Abstract Chlamydia psittaci is a zoonotic pathogen known to cause respiratory diseases in humans. Chlamydia infections are closely associated with apoptosis, in which miRNAs play regulatory roles. Herein, we demonstrated that C. psittaci infection induces apoptosis in human bronchial epithelial (HBE) cells and investigated regulatory mechanism involving miR-124-3p and the PI3K/AKT signaling pathway. Following C. psittaci infection in HBE cells, we observed an elevated of HBE cells apoptosis, accompanied by upregulation of miR-124-3p levels. Mechanistically, we identified EIF3B as a novel target gene of miR-124-3p, supported by the inverse correlation of their mRNA expressions. MiR-124-3p inhibitors reduced apoptosis induced by C. psittaci, increased the replication of C. psittaci and inhibited the PI3K/AKT activated, whereas miR-124-3p mimics produced opposite effects, and transfection with EIF3B siRNA reversed the effects of miR-124-3p inhibitors. Our findings suggest that miR-124-3p targeting EIF3B promotes apoptosis in C. psittaci-infected HBE cells through the activation of PI3K/AKT signaling pathway.

Abstract Background The persistence of latently infected cells prevents a cure of HIV. The intestinal mucosa contains numerous target cells, and high levels of HIV-1 DNA persist in this compartment under ART. While CD4+ T cells are the best characterized reservoir of HIV-1, the role of long-lived intestinal macrophages in HIV-1 persistence on ART remains controversial.Methods We collected duodenal and colonic biopsies from 12 people living with HIV (PLWH) on suppressive ART, enrolled in the ARNS EP61 GALT study. Total, integrated, intact and defective HIV-1 proviruses were quantified from sorted T cells and monocytes/macrophages. HIV-1 env quasispecies were analyzed by single-molecule next-generation sequencing and env-pseudotyped viruses were constructed to assess macrophage versus T-tropism.Results Total HIV-1 DNA levels in intestinal T cells were significantly higher than those in monocytes/macrophages (P

Abstract Tuberculosis (TB) necrotic granulomas contain triglyceride-rich macrophages (foam cells) with reduced antimicrobial functions. We assessed the ability of two compounds to reduce triglyceride content and Mycobacterium tuberculosis (Mtb) burden in infected human monocyte-derived macrophages and in the lungs of Mtb-infected C3HeB/FeJ mice: A-922500 (DGATi), an inhibitor of diacylglycerol acyltransferase 1; and LY2584702 (p70S6Ki), an inhibitor of p70 S6 kinase. DGATi and p70S6Ki significantly reduced the lipid content and bacillary burden in Mtb-infected macrophages. Each inhibitor reduced the cellular triglyceride content in bronchoalveolar lavage samples of Mtb-infected mice. After 6 weeks of treatment, p70S6Ki alone reduced the lung bacterial burden in Mtb-infected mice. However, DGATi alone, and DGATi or p70S6Ki in combination with isoniazid did not reduce lung bacterial burden or alter lung inflammation. These findings provide further insight into the role of foam cells in tuberculosis pathogenesis and the utility of interventions targeting these cell populations as adjunctive host-directed therapies.

Community-onset meticillin-resistant Staphylococcus aureus (MRSA) (CO-MRSA) has been under recognised and under described outside the USA and we welcome this themed issue comprising 4 narrative reviews on the topic which cover a wide range of issues.

ObjectivesThis study aims to evaluate and compare health outcomes and costs between home hospitalisation and traditional hospitalisation for three common diagnoses—cellulitis, urinary tract infection (UTI) and pneumonia. DesignA retrospective cohort study. SettingPrimary care, nationwide. Participants1311 patients in home hospitalisation and 992 in traditional hospitalisation. InterventionsThe primary intervention is home hospitalisation, compared with traditional hospitalisation. The intervention was performed according to medical considerations by a specialised team, and this study was done retrospectively to evaluate it. Primary and secondary outcome measuresPrimary measures included healthcare costs, length of hospitalisation, referrals for further medical services and mortality. ResultsCosts of home hospitalisation were lower compared with traditional hospitalisation (6056 vs 9619 NIS for pneumonia, 6011 vs 9767 NIS for cellulitis, 6466 vs 8552 NIS for UTI and p value

ObjectivesEffective, real-time surveillance of dengue may provide early warning of outbreaks and support targeted disease-control intervention but requires widespread accurate diagnosis and timely case reporting. Research directing innovation in diagnostics for dengue surveillance is lacking. This study aimed to describe experience and requirements of relevant prospective users. DesignA qualitative, focus group study was conducted. ParticipantsData were collected from 19 users of diagnostic technology who work across the Thai dengue surveillance system. Data collection and analysisContextual knowledge, experience and needs were explored in focus groups. Discussions were translated, transcribed, analysed thematically and mapped to Consolidated Framework for Implementation Research domains. ResultsParticipants expressed a need for rapid, accurate, serotype-specific tests which can be operated easily by non-expert users without laboratory equipment. They supported integration of diagnostics with surveillance systems and felt this would increase the quantity and speed of case reporting as well as provide healthcare professionals with up-to-date information about the number of cases locally, thereby aiding interpretation of test results. Concerns included those relating to data security and the cost of tests. ConclusionsEngagement to understand prospective user experience and requirements can improve relevance and uptake of new technology, leading to system efficiencies. The present study highlights specific needs for accurate, serotype-specific, remote-connected diagnostics which are integrated with surveillance systems and support dengue case reporting at the point-of-care. …

ObjectiveTo estimate the herd effects of anti-microbial-based decontamination (ABD) interventions on bloodstream infections (BSIs) among groups of intensive care unit (ICU) patients in relation to group mean length of stay (LOS). To deduce which of three competing hypotheses of ABD effect mediation best accounts for the observed effects. DesignArms-based meta-regression of ICU-acquired BSI incidence against group mean LOS for control and interventions arms of ABD and non-ABD controlled trials each versus that in arms of observational studies. ExposuresWithin controlled trials of ABD, intervention, concurrent control (CC) and non-concurrent (NCC) groups are directly, indirectly and non-exposed, respectively. Main outcomes and measuresBSI incidence, both overall and for BSI subtypes. ResultsIn the arms-based meta-regression, the predicted BSI incidence per 100 patients in the ABD intervention arms increased from 4.6 (95% CI 3.8 to 5.5) at mean LOS 7 days to 13.0 (10.4–16.0) at mean LOS 20 days (n=60 arms) and CC arms 8.5 (6.7–11.0) increasing to 19.3 (14.8–24.8; n=52). These increases were double those in the observational (7.2; 6.1–8.5 increasing to 12.9; 10.4–16.7; n=99) and NCC arms and non-ABD arms. These results triangulate with the notional effect size observed in contrast-based meta-analyses. ConclusionsThe increased tempo of BSI acquisition, both overall and for various BSI subtypes, within intervention and CC groups of ABD randomised concurrent controlled trials versus other groups implicate rebound and spillover, respectively. Mechanisms other than colonisation resistance mediate ABD effects. …

Abstract Background Common non-COVID respiratory viruses, such as influenza virus (IFVA/IFVB), parainfluenza virus (PIV), respiratory syncytial virus (RSV), and adenovirus (ADV), often cause acute respiratory infections (ARIs). This study aimed to explore the epidemiological characteristics of these five viruses in patients with ARIs before, during, and after the COVID-19 pandemic from 2018 to 2023. Methods A total of 37,139 serum specimens and epidemiological data from all-aged patients who presented with ARIs were collected from January 2018 to December 2023. The IgM antibodies of five non-COVID respiratory viruses were tested by an IgM kit with indirect immunofluorescent assay (lFA). Results 12,806 specimens were screened as positive for any one of the targeted viruses, with an overall positivity rate of 34.48%. Among all age groups, the most prevalent respiratory viruses were PIV (21.30%) and influenza virus (17.30% of IFVB and 9.91% of IFVA). Children aged 1–14 years were most vulnerable to lower respiratory viruses, and children aged 4–6 years have the highest prevalence no matter the positivity rate for overall viruses (53.06%) or for each virus. From 2018 to 2023, the annual percentage change (APC) revealed that the prevalence of total viruses have a 13.53% rise (p  60 years) were all the highest in 2023, and the number of samples collected in 2023 sharply increased, increasing by 77.10% compared to the average of the number of detected in 2018–2022. Conclusions The data from this study indicate that the epidemiological characteristics of five non-COVID respiratory viruses are vulnerability to the environment, age, sex, and epidemics status among AIR patients, and that the detected number and positivity rate of these viruses have increased in the “post-pandemic era”, which is critical for the late or retrospective diagnosis and can serve as a useful surveillance tool to inform local public policy in Weifang, China. …

Abstract Background The HIV epidemic in Kenya remains a significant public health concern, particularly among gay, bisexual, and other men who have sex with men (GBMSM), who continue to bear a disproportionate burden of the epidemic. This study’s objective is to describe HIV phylogenetic clusters among different subgroups of Kenyan GBMSM, including those who use physical hotspots, virtual spaces, or a combination of both to find male sexual partners. Methods Dried blood spots (DBS) were collected from GBMSM in Kisumu, Mombasa, and Kiambu counties, Kenya, in 2019 (baseline) and 2020 (endline). HIV pol sequencing was attempted on all seropositive DBS. HIV phylogenetic clusters were inferred using a patristic distance cutoff of ≤ 0.02 nucleotide substitutions per site. We used descriptive statistics to analyze sociodemographic characteristics and risk behaviors stratified by clustering status. Results Of the 2,450 participants (baseline and endline), 453 (18.5%) were living with HIV. Only a small proportion of seropositive DBS specimens were successfully sequenced (n = 36/453; 7.9%), likely due to most study participants being virally suppressed (87.4%). Among these sequences, 13 (36.1%) formed eight distinct clusters comprised of seven dyads and one triad. The clusters mainly consisted of GBMSM seeking partners online (n = 10/13; 76.9%) and who tested less frequently than recommended by Kenyan guidelines (n = 11/13; 84.6%). Conclusions Our study identified HIV phylogenetic clusters among Kenyan GBMSM who predominantly seek sexual partners online and test infrequently. These findings highlight potential unmet HIV prevention, testing, and treatment needs within this population. Furthermore, these results underscore the importance of tailoring HIV programs to address the diverse needs of GBMSM in Kenya across different venues, including both physical hotspots and online platforms, to ensure comprehensive prevention and care strategies. …

Abstract Background Commercial insurance claims data are a stable and consistent source of information on Lyme disease diagnoses in the United States and can contribute to our understanding of overall disease burden and the tracking of epidemiological trends. Algorithms consisting of diagnosis codes and antimicrobial treatment information have been used to identify Lyme disease diagnoses in claims data, but there might be opportunity to improve their accuracy. Methods We developed three modified versions of our existing claims-based Lyme disease algorithm; each reflected refined criteria regarding antimicrobials prescribed and/or maximum days between diagnosis code and qualifying prescription claim. We applied each to a large national commercial claims database to identify Lyme disease diagnoses during 2016–2019. We then compared characteristics of Lyme disease diagnoses identified by each of the modified algorithms to those identified by our original algorithm to assess differences from expected trends in demographics, seasonality, and geography. Results Observed differences in characteristics of patients with diagnoses identified by the three modified algorithms and our original algorithm were minimal, and differences in age and sex, in particular, were small enough that they could have been due to chance. However, one modified algorithm resulted in proportionally more diagnoses in men, during peak summer months, and in high-incidence jurisdictions, more closely reflecting epidemiological trends documented through public health surveillance. This algorithm limited treatment to only first-line recommended antimicrobials and shortened the timeframe between a Lyme disease diagnosis code and qualifying prescription claim. Conclusions As compared to our original algorithm, a modified algorithm that limits the antimicrobials prescribed and shortens the timeframe between a diagnosis code and a qualifying prescription claim might more accurately identify Lyme disease diagnoses when utilizing insurance claims data for supplementary, routine identification and monitoring of Lyme disease diagnoses. …

Abstract Background Brucellosis poses a significant public health challenge in China. Inner Mongolia, characterized by its developed livestock industry, is the most severe endemic area for human brucellosis. This study aims to describe the epidemiology, explore the spatial–temporal distribution patterns, and clustering characteristics of human brucellosis in Inner Mongolia. Methods Data on human brucellosis cases from 2010 to 2021 were obtained from the Centers for Disease Control and Prevention in Inner Mongolia. Spatial autocorrelation analysis was used to identify high-risk areas, while spatial–temporal scan statistics were employed to detect changes in clusters over time. Results A total of 153,792 brucellosis cases were reported in Inner Mongolia from 2010 to 2021, with an average annual incidence rate of 52.59 per 100,000 persons. The incidence showed a decreasing trend from 2010 to 2016, followed by a significant increase from 2016 to 2021. The disease exhibited distinct seasonality, peaking in spring and summer (March to August). Middle-aged individuals, males, and farmers/herdsmen had higher incidence rates. Spatially, incidence rates decreased from north to south and from the central and eastern regions to the west. Clear spatial clusters were observed during 2010–2013 and 2016–2021 in the global Moran’s I test. Local spatial autocorrelation analysis revealed that high-high clusters expanded from the central and eastern regions towards the west over time. Spatio-temporal scan analysis further indicated that high-risk clusters were primarily concentrated in the central and eastern regions, with a continuous expansion towards the west and south, leading to an increasingly broad geographical spread. Conclusion Human brucellosis cases in Inner Mongolia exhibit spatio-temporal clustering, with spatial concentration in the central and eastern regions, but also observed expansion towards the western and southern regions. The most of cases occur between March and August each year. For high-risk areas and populations, more timely and effective prevention and control measures should be implemented to mitigate the spread of brucellosis and protect public health. …

Volume 15, Issue 1, December 2024 .

Proceedings of the National Academy of Sciences, Volume 121, Issue 48, November 2024.

Objective: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti. Design: An unblinded randomized clinical trial (enrolled April 2021–March 2022) with 12-month follow-up. Setting: GHESKIO Centres, Port-au-Prince, Haiti. Participants: Two hundred fifty adults with HIV with prehypertension (SBP 120–138 or DBP 80–89) not on medication, aged 18–65 years, virally suppressed, and without pregnancy, diabetes, or kidney disease. Intervention: Participants were randomized to treatment (amlodipine 5 mg) or control (no amlodipine unless two BP ≥140/90 mmHg). Main outcome measure: Primary outcome was mean change in SBP between intervention versus control groups from enrollment to 12 months. Results: Among 250 adults, median age was 49 years, 40.8% were women. Baseline median BP was 129/78 mmHg intervention versus 128/77 mmHg control. After 12 months, the difference in mean change between study groups for SBP was -5.9 mmHg [95% confidence interval (95% CI) -8.8 to -3.0] and for DBP was -5.5 mmHg (95% CI -7.9 to -3.2). At 12 months, 5.6% intervention and 23.0% control participants developed incident hypertension (hazard ratio 0.18; 95% CI 0.07–0.47). There were no differences in viral load suppression at 12 months or drug-related serious adverse events. Intervention acceptability was high among providers and participants in qualitative interviews. Conclusion: In PWH in a resource-poor setting, prehypertension treatment was feasible, acceptable, and effective in reducing mean SBP and incident hypertension. Registration: Clinicaltrials.gov NCT04692467 JOURNAL/aids/04.03/00002030-990000000-00587/figure1/v/2024-11-13T090640Z/r/image-jpeg Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective: Falls are a significant public health concern, particularly among older adults and people with HIV (PWH). This study examines the association between alcohol consumption and falls in PWH. Methods: The PROSPER-HIV study recruited PWH from four US sites. Participants were categorized based on Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores: none, non-hazardous, and hazardous drinking. Data collection included demographics, medical history (i.e., comorbidities, treated hypertension, eGFR), alcohol consumption using AUDIT-C, daily alcohol recall in grams, and self-reported falls over the previous year. Physical performance was measured using the Short Performance Physical Battery (SPPB). Statistical analyses included Pearson\'s correlation and Poisson regression models to estimate fall prevalence ratios (PR), adjusting for confounders (SPPB, comorbidities, treated hypertension, and eGFR). Results: The study included 315 PWH, aged 52 ± 12 years, with 78% male participants. Thirty-three percent were classified as non-drinking, 50% non-hazardous, and 17% hazardous drinking. Poisson regression showed a significantly higher risk of falls (PR: 2.12, 95% CI: 1.11–4.03) and recurrent falls (PR: 3.54, 95% CI: 1.21–10.3) among hazardous drinking compared to non-hazardous drinking, even after adjusting for confounders. The PR for falls per daily intake in grams was not statistically significant. Conclusions: There is a significant association between hazardous alcohol consumption and increased fall risk in PWH using AUDIT-C, but not when accessing recall of alcohol consumption in grams. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background : Characterizing HIV clustering rates and their trends over time can improve understanding a local epidemic and enhance its control. Methods: Leveraging an academic-public health partnership in Rhode-Island, we explored longitudinal dynamics of statewide clustering rates among key populations from 1991 to 2023. Partial HIV-1 pol sequences were grouped by year of HIV-1 diagnosis. Molecular clusters were identified in cumulative annual phylogenies. Overall clustering rates, and clustering rates of newly-diagnosed and prevalent infections, and of specific socio-demographic characteristics of key populations over time were determined. Mann-Kendall statistics were used to estimate clustering rate trends and relationships among groups. Results: By the end of 2023, 2,630 individuals with sequences represented the statewide epidemic in Rhode Island. Overall clustering rates increased from 7% in 1991 to 46% in 2023, correlating with cumulative sequence increase. Clustering rates of newly-diagnosed and prevalent infections significantly increased over time, higher in newly-diagnosed individuals since the early 2000 s. Increases were also observed among groups defined by gender, age, transmission risks, race, mental illness, HIV-1 subtypes, and country of birth, with some crossovers and divergence patterns over time. Conclusions: Exploring dynamics of HIV clustering rates over three decades in a statewide HIV-1 epidemic expanded its characterization and provided insight into its evolving changes. These dynamics may indicate a gradual shift towards a more concentrated and localized HIV-1 epidemic, highlighting important opportunities for targeted interventions to effectively prevent new HIV transmissions. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Science Advances, Volume 10, Issue 47, November 2024.

Science Advances, Volume 10, Issue 47, November 2024.

Challenges in adapting natural products as antimalarials include their cryptic mechanism of action (and by extension resistance), as well as their complex and expensive synthesis without an abundant natural source. Recently, Chahine et al. presented plausible means to address these challenges in the case of the kalihinol family of isocyanoterpenes.

Leishmania (Leishmania) amazonensis is the etiological agent of cutaneous leishmaniasis (CL) and anergic diffuse cutaneous leishmaniasis (ADCL). ADCL is one of the most severe and frequently incurable clinical forms of the disease in the Americas, with 85% of the cases occurring in Brazil, Colombia, and Peru. CL is considered a zoonotic infection in sylvatic mammals, where parasites are transmitted through the bites of naturally infected phlebotomine sand flies (Diptera: Psychodidae), more specifically Bichromomyia flaviscutellata, which is widely distributed in the Amazon region and other Brazilian states.

Anthelmintic resistance (AR) in parasitic nematodes poses a global health problem in livestock and domestic animals and is an emerging problem in humans. Consequently, we must understand the mechanisms of AR, including target-site resistance (TSR), in which mutations affect drug binding, and non-target site resistance (NTSR), which involves alterations in drug metabolism and detoxification processes. Because much of the focus has been on TSR, NTSR has received less attention. Here, we describe how metabolomics approaches using Caenorhabditis elegans offer the ability to disentangle nematode drug metabolism, identify metabolic changes associated with resistance, uncover novel biomarkers, and enhance diagnostic methods.

The circumsporozoite protein (CSP) is one of the most studied proteins of the malaria parasite. It is the target of the only licensed malaria vaccines and is essential for sporozoite formation and infectivity. Yet, the mechanisms by which CSP functions and its interactions with other proteins are only beginning to be understood. Here we review the current state of knowledge of CSP structure and function, as sporozoites develop in the mosquito and establish infection in the mammalian host, and outline outstanding questions that need to be addressed.

Congenital infections are a leading preventable cause of pregnancy complications impacting both mother and fetus. Although advancements have been made in understanding various congenital infections, the mechanisms of parasitic infections during pregnancy remain poorly understood. This review covers the global incidence of three parasites capable of congenital transmission – Trypanosoma cruzi, Plasmodium spp., and Toxoplasma gondii – and the state of research into their transplacental transmission strategies. We highlight technological advancements in placental modeling that offer opportunities to reveal how parasites cause gestational pathology. Additionally, we discuss the likelihood that selective adaptation contributed to the evolution of mechanisms that facilitate placental infection. These insights provide a foundation for understanding the progression and pathology of congenital parasitic diseases and identifying future research directions.

Abstract In 2022, a bioinformatic, agnostic approach identified HPV42 as causative agent of a rare cancer, later confirmed experimentally. This unexpected association offers an opportunity to reconsider our understanding about papillomavirus infections and cancers.We have expanded our knowledge about the diversity of papillomaviruses and the diseases they cause.Yet we still lack answers to fundamental questions, such as what makes HPV16 different from the closely related HPV31 or HPV33; or why the very divergent HPV13 and HPV32 cause focal epithelial hyperplasia, while HPV6 or HPV42 do not, despite their evolutionary relatedness.Certain members of the healthy skin microbiota are associated to rare clinical conditions. We propose that a focus on cellular phenotypes, most often transient and influenced by intrinsic and extrinsic factors, may help understand the continuum between health and disease. A conceptual switch is required towards an interpretation of biology as a diversity of states connected by transition probabilities, rather than quasi-deterministic programs. Under this perspective, papillomaviruses may only trigger malignant transformation when specific viral genotypes interact with precise cellular states.Drawing on Canguilhem\'s concepts of normal and pathological, we suggest that understanding the transition between fluid cellular states can illuminate how commensal-like infections transition from benign to malignant.

Tropical Medicine &International Health, EarlyView.

Volume 13, Issue 1, December 2024 .