Expected Rates of Select Adverse Events After Immunization for Coronavirus Disease 2019 Vaccine Safety Monitoring.

Using meta-analytic methods, we calculated expected rates of 20 potential adverse events of special interest (AESI) that would occur after coronavirus disease 2019 (COVID-19) vaccination within 1-, 7-, and 42-day intervals without causal associations. Based on these expected rates, if 10 000 000 persons are vaccinated, (1) 0.5, 3.7, and 22.5 Guillain-Barre syndrome cases, (2) 0.3, 2.4, and 14.3 myopericarditis cases, (3) and 236.5, 1655.5, and 9932.8 all-cause deaths would occur coincidentally within 1, 7, and 42 days postvaccination, respectively. Expected rates of potential AESI can contextualize events associated temporally with immunization, aid in safety signal detection, guide COVID-19 vaccine health communications, and inform COVID-19 vaccine benefit-risk assessments.

Development of a Bead-Based Multiplex Assay for Use in Multianalyte Screening and Surveillance of HIV, Viral Hepatitis, Syphilis, and Herpes.

Diagnostic assays that can simultaneously determine the presence of infection with multiple pathogens are key for diagnosis and surveillance. Current multiplex diagnostic assays are complex and often have limited availability. We developed a simple, multianalyte, pathogen detection assay for screening and serosurveillance using the Luminex Magpix platform that is high throughput and can be helpful in monitoring multiple diseases. The Luminex bead-based 10-plex immunoassay for the detection of HIV-1, HIV-2, Treponema pallidum, hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus 1 (HSV-1), and HSV-2 infections was accomplished by coupling beads with specific antigens to detect IgG antibodies in plasma or serum samples. Each coupled antigen was systematically optimized, and the performance was evaluated using a panel of well-characterized specimens (n = 417) that contained antibodies to HIV-1, HIV-2, T. pallidum, HBV, HCV, HSV-1, and HSV-2. The multiplex assay had a sensitivity of 92.2% (95% Clopper-Pearson confidence interval [CI], 90.2 to 94.0%) and a specificity of 98.1% (95% CI, 97.6 to 98.7%). The sensitivities and specificities for disease-specific biomarker detection ranged from 68.7 to 100% and 95.6 to 100%, respectively. The results showed that the 10-plex immunoassay had an overall agreement of 96.7% (95% CI, 96.7 to 97.3%) with reference tests and a corresponding kappa value of 0.91 (95% CI, 0.90 to 0.93). Kappa values for the individual pathogens ranged from 0.69 to 1.00. The assay is robust and allows the simultaneous detection of antibodies to multiple antigens using a small sample volume in a high-throughput format. This assay has the potential to simplify disease surveillance by providing an alternative to expensive and highly specialized individual tests.

Metaanalysis of the Performance of a Combined Treponemal and Nontreponemal Rapid Diagnostic Test for Syphilis and Yaws.

BACKGROUND: The human treponematoses are important causes of disease. Mother-to-child transmission of syphilis remains a major cause of stillbirth and neonatal death. There are also almost 100 000 cases of endemic treponemal disease reported annually, predominantly yaws. Rapid diagnostic tests (RDTs) would improve access to screening for these diseases. Most RDTs cannot distinguish current and previous infection. The Dual Path Platform (DPP) Syphilis Screen & Confirm test includes both a treponemal (T1) and nontreponemal (T2) component and may improve the accuracy of diagnosis. METHODS: We conducted a metaanalysis of published and unpublished evaluations of the DPP-RDT for the diagnosis of syphilis and yaws. We calculated the sensitivity, specificity, and overall agreement of the test compared with reference laboratory tests. RESULTS: Nine evaluations, including 7267 tests, were included. Sensitivity was higher in patients with higher titer rapid plasma reagin (≥1:16) for both the T1 (98.2% vs 90.1%, P < .0001) and the T2 component (98.2% vs 80.6%, P < .0001). Overall agreement between the DPP test and reference serology was 85.2% (84.4%-86.1%). Agreement was highest for high-titer active infection and lowest for past infection. CONCLUSIONS: The RDT has good sensitivity and specificity of the treponemal and nontreponemal components both in cases of suspected syphilis and yaws, although the sensitivity is decreased at lower antibody titers.

Cost-effectiveness of integrated routine offering of prenatal HIV and syphilis screening in China.

BACKGROUND: In China, recent rises in syphilis and HIV cases have increased the focus on preventing mother-to-child transmission of these infections. We assess the health and economic outcomes of different strategies of prenatal HIV and syphilis screening from the local health department's perspective. METHODS: A Markov cohort decision analysis model was used to estimate the health and economic outcomes of pregnancy using disease prevalence and cost data from local sources and, if unavailable, from published literature. Adverse pregnancy outcomes included induced abortion, stillbirth, low birth weight, neonatal death, congenital syphilis in live-born infants, and perinatal HIV infection. We examined 4 screening strategies: no screening, screening for HIV only, for syphilis only, and for both HIV and syphilis. We estimated disability-adjusted life years (DALYs) for each health outcome using life expectancies and infections for mothers and newborns. RESULTS: For a simulated cohort of 10,000 pregnant women (0.07% prevalence for HIV and 0.25% for syphilis; 10% of HIV-positives were coinfected with syphilis), the estimated costs per DALY prevented were as follows: syphilis-only, $168; HIV-and-syphilis, $359; and HIV-only, $5636. The estimated incremental cost-effectiveness ratio if an existing HIV-only strategy added syphilis screening (i.e., move from the HIV-only strategy to the HIV-and-syphilis strategy) was $140 per additional DALY prevented. CONCLUSIONS: Given the increasing prevalence of syphilis and HIV among pregnant women in China, prenatal HIV screening programs that also include syphilis screening are likely to be substantially more cost-effective than HIV screening alone and prevent many more adverse pregnancy outcomes.

OnDev-LCT: On-Device Lightweight Convolutional Transformers towards federated learning.

Federated learning (FL) has emerged as a promising approach to collaboratively train machine learning models across multiple edge devices while preserving privacy. The success of FL hinges on the efficiency of participating models and their ability to handle the unique challenges of distributed learning. While several variants of Vision Transformer (ViT) have shown great potential as alternatives to modern convolutional neural networks (CNNs) for centralized training, the unprecedented size and higher computational demands hinder their deployment on resource-constrained edge devices, challenging their widespread application in FL. Since client devices in FL typically have limited computing resources and communication bandwidth, models intended for such devices must strike a balance between model size, computational efficiency, and the ability to adapt to the diverse and non-IID data distributions encountered in FL. To address these challenges, we propose OnDev-LCT: Lightweight Convolutional Transformers for On-Device vision tasks with limited training data and resources. Our models incorporate image-specific inductive biases through the LCT tokenizer by leveraging efficient depthwise separable convolutions in residual linear bottleneck blocks to extract local features, while the multi-head self-attention (MHSA) mechanism in the LCT encoder implicitly facilitates capturing global representations of images. Extensive experiments on benchmark image datasets indicate that our models outperform existing lightweight vision models while having fewer parameters and lower computational demands, making them suitable for FL scenarios with data heterogeneity and communication bottlenecks.

Contrastive encoder pre-training-based clustered federated learning for heterogeneous data.

Federated learning (FL) is a promising approach that enables distributed clients to collaboratively train a global model while preserving their data privacy. However, FL often suffers from data heterogeneity problems, which can significantly affect its performance. To address this, clustered federated learning (CFL) has been proposed to construct personalized models for different client clusters. One effective client clustering strategy is to allow clients to choose their own local models from a model pool based on their performance. However, without pre-trained model parameters, such a strategy is prone to clustering failure, in which all clients choose the same model. Unfortunately, collecting a large amount of labeled data for pre-training can be costly and impractical in distributed environments. To overcome this challenge, we leverage self-supervised contrastive learning to exploit unlabeled data for the pre-training of FL systems. Together, self-supervised pre-training and client clustering can be crucial components for tackling the data heterogeneity issues of FL. Leveraging these two crucial strategies, we propose contrastive pre-training-based clustered federated learning (CP-CFL) to improve the model convergence and overall performance of FL systems. In this work, we demonstrate the effectiveness of CP-CFL through extensive experiments in heterogeneous FL settings, and present various interesting observations.

Empowering health workers and leveraging digital technology to improve access to mental health and epilepsy care: A longitudinal quasi-experimental study in Hlaing Thar Yar Township.

Background: Despite an estimated 8% prevalence of mental disorders in Myanmar, the treatment gap is high, up to 90%. This project aimed to assess the effects of a series of activities implemented by the Myanmar Medical Association over a 2-year period in Hlaing Thar Yar Township involving community health workers (CHWs) and general practitioners (GPs) on the identification, diagnosis and management of people with psychotic disorders, depression and epilepsy. Methods: Seventy-six CHWs were trained to raise awareness, identify people with mental disorders and refer them to GPs. Fifty GPs were upskilled to diagnose and manage patients. Prevalence, treatment gap and general population's Knowledge-Attitudes-Practices (KAP) were evaluated through door-to-door surveys, whilst CHWs' and GPs' KAP were measured pre-, and post-training as well as post-intervention. Patient identification, diagnosis and management were analysed through data collected by CHWs and GPs via smartphones and tablets. Findings: At baseline, the average treatment gap was 79·7%. During the 2 year-intervention, 1,378 suspected cases were referred by CHWs to GPs and 1,186 (86%) of them saw a GP. Among the 1,088 patients (92%) diagnosed, the concordance between GPs' diagnosis and CHWs' screening was 75·6%. For CHWs, knowledge improved post-training (16·9 vs. 15·3; p = 0·0010), whilst attitudes and practices improved post-intervention (17·1 vs. 15·7; p = 0·010 and 19·4 vs. 11·2; p < 0·0001 respectively). GPs' global KAP score improved post-training (14·6 vs. 12·8; p = 0·0010), and remained stable post-intervention. General population's KAP score improved between baseline and end-line (8·3 vs. 12·7; p < 0·0001). Interpretation: This project suggests that a 2-year intervention including the training of frontline health workers and raising awareness among the population can have positive outcomes and lead to a greater number of people with mental disorders being diagnosed and managed. Funding: This project was implemented as part of a partnership involving the Myanmar Medical Association, the Myanmar Mental Health Society, the World Association of Social Psychiatry, the Université Numérique Francophone Mondiale and Sanofi Global Health. It was funded by Sanofi Global Health, within the framework of the Fight Against STigma (FAST) Program.

Molecular phylogeny of the subgenus Ceratotropis (genus Vigna, Leguminosae) reveals three eco-geographical groups and Late Pliocene-Pleistocene diversification: evidence from four plastid DNA region sequences.

BACKGROUND AND AIMS: The subgenus Ceratotropis in the genus Vigna is widely distributed from the Himalayan highlands to South, Southeast and East Asia. However, the interspecific and geographical relationships of its members are poorly understood. This study investigates the phylogeny and biogeography of the subgenus Ceratotropis using chloroplast DNA sequence data. METHODS: Sequence data from four intergenic spacer regions (petA-psbJ, psbD-trnT, trnT-trnE and trnT-trnL) of chloroplast DNA, alone and in combination, were analysed using Bayesian and parsimony methods. Divergence times for major clades were estimated with penalized likelihood. Character evolution was examined by means of parsimony optimization and MacClade. KEY RESULTS: Parsimony and Bayesian phylogenetic analyses on the combined data demonstrated well-resolved species relationships in which 18 Vigna species were divided into two major geographical clades: the East Asia-Southeast Asian clade and the Indian subcontinent clade. Within these two clades, three well-supported eco-geographical groups, temperate and subtropical (the East Asia-Southeast Asian clade) and tropical (the Indian subcontinent clade), are recognized. The temperate group consists of V. minima, V. nepalensis and V. angularis. The subtropical group comprises the V. nakashimae-V. riukiuensis-V. minima subgroup and the V. hirtella-V. exilis-V. umbellata subgroup. The tropical group contains two subgroups: the V. trinervia-V. reflexo-pilosa-V. trilobata subgroup and the V. mungo-V. grandiflora subgroup. An evolutionary rate analysis estimated the divergence time between the East Asia-Southeast Asia clade and the Indian subcontinent clade as 3·62 ± 0·3 million years, and that between the temperate and subtropical groups as 2·0 ± 0·2 million years. CONCLUSIONS: The findings provide an improved understanding of the interspecific relationships, and ecological and geographical phylogenetic structure of the subgenus Ceratotropis. The quaternary diversification of the subgenus Ceratotropis implicates its geographical dispersal in the south-eastern part of Asia involving adaptation to climatic condition after the collision of the Indian subcontinent with the Asian plate. The phylogenetic results indicate that the epigeal germination is plesiomorphic, and the germination type evolved independently multiple times in this subgenus, implying its limited taxonomic utility.

Community-based mass treatment with azithromycin for the elimination of yaws in Ghana-Results of a pilot study.

INTRODUCTION: The WHO yaws eradication strategy consists of one round of total community treatment (TCT) of single-dose azithromycin with coverage of > 90%.The efficacy of the strategy to reduce the levels on infection has been demonstrated previously in isolated island communities in the Pacific region. We aimed to determine the efficacy of a single round of TCT with azithromycin to achieve a decrease in yaws prevalence in communities that are endemic for yaws and surrounded by other yaws-endemic areas. METHODS: Surveys for yaws seroprevalence and prevalence of skin lesions were conducted among schoolchildren aged 5-15 years before and one year after the TCT intervention in the Abamkrom sub-district of Ghana. We used a cluster design with the schools as the primary sampling unit. Among 20 eligible primary schools in the sub district, 10 were assigned to the baseline survey and 10 to the post-TCT survey. The field teams conducted a physical examination for skin lesions and a dual point-of-care immunoassay for non-treponemal and treponemal antibodies of all children present at the time of the visit. We also undertook surveys with non-probabilistic sampling to collect lesion swabs for etiology and macrolide resistance assessment. RESULTS: At baseline 14,548 (89%) of 16,287 population in the sub-district received treatment during TCT. Following one round of TCT, the prevalence of dual seropositivity among all children decreased from 10.9% (103/943) pre-TCT to 2.2% (27/1211) post-TCT (OR 0.19; 95%CI 0.09-0.37). The prevalence of serologically confirmed skin lesions consistent with active yaws was reduced from 5.7% (54/943) pre-TCT to 0.6% (7/1211) post-TCT (OR 0.10; 95% CI 0.25-0.35). No evidence of resistance to macrolides against Treponema pallidum subsp. pertenue was seen. DISCUSSION: A single round of high coverage TCT with azithromycin in a yaws affected sub-district adjoining other endemic areas is effective in reducing the prevalence of seropositive children and the prevalence of early skin lesions consistent with yaws one year following the intervention. These results suggest that national yaws eradication programmes may plan the gradual expansion of mass treatment interventions without high short-term risk of reintroduction of infection from contiguous untreated endemic areas.

Losing a jewel-Rapid declines in Myanmar's intact forests from 2002-2014.

New and rapid political and economic changes in Myanmar are increasing the pressures on the country's forests. Yet, little is known about the past and current condition of these forests and how fast they are declining. We mapped forest cover in Myanmar through a consortium of international organizations and environmental non-governmental groups, using freely-available public domain data and open source software tools. We used Landsat satellite imagery to assess the condition and spatial distribution of Myanmar's intact and degraded forests with special focus on changes in intact forest between 2002 and 2014. We found that forests cover 42,365,729 ha or 63% of Myanmar, making it one of the most forested countries in the region. However, severe logging, expanding plantations, and degradation pose increasing threats. Only 38% of the country's forests can be considered intact with canopy cover >80%. Between 2002 and 2014, intact forests declined at a rate of 0.94% annually, totaling more than 2 million ha forest loss. Losses can be extremely high locally and we identified 9 townships as forest conversion hotspots. We also delineated 13 large (>100,000 ha) and contiguous intact forest landscapes, which are dispersed across Myanmar. The Northern Forest Complex supports four of these landscapes, totaling over 6.1 million ha of intact forest, followed by the Southern Forest Complex with three landscapes, comprising 1.5 million ha. These remaining contiguous forest landscape should have high priority for protection. Our project demonstrates how open source data and software can be used to develop and share critical information on forests when such data are not readily available elsewhere. We provide all data, code, and outputs freely via the internet at (for scripts: https://bitbucket.org/rsbiodiv/; for the data: http://geonode.themimu.info/layers/geonode%3Amyan_lvl2_smoothed_dec2015_resamp).

Laboratory evaluation of the Chembio Dual Path Platform HIV-Syphilis Assay.

BACKGROUND: Use of rapid diagnostic tests for HIV and syphilis has increased remarkably in the last decade. As new rapid diagnostic tests become available, there is a continuous need to assess their performance and operational characteristics prior to use in clinical settings. OBJECTIVES: In this study, we evaluated the performance of the Chembio Dual Path Platform (DPP®) HIV-Syphilis Assay to accurately diagnose HIV, syphilis, and HIV/syphilis co-infection. METHOD: In 2013, 990 serum samples from the Georgia Public Health Laboratory in Atlanta, Georgia, United States were characterised for HIV and syphilis and used to evaluate the platform. HIV reference testing combined third-generation Enzyme Immunoassay and Western Blot, whereas reference testing for syphilis was conducted by the Treponema pallidum passive particle agglutination method and the TrepSure assay. We assessed the sensitivity and specificity of the DPP assay on this panel by comparing results with the HIV and syphilis reference testing algorithms. RESULTS: For HIV, sensitivity was 99.8% and specificity was 98.4%; for syphilis, sensitivity was 98.8% and specificity was 99.4%. Of the 348 co-infected sera, 344 (98.9%) were detected accurately by the DPP assay, but 11 specimens had false-positive results (9 HIV and 2 syphilis) due to weak reactivity. CONCLUSION: In this evaluation, the Chembio DPP HIV-Syphilis Assay had high sensitivity and specificity for detecting both HIV and treponemal antibodies. Our results indicate that this assay could have a significant impact on the simultaneous screening of HIV and syphilis using a single test device for high-risk populations or pregnant women needing timely care and treatment.

HIV in Singapore--past, present, and future.

The first case of HIV infection in Singapore was reported in 1985. Between 1991 and 1998, the number of reported cases of HIV and AIDS increased rapidly before stabilizing from 1999. The epidemiology of the AIDS epidemic in Singapore is characterized by a predominance of male cases (seven to one) and heterosexual transmission. A multipronged control program comprising public education and education of high-risk groups, legislation, protection of the national blood supply, management of cases, and epidemiological surveillance has been put in place. The promotion of condom use among local sex workers has been fairly successful, with very low rates of HIV and other sexually transmitted infections (STIs). However, freelance and potential indirect sex workers such as masseuses and lounge hostesses are a concern in view of their higher prevalence of HIV and STIs. Another concern is the high proportion of cases who are diagnosed only when they develop AIDS. A better understanding of sexual networks among men who have sex with men will enable more effective intervention programs for this group. Fresh innovative approaches are needed to encourage safe sex practices and early screening.

A comparison of the analytical level of agreement of nine treponemal assays for syphilis and possible implications for screening algorithms.

OBJECTIVE: The serological diagnosis of syphilis requires the detection of two distinct antibodies, the non-treponemal and trepomenal. Center for Disease Control and Prevention (CDC) recommends screening first with a non-treponemal test such as (Rapid Plasma Reagin/Venereal Disease Research Laboratory), and then confirming those results with one of the several treponemal tests (Fluorescent Treponemal Antibody-Absorption (FTA-ABS), Enzyme Immunoassay, chemiluminescence, treponema pallidum particle agglutination (TP-PA) or Point of Care). Owing to the high volume of samples processed by some laboratories using automated systems, the screening with treponemal assays and confirming with non-treponemal tests is becoming the established norm. The purpose of this study was to evaluate eight treponemal assays using TP-PA as the predicate assay. METHODS: 290 stored serum samples were tested qualitatively according to the manufacturer's directions. RESULTS: Concordance with specimens tested as reactive or non-reactive using TP-PA was: FTA-ABS 94.5-100%, Trep-Sure 100-98.9%, BioELISA 100-98.9%, INNO-LIA 99.1-99.4%, BIOLINE 100-98.9%, CAPTIA IgG 100-97.2%, Trep-ID 100-100% and LIAISON 100-99.4%. In order to properly evaluate the performance of these assays, the analytical sensitivity was determined by endpoint titration of serial dilutions of the reactive serum samples in normal sera. The median endpoint titre varied from 1:4 for FTA-ABS to 1:512 for Trep-Sure. CONCLUSIONS: The performance of the treponemal serological assays was comparable while using medium and high-titre sera. However, the varying performance on specimen dilutions suggests that there may be differences in sensitivity with low-titre sera that are more prevalent in primary and late syphilis cases.

The risk of chikungunya fever in a dengue-endemic area.

BACKGROUND: Chikungunya, an alphavirus of the Togaviridae family, causes a febrile disease transmitted to humans by the bite of infected Aedes mosquitoes. This infection is reaching endemic levels in many Southeast Asian countries. Symptoms include sudden onset of fever, chills, headache, nausea, vomiting, joint pain with or without swelling, low back pain, and rash. According to the World Health Organization, there are 2 billion people living in Aedes-infested areas. In addition, traveling to these areas is popular, making the potential risk of infections transmitted by the bite of infected Aedes mosquitoes very high. METHODS: We proposed a mathematical model to estimate the risk of acquiring chikungunya fever in an Aedes-infested area by taking the prevalence of dengue fever into account. The basic reproduction number for chikungunya fever R(0chik) can be written as a function of the basic reproduction number of dengue R(0dengue) by calculating the ratio R(0chik)/R(0dengue). From R(0chik), we estimated the force of infection and the risk of acquiring the disease both for local residents of a dengue-endemic area and for travelers to this area. RESULTS: We calculated that R(0chik) is 64.4% that of R(0dengue). The model was applied to a hypothetical situation, namely, estimating the individual risk of acquiring chikungunya fever in a dengue-endemic area, both for local inhabitants (22% in steady state) and for visiting travelers (from 0.31% to 1.23% depending on the time spent in the area). CONCLUSIONS: The method proposed based on the output of a dynamical model is innovative and provided an estimation of the risk of infection, both for local inhabitants and for visiting travelers.

Pulmonary hypertension in patients with chronic obstructive pulmonary disease: recent advances in pathophysiology and management.

In patients with chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH) is associated with a worse prognosis. Recently, information has been increasing concerning the cellular and molecular aspects of the pathophysiology of PH in COPD. The most striking finding is the role of vascular endothelial cells and endogenous mediators released by these cells. Endothelial cell-dependent relaxation is impaired in COPD patients with PH. Moreover, vascular remodelling in these patients is mainly responsible for irreversible PH in advanced COPD. Smoking cessation will slow down the progression of the disease process and may prevent the development of PH in COPD. The timing of initiation of long-term oxygen therapy is important for the effective management of PH in COPD. Research on therapeutic agents for the effective treatment of PH is still needed in the management aspect of patients with COPD. This review focuses on the recent advances in our understanding of the pathophysiology and treatment of PH in COPD.

Can nasal continuous positive airway pressure decrease clinic blood pressure in patients with obstructive sleep apnea?

Obstructive sleep apnea (OSA) is commonly associated with systemic hypertension and now recognized as an independent risk factor for daytime hypertension. We aimed to study the short- and long-term effect of nasal continuous positive airway pressure (CPAP) in hypertensive and normotensive patients with OSA. Forty-six patients with moderated to severe OSA were treated with nasal CPAP and followed after one year of treatment. Clinic blood pressure, heart rate, and body weight were taken before and followed up for one year after beginning nasal CPAP. In this study 25 patients with OSA were found to have hypertension (54.3%). The hypertensive group showed a significant reduction in clinic blood pressure after nasal CPAP, whereas the normotensive group showed no changes. The subgroup of hypertensive patients with OSA who had no anti-hypertensive medication revealed a decrease in clinic blood pressure comparable to those with anti-hypertensive drugs. The heart rate was not significantly changed in any patients. There was no significant correlation between the decrease in body weight and the reduction in blood pressure. These results suggest that nasal CPAP alone might have a substantial blood pressure lowering effect in hypertensive patients with OSA. This effect could decrease the morbidity and mortality related to cardiovascular complications in patients with OSA.