Human Immunodeficiency Virus Research Articles

Loss to follow-up of patients after antiviral treatment as an additional barrier to HCV elimination

BackgroundEliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it.MethodsPatients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study.ResultsIn the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy.ConclusionsIn a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.

Granulomatous secondary syphilis - 2 case reports and review of the literature.

Granulomatous inflammation is usually described in association with tertiary syphilis up till recent years where there are emerging cases reporting its presence in secondary syphilis. Herein we present two patients who presented with erythematous infiltrated papules and nodules and were eventually diagnosed with granulomatous secondary syphilis, with clearance of their rashes after treatment. In this article, we highlight the important clues that point clinicians and histopathologists towards the diagnosis of syphilis compared to other similar differentials such as leprosy in reaction, cutaneous histiocytosis and lymphoma. Additionally, from literature review and own experiences, we wish to highlight that granulomatous syphilis is often palmoplantar sparing and its presence may not necessarily be a feature of immunocompromised states (e.g. human immunodeficiency virus) In this increasingly connected world, the recognition of an atypical presentation of an age-old disease in patients with different skin types needs to be underscored with close clinicopathological correlation.

Novel Approaches in HIV-1 Cure: Genetic Editing and Gene Repression Techniques. Topic Review

Introduction: The worldwide challenge presented by human immunodeficiency virus type 1, affecting 39 million individuals, endures despite the highly active antiretroviral therapy. Limitations of it, including insufficiently addressing viral reservoirs leading to prolonged drug toxicity, resistance concerns, and economic burdens, have fueled exploration into alternative approaches. Gene editing and gene repression techniques have emerged as potential solutions. Objective: Conduct a comprehensive analysis of recent research following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, focusing on genetic modification and gene repression in HIV-1-infected samples. Methods: A meticulous search identified 413 articles, of which 76 met strict criteria. Inclusion criteria involved studies on gene editing and HIV-1 expression (2019–2023), emphasizing CCR5 repression. Exclusions targeted weak evidence, lacking practical efficacy, and non-relevance to HIV-1 or genetic tools. Duplicates and non-open-access articles were also excluded. Results: The identified strategies show promise in their ability to mitigate the chronicity of the infection. However, challenges such as off-target effects, ethical considerations surrounding in vivo, ex vivo, and germline editing, and variable efficacy across studies are evident. The imperative for continued evaluation, refinement of techniques, and the development of effective administration methods is underscored. Conclusions: This topic review provides a nuanced exploration of recent advancements in gene editing and gene repression techniques for managing HIV-1. While the findings suggest promising avenues, the identified challenges necessitate ongoing research and innovation in order to harness the full potential of these strategies in the quest for an effective HIV-1 solution.

Understanding depression, anxiety and stress in young people living with HIV in Ghana

Ghanaians with perinatally acquired human immunodeficiency virus (HIV) infection now live into adulthood. It is known that adolescents and young adults living with HIV have a high risk of mental health comorbidity. Despite increasing global attention on HIV–mental health interactions, the field remains understudied in Ghana, with an attendant lack of national integrated care solutions. This study aimed to measure the burden and explore the context of depression, anxiety and stress symptoms among young people living with HIV receiving care at a tertiary care hospital in Ghana. This was an explanatory sequential mixed-methods study. Depression, anxiety and stress symptoms were measured using the Depression, Anxiety and Stress Scale, and their associations with quality of life (QoL), socioeconomic status, internalised stigma, disease stage and HIV-related risk-taking behaviours were explored. After preliminary quantitative data analysis, semi-structured interviews were conducted for those who screened positive for depression and/or anxiety to explore their experience with this comorbidity. This study found a low prevalence of depression and anxiety symptoms, which were associated with higher stigma scores and lower QoL. We believe this low prevalence to be attributable to the effect of several psychosocial interventional programmes, which were previously piloted with the study cohort that have gradually normalised mental health discussions. Participants also showed marked resilience and knowledge about their condition. The results of this study present an opportunity to advocate and scale up effective locally adapted and strength-based solutions to address the mental illness–HIV syndemic in Ghanaian young people living with HIV.

A cGAS-mediated type I interferon response in human CD4+ T cells depends on productive infection and is conserved over HIV types and strains.

Human immunodeficiency virus (HIV) type 2 is known to be less pathogenic than HIV-1, possibly due to more effective immune control mechanisms. The mechanism of innate sensing of HIV-2 by T cells is at present unclear. In this study, we show that several primary isolates of HIV-2 (CBL20 and CI85) and HIV-1 (A8 and D2), similar to the molecular clone HIV-1 NL4.3-GFP-I, induce a significant type I interferon response in its main target, activated CD4+ T cells. However, they are unable to do so after shRNA-mediated knock-down of cGAS. In addition, both HIV-1- and HIV-2-induced type I interferon response in CD4+ T cells was dependent on productive infection and integration, as the presence of RT or integrase inhibitor dramatically suppressed the sensing. Our findings collectively showed that the cGAS-dependent type I interferon response of CD4+ T cells to HIV infection is conserved over HIV types and critically depends on productive infection.IMPORTANCEBy unveiling the role of cGAS in sensing Human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) across CD4+ T cells and highlighting its broader relevance that might be mirrored in other cell types, our research provides insights into the uniform mechanism of innate immune activation by different HIV isolates. By demonstrating the necessity of productive infection, we highlight the robust and specific nature of the observed cGAS-mediated innate response, dispelling concerns about contaminating plasmids triggering an immune response. Our preliminary data suggest that the lower pathogenicity of HIV-2 may not be directly correlated to superior innate immune control mediated by cGAS.

Role of RNA G-Quadruplexes in the Japanese Encephalitis Virus Genome and Their Recognition as Prospective Antiviral Targets.

G-quadruplexes (GQs) have been primarily studied in the context of cancer and neurodegenerative pathologies. However, recent research has shifted focus to their existence and functional roles in viral genomes, revealing GQ-regulated key pathways in various human pathogenic viruses. While GQ structures have been reported in the genomes of emerging and re-emerging viruses, RNA viruses have been understudied compared to DNA viruses, including notable examples such as human immunodeficiency virus-1, hepatitis C virus, Ebola virus, Nipah virus, Zika virus, and SARS-CoV-2. The flavivirus family, comprising the Japanese encephalitis virus (JEV), poses a significant global threat due to recurring outbreaks yet lacks approved antivirals. In this study, we identified and characterized eight putative G-quadruplex-forming motifs within essential genes involved in genome replication, assembly, and internalization in the host cell, conserved across different JEV isolates. The formation and stability of these motifs were validated through a multitude of biophysical and cell-based assays. The interaction and binding affinity of these motifs with the known GQ-binding ligand BRACO-19 were supported by biophysical assays, confirming the capability of these motifs to form GQ structures. Notably, BRACO-19 also exerted antiviral properties through reduction of viral replication and infectious virus titers as well as inhibition of viral protein expression, as evaluated by the cell-based assays. This comprehensive molecular characterization of G-quadruplex structures within the JEV genome highlights their potential as promising antiviral targets for intervention strategies against JEV infection through GQ-specific ligands.

Assessing Vaccine Intentions, Knowledge, Self-Efficacy, and Trust: A Cross-Sectional Study on Perceptions of Monkeypox Vaccination and Public Health Risk Awareness in Makurdi, Benue State, Nigeria.

Introduction The global emergence of monkeypox has heightened public health concerns, particularly in regions with limited vaccine uptake. In Nigeria, understanding the factors influencing vaccination intentions is essential for developing effective public health strategies. Despite vaccine availability, hesitancy and varying degrees of acceptance persist, driven by factors such as self-efficacy, vaccine trust, and overall attitudes toward vaccination. Previous research highlights the importance of these factors in shaping health behaviors, particularly in vulnerable populations. In Benue State, where distinct health challenges affect key demographic groups such as people living with human immunodeficiency virus(PLHIV) and men who have sex with men (MSM), addressing vaccination intentions is critical for public health efforts. Objectives The objective was to assess the intention to receive the monkeypox vaccine, self-assessed knowledge levels, self-efficacy, and risk perception among the PLHIV, MSM, and the healthcare populationin Benue State, Nigeria. Additionally, the study aimed to evaluate public trust in vaccines and health authorities and to understand how these factors influence attitudes toward vaccination and overall perceptions of monkeypox-related health risks. Methodology A cross-sectional survey was conducted among 377 participants in Makurdi, Benue State, Nigeria, focusing onPLHIV, MSM, and healthcare workers. Participants were recruited using a snowball sampling technique, which leveraged social media platforms (WhatsApp, Facebook, and Telegram) and the Federal Medical Center in Makurdi. Data were collected using a structured questionnaire designed to assess self-efficacy, trust in vaccines, vaccination attitudes, and prior vaccination experiences. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY). Descriptive statistics were used to summarize the characteristics of the study population. Bivariate analyses, including chi-square tests and independent t-tests, were employed to explore the relationships between socio-demographic characteristics and vaccination intentions. Statistical significance was set at p < 0.05 for all analyses. Results The study revealed a significant positive relationship between self-efficacy and vaccination intention (p = 0.001). Trust in vaccinations and health authorities was also found to be a significant predictor of vaccination intention (p < 0.05). Furthermore, participants who had previously received the coronavirus disease 2019 (COVID-19) vaccine were more likely to express intention to receive the monkeypox vaccine (p = 0.000). However, the perception that the threat of monkeypox was exaggerated did not significantly impact vaccination intention (p = 0.4). Conclusion This study highlights the critical role of self-efficacy, trust in vaccines, and prior vaccination experiences in shaping the intention to receive the monkeypox vaccine in Benue State, Nigeria. The findings suggest that public health policies should prioritize enhancing trust in vaccines and health authorities, as well as boosting self-efficacy, to improve vaccination uptake. Addressing these factors may lead to more effective public health interventions against monkeypox and other infectious diseases.

Relationship Between Psychotherapy and Mitigation of Self-Stigmitization Among Adult Persons Living with HIV in Nairobi City, Kenya

Human Immunodeficiency virus (HIV) has caused a lot of suffering ever since the first case was reported. To date there are about 80,000,000 People living with HIV (PLWH). Although the rate of new infections has reduced, the effects remain far reaching, especially in Sub-Sahara Africa. Apprehension associated with HIV often scares many from finding out their HIV standing, considering restraint methods, avoiding risky conducts, and uplifting of PLWH endeavours. Many studies focused on HIV testing and counselling services which is for now mainly service provider driven. The drive of this study was showing the relationship between psychotherapy and mitigation of self-stigmatization (SS) among Adult PLWH in Embakasi East Sub-County (herein denoted Embakasi East), Nairobi City, County (herein denoted Nairobi City), Kenya; Social Cognitive Theory guided this study, employing descriptive research design on a target population of 3,886 PLWH registered for ART treatment at 7 public health centres in Embakasi East, Nairobi City. Cochran’s sample size formula was applied in determining the suitable sample size of 246 that was confirmed by the sampling table. Purposive sampling was used to select both the public health centres and the informants from each centre. Proportionate random sampling assisted in picking participants (both male and female), then random sampling was used to construct the sample. The sample of 246 (74 males and 172 females) was drawn, with 6 informants. Informants were interviewed and questionnaires completed by PLWH. In the analysis of the data, descriptive statistics, mainly frequencies, percentages and mean were applied on facts while thematic analysis on qualitative data. The study results showed that SS was very prevalent, caused by the respondents themselves and those around them. They acknowledged being hated, them hating themselves and did not want their HIV status known. Just a few had utilized psychotherapy service, who agreed that they were relieved a lot of pain they were undergoing, and they recommended it to others. The study recommended that authorities need to consider promoting and committing resources for psychotherapy as a solution to SS among PLWH, invest more in advocacy work, and invigorating sensitization among families on their role in supporting PLWH being

Factors associated with positive human papillomavirus (HPV) test results in cervical precancer screening: a cross-sectional study at Souro Sanou National Teaching Hospital (SSNTH) in Bobo Dioulasso, Burkina Faso.

Human papilloma virus testing is a new method of screening for precancerous cervical lesions. Here we identified factors associated to the positive Human papilloma virus-testing in the context of cervical precancer screening at the Souro Sanou National Teaching Hospital in Burkina Faso. Conducted from June 2021-May 2022, this was a cross-sectional study, including patients aged between 25 and 55years-old and screened for precancerous lesions and received HPV-testing at the Department of Gynecology, Obstetrics and Reproductive Medicine (DGORM) of the SSNTH. The proportion of positive HPV-test was calculated, and we identified factors associated to positive HPV-test using logistic regression. Of the 759 patients came for precancerous lesions screening, 559 patients were included. Their mean-age was 38.8 ± 7.9years-old, 94.3% were from urban area and 50.3% identified as housewives. Regarding the past medical history, it noted: number of gestures (3.2 ± 2.0), parity (2.8 ± 1.9), number of living children (2.8 ± 1.9), having abortion experience (24.0%), age of first-sexual-intercourse(18.6 ± 2.3years), alcohol (9.1%) and tobacco (1.0%) consumption, sexually-transmitted-infection (27.0%), Human immunodeficiency virus (HIV)infection (5.0%); none had been vaccinated against HPV. Biologically, 16.6% [95% CI: 13.6-20] of the women had a positive HPV-test. The factors significantly associated with positive HPV-test were: occupation in the private sector [OR: 0.06(0.0-0.5); p < 0.001], having a sexually-transmitted-infection [OR: 3.9(2.0-7.7); p < 0.001], age of first-sexual-intercourse [OR: 0.7(0.6-0.9); p < 0.001], sexual-multiple-partnership [OR: 17.5(8.1-39.6); p < 0.001], and HIV status [OR: 13.2(4.4-40.5); p < 0.001]. These results call for health actions through the reinforcement for behavioral change mainly about sexually-transmitted-infections, and for the raising awareness of the population for the screening related to the precancerous lesions and HIV.

Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.

Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases. We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool. Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities. Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.

Human immunodeficiency virus-1 genome from patient with fever, Nepal.

A patient with fever presented to the referral infectious disease hospital in Kathmandu, Nepal. Metagenomic sequencing of the patient's serum recovered a near-complete genome of human immunodeficiency virus-1 (HIV-1), distinct from previous HIV-1 genomes from Nepal in GenBank. It shared 92.48% nucleotide identity with an HIV-1 subtype C isolate from India.

Immunoregulatory protein B7-H3 upregulated in bacterial and viral infection and its diagnostic potential in clinical settings.

Bacterial and viral infections cause a huge burden to healthcare settings worldwide, and mortality rates associated with infectious microorganisms have remained high in recent decades. Despite tremendous efforts and resources worldwide to explore diagnostic biomarkers, rapid and easily assayed indicators for the diagnosis of bacterial and viral infections remain a challenge. B7 homolog 3 (B7-H3), a member of the B7 family of immunoregulatory proteins, is overexpressed in patients with septicemia, meningitis, pneumonia, and hepatitis. Therefore, B7-H3 could be used as a potential clinical indicator and therapeutic target for bacterial and viral infections caused by H. pylori, S. pneumoniae, M. pneumoniae, hepatitis B virus (HBV), viral hemorrhagic septicemia virus (VHSV), respiratory syncytial virus (RSV), and human immunodeficiency virus (HIV). Moreover, the interplay between infectious microorganisms and B7-H3 and exploration of the functional roles of the B7-H3 molecule could aid in the development of novel strategies for disease diagnosis and immunotherapy.

Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.

Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.

Left hand abscess as a paradoxical reaction during treatment of disseminated tuberculosis in immunocompetent patient: case report and review of literature

A paradoxical reaction (PR) during the treatment of tuberculosis was defined as the worsening of preexisting disease either clinically or radiologically or the appearance of a new tuberculous lesion. These reactions are frequently observed in patients coinfected with human immunodeficiency virus (HIV) upon the initiation of antiretroviral therapy (ART). Herein, we present a unique case of a paradoxical reaction in a previously healthy 19-year-old female who started anti-tuberculosis treatment for disseminated tuberculosis. Four weeks after treatment initiation, she developed two new swollen masses in her left dorsum of the hand, accompanied by fever and new right submandibular painful lymphadenopathy, with worsening of the preexisting left lower neck lymph node. The patient underwent needle aspiration from her new skin abscess on the dorsum of her left hand, which revealed positive polymerase chain reaction (PCR) for Mycobacterium tuberculosis. Anti-tuberculosis treatment was continued, and the patient fully recovered. We described an unusual presentation of paradoxical reaction manifested by a skin abscess at a site distant from her primary disease in an immunocompetent TB patient, which demonstrated the importance of considering paradoxical reactions in HIV-negative patients who present with worsening signs and symptoms after initial improvement following treatment initiation.

An analytical observational study for diagnostic accuracy of volume, conductivity &amp; scatter (VCS) indices of neutrophils for diagnosis of sepsis in an emergency hospital setting

Background &amp; objectives The newer technique using an innovative volume conductivity scatter (VCS) technology is emerging as a surrogate for sepsis diagnosis. The VCS technology offers a more objective method to measure cell volume (V), characterize conductivity (C) and light scatter (S) directly from more than 8,000 white blood cells (WBCs). However, diagnostic performance of VCS parameters in sepsis has not been extensively tested in routine hospital emergency settings. Therefore, the present study aimed to investigate the diagnostic and prognostic performance of VCS markers of neutrophils in our local hospital emergency setting. Methods It was an observational analytical study with 41 cases of sepsis and 43 healthy controls aged above 18 yr. Individuals with acute coronary syndrome and individuals with already diagnosed Human Immunodeficiency Virus (HIV) infection were excluded from the study. Results The mean neutrophil volume (MNV) values were not significantly different between cases and controls (P 0.138) whereas mean neutrophil conductance (MNC) and mean neutrophil scatter (MNS) measurements were significantly higher among cases as compared to controls (both P-values &lt;0.001). According to Receiver Operating Characteristics (ROCs) curve analysis, MNV in our study failed to show statistically significant discriminatory ability in sepsis (AUC 0.54) whereas MNC (AUC 0.98) and MNS (AUC 0.95) showed marked discriminatory ability in diagnosing sepsis in this study cohort. Interpretation &amp; conclusions Among VCS parameters, MNV failed as a standalone biomarker of sepsis in routine emergency setting whereas MNC and MNS had statistically significant diagnostic and discriminatory accuracies among hospitalized affected individuals with sepsis.

Impact of Infections During Pregnancy on Transplacental Antibody Transfer.

Vaccination in pregnancy is important to protect the mother and fetus from infectious diseases. The transfer of maternal antibodies across the placenta during pregnancy can continue to protect the neonate for several months after birth while the neonatal adaptive immune system develops. Several pathogens have been shown to impair the transplacental transfer of maternal antibodies, including human immunodeficiency virus, malaria, the severe acute respiratory syndrome coronavirus 2, and cytomegalovirus. This review discusses the mechanisms contributing to decreased transplacental antibody transfer in the setting of maternal infections, such as changes in antibody glycosylation profile, maternal hypergammaglobulinemia, and placental injury. The frequency of epidemics is increasing, and pregnant people are more likely to become exposed to novel pathogens now than they were in the past. Understanding the mechanisms by which infectious diseases impair maternal-fetal antibody transfer is important for pandemic preparedness to maximize the impact of maternal vaccination for child health.

Next-Generation Sequencing Methods for Near-Real-Time Molecular Epidemiology of HIV and HCV.

The World Health Organisation has set targets of reducing the transmission of new hepatitis C (HCV) infections by 90%, and ending human immunodeficiency virus-1 (HIV) as a public health threat, by 2030. To achieve this, efficient and timely viral surveillance, and effective public health interventions, are required. Traditional epidemiological methods are largely dependent on the recognition of incident cases with symptomatic illness; acute HIV and HCV infections are commonly asymptomatic, which may lead to delays in the recognition of such new infections. Instead, for these viruses, molecular epidemiology may improve the detection of, and response to, clusters of viral transmission. Molecular epidemiology using historical datasets has highlighted key populations that may have benefitted from a timely intervention. Similar analyses performed on contemporary samples are needed to underpin the 2030 targets, but this requires the generation of a cohesive dataset of viral genome sequences in near-real-time. To generate such data, methodologies harnessing next-generation sequencing (NGS) should be utilised. Here we discuss the opportunity presented by NGS for public health surveillance of HIV and HCV, and discuss three methods that can generate sequences for such analysis. These include full-length genome amplification, utilised for analysis of HCV in the research space; tiling PCR, which was the method of choice for many diagnostic laboratories in the SARS-CoV-2 pandemic; and bait-capture hybridisation, which has been utilised in local HIV outbreaks. These techniques could be applied for near-real-time HIV and HCV surveillance, informing public health strategies that will be key to achieving 2030 targets.

Temporal variations in and predictive values of ABG results prior to in-hospital cardiac arrest

In-hospital cardiac arrest (IHCA) has been understudied relative to out-of-hospital cardiac arrest. Further, studies of IHCA have mainly focused on a limited number of pre-arrest patient characteristics (e.g., demographics, number and types of comorbidities). Arterial blood gas (ABG) analysis, one of the most common diagnostic tests for assessing and managing critically or acutely ill hospitalized patients, reflects pathophysiological changes associated with adverse events or complications, including IHCA. Yet the predictive and prognostic values of patterns of pre-arrest ABG parameters for IHCA have not been fully studied. The purpose of this retrospective pilot cohort study was to investigate temporal variations in and predictive values of pre-IHCA ABG values among patients with a history of cardiopulmonary diseases. Eligible patients had a history of structural heart disease, heart failure, or pulmonary diseases. Patients were excluded if their IHCA was due to trauma, drug overdose, hypothermia, drowning, chronic terminal illness such as cancer or human immunodeficiency virus, or bleeding not caused by hemorrhage in the brain or heart. Also collected were dates, times, and causes of mechanical intubation prior to IHCA and causes of mortality. Co-primary outcomes were initial rhythms of IHCA and return of spontaneous circulation (ROSC). We conducted a pilot study and the ABG results (pH, partial pressure of carbon dioxide [PaCO2], partial pressure of oxygen [PaO2], bicarbonate [HCO3-] , and lactate) from each of the 3 days prior to IHCA were extracted from the electronic health records (EHRs) of patients (N = 44) who had experienced IHCA at a single medical center. To characterize differences in ABG parameters among study days, coefficients of variation (CVs) were compared using the modified likelihood ratio test (MLRT) using the worst ABG values. Linear regression models were run for the continuous ABG parameters and logistic regression models for the dichotomous ABG variables. Overall model effect and least squares means, SDs, mean differences within and between days (with 95 % confidence intervals), p-values and effect sizes were reported for continuous variables. For categorical variables, estimates and standard errors, 95 % confidence intervals, Wald X2 variables and p-values were presented. The CVs for pH, PaCO2, and HCO3- differed significant between study days (p <.05). The least squares means with 95 % confidence intervals for pH and lactate differed significantly in days (p <.01). Moderate to large effect sizes were obtained for all ABG parameters. Arterial lactate predicted initial rhythm (shockable versus non-shockable) and ROSC, while pH and HCO3- predicted ROSC. Results demonstrate, for the first time, the presence of significant variability in ABG parameters across 72 h prior to IHCA and the predictive potential of these parameters for initial rhythms of IHCA and ROSC. While validation in a larger sample is necessary, this study confirms the feasibility and potential value of exploring temporal patterns of pre-arrest ABG values from the EHRs. Findings of future larger studies on pre-arrest patterns of ABG parameters and other laboratory values may be used to design models that better predict risk for IHCA and guide patient care in the pre and intra-arrest periods.

Loop-Mediated Isothermal Amplification Assay Using Gold Nanoparticles for Detecting Treponema pallidum subspp. pallidum.

Venereal syphilis in humans is caused by Trepenoma pallidum subspp. pallidum. A study has shown that 30,302 individuals in Thailand had syphilis in 2020, with a male-to-female ratio of 1:0.8 and the highest incidence rate at ages between fifteen and twenty-four. This research aimed to develop a loop-mediated isothermal amplification assay using gold nanoparticles (LAMP-AuNPs). Analytical sensitivity, diagnostic specificity, accuracy, and predictive values for each technique are provided. The diagnosis sensitivities of polymerase chain reaction using agarose gel electrophoresis (PCR-AGE), loop-mediated isothermal amplification assay using agarose gel electrophoresis (LAMP-AGE), and LAMP-AuNPs were 116 ng/µL, 11.6 ng/µL, and 11.6 ng/µL, respectively. We evaluated the analytical specificity using PCR and a LAMP-based assay, and there was no cross-reactivity to Leptospira interrogans, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, human immunodeficiency virus (HIV), and healthy humans. After analyzing 400 serum samples of patients suspected of syphilis, the LAMP-AGE and LAMP-AuNPs assays displayed 100% diagnostic sensitivity scores, 91% diagnostic specificity scores, 95.5% accuracy rates, 100% positive predictive values (PPVs), and 91% negative predictive values (NPVs), the positive likelihood ratio (LR+) was 11.11, while the negative likelihood ratio (LR-) was 0. Conversely, for PCR assays displayed 100% diagnostic sensitivity scores, 94.5% diagnostic specificity scores, 97.25% accuracy rates, 100% PPVs, and 94.5% NPVs, LR+ was 18.18, and LR- was 0. The LAMP-AuNPs technique demonstrates rapidity, affordability, and convenience, rendering it well-suited for point-of-care applications in the diagnosis, prevention, and management of pathogenic infections.

Association Between Variables and Transitions Among No Opioid Use, Opioid Use, and Subsequent Dropout Among Participants on Methadone Treatment: A Retrospective Study Utilizing a Multistate Model.

Although previous studies have reported the variables that influence opioid use or dropout among participants receiving methadone treatment, limited attention has been given to the variables related to transitions among no opioid use, opioid use, and dropout. This retrospective study utilized data collected from June 2010 to June 2022 at 11 methadone treatment clinics in Guangdong Province, China. Two transient states (no opioid use and opioid use) and 1 absorbing state (dropout) were defined based on monthly urine morphine test results and daily methadone intake records. We used a multistate model to explore the variables associated with transitions among no opioid use, opioid use, and dropout among participants. Among 3136 participants, with an average treatment duration of 497 days, 1646 (52.49%) underwent at least 1 period of opioid use, resulting in 3283 transitions from no opioid use to opioid use. The transitions between no opioid use and opioid use were significantly associated with variables such as age, gender, employment status, marital status, living situation, travel time to the clinic, human immunodeficiency virus and hepatitis C virus infection statuses, average methadone dosage, and attendance rates. The variables influencing participants' dropout varied depending on their opioid use behaviors. Additionally, the probability of a specified opioid use state remaining unchanged or transitioning to a different state at a defined time point would change over time. The opioid use behaviors of participants are dynamic. Methadone providers should offer targeted interventions based on participants' opioid use behaviors to effectively decrease rates of opioid use and improve retention.