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Frontiers in Pediatrics 2024Acute upper respiratory tract infection (AURI) includes infections caused by a variety of pathogens and is one of the most common diseases in children. Traditional...
BACKGROUND
Acute upper respiratory tract infection (AURI) includes infections caused by a variety of pathogens and is one of the most common diseases in children. Traditional Chinese medicine (TCM) injections are widely used for treating AURI in clinical practice, but their efficacy is unclear because of the lack of clear evidence. In this study, a network meta-analysis (NMA) was used to evaluate the efficacy and safety of TCM injections in the treatment of AURI and to provide a reference for clinical treatment.
METHODS
Eight databases were searched, namely, PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), the Wanfang database, and the Chinese Scientific Journal database (VIP). The search time period was from 1 January 2013 to 1 November 2023. Randomized controlled trials of herbal injections for treating AURI were searched. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of these studies. Review Manager 5.4 and Stata 15.0 were used for the NMA.
RESULTS
A total of 81 papers involving 11,736 patients were included. These involved five different TCM injections, namely, Xiyanping injection (XYPI), Qingkailing injection (QKLI), Reduning injection (RDNI), Yanhuning injection (YHNI), and Tanreqing injection (TRQI). QKLI was most effective in alleviating symptoms of fever and improving overall clinical effectiveness. TRQI was most effective in relieving cough symptoms. YHNI was most effective in alleviating sore throat, runny nose, and nasal congestion. The overall incidence of adverse effects of these herbal injections in the treatment of AURI was lower, and their safety profiles were better.
CONCLUSIONS
The herbal injections combined with ribavirin improved clinical outcomes, and were superior to ribavirin injection alone in alleviating clinical symptoms such as fever, cough, sore throat, runny nose, and nasal congestion, and have favorable safety profiles.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023484099, CRD42023484099.
PubMed: 38915872
DOI: 10.3389/fped.2024.1358639 -
Health Science Reports Jun 2024Crimean-Congo hemorrhagic fever (CCHF) is a severe and potentially lethal illness. Tick bites of the Hyalomma genus are the primary source of transmission of CCHF to...
BACKGROUND AND AIMS
Crimean-Congo hemorrhagic fever (CCHF) is a severe and potentially lethal illness. Tick bites of the Hyalomma genus are the primary source of transmission of CCHF to humans. The virus responsible for CCHF is the CCHF virus (CCHFV). It is a single-stranded negative sensed RNA virus. The virus belongs to the Orthonairoviridae genus within the Nairoviridae family. It occurs in an extensive geographical area spanning the Middle East, western China, southern Asia, southeastern Europe, and much of Africa. The current study aimed to evaluate the pathogenicity and potential risk of CCHFV to cause a public health emergency of international concern.
METHODS
We searched updated relevant information from PubMed, Google Scholar, and Scopus databases using Crimean-Congo hemorrhagic fever, tick-borne virus, and Nairovirus as keywords.
RESULTS
The case fatality rate (CFR) varies by region. It can be more than 30% in some cases. Three segments in the genome of CCHFV (L, M, and S) are different in size and function. It is unknown whether the pathogenicity of CCHFV varied based on the genomic diversity. CCHFV can be transmitted through tick bites, handling of infected ticks, contact with infected humans, contaminated body fluids, and so on. A wide range of severity is associated with CCHF, ranging from a moderate fever with no apparent cause to increased vascular permeability, failure of several organs, bleeding, and shock. Hospitals with high-level isolation units should be the first choice for treating CCHF patients. Individual safety equipment is crucial in healthcare to prevent the spread of the virus. In the farm environment, using integrated pest management techniques, minimizing activity in tick-infested regions, and dressing appropriately in long sleeves and pants will help to reduce the risk of CCHFV infection via tick bites.
CONCLUSION
There are no approved vaccinations or therapeutics for CCHF except supportive therapeutic approaches. Therefore, scientists recommend early ribavirin therapy for cases of high-risk exposures.
PubMed: 38915357
DOI: 10.1002/hsr2.2209 -
Frontiers in Immunology 2024Anti-rods and rings (anti-RR) antibodies have recently been described as a cytoplasmic pattern in IIF-based screening of autoantibodies on HEp-2 cells and ICAP has named...
INTRODUCTION
Anti-rods and rings (anti-RR) antibodies have recently been described as a cytoplasmic pattern in IIF-based screening of autoantibodies on HEp-2 cells and ICAP has named it as AC-23. It is most frequently related to drug-induced antibody generation. This study aimed to investigate the clinical significance of AC-23 positivity and its relevance to the diagnosis and/or follow-up of the associated diseases and/or drug use.
METHODS
A multicenter retrospective study was conducted among 10 hospitals from six different provinces in Türkiye from January 2017 to December 2021. The laboratory data and clinical information of 600 patients with positive anti-RR antibodies out of 547.558 HEp-2 IIF ANA samples were analyzed.
RESULTS
The distribution of AC-23 positive patients by year indicated a steady increase between 2017-2021. Anti-RR prevalence in post-COVID-19 period was significantly higher than that of pre-COVID-19 period (p=0.00). Concomitant ANA positivity was detected in 56.5% of patients, the most common patterns being AC-4 and AC-5 (41.1%). The most frequent pathology among the anti-RR positive patients was an autoimmune disease (19.83%); 28.57% of which had rheumatoid arthritis and 17.65% autoimmune liver disease. Among the 600 patients, 65 (10.83%) were diagnosed as hepatitis C virus (HCV) infection. Available data for 38 of the HCV patients revealed that 71.05% of them had a history of interferon alfa+ribavirin and 28.95% of them had a history of NS3/4/5A/5B polymerase inhibitor or protease inhibitor drug use. Significant increase in the rate of anti-RR positivity was observed in the post-COVID-19 period when compared to pre-COVID-19 period (p:0.00).
DISCUSSION
This is the first multicenter study in Türkiye about the clinical association of anti-RR antibodies which may be ignored during routine HEp-2 IIF testing. Pathologies other than HCV should be taken into consideration in terms of the possible role of anti-RR in autoimmune diseases and other pathologies. The preliminary data obtained in this study suggest that anti-RR antibody development might also be associated to COVID-19, supporting the several previous data related to the potential of viruses triggering the formation of autoantibodies. Large-scale prospective studies should elucidate the clinical significance of RR pattern and determine its role in patient diagnosis and follow-up.
Topics: Humans; Retrospective Studies; Antibodies, Antinuclear; Female; Male; COVID-19; Middle Aged; Fluorescent Antibody Technique, Indirect; Aged; Adult; SARS-CoV-2; Autoimmune Diseases
PubMed: 38911869
DOI: 10.3389/fimmu.2024.1359030 -
The Lancet. Microbe Jun 202410 million people are chronically infected with the hepatitis C virus (HCV) in sub-Saharan Africa. The assessment of viral genotypes and treatment response in this...
BACKGROUND
10 million people are chronically infected with the hepatitis C virus (HCV) in sub-Saharan Africa. The assessment of viral genotypes and treatment response in this region is necessary to achieve the WHO target of worldwide elimination of viral hepatitis by 2030. We aimed to investigate the prevalence of HCV genotypes and outcomes of treatment with direct-acting antiviral agents in Benin, a country with a national HCV seroprevalence of 4%.
METHODS
This prospective cohort study was conducted at two referral hospitals in Benin. Individuals were eligible for inclusion if they were seropositive for HCV and willing to consent to participation in the study; exclusion criteria were an inability to give consent or incarceration. Viraemia was confirmed by PCR. The primary outcomes were to identify HCV genotypes and measure sustained virological response rates 12 weeks after completion of treatment (SVR12) with a 12-week course of sofosbuvir-velpatasvir or sofosbuvir-ledipasvir, with or without ribavirin. We conducted phylogenetic and resistance analyses after the next-generation sequencing of samples with a cycle threshold (Ct) value of 30 or fewer cycles. The in-vitro efficacy of NS5A inhibitors was tested using a subgenomic replicon assay.
FINDINGS
Between June 2, 2019, and Dec 30, 2020, 148 individuals were screened for eligibility, of whom 100 were recruited prospectively to the study. Plasma samples from 79 (79%) of the 100 participants were positive for HCV by PCR. At the time of the study, 52 (66%) of 79 patients had completed treatment, with an SVR12 rate of 94% (49 of 52). 57 (72%) of 79 samples had a Ct value of 30 or fewer cycles and were suitable for whole-genome sequencing, from which we characterised 29 (51%) samples as genotype 1 and 28 (49%) as genotype 2. Three new genotype 1 subtypes (1q, 1r, and 1s) and one new genotype 2 subtype (2xa) were identified. The most commonly detected subtype was 2d (12 [21%] of 57 samples), followed by 1s (eight [14%]), 1r (five [9%]), 1b (four [7%]), 1q (three [5%]), 2xa (three [5%]), and 2b (two [3%]). 20 samples (11 genotype 2 and nine genotype 1) were unassigned new singleton lineages. 53 (93%) of 57 sequenced samples had at least two resistance-associated substitutions within the NS5A gene. Subtype 2d was associated with a lower-than-expected SVR12 rate (eight [80%] of ten patients). For one patient, with subtype 2b, treatment was not successful.
INTERPRETATION
This study revealed a high SVR rate in Benin among individuals treated for HCV with sofosbuvir-velpatasvir, including those with highly diverse viral genotypes. Further studies of treatment effectiveness in genotypes 2d and 2b are indicated.
FUNDING
Medical Research Council, Wellcome, Global Challenges Research Fund, Academy of Medical Sciences, and PHARMBIOTRAC.
PubMed: 38889738
DOI: 10.1016/S2666-5247(24)00041-7 -
Virology Journal Jun 2024Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and... (Review)
Review
BACKGROUND
Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and death. In Europe, transmission occurs most often through the consumption of raw or undercooked pork, more rarely through blood transfusion, but also after solid organ transplantation. Here we describe a case of Hepatitis E virus (HEV) infection transmitted following kidney transplantation and review the literature describing cases of HEV infection transmitted by solid organ transplantation.
CASE PRESENTATION
Three weeks after kidney transplantation, the patient presented with an isolated minimal increase in GGT and hepatic cytolysis 6 months later, leading to the diagnosis of genotype 3c hepatitis E, with a plasma viral load of 6.5 logIU/mL. In retrospect, HEV RNA was detected in the patient's serum from the onset of hepatitis, and in the donor's serum on the day of donation, with 100% identity between the viral sequences, confirming donor-derived HEV infection. Hepatitis E had a chronic course, was treated by ribavirin, and relapsed 10 months after the end of treatment.
DISCUSSION
Seven cases of transmission of HEV by solid organ transplantation have been described since 2012 without systematic screening for donors, all diagnosed at the chronic infection stage; two patients died. HEV organ donor transmission may be underestimated and there is insufficient focus on immunocompromised patients in whom mild liver function test impairment is potentially related to hepatitis E. However, since HEV infection is potentially severe in these patients, and as evidence accumulates, we believe that systematic screening of organ donors should be implemented for deceased and living donors regardless of liver function abnormalities, as is already the case in the UK and Spain. In January 2024, the French regulatory agency of transplantation has implemented mandatory screening of organ donors for HEV RNA.
Topics: Hepatitis E; Humans; Kidney Transplantation; Hepatitis E virus; France; Tissue Donors; Male; RNA, Viral; Middle Aged; Genotype; Viral Load; Antiviral Agents
PubMed: 38867299
DOI: 10.1186/s12985-024-02401-2 -
Nature Communications Jun 2024Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very...
Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.
Topics: Virus Replication; Hepatitis E virus; Humans; Hepatitis E; Ribavirin; Mutagenesis, Insertional; Antiviral Agents; RNA, Viral; Genome, Viral; Replicon
PubMed: 38844458
DOI: 10.1038/s41467-024-49219-8 -
GE Portuguese Journal of... Jun 2024Common variable immunodeficiency enteropathy is a sprue-like disease, which may manifest as a severe malabsorption syndrome with nutritional deficits and cachexia. The...
Common variable immunodeficiency enteropathy is a sprue-like disease, which may manifest as a severe malabsorption syndrome with nutritional deficits and cachexia. The authors report a case of a 33-year-old Afghan man, who presented to the emergency department due to chronic watery diarrhea and severe malnourishment. He had been previously misdiagnosed with celiac disease in his early adulthood; however, this was based on inconclusive findings. After a thorough diagnostic workup, the final diagnosis of common variable immunodeficiency enteropathy with symptomatic infection of the gut was obtained during his prolonged hospitalization. A slow but progressive improvement was observed with immunoglobulin replacement therapy, corticotherapy, and ribavirin treatment. This is a noteworthy case of a rare malabsorption disorder, and it reviews important aspects concerning the differential diagnosis of small bowel villous atrophy of unknown etiology, as well as gastrointestinal manifestations of common variable immunodeficiency disorder.
PubMed: 38836127
DOI: 10.1159/000531396 -
Antiviral Research Jul 2024Hepatitis E is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic, but can reach...
Hepatitis E is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic, but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. Hepatitis E virus (HEV) infection have been associated with a range of extrahepatic manifestations, including a spectrum of neurological symptoms. Current therapy options are limited to non-specific antivirals like ribavirin, but recently, repurposed viral polymerase inhibitors like sofosbuvir and NITD008 were described to inhibit HEV replication. Here, we evaluated the efficacy of these drugs in various neuronal-derived cell lines to determine their potency outside the liver. Our findings indicate that both drugs, especially sofosbuvir, exhibited reduced efficacy in neuronal cells compared to hepatic cells. These results should be taken into account in the development of direct-acting antivirals for HEV and their potency at extrahepatic replication sites.
Topics: Sofosbuvir; Antiviral Agents; Humans; Hepatitis E virus; Virus Replication; Neurons; Cell Line; Hepatitis E; Adenosine
PubMed: 38825018
DOI: 10.1016/j.antiviral.2024.105922 -
Journal of Biomedical Research Mar 2024Despite achieving a high cure rate with direct-acting antivirals (DAAs) in hepatitis C treatment, further research is needed to identify additional benefits of the DAA...
Despite achieving a high cure rate with direct-acting antivirals (DAAs) in hepatitis C treatment, further research is needed to identify additional benefits of the DAA therapy. The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs, who also achieved sustained virologic response (SVR). Using the fibrosis-4 (FIB-4) index, patients were categorized based on their baseline fibrosis level, and improvements in fibrosis were analyzed in both the short-term (9-26 weeks) and long-term (≥ 36 weeks) follow-up. The results showed a significant decrease in the FIB-4 index, indicating an improvement in liver fibrosis, in 63.00% of the patients during the short-term follow-up and 67.56% during the long-term follow-up. Short-term improvement was associated with factors including ribavirin (RBV) usage, blood cholinesterase levels, alanine transaminase levels, albumin levels, and the baseline FIB-4 index. Additionally, long-term improvement was associated with factors such as aspartate transaminase levels, total protein level, and the baseline FIB-4 index. The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis, providing crucial insights for enhancing patient care in hepatitis C management.
PubMed: 38808546
DOI: 10.7555/JBR.37.20230284