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Virus Evolution 2024We investigated transmission dynamics of a large human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in KY and OH during 2017-20 by using...
We investigated transmission dynamics of a large human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in KY and OH during 2017-20 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase () sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including Subtype B (44.6 per cent); numerous circulating recombinant forms (CRFs) including CRF02_AG (2.5 per cent) and CRF02_AG-like (21.8 per cent); and many unique recombinant forms composed of CRFs with major subtypes and sub-subtypes [CRF02_AG/B (24.3 per cent), B/CRF02_AG/B (0.5 per cent), and A6/D/B (6.4 per cent)]. Cluster analysis of sequences using a 1.5 per cent genetic distance identified thirteen clusters, including a seventy-five-member cluster composed of CRF02_AG-like and CRF02_AG/B, an eighteen-member CRF02_AG/B cluster, Subtype B clusters of sizes ranging from two to twenty-three, and a nine-member A6/D and A6/D/B cluster. Recombination and phylogenetic analyses identified CRF02_AG/B variants with ten unique breakpoints likely originating from Subtype B and CRF02_AG-like viruses in the largest clusters. The addition of contact tracing results from OH to the genetic networks identified linkage between persons with Subtype B, CRF02_AG, and CRF02_AG/B sequences in the clusters supporting recombinant generation. Superinfection prevalence was 13.3 per cent (8/60) in persons with multiple specimens and included infection with B and CRF02_AG; B and CRF02_AG/B; or B and A6/D/B. In addition to the presence of multiple, distinct molecular clusters associated with this outbreak, cluster dating inferred transmission associated with the largest molecular cluster occurred as early as 2006, with high transmission rates during 2017-8 in certain other molecular clusters. This outbreak among PWID in KY and OH was likely driven by rapid transmission of multiple HIV-1 variants including viral recombinants from circulating viruses within the community. Our findings documenting the high HIV-1 transmission rate and clustering through partner services and molecular clusters emphasize the importance of leveraging multiple different data sources and analyses, including those from disease intervention specialist investigations, to better understand outbreak dynamics and interrupt HIV spread.
PubMed: 38510920
DOI: 10.1093/ve/veae015 -
Frontiers in Immunology 2024Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and...
Whole genome sequencing of recombinant viruses obtained from co-infection and superinfection of Vero cells with modified vaccinia virus ankara vectored influenza vaccine and a naturally occurring cowpox virus.
Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential for MVA to recombine with naturally occurring orthopoxviruses in cells and hosts in which it multiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semi-permissive to MVA infection) and showed that recombination occurred in both co-infected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that some MVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals.
Topics: Chlorocebus aethiops; Animals; Cats; Humans; Influenza Vaccines; Cowpox virus; Vero Cells; Coinfection; Superinfection; Vaccinia virus; Vaccines, Synthetic; Whole Genome Sequencing
PubMed: 38633245
DOI: 10.3389/fimmu.2024.1277447 -
Viruses Sep 2023The control of tristeza quick decline (QD) of citrus is based on the use of rootstocks that are tolerant or resistant to the Citrus tristeza virus (CTV), but some of...
Minor Variants of Orf1a, p33, and p23 Genes of VT Strain Citrus Tristeza Virus Isolates Show Symptomless Reactions on Sour Orange and Prevent Superinfection of Severe VT Isolates.
The control of tristeza quick decline (QD) of citrus is based on the use of rootstocks that are tolerant or resistant to the Citrus tristeza virus (CTV), but some of them show bio-agronomic limits. The application of cross-protection (CP) has been insufficiently explored. The present study examined the possibility of QD control by cross-protection (CP) following reports showing the dependence of the CP strategy on the close genetic relationships between the protective and challenging CTV isolates. Taking advantage of deep sequencing technologies, we located six naturally infected trees harboring no-seedling yellow (no-SY) and no QD decline (mild) VT isolates and used these for challenge inoculation with three QD VT isolates. Symptom monitoring showed that all six Sicilian mild no-SY isolates, based on their genomic relatedness and mild symptoms reactions, provide effective protection against the three severe local VT isolates. The differences between the six mild and three severe isolates were confined to just a few nucleotide variations conserved in eight positions of three CTV genes (p23, p33, and Orf1a). These results confirm that the superinfection exclusion (SIE mechanism) depends on close genetic relatedness between the protective and challenging severe VT strain isolates. Ten years of investigation suggest that CP could turn into an efficient strategy to contain CTV QD infections of sweet orange trees on SO rootstock.
Topics: Superinfection; Citrus; Genome, Viral; Closterovirus; Plant Diseases
PubMed: 37896814
DOI: 10.3390/v15102037 -
Die Anaesthesiologie Jun 2024Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease progression. Comorbidities, such as chronic arterial hypertension,...
BACKGROUND
Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease progression. Comorbidities, such as chronic arterial hypertension, diabetes mellitus, advanced maternal age and high body mass index, may predispose to severe disease. The management of pregnant COVID-19 patients on the intensive care unit (ICU) is challenging and requires careful consideration of maternal, fetal and ethical issues.
OBJECTIVE
Description and discussion of intensive care treatment strategies and perinatal anesthesiological management in patients with COVID-19 acute respiratory distress syndrome (CARDS).
MATERIAL AND METHODS
We analyzed the demographic data, maternal medical history, clinical intensive care management, complications, indications and management of extracorporeal membrane oxygenation (ECMO) and infant survival of all pregnant patients treated for severe CARDS in the anesthesiological ICU of a German university hospital between March and November 2021.
RESULTS
The cohort included 9 patients with a mean age of 30.3 years (range 26-40 years). The gestational age ranged from 21 + 3 weeks to 37 + 2 weeks. None of the patients had been vaccinated against SARS-CoV‑2. Of the nine patients seven were immigrants and communication was hampered by inadequate Central European language skills. Of the patients five had a PO/FO index < 150 mm Hg despite escalated invasive ventilation (FO > 0.9 and a positive end-expiratory pressure [PEEP] of 14 mbar) and were therefore treated with repeated prolonged prone positioning maneuvers (5-14 prone positions for 16 h each, a total of 47 prone positioning treatments) and 2 required treatment with inhaled nitric oxide and venovenous ECMO. The most common complications were bacterial superinfection of the lungs, urinary tract infection and delirium. All the women and five neonates survived. All newborns were delivered by cesarean section, two patients were discharged home with an intact pregnancy and two intrauterine fetal deaths were observed. None of the newborns tested positive for SARS-CoV‑2 at birth.
CONCLUSION
High survival rates are possible in pregnant patients with CARDS. The peripartum management of pregnant women with CARDS requires close interdisciplinary collaboration and should prioritize maternal survival in early pregnancy. In our experience, prolonged prone positioning, an essential evidence-based cornerstone in the treatment of ARDS, can also be safely used in advanced stages of pregnancy. Inhaled nitric oxide (iNO) and ECMO should be considered as life-saving treatment options for carefully selected patients. For cesarean section, neuraxial anesthesia can be safely performed in patients with mild CARDS if well planned but the therapeutic anticoagulation recommended for COVID-19 may increase the risk of bleeding complications, making general anesthesia a more viable alternative, especially in severe disease.
Topics: Humans; Female; Pregnancy; COVID-19; Pregnancy Complications, Infectious; Extracorporeal Membrane Oxygenation; Adult; Intensive Care Units; Infant, Newborn; Respiratory Distress Syndrome; Critical Care; Cesarean Section; Germany; Cohort Studies; Pregnancy Outcome
PubMed: 38671334
DOI: 10.1007/s00101-024-01405-5 -
Clinical Case Reports May 2024In the setting of Fournier's gangrene, atypical clinical manifestations and complications in an immunocompetent patient warrant consideration of perineal tuberculosis as...
KEY CLINICAL MESSAGE
In the setting of Fournier's gangrene, atypical clinical manifestations and complications in an immunocompetent patient warrant consideration of perineal tuberculosis as a potential underlying cause.
ABSTRACT
is a rare form of extrapulmonary tuberculosis that affects the perianal region. Fournier's gangrene is an aggressive necrotizing fasciitis that primarily involves the perianal area and external genitalia. A previously healthy 38-year-old man presented with a left perianal abscess. His condition deteriorated, leading to septic shock and multiorgan dysfunction syndrome. A CT scan displayed extensive necrotizing fasciitis. Treatment included broad-spectrum antibiotics, numerous surgical perineal debridements, a transverse loop colostomy, and hyperbaric oxygen therapy. We believe the patient had pre-existing asymptomatic, non-diagnosed perianal tuberculosis, and a subsequent bacterial superinfection resulted in a perineal local abscess that progressed to severe Fournier's gangrene. The diagnosis of tuberculosis was confirmed through positive cultures and molecular identification in perineal biopsies. The patient experienced a complex clinical course with complications such as myocardial necrosis, acute respiratory distress syndrome, rhabdomyolysis with severe critical illness polyneuromyopathy and internal jugular thrombosis. Fournier's gangrene resulted in air dissection throughout the perineal fasciae, extending to the abdominal wall muscles resulting in an infected extraperitoneal spontaneous hematoma, probably caused by therapeutic anticoagulation. An extraperitoneal surgical drainage was performed. This case emphasizes the complexities in diagnosing and managing both perianal tuberculosis and Fournier's gangrene.
PubMed: 38707606
DOI: 10.1002/ccr3.8882 -
International Journal of Surgery Case... Oct 2023Gigantic borderline ovarian cancer, also known as giant borderline ovarian tumor, is a rare subtype of borderline ovarian cancer. This type of ovarian cyst can be...
INTRODUCTION AND IMPORTANCE
Gigantic borderline ovarian cancer, also known as giant borderline ovarian tumor, is a rare subtype of borderline ovarian cancer. This type of ovarian cyst can be associated to various complication, including superinfection.
CASE PRESENTATION
We present the case of a 30-year-old woman who sought medical attention due to chronic abdominal pain and a rapid increase in abdominal girth over the past four months. Pelvic ultrasound and pelvic magnetic resonance imaging (MRI) revealed an abdominal-pelvic mass of 27 ∗ 12 cm. The tumoral markers were elevated. During her hospitalization, she developed a fever along with abdominal pain and biological inflammatory syndrome. Surgical intervention a 30-cm-long solid cystic mass located on the right ovary, accompanied by moderate ascites. The surgical procedure included a right adnexectomy, omentectomy, and appendicectomy, with cytology performed. Postoperative antibiotics were administered, and the patient showed favorable clinical and biological progress. The anatomopathological examination confirmed a 35-cm borderline mucinous tumor with signs of infection.
CLINICAL DISCUSSION
Giant borderline ovarian tumor is characterized by the presence of an ovarian mass measuring at least 10 cm in diameter. Infectious complications are rare, and their clinical features usually mimic those of a peritonitis. Treatment is based on antibiotics and chirurgical removal of the tumor based on the FIGO classification along with peritoneal biopsies and cytology.
CONCLUSION
This study explores the diagnosis, treatment, and prognosis of infected giant borderline ovarian tumors.
PubMed: 37801963
DOI: 10.1016/j.ijscr.2023.108873 -
Critical Care Explorations Apr 2024We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and... (Review)
Review
OBJECTIVES
We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness.
DATA SOURCES
We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials.
STUDY SELECTION
We included randomized controlled trials (RCTs) that compared corticosteroids to no corticosteroids or placebo in patients with sepsis, ARDS, and CAP.
DATA EXTRACTION
We summarized data addressing the most described side effects of corticosteroid use in critical care: gastrointestinal bleeding, hyperglycemia, hypernatremia, superinfections/secondary infections, neuropsychiatric effects, and neuromuscular weakness.
DATA SYNTHESIS
We included 47 RCTs ( = 13,893 patients). Corticosteroids probably have no effect on gastrointestinal bleeding (relative risk [RR], 1.08; 95% CI, 0.87-1.34; absolute risk increase [ARI], 0.3%; moderate certainty) or secondary infections (RR, 0.97; 95% CI, 0.89-1.05; absolute risk reduction, 0.5%; moderate certainty) and may have no effect on neuromuscular weakness (RR, 1.22; 95% CI, 1.03-1.45; ARI, 1.4%; low certainty) or neuropsychiatric events (RR, 1.19; 95% CI, 0.82-1.74; ARI, 0.5%; low certainty). Conversely, they increase the risk of hyperglycemia (RR, 1.21; 95% CI, 1.11-1.31; ARI, 5.4%; high certainty) and probably increase the risk of hypernatremia (RR, 1.59; 95% CI, 1.29-1.96; ARI, 2.3%; moderate certainty).
CONCLUSIONS
In ARDS, sepsis, and CAP, corticosteroids are associated with hyperglycemia and probably with hypernatremia but likely have no effect on gastrointestinal bleeding or secondary infections. More data examining effects of corticosteroids, particularly on neuropsychiatric outcomes and neuromuscular weakness, would clarify the safety of this class of drugs in critical illness.
PubMed: 38567382
DOI: 10.1097/CCE.0000000000001071 -
Microorganisms May 2024Pneumonia is one of the most common infectious diseases, mostly caused by viruses or bacteria. In response to bacteria or viruses which are different but which also are...
BACKGROUND
Pneumonia is one of the most common infectious diseases, mostly caused by viruses or bacteria. In response to bacteria or viruses which are different but which also are partly overlapping, innate and adaptive immune responses are induced, which can be quantified using the determination of specific biomarkers. Among these, C-reactive protein (CRP) has been established as a marker of innate immune function, whereas Neopterin, which is mainly produced upon stimulation with interferon-gamma, reflects cellular immune activation.
AIM
We investigated inflammation markers in patients with microbiologically confirmed viral or bacterial pneumonia, and studied the potential of CRP, Neopterin, and the CRP/Neopterin ratio to distinguish between viral and bacterial pathogenesis. Furthermore, we examined, how often neuropsychiatric symptoms occur in patients suffering from different kinds of pneumonia.
PATIENTS AND METHOD
A total of 194 patients diagnosed with either coronavirus disease 2019 (COVID-19) (n = 63), bacterial pneumonia (n = 58), infection (n = 10), and a bacterial superinfection (n = 9), and COVID-19 patients with a bacterial superinfection (n = 54) were included in our pilot study. Clinical as well as laboratory parameters were determined shortly after admission.
RESULTS
We found significantly higher CRP/Neopterin ratios in patients with bacterial pneumonia (median: 0.34) and lower CRP/Neopterin ratios in patients hospitalized with COVID-19 infection (median: 0.03; < 0.001). Both in men and in women, the CRP/Neopterin ratio was able to distinguish between viral and bacterial pathogens, but also was able to detect bacterial super-infection (BSI) in subjects with initial viral pneumonia ( < 0.001). Patients with BSI presented with significantly lower CRP/Neopterin ratios (median 0.08) than patients with bacterial infection only (median 0.34; < 0.001). Interestingly, COVID-19 patients had a decreased physical functioning (as reflected in the ECOG score) and a higher frequency of fatigue (84.1%) and neurological symptoms (54.8%) than patients with pneumonia, due to other underlying pathogens. Patients that reported fatigue during viral and bacterial pneumonia presented with lower CRP concentrations than patients without it.
CONCLUSIONS
The CRP/Neopterin ratio is useful to differentiate between viral and bacterial pathogenesis. The occurrence of neuropsychiatric symptoms in pneumonia appears to depend on the kind of pathogen causing the infection. Lower CRP concentrations at admission appear to be related to fatigue during acute viral and bacterial infection.
PubMed: 38930481
DOI: 10.3390/microorganisms12061099 -
Medecine Tropicale Et Sante... Sep 2023Tetanus still remains a public health problem in Togo despite the existence of the Expanded Program on Immunization.
INTRODUCTION
Tetanus still remains a public health problem in Togo despite the existence of the Expanded Program on Immunization.
PATIENTS AND METHOD
A retrospective and descriptive cohort study was performed from January 1, 2008 to December 31, 2018 in the infectious and tropical diseases department of Sylvanus Olympio teaching hospital of Lome (Togo) on tetanus cases.
RESULTS
We included 208 tetanus cases accounting for 6.5% of the whole hospitalizations in the infectious and tropical diseases department at this hospital. The median age of the patients was 23 [13-38 years] with male predominance (81.2%). The patients were workers (63.5%) and came mainly from urban areas (65.9%). Tetanus vaccination was only up to date in 9.3% of patients. Gateways were dominated by skin wounds (66.8%). Antitetanus serum was administered in 191 patients (91.8%) mainly through intrathecal route (189 patients (91.1%)). Complications were marked by superinfection of the wound (n=8), septic shock (n=3), acute respiratory failure and skin necrosis in 1 case respectively. The lethality was 27.4%.
CONCLUSION
The morbidity of tetanus, in particular juvenile morbidity, remains high with significant lethality. It is therefore important to place particular emphasis on the vaccine booster component.
Topics: Humans; Male; Adolescent; Young Adult; Adult; Female; Tetanus; Cohort Studies; Retrospective Studies; Togo; Hospitals, Teaching; Tetanus Toxoid; Communicable Diseases
PubMed: 38094481
DOI: 10.48327/mtsi.v3i3.2023.273 -
MSystems Apr 2024Secondary bacterial challenges during influenza virus infection "superinfection") cause excessive mortality and hospitalization. Here, we present a longitudinal study of...
UNLABELLED
Secondary bacterial challenges during influenza virus infection "superinfection") cause excessive mortality and hospitalization. Here, we present a longitudinal study of bulk gene expression changes in murine lungs during superinfection, with an initial influenza A virus infection and a subsequent infection. In addition to the well-characterized impairment of the host response, we identified superinfection-specific alterations in the global transcriptional program that are linked to the host's ability to resist the pathogens. Particularly, whereas superinfected mice manifested an excessive rapid induction of the resistance-to-infection program, there was a substantial tissue-level rewiring of this program: upon superinfection, interferon-regulated genes were switched from positive to negative correlations with the host's resistance state, whereas genes of fatty acid metabolism switched from negative to positive correlations with resistance states. Thus, the transcriptional resistance state in superinfection is reprogrammed toward repressed interferon signaling and induced fatty acid metabolism. Our findings suggest new insights into a tissue-level remodeling of the host defense upon superinfection, providing promising targets for future therapeutic interventions.
IMPORTANCE
Secondary bacterial infections are the most frequent complications during influenza A virus (IAV) pandemic outbreaks, contributing to excessive morbidity and mortality in the human population. Most IAV-related deaths are attributed to (SP) infections, which usually begin within the first week of IAV infection in the respiratory tracts. Here, we focused on longitudinal transcriptional responses during a superinfection model consisting of an SP infection that follows an initial IAV infection, comparing superinfection to an IAV-only infection, an SP-only infection, and control treatments. Our longitudinal data allowed a fine analysis of gene expression changes during superinfection. For instance, we found that superinfected mice exhibited rapid gene expression induction or reduction within the first 12 h after encountering the second pathogen. Cell proliferation and immune response activation processes were upregulated, while endothelial processes, vasculogenesis, and angiogenesis were downregulated, providing promising targets for future therapeutic interventions. We further analyzed the longitudinal transcriptional responses in the context of a previously defined spectrum of the host's resistance state, revealing superinfection-specific reprogramming of resistance states, such as reprogramming of fatty acid metabolism and interferon signaling. The reprogrammed functions are compelling new targets for switching the pathogenic superinfection state into a single-infection state.
Topics: Mice; Humans; Animals; Streptococcus pneumoniae; Influenza A virus; Superinfection; Longitudinal Studies; Influenza, Human; Pneumococcal Infections; Immunity, Innate; Interferons; Fatty Acids
PubMed: 38446104
DOI: 10.1128/msystems.01048-23