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BMC Infectious Diseases, 30.04.2024
Tilføjet 30.04.2024
Jeffrey V. Lazarus, Trenton M. White, Katarzyna Wyka, Scott C. Ratzan, Kenneth Rabin, Heidi J. Larson, Federico Martinon-Torres, Ernest Kuchar, Salim S. Abdool Karim, Tamara Giles-Vernick, Selina Müller, Carolina Batista, Nellie Myburgh, Beate Kampmann, Ayman El-Mohandes
Nature, 30.04.2024
Tilføjet 30.04.2024
Feba Ann John, Valeria Criollo, Carissa Gaghan, Abigail Armwood, Jennifer Holmes, Anil J. Thachil, Rocio Crespo, Raveendra R. Kulkarni
PLoS One Infectious Diseases, 29.04.2024
Tilføjet 29.04.2024
by Feba Ann John, Valeria Criollo, Carissa Gaghan, Abigail Armwood, Jennifer Holmes, Anil J. Thachil, Rocio Crespo, Raveendra R. Kulkarni Clostridial dermatitis (CD), caused by Clostridium septicum, is an emerging disease of increasing economic importance in turkeys. Currently, there are no effective vaccines for CD control. Here, two non-toxic domains of C. septicum alpha toxin, namely ntATX-D1 and ntATX-D2, were identified, cloned, and expressed in Escherichia coli as recombinant subunit proteins to investigate their use as potential vaccine candidates. Experimental groups consisted of a Negative control (NCx) that did not receive C. septicum challenge, while the adjuvant-only Positive control (PCx), ntATX-D1 immunization (D1) and ntATX-D2 immunization (D2) groups received C. septicum challenge. Turkeys were immunized subcutaneously with 100 μg of protein at 7, 8 and 9 weeks of age along with an oil-in-water nano-emulsion adjuvant, followed by C. septicum challenge at 11 weeks of age. Results showed that while 46.2% of birds in the PCx group died post-challenge, the rate of mortality in D1- or D2-immunization groups was 13.3%. The gross and histopathological lesions in the skin, muscle and spleen showed that the disease severity was highest in PCx group, while the D2-immunized birds had significantly lower lesion scores when compared to PCx. Gene expression analysis revealed that PCx birds had significantly higher expression of pro-inflammatory cytokine genes in the skin, muscle and spleen than the NCx group, while the D2 group had significantly lower expression of these genes compared to PCx. Peripheral blood cellular analysis showed increased frequencies of activated CD4+ and/or CD8+ cells in the D1 and D2-immunized groups. Additionally, the immunized turkeys developed antigen-specific serum IgY antibodies. Collectively, these findings indicate that ntATX proteins, specifically the ntATX-D2 can be a promising vaccine candidate for protecting turkeys against CD and that the protection mechanisms may include downregulation of C. septicum-induced inflammation and increased CD4+ and CD8+ cellular activation.
Læs mere Tjek på PubMedPfariso Maumela, Sinomncedi Magida, Mahloro Hope Serepa-Dlamini
PLoS One Infectious Diseases, 29.04.2024
Tilføjet 29.04.2024
by Pfariso Maumela, Sinomncedi Magida, Mahloro Hope Serepa-Dlamini The Pb bioremediation mechanism of a multi-metal resistant endophytic bacteria Bacillus sp. strain MHSD_36, isolated from Solanum nigrum, was characterised. The strain tested positive for the presence of plant growth promoters such as indoleacetic acid, 1-aminocyclopropane-1-carboxylate deaminase, siderophores, and phosphate solubilization. The experimental data illustrated that exopolysaccharides and cell hydrophobicity played a role in Pb uptake. The data further showed that the cell wall biosorbed a significant amount (71%) of the total Pb (equivalent to 4 mg/L) removed from contaminated water, compared to the cell membrane (11%). As much as 11% of the Pb was recovered from the cytoplasmic fraction, demonstrating the ability of the strain to control the influx of toxic heavy metals into the cell and minimize their negative impacts. Pb biosorption was significantly influenced by the pH and the initial concentration of the toxic ions. Furthermore, the presence of siderophores and biosurfactants, when the strain was growing under Pb stress, was detected through liquid chromatography mass spectrometry. The strain demonstrated a multi-component based Pb biosorption mechanism and thus, has a great potential for application in heavy metal bioremediation.
Læs mere Tjek på PubMedMuhammad Asim Khan, Kiran Afshan, Sabika Firasat, Muhammad Abbas, Neil D. Sargison, Martha Betson, Umer Chaudhry
PLoS One Infectious Diseases, 29.04.2024
Tilføjet 29.04.2024
by Muhammad Asim Khan, Kiran Afshan, Sabika Firasat, Muhammad Abbas, Neil D. Sargison, Martha Betson, Umer Chaudhry Dicrocoelium lancet flukes cause significant production loss in ruminant livestock. Although co-infection with multiple Dicrocoelium species within a host is common, techniques for studying the composition of these complex parasite communities are lacking. The pathogenicity, epidemiology, and therapeutic susceptibility of different helminth species vary, and little is known about the interactions that take place between co-infecting species and their hosts. Here, we describe the first applicationof metabarcoding deep amplicon sequencing method to studythe Dicrocoelium species in sheep and goats. First, rDNA ITS-2 sequences of four Dicrocoelium species (Dicrocoelium dendriticum, Dicrocoelium hospes, Dicrocoelium orientalis, and Dicrocoelium chinensis) were extracted from the NCBI public database. Phylogenetic analysis revealed separate clades of Dicrocoelium species; hence, molecular differentiation between each species is possible in co-infections. Second, 202 flukes belonging to seventeen host populations (morphologically verified as belonging to the Dicrocoelium genus) were evaluated to determine the deep amplicon sequencing read threshold of an individual fluke for each of the four species. The accuracy of the method in proportional quantification of samples collected from single hosts was further assessed. Overall, 198 (98.01%) flukes were confirmed as D. dendriticum and 1.98% produced no reads. The comparison of genetic distances between rDNA ITS-2 revealed 86% to 98% identity between the Dicrocoelium species. Phylogenetic analysis demonstrated a distinct clustering of species, apart from D. orientalis and D. chinensis, which sit very close to each other in a single large clade whereas D. hospes and D. dendriticum are separated into their own clade. In conclusion each sample was identified as D. dendriticum based on the proportion of MiSeq reads and validated the presence of this group of parasites in the Gilgit Baltistan and Khyber Pakhtunkhwa provinces of Pakistan. The metabarcoding deep amplicon sequencing technology and bioinformatics pathway have several potential applications, including species interactions during co-infections, identifying the host and geographical distribution of Dicrocoelium in livestock, drug therapy response evaluation and understanding of the emergence and spread of drug resistance.
Læs mere Tjek på PubMedApolinar M. Hernández, Luis D. Alcaraz, Cristóbal Hernández-Álvarez, Miguel F. Romero, Angélica Jara-Servín, Hugo Barajas, Carlos M. . Ramírez, Mariana Peimbert
PLoS One Infectious Diseases, 29.04.2024
Tilføjet 29.04.2024
by Apolinar M. Hernández, Luis D. Alcaraz, Cristóbal Hernández-Álvarez, Miguel F. Romero, Angélica Jara-Servín, Hugo Barajas, Carlos M. . Ramírez, Mariana Peimbert The mosquito Aedes spp. holds important relevance for human and animal health, as it serves as a vector for transmitting multiple diseases, including dengue and Zika virus. The microbiome’s impact on its host’s health and fitness is well known. However, most studies on mosquito microbiomes have been conducted in laboratory settings. We explored the mixed microbial communities within Aedes spp., utilizing the 16S rRNA gene for diversity analysis and shotgun metagenomics for functional genomics. Our samples, which included Ae. aegypti and Ae. albopictus, spanned various developmental stages—eggs, larvae, and adults—gathered from five semiurban areas in Mexico. Our findings revealed a substantial diversity of 8,346 operational taxonomic units (OTUs), representing 967 bacterial genera and 126,366 annotated proteins. The host developmental stage was identified as the primary factor associated with variations in the microbiome composition. Subsequently, we searched for genes and species involved in mosquito biocontrol. Wolbachia accounted for 9.6% of the 16S gene sequences. We observed a high diversity (203 OTUs) of Wolbachia strains commonly associated with mosquitoes, such as wAlb, with a noticeable increase in abundance during the adult stages. Notably, we detected the presence of the cifA and cifB genes, which are associated with Wolbachia’s cytoplasmic incompatibility, a biocontrol mechanism. Additionally, we identified 221 OTUs related to Bacillus, including strains linked to B. thuringiensis. Furthermore, we discovered multiple genes encoding insecticidal toxins, such as Cry, Mcf, Vip, and Vpp. Overall, our study contributes to the understanding of mosquito microbiome biodiversity and metabolic capabilities, which are essential for developing effective biocontrol strategies against this disease vector.
Læs mere Tjek på PubMedZerin Jannat, Hemel Das, Md. Wazed Ali, Tasnuva Wahed, Md. Nurul Alam, Md. Jasim Uddin
PLoS One Infectious Diseases, 29.04.2024
Tilføjet 29.04.2024
by Zerin Jannat, Hemel Das, Md. Wazed Ali, Tasnuva Wahed, Md. Nurul Alam, Md. Jasim Uddin Background Vaccination has been an indispensable step in controlling the coronavirus disease pandemic. In early 2021, Bangladesh launched a mass vaccination campaign to boost the COVID-19 vaccination rate when doses were available and immunized millions in the country. Although deemed a success, disparities became conspicuous in vaccination coverage across population of different socioeconomic background. Methods The purpose of this cross-sectional study was to assess the vaccination coverage for three doses and detect disparities in uptake of the COVID-19 vaccine among rural population of hard-to-reach areas and urban individuals belonging to the high-risk group -defined in our study as individuals from elusive population such as floating population/street dwellers, transgender, addicts and disabled population. We conducted household survey (n = 12,298) and survey with high risk group of people (2,520). The collected primary data were analysed using descriptive statistical analysis. Results Our findings show that coverage for the first dose of COVID-19 vaccination was high among respondents from both rural Hard-to-reach (HTR) (92.9%) and non-HTR (94.6%) areas. However, the coverage for subsequent doses was observed to reduce significantly, especially for third dose (52.2% and 56.4% for HTR and non-HTR, respectively). Conclusion Vaccination coverage among urbanites of high-risk group was found to be critically low. Vaccine hesitancy was also found to be high among individuals of this group. It is essential that the individuals of urban high-risk group be prioritized. Individuals from this group could be provided incentives (transport for disabled, monetary incentive to transgenders; food and medicine for drug user and floating people) and vaccination centers could be established with flexible schedule (morning/afternoon/evening sessions) so that they receive vaccine at their convenient time. Community engagement can be used for both high-risk group and rural population to enhance the COVID-19 vaccination coverage and lower disparities in uptake of the vaccine doses nationwide.
Læs mere Tjek på PubMedPavla Vrabcová, Petr Scholz, Ivica Linderová, Hana Kotoučková
PLoS One Infectious Diseases, 29.04.2024
Tilføjet 29.04.2024
by Pavla Vrabcová, Petr Scholz, Ivica Linderová, Hana Kotoučková The economic recovery of the tourism industry after the Covid-19 pandemic to find modern and efficient trends to increase profitability is accompanied by the adoption of comprehensive accommodation approaches towards resilience and environmental sustainability. The research aims at the application of environmental management elements and measures in all types of accommodation facilities in the Czech Republic (n1 = 1,016). A qualitative focus group method complemented the quantitative research using correspondence analysis, Levene’s, Kruskal-Wallis, and Tukey’s HSD tests (n2 = 9 + moderator). The results indicate that the differences in the number of environmental measures implemented were minimal for the monitored hotels and guesthouses. On the other hand, the star rating of accommodation facilities is not a key parameter in the environmental impact assessment. The most used environmental measures were devices reducing electricity consumption (hotels 94%, guesthouses 94%), separating waste (hotels 88%, guesthouses 89%), and water consumption reduction (hotels 85%, guesthouses 86%). At the same time, the most minor used were measures reducing chemical consumption (hotels 23%, guesthouses 22%) communication and environmental education of employees and guests (hotels 32%, guesthouses 18%).
Læs mere Tjek på PubMedYing Kong, Liang Hong, Xiao-cheng Xu, Yun-feng Chen, Jia Xu
PLoS One Infectious Diseases, 29.04.2024
Tilføjet 29.04.2024
by Ying Kong, Liang Hong, Xiao-cheng Xu, Yun-feng Chen, Jia Xu Objective Immune checkpoint inhibitor pneumonitis (CIP) is a prevalent form of immunotherapy-induced pulmonary toxicity, ranking among the leading causes of mortality associated with immune checkpoint inhibitors (ICIs). Despite its significance, the risk stratification of CIP in advanced non-small cell lung cancer (NSCLC) remains uncertain. In this study, we conducted a comprehensive analysis, comparing various factors such as histological types, treatment regimens, PD-L1 expression levels, and EGFR/ALK negativity in advanced NSCLC. Our investigation extends to evaluating the relative risk of developing CIP based on previous treatment history. This analysis aims to provide valuable insights for the identification of specific patient subgroups at higher risk, facilitating more effective risk management and precision therapy approaches. Methods PubMed, Embase, and Cochrane databases were systematically searched up to February 16, 2023. We conducted a screening of randomized controlled trials (RCTs) that compared ICI monotherapy or its combination with chemotherapy in advanced NSCLC. The trials were categorized based on histological type, treatment regimen, PD-L1 expression level, EGFR/ALK-negative status, and prior treatment history. Subsequently, the data were stratified into five subgroups, and the occurrences of all-grades (1–5) and high-grades (3–5) pneumonia events were extracted. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were then calculated for further analysis. Results Twenty-two RCTs, encompassing 13,725 patients with advanced NSCLC, were included in this analysis. Regardless of histology (OR = 2.47, 95% CI 1.41–4.33, P = 0.002; OR = 1.84, 95% CI 1.10–3.09, P = 0.02), treatment regimen (OR = 3.27, 95% CI 2.00–5.35, P < 0.00001; OR = 2.91, 95% CI 1.98–4.27, P < 0.00001), PD-L1 expression level (OR = 5.11, 95% CI 2.58–10.12, P < 0.00001; OR = 5.15, 95% CI 2.48–10.70, P < 0.0001), negative EGFR/ALK expression (OR = 4.32, 95% CI 2.22–8.41, P < 0.0001; OR = 3.6, 95% CI 1.56–8.28, P = 0.003), whether there is a history of treatment (OR = 3.27, 95% CI 2.00–5.35, P < 0.00001; OR = 2.74, 95% CI 1.75–4.29, P < 0.0001), ICI use was associated with a higher risk of all-grade (1–5) and high-grade (3–5) pneumonia compared to chemotherapy. Subgroup analysis revealed that the squamous group, the ICI vs. combination chemotherapy (CT) group, the PD-L1 > 50% group, and the previously untreated group had a higher risk of developing all-grade and grade 3–5 CIP (P < 0.05). Conclusions In advanced NSCLC, ICI treatment was linked to an elevated risk of pneumonitis across all grades (1–5) as well as high-grade occurrences (3–5) compared to chemotherapy. Notably, individuals with squamous histology and high PD-L1 expression, along with those lacking a history of prior treatment, demonstrated a heightened susceptibility to developing immune-related pneumonitis of all grades (1–5) and high grades (3–5). These observations provide valuable insights for clinicians seeking to enhance the management of pulmonary toxicity associated with immunotherapy.
Læs mere Tjek på PubMedFrancisco Guillén-Chable, Johnny Omar Valdez Iuit, Luis Alejandro Avila Castro, Carlos Rosas, Enrique Merino, Zuemy Rodríguez-Escamilla, Mario Alberto Martínez-Núñez
PLoS One Infectious Diseases, 29.04.2024
Tilføjet 29.04.2024
by Francisco Guillén-Chable, Johnny Omar Valdez Iuit, Luis Alejandro Avila Castro, Carlos Rosas, Enrique Merino, Zuemy Rodríguez-Escamilla, Mario Alberto Martínez-Núñez Horizontal gene transfer (HGT) is a well-documented strategy used by bacteria to enhance their adaptability to challenging environmental conditions. Through HGT, a group of conserved genetic elements known as mobile genetic elements (MGEs) is disseminated within bacterial communities. MGEs offer numerous advantages to the host, increasing its fitness by acquiring new functions that help bacteria contend with adverse conditions, including exposure to heavy metal and antibiotics. This study explores MGEs within microbial communities along the Yucatan coast using a metatranscriptomics approach. Prior to this research, nothing was known about the coastal Yucatan’s microbial environmental mobilome and HGT processes between these bacterial communities. This study reveals a positive correlation between MGEs and antibiotic resistance genes (ARGs) along the Yucatan coast, with higher MGEs abundance in more contaminated sites. The Proteobacteria and Firmicutes groups exhibited the highest number of MGEs. It’s important to highlight that the most abundant classes of MGEs might not be the ones most strongly linked to ARGs, as observed for the recombination/repair class. This work presents the first geographical distribution of the environmental mobilome in Yucatan Peninsula mangroves.
Læs mere Tjek på PubMedMalaria Journal, 29.04.2024
Tilføjet 29.04.2024
Abstract Background Despite efforts made to reduce morbidity and mortality associated with malaria, especially in sub-Saharan Africa, malaria continues to be a public health concern that requires innovative efforts to reach the WHO-set zero malaria agenda. Among the innovations is the use of artemisinin-based combination therapy (ACT) that is effective against Plasmodium falciparum. Generic artemether–lumefantrine (AL) is used to treat uncomplicated malaria after appropriate diagnosis. AL is metabolized by the cytochrome P450 family of enzymes, such as CYP2B6, CYP3A4 and CYP3A5, which can be under pharmacogenetic influence. Pharmacogenetics affecting AL metabolism, significantly influence the overall anti-malarial activity leading to variable therapeutic efficacy. This study focused on generic AL drugs used in malarial treatment as prescribed at health facilities and evaluated pharmacogenomic influences on their efficacy. Methods Patients who have been diagnosed with malaria and confirmed through RDT and microscopy were recruited in this study. Blood samples were taken on days 1, 2, 3 and 7 for parasite count and blood levels of lumefantrine, artemisinin, desbutyl-lumefantrine (DBL), and dihydroartemisinin (DHA), the active metabolites of lumefantrine and artemether, respectively, were analysed using established methods. Pharmacogene variation analysis was undertaken using iPLEX microarray and PCR–RFLP. Results A total of 52 patients completed the study. Median parasite density from day 1 to 7 ranged from 0–2666/μL of blood, with days 3 and 7 recording 0 parasite density. Highest median plasma concentration for lumefantrine and desbutyl lumefantrine, which are the long-acting components of artemisinin-based combinations, was 4123.75 ng/mL and 35.87 ng/mL, respectively. Day 7 plasma lumefantrine concentration across all generic ACT brands was ≥ 200 ng/mL which potentially accounted for the parasitaemia profile observed. Monomorphism was observed for CYP3A4 variants, while there were observed variations in CYP2B6 and CYP3A5 alleles. Among the CYP3A5 genotypes, significant differences in genotypes and plasma concentration for DBL were seen on day 3 between 1/*1 versus *1/*6 (p = 0.002), *1/*3 versus *1/*6 (p = 0.006) and *1/*7 versus *1/*6 (p = 0.008). Day 7 plasma DBL concentrations showed a significant difference between *1/*6 and *1/*3 (p = 0.026) expressors. Conclusions The study findings show that CYP2B6 and CYP3A5 pharmacogenetic variations may lead to higher plasma exposure of AL metabolites.
Læs mere Tjek på PubMedInfection, 29.04.2024
Tilføjet 29.04.2024
Infection, 29.04.2024
Tilføjet 29.04.2024
Abstract Purpose Bloodstream infections (BSI) and sepsis are important causes of hospitalization, loss of health, and death globally. Targetable risk factors need to be identified to improve prevention and treatment. In this study, we aimed to evaluate the association of chronic kidney disease (CKD) and risk of and mortality from BSI and sepsis in the general population during a 22-year period. Methods We conducted a prospective cohort study among participants in the population-based Norwegian HUNT Study, where 68,438 participated. The median follow-up time was 17.4 years. The exposures were estimated glomerular filtration rate (eGFR) and albumin–creatinine ratio (ACR) in urine. The outcomes were hazard ratios (HR) of hospital admission or death due to BSI or sepsis. The associations were adjusted for age, sex, diabetes, obesity, systolic blood pressure, smoking status, and cardiovascular disease. Results Participants with eGFR 30 mg/mmol) had HR 3.60 for BSI (95% CI 2.30–5.6) and 3.14 for sepsis (95% CI 1.94–5.1) compared to normal albumin excretion (ACR
Læs mere Tjek på PubMedJournal of the American Medical Association, 29.04.2024
Tilføjet 29.04.2024
Observational studies have suggested that rapid viral testing for respiratory viruses is tied to lower use of antibiotics. Now, a meta-analysis published in JAMA Internal Medicine suggests that may not be the case, based on results from 11 randomized clinical trials involving about 6100 participants.
Læs mere Tjek på PubMedJournal of the American Medical Association, 29.04.2024
Tilføjet 29.04.2024
Currently, the World Health Organization (WHO) recommends using dolutegravir, an integrase strand transfer inhibitor approved by the US Food and Drug Administration in 2013, as a first- and second-line drug for treating people with HIV. But resistance to the treatment is on the rise. About 4% to as many as about 20% of people in 4 countries reporting data—Malawi, Mozambique, Uganda, and Ukraine—who had not achieved viral suppression exhibited resistance while taking the drug as part of their antiretroviral therapy, a recent report by the WHO found.
Læs mere Tjek på PubMedJournal of the American Medical Association, 29.04.2024
Tilføjet 29.04.2024
Deaths associated with excessive alcohol use have been rising over the past 20 years. But during 2020-2021 they went up dramatically—from an average of about 138 000 deaths during 2016-2017 to more than 178 000 deaths during the COVID-19 pandemic. The change represents a 29% increase in lives lost, according to results published in the MMWR.
Læs mere Tjek på PubMedJournal of the American Medical Association, 29.04.2024
Tilføjet 29.04.2024
This Medical News article is an interview with JAMA Editor in Chief Kirsten Bibbins-Domingo and Virologist Davey Smith, head of the Division of Infectious Diseases and Global Public Health at the University of California, San Diego.
Læs mere Tjek på PubMedJournal of the American Medical Association, 29.04.2024
Tilføjet 29.04.2024
This study discusses whether facilitated telemedicine for hepatitis C treatment increases cure rates compared with standard-of-care referral to hepatitis specialists.
Læs mere Tjek på PubMedBloom, J. E., Nehme, E., Paratz, E. D., Dawson, L., Nelson, A. J., Ball, J., Eliakundu, A., Voskoboinik, A., Anderson, D., Bernard, S., Burrell, A., Udy, A. A., Pilcher, D., Cox, S., Chan, W., Mihalopoulos, C., Kaye, D., Nehme, Z., Stub, D.
BMJ Open, 29.04.2024
Tilføjet 29.04.2024
ObjectivesWe aimed to assess the healthcare costs and impact on the economy at large arising from emergency medical services (EMS) treated non-traumatic shock. DesignWe conducted a population-based cohort study, where EMS-treated patients were individually linked to hospital-wide and state-wide administrative datasets. Direct healthcare costs (Australian dollars, AUD) were estimated for each element of care using a casemix funding method. The impact on productivity was assessed using a Markov state-transition model with a 3-year horizon. SettingPatients older than 18 years of age with shock not related to trauma who received care by EMS (1 January 2015–30 June 2019) in Victoria, Australia were included in the analysis. Primary and secondary outcome measuresThe primary outcome assessed was the total healthcare expenditure. Secondary outcomes included healthcare expenditure stratified by shock aetiology, years of life lived (YLL), productivity-adjusted life-years (PALYs) and productivity losses. ResultsA total of 21 334 patients (mean age 65.9 (±19.1) years, and 9641 (45.2%) females were treated by EMS with non-traumatic shock with an average healthcare-related cost of $A11 031 per episode of care and total cost of $A280 million. Annual costs remained stable throughout the study period, but average costs per episode of care increased (Ptrend=0.05). Among patients who survived to hospital, the average cost per episode of care was stratified by aetiology with cardiogenic shock costing $A24 382, $A21 254 for septic shock, $A19 915 for hypovolaemic shock and $A28 057 for obstructive shock. Modelling demonstrated that over a 3-year horizon the cohort lost 24 355 YLLs and 5059 PALYs. Lost human capital due to premature mortality led to productivity-related losses of $A374 million. When extrapolated to the entire Australian population, productivity losses approached $A1.5 billion ($A326 million annually). ConclusionThe direct healthcare costs and indirect loss of productivity among patients with non-traumatic shock are high. Targeted public health measures that seek to reduce the incidence of shock and improve systems of care are needed to reduce the financial burden of this syndrome.
Læs mere Tjek på PubMedHardman, K., Davies, A., Demetri, A., Clayton, G., Bakhbakhi, D., Birchenall, K., Barnfield, S., Fraser, A., Burden, C., McGuinness, S., Miller, R., Merriel, A.
BMJ Open, 29.04.2024
Tilføjet 29.04.2024
ObjectivesTo explore and characterise maternity healthcare professionals’ (MHCPs) experience and practice of shared decision-making (SDM), to inform policy, research and practice development. DesignQualitative focus group study. SettingLarge Maternity Unit in the Southwest of England. ParticipantsMHCPs who give information relating to clinical procedures and pregnancy care relating to labour and birth and are directly involved in decision-making conversations were purposively sampled to ensure representation across MHCP groups. Data collectionA semistructured topic guide was used. Data analysisReflexive thematic analysis was undertaken. ResultsSeven focus groups were conducted, comprising a total of 24 participants (3–5 per group). Two themes were developed: contextualising decision-making and controversies in current decision-making. Contextual factors that influenced decision-making practices included lack of time and challenges faced in intrapartum care. MHCPs reported variation in how they approach decision-making conversations and asked for more training on how to consistently achieve SDM. There were communication challenges with women who did not speak English. Three controversies were explored: the role of prior clinical experience, the validity of informed consent when women were in pain and during life-threatening emergencies and instances where women declined medical advice. ConclusionsWe found that MHCPs are committed to SDM but need better support to deliver it. Structured processes including Core Information Sets, communication skills training and decision support aids may help to consistently deliver SDM in maternity care.
Læs mere Tjek på PubMedKadiyala, Gayatri Nikhila; Telwatte, Sushama; Wedrychowski, Adam; Janssens, Julie; Kim, Sun Jin; Kim, Peggy; Deeks, Steven; Wong, Joseph K.; Yukl, Steven A.
AIDS, 29.04.2024
Tilføjet 29.04.2024
Objectives: Some drugs that augment cell-intrinsic defenses or modulate cell death/survival pathways have been reported to selectively kill cells infected with HIV or SIV, but comparative studies are lacking. We hypothesized that these drugs may differ in their ability to kill cells infected with intact and defective proviruses. Design: To investigate this hypothesis, drugs were tested ex vivo on Peripheral Blood Mononuclear Cells (PBMC) from nine ART-suppressed individuals. Methods: We tested drugs currently in clinical use or human trials, including auranofin (p53 modulator), interferon alpha2A, interferon gamma, acitretin (RIG-I inducer), GS-9620/vesatolimod (TLR7 agonist), nivolumab (PD-1 blocker), obatoclax (Bcl-2 inhibitor), birinapant (IAP inhibitor), bortezomib (proteasome inhibitor), and INK128/sapanisertib (mTOR[c]1/2 inhibitor). After six days of treatment, we measured cell counts/viabilities and quantified levels of total, intact, and defective HIV DNA by droplet digital PCR (Intact Proviral DNA Assay). Results: Obatoclax reduced intact HIV DNA (median = 27–30% of DMSO) but not defective or total HIV DNA. Other drugs showed no statistically significant effects. Conclusions: Obatoclax and other Bcl-2 inhibitors deserve further study in combination therapies aimed at reducing the intact HIV reservoir in order to achieve a functional cure and/or reduce HIV-associated immune activation.
Læs mere Tjek på PubMedFilip, Iulia
AIDS, 29.04.2024
Tilføjet 29.04.2024
Siyue JiaZundong YinHongxing PanFuzhen WangXiaoqiang LiuQing WangLi ZhangJihai TangHao YangJiangbo DuZhiguo WangPengfei JinZhihang PengRong TangGuodong KangXuewen WangSimin LiWeixiao WangJingxin LiHongbing ShenFengcai Zhua NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of Chinab National Vaccine Innovation Platform and Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of Chinac China Center for Disease Control and Prevention, Beijing, People’s Republic of Chinad Yunnan Provincial Center for Disease Control and Prevention, Kunming, People’s Republic of Chinae Chongqing Provincial Center for Disease Control and Prevention, Chongqing, People’s Republic of Chinaf Shandong Provincial Center for Disease Control and Prevention, Jinan, People’s Republic of Chinag Anhui Provincial Center for Disease Control and Prevention, Hefei, People’s Republic of Chinah Hunan Provincial Center for Disease Control and Prevention, Changsha, People’s Republic of Chinai School of Public Health, Southeast University; Nanjing, People’s Republic of Chinaj Canming Medical Technology Co., Ltd, Shanghai, People’s Republic of China
Emerg Microbes Infect, 29.04.2024
Tilføjet 29.04.2024
Coburn, Sally B.; Pimentel, Noel; Leyden, Wendy; Kitahata, Mari; Moore, Richard D.; Althoff, Keri N.; Gill, M. John; Lang, Raynell; Horberg, Michael A.; D’Souza, GypsyAmber; Hussain, Shehnaz K.; Dubrow, Robert; Novak, Richard M.; Rabkin, Charles S.; Park, Lesley S.; Sterling, Timothy R.; Neugebauer, Romain S.; Silverberg, Michael J.; for the North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear. Setting: Cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design. Methods: We followed individuals from ART initiation (protease inhibitor [PI]-, non-nucleoside reverse transcriptase inhibitor [NNRTI]-, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, 12/31/2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (non-mutually exclusive) as: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials. Results: We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up) and 1,782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85 months follow-up indicated no cancer risk differences. In truncated analyses, risk of ADCs (aHR 1.33; 95% CI 1.00, 1.77 [PP-analysis]) and NADCs (aHR 1.23; 95% CI 1.00, 1.51[ITT-analysis]) were higher comparing PIs vs. NNRTIs. Conclusions: Results with longer-term follow-up suggest being on a PI- versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedD’Antoni, Michelle L.; Andreatta, Kristen; Chang, Silvia; Cox, Stephanie; Hindman, Jason T.; Avihingsanon, Anchalee; Martin, Hal; VanderVeen, Laurie A.; Callebaut, Christian
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: In the Phase 3 ALLIANCE study, both bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (DTG + F/TDF) achieved high rates of HIV-1 RNA suppression through Week 96 in adults with HIV-1 and hepatitis B virus (HBV) initiating treatment (NCT03547908). Here, we quantify preexisting HIV-1 resistance, evaluate its effect on HIV-1 virologic suppression, and describe postbaseline HIV-1 resistance through Week 96. Methods: Preexisting HIV-1 resistance was assessed by historical and/or screening genotyping. HIV-1 RNA suppression to
Læs mere Tjek på PubMedAudet, Carolyn M.; Graves, Erin; Shepherd, Bryan E.; Prigmore, Heather L.; Brooks, Hannah L.; Emílio, Almiro; Matino, Ariano; Paulo, Paula; Diemer, Matthew A.; Frisby, Michael; Sack, Daniel E.; Aboobacar, Arifo; Barreto, Ezequiel; Van Rompaey, Sara; De Schacht, Caroline
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Introduction: There is evidence that a supportive male partner facilitates maternal HIV testing during pregnancy, increases maternal ART initiation and adherence, and increases HIV-free infant survival. Most male partner engagement clinical strategies have focused on increasing uptake of couple-based HIV testing and counseling. We delivered a couple-based care and treatment intervention to improve of ART adherence in expectant couples living with HIV. Methods: We implemented a cluster randomized controlled trial for seroconcordant couples living with HIV, comparing retention (patient’s medication possession ratio) in HIV care for a couple-based care and treatment intervention versus standard of care services in rural Mozambique. The intervention included couple-based treatment, couple-based education and skills building, and couple-peer educator support. Results: We recruited 1080 couples to participate in the study. Using a linear mixed effect model with a random effect for clinic, the intervention had no impact on the medication possession ratio among women at 12 months. However, the intervention increased men’s medication ratio by 8.77%. Our unadjusted logistic regression model found the odds of an infant seroconverting in the intervention group was 30% less than in the control group, but the results were not statistically significant. Discussion: Our intervention resulted in no difference in maternal outcomes, but improved medication possession ratio among male partners. We provide a community/clinic-based treatment framework that can improve outcomes among male partners. Further work needs to be done to improve social support for pregnant women and to facilitate prevention of vertical transmission to infants among couples living with HIV. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedNeary, Jillian; Njuguna, Irene; Wagner, Anjuli D.; Richardson, Barbra A.; Chebet, Daisy; Langat, Agnes; Ngugi, Evelyn; Benki-Nugent, Sarah; Moraa, Hellen; Hawes, Stephen E.; Overbaugh, Julie; Slyker, Jennifer A.; Lehman, Dara A.; Wamalwa, Dalton; John-Stewart, Grace
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: Identifying determinants of longitudinal HIV viral load (VL) trajectories using group-based trajectory modeling (GBTM) can inform clinical strategies and mechanisms of non-adherence among children. Methods: Children under 12 months of age who were newly diagnosed with HIV were enrolled in the Optimizing Pediatric HIV Therapy (OPH; NCT00428116) from 2007-2010. Children initiated antiretroviral therapy (ART) at enrollment, and VL was assessed every 3 months for 24 months post-ART and 6-monthly thereafter up to 8 years of age. VL trajectory groups were defined using GBTM. Fisher’s exact and Kruskal-Wallis tests were used to determine correlates of each trajectory group compared to the sustained-low VL group. Results: Five VL trajectory groups were identified among 89 children with 522 VL visits from 6-24 months: sustained-low VL (63% of children), sustained-very-high (16%), sustained-high (9%), low-to-high (7%), and high-with-periods-of-low (6%). Children in the sustained-high group were more frequently on a first-line protease inhibitor (PI)-based regimen (63% vs 38%; p=0.03) and had younger caregivers (median: 22 vs 28 years; p=0.02). Among 54 children with 560 VL visits followed from 48-96 months, 5 trajectory groups were identified: sustained-low (74%), mid-range (4%), periods-of-low (7%), high-to-low (7%), and sustained-high (7%). Those in the high-to-low group had younger caregivers (21 vs 29 years; p=0.01). Conclusions: GBTM identified unique VL patterns among children with unsuppressed VL. Caregiver and regimen-related characteristics were associated with patterns of non-suppression. Younger caregivers may benefit from tailored counseling to help them support child ART adherence. Palatable regimens are necessary for viral suppression among children with HIV. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedNoorman, Maaike A.J.; de Wit, John B.F.; Marcos, Tamika A.; Stutterheim, Sarah E.; Jonas, Kai J.; Den Daas, Chantal
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Objective: As the developments towards HIV cure are gaining prominence, engagement of people with HIV (PWH) becomes crucial. This study aims to gain deeper insight into how PWH engage with HIV cure (research) by exploring their perspectives regarding awareness, importance, and meaning of HIV cure (research). Methods: Semi-structured interviews were conducted with 30 purposively sampled PWH in the Netherlands. Interviews were transcribed verbatim and thematic data analysis was undertaken. Results: The overall necessity for an HIV cure was high, but personal perceived necessity varied based on participants’ lived experiences with HIV. Most participants saw less personal necessity due to their high quality of life, while those more affected by their HIV status expressed a stronger need for a cure. Participants held high expectations for an HIV cure, considering viral eradication as the only cure. Lack of awareness of potential HIV cure strategies and techniques shaped concerns. Antiretroviral treatment-free viral suppression was met with concerns and not considered a cure, but rather an improved form of treatment. Engagement with HIV cure manifested in various forms and levels, with only a few participants actively engaged or willing to participate in HIV cure clinical research. Most participants were interested but inactive and unsure about participating in HIV cure clinical research. Conclusions: PWH’s social engagement in HIV cure (research) is shaped by their perceived necessity and concerns. Understanding these perceptions can increase social engagement. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedMurphy, Matthew; Rogers, Brooke; Galipeau, Drew; Toma, Emily; Almonte, Alexi; Napoleon, Siena; Schmid, Christopher H.; Ahluwalia, Jasjit S.; Chan, Philip
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: Pre-exposure prophylaxis (PrEP) is an effective approach to preventing HIV acquisition and is recommended for populations overrepresented in carceral systems given the overlap with populations disproportionately impacted by HIV. However, few studies have focused on PrEP initiation outcomes in a carceral setting to maximize public health impact. Setting: This study was conducted in a unified jail/prison system within the state of Rhode Island located in the United States. Methods: A prospective observational cohort of men initiating PrEP within a jail setting were enrolled in this trial. Men were referred by providers, staff, or after self-presenting for HIV preventive care, these individuals were offered enrollment in the study which involved evaluation for clinical PrEP eligibility, PrEP initiation while incarcerated, continuation upon community re-entry and linkage to a community PrEP provider post-release. Results: A total of (N=100) men in the jail facility (e.g. “intake”) were enrolled in the cohort. Of the 100 men enrolled, 83% were determined to be PrEP eligible through standard clinical evaluation, 37% were prescribed PrEP, and 26% initiated PrEP while incarcerated. In total, 5% of enrolled individuals were linked successfully to PrEP care in the community. Conclusion: Our findings suggest preliminary feasibility and acceptability of initiating PrEP within a jail setting. There were significant challenges across the PrEP care continuum that can be used to inform future studies and practice. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedMutetwa, Tinaye; Liu, Yuxin; Silvera, Richard; Evans, Michelle; Yurich, Michael; Tripodi, Joseph; Leonard, Issa; Houldsworth, Jane; Gümüş, Zeynep; Bowcock, Anne M.; Sigel, Keith; Gaisa, Michael; Polak, Paz
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
BACKGROUND: People living with HIV (PLWH) have substantially increased incidence of anal precancer and cancer. There are very little data regarding genomic disturbances in anal precancers among PLWH. Here, we identified specific chromosomal variants in anal squamous intraepithelial lesions. METHODS: We collected 63 anal biopsy specimens (27 low-grade intraepithelial lesions [LSIL] and 36 high-grade intraepithelial lesions [HSIL]) from PLWH obtained as part of anal cancer screening in our NYC-based health system. Data on patient demographics, anal cytological and high-risk human papillomavirus (HR-HPV) diagnoses were collected. Specimens were tested for a panel of chromosomal alterations associated with HPV-induced oncogenesis using Fluorescence In-Situ Hybridization (FISH) and analyses compared the associations of these alterations with clinical characteristics. RESULTS: Gains of 3q26, 5p15, 20q13 and cen7 were detected in 42%, 31%, 31%, and 19% of HSIL compared to 7%, 0%, 4%, and 0% of LSIL, respectively. Where at least one abnormality was seen, 89% had a 3q26 gain. In lesions with 5p15 gains, 20q13 gains co-occurred in 91% of cases, while cen7 gain only co-occurred with the other three alterations. Sensitivity and specificity of any alteration to predict HSIL was 47% (95% CI: 30-65%) and 93% (95% CI: 76%-99%) respectively. CONCLUSIONS: Genomic alterations seen in HPV-associated cancers may help distinguish anal LSIL from HSIL. 3q26 amplification may be an early component of anal carcinogenesis, preceding 5p16, 20q13 and/or chr7. IMPACT: We share insights on potential genomic biomarkers for discriminating high-risk anal precancers. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedRosenthal, Mark; Patterson, Wendy; Rajulu, Deepa T.
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: Late HIV diagnosis is associated with a wide range of negative outcomes. This study aims to identify characteristics of individuals who received a concurrent diagnosis (CDX) in New York State (NYS) so that more effective interventions can be developed to encourage earlier testing among these populations. Methods: The NYS HIV registry was used to identify people who received a CDX from 2016 – 2021. A CDX was a diagnosis that met the criteria for a stage 3 HIV infection within 30 days of the initial HIV diagnosis. Sex at birth, race/ethnicity, transmission risk group, age at diagnosis, region of residence at diagnosis, urbanicity of zip code of diagnosis, and type of diagnosing facility were used as covariates. Bivariate and multivariate risk ratios were calculated to quantify associations between CDX and covariates. Results: There were 14,866 people newly diagnosed with HIV in NYS from 2016 – 2021, of which 19.0% had a CDX. Those with female sex at birth, IDU, or MSM/IDU risk were less likely to have a CDX. Increased age, Asian race/ethnicity, residence outside of New York City, and diagnosis at inpatient facilities or emergency rooms were associated with an increased likelihood of a CDX. Conclusion: Populations with the highest proportions of CDX were ones that made up a small percentage of all new HIV diagnoses and may not be benefiting as much from current HIV prevention efforts. There are complex interactions between many factors including geographic and social characteristics which may lead to delayed diagnostic testing. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedWhite, Douglas AE; Godoy, Ashley; Jewett, Montana; Burns, Molly; Pinto, Cinthya Mujica; Packel, Laura J; Garcia-Chinn, Maria; Anderson, Erik S; McCoy, Sandra I
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: Emergency departments (ED) provide care to patients at increased risk for acquiring HIV and for many of them, the ED serves as their sole point of entry into the healthcare system. We implemented the HIV PreventED Program to increase access to HIV prevention services for ED patients. Setting: Emergency department in Oakland, CA with an annual census of 57,000 visits. Methods: This cross-sectional study evaluated the first 9 months of the HIV PreventED Program. In this program, a navigator surveyed adult HIV negative ED patients to determine their risk for acquiring HIV infection, incorporating HIV prevention counseling into their assessments. Patients at higher risk for acquiring HIV were referred to outpatient prevention services, if interested. The primary outcome measure was the number and proportion of ED patients at higher risk for acquiring HIV that followed up for outpatient prevention services. Results: There were 1,233 HIV negative patients assessed by the navigator and who received ED-based HIV prevention counseling. Of these, 193 (15.7%) were identified at higher risk and offered an outpatient referral for prevention services, of which 104 accepted (53.9%), 23 (11.9%) attended the referral, and 13 (6.7%) were prescribed pre-exposure prophylaxis (PrEP). The median time to linkage was 28 days (interquartile range 15 to 41 days). Conclusion: A navigator focused on providing ED-based HIV prevention counseling and linkage to outpatient services is feasible. Strategies to more efficiently identify ED patients at higher risk for HIV acquisition, such as automated identification of risk data from the electronic health record, and policies to improve follow up and the receipt of PrEP, such as same-day PrEP initiation, should be prospectively evaluated. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedBennett, Christopher L; Saxena, Monica; Boothroyd, Derek; Mahmoud-Werthmann, Sally; Lin, Michelle P
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
BECKER, Marissa; MISHRA, Sharmistha; BHATTACHARJEE, Parinita; MUSYOKI, Helgar; TENNAKOON, Aruni; LEUNG, Stella; CHEUK, Eve; LORWAY, Rob; ISAC, Shajy; MA, Huiting; CHOLETTE, Francois; SANDSTROM, Paul; GICHANGI, Peter; MWATELAH, Ruth; MCKINNON, Lyle; BLANCHARD, James; PICKLES, Michael; the Transitions Study Team
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Background: The design of HIV prevention programs for adolescent girls and young women (AGYW) are informed by data on who is at highest risk, and where they can be reached. Places (hotspots) associated with selling sex are an established outreach strategy for sex work programs, but could be used to reach other AGYW at high risk. Setting: This study took place in Mombasa, Kenya. Methods: We conducted a cross-sectional, bio-behavioural survey among (N=1,193) sexually active AGYW aged 14-24 years recruited at hotspots. We compared HIV prevalence by sub-group (sex work, SW; transactional sex, TS; and non-transactional sex, NTS), stratified by hotspot type (venues and non-venues). We examined whether associations between HIV prevalence and hotspot/subgroup remained after adjustment for individual-level risk factors, and estimated HIV prevalence ratio (PR) with and without adjustment for these individual-level factors. Results: Overall HIV prevalence was 5.6%, 5.3% in venues and 7.3% in non-venues. Overall SW HIV prevalence was two-fold higher than among participants engaged in NTS. After adjusting for age and individual-level risk factors, HIV prevalence was 2.72 times higher among venue-based SWs (95% CI: 1.56-4.85) and 2.11 times higher among non-venue AGYW not engaged in SW (95% CI: 0.97-4.30) compared to venue-based AGYW not engaged in SW. Conclusion: AGYW who sell sex remain at high risk of HIV across types of hotspots. The residual pattern of elevated HIV burden by AGWY subgroup and hotspot type suggests that unmeasured, network-level factors underscore differential risks. As such, hotspots constitute a “place” to reach AGYW at high risk of HIV. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedMcCrimmon, Tara; Collins, Lauren F.; Pereyra, Margaret; Platamone, Corbin; Perez-Brumer, Amaya; Shaffer, Victoria A.; Kerrigan, Deanna; Sheth, Anandi N; Cohen, Mardge H; Hanna, David B.; Ramirez, Catalina; Gange, Stephen J.; Rana, Aadia; Tamraz, Bani; Goparaju, Lakshmi; Wilson, Tracey E; Alcaide, Maria; Philbin, Morgan M.
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Iannone, V.; Ciccullo, A.; Moschese, D.; Giacomelli, A.; Fabbiani, M.; Lagi, F.; Papalini, C.; De Vito, A.; Cossu, M.V.; Di Giambenedetto, S.; Borghetti, A.
Journal of Acquired Immune Deficiency Syndromes, 29.04.2024
Tilføjet 29.04.2024
Infectious Disease Modelling, 29.04.2024
Tilføjet 29.04.2024
Publication date: Available online 28 April 2024 Source: Infectious Disease Modelling Author(s): Cristiano Trevisin, Lorenzo Mari, Marino Gatto, Andrea Rinaldo
Læs mere Tjek på PubMedInfection, 28.04.2024
Tilføjet 28.04.2024
Abstract Background Herpes simplex encephalitis (HSE) is a disease with unfavorable vital and functional prognoses. There are no recent epidemiological data on HSE at a national level using real-life databases, especially in France. This study aimed to report the incidence, the clinical characteristics and outcomes of the patients with HSE. Methods We conducted a comprehensive retrospective cohort study on all patients hospitalized for HSE in France between 2015 and 2022 using national hospital discharge databases. Incidence, socio-demographic and clinical characteristics (including comorbidities, seizure, stays’ features, intensive care supports) were described. The short- (first stay) and long-term (6-month) outcomes were reported, in terms of mortality and rehospitalizations. Results 1425 HSE patients were included (median age 67 [54–77] years old, M/F sex ratio 1.07), giving a mean yearly hospital incidence of 2.3 [2.1–2.5] per 1,000,000 inhabitants. 51.2% of the patients were admitted in ICU (n = 730), of whom 59.0% were mechanically ventilated. The overall mortality during the first stay was 14.3% (n = 204), up to 17.9% for ICU patients. Within 6 months, among the survivors, 10.1% had at least one rehospitalization related to HSE. At 6 months, 16.5% of all patients had died (n = 235), 20.8% for ICU patients. Conclusion In France, the incidence of hospitalizations for HSE was 2.3 per 1,000,000 inhabitants with more than half of the patients admitted in ICU and a 6-month in-hospital mortality about 16.5%. This real-life update on the characteristics and severe outcomes of the disease raises awareness among care practitioners, of the serious nature of the disease, and thus can lead to higher vigilance.
Læs mere Tjek på PubMedInfection, 28.04.2024
Tilføjet 28.04.2024
Abstract Background The stress hyperglycemia ratio (SHR), adjusted for average glycemic status, is suggested for assessing actual blood glucose levels. Its link with adverse outcomes is known in certain populations, yet its impact on sepsis patients’ prognosis is unclear. This study explores the association between SHR and mortality in sepsis. Methods We included 13,199 sepsis patients in this study and categorized SHR into distinct groups. Additionally, we utilized restricted cubic spline analysis to evaluate the correlation between SHR as a continuous variable and mortality. The primary outcome was 1-year all-cause mortality. Logistic regression and Cox proportional hazards models were employed to assess the associations between the SHR and both in-hospital mortality and 1-year mortality, respectively. Results Among the study participants, 4,690 (35.5%) patients died during the 1-year follow-up. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and 1-year mortality. Using an SHR of 0.99 as the reference point, the hazard ratio for predicted 1-year mortality increased by 1.17 (95% CI 1.08 to 1.27) per standard deviation above 0.99, whereas each standard deviation increase predicted the hazard ratio of 0.52 (95% CI 0.39 to 0.69) below 0.99. Furthermore, we found that SHR could enhance the predictive performance of conventional severity scores. Conclusion There exists a U shaped association between SHR and mortality in sepsis patients, where both low and high SHR values are associated with an increased risk of poor outcomes.
Læs mere Tjek på PubMedInfection, 28.04.2024
Tilføjet 28.04.2024
Abstract Purpose Surgery is required in 20–50% of patients with infective endocarditis (IE). Frailty increases surgical risk; however, the prognostic implications of frailty in patients undergoing IE-related surgery remain poorly understood. We aimed to assess the association between frailty and all-cause mortality or rehospitalization after discharge (≥ 14 days). Methods We identified all IE patients who underwent surgery during admission (2010–2020) in Denmark. The Hospital Frailty Risk Score was used to categorize patients into two frailty risk groups, patients with low frailty scores ( 14 days) in the first post-discharge year (19.1% vs.12.3%) compared to patients with low frailty scores. Additionally, frail patients had higher rates of all-cause mortality including in-hospital deaths (27% vs. 15%) and rehospitalizations (43.5% vs 26.1%) compared to patients with low frailty scores. This was also evident in the adjusted analysis (hazard ratio 1.36 [CI 95% 1.09–1.71]). Conclusion Frailty was associated with an ≈40% increased rate of rehospitalization (≥ 14 days) or death. Further studies are needed to assess the effectiveness of surgery with a focus on frailty to improve prognostic outcomes in these patients.
Læs mere Tjek på PubMedInfection, 28.04.2024
Tilføjet 28.04.2024
Abstract Background Meningococcal meningitis is still a severe disease causing high mortality and morbidity rates. Early diagnosis is crucial to ensure prompt antibiotic therapy. However, identification of the pathogen can be challenging. Case presentation A 32-year-old male patient with systemic lupus erythematosus (SLE) presented to the emergency room with fever, nausea, vomiting, headache and lower back pain as well as multiple petechial bleedings. On suspicion of meningococcal infection, the emergency doctor had already administered one dose of ceftriaxone before arrival to the clinic. Blood works showed massive inflammation due to bacterial infection. Cerebrospinal fluid (CSF) analysis showed normal cell count, protein and glucose levels but PCR was positive for Neisseria meningitis and IL-6 as well as IL-8 were elevated. On antibiotic therapy with ceftriaxone, the patient’s condition improved quickly. Conclusions We present a rare case of meningococcal infection of the CSF in a SLE patient without further CSF abnormalities. We discuss the involvement of early antibiotic treatment and the role of the patient’s immune status in the normal CSF findings of this case. Moreover, this case demonstrates the importance of early antibiotic therapy in bacterial meningitis for the clinical outcome.
Læs mere Tjek på PubMedBeagle, Alexander J.; Prasad, Priya A.; Hubbard, Colin C.; Walderich, Sven; Oreper, Sandra; Abe-Jones, Yumiko; Fang, Margaret C.; Kangelaris, Kirsten N.
Critical Care Explorations, 28.04.2024
Tilføjet 28.04.2024
OBJECTIVES: To evaluate the relationship between early IV fluid volume and hospital outcomes, including death in-hospital or discharge to hospice, in septic patients with and without heart failure (HF). DESIGN: A retrospective cohort study using logistic regression with restricted cubic splines to assess for nonlinear relationships between fluid volume and outcomes, stratified by HF status and adjusted for propensity to receive a given fluid volume in the first 6 hours. An ICU subgroup analysis was performed. Secondary outcomes of vasopressor use, mechanical ventilation, and length of stay in survivors were assessed. SETTING: An urban university-based hospital. PATIENTS: A total of 9613 adult patients were admitted from the emergency department from 2012 to 2021 that met electronic health record-based Sepsis-3 criteria. Preexisting HF diagnosis was identified by the International Classification of Diseases codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1449 admissions from patients with HF. The relationship between fluid volume and death or discharge to hospice was nonlinear in patients without HF, and approximately linear in patients with HF. Receiving 0–15 mL/kg in the first 6 hours was associated with lower likelihood of death or discharge to hospice compared with 30–45 mL/kg (odds ratio = 0.61; 95% CI, 0.41–0.90; p = 0.01) in HF patients, but no significant difference for non-HF patients. A similar pattern was identified in ICU admissions and some secondary outcomes. Volumes larger than 15–30 mL/kg for non-HF patients and 30–45 mL/kg for ICU-admitted non-HF patients were not associated with improved outcomes. CONCLUSIONS: Early fluid resuscitation showed distinct patterns of potential harm and benefit between patients with and without HF who met Sepsis-3 criteria. Restricted cubic splines analysis highlighted the importance of considering nonlinear fluid outcomes relationships and identified potential points of diminishing returns (15–30 mL/kg across all patients without HF and 30–45 mL/kg when admitted to the ICU). Receiving less than 15 mL/kg was associated with better outcomes in HF patients, suggesting small volumes may be appropriate in select patients. Future studies may benefit from investigating nonlinear fluid–outcome associations and a focus on other conditions like HF.
Læs mere Tjek på PubMedFEMS Microbiology Reviews, 28.04.2024
Tilføjet 28.04.2024
Abstract Group B Streptococcus (GBS; also known as Streptococcus agalactiae) is an opportunistic bacterial pathogen that causes sepsis, meningitis, pneumonia and skin and soft tissue infections in neonates and healthy or immunocompromised adults. GBS is well-adapted to survive in humans due to a plethora of virulence mechanisms that afford responses to support bacterial survival in dynamic host environments. These mechanisms and responses include counteraction of cell death from exposure to excess metal ions that can cause mismetallation and cytotoxicity, and strategies to combat molecules such as reactive oxygen and nitrogen species that are generated as part of innate host defence. Cytotoxicity from reactive molecules can stem from damage to proteins, DNA, and membrane lipids, potentially leading to bacterial cell death inside phagocytic cells or within extracellular spaces within the host. Deciphering the ways in which GBS responds to the stress of cytotoxic reactive molecules within the host will benefit the development of novel therapeutic and preventative strategies to manage the burden of GBS disease. This review summarises knowledge of GBS carriage in humans and the mechanisms used by the bacteria to circumvent killing by these important elements of host immune defence: oxidative stress, nitrosative stress, and stress from metal ion intoxication/mismetallation.
Læs mere Tjek på PubMedTianxu LiuYalei CaoJiaming WengSongzhan GaoZirun JinYun ZhangYuzhuo YangHe ZhangChangyou XiaXin YinYong LuoQiyu HeHui JiangLin WangZhe Zhanga Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People’s Republic of Chinab Department of Urology, Peking University Third Hospital, Beijing, People’s Republic of Chinac Center for Reproductive Medicine, Peking University Third Hospital, Beijing, People’s Republic of Chinad Department of Andrology, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of Chinae Department of Urology, Peking University First Hospital, Beijing, People’s Republic of Chinaf State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of China
Emerg Microbes Infect, 28.04.2024
Tilføjet 28.04.2024
Patricia Bernal
Trends in Microbiology, 28.04.2024
Tilføjet 28.04.2024
Gram-negative bacteria use the T6SS to eject effectors into prey cells, aided by delivery domains. Recently uncovered by Carobbi et al., a new delivery domain, PIX, allowed the identification of hundreds of new effectors. They are order- and function-specific and exclusively orphan effectors, raising novel questions in the field.
Læs mere Tjek på PubMedMalaria Journal, 28.04.2024
Tilføjet 28.04.2024
Abstract Background Malaria is still a disease of global public health importance and children under-five years of age are the most vulnerable to the disease. Nigeria adopted the “test and treat” strategy in the national malaria guidelines as one of the ways to control malaria transmission. The level of adherence to the guidelines is an important indicator for the success or failure of the country’s roadmap to malaria elimination by 2030. This study aimed to assess the fidelity of implementation of the national guidelines on malaria diagnosis for children under-five years and examine its associated moderating factors in health care facilities in Rivers State, Nigeria. Methods This was a descriptive, cross-sectional study conducted in Port Harcourt metropolis. Data were collected from 147 public, formal private and informal private health care facilities. The study used a questionnaire developed based on Carroll’s Conceptual Framework for Implementation Fidelity. Frequency, mean and median scores for implementation fidelity and its associated factors were calculated. Associations between fidelity and the measured predictors were examined using Mann Whitney U test, Kruskal Wallis test, and multiple linear regression modelling using robust estimation of errors. Regression results are presented in adjusted coefficient (β) and 95% confidence intervals. Results The median (IQR) score fidelity score for all participants was 65% (43.3, 85). Informal private facilities (proprietary patent medicine vendors) had the lowest fidelity scores (47%) compared to formal private (69%) and public health facilities (79%). Intervention complexity had a statistically significant inverse relationship to implementation fidelity (β = − 1.89 [− 3.42, − 0.34]). Increase in participant responsiveness (β = 8.57 [4.83, 12.32]) and the type of malaria test offered at the facility (e.g., RDT vs. no test, β = 16.90 [6.78, 27.03]; microscopy vs. no test, β = 21.88 [13.60, 30.16]) were positively associated with fidelity score. Conclusions This study showed that core elements of the “test and treat” strategy, such as testing all suspected cases with approved diagnostic methods before treatment, are still not fully implemented by health facilities. There is a need for strategies to increase fidelity, especially in the informal private health sector, for malaria elimination programme outcomes to be achieved.
Læs mere Tjek på PubMedMalaria Journal, 28.04.2024
Tilføjet 28.04.2024
Abstract Background Malaria contributes to excess child mortality in The Gambia. Children under five are at risk of severe malaria and death if not treated promptly and appropriately. It is crucial that a child with fever receive appropriate care from a trained provider. The aim was to identify influences on child fever care-seeking in The Gambia to inform malaria control strategies. Methods This cross-sectional analysis of The Gambia 2019–20 Demographic and Health Survey used logistic regression analysis to identify associations between source of care for a child with fever (public or private healthcare provider, other, or no treatment) and mother, child, and household characteristics. Results Only 52.0% of mothers sought care from a trained healthcare provider for a child with fever—45.1% from a public facility and 7.0% from the private sector. 35.2% of mothers did not seek treatment. Mothers in urban households were 2.67 times as likely (aOR, 95% CI 1.504–4.736) as mothers in rural households to seek care from an informal source (e.g., pharmacy) versus not seeking treatment, and 0.29 times as likely (aOR, 95% CI 0.165–0.515) as mothers in rural households to seek care from a public provider versus informal source. Mothers in wealthier households were 2.30 times as likely (aOR, 95% CI 1.274–4.164) as mothers in poorer households to seek care from an informal source versus no treatment and half as likely as mothers in poorer households to seek care from a public provider versus informal source (aOR 0.53, 95% CI 0.291–0.959). Conclusions Maintaining The Gambia’s malaria control achievements will require the active engagement and oversight of private pharmacies along with continued integrated community case management to reach mothers who do not seek care for a child with fever, and remove challenges to seeking appropriate care from trained providers. Whether influenced by convenience, costs, perceived urgency, or other factors, given the likelihood of urban mothers and mothers in wealthier households to seek care from private pharmacies, it will be necessary to incorporate private pharmacies into malaria control strategies while building public sector capacity and workforce, and initiating more effective attitude and behavioural change among mothers and households.
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