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Lancet Regional Health. Americas Jul 2024Few studies have evaluated the effects of the Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, on maternal and perinatal health at a...
Maternal and perinatal health indicators in Brazil over a decade: assessing the impact of the COVID-19 pandemic and SARS-CoV-2 vaccination through interrupted time series analysis.
BACKGROUND
Few studies have evaluated the effects of the Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, on maternal and perinatal health at a populational level. We investigated maternal and perinatal health indicators in Brazil, focusing on the effects of the COVID-19 pandemic, and SARS-CoV-2 vaccination campaign for pregnant women.
METHODS
Utilizing interrupted time series analysis (January 2013-December 2022), we examined Maternal Mortality Ratio, Perinatal Mortality Rate, Preterm Birth Rate, Cesarean Section Rate, and other five indicators. Interruptions occurred at the pandemic's onset (March 2020) and pregnant women's vaccination (July 2021). Results were expressed as percent changes on time series' level and slope.
FINDINGS
The COVID-19 onset led to immediate spikes in Maternal Mortality Ratio (33.37%) and Perinatal Mortality Rate (3.20%) (p < 0.05). From March 2020 to December 2022, Cesarean Section and Preterm Birth Rates exhibited upward trends, growing monthly at 0.13% and 0.23%, respectively (p < 0.05). Post start of SARS-CoV-2 vaccination (July 2021), Maternal Mortality Ratio (-34.10%) and Cesarean Section Rate (-1.87%) promptly declined (p < 0.05). Subsequently, we observed a monthly decrease of Maternal Mortality Ratio (-9.43%) and increase of Cesarean Section Rate (0.25%) (p < 0.05), while Perinatal Mortality Rate and Preterm Birth Rate showed a stationary pattern.
INTERPRETATION
The pandemic worsened all analyzed health indicators. Despite improvements in Maternal Mortality Ratio, following the SARS-CoV-2 vaccination campaign for pregnant women, the other indicators continued to sustain altered patterns from the pre-pandemic period.
FUNDING
No funding.
PubMed: 38828284
DOI: 10.1016/j.lana.2024.100774 -
HIV/AIDS (Auckland, N.Z.) 2024HIV-associated neurocognitive disorders (HAND) are becoming a significant public health concern in the continuum of human immune virus (HIV) treatment. These disorders...
Healthcare Workers' Perspectives on the Utilization of the International HIV Dementia Scale for the Screening HIV-Associated Neurocognitive Disorders: A Qualitative Study at TASO Centres in Central and Southwestern Uganda.
INTRODUCTION
HIV-associated neurocognitive disorders (HAND) are becoming a significant public health concern in the continuum of human immune virus (HIV) treatment. These disorders range from subtle cognitive impairments to severe dementia. Despite many early-stage HAND cases being asymptomatic, healthcare workers (HCWs) rarely perform routine neurocognitive assessments. This leads to a high number of unrecognized cases and increases the risk of HAND among people living with HIV (PLWH).
MATERIAL AND METHODS
We aimed to explore HCWs' perspectives on integrating the International HIV Dementia Scale (IHDS) into routine care for screening HAND at The AIDS Support Organization (TASO) centres in central and southwestern Uganda.
RESULTS
We conducted five focus group discussions with 37 HCWs from five TASO centres. Thematic analysis revealed eight key theme: 1) Impaired brain function, 2) Changes in activities of daily living, 3) Promotion of quality care perspectives, 4) Tool applicable and user-friendly, 5) Client increased self-awareness and self-confidence, 6) Integration of IHDS into routine HIV care, 7) Uncertainty about IHDS use, and 8) Continuous training for HCWs.
CONCLUSION
As PLWH enjoy longer and healthier lives, their risk for HAND increases, potentially affecting their quality of life. The use of the IHDS has raised awareness among HCWs and improved decision-making through cognitive assessments, emphasizing it value in PLWH. We recommend a prospective study to assess the long-term outcomes and efficacy of increased HAND screening. Furthermore, integrating a HAND screening module into the consolidated HIV guidelines is recommended to enhance its relevance.
PubMed: 38827783
DOI: 10.2147/HIV.S444668 -
Molecular Therapy. Methods & Clinical... Jun 2024Prenatal somatic cell gene therapy (PSCGT) could potentially treat severe, early-onset genetic disorders such as spinal muscular atrophy (SMA) or muscular dystrophy....
Prenatal somatic cell gene therapy (PSCGT) could potentially treat severe, early-onset genetic disorders such as spinal muscular atrophy (SMA) or muscular dystrophy. Given the approval of adeno-associated virus serotype 9 (AAV9) vectors in infants with SMA by the U.S. Food and Drug Administration, we tested the safety and biodistribution of AAV9-GFP (clinical-grade and dose) in fetal lambs to understand safety and efficacy after umbilical vein or intracranial injection on embryonic day 75 (E75) . Umbilical vein injection led to widespread biodistribution of vector genomes in all examined lamb tissues and in maternal uteruses at harvest (E96 or E140; term = E150). There was robust GFP expression in brain, spinal cord, dorsal root ganglia (DRGs), without DRG toxicity and excellent transduction of diaphragm and quadriceps muscles. However, we found evidence of systemic toxicity (fetal growth restriction) and maternal exposure to the viral vector (transient elevation of total bilirubin and a trend toward elevation in anti-AAV9 antibodies). There were no antibodies against GFP in ewes or lambs. Analysis of fetal gonads demonstrated GFP expression in female (but not male) germ cells, with low levels of integration-specific reads, without integration in select proto-oncogenes. These results suggest potential therapeutic benefit of AAV9 PSCGT for neuromuscular disorders, but warrant caution for exposure of female germ cells.
PubMed: 38827250
DOI: 10.1016/j.omtm.2024.101263 -
Scientific Reports May 2024Respiratory diseases, including influenza and coronaviruses, pose recurrent global threats. This study delves into the respiratory surveillance systems, focusing on the...
Respiratory diseases, including influenza and coronaviruses, pose recurrent global threats. This study delves into the respiratory surveillance systems, focusing on the effectiveness of SARI sentinel surveillance for total and severe cases incidence estimation. Leveraging data from the COVID-19 pandemic in Chile, we examined 2020-2023 data (a 159-week period) comparing census surveillance results of confirmed cases and hospitalizations, with sentinel surveillance. Our analyses revealed a consistent underestimation of total cases and an overestimation of severe cases of sentinel surveillance. To address these limitations, we introduce a nowcasting model, improving the precision and accuracy of incidence estimates. Furthermore, the integration of genomic surveillance data significantly enhances model predictions. While our findings are primarily focused on COVID-19, they have implications for respiratory virus surveillance and early detection of respiratory epidemics. The nowcasting model offers real-time insights into an outbreak for public health decision-making, using the same surveillance data that is routinely collected. This approach enhances preparedness for emerging respiratory diseases by the development of practical solutions with applications in public health.
Topics: Humans; COVID-19; Sentinel Surveillance; Chile; SARS-CoV-2; Pandemics; Incidence; Hospitalization
PubMed: 38822070
DOI: 10.1038/s41598-024-62965-5 -
The ISME Journal Jan 2024When phage infect their bacterial hosts, they may either lyse the cell and generate a burst of new phage, or lysogenize the bacterium, incorporating the phage genome...
When phage infect their bacterial hosts, they may either lyse the cell and generate a burst of new phage, or lysogenize the bacterium, incorporating the phage genome into it. Phage lysis/lysogeny strategies are assumed to be highly optimized, with the optimal tradeoff depending on environmental conditions. However, in nature, phage of radically different lysis/lysogeny strategies coexist in the same environment, preying on the same bacteria. How can phage preying on the same bacteria coexist if one is more optimal than the other? Here, we address this conundrum within a modeling framework, simulating the population dynamics of communities of phage and their lysogens. We find that coexistence between phage of different lysis/lysogeny strategies is a natural outcome of chaotic population dynamics that arise within sufficiently diverse communities, which ensure no phage is able to absolutely dominate its competitors. Our results further suggest a bet-hedging mechanism at the level of the phage pan-genome, wherein obligate lytic (virulent) strains typically outcompete temperate strains, but also more readily fluctuate to extinction within a local community.
Topics: Bacteriophages; Lysogeny; Bacteria; Population Dynamics; Models, Biological; Genome, Viral
PubMed: 38818736
DOI: 10.1093/ismejo/wrae093 -
BMC Health Services Research May 2024Adolescents living with Human Immunodeficiency Virus (HIV) have an increased risk of depression, negatively affecting their adherence to antiretroviral therapy (ART) and...
BACKGROUND
Adolescents living with Human Immunodeficiency Virus (HIV) have an increased risk of depression, negatively affecting their adherence to antiretroviral therapy (ART) and treatment outcomes. Integrating mental health care in HIV care and treatment settings improves comprehensive care. However, integration remains challenging in Tanzania, like in other high-burden and low-resource settings. The overall objective of this work is to inform the development of a psychological intervention for depression in adolescents living with HIV (ALWHIV). We describe perceived barriers and opportunities for implementing an integrated, evidence-based psychological intervention to manage adolescent depression in HIV care and treatment centers (HIV-CTC) from the perspectives of adolescents, caregivers, and healthcare providers (HCPs) in Dar es Salaam, Tanzania.
METHODS
To inform intervention development and implementation, this study utilized a qualitative design through a phenomenological approach informed by the Consolidated Framework for Implementation Research (CFIR) to explore implementation barriers and facilitators in ALWHIV, HCPs, and caregivers. Forty-five in-depth interviews were conducted in three HIV-CTCs in Kinondoni Dar es Salaam. Audio records were transcribed verbatim and analyzed deductively through NVIVO software.
RESULTS
Barriers to implementing an integrated psychological intervention to address depression in ALWHIV included (A) poor mental health awareness among caregivers, adolescents, HCPs, and policy-makers, (B) high level of stigma against mental health care, (C) poor communication between adolescents and HCPs concerning mental health care, (D) lack of contextualized intervention of proven effectiveness and guidelines of mental health care, and (E) inadequate mental health care supportive supervision and mentorship. Facilitators for implementation included supportive infrastructure, positive pressure from HIV implementing partners, tension for change, and participant's perception of the advantage of a psychological intervention as compared to just usual HIV care and treatment counseling.
CONCLUSION
Despite several modifiable barriers to implementing a psychological intervention in HIV CTC, there were encouraging facilitators and opportunities for implementing an integrated, evidence-based psychological intervention to address depression in ALWHIV in Kinondoni Dar es Salaam, Tanzania.
Topics: Humans; Adolescent; Tanzania; HIV Infections; Male; Female; Qualitative Research; Depression; Psychosocial Intervention; Caregivers; Social Stigma; Interviews as Topic; Delivery of Health Care, Integrated
PubMed: 38807134
DOI: 10.1186/s12913-024-11118-5 -
PLoS Pathogens May 2024Marek's disease virus (MDV) vaccines were the first vaccines that protected against cancer. The avirulent turkey herpesvirus (HVT) was widely employed and protected...
Marek's disease virus (MDV) vaccines were the first vaccines that protected against cancer. The avirulent turkey herpesvirus (HVT) was widely employed and protected billions of chickens from a deadly MDV infection. It is also among the most common vaccine vectors providing protection against a plethora of pathogens. HVT establishes latency in T-cells, allowing the vaccine virus to persist in the host for life. Intriguingly, the HVT genome contains telomeric repeat arrays (TMRs) at both ends; however, their role in the HVT life cycle remains elusive. We have previously shown that similar TMRs in the MDV genome facilitate its integration into host telomeres, which ensures efficient maintenance of the virus genome during latency and tumorigenesis. In this study, we investigated the role of the TMRs in HVT genome integration, latency, and reactivation in vitro and in vivo. Additionally, we examined HVT infection of feather follicles. We generated an HVT mutant lacking both TMRs (vΔTMR) that efficiently replicated in cell culture. We could demonstrate that wild type HVT integrates at the ends of chromosomes containing the telomeres in T-cells, while integration was severely impaired in the absence of the TMRs. To assess the role of TMRs in vivo, we infected one-day-old chickens with HVT or vΔTMR. vΔTMR loads were significantly reduced in the blood and hardly any virus was transported to the feather follicle epithelium where the virus is commonly shed. Strikingly, latency in the spleen and reactivation of the virus were severely impaired in the absence of the TMRs, indicating that the TMRs are crucial for the establishment of latency and reactivation of HVT. Our findings revealed that the TMRs facilitate integration of the HVT genome into host chromosomes, which ensures efficient persistence in the host, reactivation, and transport of the virus to the skin.
Topics: Animals; Chickens; Telomere; Virus Integration; Marek Disease; Virus Latency; Genetic Vectors; Herpesvirus 1, Meleagrid; Marek Disease Vaccines; Genome, Viral; Herpesvirus 2, Gallid; Repetitive Sequences, Nucleic Acid; Poultry Diseases
PubMed: 38805555
DOI: 10.1371/journal.ppat.1012261 -
Computational and Structural... Dec 2024Understanding the structural similarity between genomes is pivotal in classification and phylogenetic analysis. As the number of known genomes rockets, alignment-free...
Understanding the structural similarity between genomes is pivotal in classification and phylogenetic analysis. As the number of known genomes rockets, alignment-free methods have gained considerable attention. Among these methods, the natural vector method stands out as it represents sequences as vectors using statistical moments, enabling effective clustering based on families in biological taxonomy. However, determining an optimal metric that combines different elements in natural vectors remains challenging due to the absence of a rigorous theoretical framework for weighting different -mers and orders. In this study, we address this challenge by transforming the determination of optimal weights into an optimization problem and resolving it through gradient-based techniques. Our experimental results underscore the substantial improvement in classification accuracy achieved by employing these optimal weights, reaching an impressive 92.73% on the testing set, surpassing other alignment-free methods. On one hand, our method offers an outstanding metric for virus classification, and on the other hand, it provides valuable insights into feature integration within alignment-free methods.
PubMed: 38803517
DOI: 10.1016/j.csbj.2024.05.005 -
Frontiers in Immunology 2024Macrophage function is determined by microenvironment and origin. Brain and retinal microglia are both derived from yolk sac progenitors, yet their microenvironments...
INTRODUCTION
Macrophage function is determined by microenvironment and origin. Brain and retinal microglia are both derived from yolk sac progenitors, yet their microenvironments differ. Utilizing single-cell RNA sequencing (scRNA-seq) data from mice, we tested the hypothesis that retinal and brain microglia exhibit distinct transcriptional profiles due to their unique microenvironments.
METHODS
Eyes and brains from 2-4 month wildtype mice were combined (20 eyes; 3 brains) to yield one biologically diverse sample per organ. Each tissue was digested into single cell suspensions, enriched for immune cells, and sorted for scRNA-seq. Analysis was performed in Seurat v3 including clustering, integration, and differential expression. Multi-parameter flow cytometry was used for validation of scRNA-seq results. Lymphocytic choriomeningitis virus (LCMV) Clone 13, which produces a systemic, chronic, and neurotropic infection, was used to validate scRNA-seq and flow cytometry results .
RESULTS
Cluster analysis of integrated gene expression data from eye and brain identified 6 microglial clusters. Differential expression analysis revealed that eye microglia were enriched for more pro-inflammatory processes including antigen processing via MHC class I (14.0-fold, and ) and positive regulation of T-cell immunity (8.4-fold) compared to brain microglia. Multi-parameter flow cytometry confirmed that retinal microglia expressed 3.2-fold greater H2-Db and 263.3-fold more H2-Kb than brain microglia. On Day 13 and 29 after LCMV infection, CD8 T-cell density was greater in the retina than the brain.
DISCUSSION
Our data demonstrate that the microenvironment of retina and brain differs, resulting in microglia-specific gene expression changes. Specifically, retinal microglia express greater MHC class I by scRNA-seq and multi-parameter flow cytometry, resulting in a possibly enhanced capability to stimulate CD8 T-cell inflammation during LCMV infection. These results may explain tissue-specific differences between retina and brain during systemic viral infections and CD8 T-cell driven autoimmune disease.
Topics: Animals; Microglia; Mice; Retina; Brain; Mice, Inbred C57BL; Lymphocytic choriomeningitis virus; Histocompatibility Antigens Class I; T-Lymphocytes; Inflammation; Lymphocytic Choriomeningitis; Single-Cell Analysis; CD8-Positive T-Lymphocytes; Transcriptome
PubMed: 38799448
DOI: 10.3389/fimmu.2024.1399989 -
Vaccine Jun 2024In 2020-2021, all countries of the WHO Eastern Mediterranean Region [EMR] introduced COVID-19 vaccine with inequalities in coverage across countries. As for 2023, we...
In 2020-2021, all countries of the WHO Eastern Mediterranean Region [EMR] introduced COVID-19 vaccine with inequalities in coverage across countries. As for 2023, we reviewed subsequent progress in deployment, coverage, acceptance, and integration. As of 31 December 2023, coverage in EMR reached 51% for primary series and 19 % for the first booster, higher in high income countries (77 % and 44 %, respectively) than in upper middle-income countries (49 % and 20 %), Advance Market Commitment [AMC] non-Gavi eligible countries (47 % and 15 %) and AMC Gavi eligible countries (49 % and 16 %). Thirteen countries measured coverage among healthcare workers (76 % and 43 %, respectively) and 15 among elderly (69 % and 38 %, respectively). Three rounds of the regional Knowledge, Attitudes, and Practices [KAP] survey on COVID-19 vaccine acceptance in 2021-2022 indicated that acceptance increased from 20 % in June-July 2021 to 62 % in October-November 2021, and 77 % in June-July 2022. Those unvaccinated but intending to be vaccinated decreased from 60 % to 23 % and 11 %, respectively. Unvaccinated without intention to be vaccinated decreased from 15 % to 10 % and 11 %, respectively. Twenty out of 22 countries in the region had completely or partially integrated COVID-19 vaccination into the Expanded Programme on Immunization [EPI] and Primary Health Care [PHC]. Overall, challenges to reach high-risk groups persisted as the population was less concerned about Omicron variant of the SARS-CoV-2 virus. Countries should build on the trust, momentum, and lesson-learned generated from COVID-19 vaccination to get the highest risk groups vaccinated and switch from a time bound and project type approach to a sustainable and long-term approach for COVID-19 vaccine delivery that would be integrated into the routine EPI and PHC.
Topics: Humans; COVID-19 Vaccines; COVID-19; Mediterranean Region; World Health Organization; SARS-CoV-2; Vaccination Coverage; Health Personnel; Vaccination; Immunization Programs; Health Knowledge, Attitudes, Practice
PubMed: 38796325
DOI: 10.1016/j.vaccine.2024.05.013