in introduced populations, calling into question the stability of this unicolonial system in which indirect fitness benefits to workers is apparently absent.

Updates to the Spectrum/Estimations and Projections Package model for estimating trends and current values for key HIV indicators.

BACKGROUND: The Spectrum model is used by national programs and UNAIDS to prepare annual estimates of the status of the HIV epidemic in 160 countries. The model and assumptions are updated regularly under the guidance of the UNAIDS Reference Group on Estimates, Modelling and Projections in response to new data, studies, and program needs. This study describes the most recent updates for the 2016 round of estimates. METHODS: Meetings of the UNAIDS Reference Group include individuals with extensive knowledge of HIV programs, research, statistics, and public policy. The Reference Group also collaborates with other institutions (such as the United Nations Population Division and the US Census Bureau) and projects (such as the ALPHA Network and IeDEA Consortium) to ensure that latest methods and data are used in the preparation of the annual estimates. In the past year new methods and data have been introduced for pediatric estimates, incidence fitting, and ART mortality (described elsewhere in this supplement). RESULTS: The 2016 version of Spectrum includes a number of other enhancements, including updated demographic data from the United Nations Population Division, program options for treatment (treat all), and programs to prevent mother-to-child transmission (option B+), improved methods to aggregate uncertainty to regional and global levels, several options for generating incidence trends, adjustments to the Estimations and Projections Package model to better incorporate aging effects, adjustments to account for the changing bias in prevalence from antenatal clinic surveillance, and an option to fit incidence among all adults 15+ in addition to 15-49. CONCLUSION: The new methods and data implemented in the 2016 version of Spectrum allow national programs more flexibility in describing their programs and improve the estimates of key indicators and their uncertainty.

Incorporation of hierarchical structure into estimation and projection package fitting with examples of estimating subnational HIV/AIDS dynamics.

OBJECTIVES: The article aims to give Spectrum/estimation and projection package (EPP) users and the scientific community a basic understanding of the underlying statistical model used to incorporate hierarchical structure in HIV subnational estimation, and to show how it has been implemented in the Spectrum/EPP interface for improving subepidemic estimation. The article also provides recommended default settings for this new model. METHODS: We apply a generalized linear mixed-effects model on antenatal clinics prevalence data to get area-specific prevalence and uncertainty estimates, and transform those estimates to auxiliary data. We then fit the EPP model to both the observed data and auxiliary data. RESULTS: We apply the proposed methods to four countries with different levels of data availability. We compare the out-of-sample prediction accuracy of the proposed method with varying auxiliary sample sizes and EPP without auxiliary data. CONCLUSION: We find that borrowing information from data-rich areas to data-sparse areas using our proposed method improves EPP fit in data-sparse areas. We recommend using the sample size estimated from generalized linear mixed-effects model as the default auxiliary sample size.

Field Trials With 0.5% Novaluron Insecticide Applied as a Bait to Control Subterranean Termites (Reticulitermes sp. and Coptotermes formosanus [Isoptera: Rhinotermitidae]) on Structures.

A field study was initiated in 2009 with 0.5% novaluron the BASF Advance Termite Bait System, which was 100% effective in controlling Reticulitermes sp. Holmgren and Coptotermes formosanus Shiraki infestations on 11 structures in the Texas City, TX area. Stations with inspection cartridges (cellulose tablets) and monitoring bases (southern yellow pine) and independent monitoring devices were installed in an alternating pattern around each structure and were inspected every 30 d postinstallation. When subterranean termite activity was confirmed on the inspection cartridge or the monitoring base, the inspection cartridge was removed and replaced with a bait cartridge containing 0.5% novaluron insecticide on a proprietary matrix (124 g/cartridge) in a station. Once the novaluron-treated bait was inserted, inspections of that station were made on a 4-mo cycle until no termite activity was observed. The mean time to achieve control of the subterranean termites on the structures was 10.5 mo post initial installation of bait. Mean time to achieve control of the termites on the structures after the baits were installed was 5.4 mo. Control of the termites on the structures required consumption of a mean of 1.3 bait cartridges (166.2 g) of 0.5% novaluron bait matrix per structure. These results indicate that the baits with 0.5% novaluron were effective in controlling termites on the structures used in this study.

Improvements in prevalence trend fitting and incidence estimation in EPP 2013.

OBJECTIVE: Describe modifications to the latest version of the Joint United Nations Programme on AIDS (UNAIDS) Estimation and Projection Package component of Spectrum (EPP 2013) to improve prevalence fitting and incidence trend estimation in national epidemics and global estimates of HIV burden. METHODS: Key changes made under the guidance of the UNAIDS Reference Group on Estimates, Modelling and Projections include: availability of a range of incidence calculation models and guidance for selecting a model; a shift to reporting the Bayesian median instead of the maximum likelihood estimate; procedures for comparison and validation against reported HIV and AIDS data; incorporation of national surveys as an integral part of the fitting and calibration procedure, allowing survey trends to inform the fit; improved antenatal clinic calibration procedures in countries without surveys; adjustment of national antiretroviral therapy reports used in the fitting to include only those aged 15-49 years; better estimates of mortality among people who inject drugs; and enhancements to speed fitting. RESULTS: The revised models in EPP 2013 allow closer fits to observed prevalence trend data and reflect improving understanding of HIV epidemics and associated data. CONCLUSION: Spectrum and EPP continue to adapt to make better use of the existing data sources, incorporate new sources of information in their fitting and validation procedures, and correct for quantifiable biases in inputs as they are identified and understood. These adaptations provide countries with better calibrated estimates of incidence and prevalence, which increase epidemic understanding and provide a solid base for program and policy planning.

Alate trap-based assessment of Formosan subterranean termite (Isoptera: Rhinotermitidae) dispersal flight phenology associated with an urbanized barrier island ecosystem.

During 2009, 2010, and 2011, the reproductive dispersal flight phenology of Formosan subterranean termites (Coptotermes formosanus Shiraki) was assessed on Galveston Island, TX, via LED light-based termite alate traps. In all three years, traps were deployed at sampling sites before the initiation of C. formosanus dispersal flights, and retrieved weekly until the cessation flights. In total, 45, 102, and 90 traps were deployed during 2009, 2010, and 2011, respectively. In all years, C. formosanus flights began during the second full week of May; however, peak dispersal flight activity occurred 2 wk earlier in 2009 and 2011 than in 2010. Significantly more alates were collected during the 2009 flight peak than in 2010 and 2011 despite the fact that greater than twice the number of traps were deployed in 2010 and 2011, versus 2009. Additionally, a greater percentage of traps collected C. formosanus alates in 2009 (71.1%) than in 2010 (38.2%) or 2011 (20.0%). A relatively inexpensive trap design (∼US$25.00 per trap) was developed for this project. The traps used in this work yielded results that were similar to those of other researchers using a variety of different trap designs. It is hoped that these results will allow for more targeted surveillance of C. formosanus dispersal flights by residents and pest management professionals at this location and elsewhere.

Comparison of multiple steam treatment durations for control of bed bugs (Cimex lectularius L.).

BACKGROUND: The factors contributing to the current resurgence of bed bug Cimex lectularius L. populations across the United States and elsewhere include, among others, the development of resistance to chemical insecticides and population management practices. This has led to the development and attempted refinement of many non-chemical control methods that contribute to an IPM approach to solving the current bed bug population density increase in urban dwellings. One such approach is the use of heat in the form of steam to provide an effective mechanism for controlling localized infestations of bed bugs. RESULTS: The work reported herein was designed to refine our understanding of the duration of bed bug/steam contact necessary to affect mortality of bed bugs in laboratory trials. Beg bug eggs, nymphs and adults were exposed to three steam treatment exposure periods in these trials. Mean percentage mortality of bed bug eggs was 100% (regardless of duration of exposure), and that of nymphs and adults ranged from 88.0 to 94.0%. Survivorship of nymphs and adults in the trials was the result of experimental protocol restrictions that would not usually be associated with actual pest management efforts. CONCLUSIONS: The treatment equipment used in these trials is portable and relatively inexpensive and represents a non-chemical means of killing all life stages of bed bugs. While this method would likely be seen as an inefficient means of remediating a mature bed bug infestation within a structure, it does represent a practical component of integrated management of this pest insect.