Science, Volume 385, Issue 6715, Page 1262-1263, September 2024.

Science, Volume 385, Issue 6715, September 2024.

This year\'s recipients have been recognised for their work on the HIV epidemic, GLP-1-based drugs, and how DNA can stimulate immune and inflammatory responses. Talha Burki reports.

The global burden of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children is high. The RSV prevention strategies approved in 2023 will be essential to lowering the global disease burden. In this Series paper, we describe clinical presentation, burden of disease, hospital management, emerging therapies, and targeted prevention focusing on developments and groundbreaking publications for RSV. We conducted a systematic search for literature published in the past 15 years and used a non-systematic approach to analyse the results, prioritising important papers and the most recent reviews per subtopic.

The search for safe and efficacious products to prevent severe respiratory syncytial virus (RSV) disease in young infants has lasted more than 60 years. In high-income and middle-income countries, two new products have been authorised: an RSV monoclonal antibody for administration to infants (nirsevimab) and an RSV prefusion F maternal vaccine (RSVpreF [Pfizer, Puurs, Belgium]) for administration to pregnant people. These products are not yet available in low-income and lower-middle-income countries, where most RSV deaths occur.

Our results suggest that MDPPF can help prevent dengue under the many operational constraints of real-world vector-control interventions and despite incomplete coverage and potential dilution of intervention effects. MDPPF holds promise as an additional tool for dengue control.

Publication date: Available online 18 September 2024 Source: Infectious Disease Modelling Author(s): Olaiya Mathilde Adéoti, Schadrac Agbla, Aliou Diop, Romain Glèlè Kakaï …

by Tigabu Kidie Tesfie, Werkneh Melkie Tilahun Background While HIV testing and counselling play a crucial role in preventing mother-to-child transmission, numerous pregnant women did not receive these services. Understanding the spatial variation of HIV testing and counselling and its associated factors during antenatal care in Ethiopia remains limited. Thus, this study was aimed at assessing the spatial patterns and factors associated with HIV testing and counselling during antenatal care visits in Ethiopia. Methods A cross-sectional study design was employed with a two-stage stratified cluster sampling technique. A total of 2,789 women who gave birth in the two years prior to the survey and had at least one antenatal care visit were included in the study. Stata version 16 and ArcGIS version 10.8 software were used for analysis. A multilevel robust Poisson regression model was fitted to identify significantly associated factors since the prevalence of HIV testing and counselling was higher than 10%. A statistically significant association was declared based on multivariable multilevel robust Poisson regression analysis using an adjusted prevalence ratio with its 95% confidence interval at a p-value < 0.05. Spatial regression analysis was conducted, and the local coefficients of statistically significant spatial covariates were visualised. Results In Ethiopia, the overall prevalence of HIV testing and counselling during antenatal care visits was 29.5% (95% CI: 27.8%, 31.2%). Significant spatial clustering was observed (Global Moran’s I = 0.138, p-value…

by Manash Shrestha, Penchan Pradubmook Sherer, Seung Chun Paek, Kriengkrai Prasert, Sutthinan Chawalchitiporn, Prabda Praphasiri Background Healthcare workers (HCWs) are an important target group for influenza vaccination due to their increased risk of infection. However, their uptake remains a challenge. This study aimed to identify and measure influenza vaccine hesitancy among HCWs in Nakhon Phanom province, Thailand. Methods A representative cross-sectional survey was conducted during August–September 2020, among 350 HCWs at six hospitals in the province selected by a two-stage cluster sampling using a self-administered questionnaire. HCWs who either delayed getting influenza vaccines, accepted the vaccines but were unsure, or refused the vaccine with doubts were categorized as hesitant. HCWs who accepted the influenza vaccine without any doubts were classified as non-hesitant. Determinants of vaccine hesitancy were identified by a multivariable logistic regression analysis. Results A total of 338 participants (97%) filled the questionnaires. The mean age of the participants was 37.2 years. Most participants were female (280; 83%), nurses (136; 40%), working at district hospitals (238; 71%), with bachelor’s degree (223; 66%), and without any pre-existing chronic medical conditions (264; 78%). Influenza vaccine hesitancy was evident among nearly 60% of the participants (197/338), who had varying patterns of hesitancy. Significant factors of influenza vaccine hesitancy were found to be age above 50 years (adjusted odds ratio [aOR] 3.2, 95% CI 1.3–8.5), fair knowledge of influenza and vaccination (aOR 0.4, 95% CI 0.2–0.8), and negative influence of other HCW (High level–aOR 2.3, 95% CI 1.1–4.8; Moderate level- aOR 2.1, 95% CI 1.1–4.4). Conclusion Influenza vaccine hesitancy was highly prevalent among the Thai HCWs in Nakhon Phanom province. Imparting updated information to the HCW, in combination with positive guidance from influential HCWs in the hospital, may help reduce hesitancy. These data may be useful to the National Immunization Program to design appropriate approaches to target hesitant HCWs in Thailand to improve influenza vaccine coverage. …

by Easha Fatima, Iqra Arooj, Hamna Shahid, Abida Aziz Nanotechnology is a treasure trove of diversified themes which are endowed with broad applications. Herein, iron oxide (Fe2O3) nanoparticles were synthesized using Phyllanthus emblica aqueous fruit extract. The UV-Visible spectrum exhibited a surface plasmon resonance peak at 295nm. Fourier Transform Infrared Spectroscopy provided insight into the functional groups responsible for capping. X-ray diffraction analysis authenticated the crystalline nature of nanoparticles, while energy dispersive X-ray spectroscopy divulged that iron and oxygen comprised 54% of the nanoparticles’ weight. Scanning electron microscopy established irregular morphology and agglomeration of nanoparticles. The Fe2O3 nanoparticles validated potent antimicrobial activity against 11 bacterial and 1 fungal isolates. The biggest zone of inhibition (23mm) was measured against S. enterica, whereas the smallest zone of inhibition (12mm) was documented against C. albicans and E. coli. The values for minimum inhibitory concentration ranged between 10 and 15μg/ml for all microbes. Nevertheless, no synergy was exhibited by the nanoparticles with any of the selected antibiotics (Fractional Inhibitory Concentration Index > 1). The photocatalytic dye degradation capability of Fe2O3 nanoparticles was assessed and the observations implied a significant increase in degradation of methyl red although, not of methylene blue. Furthermore, the nanoparticles were in possession of substantial antioxidant (34–38%) and anti-inflammatory (31–38%) capacities. Consequent upon the robust activities of P. emblica-mediated nanoparticles, these can be scrutinized for biomedical and environmental implementations in future.

by Sarah Hafsia, Tatiana Barbar, Haoues Alout, Fiona Baudino, Cyrille Lebon, Yann Gomard, David A. Wilkinson, Toscane Fourié, Patrick Mavingui, Célestine Atyame Dengue virus (DENV) is the most prevalent mosquito-borne Flavivirus that affects humans worldwide. Aedes albopictus, which is naturally infected with the bacteria Wolbachia, is considered to be a secondary vector of DENV. However, it was responsible for a recent DENV outbreak of unprecedented magnitude in Reunion Island, a French island in the South West Indian Ocean. Moreover, the distribution of the cases during this epidemic showed a spatially heterogeneous pattern across the island, leading to questions about the differential vector competence of mosquito populations from different geographic areas. The aim of this study was to gain a better understanding of the vector competence of the Ae. albopictus populations from Reunion Island for local DENV epidemic strains, while considering their infection by Wolbachia. Experimental infections were conducted using ten populations of Ae. albopictus sampled across Reunion Island and exposed to three DENV strains: one strain of DENV serotype 1 (DENV-1) and two strains of DENV serotype 2 (DENV-2). We analyzed three vector competence parameters including infection rate, dissemination efficiency and transmission efficiency, at different days post-exposition (dpe). We also assessed whether there was a correlation between the density of Wolbachia and viral load/vector competence parameters. Our results show that the Ae. albopictus populations tested were not able to transmit the two DENV-2 strains, while transmission efficiencies up to 40.79% were observed for the DENV-1 strain, probably due to difference in viral titres. Statistical analyses showed that the parameters mosquito population, generation, dpe and area of sampling significantly affect the transmission efficiencies of DENV-1. Although the density of Wolbachia varied according to mosquito population, no significant correlation was found between Wolbachia density and either viral load or vector competence parameters for DENV-1. Our results highlight the importance of using natural mosquito populations for a better understanding of transmission patterns of dengue.

by Emily A. Waters, Chad R. Haney, Lauren A Vaught, Elizabeth M. McNally, Alexis R. Demonbreun Background The pathology in Duchenne muscular dystrophy (DMD) is characterized by degenerating muscle fibers, inflammation, fibro-fatty infiltrate, and edema, and these pathological processes replace normal healthy muscle tissue. The mdx mouse model is one of the most commonly used preclinical models to study DMD. Mounting evidence has emerged illustrating that muscle disease progression varies considerably in mdx mice, with inter-animal differences as well as intra-muscular differences in pathology in individual mdx mice. This variation is important to consider when conducting assessments of drug efficacy and in longitudinal studies. We developed a magnetic resonance imaging (MRI) segmentation and analysis pipeline to rapidly and non-invasively measure the severity of muscle disease in mdx mice. Methods Wildtype and mdx mice were imaged with MRI and T2 maps were obtained axially across the hindlimbs. A neural network was trained to rapidly and semi-automatically segment the muscle tissue, and the distribution of resulting T2 values was analyzed. Interdecile range and Pearson Skew were identified as biomarkers to quickly and accurately estimate muscle disease severity in mice. Results The semiautomated segmentation tool reduced image processing time approximately tenfold. Measures of Pearson skew and interdecile range based on that segmentation were repeatable and reflected muscle disease severity in healthy wildtype and diseased mdx mice based on both qualitative observation of images and correlation with Evans blue dye uptake. Conclusion Use of this rapid, non-invasive, semi-automated MR image segmentation and analysis pipeline has the potential to transform preclinical studies, allowing for pre-screening of dystrophic mice prior to study enrollment to ensure more uniform muscle disease pathology across treatment groups, improving study outcomes. …

by Yuanqing Lu, Naweed S. Mohammad, Jungnam Lee, Alek M. Aranyos, Karina A. Serban, Mark L. Brantly Background Alpha-1 antitrypsin deficiency (AATD) is an inherited disease, the common variant caused by a Pi*Z mutation in the SERPINA1 gene. Pi*Z AAT increases the risk of pulmonary emphysema and liver disease. Berberine (BBR) is a nature dietary supplement and herbal remedy. Emerging evidence revealed that BBR has remarkable liver-protective properties against various liver diseases. In the present study, we investigated the therapeutic effects and toxicities of BBR in Pi*Z hepatocytes and Pi*Z transgenic mice. Methods Huh7.5 and Huh7.5Z (which carries the Pi*Z mutation) cells were treated with different concentrations of BBR for 48 hours. MTT was performed for cell viability assay. Intracellular AAT levels were evaluated by western blot. In vivo studies were carried out in wild type, native phenotype AAT (Pi*M), and Pi*Z AAT transgenic mice. Mice were treated with 50 mg/kg/day of BBR or solvent only by oral administration for 30 days. Western blot and liver histopathological examinations were performed to evaluate therapeutic benefits and liver toxicity of BBR. Results BBR reduced intracellular AAT levels in Huh7.5Z cells, meanwhile, no Pi*Z-specific toxicity was observed. However, BBR did not reduce liver AAT load but significantly potentiated liver inflammation and fibrosis accompanying the activation of unfolded protein response and mTOR in Pi*Z mice, but not in wild type and Pi*M mice. Conclusions BBR exacerbated liver inflammation and fibrosis specifically in Pi*Z mice. This adverse effect may be associated with the activation of unfolded protein response and mTOR. This study implicates that BBR should be avoided by AATD patients. …

by Madhusudan Prasad Singh, Nitin Rewaram Gaikwad, Yogendra Narayanrao Keche, Atul Jindal, Suryaprakash Dhaneria, Meenalotchini Prakash Gurunthalingam Antimicrobials are frequently used in critically ill children admitted to the Paediatric Intensive Care Unit (PICU). The antimicrobial use data from Indian PICUs is limited using standard metrics such as Days of therapy (DOT). This study aimed to determine the baseline trend of antimicrobial use in PICU of a tertiary care teaching hospital of Raipur district of Chhattisgarh, India using standard metrics with the goal of developing facility-wide antibiotic policy and strengthening the antimicrobial stewardship activities. This active surveillance was conducted over a period of 18 months, from November 1, 2019, to March 21, 2021, in patients aged one month to 14 years who were admitted for ≥ 48 hours to the PICU at a tertiary care teaching hospital of Raipur District. Data on patient characteristics, antimicrobial indications, antimicrobial prescription information, and clinical outcomes were collected using pre-designed data abstraction forms. The descriptive statistic was used to represent the results. The antimicrobial consumption was analyzed according to the WHO AWaRe Class (Access, Watch, and Reserve groups) of antibiotics. The antimicrobial consumption was expressed as DOT/1000 patient-days (PD). A total of 216 patients were surveyed during the study period. The average number of antimicrobials prescribed per hospitalisation was 2.60 (range: 1–12), with 97.22% administered via parenteral route. Overall, DOT/1000-PD was 1318. The consumption of Watch Group antimicrobials was highest with 949 DOT/1000-PD, followed by Access (215) and Reserve Group (154), respectively. Ceftriaxone (208 DOT/1000 PD) was the most commonly prescribed antimicrobial agent, followed by Vancomycin (201), Meropenem (175), Piperacillin-Tazobactam (122) and Colistin (91). The patients who were escalated (28.24%) from empirical antimicrobial therapy had longer median PICU stay (8 days) compared those who were de-escalated (23.6%). Targeted therapy was given in 10.2% patients. The overall mortality rate was 14.35% and was higher (29.3%) in patients in whom empirical therapy was escalated compared to those who were de-escalated or continued. The study established a benchmark for antimicrobials use in the PICU and highlighted priority areas for antimicrobial stewardship intervention to enhance de-escalation rates, enhance targeted therapy, and reduce the overuse of antimicrobials especially belonging to the reserve group.

New England Journal of Medicine, Ahead of Print.

Infection and Immunity, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Background: Maternal and pregnancy outcomes among women with perinatally acquired HIV (PHIV) versus women with HIV acquired through other routes (NPHIV), are not fully understood. Setting: U.S.-born women during 2005–2015 in New York City (NYC) Methods: We utilized data from the NYC HIV surveillance registry, Expanded Perinatal Surveillance (EPS) database, and Vital Statistics, to compare pregnancy and all-cause mortality outcomes among women with PHIV versus NPHIV delivering infants during 2005–2015. Results: There were 186 deliveries among 137 women with PHIV and 1188 deliveries among 910 women with NPHIV. Women with PHIV were younger at delivery, more likely to be aware of their HIV status, and less likely to use substances or be incarcerated. At the time of delivery, women with PHIV were more likely to have HIV RNA>1,000 copies/mL (34% vs. 19%), CD4…

Background: The Covid-19 pandemic had great impact on HIV care and prevention worldwide, including in Brazil. We compared HIV testing, recent infection, and annualized incidence according to Covid-19 pandemic period among men who have sex with men (MSM) and transgender women (TGW). Setting: HIV/STI testing, prevention and treatment referral service in Rio de Janeiro, Brazil Methods: We used Maxim HIV-1 Limiting Antigen Avidity EIA as part of recent infection testing algorithm to identify recent HIV infections and estimate annualized HIV incidences in pre- (March/2018-February/2020) and post-Covid-19 pandemic onset period (March/2020-January 2022). Multivariable logistic regression model assessed factors associated with recent HIV infection. Results: Among 4590 MSM and TGW, 593 (12.9%) tested positive for HIV and 119 (2.6%) were identified as having recent infection. Percentage of recent HIV infection did not differ between Covid-19 periods. Overall annualized HIV incidence rates were 6.0% (95%CI:4.2-7.7) and 6.6% (95%CI:4.3-9.0) in pre- and post-Covid-19 periods, respectively. During the post-Covid-19 period, higher incidence rates were observed among TGW (8.4%[95%CI:2.9-13.9]), those aged 18-24 years (7.8%[ 95%CI:4.0-11.7]), Black race (7.9%[95%CI:3.8-12.0]), and with 30 years and TGW, and lower for those with more years of schooling. Conclusion: HIV incidence estimates remain high among MSM and TGW in Brazil, especially among the most vulnerable. The consequences of the Covid-19 pandemic on the HIV epidemic will likely persist and contribute to worsening HIV outcomes. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Background: HIV envelope (env) diversity may result in resistance to broadly neutralizing antibodies (bNAbs). Assessment of genotypic or phenotypic susceptibility to antiretroviral treatment is often performed in people with HIV-1 (PWH) and used for clinical trial screening for HIV-1 bNAb susceptibility. Optimal bNAb susceptibility screening methods are not yet clear. Methods: Phenotypic and genotypic analyses were conducted on 124 screening samples from a Phase 1b study of bNAbs teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS) administered with lenacapavir in virally suppressed PWH. Phenotypic analysis was conducted on integrated HIV-1 provirus and stimulated outgrowth virus, with susceptibility to bNAbs defined as 90% inhibitory concentration ≤2 μg/mL. The proviral DNA HIV env gene was genotyped using deep sequencing, and bNAb susceptibility predicted using published env amino acid signatures. Results: Proviral phenotypic results were reported for 109 of 124 samples; 75% (82/109) were susceptible to teropavimab, 65% (71/109) to zinlirvimab, and 50% (55/109) to both bNAbs. Phenotypic susceptibility of outgrowth viruses was available for 39 samples; 56% (22/39) were susceptible to teropavimab, and 64% (25/39) to zinlirvimab. Phenotypic susceptibilities correlated between these methods: teropavimab r = 0.82 (P…

Objectives. It is important to monitor national HIV preexposure prophylaxis (PrEP) use in the United States. However, PrEP use data in the Veterans Health Administration (VHA) system are not included in the current monitoring surveillance. To address this gap, we examined the trends in PrEP use among U.S. Veterans receiving health services in the VHA system. Methods. We analyzed 2014-2022 VHA data to identify the annual number and prevalence of persons aged ≥18 years prescribed PrEP, stratified by sex, age, race and ethnicity, and region. We also assessed trends by calculating the estimated annual percent change (EAPC) and 95% confidence intervals (CIs) using Poisson models. Results. The number of Veterans prescribed PrEP increased from 361 in 2014 to 6,050 in 2022 with an EAPC of 29.6% (95% CI, 22.6–37.1). Of 6,050 Veterans with PrEP prescriptions in 2022, 95.2% were men, 4.8% were women, 50.4% were White, 24.5% Black or African American (Black) and 14.0% Hispanic or Latino. The prevalence of Black and Hispanic or Latino individuals prescribed PrEP increased significantly from 2014-2022. Conclusion. VHA data fill a gap in monitoring PrEP use in the United States. We observed an increasing trend in the number of Veterans prescribed PrEP similar to trends among persons with commercial or public health insurance. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background: Adolescents and young adults (age 13 – 24) accounted for 20% of HIV diagnoses in the United States and 6 dependent areas in 2020. Optimal treatment adherence during adolescence and young adulthood decreases the pool of infectious individuals during the risky sexual activity commonly reported among AYAs living with HIV. Methods: Adolescents and young adults newly recommended to start antiretroviral therapy (ART) were recruited, nationally, from seven clinical sites. At each clinical site, participants were randomized to receive a two-session (baseline and 1- month) online intervention. For the Motivational Enhancement System for Health (MESA) intervention condition, based on the principles of motivational interviewing, participants received ART information and personalized feedback + ART standard of care (n = 86), while for the System for Health (SH) control condition, participants received information on healthy eating and physical activity + ART standard of care (n = 66). Results: Adherence was 21% greater in the MESA intervention group compared to the SH control group at 6 months. Additionally, the MESA intervention group was significantly more adherent during the post intervention, and was more likely to maintain viral suppression up to 12 months after initiating ART if both doses of the intervention were received compared to the SH control group. Conclusion: A brief, scalable online computer-delivered intervention shows promise for achieving long-term health outcomes due to improved adherence when intervention occurs early in the course of treatment. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

No abstract available…

Airway infections with Burkholderia cepacia complex (Bcc) or Burkholderia gladioli [1] currently affect less than two percent of people with cystic fibrosis (pwCF) [2], but they are burdened by patient-to-patient transmission [3, 4], spread of virulent epidemic strains [5] and poor clinical outcomes [4, 6]. For example, infection with the Burkholderia cenocepacia ET12 epidemic strain has been associated with accelerated lung function decline, rapid, usually fatal deterioration in previously mildly affected patients (‘cepacia’ syndrome) [4, 6] and increased mortality both before and after lung transplantation [7].

Lyme borreliosis (LB), an infection caused by the spirochete Borrelia burgdorferi sensu lato complex (Bbsl), is the most common tick-borne disease in Europe [1]. Although LB commonly presents as erythema migrans (EM), Bbsl infection can disseminate resulting in Lyme neuroborreliosis (LNB), arthritis, or carditis [1].

Tuberculosis infection (TBI) refers to the state when an immune response to Mycobacterium tuberculosis (Mtb) is detected in the absence of clinical, microbiological, or radiological signs of active disease. In some cases, TBI can progress to TB disease via stages of incipient and subclinical TB [1]. Given that Mtb remains in a low replicative state during TBI, no reliable tool for the direct detection of bacteria is currently available. Instead, an indirect evaluation of infection based on measuring the Mtb-specific immune response is applied using tuberculin skin test (TST) and interferon-γ release assays (IGRAs) [1].

Virulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates.

For nearly two decades, posaconazole has been a preferred choice for primary antifungal prophylaxis in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) who are at high risk for mould infections [1]. When first approved in 2006, posaconazole was available only as an oral suspension that required frequent dosing with a high fat meal and low gastric pH for absorption. These characteristics made the drug difficult to use in the HSCT population, where gastrointestinal complications such as nausea, vomiting, diarrhoea, and intestinal graft-versus-host disease (GvHD) are common.

We have, with interest, read the article titled “Impact of C-reactive protein point-of-care testing on antibiotic prescriptions for children and adults with suspected respiratory tract infections in primary care: a French patient-level randomised controlled superiority trial” and commend the authors for their valuable contribution [1]. However, caution should be considered in interpreting the results.