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JAMA Dec 2023Hepatitis D virus (HDV) infection occurs in association with hepatitis B virus (HBV) infection and affects approximately 12 million to 72 million people worldwide. HDV... (Review)
Review
IMPORTANCE
Hepatitis D virus (HDV) infection occurs in association with hepatitis B virus (HBV) infection and affects approximately 12 million to 72 million people worldwide. HDV causes more rapid progression to cirrhosis and higher rates of hepatocellular carcinoma than HBV alone or hepatitis C virus.
OBSERVATIONS
HDV requires HBV to enter hepatocytes and to assemble and secrete new virions. Acute HDV-HBV coinfection is followed by clearance of both viruses in approximately 95% of people, whereas HDV superinfection in an HBV-infected person results in chronic HDV-HBV infection in more than 90% of infected patients. Chronic hepatitis D causes more rapidly progressive liver disease than HBV alone. Approximately 30% to 70% of patients with chronic hepatitis D have cirrhosis at diagnosis and more than 50% die of liver disease within 10 years of diagnosis. However, recent studies suggested that progression is variable and that more than 50% of people may have an indolent course. Only approximately 20% to 50% of people infected by hepatitis D have been diagnosed due to lack of awareness and limited access to reliable diagnostic tests for the HDV antibody and HDV RNA. The HBV vaccine prevents HDV infection by preventing HBV infection, but no vaccines are available to protect those with established HBV infection against HDV. Interferon alfa inhibits HDV replication and reduces the incidence of liver-related events such as liver decompensation, hepatocellular carcinoma, liver transplant, or mortality from 8.5% per year to 3.3% per year. Adverse effects from interferon alfa such as fatigue, depression, and bone marrow suppression are common. HBV nucleos(t)ide analogues, such as entecavir or tenofovir, are ineffective against HDV. Phase 3 randomized clinical trials of bulevirtide, which blocks entry of HDV into hepatocytes, and lonafarnib, which interferes with HDV assembly, showed that compared with placebo or observation, these therapies attained virological and biochemical response in up to 56% of patients after 96 weeks of bulevirtide monotherapy and 19% after 48 weeks of lonafarnib, ritonavir, and pegylated interferon alfa treatment.
CONCLUSIONS AND RELEVANCE
HDV infection affects approximately 12 million to 72 million people worldwide and is associated with more rapid progression to cirrhosis and liver failure and higher rates of hepatocellular carcinoma than infection with HBV alone. Bulevirtide was recently approved for HDV in Europe, whereas pegylated interferon alfa is the only treatment available in most countries.
Topics: Humans; Antiviral Agents; Carcinoma, Hepatocellular; Coinfection; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis D, Chronic; Hepatitis Delta Virus; Interferon-alpha; Liver Cirrhosis; Liver Neoplasms; Polyethylene Glycols
PubMed: 37943548
DOI: 10.1001/jama.2023.23242 -
Molecular Aspects of Medicine Dec 2023Invasive fungal diseases are common complications in critically ill patients and in those with significant underlying imbalanced immune systems. Fungal co-, and/or... (Review)
Review
Invasive fungal diseases are common complications in critically ill patients and in those with significant underlying imbalanced immune systems. Fungal co-, and/or super-infections are emerging and have become a rising concern within the last few years. In Europe, cases of candidiasis and aspergillosis dominate, followed by mucormycosis in India. Epidemiological studies show an increasing trend in the incidence of all three entities. Parallel to this, a shift within the underlying fungal pathogens is observed. More non-albicans Candida infections and aspergillosis with cryptic species are on the rise; cryptic species may cover intrinsic resistance to azoles and other antifungal drugs. The recent COVID-19 pandemic led to a significantly increasing incidence of invasive fungal diseases among hospitalized patients.
Topics: Humans; Pandemics; Mycoses; Antifungal Agents; Aspergillosis
PubMed: 37804792
DOI: 10.1016/j.mam.2023.101215 -
Digestive Diseases and Sciences Aug 2023Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease.... (Review)
Review
Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease. HDV accelerates liver fibrosis, increases the risk of hepatocellular carcinoma, and hastens hepatic decompensation compared to chronic HBV monoinfection. The Chronic Liver Disease Foundation (CLDF) formed an expert panel to publish updated guidelines on the testing, diagnosis, and management of hepatitis delta virus. The panel group performed network data review on the transmission, epidemiology, natural history, and disease sequelae of acute and chronic HDV infection. Based on current available evidence, we provide recommendations for screening, testing, diagnosis, and treatment of hepatitis D infection and review upcoming novel agents that may expand treatment options. The CLDF recommends universal HDV screening for all patients who are Hepatitis B surface antigen-positive. Initial screening should be with an assay to detect antibodies generated against HDV (anti-HDV). Patients who are positive for anti-HDV IgG antibodies should then undergo quantitative HDV RNA testing. We also provide an algorithm that describes CLDF recommendations on the screening, diagnosis, testing, and initial management of Hepatitis D infection.
Topics: Coinfection; Humans; Hepatitis Delta Virus; Hepatitis D; Superinfection; Hepatitis B virus
PubMed: 37338616
DOI: 10.1007/s10620-023-07960-y -
Nature Reviews. Microbiology Dec 2023Antibiotics have transformed medicine, saving millions of lives since they were first used to treat a bacterial infection. However, antibiotics administered to target a... (Review)
Review
Antibiotics have transformed medicine, saving millions of lives since they were first used to treat a bacterial infection. However, antibiotics administered to target a specific pathogen can also cause collateral damage to the patient's resident microbial population. These drugs can suppress the growth of commensal species which provide protection against colonization by foreign pathogens, leading to an increased risk of subsequent infection. At the same time, a patient's microbiota can harbour potential pathogens and, hence, be a source of infection. Antibiotic-induced selection pressure can cause overgrowth of resistant pathogens pre-existing in the patient's microbiota, leading to hard-to-treat superinfections. In this Review, we explore our current understanding of how antibiotic therapy can facilitate subsequent infections due to both loss of colonization resistance and overgrowth of resistant microorganisms, and how these processes are often interlinked. We discuss both well-known and currently overlooked examples of antibiotic-associated infections at various body sites from various pathogens. Finally, we describe ongoing and new strategies to overcome the collateral damage caused by antibiotics and to limit the risk of antibiotic-associated infections.
Topics: Humans; Anti-Bacterial Agents; Bacterial Infections; Microbiota
PubMed: 37542123
DOI: 10.1038/s41579-023-00936-9 -
Clinical and Molecular Hepatology Jul 2023Acute hepatitis C virus (HCV) infection is a global health concern with substantial geographical variation in the incidence rate. People who have received unsafe medical... (Review)
Review
Acute hepatitis C virus (HCV) infection is a global health concern with substantial geographical variation in the incidence rate. People who have received unsafe medical procedures, used injection drugs, and lived with human immunodeficiency virus are reported to be most susceptible to acute HCV infection. The diagnosis of acute HCV infection is particularly challenging in immunocompromised, reinfected, and superinfected patients due to difficulty in detecting anti-HCV antibody seroconversion and HCV ribonucleic acid from a previously negative antibody response. With an excellent treatment effect on chronic HCV infection, recently, clinical trials investigating the benefit of direct-acting antivirals (DAAs) treatment for acute HCV infection have been conducted. Based on the results of cost-effectiveness analysis, DAAs should be initiated early in acute HCV infection prior to spontaneous viral clearance. Compared to the standard 8-12 week-course of DAAs for chronic HCV infection, DAAs treatment duration may be shortened to 6-8 weeks in acute HCV infection without compromising the efficacy. Standard DAA regimens provide comparable efficacy in treating HCV-reinfected patients and DAA-naïve ones. For cases contracting acute HCV infection from HCV-viremic liver transplant, a 12-week course of pangenotypic DAAs is suggested. While for cases contracting acute HCV infection from HCV-viremic non-liver solid organ transplants, a short course of prophylactic or pre-emptive DAAs is suggested. Currently, prophylactic HCV vaccines are unavailable. In addition to treatment scale-up for acute HCV infection, practice of universal precaution, harm reduction, safe sex, and vigilant surveillance after viral clearance remain critical in reducing HCV transmission.
Topics: Humans; Antiviral Agents; Hepacivirus; Hepatitis C, Chronic; Hepatitis C; Liver Transplantation
PubMed: 36800699
DOI: 10.3350/cmh.2022.0349 -
Medicina Clinica Feb 2024
Topics: Humans; Scabies; Superinfection
PubMed: 37567823
DOI: 10.1016/j.medcli.2023.06.048 -
Deutsches Arzteblatt International Apr 2024Postoperative surgical site infections (SSI) account for almost 25% of all nosocomial infections in Germany and are a source of increased morbidity and mortality. (Review)
Review
BACKGROUND
Postoperative surgical site infections (SSI) account for almost 25% of all nosocomial infections in Germany and are a source of increased morbidity and mortality.
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed and on national and international guidelines.
RESULTS
The individual risk factors for SSI must be assessed before any surgical procedure. A body-mass index above 30 kg/m2 is associated with an unadjusted risk ratio of 1.35 [1.28; 1.41] for SSI, which rises to 3.29 [2.99; 3.62] if the patient is also immunosuppressed. The risk of SSI is also significantly higher with certain types of procedure. Perioperative antibiotic prophylaxis (PAP) is clearly indicated for operations that carry a high risk of SSI (e.g., colorectal surgery) and for those that involve the implantation of alloplastic material (e.g., hip endoprostheses). PAP can usually be administered with basic antibiotics such as cefazoline. The basic principles of PAP are that it should be given by the anesthesia team in the interval from 60 minutes preoperatively up to shortly before the incision, and that its administration should only be for a short period of time, usually as a single shot. Continuing PAP onward into the postoperative period leads to increased toxicity, bacterial superinfections, and antibiotic resistance.
CONCLUSION
The evidence shows that perioperative antibiotic prophylaxis is a component of a bundle of measures that can help prevent SSI. Strict indications and adherence to the basic principles of PAP are essential for therapeutic success.
Topics: Humans; Surgical Wound Infection; Antibiotic Prophylaxis; Anti-Bacterial Agents; Perioperative Care; Treatment Outcome; Germany; Evidence-Based Medicine; Risk Factors
PubMed: 38440828
DOI: 10.3238/arztebl.m2024.0037 -
Advances in Experimental Medicine and... 2024Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral... (Review)
Review
Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral pneumonia (with or without bacterial superinfections). Historically variola virus has been the poxviridae most frequently associated with the development of pneumonia with many large outbreaks worldwide before its eradication in 1980. It is still considered a biological threat for its potential in biological warfare and bioterrorism. Smallpox pneumonia can be severe with the onset of acute respiratory distress syndrome (ARDS) and death. Vaccinia virus, used for vaccination against smallpox exceptionally, in immunocompromised patients, can induce generalized (with also lung involvement) severe disease after vaccination. MPXV virus occasionally can cause pneumonia particularly in immunocompromised patients. The pathophysiology of poxviridae pneumonia is still an area of active research; however, in animal models these viruses can cause both direct damage to the lower airways epithelium and a hyperinflammatory syndrome, like a cytokine storm. Multiple mechanisms of immune evasion have also been described. The treatment of poxviridae pneumonia is mainly based on careful supportive care. Despite the absence of randomized clinical trials in patients with poxviridae pneumonia there are antiviral drugs, such as tecovirimat, cidofovir and brincidofovir, FDA-approved for use in smallpox and also available under an expanded access protocol for treatment of MPXV. There are 2 (replication-deficient modified vaccinia Ankara and replication-competent vaccinia virus) smallpox vaccines FDA-approved with the first one also approved for prevention of MPXV in adults that are at high risk of infection.
Topics: Humans; Animals; Poxviridae Infections; Antiviral Agents; Pneumonia, Viral; Poxviridae; Vaccinia virus; Smallpox; Variola virus
PubMed: 38801579
DOI: 10.1007/978-3-031-57165-7_12 -
Pathogens (Basel, Switzerland) Jul 2023Kala-azar, also known as visceral leishmaniasis (VL), is a disease caused by and . Patients experience symptoms such as fever, weight loss, paleness, and enlarged liver... (Review)
Review
Kala-azar, also known as visceral leishmaniasis (VL), is a disease caused by and . Patients experience symptoms such as fever, weight loss, paleness, and enlarged liver and spleen. The disease also affects immunosuppressed individuals and has an overall mortality rate of up to 10%. This overview explores the literature on the pathogenesis of preclinical and clinical stages, including studies in vitro and in animal models, as well as complications and death. Asymptomatic infection can result in long-lasting immunity. VL develops in a minority of infected individuals when parasites overcome host defenses and multiply in tissues such as the spleen, liver, and bone marrow. Hepatosplenomegaly occurs due to hyperplasia, resulting from parasite proliferation. A systemic inflammation mediated by cytokines develops, triggering acute phase reactants from the liver. These cytokines can reach the brain, causing fever, cachexia and vomiting. Similar to sepsis, disseminated intravascular coagulation (DIC) occurs due to tissue factor overexpression. Anemia, hypergammaglobulinemia, and edema result from the acute phase response. A regulatory response and lymphocyte depletion increase the risk of bacterial superinfections, which, combined with DIC, are thought to cause death. Our understanding of VL's pathogenesis is limited, and further research is needed to elucidate the preclinical events and clinical manifestations in humans.
PubMed: 37513817
DOI: 10.3390/pathogens12070969 -
American Family Physician Jul 2023Mpox (formerly monkeypox) is a DNA virus of the Orthopoxvirus genus, similar to smallpox. Although mpox was endemic to the Democratic Republic of the Congo and parts of... (Review)
Review
Mpox (formerly monkeypox) is a DNA virus of the Orthopoxvirus genus, similar to smallpox. Although mpox was endemic to the Democratic Republic of the Congo and parts of Africa, increasing numbers of cases were reported worldwide in 2022. More than 30,000 cases have been reported in the United States, and worldwide 98% of cases are found in men who have sex with men. Transmission is primarily through contact with skin lesions. The rash of mpox is often vesiculopustular and may be localized to the anogenital region or distributed on the face, trunk, limbs, palms, and soles. Two vaccines are available for pre- or postexposure prophylaxis. Jynneos (smallpox and mpox vaccine, live, nonreplicating) is a live, attenuated vaccine that is safe for patients who are immunocompromised. ACAM2000 (smallpox [vaccinia] vaccine, live) is a live vaccinia virus vaccine that should be given only to immunocompetent, nonpregnant people and should be avoided in those with skin conditions such as atopic dermatitis. For most people infected with mpox, the disease is mild and self-limiting. Antiviral treatments such as tecovirimat, cidofovir, or brincidofovir may be considered for use in individuals who have or are at high risk of severe disease. Possible complications of mpox include anogenital pain, bacterial superinfections of skin lesions, dehydration secondary to oral lesions, encephalitis, keratitis, and respiratory distress. To date, 38 deaths have been reported in the United States.
Topics: Humans; Male; Exanthema; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities; Smallpox
PubMed: 37440743
DOI: No ID Found