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Jonsson-Oldenbüttel, Celia; Ghosn, Jade; van der Valk, Marc; Florence, Eric; Vera, Francisco; De Wit, Stéphane; Rami, Agathe; Bonnet, Fabrice; Hocqueloux, Laurent; Hove, Kai; Ait-Khaled, Mounir; DeMoor, Rebecca; Bontempo, Gilda; Latham, Christine L.; Gutner, Cassidy A.; Iyer, Supriya; Gill, Martin; Czarnogorski, Maggie; D’Amico, Ronald; van Wyk, Jean
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background: Cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months (Q2M) is a complete regimen for the maintenance of HIV-1 virologic suppression. Here, we report Month 12 clinical outcomes in patient study participants (PSPs) in the CARISEL study. Setting: CARISEL is a Phase 3b implementation–effectiveness study. Methods: CARISEL was designed as a two-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, the study is single arm, unblinded, and interventional; all PSPs switched from daily oral therapy to CAB + RPV LA dosed Q2M. The primary objective was to evaluate the perceived acceptability, appropriateness, and feasibility of CAB + RPV LA implementation for staff participants (presented separately). Clinical secondary endpoints assessed through Month 12 included: the proportion of PSPs with plasma HIV-1 RNA ≥50 copies/mL and
Læs mere Tjek på PubMedBarth, Shannon K.; Monroe, Anne K.; Houston, Patricia; Benator, Debra; Horberg, Michael; Castel, Amanda D.; On behalf of the DC Cohort Executive Committee
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background: Studies on the incidence of COVID-19 among persons with HIV (PWH) present varied results. Few studies have investigated the impact of COVID-19 infection on health and socioeconomic factors or COVID-19 stigma. We sought to measure the incidence and severity of COVID-19 infection among a cohort of PWH, characterize associated risk factors and impact, and document perceptions of COVID-19-related stigma. Methods: Data for this cross-sectional study come from the COVID-19 survey of participants in the DC Cohort longitudinal study from October 30, 2020 through December 31, 2022. Survey results were linked to electronic health records, including HIV labs and COVID test results. We conducted analyses comparing demographic, socioeconomic, HIV measures, and stigma among those with and without self-reported COVID-19. Results: Out of 1,972 survey respondents, 17% self-reported COVID-19 infection, with greatest incidence in the Omicron wave of the pandemic. We found statistically significant differences by age, employment status, essential worker status, education, and household income. Longer duration of HIV diagnosis was associated with greater incidence of COVID-19. PWH who were overweight or obese had greater incidence of COVID-19 compared to those who were not. Over 40% of PWH with COVID-19 reported experiencing at least one form of COVID-19-related stigma. Conclusion: We observed a high incidence of COVID-19 infection among PWH in DC. Further, a substantial proportion of PWH with COVID-19 reported experiencing COVID-19 related stigma. These findings add to the existing literature on COVID-19 co-infection among PWH and highlight the need for awareness and support for those experiencing COVID-19 stigma. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedJi, Cheng; Chen, Liting; Kaypaghian, Marina
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Garrett, Nigel; Dintwe, One; Monaco, Cynthia L.; Jones, Megan; Seaton, Kelly E.; Church, E. Chandler; Grunenberg, Nicole; Hutter, Julia; deCamp, Allan; Huang, Yunda; Lu, Huiyin; Mann, Philipp; Robinson, Samuel T.; Heptinstall, Jack; Jensen, Ryan L.; Pantaleo, Giuseppe; Ding, Song; Koutsoukos, Marguerite; Hosseinipour, Mina C.; Van Der Meeren, Olivier; Gilbert, Peter B.; Ferrari, Guido; Andersen-Nissen, Erica; McElrath, M. Juliana; Tomaras, Georgia D.; Gray, Glenda E.; Corey, Lawrence; Kublin, James G.; on behalf of the HVTN 108 and HVTN 111 Study Teams
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Despite progress in HIV prevention and treatment, an estimated 1.3 million people were newly infected with HIV in 2022,1 highlighting the urgent need for an effective vaccine. To date, the RV144 trial remains the only HIV vaccine trial that has demonstrated partial efficacy against acquisition.2 The Pox-Protein Public-Private Partnership (P5) was established with the aims of improving on RV144 by developing a vaccine capable of protecting against a broader diversity of HIV strains and achieving a better understanding of immune responses associated with preventing HIV infection.3 Vaccine concepts in the P5 program have focused on clade C immunogens, targeting predominant strains of East and Southern Africa, where approximately half of the 39 million people living with HIV reside.1 Despite progress in HIV prevention and treatment, an estimated 1.3 million people were newly infected with HIV in 2022,1 highlighting the urgent need for an effective vaccine. To date, the RV144 trial remains the only HIV vaccine trial that has demonstrated partial efficacy against acquisition.2 The Pox-Protein Public-Private Partnership (P5) was established with the aims of improving on RV144 by developing a vaccine capable of protecting against a broader diversity of HIV strains and achieving a better understanding of immune responses associated with preventing HIV infection.3 Vaccine concepts in the P5 program have focused on clade C immunogens, targeting predominant strains of East and Southern Africa, where approximately half of the 39 million people living with HIV reside.1 The RV144 regimen, originally designed to protect against subtype B/E strains, was adapted to incorporate clade C antigens and adjuvanted with MF59®.4 This regimen demonstrated adequate immunogenicity in the HVTN100 phase 1/2a trial,5 and was further evaluated in the HVTN702 efficacy trial in South Africa, but ultimately discontinued due to non-efficacy.6 In parallel, the P5 designed the correlates program: a series of phase 1/2a trials to evaluate vaccine candidates based on favorable immune profiles of putative correlates of protection. These trials employed novel prime-boost and co-administration regimens, varied protein doses, and used new adjuvants and vaccine delivery systems, with an emphasis on shared immunological endpoints to allow for cross-study comparisons. Preclinical studies have shown promising immune responses using DNA/protein combination vaccines.7,8 A comparison of responses between HVTN100 (ALVAC) and HVTN111 (DNA) trials indicated that DNA priming with a protein boost led to increased antibody and cellular responses compared to priming with the canarypox vector.9 In the HVTN105 trial, both a DNA prime-protein boost and a co-administration regimen induced potent and durable V1/V2 binding antibody responses (a known correlate of lower HIV-1 infection risk in RV144), with co-administration inducing early antibody responses.10 Furthermore, in the HVTN096 trial, including gp120 Env protein at the priming stage, co-administered with either NYVAC or DNA, elicited earlier and even greater antibody responses.11 The adjuvant system 01 (AS01) has been successfully tested in vaccine trials for other infectious diseases including malaria,12 shingles,13,14 and tuberculosis.15 Some HIV vaccine studies have also used AS01 and have shown that it contributes to the induction of robust and persistent cellular and humoral responses.16,17 MF59® has likewise been used in several licensed vaccines and pre-clinical studies,18 inducing strong and durable T-cell memory and humoral responses. MF59® was also used in HVTN studies with ALVAC 5 and was therefore chosen for comparison with AS01B in this trial. Thus, the aim of the HVTN108 trial was to evaluate the safety and immunogenicity of the DNA vaccine with different HIV clade C protein doses, adjuvanted with MF59® or AS01B, and dosed in prime-boost or co-administration regimens. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedHernandez, Alexandra L.; Hilton, Joan F.; Weatherly, Christopher Scott; Berry-Lawhorn, J. Michael; Jay, Naomi; Brickman, Cristina; Wang, Chia-ching J; Kauffman, Jason; Calderon, Joanne; Farhat, Sepideh; Costa, Maria DA; Akha, Arezou Sadighi; Darragh, Teresa; Palefsky, Joel M.
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background: Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSIL). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years of age, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). Setting: We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, California. Methods: 129 MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with biopsy of visible lesions. Results: Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (OR:45.1, 95% CI:15.8-129), other oncogenic HPV types (OR:5.95, 95% CI:2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. Conclusion: The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remain very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedRohr, Julia K.; Manne-Goehler, Jennifer; Gómez-Olivé, F. Xavier; Kahn, Kathleen; Bärnighausen, Till W.
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background: As people with HIV grow older, stable engagement in care is essential for healthy aging. We evaluate the HIV care cascade for older adults in rural South Africa at two time points cross-sectionally and assess movement in the cascade over time. Setting: We evaluated cascade stage at Waves 1 (2014-2015) and 2 (2018-2019) of HAALSI, a population-based longitudinal cohort study in Mpumalanga Province, South Africa. Methods: Biomarker screening defined cascade stages (HIV+/No antiretroviral therapy [ART]; ART+/Unsuppressed viral load; ART+/Suppressed viral load). Between-wave probability of death, cascade progression, regression, cascade transitions, and sociodemographic predictors were assessed with Poisson regression. The impact of death was considered using the Fine and Gray competing risk model. Results: We observed higher prevalence of ART with viral suppression over time (50% in Wave 1 vs. 70% in Wave 2). Among those alive, the oldest age group (70+ yo) was most likely to have cascade progression (aRR for treatment initiation vs. 40-49 yo: 1.38 (95% CI: 1.02-1.86)). However, there was significant risk of death and cascade regression. Death between waves reached 40% for 70+ year olds who were ART+/Unsuppressed. In competing risk models, older age was associated with equivalent or less cascade progression. Conclusion: Older age groups who were unsuppressed on treatment and males had poorer cascade outcomes. Improvements observed in HIV treatment coverage over time for older adults must be interpreted in the context of high risk of death for older HIV-positive adults, especially among those failing treatment. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedRoss, Jeremy L; Teeraananchai, Sirinya; Avihingsanon, Anchalee; Lee, Man Po; Ditangco, Rossana; Rajasuriar, Reena; Kim, Jung Ho; Gatechompol, Sivaporn; Chan, Iris; Echanis Melgar, Maria Isabel; Chong, Meng Li; Jiamsakul, Awachana; Sohn, Annette H.; Law, Matthew; Choi, Jun Yong; on behalf of the Substance use, Stigma, Depression and Disability (S2D2) study group of IeDEA Asia-Pacific
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background Mental health and substance use disorders are common among people living with HIV and are associated with high-risk sexual behaviors, such as unprotected sex and multiple sexual partners, but Asia-Pacific data are limited. Methods Adult PLHIV in care at five Asia-Pacific HIV clinics were enrolled at routine clinic visits between July 2019 and June 2020. Depression, substance use, sexual practice and socio-demographic data were collected using PHQ-9, ASSIST, and a study-specific questionnaire. Clinical data were accessed from medical records. Risk factors for medium- to high-risk sexual practices, defined based on total scores from the sexual practice questionnaire assessing number of sexual partners and condom use, were analyzed using logistic regression. Moderate to severe depression was defined as a PHQ-9 score >9, and moderate- to high-risk substance use as an ASSIST score >11 for alcohol or >4 for other substances. Results Among 723 participants, median age was 38 years, 89% were male, 99% were on ART and 37% had medium- to high-risk sexual practices. Medium- to high-risk sexual practices were more common among those
Læs mere Tjek på PubMedLouise Dahl HultqvistJens Bo AndersenCarl Martin NilssonCharlotte Uldahl JansenMorten RybtkeTim Holm JakobsenThomas Eiland NielsenKlaus QvortrupClaus MoserMichael GrazKatrine QvortrupTim Tolker-NielsenMichael Givskov1Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark2Department of Chemistry, Technical University of Denmark, Lyngby, Denmark3Department of Biomedical Sciences, CFIM, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark4Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, Anne-Catrin Uhlemann
Antimicrobial Agents And Chemotherapy, 9.05.2024
Tilføjet 9.05.2024
Journal of Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin improves the treatment of primary pneumonia or superinfection caused by amoxicillin-sensitive or -resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and -resistant bacteria and population dynamics analysis. Our findings demonstrate that flagellin allows for a 200-fold reduction in the antibiotic dose, achieving the same therapeutic effect observed with antibiotic alone. Adjunct treatment also reduced the selection of antibiotic-resistant bacteria in contrast to the antibiotic monotherapy. Finally, we developed a mathematical model that captured the population dynamics and estimated a 20-fold enhancement immune-modulatory factor on bacterial clearance. This work paves the way for the development of host-directed therapy and refinement of treatment by modeling.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract Background Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs).Methods We used data from UK Biobank, The Trøndelag Health Study (HUNT), and Michigan Genomics Initiative (MGI) to conduct genome-wide association studies (GWASs) and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs.Results One genome-wide significant (P ≤ 5E-08) locus was associated with the susceptibility to upper UTI, located near TSN in the female-only analysis. Additionally, we identified suggestive (P ≤ 5E-06) loci near DNAI3 for the females, SCAMP1−AS1 for the males, and near TSN, LINC00603, and HLA-DQA2 for both sexes. In MR analyses, higher genetically predicted lifetime smoking scores were associated with an increased risk of developing upper UTI for females and both sexes (OR of 4.84, P = 4.50E-06 and OR of 2.79, P = 3.02E-05, respectively).Conclusions We found that genetic variants near TSN was associated with the risk of upper UTIs among females. In addition, we found several genetic loci with suggestive associations with the risk of upper UTIs. Finally, MR analyses found smoking to be a potential causal risk factor for upper UTIs.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract In an area endemic with Indian visceral leishmaniasis (VL), we performed direct xenodiagnosis to evaluate the transmission of Leishmania donovani from patients with VL–human immunodeficiency virus (HIV) coinfection to the vector sandflies, Phlebotomus argentipes. Fourteen patients with confirmed VL-HIV coinfection, with a median parasitemia of 42 205 parasite genome/mL of blood, were exposed to 732 laboratory-reared pathogen-free female P argentipes sandflies on their lower arms and legs. Microscopy revealed that 16.66% (122/732) of blood-fed flies were xenodiagnosis positive. Notably, 93% (13/14) of the VL-HIV group infected the flies, as confirmed by quantitative polymerase chain reaction and/or microscopy, and were 3 times more infectious than those who had VL without HIV.
Læs mere Tjek på PubMedMarshall, H., Ward, J., Wang, B., Andraweera, P., McMillan, M., Flood, L., Bell, C., Sisnowski, J., Krause, V., Webby, R., Childs, E., Gunathilake, M., Egoroff, N., Leong, L., Lawrence, A., Baird, R., Freeman, K., Menouhos, D., Whiley, D. M., Karnon, J., van Hal, S., Lahra, M. M.
BMJ Open, 8.05.2024
Tilføjet 8.05.2024
IntroductionThe effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections. Methods and analysesThis observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4–7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison. Ethics and disseminationThe protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.
Læs mere Tjek på PubMedSalamun, J., Da Silva, T., Ustero, P., Gosmain, Y., Guessous, I., Calmy, A., Spechbach, H.
BMJ Open, 8.05.2024
Tilføjet 8.05.2024
IntroductionSARS-CoV-2 mainly infects respiratory endothelial cells, which is facilitated through its spike protein binding to heparan sulphate. Calcium dobesilate (CaD) is a well-established, widely available vasoactive and angioprotective drug interacting with heparan sulphate, with the potential to interfere with the uptake of SARS-CoV-2 by epithelial cells. The CADOVID trial aims to evaluate the efficacy and safety of CaD in reducing the SARS-CoV-2 viral load in non-hospitalised adult patients diagnosed with COVID-19, confirmed by a positive SARS-CoV-2 PCR, including its efficacy to reduce the impact of persistent COVID-19 symptoms. Methods and analysisThis is a randomised, placebo-controlled, double-blind, monocentric phase II trial. Enrolment began in July 2022. A total of 74 adult patients will be randomly allocated to the CaD arm or the placebo group with a 1:1 ratio, respectively. Participants in the intervention arm will receive two capsules of CaD 500 mg two times per day and the placebo arm will receive two matching capsules of mannitol 312.5 mg two times per day, with a treatment period of 7 days for both arms, followed by a 77-day observational period without treatment administration. Participants will be asked to complete secured online questionnaires using their personal smartphone or other electronic device. These include a COVID-19 questionnaire (assessing symptoms, temperature measurement, reporting of concomitant medication and adverse events), a COVID-19 persistent symptoms’ questionnaire and the Short Form 12-Item (SF-12) survey. SARS-CoV-2 PCR testing will be performed on nasopharyngeal swabs collected on days 1, 4, 8 and 21. The primary endpoint is the reduction from baseline of SARS-CoV-2 viral load determined by RT-PCR at day 4. Ethics and disseminationThis trial has received approval by the Geneva Regional Research Ethics Committee (2022-00613) and Swissmedic (701339). Dissemination of results will be through presentations at scientific conferences and publication in scientific journals. Trial registration number NCT05305508; Clinicaltrials.gov; Swiss National Clinical Portal Registry (SNCTP 000004938).
Læs mere Tjek på PubMedKidman, R., Mwera, J., Rui, Y., Breton, E., Zulu, A., Behrman, J., Kohler, H.-P.
BMJ Open, 8.05.2024
Tilføjet 8.05.2024
PurposeThe Adverse Childhood Experiences (ACE) cohort of the Malawi Longitudinal Study of Families and Health (MLSFH-ACE) is a study of adolescents surveyed during 2017–2021. It provides an important opportunity to examine the longitudinal impact of ACEs on health and development across the early life course. The MLSFH-ACE cohort provides rich data on adolescents, their children and adult caregivers in a low-income, high-HIV-prevalence context in sub-Saharan Africa (SSA). ParticipantsThe MLSFH-ACE cohort is a population-based study of adolescents living in three districts in rural Malawi. Wave 1 enrolment took place in 2017–2018 and included 2061 adolescents aged 10–16 years and 1438 caregivers. Wave 2 took place in 2021 and included data on 1878 adolescents and 208 offspring. Survey instruments captured ACEs during childhood and adolescence, HIV-related behavioural risk, mental and physical health, cognitive development and education, intimate partner violence (IPV), marriage and aspirations, early transitions to adulthood and protective factors. Biological indicators included HIV, herpes simplex virus and anthropometric measurements. Findings to dateKey findings include a high prevalence of ACEs among adolescents in Malawi, a low incidence of HIV and positive associations between ACE scores and composite HIV risk scores. There were also strong associations between ACEs and both IPV victimisation and perpetration. Future plansMLSFH-ACE data will be publicly released and will provide a wealth of information on ACEs and adolescent outcomes in low-income, HIV-endemic SSA contexts. Future expansions of the cohort are planned to capture data during early adulthood.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Prior to September 2021, 55,000–90,000 hospital inpatients in England were identified as having a potentially nosocomial SARS-CoV-2 infection. This includes cases that were likely missed due to pauci- or asymptomatic infection. Further, high numbers of healthcare workers (HCWs) are thought to have been infected, and there is evidence that some of these cases may also have been nosocomially linked, with both HCW to HCW and patient to HCW transmission being reported. From the start of the SARS-CoV-2 pandemic interventions in hospitals such as testing patients on admission and universal mask wearing were introduced to stop spread within and between patient and HCW populations, the effectiveness of which are largely unknown. Materials/methods Using an individual-based model of within-hospital transmission, we estimated the contribution of individual interventions (together and in combination) to the effectiveness of the overall package of interventions implemented in English hospitals during the COVID-19 pandemic. A panel of experts in infection prevention and control informed intervention choice and helped ensure the model reflected implementation in practice. Model parameters and associated uncertainty were derived using national and local data, literature review and formal elicitation of expert opinion. We simulated scenarios to explore how many nosocomial infections might have been seen in patients and HCWs if interventions had not been implemented. We simulated the time period from March-2020 to July-2022 encompassing different strains and multiple doses of vaccination. Results Modelling results suggest that in a scenario without inpatient testing, infection prevention and control measures, and reductions in occupancy and visitors, the number of patients developing a nosocomial SARS-CoV-2 infection could have been twice as high over the course of the pandemic, and over 600,000 HCWs could have been infected in the first wave alone. Isolation of symptomatic HCWs and universal masking by HCWs were the most effective interventions for preventing infections in both patient and HCW populations. Model findings suggest that collectively the interventions introduced over the SARS-CoV-2 pandemic in England averted 400,000 (240,000 – 500,000) infections in inpatients and 410,000 (370,000 – 450,000) HCW infections. Conclusions Interventions to reduce the spread of nosocomial infections have varying impact, but the package of interventions implemented in England significantly reduced nosocomial transmission to both patients and HCWs over the SARS-CoV-2 pandemic.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins——nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Early prediction of mortality in individuals with HIV (PWH) has perpetually posed a formidable challenge. With the widespread integration of machine learning into clinical practice, some researchers endeavor to formulate models predicting the mortality risk for PWH. Nevertheless, the diverse timeframes of mortality among PWH and the potential multitude of modeling variables have cast doubt on the efficacy of the current predictive model for HIV-related deaths. To address this, we undertook a systematic review and meta-analysis, aiming to comprehensively assess the utilization of machine learning in the early prediction of HIV-related deaths and furnish evidence-based support for the advancement of artificial intelligence in this domain. Methods We systematically combed through the PubMed, Cochrane, Embase, and Web of Science databases on November 25, 2023. To evaluate the bias risk in the original studies included, we employed the Predictive Model Bias Risk Assessment Tool (PROBAST). During the meta-analysis, we conducted subgroup analysis based on survival and non-survival models. Additionally, we utilized meta-regression to explore the influence of death time on the predictive value of the model for HIV-related deaths. Results After our comprehensive review, we analyzed a total of 24 pieces of literature, encompassing data from 401,389 individuals diagnosed with HIV. Within this dataset, 23 articles specifically delved into deaths during long-term follow-ups outside hospital settings. The machine learning models applied for predicting these deaths comprised survival models (COX regression) and other non-survival models. The outcomes of the meta-analysis unveiled that within the training set, the c-index for predicting deaths among people with HIV (PWH) using predictive models stands at 0.83 (95% CI: 0.75–0.91). In the validation set, the c-index is slightly lower at 0.81 (95% CI: 0.78–0.85). Notably, the meta-regression analysis demonstrated that neither follow-up time nor the occurrence of death events significantly impacted the performance of the machine learning models. Conclusions The study suggests that machine learning is a viable approach for developing non-time-based predictions regarding HIV deaths. Nevertheless, the limited inclusion of original studies necessitates additional multicenter studies for thorough validation.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding. Case presentation We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment. Conclusions The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Sepsis is a common syndrome of multiorgan system dysfunction secondary to the dysregulated inflammatory response to infection. The role of pancreatic stone protein (PSP) in diagnosing sepsis has been investigated in previous studies. The meta-analysis aimed to comprehensively investigate the diagnostic value of PSP in identifying sepsis. Methods PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), were systematically searched. Studies investigating the diagnostic performance of PSP were included. Pooled sensitivity, specificity, positive Likelihood Ratio (+ LR) and negative Likelihood Ratio (-LR), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (SROC) were calculated. Results The sensitivity of PSP was 0.88 (95% CI: 0.77–0.94), and the pooled specificity was 0.78 (95% CI: 0.65–0.87). Pooled + LR, -LR, and DOR were 4.1 (2.3, 7.3), 0.16 (0.07, 0.34), and 26 (7, 98). The AUC value for the SROC of PSP was 0.90 (0.87, 0.92). The pooled sensitivity, specificity, + LR and - LR, and DOR for PSP among neonates were 0.91 (95% CI: 0.84, 0.96), 0.66 (95% CI: 0.58, 0.74), 3.97 (95% CI: 0.53, 29.58), 0.13 (95% CI: 0.02, 1.00), and 31.27 (95% CI: 0.97, 1004.60). Conclusions This study indicates that PSP demonstrated favorable diagnostic accuracy in detecting sepsis. Well-designed studies are warranted to ascertain the value of PSP measurement to guide early empirical antibiotic treatment, particularly in neonates.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic review and meta-analysis aimed to determine the pooled incidence density of mortality and identify potential predictors among HIV-infected children receiving ART, from studies conducted in various parts of Ethiopia. Methods A comprehensive database search was made in Excerpta Medica, PubMed, Web of Science, African Journals Online, Google Scholar, and Scopus. We reported results following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. Excel Spreadsheet and STATA Version 14 software were used for data abstraction and meta-analysis, respectively. Statistical heterogeneity among studies was assessed using I2 statistics. Meta-regression and subgroup analysis were performed to further explore the sources of statistical heterogeneity. Moreover, publication bias and a leave-out-one sensitivity analysis were performed. Results Twenty-two articles involving 8,731 participants met inclusion criteria and were included. The pooled incidence density of mortality was 3.08 (95% confidence interval (CI), 2.52 to 3.64) per 100 child years. Predictors of mortality were living in rural areas (hazard ratio (HR), 2.18 [95% CI, 1.20 to 3.98]), poor adherence to ART (HR, 2.85 [ 95% CI, 1.39 to 5.88]), failure to initiate co-trimoxazole preventive therapy (HR, 2.16 [95% CI, 1.52 to 3.07]), anemia (HR, 2.28 [95% CI, 1.51 to 3.45]), opportunistic infections (HR, 1.52 [ 95% CI, 1.15 to 2.00]), underweight (HR, 1.74 [95% CI, 1.26 to 2.41]), wasting (HR, 2.54 [95% CI, 1.56 to 4.16]), stunting (HR, 2.02 [95% CI, 1.63 to 2.51]), World Health Organization classified HIV clinical stages III and IV (HR, 1.71 [95% CI, 1.42 to 2.05]), and Nevirapine-based regimens (HR, 3.91 [95% CI, 3.09 to 4.95]). Conclusions This study found that the overall mortality rate among HIV-infected children after ART initiation was high. Therefore, high-level commitment and involvement of responsible caregivers, healthcare providers, social workers, and program managers are of paramount importance to identify these risk factors and thus enhance the survival of HIV-infected children receiving ART.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. Methods After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants’ receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. Results 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1–14.3%), and 8.9% (95%CI 5.6–12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12–5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38–13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07–3.87). Conclusion We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community). Methods This Swedish nationwide population-based cohort study (2006–2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up. Results Overall, 91.6% of CDI cases were hospital acquired, and 16.8% presented with recurrence(s); 74.8%of cases were ≥ 65 years and 54.2% were women. Compared to individuals without CDI, in-hospital stay rates were 18.01 times higher after CDI (95% CI 17.40–18.63, first-year: 27.4 versus 1.6 days), 9.45 times higher in-hospital admission (95% CI 9.16–9.76, first-year: 2.6 versus 1.3 hospitalisations), 3.94 times higher outpatient visit (95% CI 3.84–4.05, first-year: 4.0 versus 1.9 visits) and 3.39 times higher dispensed prescriptions rates (95% CI 3.31–3.48, first-year: 25.5 versus 13.7 prescriptions). For all outcomes, relative risks were higher among the younger (
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Chile rapidly implemented an extensive COVID-19 vaccination campaign, deploying a diversity of vaccines with a strategy that prioritized the elderly and individuals with comorbidities. This study aims to assess the direct impact of vaccination on the number of COVID-19 related cases, hospital admissions, ICU admissions and deaths averted during the first year and a half of the campaign. Methods Via Chile’s transparency law, we obtained access to weekly event counts categorized by vaccination status and age. Integrating this data with publicly available census and vaccination coverage information, we conducted a comparative analysis of weekly incidence rates between vaccinated and unvaccinated groups from December 20, 2020 to July 2, 2022 to estimate the direct impact of vaccination in terms of the number of cases, hospitalizations, ICU admissions and deaths averted, using an approach that avoids the need to explicitly specify the effectiveness of each vaccine deployed. Results We estimated that, from December 20, 2020 to July 2, 2022 the vaccination campaign directly prevented 1,030,648 (95% Confidence Interval: 1,016,975-1,044,321) cases, 268,784 (95% CI: 264,524-273,045) hospitalizations, 85,830 (95% CI: 83,466-88,194) ICU admissions and 75,968 (95% CI: 73,909-78,028) deaths related to COVID-19 among individuals aged 16 years and older. This corresponds to a reduction of 26% of cases, 66% of hospital admissions, 70% of ICU admissions and 67% of deaths compared to a scenario without vaccination. Individuals 55 years old or older represented 67% of hospitalizations, 73% of ICU admissions and 89% of deaths related to COVID-19 prevented. Conclusions This study highlights the role of Chile\'s vaccination campaign in reducing COVID-19 disease burden, with the most substantial reductions observed in severe outcomes.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract South Korea’s remarkable success in controlling the spread of COVID-19 during the pre-Omicron period was based on extensive contact tracing and large-scale testing. Here we suggest a general criterion for tracing and testing based on South Korea’s experience, and propose a new framework to assess tracing and testing. We reviewed papers on South Korea’s response to COVID-19 to capture its concept of tracing and testing. South Korea expanded its testing capabilities to enable group tracing combined with preemptive testing, and to conduct open testing. According to our proposed model, COVID-19 cases are classified into 4 types: confirmed in quarantine, source known, source unknown, and unidentified. The proportion of the first two case types among confirmed cases is defined as “traced proportion”, and used as the indicator of tracing and testing effectiveness. In conclusion, South Korea successfully suppressed COVID-19 transmission by maintaining a high traced proportion (> 60%) using group tracing in conjunction with preemptive testing as a complementary strategy to traditional contact tracing.
Læs mere Tjek på PubMedKento TominagaShogo OzakiShohei SatoTsutomu KatayamaYuki NishimuraKimiho OmaeWataru IwasakiaDepartment of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-0882, JapanbDepartment of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, JapancDepartment of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, JapandDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-0882, JapaneAtmosphere and Ocean Research Institute, The University of Tokyo, Chiba 277-8564, JapanfInstitute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0032, JapangCollaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8657, Japan
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedAlexandra BlancoRobert A. CoronadoNeha ArunKelly MaRoy D. DarCollin KiefferaDepartment of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801bDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedDan PollackTakashi NozoeEdo KussellaDepartment of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10003bDepartment of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo 153-8902, JapancResearch Center for Complex Systems Biology, The University of Tokyo, Tokyo 153-8902, JapandUniversal Biology Institute, The University of Tokyo, Tokyo 113-0033, JapaneDepartment of Physics, New York University, New York, NY 10003
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedJosé L. FachiBlanda Di LucciaSusan GilfillanHao-Wei ChangChristina SongJiye ChengMarina CellaMarco Aurelio VinoloJeffrey I. GordonMarco ColonnaaDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110bDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305cClinical Biomarkers and Diagnostics, Amgen Inc., South San Francisco, CA 94080dEdison Family Center for Genome Sciences and Systems Biology, and the Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110eDepartment of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, Sao Paulo 13083-862, Brazil
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedDaisuke KobayashiYusuke InoueRyosuke SuzukiMami MatsudaHiroshi ShimodaAstri Nur FaizahYoshihiro KakuKeita IshijimaYudai KurodaKango TatemotoMilagros Virhuez-MendozaMichiko HaradaAyano NishinoMizue InumaruKenzo YonemitsuRyusei KuwataAi TakanoMamoru WatanabeYukiko HigaKyoko SawabeKen MaedaHaruhiko IsawaaDepartment of Medical Entomology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, JapanbManagement Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, JapancDepartment of Veterinary Science, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, JapandJoint Graduate School of Veterinary Medicine, Yamaguchi University, Yamaguchi City, Yamaguchi 753-8515, JapaneDepartment of Virology II, National Institute of Infectious Diseases, Musashimurayama City, Tokyo 208-0011, JapanfFaculty of Veterinary Medicine, Okayama University of Science, Imabari City, Ehime 794-8555, Japan
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedDongHo KimMichael A. CianfroccoKristen J. VerheyGregory A. SmithaDepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611bLife Sciences Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109cDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedRachel L. PatersonMarco P. La MannaVictoria Arena De SouzaAndrew WalkerDawn Gibbs-HoweRakesh KulkarniJoannah R. FergussonNitha Charles MulakkalMauro MonteiroWilawan BunjobpolMarcin DembekMagdalena Martin-UrdirozTressan GrantClaire BarberDiana J. Garay-BaqueroLiku Bekele TezeraDavid LowneCamille Britton-RivetRobert PengellyNatalia ChepisiukPraveen K. SinghAmanda P. WoonAlex S. PowleslandMichelle L. McCullyNadia CaccamoMariolina SalioGiusto Davide BadamiLucy DorrellAndrew KnoxRoss RobinsonPaul ElkingtonFrancesco DieliMarco LeporeSarah LeonardLuis F. GodinhoaImmunocore Ltd., Abingdon, Oxfordshire OX14 4RY, United KingdombDepartment of Biomedicine, Neurosciences and Advanced Diagnostic, University of Palermo, Palermo 90127, ItalycCentral Laboratory of Advanced Diagnosis and Biomedical Research, Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone, University of Palermo, Palermo 90127, ItalydNational Institute for Health and Care Research, Biomedical Research Centre and Institute for Life Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, United Kingdom
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedRichard J. LamontaDepartment of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, KY 40202
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedAbbas YadegarHaggai Bar-YosephTanya Marie MonaghanSepideh PakpourAndrea SeverinoEd J. KuijperWiep Klaas SmitsElisabeth M. TerveerSukanya NeupaneAli Nabavi-RadJavad SadeghiGiovanni CammarotaGianluca IaniroEstello Nap-HillDickson LeungKaren WongDina Kao1Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran2Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel3Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel4National Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom5Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom6School of Engineering, Faculty of Applied Sciences, UBC, Okanagan Campus, Kelowna, British Columbia, Canada7Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy8Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy9Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy10Center for Microbiota Analysis and Therapeutics (CMAT), Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands11Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada12Department of Medicine, Division of Gastroenterology, St Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada, Christopher Staley
Clinical Microbiology Reviews, 8.05.2024
Tilføjet 8.05.2024
Lorenzo Subissi, James Richard Otieno, Nathalie Worp, Homa Attar Cohen, Bas B. Oude Munnink, Laith J. Abu-Raddad, Erik Alm, Amal Barakat, Wendy S. Barclay, Jinal N. Bhiman, Leon Caly, Meera Chand, Mark Chen, Ann Cullinane, Tulio de Oliveira, Christian Drosten, Julian Druce, Paul Effler, Ihab El Masry, Adama Faye, Elodie Ghedin, Rebecca Grant, Bart L. Haagmans, Christian Happi, Belinda L. Herring, Emma B. Hodcroft, Juniorcaius Ikejezie, Victoria Katawera, Zyleen Alnashir Kassamali, Yee-Sin Leo, Gabriel M. Leung, Rebecca J. Kondor, Marco Marklewitz, Jairo Mendez-Rico, Nada M. Melhem, Vincent Munster, Karen Nahapetyan, Dhamari Naindoo, Djin-Ye Oh, Thomas P. Peacock, Malik Peiris, Zhibin Peng, Leo L. M. Poon, Andrew Rambaut, Senjuti Saha, Yinzhong Shen, Marilda M. Siqueira, Erik Volz, Sofonias K. Tessema, Volker Thiel, Henda Triki, Sylvie van der Werf, Karin von Eije, Jane Cunningham, Marion P. G. Koopmans, Anne von Gottberg, Anurag Agrawal, Maria D. Van Kerkhove
Nature, 8.05.2024
Tilføjet 8.05.2024
Infectious Disease Modelling, 8.05.2024
Tilføjet 8.05.2024
Publication date: Available online 7 May 2024 Source: Infectious Disease Modelling Author(s): J. Vanderlocht, S. Møgelmose, K. Van Kerckhove, P. Beutels, N. Hens
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013–2019) was characterized. Methods Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13—a molecular marker of artemisinin resistance. Result The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Universal coverage with insecticide-treated nets (ITNs) is important for malaria control and elimination. The emergence and intensification of insecticide resistance threatens progress made through the deployment of these interventions and has required the development of newer, more expensive ITN types. Understanding malaria prevention behaviour, including barriers and facilitators to net access and use, can support effective decision-making for the promotion and distribution of ITNs. Methods In-depth interviews and focus group discussions were conducted in 3 to 4 villages per district, in 13 districts across Burkina Faso, Mozambique, Nigeria and Rwanda from 2019 to 2022. Interviews were conducted in the local language, translated and transcribed in English, French or Portuguese. Transcripts were coded and analysed using Nvivo and ATLAS.ti. Results ITNs were obtained from mass distribution campaigns, antenatal care and immunization visits, and purchased on the private market in some locations. While there were divergent perspectives in whether the number of distributed nets were adequate, participants consistently expressed concerns of bias, discrimination, and a lack of transparency with the distribution process. ITNs were frequently used alongside other malaria prevention methods. The primary motivation for use was malaria prevention. While some participants reported using nets nightly throughout the year, other participants reported seasonal use, both due to the perceived higher density of mosquitoes and discomfort of sleeping under a net in the increased heat. Other barriers to consistent net use included activities that take place away from the home, sleeping patterns and arrangements, and sensitivity to the insecticides on the nets. Conclusions ITNs remain an important malaria control intervention. To ensure adequate and increased net access, distribution campaigns should consider family structures, available sleeping spaces, and other bed sharing preferences when identifying the number of nets needed for distribution. In addition, campaigns should allow for multiple options for net distribution points and timing to accommodate households remote to health services. Continuous distribution channels and complimentary distribution through the private sector could help fill gaps in coverage. Solutions are needed for outdoor malaria transmission, including alternative designs for ITNs, and improving access to complementary personal protective measures.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background The direct membrane feeding assay (DMFA), whereby gametocyte-infected blood is collected from human donors and from which mosquitoes feed through a membrane, is proving essential for assessing parameters influencing Plasmodium transmission potential in endemic countries. The success of DMFAs is closely tied to gametocyte density in the blood, with relatively high gametocytaemia ensuring optimal infection levels in mosquitoes. As transmission intensity declines with control efforts, the occurrence of asymptomatic individuals with low gametocyte densities, who can significantly contribute to the infectious reservoir, is increasing. This poses a limitation to studies relying on the experimental infection of large numbers of mosquitoes with natural isolates of Plasmodium. A simple, field-applicable method is presented for improving parasite infectivity by concentrating Plasmodium falciparum gametocytes. Methods Anopheles gambiae received one of the following 5 blood treatments through DMFA: (i) whole blood (WB) samples from naturally-infected donors; (ii) donor blood whose plasma was replaced with the same volume of Plasmodium-naive AB + serum (1:1 control); (iii) plasma replaced with a volume of malaria-naïve AB + serum equivalent to half (1:1/2), or to a quarter (1:1/4), of the initial plasma volume; and (v) donor blood whose plasma was fully removed (RBC). The experiment was repeated 4 times using 4 distinct wild parasite isolates. Seven days post-infection, a total of 1,095 midguts were examined for oocyst presence. Results Substituting plasma with reduced amounts (1:1/2 and 1:1/4) of Plasmodium-naive AB + serum led to a 31% and 17% increase of the mosquito infection rate and to a 85% and 308% increase in infection intensity compared to the 1:1 control, respectively. The full removal of plasma (RBC) reduced the infection rate by 58% and the intensity by 64% compared to the 1:1 control. Reducing serum volumes (1:1/2; 1:1/4 and RBC) had no impact on mosquito feeding rate and survival when compared to the 1:1 control. Conclusions Concentrating gametocytic blood by replacing natural plasma by lower amount of naive serum can enhance the success of mosquito infection. In an area with low gametocyte density, this simple and practical method of parasite concentration can facilitate studies on human-to-mosquito transmission such as the evaluation of transmission-blocking interventions.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Malaria vaccine introduction in endemic countries is a game-changing milestone in the fight against the disease. This article examines the inequity in the global pharmaceutical research, development, manufacturing, and trade landscape. The role of inequity in hindering progress towards malaria elimination is explored. The analysis finds that transformational changes are required to create an equity-enabling environment. Addressing the inequity is critical to maximizing the public health impact of vaccines and attaining sustainability. Avenues to catalyze progress by leveraging malaria vaccines and messenger ribonucleic acid (mRNA) technology are discussed.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Studies on haemosporidian diversity, including origin of human malaria parasites, malaria\'s zoonotic dynamic, and regional biodiversity patterns, have used target gene approaches. However, current methods have a trade-off between scalability and data quality. Here, a long-read Next-Generation Sequencing protocol using PacBio HiFi is presented. The data processing is supported by a pipeline that uses machine-learning for analysing the reads. Methods A set of primers was designed to target approximately 6 kb, almost the entire length of the haemosporidian mitochondrial genome. Amplicons from different samples were multiplexed in an SMRTbell® library preparation. A pipeline (HmtG-PacBio Pipeline) to process the reads is also provided; it integrates multiple sequence alignments, a machine-learning algorithm that uses modified variational autoencoders, and a clustering method to identify the mitochondrial haplotypes/species in a sample. Although 192 specimens could be studied simultaneously, a pilot experiment with 15 specimens is presented, including in silico experiments where multiple data combinations were tested. Results The primers amplified various haemosporidian parasite genomes and yielded high-quality mt genome sequences. This new protocol allowed the detection and characterization of mixed infections and co-infections in the samples. The machine-learning approach converged into reproducible haplotypes with a low error rate, averaging 0.2% per read (minimum of 0.03% and maximum of 0.46%). The minimum recommended coverage per haplotype is 30X based on the detected error rates. The pipeline facilitates inspecting the data, including a local blast against a file of provided mitochondrial sequences that the researcher can customize. Conclusions This is not a diagnostic approach but a high-throughput method to study haemosporidian sequence assemblages and perform genotyping by targeting the mitochondrial genome. Accordingly, the methodology allowed for examining specimens with multiple infections and co-infections of different haemosporidian parasites. The pipeline enables data quality assessment and comparison of the haplotypes obtained to those from previous studies. Although a single locus approach, whole mitochondrial data provide high-quality information to characterize species pools of haemosporidian parasites.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Malaria is a potentially life-threatening disease caused by Plasmodium protozoa transmitted by infected Anopheles mosquitoes. Controlled human malaria infection (CHMI) trials are used to assess the efficacy of interventions for malaria elimination. The operating characteristics of statistical methods for assessing the ability of interventions to protect individuals from malaria is uncertain in small CHMI studies. This paper presents simulation studies comparing the performance of a variety of statistical methods for assessing efficacy of intervention in CHMI trials. Methods Two types of CHMI designs were investigated: the commonly used single high-dose design (SHD) and the repeated low-dose design (RLD), motivated by simian immunodeficiency virus (SIV) challenge studies. In the context of SHD, the primary efficacy endpoint is typically time to infection. Using a continuous time survival model, five statistical tests for assessing the extent to which an intervention confers partial or full protection under single dose CHMI designs were evaluated. For RLD, the primary efficacy endpoint is typically the binary infection status after a specific number of challenges. A discrete time survival model was used to study the characteristics of RLD versus SHD challenge studies. Results In a SHD study with the continuous time survival model, log-rank test and t-test are the most powerful and provide more interpretable results than Wilcoxon rank-sum tests and Lachenbruch tests, while the likelihood ratio test is uniformly most powerful but requires knowledge of the underlying probability model. In the discrete time survival model setting, SHDs are more powerful for assessing the efficacy of an intervention to prevent infection than RLDs. However, additional information can be inferred from RLD challenge designs, particularly using a likelihood ratio test. Conclusions Different statistical methods can be used to analyze controlled human malaria infection (CHMI) experiments, and the choice of method depends on the specific characteristics of the experiment, such as the sample size allocation between the control and intervention groups, and the nature of the intervention. The simulation results provide guidance for the trade off in statistical power when choosing between different statistical methods and study designs.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background In Nigeria, seasonal malaria chemoprevention (SMC) is typically administered door-to-door to children under five by community medicine distributors during high transmission seasons. While door-to-door distribution (DDD) is exclusively employed in Nigeria as part of standard operating procedures of SMC programmes, some households access SMC through non-DDD channels, such as fixed-point distributions, health facilities, and private purchase. However, analysis of access to SMC medicines through non-DDD has been limited, with little evidence of its outcomes on adherence to the three-day complete course of SMC medicines and caregiver actions in the event of adverse reactions to SMC medicines. Methods Data were obtained from SMC end-of-round coverage surveys conducted in Nigeria in 2021 and 2022, including 25,278 households for the analysis. The proportion of households accessing SMC medicine through non-DDD and the distribution of various non-DDD sources of SMC medicines were described. Multivariate random-effects logistic regression models were performed to identify predictors of accessing SMC medicines through non-DDD. The associations between non-DDD, and caregiver-reporting of adherence to complete administration of SMC medicines and caregiver actions in the event of adverse reactions to SMC medicines were also assessed. Results Less than 2% (314/24003) of households accessed SMC medicines through non-DDD in the states surveyed. Over 60% of non-DDD access was via health facility personnel and community medicine distributors from different locations. Variables associated with non-DDD access included heads of household being born in the local state (OR = 0.68, 95% CI 0.47 to 0.90), households residing in the study state since the first cycle of the SMC round (OR = 0.39, 95% CI 0.17 to 0.88), households with high wealth index (OR = 1.36, 95% CI 1.01 to 1.82), and caregivers hearing about date of SMC delivery in the previous cycle (OR = 0.18, 95%CI 0.14 to 0.24). Furthermore, non-DDD was associated with reduced SMC adherence and higher caregiver non-reporting of adverse reactions to SMC medicines in children compared with DDD. Conclusion This study provides evidence on the characteristics of households accessing SMC medicines through non-DDD and its potential negative outcomes on adherence to SMC medicine and adverse reaction reporting, underscoring potential implementation issues that may arise if non-DDD delivery models are adopted in SMC, particularly in places where DDD had been firstly used.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Drug repurposing offers a strategic alternative to the development of novel compounds, leveraging the known safety and pharmacokinetic profiles of medications, such as linezolid and levofloxacin for tuberculosis (TB). Anti-malarial drugs, including quinolones and artemisinins, are already applied to other diseases and infections and could be promising for TB treatment. Methods This review included studies on the activity of anti-malarial drugs, specifically quinolones and artemisinins, against Mycobacterium tuberculosis complex (MTC), summarizing results from in vitro, in vivo (animal models) studies, and clinical trials. Studies on drugs not primarily developed for TB (doxycycline, sulfonamides) and any novel developed compounds were excluded. Analysis focused on in vitro activity (minimal inhibitory concentrations), synergistic effects, pre-clinical activity, and clinical trials. Results Nineteen studies, including one ongoing Phase 1 clinical trial, were analysed: primarily investigating quinolones like mefloquine and chloroquine, and, to a lesser extent, artemisinins. In vitro findings revealed high MIC values for anti-malarials versus standard TB drugs, suggesting a limited activity. Synergistic effects with anti-TB drugs were modest, with some synergy observed in combinations with isoniazid or pyrazinamide. In vivo animal studies showed limited activity of anti-malarials against MTC, except for one study of the combination of chloroquine with isoniazid. Conclusions The repurposing of anti-malarials for TB treatment is limited by high MIC values, poor synergy, and minimal in vivo effects. Concerns about potential toxicity at effective dosages and the risk of antimicrobial resistance, especially where TB and malaria overlap, further question their repurposing. These findings suggest that focusing on novel compounds might be both more beneficial and rewarding.
Læs mere Tjek på PubMedLuisa Weisbrod, Luigi Capriotti, Marco Hofmann, Valerie Spieler, Herbert Dersch, Bernd Voedisch, Peter Schmidt, Susanne Knake
Frontiers in Immunology, 8.05.2024
Tilføjet 8.05.2024
The study of peptide repertoires presented by major histocompatibility complex (MHC) molecules and the identification of potential T-cell epitopes contribute to a multitude of immunopeptidome-based treatment approaches. Epitope mapping is essential for the development of promising epitope-based approaches in vaccination as well as for innovative therapeutics for autoimmune diseases, infectious diseases, and cancer. It also plays a critical role in the immunogenicity assessment of protein therapeutics with regard to safety and efficacy concerns. The main challenge emerges from the highly polymorphic nature of the human leukocyte antigen (HLA) molecules leading to the requirement of a peptide mapping strategy for a single HLA allele. As many autoimmune diseases are linked to at least one specific antigen, we established FASTMAP, an innovative strategy to transiently co-transfect a single HLA allele combined with a disease-specific antigen into a human cell line. This approach allows the specific identification of HLA-bound peptides using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Using FASTMAP, we found a comparable spectrum of endogenous peptides presented by the most frequently expressed HLA alleles in the world’s population compared to what has been described in literature. To ensure a reliable peptide mapping workflow, we combined the HLA alleles with well-known human model antigens like coagulation factor VIII, acetylcholine receptor subunit alpha, protein structures of the SARS-CoV-2 virus, and myelin basic protein. Using these model antigens, we have been able to identify a broad range of peptides that are in line with already published and in silico predicted T-cell epitopes of the specific HLA/model antigen combination. The transient co-expression of a single affinity-tagged MHC molecule combined with a disease-specific antigen in a human cell line in our FASTMAP pipeline provides the opportunity to identify potential T-cell epitopes/endogenously processed MHC-bound peptides in a very cost-effective, fast, and customizable system with high-throughput potential.
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Purpose The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. Methods We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. Results We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73–0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. Conclusion With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. Clinical Trail registration The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024