Abstract The IA-DUET study aimed to compare azole-echinocandin combination with azole monotherapy for invasive aspergillosis. Recruitment was hindered by patient ineligibility, competing studies, and guidelines favoring combination therapy when azole resistance was unknown. The low IA-attributable mortality suggests future trials may benefit from cluster randomization or composite endpoints to enhance efficiency.

by Kai Liu, Jing An, Jing Zhang, Jihu Zhao, Peng Sun, Zhaohui He The exploration of novel natural products for Parkinson’s disease (PD) is a focus of current research, as there are no definitive drugs to cure or stop the disease. Campsis grandiflora (Thunb.) K. Schum (Lingxiaohua) is a traditional Chinese medicine (TCM), and the exact active constituents and putative mechanisms for treating PD are unknown. Through data mining and network pharmacology, apigenin (APi) was identified as the main active ingredient of Lingxiaohua, and key targets (TNF, AKT1, INS, TP53, CASP3, JUN, BCL2, MMP9, FOS, and HIF1A) of Lingxiaohua for the treatment of PD were discovered. The primary routes implicated were identified as PI3K/AKT, Apoptosis, TNF, and NF-κB pathways. Subsequently, therapeutic potential of APi in PD and its underlying mechanism were experimentally evaluated. APi suppressed the release of mediators of inflammation and initiation of NF-κB pathways in MES23.5 cells induced by MPP+. APi suppressed caspase-3 activity and apoptosis and elevated p-AKT levels in MES23.5 cells. Pretreatment with LY294002, a PI3K inhibitor, resulted in APi treatment blocking the activation of NF-κB pathway and expression of inflammatory factors in MES23.5 cells by activating the PI3K/AKT pathway. In conclusion, APi protects dopaminergic neurons by controlling the PI3K/AKT/NF-κB pathway, giving novel insights into the pharmacological mechanism of Lingxiaohua in treating PD.

by Fatemehe Majdi, Behrooz Alizadeh Behbahani, Hassan Barzegar, Mohammad Amin Mehrnia, Morteza Taki Buffalo meat is naturally perishable, making it susceptible to spoilage due to its high moisture content and vulnerability to microbial contamination. Edible coatings have attracted attention as a packaging method that can prolong the shelf life of meat. The study aimed to examine the impact of a combination of Lepidium sativum mucilage (LS) coating and propolis extract (PE) on prolonging the shelf life of buffalo meat. The chemical characteristics (chemical compounds, total phenol content (TPC), total flavonoid content (TFC), antioxidant activity, and cytotoxicity) and antimicrobial activity of the PE (disk diffusion agar, well diffusion agar, minimum inhibitory concentration, and minimum bactericidal concentration) were investigated. The effect of the PE on the cell wall of pathogenic bacteria was examined using a scanning electron microscope. Biological properties of LS (TPC, TFC, antioxidant activity and antimicrobial effect (pour plate method)) was investigated. Different concentrations of PE (0, 0.5, 1.5, and 2.5%) were added to the coating mixture containing LS, and their effects on extending the shelf life of buffalo meat samples stored at 4°C for 9 days were assessed. The PE included gallic acid, benzoic acid, syringic acid, 4–3 dimethoxy cinnamic acid, p-coumaric acid, myricetin, caffeic acid, luteolin, chlorogenic acid, and apigenin. The PE was determined to have a TPC of 36.67 ± 0.57 mg GAE/g and a TFC of 48.02 ± 0.65 mg QE/g. The extract’s radical scavenging activity ranged from 0 to 76.22% for DPPH radicals and from 0 to 50.31% for ABTS radicals. The viability of C115 HeLa cell was observed to be 94.14 μg/mL. The PE and LS, exhibited strong antimicrobial properties against pathogenic bacteria. The LS was determined to have a TPC of 15.23 ± 0.43 mg GAE/g and a TFC of 11.51± 0.61 mg QE/g. The LS was determined to have a DPPH of 429.65 ± 1.28 μg/mL and a ABTS of 403.59 ± 1.46 μg/mL. The microbiological analysis revealed that the LS+2.5%PE treatment was the most effective in inhibiting the growth of total viable count (6.23 vs. 8.00 log CFU/g), psychrotrophic bacteria count (3.71 vs. 4.73 log CFU/g), coliforms count (2.78 vs. 3.70 log CFU/g), and fungi count (2.39 vs. 3.93 log CFU/g) compared to the control sample. The addition of PE to the edible coating also demonstrated a concentration-dependent effect on preserving the moisture, pH, color, and hardness of the buffalo meat. Sensory evaluation results suggested that incorporating PE into the edible coating extended the shelf life of buffalo meat by three days. In the second stage of this paper, this investigation employed two distinct forecasting methodologies: the Radial Basis Function (RBF) and the Support Vector Machine (SVM), to predict a range of quality indicators for coated meat products. Upon comparison, the RBF model exhibited a higher level of accuracy, showcasing its exceptional capacity to closely match the experimental outcomes. Therefore, this type of food coating, renowned for its strong antimicrobial properties, has the potential to effectively package and preserve perishable and delicate food items, such as meat.

by Arega Tsegaye, Assalif Demissew, Ashenafi Abossie, Hallelujah Getachew, Kassahun Habtamu, Teshome Degefa, Xiaoming Wang, Ming-Chieh Lee, Daibin Zhong, James W. Kazura, Guiyun Yan, Delenasaw Yewhalaw Background Thioester-containing protein 1 (TEP1) is a crucial component of mosquitoes’ natural resistance to parasites. To effectively combat malaria, there is a need to better understand how TEP1 polymorphism affects phenotypic traits during infections. Therefore, the purpose of this study was to determine the Tep1 genotype frequency in malaria vector populations from south-western Ethiopia and investigate its effect on Plasmodium oocyst development in Anopheles arabiensis populations. Methods Using standard dippers, Anopheles mosquito larvae were collected from aquatic habitats in Asendabo, Arjo Dedessa, and Gambella in 2019 and 2020. Collected larvae were reared to adults and identified morphologically. Female An. gambiae s.l. were allowed to feed on infected blood containing the same number of gametocytes obtained from P. falciparum and P. vivax gametocyte-positive individuals using indirect membrane feeding methods. Polymerase Chain Reaction (PCR) was used to identify An. gambiae s.l. sibling species. Three hundred thirty An. gambiae s.l. were genotyped using Restricted Fragment Length Polymorphism (RFLP) PCR and sub samples were sequenced to validate the TEP1 genotyping. Results Among the 330 samples genotyped, two TEP1 alleles, TEP1*S1 (82% frequency) and TEP1*R1 (18% frequency), were identified. Three equivalent genotypes, TEP1*S1/S1, TEP1*R1/R1, and TEP1*S1/R1, had mean frequencies of 65.15%, 2.12%, and 32.73%, respectively. The nucleotide diversity was ranging from 0.36554 to 0. 46751 while haplotype diversity ranged from 0.48871 to 0.63161, across all loci. All sample sites had positive Tajima’s D and Fu’s Fs values. There was a significant difference in the TEP1 allele frequency and genotype frequency among mosquito populations (p < 0.05), except populations of Anopheles arabiensis from Asendabo and Gambella (p > 0.05). In addition, mosquitoes with the TEP1 *RR genotype were susceptible and produced fewer Plasmodium oocysts than mosquitoes with the TEP1 *SR and TEP1 *SS genotypes. Conclusion The alleles identified in populations of An. arabiensis were TEP1*R1 and TEP1*S1. There was no significant variation in TEP1*R1 allele frequency between the high and low transmission areas. Furthermore, An. arabiensis carrying the TEP1*R1 allele was susceptible to Plasmodium infection. Further studies on vector-parasite interactions, particularly on the TEP1 gene, are required for vector control techniques. …

by Veronica Martinez Martinez, Hermen Ormel, Eline L. M. Op de Coul Background Heterosexual migrant men and women in the Netherlands often face barriers to accessing health services, including HIV testing, that may lead to late-stage HIV diagnoses. This study explored factors of influence in the usage of HIV testing among heterosexual migrants. Methods Qualitative evaluation with semi-structured interviews at the Amsterdam-based AIDS Healthcare Foundation (AHF) Checkpoint and one focus group discussion (FGD) conducted during June-July 2023 with 19 participants: interviews with 12 heterosexual migrants from low- or middle-income countries (LMICs) and FGD (n = 5) and interviews (n = 2) with 7 key informants from the (public) health sector. Recorded interviews were transcribed and thematically analyzed, using the framework of Andersen’s Expanded Behavioral Model of Health Services Use. Results In total, 55 themes emerged from the interviews and the FGD. Examples include insufficient availability of information on HIV and testing services, and difficulty in accessing these services (e.g. the barrier of the online appointment system of the Centre for Sexual Health (CSH)). HIV test participants expressed free, rapid testing, no appointment required, and a positive experience during their HIV test as enablers to test in the future. Results from key informants showed that poor health literacy and lack of clarity on the healthcare system’s guidelines were barriers for heterosexual migrants in accessing information on HIV and testing services. It also revealed past initiatives and interventions that were successful in reaching at-risk groups such as the integration of HIV testing into sexually transmitted infection (STI) testing, but that were subsequently discontinued due to financial constraints. Conclusion Factors contributing to a low HIV test uptake were participants’ perception of limited accessibility of CSH facilities, insufficient available information on HIV (testing) services, and low perception of HIV risk. Unclear policies on accessing HIV/STI testing services at CSHs, and potential missed opportunities for HIV testing at general practitioners were contributing factors identified by key informants. …

by Tianxiang Jiang, Zhaolun Cai, Chunjuan Liu, Bo Zhang Background Crohn’s disease (CD) is a chronic inflammatory condition primarily affecting the digestive system. When dealing with complex cases like intestinal blockages or perforations, surgery becomes the primary treatment option. However, surgery doesn’t offer a complete cure, and the possibility of recurrence remains. To manage CD recurrence after surgery, various treatment choices are available, including steroids, monoclonal antibodies, immunomodulators, and further surgery. Regrettably, the current body of evidence doesn’t definitively establish which of these treatments is the most effective and safe. Thus, our research aims to provide insights into the Validity and security of different treatment approaches for managing CD recurrence after surgery. Methods Search of EMBASE, PubMed, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials will be conducted to include researches that examine the validity of treatments for recurrent CD after surgery. Our analysis will distinguish between two types of studies: randomized controlled trials (RCTs) and non-randomized studies with at least two different treatments, each evaluated separately. We will employ Bayesian network meta-analyses to systematically compare the effectiveness and safety of these treatments. Additionally, subgroup analyses will be performed according to recurrence status and postoperative prophylactic medication. To clarify the variation of studies, sensitivity analyses will be performed. And we may use meta-regression as an additional approach if relevant data are available. We will also rigorously access the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Discussion This analysis will provide a comprehensive assessment of the latest evidence on available treatments for patients with postoperative recurrence of CD, which will provide recommendations for clinical practice. Trial registration Systematic review registrationINPLASY2023110021. (DOI: 10.37766/inplasy2023.11.0021). …

by April McNeill-Johnson, Zuri Hudson, Brittany Moore, Dumebi Okocha, Megha Ramaswamy, Kimberly Randell Despite the worsening health disparities among youth in detention during the COVID-19 pandemic, there has been minimal exploration into the pandemic experiences of detained youth and opportunities for pandemic mitigation. This paper analyzes the perspectives of youth in detention on the pandemic, including the effect of the pandemic on their detention experience and their perceptions about COVID-19 vaccination. The study used purposive sampling to recruit 16 participants (aged 14–17 years) from two juvenile detention centers in the urban Midwest. We conducted semi-structured interviews and analyzed verbatim transcripts using a hybrid deductive-inductive approach and thematic analysis. Four themes emerged: 1) personal experience influenced youth perceptions of pandemic severity and risk; 2) distrust and misconceptions contributed to youth vaccine hesitancy or refusal; 3) desired opportunities and parental opinion motivated youth to get the COVID-19 vaccine; and 4) pandemic mitigation strategies negatively impacted youths’ detention center experience. Study findings identify opportunities for detention centers to minimize the negative impacts of pandemic mitigation strategies on youth in detention, expand vaccination knowledge and uptake, and build trust to positively impact the health and wellbeing of detained youth currently and during future pandemics.

New England Journal of Medicine, Volume 391, Issue 14, Page 1302-1312, October 10, 2024.

New England Journal of Medicine, Volume 391, Issue 14, Page 1358-1359, October 10, 2024.

New England Journal of Medicine, Volume 391, Issue 14, Page 1343-1354, October 10, 2024.

New England Journal of Medicine, Ahead of Print.

Abstract Background Malaria is one of the world’s most lethal vector-borne diseases, causing significant health burdens in endemic countries. Several studies on the prevalence of malaria among pregnant women in Ghana have been conducted in various parts of the country, yielding evidence pointing to intra- and inter-regional variations. The current study assessed the prevalence, risk factors, and sociodemographic predictors of malaria among pregnant women in the Bono East Region of Ghana. Methods This multicentre hospital-based study employed a mixed-method cross-sectional design. A multistage sampling technique was used to select seven health facilities and recruited 1452 pregnant women who attended ANC at seven selected health facilities. Haematological examination, a structured closed-ended questionnaire, in-depth interviews (IDIs), and focus group discussions (FGDs) were used to obtain relevant data. Quantitative data were analysed with STATA 14 (StataCorp, College Station, USA). Likewise, the four-step thematic analysis was used to analyse qualitative data. A significant level was set at (p 

Abstract Background Vector-borne diseases, such as malaria, pose a significant global threat, and climatological factors greatly influence their intensity. Tropical countries, like India, are particularly vulnerable to such diseases, making accurate estimation of malaria risk crucial. Methods This study utilized the well-known Vector-borne Disease Community Model, VECTRI, developed by the International Centre for Theoretical Physics in Trieste. The model was implemented to estimate malaria’s Entomological Inoculation Rate (EIR). Future climatic prediction datasets, including CMIP 5 and population data sets, were used as inputs for the analysis. Three RCP scenarios are considered (Representative Concentration Pathways are climate change scenarios that project radiative forcing to 2100 due to future greenhouse gas concentrations). The projections covered the period from 1 Jan, 2020, to 31 Dec, 2029. Results The estimated mean EIR for the years 2020–2029 ranged, and a significant decline in malaria risk was observed with all RCP 2.6, 4.5, and 8.5 scenarios. Each year 0.3 to 2.6 [min–max] EIR/person/day decline is observed with a strong decline in man rainfall ranging from 5 to 17 [min–max] mm/year and associated high temperatures ranging from 0.03 to 0.06 [min–max] °C/year. During the post-monsoon period, August to November were identified as highly prone to malaria transmission. Spatial analysis revealed that the east coast of India faced a higher vulnerability to malaria risk, which kept increasing through RCP scenarios. Thus, it is essential to exercise caution, especially in areas with heavy rainfall. Conclusion This research provides valuable insights for policy-makers, highlighting the need to implement future strategies to mitigate malaria risk effectively. By utilizing these findings, appropriate measures can be taken to combat the threat posed by malaria and protect public health. …

Abstract Background Plasmodium vivax is the second most common malaria parasite in Ethiopia. It has been treated with chloroquine (CQ) for the past seven decades. However, the emergence of CQ-resistant strains in the nation urged the Federal Ministry of Health of Ethiopia to review its national malaria treatment guideline in 2018. In the revised guideline, the first-line treatment for uncomplicated P. vivax infection is a combination of CQ and primaquine (PQ). Thus, the present study was designed to evaluate the in vivo efficacy of CQ and PQ combination therapy against clinical P. vivax mono-infection in one of the malaria-endemic areas of Ethiopia. Methods An open-label prospective clinical trial was conducted in the Limmu Kossa District, Jimma zone, Southwest Ethiopia, from September 2023 to March 2024. A total of 108 patients were recruited for the study. All participants received treatment with CQ at a dosage of 25 mg/kg over three days, followed by PQ at 0.25 mg/kg for 14 consecutive days. Patients were monitored for 42 days for any signs of treatment failure and malaria clinical symptoms, as per the World Health Organization (WHO) guidelines for anti-malarial drug evaluation. Additionally, haemoglobin (Hb) levels, body temperature, any adverse events, and signs of haemolysis were assessed. Data was analysed using R-software (version 4.0.0) and a significant level was considered at p 

Abstract Purpose To compare the clinical severity of Human Adenovirus (HAdV) infection with other viral diseases in a cohort of children, evaluating presentation, therapy, and outcome. Methods We conducted a retrospective multicenter cohort study in Italian children hospitalized from January to December 2023 for respiratory symptoms. The study included children with HAdV infection presenting primarily with respiratory symptoms. Patients with isolated gastrointestinal involvement or coinfection with bacteria were excluded. Results A total of 171 children were enrolled: 98 with HAdV infection (age 44.3 ± 37.9 months) and 73 with other viruses (age 20.4 ± 27.2 months). In the first group, 57.1% had a coinfection with one or more additional viruses. The most common symptoms were fever (89.8%), cough (73.5%) and sore throat (52%). Respiratory distress and hypoxemia were more frequent in the non-HAdV group. Children with HAdV infection demonstrated significantly higher C-reactive protein levels (50.8 ± 54.2 vs. 16.5 ± 33.8 mg/L, p 

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Journal of Medical Virology, Volume 96, Issue 10, October 2024.

Journal of Medical Virology, Volume 96, Issue 10, October 2024.

Background: The aim of this study is to assess the acceptability of HIV pre-exposure prophylaxis (PrEP) among individuals eligible for prophylaxis. Setting: Retrospective study of individuals receiving their first HIV test at the Infectious Diseases Unit of IRCCS San Raffaele Scientific Institute, Milan, Italy. Methods: People i) who received their first HIV test (baseline date) between January 2018 (availability of PrEP in Italy) and December 2023 (data lock), ii) with an indication for PrEP based on condomless sex were included; those already on PrEP were excluded. Individuals with a negative HIV test result were offered PrEP counselling and prescription according to guidelines. Characteristics of people who accepted or declined HIV PrEP were compared using Mann-Whitney or Chi-square tests, as appropriate. Results: A total of 2627 people were tested for HIV: 175 (6.6%) were diagnosed with HIV. Of the 2452 people with negative HIV test results, 2165 (88.3%) were men; median age was 34.3 years (interquartile range, IQR=28.7-42.4). Sexually transmitted infections (STIs) were detected in 478/2452 (19.5%), most commonly gonorrhoea (206/2452, 8.4%). Overall, 982/2452 (40.0%) people accepted PrEP, including only three women. Non-acceptance was higher among women (p…

No abstract available…

Background: To compare racial and ethnic disparities in HIV diagnosis rates among adults in census tracts with most disadvantaged vs advantaged levels of social determinants of health (SDOH). Methods: In this ecological analysis, we used the National HIV Surveillance System data in 2021 and SDOH data from 2017–2021 American Community Survey. We measured racial and ethnic disparities stratified by sex in the most disadvantaged quartiles and advantaged quartiles for: 1) Poverty 2) Education level 3) Median household income and 4) Insurance coverage. We calculated 8 relative disparity measures (Black-to-White rate ratio [RR], Hispanic/Latino-to-White RR, Index of Disparity [ID], population-weighted ID, Mean Log Deviation, Theil Index, Population Attributable Proportion, Gini coefficient) and 4 absolute disparity measures (Black-to-White rate difference [RD], Hispanic/Latino-to-White RD, absolute ID, and population-weighted absolute ID). Results: Comparing the most disadvantaged quartiles to the most advantaged quartiles, all four absolute disparity measures decreased, but 7 of the 8 relative disparity measures increased: the median percentage decrease in the absolute measures for males and females respectively was 38.1% and 47.6% for poverty, 12.4% and 42.6% for education level, 43.6% and 44.0% for median household income, and 44.2% and 45.4% for insurance coverage. The median percentage increases for the relative measures for males and females respectively were 44.3% and 61.3% for poverty, 54.9% and 95.3% for education level, 19.6% and 90.0% for median household income, and 32.8% and 46.4% for insurance coverage. Conclusion: Racial and ethnic disparities in the most disadvantaged and advantaged quartiles highlight the need for strategies addressing the root causes of disparities. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background: Transgender women continue to face a significant burden of health disparities with HIV infection as a critical public health concern. Substance use is higher among transgender women compared to cisgender women. However, little is known about transgender women who inject drugs and risk for HIV in the United States. The objectives were to explore HIV prevalence, injection-related behaviors, and HIV prevention and care outcomes among transgender women who inject drugs and to compare transgender women to a general sample of people who inject drugs (PWID). Methods: Participants from National HIV Behavioral Surveillance were recruited via respondent-driven sampling, interviewed, and tested for HIV infection in 2019-2020. Log-linked Poisson regression models were used to test for associations between injection drug use and selected characteristics. Results: Among 1,561 transgender women, 7% injected drugs in the past 12 months. HIV prevalence was higher among transgender women who inject (aPR=1.5, 95%CI=1.2-1.8) than those who do not. Multiple psychosocial conditions were associated with injection drug use. Among transgender women with HIV, those who inject were less likely to take antiretroviral therapy (aPR=0.8, 95%CI=0.7-1.0) than those who do not. Methamphetamine was the most commonly injected drug (67%); most accessed a syringe services program (66%). Conclusion: Transgender women who inject have substantial challenges related to health outcomes including high HIV prevalence and exposure to psychosocial conditions, such as homelessness, incarceration, and exchange sex, that may exacerbate risks associated with injection drug use. This population may benefit from increased access to non-judgmental and culturally competent harm reduction services. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background: As people living with HIV (PWH) age, they face new challenges that can have a negative impact on their quality of life (QOL) and mental health. Setting: This study enrolled PWH at the end of life (EOL) who were actively engaged in cure-related research in Southern California, United States. EOL was defined as having a prognosis of six months or less to live. We examined the relationship between QOL, mental health, and research participation. Methods: Structured assessments were used to collect comprehensive data on QOL and mental health. Results: From 2017 to 2023, 35 PWH in their final stages of life who were actively engaged in cure-related research were enrolled. Their median age was 62.7 years, and most were White or otherwise non-Hispanic/non-Latino (90.6%), and male (86.7%). Changes in QOL and the presence of neurologic and psychiatric conditions, with a focus on depression and anxiety, were the primary outcomes assessed in this study. Participants had stable QOL scores throughout the study. There was an inverse relationship between QOL and BDI scores, with higher mean QOL scores being associated with lower mean BDI scores (p < 0.001). Conclusion: QOL remained stable among PWH who participate in cure-related research at EOL. The inverse relationship between QOL and depressive symptoms suggests that participation in cure-related research may improve QOL or reduce depressive symptoms in this population. Future interventions should look into ways to improve the well-being of PWH at EOL through research and customized mental health interventions. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Introduction: Adolescents 10-19 years account for a growing proportion of people living with HIV (PLHIV). In 2023, 140,000 adolescents were diagnosed with HIV, yet knowledge of HIV status and uptake of testing services remain critically low. Index testing – offering testing to contacts of PLHIV – is an important case-finding strategy. In 2021, PEPFAR expanded guidance to explicitly include older adolescents 15 to 19 years. We reviewed index testing data to assess uptake and case-finding trends among biological adolescent-aged children and siblings of PLHIV 10-19 years. Methods: Routinely collected programmatic data from 27 USAID-supported PEPFAR country and regional programs were analyzed for fiscal years (FY) 2017 through FY2022 (October 2016 - September 2022). We compared the volume of index testing and subsequent new diagnoses across FYs and countries among biological adolescent-aged children and siblings of PLHIV, and disaggregated by age, 10-14 and 15-19 years, and sex. Results: Index testing among adolescents 10-19 years increased from FY17 to FY22, nearly doubling from 147,088 to 291,534. Similarly, new diagnoses among adolescents increased between FY17 and FY22 (3,721 vs 10,730). Overall, across FYs, index testing uptake and case-finding were higher among females than males, and the gap in testing uptake between sexes was larger for older than younger adolescents. Conclusion: Index testing uptake has increased substantially among adolescents over time, with rebounded gains for adolescents 15-19 years noted beginning in FY21. However, uptake across age and sex remained uneven, highlighting an opportunity to ensure targeted testing strategies are employed to reach adolescents 15-19 years and males. Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.

The SARS-CoV-2 pandemic caused chaos in healthcare systems worldwide. As we move into the current endemic stage, concern is angled more towards COVID-19 high-risk patients care and the management of long-term consequences of the disease. Key considerations have shifted to early treatments efficacy, and formulation of public policies to help restore and maintain patients’ quality of life and a functional society.

Abstract Traditional Randomized Controlled Trials often fall short in addressing the specific needs of clinical practice due to their one-size-fits-all treatment approaches. Sequential Multiple Assignment Randomized Trials (SMARTs) offer a dynamic and adaptive approach, allowing for multiple randomizations based on patient responses and evolving conditions. SMARTs enable personalized treatment pathways, such as in the trial for antiretroviral therapy (ART) in South Africa, which adjusts treatment based on patient outcomes. Despite these advantages, the use of SMARTs in infectious diseases remains limited. Greater adoption of SMARTs could promote more personalized treatment approaches, improve flexibility in response to public health needs, and enhance the effectiveness of interventions. However, challenges such as recruitment and increased expertise needed for more complex analyses must be addressed. Additionally, combining SMARTs with other adaptive designs could further improve the relevance and outcomes of clinical research.

Abstract Background Hemodialysis (HD) patients represent a high-risk group for hepatitis B infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of anti-HBs. Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedule regimen in HD patients.Methods We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 HD patients were enrolled. All participants randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 μg) at 0-1-6 months (IM20×3 group), 4 standard doses at 0-1-2-6 months (IM20×4 group), or 4 triple doses (60 μg) at 0-1-2-6 months (IM60×4 group).Results The vaccine-elicited antibody response peaked at month 7. The follow-up outcomes ranging from month 7 to 30 revealed that the response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20×3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20×4 group and from 95.4% (145/152) to 57.3% (55/96) in IM60×4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 21.0 months in IM20×3 group, 25.7 months in IM20×4 group (vs. IM20×3 group, P=0.056) and 29.2 months in IM60×4 group (vs. IM20×3 group, P=0.034). All the adverse reactions were mild.Conclusions The four-triple-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in HD patients.The trial was registered with Clinical Trials.gov, number NCT03962881. https://classic.clinicaltrials.gov/ct2/show/NCT03962881?term=NCT03962881&draw=2&rank=1.

Abstract Using the VA COVID-19 National Database, we created matched pairs of previously uninfected vaccinated (≥2 doses of an mRNA vaccine) and previously infected unvaccinated individuals.The incidence rate (per 1000 person-days) of breakthrough infection among vaccinated individuals (0.30, 95% CI 0.29-0.32) was similar to reinfection rate among unvaccinated individuals (0.31, 95% CI 0.30-0.32; p=0.5). The incidence rate of hospitalization/death was higher after reinfection (7.31, 95% CI 6.66-8.03) compared with rate after breakthrough infection (4.69, 95% CI 4.06-5.42; P

On Sept 3, WHO published Guidance on wastewater and solid waste management for manufacturing of antibiotics, its first such document on antibiotic pollution by manufacturers. Noted early on in the guidance, there was substantial demand for it from many international bodies. While it is acknowledged that pollution is also created through the necessary use of antibiotics to treat infections, this is impossible to mitigate entirely; however, pollution from manufacturers should be possible to avoid.

As of June 30, the Nigeria Centre for Disease Control and Prevention (NCDC) has reported 928 confirmed cases of Lassa fever and 162 associated deaths, a case fatality rate of 17·5%. Over 30 cases have been confirmed among health-care workers, an even male-to-female ratio among confirmed cases has been observed, individuals aged 21–30 years are the most affected age group, and the number of suspected cases has increased compared to the same period last year. NCDC has established a national technical working group to coordinate response activities at all levels. Lassa fever is an acute viral haemorrhagic disease caused by Lassa virus (LASV) that is primarily found in multimammate rodents in west Africa.

On June 14, 2024, WHO published a global report on antibacterial agents in preclinical and clinical development. The resource provides an update to the WHO antibacterial pipeline analysis report in 2022 and includes both traditional and non-traditional antibacterial agents currently in development worldwide.

We provide evidence that functional antibody responses mediated by IgG and IgA are associated with protection against malaria in young children vaccinated with RTS,S, and suggest potential differences in the correlates of immunity between males and females. These findings reveal new avenues that could be used to achieve malaria vaccines with higher efficacy.

Implementation of WBS could enable targeted clinical investigations and improve cost-effectiveness of COVID-19 outbreak management in LTCFs. WBS and serostatus provided informed dynamic changes of infections and immunity. Critical evidence was that LTCF WBS is an effective early warning system to support rapid public health outbreak management and protect vulnerable older populations.

We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence.

Our findings suggest that OSP-specific functional IgA responses contribute to protective immunity against Shigella infection in a high-burden setting. These findings will assist in the development and evaluation of Shigella vaccines.

Our study shows that a culture-based deep-sequencing approach is a possible route towards improving future pathogen surveillance and infection control at hospitals. Future studies should be designed to directly compare the accuracy, cost, and feasibility of culture-based deep sequencing with single colony whole-genome sequencing on a range of bacterial species.

Our study reported a high prevalence of GBS colonisation in most settings, with some geographical variability even within African countries. Our findings suggest that serotypes not included in current multivalent capsular-polysaccharide GBS vaccines prevail in some regions, so vaccine efficacy and post-licensure effectiveness studies should assess the effect of vaccination on maternal GBS colonisation given the potential for replacement by non-vaccine serotypes.

These findings show that the k13 Arg561His mutation is common in northwest Tanzania and that multiple emergences of ART-R, similar as to what was seen in southeast Asia, have occurred. Mutations associated with high levels of sulfadoxine–pyrimethamine resistance are common. These results raise concerns about the long-term efficacy of artemisinin and chemoprevention antimalarials in the region. Understanding how multiple emergences interact with drivers of regional spread is essential for combating ART-R in Africa.

This study highlights the role of environmental surveillance in the early detection and monitoring of poliovirus circulation, enabling a prompt public health response involving enhanced surveillance and a catch-up campaign with inactivated polio vaccine. Whole-genome sequencing offered valuable insights into the origins of the outbreak, linkage across detections, and the geographical distribution of the virus, with higher resolution than would have been possible with the standard analysis of the VP1 gene alone.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, presents a substantial global health burden, affecting millions of individuals worldwide and posing a continual risk of infection. Despite the high mortality and morbidity rates, effective vaccines to prevent infection by the parasite remain elusive, and the drugs currently available are suboptimal. Understanding the intricate dynamics of parasite–host interactions and the resulting immune responses, which contribute to both protection and pathology, is crucial for the development of effective vaccines and therapies against Chagas disease.

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease in humans. Transmission of T cruzi by triatomine vectors is dependent on diverse environmental and socioeconomic factors. Climate change, which is disrupting patterns of human habitation and land use, can affect the epidemiology of Chagas disease by influencing the distribution of vector and host species. We conducted a review using triatomine distribution as a proxy for T cruzi transmission in North America (Canada, Mexico, and the USA) and central America (Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama) and investigated the association of T cruzi transmission with climate change, identifying 12 relevant studies.

To determine the proportion of individuals with detectable antigen in plasma or serum after SARS-CoV-2 infection and the association of antigen detection with postacute sequelae of COVID-19 (PASC) symptoms.

ObjectiveIn high HIV-burden countries like Uganda, financing and resource allocation for HIV services have rapidly evolved. This study aimed to employ time-driven activity-based costing (TDABC) to examine the allocation of resources and associated costs for HIV care throughout the country. DesignA cross-sectional study. SettingThis study was conducted at 31 health facilities throughout Uganda: 16 level III health centres, 10 level IV health centres and 5 district hospitals. Participants1119 persons receiving HIV services in 2020. MethodsWe conducted TDABC to quantify costs, resource consumption and duration of service provision associated with antiretroviral therapy, prevention of mother-to-child transmission, HIV counselling and testing (HCT), voluntary medical male circumcision (VMMC) and pre-exposure prophylaxis. We also quantified disparities in resource consumption according to client-level and facility-level characteristics to examine equity. Fixed-effects multivariable regression analyses were employed to inspect factors associated with service costs and provider-client interaction time. ResultsThe mean cost of services ranged from US$8.18 per visit for HCT to US$32.28 for VMMC. In terms of disparities, those in the Western region received more provider time during visits compared with other regions (35 more minutes, p

ObjectivesTo describe the development, validation and reliability of the Oxford Vaccine Hesitancy Scale (OVHS), a new instrument to assess vaccine hesitancy in the general population. DesignCross-sectional validation study. SettingInternet-based study with participants in the UK and USA. ParticipantsDemographically representative (stratified by age, sex and race) samples from the UK and USA recruited through the Prolific Academic platform. Main outcome measuresTo demonstrate OVHS development, exploratory factor analysis with categorical variables and a polychoric correlation matrix followed by promax oblique rotation on the UK sample was performed. Confirmatory factor analysis with a Satorra-Bentler scaled test statistic evaluating goodness of fit statistics including the root mean squared error of approximation (RMSEA), standardised root mean squared residual (SRMR) and comparative fit index (CFI) was performed on the US sample. Reliability as internal consistency was assessed using McDonald’s omega. Evidence in support of the predictive, convergent and discriminant validity of the scale was assessed using logistic regression ORs of association (OR) or Pearson correlation coefficients. ResultsData for factor analysis were obtained from 1004 respondents, 504 in the UK and 500 in the USA. A scree plot, minimum average partial correlation analysis and parallel analysis suggested a three-factor 13-item scale with domains of vaccine beliefs (seven items), pain (three items) and personal deliberation (three items). Responses were recorded on a Likert scale ranging from disagree completely to agree completely, with higher score reflecting greater hesitancy. Potential total scores ranged from 13 to 65. Goodness of fit was excellent, with RMSEA=0.044, SRMR=0.041 and CFI=0.977. Predictive validity for COVID-19 vaccination status was excellent, with logistic regression ORs of association (95% CI) of 0.07 (0.04, 0.13), p

IntroductionCancer treatment with high-dose chemotherapy damages the mucosal barrier of the gastrointestinal (GI) tract and is associated with severe toxicity involving mucositis, severe inflammation and organ dysfunction. Currently, there is no effective prophylaxis against this. Glucagon-like peptide 1 (GLP-1), a well-known regulator of blood glucose, has been suggested in mouse studies to possess trophic effects on gut epithelial cells as well as anti-inflammatory properties. In line with this, endogenous GLP-1 levels have been shown to be inversely correlated with toxicities after haematopoietic stem cell transplantation (HSCT) and treatment with a GLP-1 receptor agonist (GLP-1RA) was shown to limit chemotherapy-induced mucositis in rodents. This present study investigates the effects of the GLP-1RA semaglutide on GI mucositis severity score in patients with lymphoma undergoing high-dose chemotherapy followed by autologous (auto) HSCT. Methods and analysisThis is a randomised, double-blind, placebo-controlled, two-centre investigator-initiated clinical study. Forty adult patients with malignant lymphoma referred for auto-HSCT will be randomised in a 1:1 manner to receive either semaglutide or placebo once-weekly for 8 weeks. This includes a run-in period of 3–4 weeks with semaglutide 0.25 mg prior to high-dose chemotherapy treatment followed by a period of 4–5 weeks with semaglutide 0.5 mg including the 1 week of high-dose chemotherapy treatment. Clinical assessment of endpoint measurements and safety will be performed weekly during treatment and in a follow-up period of 10 weeks. The primary endpoint is GI mucositis severity (mean severity grade (0–II) during week 1–4 after auto-HSCT). Secondary endpoints include C-reactive protein increment, quality of life and safety. Fever, bacteraemia, antibiotic use, weight loss, morphine consumption, duration of hospitalisation, use of parenteral nutrition, change in muscle mass and clinical and laboratory evidence of organ toxicities will also be assessed. Ethics and disseminationThe study complies with Danish and European Union legislation and is approved by the Danish Medicines Agency, the Danish National Medical Research Ethics Committee (EU CT #2022-502139-20-00) and the Danish Data Protection Agency. The study is monitored by the Capital Region of Denmark’s good clinical practice unit. All results, positive, negative and inconclusive, will be disseminated at national and international scientific meetings and in peer-reviewed scientific journals. Trial registration numberNCT06449625 …

ObjectivesWith the emergence of new COVID-19 variants (Omicron BA.5.2.48 and B.7.14), predicting the mortality of infected patients has become increasingly challenging due to the continuous mutation of the virus. Existing models have shown poor performance and limited clinical utility. This study aims to identify the independent risk factors and develop practical predictive models for mortality among patients infected with new COVID-19 variants. DesignA retrospective study. Setting and participantsWe extracted data from 1029 COVID-19 patients in the respiratory disease wards of a general hospital in China between 22 December 2022 and 15 February 2023. Outcome measuresMortality within 15 days after hospital discharge. ResultsA total of 987 cases with new COVID-19 variants (Omicron BA.5.2.48 and B.7.14) were eventually included, among them, 153 (15.5%) died. Non-invasive ventilation, intubation, myoglobin, international normalised ratio, age, number of diagnoses, respiratory rate, pulse, neutrophil count and albumin were the most important predictors of mortality among new COVID-19 variants. The area under the curve of logistic regression (LR), decision tree (DT) and Extreme Gradient Boosting (XGBoost) models were 0.959, 0.883 and 0.993, respectively. The diagnostic accuracy was 0.926 for LR, 0.918 for DT and 0.977 for XGBoost. XGBoost model had the highest sensitivity (0.908) and specificity (0.989). ConclusionOur study developed and validated three practical models for predicting mortality in patients with new COVID-19 variants. All models performed well, and XGBoost was the best-performing model. …

ObjectiveTo investigate reasons for encounter in telephone triage contacts to an out-of-hours primary care service for which general practitioners (GPs) use video consultations (video contact), overall and stratified for patient age and time of day. DesignA cross-sectional questionnaire study among GPs doing telephone triage in an out-of-hours primary care service. The questionnaire was integrated into the electronic patient registration system, popping up after every third video contact. This setup automatically linked patient register data, including age and sex, with the questionnaire data. SettingThe study was conducted from 5 September 2022 to 21 December 2022 at the out-of-hours primary care service in the Central Denmark Region. Participants649 volunteer GPs who answered 2452 questionnaires. Main outcome measuresReasons for encounter in video contacts registered with codes from International Classification of Primary Care (ICPC) coding system, V.2 (ICPC-2). ResultsGPs doing telephone triage in out-of-hours primary care used video contacts for a broad range of ICPC-2 codes within few ICPC-2 chapters. 83% of all reasons for encounter were due to symptoms in chapters S ‘Skin’ (34.5%), R ‘Respiratory’ (21.8%), A ‘General and unspecified’ (14.7%) and L ‘Musculoskeletal’ (12.0%) in the ICPC-2 classification system. Video contacts concerning skin and musculoskeletal symptoms were more frequent among older children and adults compared with young children. Respiratory symptoms and general and unspecified symptoms dominated by fever were more frequent among video contacts for young children compared with older children and adults. ConclusionOur study suggests a focused use of video contacts in an out-of-hours primary care setting; the majority of registered ICPC-2 codes were within few ICPC-2 chapters. …