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Aubrey Dissinger, Simona Rimoldi, Genciana Terova, Karolina Kwasek
PLoS One Infectious Diseases, 27.07.2024
Tilføjet 27.07.2024
by Aubrey Dissinger, Simona Rimoldi, Genciana Terova, Karolina Kwasek Many organisms exhibit social behaviors and are part of some scheme of social structure. Zebrafish are highly social, shoaling fish and therefore, social isolation may have notable impacts on their physiology and behavior. The objective of this study was to evaluate the effects of social isolation on feed intake, monoaminergic system related gene expression, and intestinal health of juvenile zebrafish fed a high-inclusion soybean meal based diet. At 20 days post-fertilization zebrafish were randomly assigned to chronic isolation (1 fish per 1.5 L tank) or social housing (6 fish per 9 L tank) with 18 tanks per treatment group (n = 18). Dividers were placed between all tanks to prevent visual cues between fish. Zebrafish were fed a commercial fishmeal based diet until 35 days post-fertilization and then fed the experimental high-inclusion soybean meal based diet until 50 days post-fertilization. At the end of the experiment (51 days post-fertilization), the mean total length, weight, and weight gain were not significantly different between treatment groups. Feed intake and feed conversion ratio were significantly higher in chronic isolation fish than in social housing fish. Expression of monoaminergic and appetite-related genes were not significantly different between groups. The chronic isolation group showed higher expression of the inflammatory gene il-1b, however, average intestinal villi width was significantly smaller and average length-to-width ratio was significantly higher in chronic isolation fish, suggesting morphological signs of inflammation were not present at the time of sampling. These results indicate that chronic isolation positively affects feed intake of juvenile zebrafish and suggest that isolation may be useful in promoting feed intake of less-palatable diets such as those based on soybean meal.
Læs mere Tjek på PubMedPiter Oosterhof, Ferdinand W. N. M. Wit, Matthijs van Luin, Marc van der Valk, Kees Brinkman, David M. Burger
PLoS One Infectious Diseases, 27.07.2024
Tilføjet 27.07.2024
by Piter Oosterhof, Ferdinand W. N. M. Wit, Matthijs van Luin, Marc van der Valk, Kees Brinkman, David M. Burger Introduction HIV treating physicians in the Netherlands follow the guidelines of the Department of Health and Human Services (DHHS). Most of these recommended initial regimens are single-tablet regimens (STRs), which incur higher costs. By the end of 2017, generic NRTI backbones had become widely available, offering a potentially cheaper multi-tablet regimen. This study aimed to evaluate guideline compliance in people with HIV who started antiretroviral therapy (ART), the uptake of generic multi-tablet regimens (gMTRs), and associated medication costs. Methods This retrospective cohort study used data from the Dutch HIV Monitoring Foundation to determine the proportion of treatment-naïve people entering care who initiated ART according to the DHHS and type of ART regimens prescribed between January 2016 and December 2020. We analyzed ART prescriptions, both at the national level and per individual HIV treatment centers. We calculated the monthly ART costs based on Dutch medicine prices listed on www.medicijnkosten.nl for each calendar year. Results In 2016, an integrase inhibitor-containing regimen was initiated in 77.3% which increased to 87.8% in 2020. The compliance rate to DHHS-recommended initial regimens ranged from 82.8% in 2016 to 90.9% in 2020. Most patients received single-tablet regimens, 81.3% in 2016 to 60.3% in 2020. After the introduction the gMTRs showed a steady increase from 17.8% in 2018 to 37.8% in 2020. The cost of the first-line regimen per patient decreased by 22.9% in 2020 compared with 2017. The decrease was larger in centers where treatment-naïve individuals with HIV were preferentially initiated on a gMTR. Conclusions There was a high compliance to the “DHHS-recommended initial regimens for most people with HIV” in the Netherlands. Most people who initiated ART received STRs, although the percentage of people who started on STRs gradually decreased over time. The use of gMTRs increased over time and was associated with lower medication costs.
Læs mere Tjek på PubMedRena Okawa, Misato Takagi, Takashi Nakamoto, Naoya Kakimoto, Kazuhiko Nakano
PLoS One Infectious Diseases, 27.07.2024
Tilføjet 27.07.2024
by Rena Okawa, Misato Takagi, Takashi Nakamoto, Naoya Kakimoto, Kazuhiko Nakano Background X-linked hypophosphatemia (XLH) is the most common inherited form of rickets. The presence of sequence variations in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene is associated with increased production of fibroblast growth factor 23 (FGF23). This results in renal phosphate wasting and impaired skeletal mineralization. Spontaneous dental abscesses, caused by endodontic infections resulting from hypomineralization of dentin, are a known dental complication of XLH. There is no objective method to evaluate the severity of dentin dysplasia. The purpose of this study was to develop a quantitative method to evaluate dentin dysplasia using orthopantomography that would allow the values in patients with XLH to be compared with the values in healthy participants of the same age. Methods The severity of dentin dysplasia was analyzed by measuring the pulp cavity area of the tooth using orthopantomographic images. The teeth analyzed were mandibular second primary molars and mandibular first permanent molars with complete root formation. Teeth with dental caries, restorations, or root resorption were excluded. Results This retrospective observational study included a total of 200 images of healthy participants (aged 2–15 years) divided into five age groups and 42 images of 17 patients with XLH. There was a significant tendency for the pulp cavity area to decrease with increasing age in primary and permanent teeth. The pulp chambers of patients with XLH were larger than those of healthy participants in primary and permanent teeth. Conclusion We have established a method of using orthopantomography for quantitative assessment of dentin dysplasia in XLH from the primary dentition to the permanent dentition. Evaluating the severity of dentin hypomineralization by this method is useful in the diagnosis of the dental manifestations of XLH. Early diagnosis of XLH enables oral management and leads to prevention of dental abscesses.
Læs mere Tjek på PubMedAndrea Foppiani, Chiara Montanari, Sara Zanelli, Michele Davide Maria Lombardo, Valeria Calcaterra, Gianvincenzo Zuccotti
PLoS One Infectious Diseases, 27.07.2024
Tilføjet 27.07.2024
by Andrea Foppiani, Chiara Montanari, Sara Zanelli, Michele Davide Maria Lombardo, Valeria Calcaterra, Gianvincenzo Zuccotti Background The diverse manifestations of Long-COVID have become increasingly important due to their significant impact on patients’ lives. Telemedicine has emerged as an important tool for post COVID-19 follow-up. This study is part of a large cohort study involving COVID-positive patients monitored by the COD19 telemedicine platform operations center. We recontacted patients who were initially monitored from February 2020 to May 2020 to assess the presence of Long-COVID symptoms at a 2-year follow-up. Methods We conducted interviews to evaluate Long-COVID symptoms at the 2-year mark and investigated whether patients had contracted a second COVID-19 infection between the 1-year and 2-year follow-ups, and recorded their vaccination status. Results Out of 165 patients, 139 (84%) reported symptoms at the 1-year follow-up, while only 101 (61%) reported symptoms at the 2-year follow-up. Among patients with Long-COVID symptoms at the 2-year follow-up, the majority (80, 49%) had experienced Long-COVID at the 1-year follow-up, received the SARS-CoV-2 vaccine, and had not experienced a second infection between the two follow-ups. Both having Long-COVID at the 1-year follow-up and contracting a second infection were significant risk factors for presenting with Long-COVID at the 2-year follow-up. Conclusions To the best of our knowledge, this study stands out as one of the few that includes a 2-year follow-up on Long-COVID symptoms using telemedicine. Telemedicine has proven to be an effective and innovative tool for long-term patient monitoring, early diagnosis, and treatment. Telemedicine represents a significant future challenge for healthcare.
Læs mere Tjek på PubMedCheng-Lan Sheng, Bang-Dong Jiang, Chun-Qiu Zhang, Jin-Hua Huang, Zi Wang, Chao Xu
PLoS One Infectious Diseases, 27.07.2024
Tilføjet 27.07.2024
by Cheng-Lan Sheng, Bang-Dong Jiang, Chun-Qiu Zhang, Jin-Hua Huang, Zi Wang, Chao Xu Deubiquitinating enzymes (DUBs) play a pivotal role in regulating the antiviral immune response by targeting members of the RLR signaling pathway. As a pivotal member of the RLR pathway, TRAF3 is essential for activating the MAVS/TBK-1/IRF3 signaling pathway in response to viral infection. Despite its importance, the function of DUBs in the TRAF3-mediated antiviral response is poorly understood. Ubiquitin-specific protease 26 (USP26) regulates the RLR signaling pathway to modulate the antiviral immune response. The results demonstrate that EV71 infection upregulates the expression of USP26. Knockdown of USP26 significantly enhances EV71-induced expression of IFN-β and downstream interferon-stimulated genes (ISGs). Deficiency of USP26 not only inhibits EV71 replication but also weakens the host’s resistance to EV71 infection. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. Conversely, knockdown of USP26 leads to an increase in the K63-linked polyubiquitination of TRAF3. These findings unequivocally establish the essential role of USP26 in RLR signaling and significantly contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.
Læs mere Tjek på PubMedCatherine SchlenkerKatharina RichardSofia SkobelkinaR. Paige MathenaDarren J. Perkins1Program in Oncology University of Maryland, Baltimore (UMB), School of Medicine, Baltimore, Maryland, USA2Department of Microbiology and Immunology, School of Medicine, Baltimore, Maryland, USADenise M. Monack
Infection and Immunity, 27.07.2024
Tilføjet 27.07.2024
Victor ChaumeauPraphan WasisakunJames A. WatsonThidar OoSarang AryalamloedMu Phang SueGay Nay HtooNaw Moo ThaLaypaw ArchusuksanSunisa SawasdichaiGornpan GornsawunSomya MehraNicholas J. WhiteFrançois H. Nosten1Shoklo Malaria Research Unit, Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Ramat, Tak, Thailand2Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, England, United Kingdom3Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam4Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandAudrey Odom John
Antimicrobial Agents And Chemotherapy, 27.07.2024
Tilføjet 27.07.2024
Madison E. NelsonJaime L. LittleChristopher J. Kristich1Department of Microbiology and Immunology, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USABoudewijn L. de Jonge
Antimicrobial Agents And Chemotherapy, 27.07.2024
Tilføjet 27.07.2024
Massimo Franchini, Mario Cruciani, Carlo Mengoli, Arturo Casadevall, Claudia Glingani, Michael J. Joyner, Liise-anne Pirofski, Jonathon W. Senefeld, Shmuel Shoham, David J. Sullivan, Matteo Zani, Daniele Focosi
Clinical Microbiology and Infection, 27.07.2024
Tilføjet 27.07.2024
Plasma collected from recovered COVID-19 patients (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the COVID-19 pandemic. While the therapeutic effect of early administration of CCP in COVID-19 outpatients has been recognized, conflicting data exist regarding the efficacy of CCP administration in hospitalized patients.
Læs mere Tjek på PubMedCao Jiaxin, Pan Pan, Feng Dan, Wang Mingyang, Zheng Yawei, Yang Nan, Chen Xin, Zhai Weihua, Zhang Rongli, Ma Qiaoling, Wei Jialin, Yang Donglin, He Yi, Wang Xiaodan, Pang Aiming, Feng Sizhou, Han Mingzhe, Jiang Erlie
Clinical Microbiology and Infection, 27.07.2024
Tilføjet 27.07.2024
To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in hematopoietic stem cell transplantation (HSCT) patients and analyze POS plasma concentrations.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 27.07.2024
Tilføjet 27.07.2024
Abstract T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. 21 responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4β7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17 shifted phenotype The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 27.07.2024
Tilføjet 27.07.2024
Abstract T-cell immunoglobulin and mucin domain-containing molecule 4 (Tim-4) is an immune checkpoint molecule, which involves in numerous inflammatory diseases. Tim-4 is mainly expressed on antigen presenting cells. However, increasing evidences have shown that Tim-4 is also expressed on natural killer T (NKT) cells. The role of Tim-4 in maintaining NKT cell homeostasis and function remains unknown. In this study, we explored the effect of Tim-4 on NKT cells in acute liver injury. This study found that Tim-4 expression on hepatic NKT cells was elevated during acute liver injury. Tim-4 deficiency enhanced IFN-γ, TNF-α expression while impaired IL-4 production in NKT cells. Loss of Tim-4 drove NKT cell effector lineages to be skewed to NKT1 subset. Furthermore, Tim-4 KO mice were more susceptible to α-GalCer challenge. In conclusion, our findings indicate that Tim-4 plays an important role in regulating homeostasis and function of NKT cells in acute liver injury. Therefore, Tim-4 might become a new regulator of NKT cells and a potential target for the therapy of acute hepatitis.
Læs mere Tjek på PubMedHarrison, E., Kathir Kamarajah, S., NIHR Global Health Research Unit on Global Surgery, Kamarajah, Kouli, Alexander, Avellaneda, Cameron, Dawson, Dermanis, Ghosh, Griffiths, Guest, Haque, Kehoe, Lawani, Martin, Medina, Bravo, Morton, Pius, Primrose, Roberts, Siriwardena, Satoi, Shaw, Sutcliffe, Han, Harrison
BMJ Open, 26.07.2024
Tilføjet 26.07.2024
IntroductionCholecystectomy is one of the most common operations performed worldwide. Although laparoscopic surgery has been the ‘gold-standard’ approach for this operation, there is a paucity of global evidence around the variations of safe provision of cholecystectomy, including low-income and middle-income countries. This international collaborative study will allow contemporaneous data collection on the quality of cholecystectomies using measures covering infrastructure, care processes and outcomes, with the primary aim define the global variation in compliance with preoperative, intraoperative and postoperative audit standards. Methods and analysisGlobal Evaluation of Cholecystectomy Knowledge and Outcomes is a prospective, international, multicentre, observational cohort study delivered by the GlobalSurg Collaborative. Consecutive patients undergoing cholecystectomy between 31 July 2023 and 19 November 2023 will be recruited, with follow-up at 30 days and 1-year postoperatively. The study will be undertaken at any hospital providing emergency or elective surgical services for biliary disease. The primary endpoint of this study is compliance with preoperative, intraoperative and postoperative audit standards. Secondary outcomes include rates of 30-day complications, achievement of critical view of safety and rates of gallbladder cancer. Ethics and disseminationThis project will not affect clinical practice and has been classified as clinical audit following research ethics review at University Hospital Birmingham NHS Trust. The protocol will be disseminated through the international GlobalSurg and CovidSurg network. Trial registration numberNCT06223061.
Læs mere Tjek på PubMedBMJ Open, 26.07.2024
Tilføjet 26.07.2024
Winkler NE, Koirala A, Kaur G, et al. Seroprevalence of Japanese encephalitis virusspecific antibodies in Australia following novel epidemic spread: protocol for a national crosssectional study. BMJ Open 2024;14:e075569. doi:10.1136/ bmjopen-2023-075569 This article has been corrected since it was published online. The changes clarify statements that were unclear on the status of and requirements for ethical approvals. The changes made are mentioned below. EthicsNational Mutual Acceptance ethical approval was obtained from the Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC). Local approvals were planned to be sought in each jurisdiction, as per local ethics processes. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC. Active collections are proposed for populations with geographical distribution mirroring locations of human, animal and vector detections in the Northern Territory, Queensland, New South Wales, Victoria, South Australia and Western Australia, (table 1,figure 1B) subject to local...
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Background In contemporary times, increased prevalence of Helicobacter pylori (H. pylori) infection and elevated dyslipidemia levels present substantial public health challenges. However, the relationship between H. pylori and dyslipidemia remains inconclusive. No studies have yet conducted a population-based classification to investigate the impact of H. pylori infection on dyslipidemia in individuals with diabetes. Methods A retrospective cohort study was carried out on a total of 60,535 individuals who underwent health check-ups at the Health Examination Center in Taizhou Hospital from 2017 to 2022. Physical measurements, hematological markers and detection of H. pylori were gathered from all patients. The study population was further stratified into diabetic and non-diabetic groups for analysis. Results H. pylori infection was found to be an autonomous risk factor for dyslipidemia based on the results of multivariate logistic regression analysis (OR = 1.13, 95% CI: 1.03–1.24). However, no notable effect on dyslipidemia in the non-diabetic group was observed. Furthermore, at the follow-up, the group with persistent negative showed a significantly lower incidence ratio of dyslipidemia compared to the group with persistent infection (P = 0.006). The persistent negative group exhibited a significantly higher rate of improvement in dyslipidemia compared to the new infection group (P = 0.038). Conclusions In the diabetic population, the presence of H. pylori infection heightens the propensity for developing dyslipidemia. Therefore, the implementation of efficient eradication strategies for H. pylori infection could potentially lead to a decrease in the occurrence of dyslipidemia among individuals with diabetes.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Background Dengue infection is a mosquito-borne, endemic viral disease, particularly in developing countries. Here, we report the results of the clinicodemographic, serologic profile and the monthly occurrence of a recent dengue fever outbreak in Puntland State (Somalia). Methodology We analyzed the data of 956 dengue-suspected patients who were investigated using the rapid diagnostic testing (RDT) method for detecting NS1 (dengue virus non-structural protein) and IgM antibodies employing the SD Biosensor Dengue Dou NS Ag and IgM test kit (Germany) at the Puntland Public Health Referral Laboratory from November 21, 2022, to May 27, 2023. Results We found that 118 cases were positive for dengue among the suspected patients enrolled in the present study. Of these cases, 76.2% were dengue NSI positive, 13.6% were dengue IgM positive, and 10.2% were both NSI and IgM positive. The number of females and males in the confirmed cases was equal, and most (48.3%) were aged 20 years or less. 43.1% of them lived in the Nugal region, particularly in Garowe. Clinically, fever was the most frequent symptom (88.9%). The cases peaked in December 2022 but dropped from January to March, with a slight rise in February, and then increased in April and May 2023. Conclusion This study highlights the clinicodemographic characteristics, seroprevalence, and monthly occurrence of dengue in Puntland. We recommend improving vector control measures, enhancing case management, strengthening dengue surveillance, developing an early warning system, and conducting future studies to characterize the circulating strains.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Background The causative agents of Acute Encephalitis Syndrome remain unknown in 68–75% of the cases. In Nepal, the cases are tested only for Japanese encephalitis, which constitutes only about 15% of the cases. However, there could be several organisms, including vaccine-preventable etiologies that cause acute encephalitis, when identified could direct public health efforts for prevention, including addressing gaps in vaccine coverage. Objectives This study employs metagenomic next-generation-sequencing in the investigation of underlying causative etiologies contributing to acute encephalitis syndrome in Nepal. Methods In this study, we investigated 90, Japanese-encephalitis-negative, banked cerebrospinal fluid samples that were collected as part of a national surveillance network in 2016 and 2017. Randomization was done to include three age groups (15-years). Only some metadata (age and gender) were available. The investigation was performed in two batches which included total nucleic-acid extraction, followed by individual library preparation (DNA and RNA) and sequencing on Illumina iSeq100. The genomic data were interpreted using Chan Zuckerberg-ID and confirmed with polymerase-chain-reaction. Results Human-alphaherpes-virus 2 and Enterovirus-B were seen in two samples. These hits were confirmed by qPCR and semi-nested PCR respectively. Most of the other samples were marred by low abundance of pathogen, possible freeze-thaw cycles, lack of process controls and associated clinical metadata. Conclusion From this study, two documented causative agents were revealed through metagenomic next-generation-sequencing. Insufficiency of clinical metadata, process controls, low pathogen abundance and absence of standard procedures to collect and store samples in nucleic-acid protectants could have impeded the study and incorporated ambiguity while correlating the identified hits to infection. Therefore, there is need of standardized procedures for sample collection, inclusion of process controls and clinical metadata. Despite challenging conditions, this study highlights the usefulness of mNGS to investigate diseases with unknown etiologies and guide development of adequate clinical-management-algorithms and outbreak investigations in Nepal.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Elevated resistance to pyrethroids in major malaria vectors has led to the introduction of novel insecticides including neonicotinoids. There is a fear that efficacy of these new insecticides could be impacted by cross-resistance mechanisms from metabolic resistance to pyrethroids. In this study, after evaluating the resistance to deltamethrin, clothianidin and mixture of clothianidin + deltamethrin in the lab using CDC bottle assays, the efficacy of the new IRS formulation Fludora® Fusion was tested in comparison to clothianidin and deltamethrin applied alone using experimental hut trials against wild free-flying pyrethroid-resistant Anopheles funestus from Elende and field An. gambiae collected from Nkolondom reared in the lab and released in the huts. Additionally, cone tests on the treated walls were performed each month for a period of twelve months to evaluate the residual efficacy of the sprayed products. Furthermore, the L1014F-kdr target-site mutation and the L119F-GSTe2 mediated metabolic resistance to pyrethroids were genotyped on a subset of mosquitoes from the EHT to assess the potential cross-resistance. All Anopheles species tested were fully susceptible to clothianidin and clothianidin + deltamethrin mixture in CDC bottle assay while resistance was noted to deltamethrin. Accordingly, Fludora® Fusion (62.83% vs 42.42%) and clothianidin (64.42% vs 42.42%) induced significantly higher mortality rates in EHT than deltamethrin (42.42%) against free flying An. funestus from Elende in month 1 (M1) and no significant difference in mortality was observed between the first (M1) and sixth (M6) months of the evaluation (P > 0.05). However, lower mortality rates were recorded against An. gambiae s.s from Nkolondom (mortality rates 50%, 45.56% and 26.68%). In-situ cone test on the wall showed a high residual efficacy of Fludora® Fusion and clothianidin on the susceptible strain KISUMU (> 12 months) and moderately on the highly pyrethroid-resistant An. gambiae strain from Nkolondom (6 months). Interestingly, no association was observed between the L119F-GSTe2 mutation and the ability of mosquitoes to survive exposure to Fludora® Fusion, whereas a trend was observed with the L1014F-kdr mutation. This study highlights that Fludora® Fusion, through its clothianidin component, has good potential of controlling pyrethroid-resistant mosquitoes with prolonged residual efficacy. This could be therefore an appropriate tool for vector control in several malaria endemic regions.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Background The prognosis of immunocompromised individuals with COVID-19 remains a significant concern. Information regarding the clinical and virological characteristics of immunocompromised patients infected with SARS-CoV-2 during the Omicron variant period is limited. Methods Medical records of patients admitted to our hospital with COVID-19 during the Omicron (BA.1–5) epidemic were retrospectively reviewed. Clinical, virological (nasopharyngeal swabs and blood), and serological data were compared between immunocompromised patients receiving immunosuppressive medications (calcineurin inhibitors, mycophenolate mofetil, or steroids) and control patients not receiving immunosuppressive medications. Results Twenty-eight immunocompromised patients (25 transplant recipients) and 26 control patients were included. Fourteen of the immunocompromised patients (50%) received monoclonal antibodies. The immunocompromised group included 15 mild/moderate (53.6%), 10 severe (35.7%), and three critical (10.7%) disease severities. The mortality rate due to COVID-19 during hospitalization was 3.6% (1/28) in the immunocompromised group, with no difference between the two groups. Three cases of re-exacerbation after discharge occurred in the immunocompromised group and none in the control group. Linear regression based on nasopharyngeal real-time-PCR cycle threshold (Ct) values according to the time since symptom onset showed markedly slower viral clearance in the immunocompromised group than in the control group (Pslope = 0.078). In the immunocompromised group, patients who received monoclonal antibodies showed faster viral clearance than those who did not receive monoclonal antibodies. The convalescent anti-spike IgG titers were comparable to those in the control group in patients who received monoclonal antibodies and significantly lower than those in the control patients in patients who did not receive monoclonal antibodies (P
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Background Cystic echinococcosis (CE) is a chronic disease considered a neglected one. Cystic echinococcosis is endemic in Uruguay and the region. Surgery, using various technical approaches, has the potential to safely remove the cyst(s) and lead to a complete cure in a high number of patients with simple forms of CE. However, surgery may be impractical in patients with multiple cysts in several organs, high surgical risk, or in patients with previous multiple surgeries. In these cases, the pharmacological treatment with the benzimidazolic drug Albendazole (ABZ) alone or combined with Praziquantel (PZQ), has been promising as the best choice to achieve improvement or cure. Methods In this study, we analyze the results obtained on the anti-parasitic treatment of 43 patients diagnosed with CE between the years 2003 and 2020. Patients were treated before and/or after surgery with ABZ or the combination ABZ/PZQ. The standardize protocol of the anti-parasitic drug treatment before surgery was 7 days, 15 days or 1 month depending on the urgency and availability of the surgical procedure. All cases that involved confirmed locations on lungs underwent immediate surgery with minimal pre-treatment when possible. After surgery, the standardize protocol of anti-parasitic drug treatment consisted of six cycles of 30 days each and resting intervals of 15 days in between. ABZ was used in all cases, administered orally, twice daily, at a total dosage of 15 mg/kg/day, with food high in fat content for improved absorption. The follow up was carried out according to WHO-IWGE guidelines for 5 years. Results Of the 43 patients fourteen were ≤ 15 years of age and had a differentiated pre-surgical treatment. From the ≥ 16 years of age, 36 completed the treatments and the 5 years follow up. Four patients changed geographical locations, without a forwarding contact, after the post-surgery treatment. No patient died during the study. Of the 36 patients that completed the study, 32 were treated only with ABZ; 93.75% achieved treatment success as determined by improvement or cure, and 6.25% treatment failure determined by no change or worsening. The last four patients received the ABZ/PZQ combination therapy and achieved 100% treatment success. Conclusion The pharmacological treatment resulted in a good option not only as palliative but also as potentially curative. The main relevance of its use was in cases with previous multiple surgeries or surgeries with potential life-threatening complications due to the number and location of cysts and concurrent comorbidities. A follow-up of at least 5 years would be recommended to assure remission and control of the transmission. More randomized trials are needed to provide clear clinical evidence of different pharmacological treatments for CE.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Background Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients. Methods New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment. Results Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1–97.8) and 94.5% (95% CI: 90.8–98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction. Conclusion The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Background In late 2021, Ghana was hit by a Yellow Fever outbreak that started in two districts in the Savannah region and spread to several other Districts in three regions. Yellow fever is endemic in Ghana. However, there is currently no structured vector control programme for Aedes the arboviral vector in Ghana. Knowledge of Aedes bionomics and insecticide susceptibility status is important to control the vectors. This study therefore sought to determine Aedes vector bionomics and their insecticide resistance status during a yellow fever outbreak. Methods The study was performed in two yellow fever outbreak sites (Wenchi, Larabanga) and two non-outbreak sites (Kpalsogu, Pagaza) in Ghana. Immature Aedes mosquitoes were sampled from water-holding containers in and around human habitations. The risk of disease transmission was determined in each site using stegomyia indices. Adult Aedes mosquitoes were sampled using Biogents Sentinel (BG) traps, Human Landing Catch (HLC), and Prokopack (PPK) aspirators. Phenotypic resistance to permethrin, deltamethrin and pirimiphos-methyl was determined with WHO susceptibility tests using Aedes mosquitoes collected as larvae and reared into adults. Knockdown resistance (kdr) mutations were detected using allele-specific multiplex PCR. Results Among the 2,664 immature Aedes sampled, more than 60% were found in car tyres. Larabanga, an outbreak site, was classified as a high-risk zone for the Yellow Fever outbreak (BI: 84%, CI: 26.4%). Out of 1,507 adult Aedes mosquitoes collected, Aedes aegypti was the predominant vector species (92%). A significantly high abundance of Aedes mosquitoes was observed during the dry season (61.2%) and outdoors (60.6%) (P
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
Abstract Aim To analyze the clinicopathological features of schistosomal and non-schistosomal colorectal cancer in Central China and compare them with other areas of the Yangtze River Basin. Method The 501 cases of colorectal cancer (CRC) were retrospectively analyzed from 2020 to 2022. They were divided into two groups: 406 cases of colorectal cancer without schistosomiasis (CRC-NS) and 95 cases of colorectal cancer with schistosomiasis (CRC-S).The clinicopathological characteristics included the distribution of schistosomiasis eggs, patient age, sex, tumor differentiation, lymph node metastasis, and clinical stage. By retrieving the database, this study compared the clinicopathological differences of colorectal cancer with schistosomiasis in other areas of the Yangtze River basin. Results The cases of colorectal cancer with schistosomiasis accounted for 18.9%(95/501) in the study. The patients of CRC-S were older than the patients of CRC-NS (P = 0.002, P
Læs mere Tjek på PubMedHinh Ly Department of Veterinary & Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Twin Cities, MN, USA
Virulence, 26.07.2024
Tilføjet 26.07.2024
Gabriele Neumann, Yoshihiro Kawaoka
Nat Rev Microbiol, 26.07.2024
Tilføjet 26.07.2024
Lina Antounians, Rebeca Lopes Figueira, Bharti Kukreja, Michael L. Litvack, Elke Zani-Ruttenstock, Kasra Khalaj, Louise Montalva, Fabian Doktor, Mikal Obed, Matisse Blundell, Taiyi Wu, Cadia Chan, Richard Wagner, Martin Lacher, Michael D. Wilson, Martin Post, Brian T. Kalish, Augusto Zani
Science Advances, 26.07.2024
Tilføjet 26.07.2024
Guangshuai Zhang, Dandan Song, Ruilong Ma, Mo Li, Bingyang Liu, Zhonggui He, Qiang Fu
Science Advances, 26.07.2024
Tilføjet 26.07.2024
Yi Zhang, Miaomiao Luo, Xiangling Shi, Aimin Li, Wei Zhou, Yuyao Yin, Hui Wang, Wing-Leung Wong, Xinxin Feng, Qing He
Science Advances, 26.07.2024
Tilføjet 26.07.2024
The Lancet
Lancet, 26.07.2024
Tilføjet 26.07.2024
2024 is the worst year for dengue cases on record. As of July 23, over 10 million cases of dengue have been reported from 176 countries across all WHO regions (although the Americas account for most cases), with more than 24 000 severe cases and 6508 deaths. This figure already surpasses the number of cases in 2023, which was also a record year. There is no doubt that dengue, a vector-borne disease caused by four serologically related viruses, is a major infectious disease threat to health. Over the past two decades, there has been a tenfold increase in reported cases, and even this figure is likely an underestimate.
Læs mere Tjek på PubMedMarcia Triunfol
Lancet, 26.07.2024
Tilføjet 26.07.2024
Several employees of the Prevent Senior hospital chain have been charged over the care of patients during the COVID-19 pandemic. Marcia Triunfol reports.
Læs mere Tjek på PubMedMary T Bassett
Lancet, 26.07.2024
Tilføjet 26.07.2024
In 2022 about 48 000 people died of gun-related injuries in the USA. The same year, there were almost 25 000 homicides and nearly 80% of them resulted from guns. Gun violence increased during the COVID-19 pandemic in the USA and although rates are now declining, the number of deaths from gun violence remains among the highest in decades. Gun violence is a leading cause of death nationally among young people aged up to 19 years. Young Black people in the USA make up a disproportionate share of these numbing statistics.
Læs mere Tjek på PubMedMingfang Li, Joon Bum Kim, B K S Sastry, Minglong Chen
Lancet, 26.07.2024
Tilføjet 26.07.2024
First described more than 350 years ago, infective endocarditis represents a global health concern characterised by infections affecting the native or prosthetic heart valves, the mural endocardium, a septal defect, or an indwelling cardiac device. Over recent decades, shifts in causation and epidemiology have been observed. Echocardiography remains pivotal in the diagnosis of infective endocarditis, with alternative imaging modalities gaining significance. Multidisciplinary management requiring expertise of cardiologists, cardiovascular surgeons, infectious disease specialists, microbiologists, radiologists and neurologists, is imperative.
Læs mere Tjek på PubMedKaiyuan Sun, Jinal N. Bhiman, Stefano Tempia, Jackie Kleynhans, Vimbai Sharon Madzorera, Qiniso Mkhize, Haajira Kaldine, Meredith L. McMorrow, Nicole Wolter, Jocelyn Moyes, Maimuna Carrim, Neil A. Martinson, Kathleen Kahn, Limakatso Lebina, Jacques D. du Toit, Thulisa Mkhencele, Anne von Gottberg, Cécile Viboud, Penny L. Moore, Cheryl Cohen, Amelia Buys, Maimuna Carrim, Linda de Gouveia, Mignon du Plessis, Jacques du Toit, Francesc Xavier Gómez-Olivé, Kgaugelo Patricia Kgasago, Retshidisitswe Kotane, Meredith L. McMorrow, Tumelo Moloantoa, Stephen Tollman, Anne von Gottberg, Floidy Wafawanaka, Nicole Wolter
Nature, 26.07.2024
Tilføjet 26.07.2024
Isabel Leroux-Roels, Chittappen Kandiyil Prajeeth, Amare Aregay, Niranjana Nair, Guus F Rimmelzwaan, Albert D M E Osterhaus, Simone Kardinahl, Sabrina Pelz, Stephan Bauer, Valentino D'Onofrio, Azhar Alhatemi, Bart Jacobs, Fien De Boever, Sharon Porrez, Gwenn Waerlop, Carine Punt, Bart Hendriks, Ellemieke von Mauw, Sandra van de Water, Jose Harders-Westerveen, Barry Rockx, Lucien van Keulen, Jeroen Kortekaas, Geert Leroux-Roels, Paul J Wichgers Schreur
Lancet Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
The hRVFV-4s vaccine showed a high safety profile and excellent tolerability across all tested dose regimens, eliciting robust immune responses, particularly with the high-dose administration. The findings strongly support further clinical development of this candidate vaccine for human use.
Læs mere Tjek på PubMedWai Hon Chooi Winanto Yingying Zeng Cheryl Yi-Pin Lee Ze Qin Lim Pradeep Gautam Justin Jang Hann Chu Yuin-Han Loh Sylvie Alonso Shi-Yan Ng a Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singaporeb National University of Singapore, Faculty of Science (Department of Biological Science), Singaporec Infectious Diseases Translational Research Programme (IDTRP); Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapored Immunology Programme, Life Science Institute, National University of Singapore, Singaporee Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singaporef National Neuroscience Institute, Singapore
Emerg Microbes Infect, 26.07.2024
Tilføjet 26.07.2024
Katharina Bilotti, Sarah Keep, Andrew P. Sikkema, John M. Pryor, James Kirk, Katalin Foldes, Nicole Doyle, Ge Wu, Graham Freimanis, Giulia Dowgier, Oluwapelumi Adeyemi, S. Kasra Tabatabaei, Gregory J. S. Lohman, Erica Bickerton
PLoS One Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
by Katharina Bilotti, Sarah Keep, Andrew P. Sikkema, John M. Pryor, James Kirk, Katalin Foldes, Nicole Doyle, Ge Wu, Graham Freimanis, Giulia Dowgier, Oluwapelumi Adeyemi, S. Kasra Tabatabaei, Gregory J. S. Lohman, Erica Bickerton Avian infectious bronchitis is an acute respiratory disease of poultry of particular concern for global food security. Investigation of infectious bronchitis virus (IBV), the causative agent of avian infectious bronchitis, via reverse genetics enables deeper understanding of virus biology and a rapid response to emerging variants. Classic methods of reverse genetics for IBV can be time consuming, rely on recombination for the introduction of mutations, and, depending on the system, can be subject to genome instability and unreliable success rates. In this study, we have applied data-optimized Golden Gate Assembly design to create a rapidly executable, flexible, and faithful reverse genetics system for IBV. The IBV genome was divided into 12 fragments at high-fidelity fusion site breakpoints. All fragments were synthetically produced and propagated in E. coli plasmids, amenable to standard molecular biology techniques for DNA manipulation. The assembly can be carried out in a single reaction, with the products used directly in subsequent viral rescue steps. We demonstrate the use of this system for generation of point mutants and gene replacements. This Golden Gate Assembly-based reverse genetics system will enable rapid response to emerging variants of IBV, particularly important to vaccine development for controlling spread within poultry populations.
Læs mere Tjek på PubMedShu Hui Huang, Kayla Abrametz, Siobhan L. McGrath, Kerri Kobryn
PLoS One Infectious Diseases, 26.07.2024
Tilføjet 26.07.2024
by Shu Hui Huang, Kayla Abrametz, Siobhan L. McGrath, Kerri Kobryn Telomere resolvases are a family of DNA cleavage and rejoining enzymes that produce linear DNAs terminated by hairpin telomeres from replicated intermediates in bacteria that possess linear replicons. The telomere resolvase of Agrobacterium tumefaciens, TelA, has been examined at the structural and biochemical level. The N-terminal domain of TelA, while not required for telomere resolution, has been demonstrated to play an autoinhibitory role in telomere resolution, conferring divalent metal responsiveness on the reaction. The N-terminal domain also inhibits the competing reactions of hp telomere fusion and recombination between replicated telomere junctions. Due to the absence of the N-terminal domain from TelA/DNA co-crystal structures we produced an AlphaFold model of a TelA monomer. The AlphaFold model suggested the presence of two inhibitory interfaces; one between the N-terminal domain and the catalytic domain and a second interface between the C-terminal helix and the N-core domain of the protein. We produced mutant TelA’s designed to weaken these putative interfaces to test the validity of the modeled interfaces. While our analysis did not bear out the details of the predicted interfaces the model was, nonetheless, extremely useful in guiding design of mutations that, when combined, demonstrated an additive activation of TelA exceeding 250-fold. For some of these hyperactive mutants stimulation of telomere resolution has also been accompanied by activation of competing reactions. However, we have also characterized hyperactive TelA mutants that retain enough autoinhibition to suppress the competing reactions.
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