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The New England Journal of Medicine Jul 2023Coinfection with hepatitis D virus (HDV) accelerates the progression of liver disease associated with chronic hepatitis B. Bulevirtide inhibits the entry of HDV into... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Coinfection with hepatitis D virus (HDV) accelerates the progression of liver disease associated with chronic hepatitis B. Bulevirtide inhibits the entry of HDV into hepatocytes.
METHODS
In this ongoing phase 3 trial, patients with chronic hepatitis D, with or without compensated cirrhosis, were randomly assigned, in a 1:1:1 ratio, to receive bulevirtide subcutaneously at 2 mg per day (2-mg group) or 10 mg per day (10-mg group) for 144 weeks or to receive no treatment for 48 weeks followed by bulevirtide subcutaneously at 10 mg per day for 96 weeks (control group). Patients will complete 96 weeks of additional follow-up after the end of treatment. The primary end point was a combined response at week 48 of an undetectable HDV RNA level, or a level that decreased by at least 2 log IU per milliliter from baseline, and normalization of the alanine aminotransferase (ALT) level. The key secondary end point was an undetectable HDV RNA level at week 48, in a comparison between the 2-mg group and the 10-mg group.
RESULTS
A total of 49 patients were assigned to the 2-mg group, 50 to the 10-mg group, and 51 to the control group. A primary end-point response occurred in 45% of patients in the 2-mg group, 48% in the 10-mg group, and 2% in the control group (P<0.001 for the comparison of each dose group with the control group). The HDV RNA level at week 48 was undetectable in 12% of patients in the 2-mg group and in 20% in the 10-mg group (P = 0.41). The ALT level normalized in 12% of patients in the control group, 51% in the 2-mg group (difference from control, 39 percentage points [95% confidence interval {CI}, 20 to 56]), and 56% in the 10-mg group (difference from control, 44 percentage points [95% CI, 26 to 60]). Loss of hepatitis B virus surface antigen (HBsAg) or an HBsAg level that decreased by at least 1 log IU per milliliter did not occur in the bulevirtide groups by week 48. Headache, pruritus, fatigue, eosinophilia, injection-site reactions, upper abdominal pain, arthralgia, and asthenia were more common in the 2-mg and 10-mg groups combined than in the control group. No treatment-related serious adverse events occurred. Dose-dependent increases in bile acid levels were noted in the 2-mg and 10-mg groups.
CONCLUSIONS
After 48 weeks of bulevirtide treatment, HDV RNA and ALT levels were reduced in patients with chronic hepatitis D. (Funded by Gilead Sciences; MYR 301 ClinicalTrials.gov number, NCT03852719.).
Topics: Humans; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis D, Chronic; Hepatitis Delta Virus; RNA; Coinfection
PubMed: 37345876
DOI: 10.1056/NEJMoa2213429 -
Journal of Wound Care Jul 2023Intertrigo is a common inflammatory skin disorder caused by skin-on-skin friction in skin folds, due to moisture becoming trapped because of poor air circulation. This... (Review)
Review
Intertrigo is a common inflammatory skin disorder caused by skin-on-skin friction in skin folds, due to moisture becoming trapped because of poor air circulation. This can occur in any area of the body where two skin surfaces are in close contact with each other. The aim of this scoping review was to systematically map, review and synthesise evidence on intertrigo in adults. We identified a wide range of evidence and performed a narrative integration of this related to the diagnosis, management and prevention of intertrigo. A literature search was conducted within the following databases: Cochrane Library, MEDLINE, CINAHL, PubMed and EMBASE. After reviewing articles for duplicates and relevance, 55 articles were included. The incorporation of intertrigo in the ICD-11 provides a clear definition and should improve the accuracy of estimates. With regards to the diagnosis, prevention and management of intertrigo, the literature demonstrates consensus among health professionals in approach and this forms the basis for the recommendations of this review: identify predisposing factors and educate patient in reducing these; educate patients in skin fold management and adopt structured skin care routine; treat secondary infection with appropriate topical agent; consider using moisture-wicking textiles within skin folds to reduce skin-on-skin friction, wick away moisture and reduce secondary infection. Overall, the quality of evidence on which to determine the strength of any recommendations for practice remains low. There remains the need for well-designed studies to test proposed interventions and build a robust evidence base.
Topics: Humans; Adult; Coinfection; Intertrigo; Skin Diseases; Skin; Skin Care
PubMed: 37405940
DOI: 10.12968/jowc.2023.32.7.411 -
Revista Da Sociedade Brasileira de... 2023
Topics: Humans; Trypanosoma cruzi; Coinfection; HIV Infections
PubMed: 38088667
DOI: 10.1590/0037-8682-0549-2023 -
The Pediatric Infectious Disease Journal Sep 2023As the transmission of endemic respiratory pathogens returns to prepandemic levels, understanding the epidemiology of respiratory coinfections in children with...
BACKGROUND
As the transmission of endemic respiratory pathogens returns to prepandemic levels, understanding the epidemiology of respiratory coinfections in children with SARS-CoV-2 is of increasing importance.
METHODS
We performed a retrospective analysis of all pediatric patients 0-21 years of age who had a multiplexed BioFire Respiratory Panel 2.1 test performed at Children's Healthcare of Atlanta, Georgia, from January 1 to December 31, 2021. We determined the proportion of patients with and without SARS-CoV-2 who had respiratory coinfections and performed Poisson regression to determine the likelihood of coinfection and its association with patient age.
RESULTS
Of 19,199 respiratory panel tests performed, 1466 (7.64%) were positive for SARS-CoV-2, of which 348 (23.74%) also had coinfection with another pathogen. The most common coinfection was rhino/enterovirus (n = 230, 15.69%), followed by adenovirus (n = 62, 4.23%), and RSV (n = 45, 3.507%). Coinfections with SARS-CoV-2 were most commonly observed in the era of Delta (B.1.617.2) predominance (190, 54.60%), which coincided with periods of peak rhino/enterovirus and RSV transmission. Although coinfections were common among all respiratory pathogens, they were significantly less common with SARS-CoV-2 than other pathogens, with exception of influenza A and B. Children <2 years of age had the highest frequency of coinfection and of detection of any pathogen, including SARS-CoV-2. Among children with SARS-CoV-2, for every 1-year increase in age, the rate of coinfections decreased by 8% (95% CI, 6-9).
CONCLUSIONS
Respiratory coinfections were common in children with SARS-CoV-2. Factors associated with the specific pathogen, host, and time period influenced the likelihood of coinfection.
Topics: Child; Humans; SARS-CoV-2; COVID-19; Coinfection; Retrospective Studies
PubMed: 37257127
DOI: 10.1097/INF.0000000000003981 -
Revista Da Sociedade Brasileira de... 2023Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular... (Review)
Review
Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.
Topics: Humans; Chikungunya Fever; Chikungunya virus; Acute Disease; Coinfection; Abdominal Pain
PubMed: 38088664
DOI: 10.1590/0037-8682-0341-2023 -
Frontiers in Immunology 2023SARS-CoV-2 and () are major infectious causes of death, with meta-analyses and population-based studies finding increased mortality in co-infected patients... (Review)
Review
SARS-CoV-2 and () are major infectious causes of death, with meta-analyses and population-based studies finding increased mortality in co-infected patients simultaneously diagnosed with COVID-19 and tuberculosis (TB). There is a need to understand the immune interaction between SARS-CoV-2 and which impacts poor outcomes for those co-infected. We performed a PubMed and preprint search using keywords [SARS-CoV-2] AND [tuberculosis] AND [Immune response], including publications after January 2020, excluding reviews or opinions. Abstracts were evaluated by authors for inclusion of data specifically investigating the innate and/or acquired immune responses to SARS-CoV-2 and in humans and animal models, immunopathological responses in co-infection and both trials and investigations of potential protection against SARS-CoV-2 by (BCG). Of the 248 articles identified, 39 were included. Incidence of co-infection is discussed, considering in areas with a high burden of TB, where reported co-infection is likely underestimated. We evaluated evidence of the clinical association between COVID-19 and TB, discuss differences and similarities in immune responses in humans and in murine studies, and the implications of co-infection. SARS-CoV-2 and have both been shown to modulate immune responses, particularly of monocytes, macrophages, neutrophils, and T cells. Co-infection may result in impaired immunity to SARS-CoV-2, with an exacerbated inflammatory response, while T cell responses to may be modulated by SARS-CoV-2. Furthermore, there has been no proven potential COVID-19 clinical benefit of BCG despite numerous large-scale clinical trials.
Topics: Humans; Animals; Mice; Mycobacterium tuberculosis; SARS-CoV-2; COVID-19; Coinfection; Tuberculosis
PubMed: 37841282
DOI: 10.3389/fimmu.2023.1254206 -
Seminars in Liver Disease Aug 2023First discovered over 40 years ago, the hepatitis delta virus (HDV) is a unique RNA virus, requiring hepatitis B virus (HBV) antigens for its assembly, replication, and... (Review)
Review
First discovered over 40 years ago, the hepatitis delta virus (HDV) is a unique RNA virus, requiring hepatitis B virus (HBV) antigens for its assembly, replication, and transmission. HBV and HDV can be acquired at the same time (coinfection) or HDV infection can occur in persons with chronic HBV (superinfection). Screening guidelines for HDV are inconsistent. While some guidelines recommend universal screening for all people with HBV, others recommend risk-based screening. Estimates of the global HDV prevalence range from 4.5 to 14.6% among persons with HBV; thus, there may be up to 72 million individuals with HDV worldwide. HDV is the most severe form of viral hepatitis. Compared to HBV monoinfection, HDV coinfection increases the risk of cirrhosis, hepatocellular carcinoma, hepatic decompensation, mortality, and necessity for liver transplant. Despite the severity of HDV, there are few treatment options. Pegylated interferon (off-label use) has long been the only available treatment, although bulevirtide is conditionally approved in some European countries. There are many potential treatments in development, but as yet, there are few effective and safe therapies for HDV infection. In conclusion, given the severity of HDV disease and the paucity of treatments, there is a great unmet need for HDV therapies.
Topics: Humans; Hepatitis B; Coinfection; Liver Neoplasms; Hepatitis Delta Virus; Hepatitis D; Hepatitis B virus
PubMed: 37473778
DOI: 10.1055/a-2133-8614 -
Medicina (Kaunas, Lithuania) Oct 2023: The aim of this study was to identify specific rhino- and oropharyngeal microbiological pathogens as well as associated comorbidities that favor SARS-CoV-2 infection...
: The aim of this study was to identify specific rhino- and oropharyngeal microbiological pathogens as well as associated comorbidities that favor SARS-CoV-2 infection and corelate them. : This prospective clinical study enrolled 61 patients (28 COVID-19-positive and 33 controls) who were tested for other comorbidities and co-existence of associated oral pathogenic microbiota. : A total of 247 bacterial isolates were identified in the bacterial cultures in both groups. Viral hepatitis type A was more prevalent in the COVID-19-positive group ( = 0.026), as was the presence of oral candidiasis ( = 0.006). In the control group, a moderate direct relationship was observed between the group G and dermatitis, and strong direct relationships were observed between the group G and external otitis, and dental alveolitis, and and chronic lymphocytic leukemia. In the test group, strong direct relationships were observed between and pulmonary thromboembolism; and autoimmune thyroiditis; post-viral immunosuppression, chronic coronary syndrome, and hypernatremia; group C and rheumatoid polyneuropathy; group G and hyperkalemia, hypothyroidism, secondary anemia, and splenomegaly; and active oral candidiasis and SARS-CoV-2 viral pneumonia. The following relationships were strong, but inverse: group G and acute respiratory failure, and active oral candidiasis and SARS-CoV-2 viral bronchopneumonia. : Briefly, COVID-19-positive patients have the predisposition to build up associated comorbidities and coinfections, which can be the expression of the immune burden that this virus generates to the host.
Topics: Humans; COVID-19; SARS-CoV-2; Coinfection; Candidiasis, Oral; Prospective Studies; Bacteria; Streptococcus
PubMed: 37893576
DOI: 10.3390/medicina59101858 -
Antiviral Therapy Aug 2023In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease... (Review)
Review
In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.
Topics: Humans; Hepatitis B virus; Antiviral Agents; Coinfection; Hepacivirus; Hepatitis C, Chronic; Ribavirin; Liver Cirrhosis; Interferons; Liver Neoplasms
PubMed: 37489502
DOI: 10.1177/13596535231189643 -
Immunity Jan 2024Natural killer (NK) cells are present in the circulation and can also be found residing in tissues, and these populations exhibit distinct developmental requirements and...
Natural killer (NK) cells are present in the circulation and can also be found residing in tissues, and these populations exhibit distinct developmental requirements and are thought to differ in terms of ontogeny. Here, we investigate whether circulating conventional NK (cNK) cells can develop into long-lived tissue-resident NK (trNK) cells following acute infections. We found that viral and bacterial infections of the skin triggered the recruitment of cNK cells and their differentiation into Tcf1CD69 trNK cells that share transcriptional similarity with CD56TCF1 NK cells in human tissues. Skin trNK cells arose from interferon (IFN)-γ-producing effector cells and required restricted expression of the transcriptional regulator Blimp1 to optimize Tcf1-dependent trNK cell formation. Upon secondary infection, trNK cells rapidly gained effector function and mediated an accelerated NK cell response. Thus, cNK cells redistribute and permanently position at sites of previous infection via a mechanism promoting tissue residency that is distinct from Hobit-dependent developmental paths of NK cells and ILC1 seeding tissues during ontogeny.
Topics: Humans; Coinfection; Killer Cells, Natural; Cell Differentiation
PubMed: 38157853
DOI: 10.1016/j.immuni.2023.11.018