Abstract Background Lymphopenia is defined as a decrease below normal value (often 1.0 x 109 cells/L) of blood circulating lymphocyte count. In the general population, lymphopenia is associated with an increased risk of hospitalisation secondary to infection, independent of traditional clinical risk factors. In hospital, lymphopenia is associated with increased risk of healthcare-associated infection and mortality. By summarising lymphopenia’s prevalence and impact on clinical outcomes, we can identify an at-risk population and inform future studies of immune dysfunction following severe illness. Methods Peer-reviewed search strategy was performed on three databases. Primary objective was to summarise the pooled prevalence of lymphopenia. Primary outcome was infection including pre-existing lymphopenia as a risk factor for admission with infection and as an in-hospital risk factor for healthcare-associated infection. Secondary outcomes were length of stay and mortality. Mortality data extracted included in-hospital, 28/30-day (‘early’), and 90-day/1-year (‘late’) mortality. Meta-analysis was carried out using random-effects models for each outcome measure. Heterogeneity was assessed using I2 statistic. Joanna Briggs Institute checklist for cohort studies was used to assess risk of bias. The protocol was published on PROSPERO. Results Fifteen observational studies were included. The pooled prevalence of lymphopenia in all-cause hospitalisations was 38% (CI 0.34-0.42, I2= 97%, p< 0.01). Lymphopenia was not associated with an infection diagnosis at hospital admission and healthcare associated infection (RR 1.03; 95% CI 0.26-3.99, p=0.97, I2 = 55% and RR 1.31; 95% CI 0.78-2.20, p=0.31, I2=97%, respectively), but was associated with septic shock (RR 2.72; 95% CI 1.02-7.21, p=0.04, I2 =98%). Lymphopenia was associated with higher in-hospital mortality and higher ‘early’ mortality rates (RR 2.44; 95% CI 1.71-3.47, p < 0.00001, I2 = 89% and RR 2.05; 95% CI 1.64-2.56, p < 0.00001, I2 = 29%, respectively). Lymphopenia was associated with higher ‘late’ mortality (RR 1.59; 1.33-1.90, p < 0.00001, I2 = 0%). Conclusions This meta-analysis demonstrates the high prevalence of lymphopenia across all-cause hospitalisations and associated increased risk of septic shock, early and late mortality. Lymphopenia is a readily available marker that may identify immune dysfunctional patients. Greater understanding of immune trajectories following survival may provide insights into longer-term poor clinical outcomes. …

Abstract Research has shown that multidimensional approaches to Chagas disease (CD), integrating its biomedical and psycho-socio-cultural components, are successful in enhancing early access to diagnosis, treatment and sustainable follow-up. For the first time, a consulate was selected for a community-based CD detection campaign. Two different strategies were designed, implemented and compared between 2021 and 2022 at the Consulate General of Bolivia and a reference health facility in Barcelona open to all Bolivians in Catalonia. Strategy 1 consisted in CD awareness-raising activities before referring those interested to the reference facility for infectious disease screening. Strategy 2 offered additional in-situ serological CD screening. Most of the 307 participants were Bolivian women residents in Barcelona. In strategy 1, 73 people (35.8% of those who were offered the test) were screened and 19.2% of them were diagnosed with CD. Additionally, 53,4% completed their vaccination schedules and 28.8% were treated for other parasitic infections (strongyloidiasis, giardiasis, eosinophilia, syphilis). In strategy 2, 103 people were screened in-situ (100% of those who were offered the test) and 13.5% received a CD diagnosis. 21,4% completed their vaccination schedule at the reference health facility and 2,9% were referred for iron deficiency anemia, strongyloidiasis or chronic hepatitis C. The fact that the screening took place in an official workplace of representatives of their own country, together with the presence of community-based participants fueled trust and increased CD understanding. Each of the strategies assessed had different benefits. Opportunities for systematic integration for CD based on community action in consulates may enhance early access to diagnosis, care and disease prevention. …

Abstract Background Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). Methods HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell – IFN-γ activation was assessed by ELISpot. Results Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. Conclusions Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population. …

Abstract Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection. …

Abstract Objective To evaluate the association between traditional laboratory findings and death, and to find risk factors for death in infants with early onset sepsis (EOS). Study design This was a single-center, case–control, retrospective trial conducted between January 2020 and August 2021. Infants with EOS were enrolled and divided into two groups based on outcome before hospital discharge: non-survivors (Mortality group) and survivors (Survival group). Results Out of 556 eligible neonates, there were 38 (6.8%) deaths. After univariate analysis and ROC curve analysis, there were a total of 12 values with significant differences (p 

Abstract Background Whether different anti-hepatitis B virus (HBV) drugs have different effects on COVID-19 is controversial. We aimed to evaluate the incidence of COVID-19 in chronic hepatitis B (CHB) patients receiving anti-HBV treatment, and to compare the impact of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on the severity of COVID-19. Methods CHB outpatients were enrolled from December 2022 to February 2023. Questionnaires were used to collect whether subjects were currently or previously had COVID-19 within the past 2 months, and the information of symptoms, duration, and severity if infected. Results Six hundred thirty CHB patients were enrolled, 64.3% (405/630) patients were currently or previously had COVID-19. No COVID-19 patient required hospitalization, intensive care unit admission, oxygen support or died. Majority of patients reported mild (32.8% [133/405]) and moderate (48.1% [195/405]) symptoms. After propensity score matching, 400 matched patients were obtained (ETV: 238; TDF: 162), among which the incidences of COVID-19 were comparable between ETV and TDF-treated patients (60.1% [143/238] vs. 64.2% [104/162], p = 0.468). The proportion of patients complicated with any symptom caused by COVID-19 were also similar (ETV vs. TDF: 90.9% [130/143] vs. 91.3% [95/104], p = 1.000). In addition, the severity of overall symptom was comparable between ETV and TDF-treated patients, in terms of proportion of patients complicated with severe symptom (9.8% vs. 8.7%, p = 0.989), symptom duration (4.3 vs. 4.3 days, p = 0.927), and symptom severity score (4.1 vs. 4.0, p = 0.758). Subgroup analysis supported these results. Conclusions During the current pandemic, the vast majority of CHB patients experienced non-severe COVID-19, and ETV and TDF did not affect COVID-19 severity differently. …

Abstract Background The studies on SARS-CoV-2 and human microbiota have yielded inconsistent results regarding microbiota α-diversity and key microbiota. To address these issues and explore the predictive ability of human microbiota for the prognosis of SARS-CoV-2 infection, we conducted a reanalysis of existing studies. Methods We reviewed the existing studies on SARS-CoV-2 and human microbiota in the Pubmed and Bioproject databases (from inception through October 29, 2021) and extracted the available raw 16S rRNA sequencing data of human microbiota. Firstly, we used meta-analysis and bioinformatics methods to reanalyze the raw data and evaluate the impact of SARS-CoV-2 on human microbial α-diversity. Secondly, machine learning (ML) was employed to assess the ability of microbiota to predict the prognosis of SARS-CoV-2 infection. Finally, we aimed to identify the key microbiota associated with SARS-CoV-2 infection. Results A total of 20 studies related to SARS-CoV-2 and human microbiota were included, involving gut (n = 9), respiratory (n = 11), oral (n = 3), and skin (n = 1) microbiota. Meta-analysis showed that in gut studies, when limiting factors were studies ruled out the effect of antibiotics, cross-sectional and case–control studies, Chinese studies, American studies, and Illumina MiSeq sequencing studies, SARS-CoV-2 infection was associated with down-regulation of microbiota α-diversity (P 

Abstract We present a rare case of pathology-proven CMV pneumonitis in a patient with HIV infection after presenting with cough and fever. This presentation was complicated by recurrence of symptoms after treatment in the setting of continued uncontrolled HIV infection. This case raised the importance of further discussion regarding best treatment guidelines for CMV pneumonitis for patients with HIV. …

Abstract Background The elderly with severe infection increased dramatically in intensive care unit (ICU). Proper antimicrobial therapy help improve the prognosis. Linezolid, as an antimicrobial drug, is commonly utilized to treat patients infected with methicillin-resistant S. aureus and vancomycin-resistant enterococci. Clinical evidence suggests elderly patients prone to linezolid overexposure. Here, we describe the results of three years’ linezolid adjustment experiences according to therapeutic drug monitoring (TDM), especially in the oldest old. Methods Linezolid therapeutic drug monitoring data were collected between January 2020 and November 2022 from patients who were admitted to ICU and treated with linezolid. All the patients started with a dosage of 600 mg, twice daily. The first TMD was carried out ten minutes before the seventh administration. The dosage adjustment was determined by the doctor according to the first TMD and patients\' condition, and the repeated TDM was conducted as required. The dosage adjustment in different age group was recorded. Laboratory data were compared between the old and the oldest old. The high mortality risk of the oldest old was also explored. Results Data of 556 linezolid TDM from 330 patients were collected. Among which, 31.6%, 54.8%, and 75% of patients had supra-therapeutic linezolid trough concentrations at the first TDM assessment in different age group, leading to the dosage adjustment rate of 31.0%, 40.3%, 68.8% respectively. The linezolid dosage adjustments according to TDM help to reach therapeutic concentration. The oldest old was in high risk of linezolid overexposure with lowercreatinine clearance. The norepinephrine maximum dosage but not linezolid Cmin was associated with 28-day mortality in the oldest old. Conclusions Elderly patients with linezolid conventional 600 mg twice-daily dose might be at a high risk of overexposure, especially in the oldest old. The linezolid dosage adjustments according to TDM help reach the therapeutic concentration. The high mortality of the oldest old was not related with initial linezolid overexposure. …

Abstract Background Considering the fact that COVID-19 has undergone various changes over time, its symptoms have also varied. The aim of this study is to describe and compare the changes in personal characteristics, symptoms, and underlying conditions of individuals infected with different strains of COVID-19. Methods This descriptive-analytical study was conducted on 46,747 patients who underwent PCR testing during a two-year period from February 22, 2020 to February 23, 2022, in South Khorasan province, Iran. Patient characteristics and symptoms were extracted based on self-report and the information system. The data were analyzed using logistic regression and artificial neural network approaches. The R software was used for analysis and a significance level of 0.05 was considered for the tests. Results Among the 46,747 cases analyzed, 23,239 (49.7%) were male, and the mean age was 51.48 ± 21.41 years. There was a significant difference in symptoms among different variants of the disease (p 

Abstract Introduction The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis. Methods PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022. Results Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14–2.48, P-value 

Abstract Background The purpose of this study was to evaluate the diagnostic value of the GeneXpert® MTB/RIF (Xpert®), Auramine O staining method, and Lowenstein-Jensen medium for bacteriologically confirmed pulmonary tuberculosis and explore the effects of the sputum bacillary load (SBL) and qRT‒PCR threshold cycle (Ct) value on the detection methods. Methods We retrospectively analysed the results in the Department of Infectious Disease for 49 months. The χ2 test was used to compare the performances of each method, receiver operating characteristic curve analysis was used to determine the optimal cut-off values, and the factors associated with a false-negative result from Xpert® were analysed by logistic regression. Results Simultaneous analysis of 980 sputum specimens showed that the positive detection rate of Xpert® did not increase with increasing SBL, and there were differences between the three when SBL ≤ 1 + (all P 

Abstract Background The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country’s epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters’ predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI). Methods A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients. Results Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P 

Abstract Background Lymphopenia is defined as a decrease below normal value (often 1.0 x 109 cells/L) of blood circulating lymphocyte count. In the general population, lymphopenia is associated with an increased risk of hospitalisation secondary to infection, independent of traditional clinical risk factors. In hospital, lymphopenia is associated with increased risk of healthcare-associated infection and mortality. By summarising lymphopenia’s prevalence and impact on clinical outcomes, we can identify an at-risk population and inform future studies of immune dysfunction following severe illness. Methods Peer-reviewed search strategy was performed on three databases. Primary objective was to summarise the pooled prevalence of lymphopenia. Primary outcome was infection including pre-existing lymphopenia as a risk factor for admission with infection and as an in-hospital risk factor for healthcare-associated infection. Secondary outcomes were length of stay and mortality. Mortality data extracted included in-hospital, 28/30-day (‘early’), and 90-day/1-year (‘late’) mortality. Meta-analysis was carried out using random-effects models for each outcome measure. Heterogeneity was assessed using I2 statistic. Joanna Briggs Institute checklist for cohort studies was used to assess risk of bias. The protocol was published on PROSPERO. Results Fifteen observational studies were included. The pooled prevalence of lymphopenia in all-cause hospitalisations was 38% (CI 0.34-0.42, I2= 97%, p< 0.01). Lymphopenia was not associated with an infection diagnosis at hospital admission and healthcare associated infection (RR 1.03; 95% CI 0.26-3.99, p=0.97, I2 = 55% and RR 1.31; 95% CI 0.78-2.20, p=0.31, I2=97%, respectively), but was associated with septic shock (RR 2.72; 95% CI 1.02-7.21, p=0.04, I2 =98%). Lymphopenia was associated with higher in-hospital mortality and higher ‘early’ mortality rates (RR 2.44; 95% CI 1.71-3.47, p < 0.00001, I2 = 89% and RR 2.05; 95% CI 1.64-2.56, p < 0.00001, I2 = 29%, respectively). Lymphopenia was associated with higher ‘late’ mortality (RR 1.59; 1.33-1.90, p < 0.00001, I2 = 0%). Conclusions This meta-analysis demonstrates the high prevalence of lymphopenia across all-cause hospitalisations and associated increased risk of septic shock, early and late mortality. Lymphopenia is a readily available marker that may identify immune dysfunctional patients. Greater understanding of immune trajectories following survival may provide insights into longer-term poor clinical outcomes. …

Journal of Medical Virology, Volume 95, Issue 12, December 2023.

Journal of Medical Virology, Volume 95, Issue 12, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

by Shota Moriya, Hiromi Kazama, Hirotsugu Hino, Naoharu Takano, Masaki Hiramoto, Shin Aizawa, Keisuke Miyazawa We previously reported that macrolide antibiotics, such as clarithromycin (CAM), blocked autophagy flux, and simultaneous proteasome and autophagy inhibition by bortezomib (BTZ) plus CAM resulted in enhanced apoptosis induction in multiple myeloma (MM) cells via increased endoplasmic reticulum (ER) stress loading. However, in actual therapeutic settings, cell adhesion-mediated drug resistance between bone marrow stromal cells (BMSC) and MM cells has been known to be a barrier to treatment. To investigate whether CAM could enhance BTZ-induced cytotoxicity in MM cells under direct cell adhesion with BMSC, we established a co-culture system of EGFP-labeled MM cells with BMSC. The cytotoxic effect of BTZ on MM cells was diminished by its interaction with BMSC; however, the attenuated cytotoxicity was recovered by the co-administration of CAM, which upregulates ER stress loading and NOXA expression. Knockout of NOXA in MM cells canceled the enhanced cell death by CAM, indicating that NOXA is a key molecule for cell death induction by the co-administration of CAM. Since NOXA is degraded by autophagy as well as proteasomes, blocking autophagy with CAM resulted in the sustained upregulation of NOXA in MM cells co-cultured with BMSC in the presence of BTZ. Our data suggest that BMSC-associated BTZ resistance is mediated by the attenuation of ER stress loading. However, the addition of CAM overcomes BMSC-associated resistance via upregulation of NOXA by concomitantly blocking autophagy-mediated NOXA degradation and transcriptional activation of NOXA by ER stress loading.

by Bennet S. Cho, Scott C. Fligor, Gillian L. Fell, Jordan D. Secor, Savas T. Tsikis, Amy Pan, Lumeng J. Yu, Victoria H. Ko, Duy T. Dao, Lorenzo Anez-Bustillos, Thomas I. Hirsch, Jenny Lund, Arild C. Rustan, David A. Fraser, Kathleen M. Gura, Mark Puder Background Parenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis. Methods Two in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro. Results In the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both β- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake. Conclusions SEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both β- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis. …

by Tadesse Duguma, Dessalew Wudineh, Aberash Assefa, Nebeyi Fisseha, Dassalegn Muleta Background Malaria is a major cause of morbidity and mortality in children under the age of five worldwide. Although various malaria elimination measures have been implemented over the past decades, malaria remains a serious threat to public health, especially in tropical and subtropical areas. Ethiopia has set targets for eliminating malaria by 2030. No research has been conducted in the study area concerning malaria among children, who are the most malaria-prone segment of a community. The purpose of this study was to assess malaria prevalence and the factors associated with it among children under five years of age who attended the Sheko Health Center, Southwest Ethiopia, from June 1 to October 30, 2022. Materials and methods An institutional-based cross-sectional study was employed from June 1 to October 30, 2022, at the Sheko Health Center. Capillary blood samples were collected from 286 randomly selected symptomatic children. Data on socio-demographics and associated factors were collected using a pre-tested structured questionnaire, and data on parents’ and guardians’ knowledge about malaria was recorded on Excel 2016 Spreadsheets after interviewing them, and their responses were presented by a frequency table. Data were entered into Epi Data Manager (v4.0.2.101) and analyzed using the Statistical Package for Social Sciences (SPSS) version 25. Associated factors of malaria were analyzed using bivariate and multivariable logistic regression, and statistical significance was set at P < 0.05. Result Overall, 23.4% (95% CI = 18.6–28.8%) malaria infection was recorded among the children whose blood samples were examined, with Plasmodium falciparum, Plasmodium vivax, and mixed infections (both species) representing 52.2%, 34.3%, and 13.4% of the cases, respectively. The majority of the parents or guardians believed that malaria is transmissible but could be prevented, and 80% of them considered mosquito bites to be the main mode of malaria transmission. Insecticide-treated net (ITN) was mentioned as a malaria prevention strategy by more than half of the respondents, while indoor residual spraying (IRS) was considered only by 19.6%. Based on multivariable logistic regression analysis, a significant association was found in children between the ages of 12 and 36 months (adjusted odds ratio = 5.050; 95% CI: 1.964–12.982), children who lived in rural areas (adjusted odds ratio = 2.901; 95% CI: 1.439–5.845), and children who did not use ITN the past two weeks before sample collection (adjusted odds ratio = 3.341; 95% CI: 1.646–6.781). Conclusion This study revealed a high malaria prevalence among children aged under five years. Attention must be paid to improving the coverage of the ITN and its use in the study area, which could help reduce the risk of mosquito bites. Health education for the guardians of the children could also help to raise awareness about the prevention and control strategies for malaria transmission and further reduce the impact of the disease. …

by Bushra Sabri, Chakra Budhathoki, Allison M. McFall, Shruti H. Mehta, David D. Celentano, Sunil S. Solomon, Aylur K. Srikrishnan, Santhanam Anand, Canjeevaram K. Vasudevan, Gregory M. Lucas Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India.

by Izabel Alves das Chagas Valóta, Rafael Rodrigo da Silva Pimentel, Ana Paula Neroni Stina Saura, Rodrigo Marques da Silva, Ana Lucia Siqueira Costa Calache, Marcelo José dos Santos The aim of this study was to analyze levels of fatigue and resilience of Brazilian graduate students during the COVID-19 pandemic and to determine whether there is an association between fatigue and resilience and sociodemographic and academic factors. Data were analyzed using descriptive and inferential statistics, and it was discovered that the variables associated with higher levels of resilience were age; having children; being retired; receiving income above five minimum wages; having had greater problems in other phases of the research schedule; coming from private universities; being from the north of Brazil; studying the area of Health; and having their research schedule unaffected during the pandemic. On the other hand, lack of resilience was associated with not having children; being less well-off financially; being younger; being a woman; studying in a public university; and having to postpone part of the research during the pandemic. The conclusion of the study indicated the need for graduate programs to design strategies to deal with fatigue and promote resilience in Master’s and PhD students.

by Addisu Gize, Melkayehu Kassa, Solomon Ali, Yosef Tadesse, Bereket Fantahun, Yitagesu Habtu, Aman Yesuf Introduction Data regarding patients presenting with severe acute respiratory syndrome (SARS-CoV-2) illness have not adequately been documented which provides distinct insights into low-resource settings like Ethiopia. Thus, the study aimed to compare epidemiological, clinical and laboratory profiles of patients presenting with acute respiratory syndrome illness in Addis Ababa Ethiopia. Methods We used a comparative cross-sectional study design among patients with SARS-CoV-2 illness at St. Paul’s Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia from October 2020 to September 2021. Using a structured questionnaire a consecutive sampling technique was applied to collect socio-demographic data. Additionally, nasal swabs were collected to confirm SARS-CoV-2 infection using a Real-Time Polymerase Chain Reaction. Blood samples were also collected from the participants for laboratory profiles (hematological tests like; white blood cell count, hematocrit, and platelet count; and biochemical and enzymatic tests like; aspartate transaminase (AST), creatinine, etc) analysis. Data were entered and analyzed using SPSS version 23.0 and p-values ≤0.05 were considered as statistically significant. Results Of the total 413 participants presenting with SARS-CoV-2 illness, 250 (60.5%) participants tested positive for COVID-19 disease. COVID-19 patients were less likely to use an alcohol-based method of hand washing (12.5% vs 87.5%; p = 0.048). The COVID-19 patients had a higher proportion of headache (67.3% vs 32.7%, p = 0.001), sore throat (72.5% vs 27.5%, p = 0.001), and loss of sense of taste (74.4% vs 25.6%, p = 0.002). Patients with COVID-19 have significantly higher neutrophil than their counterparts (68.2% vs 31.8%; p = 0.001). Similarly, creatinine (64.9% vs 35.1%, p = 0.001) from renal function and alkaline phosphatase (66.8% vs 33.2%, p = 0.046) in the liver function tests were significantly higher in the COVID-19 patients. Conclusion Our findings suggest the need to substantially consider headache, sore throat, and loss of taste as potential clinical diagnostic symptoms for early screening and testing. Elevation of neutrophil, creatinine, alkaline phosphatase profiles are also used for potential diagnostic biomarkers in screening and testing suspected patients. …

Abstract Background Pregnant women have an increased risk of Plasmodium infections and disease. Malaria in pregnancy is a major public health problem in endemic areas. Assessment of the burden and risk factors of malaria in pregnancy across different malaria transmission settings is required to guide control strategies and for malaria elimination. Thus, the current study is generating such evidence from parturient women in northwest Ethiopia. Methods A cross-sectional study was conducted among 526 pregnant women admitted to the delivery rooms of selected health facilities in Jawi district, northwest Ethiopia, between November 2021 and July 2022. Data on the socio-demographic, clinical, obstetric, and malaria prevention practices of pregnant women were collected using interviewer-administered questionnaires and from women’s treatment cards. Malaria was diagnosed by light microscopy, rapid diagnostic test, and multiplex real-time polymerase chain reaction. Risk factors for malaria were evaluated using bivariable and multivariable logistic regression models. A P-value of 

Abstract Background Anopheles pharoensis has a major role in transmitting several human diseases, especially malaria, in Egypt?. Controlling Anopheles is considered as an effective strategy to eliminate the spread of malaria worldwide. Galaxaura rugosa is a species of red algae found in tropical to subtropical marine environments. The presence of G. rugosa is indicative of the ecosystem\'s overall health. The current work aims to investigate UPLC/ESI/MS profile of G. rugosa methanol and petroleum ether extracts and its activity against An. pharoensis and non-target organisms, Danio rerio and Daphnia magna. Methods Galaxaura rugosa specimens have been identified using DNA barcoding for the COI gene and verified as G. rugosa. The UPLC/ESI/MS profiling of G. rugosa collected from Egypt was described. The larvicidal and repellent activities of G. rugosa methanol and petroleum ether extracts against An. pharoensis were evaluated, as well as the toxicity of tested extracts on non-target organisms, Dan. rerio and Dap. magna. Results The UPLC/ESI/MS analysis of methanol and petroleum ether extracts led to the tentative identification of 57 compounds belonging to different phytochemical classes, including flavonoids, tannins, phenolic acids, phenyl propanoids. Larval mortality was recorded at 93.33% and 90.67% at 80 and 35 ppm of methanol and petroleum ether extracts, respectively, while pupal mortality recorded 44.44 and 22.48% at 35 and 30 ppm, respectively. Larval duration was recorded at 5.31 and 5.64 days by methanol and petroleum ether extracts at 80 and 35 ppm, respectively. A decrease in acetylcholinesterase (AChE) level and a promotion in Glutathione-S-transferase (GST) level of An. pharoensis 3rd instar larvae were recorded by tested extracts. The petroleum ether extract was more effective against An. pharoensis starved females than methanol extract. Also, tested extracts recorded LC50 of 1988.8, 1365.1, and 11.65, 14.36 µg/mL against Dan. rerio, and Dap. magna, respectively. Conclusions Using red algae derivatives in An. pharoensis control could reduce costs and environmental impact and be harmless to humans and other non-target organisms. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

BackgroundNavigating the organ donation and transplantation system in Canada can be challenging for individuals on transplant journeys. Although it is likely that the COVID-19 pandemic has further contributed to these challenges, the experiences of individuals during the pandemic in Canada have not been well elicited. ObjectiveTo illuminate how the COVID-19 pandemic has impacted individuals on transplant journeys in Canada. DesignConvergent parallel mixed-methods study. SettingCanada. ParticipantsAdult patients, caregivers, and donors on transplant journeys across Canada. Data collectionEight focus groups and an online survey between May and November 2021. Focus group transcripts were analysed using an inductive conventional content analysis approach. Survey data were analysed using descriptive statistics. The study was guided by individuals with lived experience of organ donation and transplantation. ResultsA total of 830 participants completed three COVID-19 related survey questions, with 21 participating in the focus groups. Survey results: over 50% of patients and caregivers reported that the pandemic impacted their access to their healthcare team, their mental health (60% and 65%, respectively) and their comfort going out in public (80% and 75%, respectively). Although many donors reported several factors that impacted their transplant journey, the impact appeared to be greater for patients and caregivers. Qualitative results: three themes emerged from the qualitative data that contextualise participant’s experiences: compounding isolation, disruption amid uncertainty and unforeseen benefits. ConclusionThe COVID-19 pandemic has exacerbated many of the challenges that individuals on transplant journeys experience. It will be critical for transplant programmes to consider these factors in future care provision. …

BackgroundNavigating the organ donation and transplantation system in Canada can be challenging for individuals on transplant journeys. Although it is likely that the COVID-19 pandemic has further contributed to these challenges, the experiences of individuals during the pandemic in Canada have not been well elicited. ObjectiveTo illuminate how the COVID-19 pandemic has impacted individuals on transplant journeys in Canada. DesignConvergent parallel mixed-methods study. SettingCanada. ParticipantsAdult patients, caregivers, and donors on transplant journeys across Canada. Data collectionEight focus groups and an online survey between May and November 2021. Focus group transcripts were analysed using an inductive conventional content analysis approach. Survey data were analysed using descriptive statistics. The study was guided by individuals with lived experience of organ donation and transplantation. ResultsA total of 830 participants completed three COVID-19 related survey questions, with 21 participating in the focus groups. Survey results: over 50% of patients and caregivers reported that the pandemic impacted their access to their healthcare team, their mental health (60% and 65%, respectively) and their comfort going out in public (80% and 75%, respectively). Although many donors reported several factors that impacted their transplant journey, the impact appeared to be greater for patients and caregivers. Qualitative results: three themes emerged from the qualitative data that contextualise participant’s experiences: compounding isolation, disruption amid uncertainty and unforeseen benefits. ConclusionThe COVID-19 pandemic has exacerbated many of the challenges that individuals on transplant journeys experience. It will be critical for transplant programmes to consider these factors in future care provision. …

IntroductionThe public’s accepting attitude toward people living with HIV is crucial in reducing HIV-related stigma and discrimination, increasing people’s access to HIV service. This study examines the inequalities in accepting attitudes toward people living with HIV in Ethiopia from 2005 to 2016. MethodsThis cross-sectional study was based on the 2005, 2011 and 2016 Ethiopian Demographic Health Surveys. A total of 17 075, 28 478 and 25 542 adults were included in the 2005, 2011 and 2016 surveys, respectively. Socioeconomic inequality was investigated using the concentration curve and Erreygers’ concentration index (ECI), which is scaled from –1 (pro-poor) to +1 (pro-rich). The ECI was decomposed to identify the contributors to socioeconomic inequality using generalised linear regression with the logit link function. ResultsAccepting attitude toward people living with HIV was 17.9% (95% CI: 16.6%, 19.3%) in 2005, which increased to 33.5% (95% CI: 31.8%, 35.3%) in 2011 and 39.6% (95% CI: 37.6%, 41.9%) in 2016. ECI was 0.342 (p

IntroductionThe public’s accepting attitude toward people living with HIV is crucial in reducing HIV-related stigma and discrimination, increasing people’s access to HIV service. This study examines the inequalities in accepting attitudes toward people living with HIV in Ethiopia from 2005 to 2016. MethodsThis cross-sectional study was based on the 2005, 2011 and 2016 Ethiopian Demographic Health Surveys. A total of 17 075, 28 478 and 25 542 adults were included in the 2005, 2011 and 2016 surveys, respectively. Socioeconomic inequality was investigated using the concentration curve and Erreygers’ concentration index (ECI), which is scaled from –1 (pro-poor) to +1 (pro-rich). The ECI was decomposed to identify the contributors to socioeconomic inequality using generalised linear regression with the logit link function. ResultsAccepting attitude toward people living with HIV was 17.9% (95% CI: 16.6%, 19.3%) in 2005, which increased to 33.5% (95% CI: 31.8%, 35.3%) in 2011 and 39.6% (95% CI: 37.6%, 41.9%) in 2016. ECI was 0.342 (p

IntroductionRecurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The aetiology of CE remains uncertain. An association between CE and recurrent miscarriage has been shown. This study will aim to determine if preconceptual administration of doxycycline, in women with recurrent miscarriages, and CE, reduces first trimester miscarriages, increasing live births. Methods and analysisChronic Endometritis and Recurrent Miscarriage is a multicentre, double-blind adaptive trial with an embedded translational substudy. Women with a history of two or more consecutive first trimester losses with evidence of CE on endometrial biopsy (defined as ≥5 CD138 positive cells per 10 mm2) will be randomised to oral doxycycline or placebo for 14 days. A subset will be recruited to a mechanistic substudy in which microbial swabs and preintervention/postintervention endometrial samples will be collected. Up to 3062 women recruited from 29 National Health Service (NHS) hospital sites across the UK are expected to be screened with up to 1500 women randomised in a 1:1 ratio. Women with a negative endometrial biopsy (defined as

IntroductionRecurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The aetiology of CE remains uncertain. An association between CE and recurrent miscarriage has been shown. This study will aim to determine if preconceptual administration of doxycycline, in women with recurrent miscarriages, and CE, reduces first trimester miscarriages, increasing live births. Methods and analysisChronic Endometritis and Recurrent Miscarriage is a multicentre, double-blind adaptive trial with an embedded translational substudy. Women with a history of two or more consecutive first trimester losses with evidence of CE on endometrial biopsy (defined as ≥5 CD138 positive cells per 10 mm2) will be randomised to oral doxycycline or placebo for 14 days. A subset will be recruited to a mechanistic substudy in which microbial swabs and preintervention/postintervention endometrial samples will be collected. Up to 3062 women recruited from 29 National Health Service (NHS) hospital sites across the UK are expected to be screened with up to 1500 women randomised in a 1:1 ratio. Women with a negative endometrial biopsy (defined as

American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 11, Page 1166-1176, December 1, 2023.

American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 11, Page e44-e46, December 1, 2023.

American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 11, Page 1234-1238, December 1, 2023.

American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 11, Page 1238-1240, December 1, 2023.

American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 11, Page 1246-1247, December 1, 2023.

Abstract Research has shown that multidimensional approaches to Chagas disease (CD), integrating its biomedical and psycho-socio-cultural components, are successful in enhancing early access to diagnosis, treatment and sustainable follow-up. For the first time, a consulate was selected for a community-based CD detection campaign. Two different strategies were designed, implemented and compared between 2021 and 2022 at the Consulate General of Bolivia and a reference health facility in Barcelona open to all Bolivians in Catalonia. Strategy 1 consisted in CD awareness-raising activities before referring those interested to the reference facility for infectious disease screening. Strategy 2 offered additional in-situ serological CD screening. Most of the 307 participants were Bolivian women residents in Barcelona. In strategy 1, 73 people (35.8% of those who were offered the test) were screened and 19.2% of them were diagnosed with CD. Additionally, 53,4% completed their vaccination schedules and 28.8% were treated for other parasitic infections (strongyloidiasis, giardiasis, eosinophilia, syphilis). In strategy 2, 103 people were screened in-situ (100% of those who were offered the test) and 13.5% received a CD diagnosis. 21,4% completed their vaccination schedule at the reference health facility and 2,9% were referred for iron deficiency anemia, strongyloidiasis or chronic hepatitis C. The fact that the screening took place in an official workplace of representatives of their own country, together with the presence of community-based participants fueled trust and increased CD understanding. Each of the strategies assessed had different benefits. Opportunities for systematic integration for CD based on community action in consulates may enhance early access to diagnosis, care and disease prevention. …

Abstract Research has shown that multidimensional approaches to Chagas disease (CD), integrating its biomedical and psycho-socio-cultural components, are successful in enhancing early access to diagnosis, treatment and sustainable follow-up. For the first time, a consulate was selected for a community-based CD detection campaign. Two different strategies were designed, implemented and compared between 2021 and 2022 at the Consulate General of Bolivia and a reference health facility in Barcelona open to all Bolivians in Catalonia. Strategy 1 consisted in CD awareness-raising activities before referring those interested to the reference facility for infectious disease screening. Strategy 2 offered additional in-situ serological CD screening. Most of the 307 participants were Bolivian women residents in Barcelona. In strategy 1, 73 people (35.8% of those who were offered the test) were screened and 19.2% of them were diagnosed with CD. Additionally, 53,4% completed their vaccination schedules and 28.8% were treated for other parasitic infections (strongyloidiasis, giardiasis, eosinophilia, syphilis). In strategy 2, 103 people were screened in-situ (100% of those who were offered the test) and 13.5% received a CD diagnosis. 21,4% completed their vaccination schedule at the reference health facility and 2,9% were referred for iron deficiency anemia, strongyloidiasis or chronic hepatitis C. The fact that the screening took place in an official workplace of representatives of their own country, together with the presence of community-based participants fueled trust and increased CD understanding. Each of the strategies assessed had different benefits. Opportunities for systematic integration for CD based on community action in consulates may enhance early access to diagnosis, care and disease prevention. …

Abstract Background Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). Methods HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell – IFN-γ activation was assessed by ELISpot. Results Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. Conclusions Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population. …

Abstract Background Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). Methods HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell – IFN-γ activation was assessed by ELISpot. Results Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. Conclusions Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population. …

No abstract available…

Introduction: Impairment of the gastrointestinal (GI) barrier leads to microbial translocation and peripheral immune activation which are linked to disease progression. Data in the setting of primary HIV/SIV infection suggest that gut barrier damage is one of the first events of the pathogenic cascade, preceding mucosal immune dysfunction and microbial translocation. We assessed gut structure and immunity as well as microbial translocation in acutely- and chronically-infected, combination cART-naïve individuals. Methods: Fifteen people with Primary HIV infection (P-HIV) and 13 with Chronic HIV infection (C-HIV) c-ART naïve participants were cross-sectionally studied. Gut biopsies were analyzed in terms of gut reservoirs (total, integrated and unintegrated HIV DNA); tight junction proteins (E-cadherin, Zonula Occludens-1), CD4 expression, neutrophil myeloperoxidase (histochemical staining); collagen deposition (Masson staining). Flow cytometry was used to assess γδ T-cell frequency (CD3+panγδ+Vδ1+/Vδ2+). In plasma we measured microbial translocation (LPS, sCD14, EndoCAb) and gut barrier function (I-FABP) markers (ELISA). Results: P-HIV displayed significantly higher tissue HIV DNA, yet neutrophil infiltration and collagen deposition in the gut were similar in the two groups. In contrast, microbial translocation markers were significantly lower in P-HIV compared to C-HIV. A trend to higher mucosal E-cadherin, and gut γδ T-cells was also observed in P-HIV. Conclusions: Early HIV infection features higher HIV DNA in the gut, yet comparable mucosal alterations to those observed in chronic infection. In contrast, microbial translocation is contained in primary HIV infection, likely due to a partial preservation of E-cadherin and mucosal immune subsets, namely γδ T-cells. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Objective: Evaluate effects of TB-HIV co-treatment on clinical and growth outcomes in children with HIV (CHIV). Design: Longitudinal study among Kenyan hospitalized ART-naive CHIV in the PUSH trial (NCT02063880). Methods: CHIV started ART within 2 weeks of enrollment; Anti-TB therapy was initiated based on clinical and TB diagnostics. Children were followed for 6 months with serial viral load, CD4%, and growth assessments (weight-for-age [WAZ], height-for-age [HAZ], and weight-for-height [WHZ]). TB-ART treated and ART-only groups were compared at 6-months post-ART for undetectable viral load [VL] (…

Objective: We aimed to explore the effect of particulate matter (PM) exposure on renal function in people living with HIV/AIDS (PWHA). Methods: A total of 37,739 repeated measurements were conducted on eGFR levels, serum creatinine (Scr), and the triglyceride-glucose (TyG) index in 6,958 PWHAs. The relationship between 1–28 day moving averages of PM concentrations with Scr and eGFR was assessed using linear mixed-effects models. Modified Poisson regression models were employed to assess the associations of cumulative PM exposure with the incidence of chronic kidney disease (CKD). Mediation analyses were used to examine the role of TyG index. Results: Short-term exposure to PM was related to reduced renal function. The strongest associations between exposure to PM1, PM2.5, and PM10 and percent changes in eGFR were observed at 7-day moving average exposure windows, with a respective decrease of 0.697% (−1.008%, −0.386%), 0.429% (−0.637%, −0.220%), and 0.373% (−0.581%, −0.164%) per IQR increment. Long-term exposure to PM1, PM2.5, and PM10 was positively linked with the incidence of CKD, with each IQR increment corresponding to fully adjusted RRs (95% CIs) of 1.631 (1.446, 1.839), 1.599 (1.431, 1.787), and 1.903 (1.665, 2.175), respectively. TyG index mediated 8.87%, 8.88%, and 7.58% of the relationship between cumulative exposure to PM1, PM2.5, and PM10 and increased risk of CKD, respectively. Conclusion: Exposure to PM among PWHAs is linked to reduced renal function, potentially contributing to increased CKD incidence, where the TyG index might serve as a partial mediator. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Background: Pregnant and breastfeeding women (PBW) in sub-Saharan Africa have high HIV incidence rates and associated risk of vertical transmission to their infants. Oral pre-exposure prophylaxis (PrEP) and injectable PrEP (long-acting cabotegravir, or CAB-LA) can potentially reduce this HIV transmission, but population-level impacts are uncertain. Methods: We extended a previously-developed model of HIV and PrEP in South Africa to allow for variable PrEP duration and preference in PBW. We considered three potential scenarios for PrEP provision to PBW: oral PrEP only, CAB-LA only and allowing oral/CAB-LA choice, with uptake and retention assumptions informed by South African data, each compared to a ‘base’ scenario without PrEP for PBW. Results: Without PrEP for PBW, the model estimates 1.31 million new infections will occur between 2025 and 2035 in South African adults and children, including 100,000 in PBW, 16,800 in infants at/before birth, and 35,200 in children through breastmilk. In the oral PrEP only scenario, these numbers would reduce by 1.2% (95% CI: 0.7–1.7%), 8.6% (4.8–12.9%), 4.0% (2.1–5.8%) and 5.3% (3.0–8.2%) respectively. In the CAB-LA only scenario, the corresponding reductions would be 6.1% (2.9–9.6%), 41.2% (19.8–65.0%), 12.6% (6.0–19.4%) and 29.5% (13.9–46.8%) respectively, and in the oral/CAB-LA choice scenario, similar reductions would be achieved (5.6% [3.4–8.0%], 39.0% [23.4–55.9%], 12.4% [7.4–16.8%] and 27.6% [16.5–39.9%] respectively). Conclusion: CAB-LA has the potential to be substantially more effective than oral PrEP in preventing HIV acquisition in PBW and vertical transmission, and can also modestly reduce HIV incidence at a population level. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Objective: To investigate the association of age at anti-retroviral therapy (ART) initiation with CD4:CD8 T cell ratio in virally suppressed people with HIV on long-term ART, and to characterize potential CD4:CD8 ratio recovery in this population by age. Design: A longitudinal study of people attending an HIV clinic at the Royal Free Hospital NHS Trust, London, who initiated ART between 2001 and 2015, and achieved and maintained HIV-1 viral suppression (VL…