Sexually transmitted infections spread across contact networks. Partner elicitation and notification are commonly used public health tools to identify, notify, and offer testing to persons linked in ...these contact networks. For HIV-1, a rapidly evolving pathogen with low per-contact transmission rates, viral genetic sequences are an additional source of data that can be used to infer or refine transmission networks.
The New York City Department of Health and Mental Hygiene interviews individuals newly diagnosed with HIV and elicits names of sexual and injection drug using partners. By law, the Department of Health also receives HIV sequences when these individuals enter healthcare and their physicians order resistance testing. Our study used both HIV sequence and partner naming data from 1342 HIV-infected persons in New York City between 2006 and 2012 to infer and compare sexual/drug-use named partner and genetic transmission networks. Using these networks, we determined a range of genetic distance thresholds suitable for identifying potential transmission partners. In 48% of cases, named partners were infected with genetically closely related viruses, compatible with but not necessarily representing or implying, direct transmission. Partner pairs linked through the genetic similarity of their HIV sequences were also linked by naming in 53% of cases. Persons who reported high-risk heterosexual contact were more likely to name at least one partner with a genetically similar virus than those reporting their risk as injection drug use or men who have sex with men.
We analyzed an unprecedentedly large and detailed partner tracing and HIV sequence dataset and determined an empirically justified range of genetic distance thresholds for identifying potential transmission partners. We conclude that genetic linkage provides more reliable evidence for identifying potential transmission partners than partner naming, highlighting the importance and complementarity of both epidemiological and molecular genetic surveillance for characterizing regional HIV-1 epidemics.
To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission.
HIV-1 pol sequence data were analyzed to infer the ...local transmission network.
We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions.
HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05).
Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.
Abstract
Invasive mould infections are an increasing cause of morbidity and mortality globally, mainly due to increasing numbers of immunocompromised individuals at risk for fungal infections. The ...introduction of broad spectrum triazoles, which are much better tolerated compared to conventional amphotericin B formulations, has increased survival, particularly in invasive mould infection. However, early initiation of appropriate antifungal treatment remains a major predictor of outcome in invasive mould infection, but despite significant advances in diagnosis of these diseases, early diagnosis remains a challenge. As a result, prophylaxis with mould-active triazoles is widely used for those patients at highest risk for invasive mould infection, including patients with prolonged neutropenia after induction chemotherapy for acute myeloid leukemia and patients with graft-versus-host-disease. Posaconazole is the recommended drug of choice for antimould prophylaxis in these high-risk patients. Voriconazole has its primary role in treatment of invasive aspergillosis but not in prophylaxis. Recently, isavuconazole has been introduced as an excellent alternative to voriconazole for primary treatment of invasive aspergillosis in patients with hematological malignancies. Compared to voriconazole, isavuconazole and posaconazole have broader activity against moulds and are therefore also an option for treatment of mucormycosis in the presence of intolerance or contraindications against liposomal amphotericin B.
Summary
Background
We compared new Aspergillus Galactomannan Lateral Flow Assay with the newly formatted Aspergillus‐specific Lateral Flow device tests for the diagnosis of invasive pulmonary ...aspergillosis (IPA) in non‐neutropenic patients.
Methods
We performed both tests in 82 bronchoalveolar lavage fluid samples from 82 patients at risk for IPA but without underlying haematologic malignancy. Samples were collected between September 2016 and September 2018 at the University of California San Diego, United States. IPA was classified following two published consensus criteria.
Results
Classification of cases varied widely between the two consensus criteria. When using criteria established for the intensive care unit, 26/82 patients (32%) met criteria for proven or putative IPA. Both point‐of‐care assays showed sensitivities ranging between 58% and 69%, with specificities between 68% and 75%. Sensitivity increased up to 81% when both tests were combined.
Conclusion
The study outlines the need for updated, unified and more broadly applicable consensus definitions for classifying IPA in non‐neutropenic patients, a work that is currently in progress. Both point‐of‐care tests showed comparable performance, with sensitivities and specificities in the 60%‐70% range when used alone and increasing to 80% when used in combination. The new point‐of‐care tests may serve a role at the bedside in those with clinical suspicion of IPA.
Abstract
Background
The Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with ...hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits.
Methods
We performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany.
Results
Cases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval CI .815–.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers.
Conclusions
In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.
Recovery of Neisseria gonorrhoeae isolates exposed to a range of transport times and temperatures was quantitatively assessed for two transport devices, BioMed Diagnostics' InTray GC® and Copan ...Diagnostics' Liquid Amies Elution Swab (ESwab®) Collection and Transport System. Respective devices were inoculated with N. gonorrhoeae, exposed to simulated transport conditions and spread-plated from serial dilutions in duplicates onto chocolate agar in order to count CFU (colony-forming units) in the range of 25-250. Baseline CFU/mL averages of time-zero transport for each device was compared to either 24 hour (Eswab) or 72 hour (InTray GC) CFU/mL average to assess recovery of six clinical isolates of N. gonorrhoeae, and differences showing no greater than a 3 log10 (± 10%) decline between comparative time points qualified as acceptable. Our findings suggest that the InTray GC system has the potential to transport clinical isolates for ≤72 hours with acceptable N. gonorrhoeae recovery.
The association between nasopharyngeal (NP) SARS-CoV-2 viral loads and clinical outcomes remains debated. Here, we examined the factors that might predict the NP viral load and the role of the viral ...load as a predictor of clinical outcomes. A convenience sample of 955 positive remnant NP swab eluent samples collected during routine care between 18 November 2020 and 26 September 2021 was cataloged and a chart review was performed. For non-duplicate samples with available demographic and clinical data (i.e., non-employees), an aliquot of eluent was sent for a droplet digital PCR quantification of the SARS-CoV-2 viral load. Univariate and multivariate analyses were performed to identify the clinical predictors of NP viral loads and the predictors of COVID-19-related clinical outcomes. Samples and data from 698 individuals were included in the final analysis. The sample cohort had a mean age of 50 years (range: 19-91); 86.6% were male and 76.3% were unvaccinated. The NP viral load was higher in people with respiratory symptoms (
= 0.0004) and fevers (
= 0.0006). In the predictive models for the clinical outcomes, the NP viral load approached a significance as a predictor for in-hospital mortality. In conclusion, the NP viral load did not appear to be a strong predictor of moderate-to-severe disease in the pre-Delta and Delta phases of the pandemic, but was predictive of symptomatic diseases and approached a significance for in-hospital mortality, providing support to the thesis that early viral control prevents the progression of disease.
Reply to Montastruc et al Birabaharan, Morgan; Martin, Thomas C S; Mehta, Sanjay R
Clinical infectious diseases,
06/2023, Letnik:
76, Številka:
11
Journal Article
HIV molecular epidemiology (HIV ME) can support the early detection of emerging clusters of new HIV infections by combining HIV sequence data routinely obtained during the clinical treatment of ...people living with HIV with behavioral, geographic, and sociodemographic information. While information about emerging clusters promises to facilitate HIV prevention and treatment efforts, the use of this data also raises several ethical concerns. We sought to assess how those working on the frontlines of HIV ME, specifically public health practitioners (PHPs) and researchers, prioritized these issues.
Ethical issues were identified through literature review, qualitative in-depth interviews, and stakeholder engagement. PHPs and researchers using HIV ME prioritized the issues using best-worst scaling (BWS). A balanced incomplete block design was used to generate 11 choice tasks each consisting of a sub-set of 5 ethical concerns. In each task, respondents were asked to assess the most and least concerning issue. Data were analyzed using conditional logit, with a Swait-Louviere test of poolability. Latent class analysis was then used to explore preference heterogeneity.
In total, 57 respondents completed the BWS experiment May-June 2023 with the Swait-Louviere test indicating that researchers and PHPs could be pooled (p = 0.512). Latent class analysis identified two classes, those highlighting "Harms" (n = 29) (prioritizing concerns about potential risk of legal prosecution, individual harm, and group stigma) and those highlighting "Utility" (n = 28) (prioritizing concerns about limited evidence, resource allocation, non-disclosure of data use for HIV ME, and the potential to infer the directionality of HIV transmission). There were no differences in the characteristics of members across classes.
The ethical issues of HIV ME vary in importance among stakeholders, reflecting different perspectives on the potential impact and usefulness of the data. Knowing these differences exist can directly inform the focus of future deliberations about the policies and practices of HIV ME in the United States.
PURPOSE OF REVIEWHIV phylogenetic and molecular epidemiology analyses are increasingly being performed with a goal of improving HIV prevention efforts. However, ethical, legal and social issues are ...associated with these analyses, and should be considered when performed.
RECENT FINDINGSSeveral working groups have recently outlined the major issues surrounding the use of molecular epidemiology for HIV prevention. First, the benefits of HIV molecular epidemiology remain unclear, and further work is needed to quantitatively demonstrate the benefits that can be expected. Second, privacy loss is an important risk, with implications of disclosure varying by the regional legal and social climate. Inferential privacy risks will increase with technological improvements in sequencing and analysis. Third, data sharing, which enhances the utility of the data, may also increase the risk of inferential privacy loss. Mitigation strategies are available to address each of these issues.
SUMMARYHIV molecular epidemiology for research and public health pose significant ethical issues that continue to evolve with improving technology, increased sampling and a changing legal and social climate. Guidance surrounding these issues needs to be developed for researchers and public health officials in an iterative and region specific manner that accounts for the potential benefits and risks of this technology.
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