Concurrent detection of human herpesvirus type 6 and measles-specific IgMs during acute exanthematic human parvovirus B19 infection

A familial outbreak of human parvovirus B19 infection is described in which serological tests carried out routinely for determining the causal agent of febrile rashes of viral etiology failed to yield a definitive diagnosis. Concurrent detection of serum IgMs to parvovirus B19 and to heterologous viruses such as human herpesvirus type 6 (HHV-6) and measles virus complicated interpretation of the data. IgG avidity tests and investigation and testing for the presence of viral DNA in sera by PCR were required to confirm parvovirus B19. The study stresses the importance of avidity and PCR tests to obtain a firm diagnosis of febrile exanthematic viral diseases.     

Clinical characteristics of acute viral lower respiratory tract infections in hospitalized children in Seoul, 1996-1998.

This study was performed to investigate the etiologic agents, age distribution, clinical manifestations and seasonal occurrence of acute viral lower respiratory tract infections in children. We confirmed viral etiologies using nasopharyngeal aspirates in 237 patients of the ages of 15 years or younger who were hospitalized for acute lower respiratory tract infection (ALRI) from March 1996 to February 1998 at Samsung Seoul Hospital, Seoul, Korea. The overall isolation rate was 22.1%. The viral pathogens identified were adenovirus (12.7%), influenza virus type A (21.1%), -type B (13.9%), parainfluenza virus type 1 (13.5%), -type 2 (1.3%), -type 3 (16.0%) and respiratory syncytial virus (21.5%). The occurrence of ALRIs was highest in the first year of life, although parainfluenza virus type 1 infection occurred predominantly in the second year of life and influenza virus caused illnesses in all age groups. The specific viruses are frequently associated with specific clinical syndromes of ALRI. The respiratory agents and associated syndromes frequently have characteristic seasonal patterns. This study will help us to estimate the etiologic agents of ALRI, and establish a program for the prevention and treatment. An annual nationwide survey is necessary to understand the viral epidemiology associated with respiratory illnesses in Korea.     

The role of genetic diagnosis in clinics--from the choice of ordering until reading the data

Genetic diagnosis is a revolutionary method that makes possible simultaneous viral isolation (detection) and identification. The method is so specific, sensitive, and rapid (non-culture) that leads not only to the diagnosis of viral infection, but also to prediction of the chemotherapy, monitoring during the therapy, and judging the efficacy of the treatment. Moreover, it contributes to understanding the disease pathophysiology. The qualitative results are sufficient for diagnosis, but quantitative analysis is sometimes necessary for the prediction of the efficacy and monitoring during treatment. It occasionally requires the numbers of genomic expression, the number of DNA/RNA copies, and the detection of point mutations for drug resistance. Many emerging and re-emerging infectious diseases, such as AIDS and viral hepatitis, are induced by viral infection via blood. The main causative agents of blood-borne viral infection are hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T cell leukemia virus type 1 (HTLV1), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human parvovirus B19. They play main roles in viral hospital infection. The risk of them being transmitted by transfusion of screened blood is very low, but it is always possible that infection may occur in a window period even after extensive blood screening tests. Therefore, to shorten a window period, genetic examinations will be accepted for screening tests in the near future. Prioritization of genetic examinations is needed to select the adequate method and sampling. After examinations, false positive and false negative results have to be extensively read out whether due to contamination or inhibition by agent such as heparin and hemoglobin. The causative virus should be decided by carefully eliminating passenger viruses or latent viruses. Because genetic examinations are so useful but occasionally yield false positive and negative results, genetic diagnosis should be judged totally by combination with other examinations, clinical signs, and clinical symptoms.     

Tick-borne virus diseases of human interest in Europe

Several human diseases in Europe are caused by viruses transmitted by tick bite. These viruses belong to the genus Flavivirus, and include tick-borne encephalitis virus, Omsk haemorrhagic fever virus, louping ill virus, Powassan virus, Nairovirus (Crimean-Congo haemorrhagic fever virus) and Coltivirus (Eyach virus). All of these viruses cause more or less severe neurological diseases, and some are also responsible for haemorrhagic fever. The epidemiology, clinical picture and methods for diagnosis are detailed in this review. Most of these viral pathogens are classified as Biosafety Level 3 or 4 agents, and therefore some of them have been classified in Categories A-C of potential bioterrorism agents by the Centers for Disease Control and Prevention. Their ability to cause severe disease in man means that these viruses, as well as any clinical samples suspected of containing them, must be handled with specific and stringent precautions.     

Fatal BK polyoma viral pneumonia associated with immunosuppression

BK polyoma virus has a worldwide distribution in the human population. Primary BK infection takes place during childhood, with the virus remaining latent in many sites. Immunosuppressive states can lead to viral reactivation associated with many clinical sequelae. We report a case of fatal BK-related pneumonia in a 69-year-old patient who was immunocompromised because of chemotherapy for chronic lymphocytic leukemia. Immunohistochemical, in situ hybridization, and polymerase chain reaction studies on paraffin-embedded lung tissue proved BK virus as the etiologic agent of pneumonia. The histological picture was remarkable for numerous intranuclear large basophilic viral inclusions with ground-glass appearance mainly in type II pneumocytes. Similar to many other infectious agents, BK virus is emerging as an important pathogen in immunocompromised patients, making it important to consider in the differential diagnosis.     

Acute viral respiratory diseases as a cause of work disability in miners during an inter-epidemic period

During the interepidemic period between October 1 and November 20 1987 96 miners from a coal mine were examined who suffered from diseases of the upper airways which caused their work incapacity. In paired sera the rise of antibodies against M. pneumoniae and respiratory viruses were examined (adeno, influenza virus A and B, Coxsackie A21, corona 229E and OC43, parainfluenza type 1, 2 and 3, rhino type 13 and 44, RS). A viral aetiology was confirmed in 31 patients (32.3%). An evident rise of antibodies against the following viruses was found: adenoviruses 3X, Coxsackie A21 5X, coronaviruses 229E 1X and OC43 2X, parainfluenza virus type 1 1X and type 2 5X, rhinovirus type 13 11X and type 44 4X, RS virus 1X. As to the period of work incapacity and clinical manifestations, there was no difference between the diseases caused by different agents. The results of the investigation indicate that also viruses which are not used in common diagnostic practice may frequently evoke diseases which cause work incapacity.     

Neurologic complications of the acquired immune deficiency syndrome

The acquired immune deficiency syndrome (AIDS) is a syndrome requiring unique knowledge of its versatile manifestations for accurate diagnosis and skillfull management of its numerous complications for successful treatment. The human T-cell lymphotropic virus type III (HTLV-III), a replication-complete virus, is now reported as the etiologic agent. The neurologic complications of AIDS cover the spectrum of neurologic diseases and usually have multiple causative factors, all of which should be appropriately managed. These complications can be successfully treated, although constant monitoring is required because recurrence is frequent. The neurologic complications are the second most frequent cause of death in AIDS patients.     

Neuropathology of the acquired immunodeficiency syndrome

This review attempts to assess critically the literature on the neuropathology of acquired immunodeficiency syndrome in light of our experience with 172 patients with acquired immunodeficiency syndrome who underwent extensive postmortem examinations of the central and peripheral nervous systems. The neuropathologic manifestations of the disease can be divided into three categories: (1) primary or putative/indirect effects of the human immunodeficiency virus, (2) opportunistic infections, and (3) neoplasms. We discuss the known etiologic agents and postulated pathogenetic mechanisms responsible for the broad range of neurologic diseases observed in patients with acquired immunodeficiency syndrome.     

Viruses causing gastroenteritis

Acute gastroenteritis is one of the most common diseases in humans worldwide. Viruses are recognized as important causes of this disease, particularly in children. Since the Norwalk virus was identified as a cause of gastroenteritis, the number of viral agents associated with diarrheal disease in humans has steadily increased. Rotavirus is the most common cause of severe diarrhea in children under 5 years of age. Astrovirus, calicivirus and enteric adenovirus are also important etiologic agents of acute gastroenteritis. Other viruses, such as toroviruses, coronaviruses, picobirnaviruses and pestiviruses, are increasingly being identified as causative agents of diarrhea. In recent years, the availability of diagnostic tests, mainly immunoassays or molecular biology techniques, has increased our understanding of this group of viruses. The future development of a safe and highly effective vaccine against rotavirus could prevent, at least, cases of severe diarrhea and reduce mortality from this disease.     

Recent advances in the detection of respiratory virus infection in humans

Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019-nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray-based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus, and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections.     

Incidence of respiratory viruses in patients with community-acquired pneumonia admitted to the intensive care unit: results from the Severe Influenza Pneumonia Surveillance (SIPS) project

Few patients with community-acquired pneumonia (CAP) require admission to the intensive care unit (ICU-CAP). However, they represent the most severe form of the disease. An understanding of the etiologic agents of ICU-CAP may lead to better treatment decisions and patient outcomes. The objective of this study was to determine the incidence of respiratory viruses in patients with ICU-CAP. This was an observational study conducted in six Kentucky hospitals from December 2008 through October 2011. A case of ICU-CAP was defined as a patient admitted to an ICU with the diagnosis of CAP. The Luminex xTAG multiplex polymerase chain reaction (PCR) assay was used for viral identification. A total of 468 adult and pediatric patients with ICU-CAP were enrolled in the study. A total of 92 adult patients (23 %) and 14 pediatric patients (19 %) had a respiratory virus identified. Influenza was the most common virus identified in adults and the second most common in pediatric patients. This study suggests that respiratory viruses may be common etiologic agents of pneumonia in patients with ICU-CAP. The Centers for Disease Control and Prevention (CDC) recommend empiric anti-influenza therapy during the winter for hospitalized patients with CAP. This study supports this recommendation in patients with ICU-CAP.     

Treatment of rheumatic diseases in patients with HCV and HIV infection

A wide variety of rheumatic diseases has been documented in the presence of hepatitis C virus (HCV) infection and in human immunodeficiency virus (HIV) infection. In this conditions, physicians are refrained from using corticosteroids and/or immunosuppressants agents because of the risk of favouring viral replication and the progression of the underlying viral disease. In the present review we have focused our attention on the possible role of cyclosporine A (CsA), anti-Tumour Necrosis Factor (TNF) alpha agents in the treatment of HIV or HCV infected autoimmune patients. The results drown from the literature and from our personal experience confirm the safety of CsA and anti-TNF alpha agents, in terms of viral load and liver toxicity. A limited experience also suggest that both therapies can be given in combination in rheumatoid arthritis patients without increasing the risk of adverse events.     

Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases

In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival.     

Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV

Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.     

Deciphering the clinical impact of acute human herpesvirus 6 (HHV-6) infections

Human herpesvirus 6 (HHV-6) is a ubiquitous virus inducing a life-long latent infection of its human host. Acute infections (AIs) have been recognized as the cause of severe diseases. These AIs correspond to primary infections (PIs), mainly occurring in young children, endogenous reactivations (ENRs), observed at any age, and putative exogenous reinfections (EXRs). The diagnosis of AIs is now essentially based on the quantification of viral load in bodily fluids and organs by means of real time PCR. However, this diagnosis is currently bothered by the lack of well established viral load thresholds for the different levels of virus replication, the concomitant infection with the two variants HHV-6A and HHV-6B, and the existence, albeit at low frequency, of chromosomal integration of viral DNA. An additional challenge is the difficulty to establish the causality relationship between AI and disease. Although many AIs are asymptomatic or poorly symptomatic with a spontaneous favourable outcome, some have been credited with serious clinical manifestations affecting central nervous system, liver, gastrointestinal tract, lungs, and bone marrow. The main favouring factor for such serious diseases is cellular immune deficiency. These severe diseases can be exemplified by encephalitis cases either associated with PI in young children or with ENR, especially in haematopoietic stem cell transplant recipients. The antiviral drugs ganciclovir, foscarnet and cidofovir have proven to be efficient against AIs and related diseases but the indications and conditions of their use are not yet formally approved. This emphasizes the need for controlled studies addressing both the clinical impact and therapy of HHV-6 AIs.     

Zygomycosis: the re-emerging fungal infection

Invasive fungal infections are major medical complications in immunocompromised patients. The recent rise in the incidence of cancer and the increased use of newer medical treatment modalities, including organ transplantations, have resulted in growing numbers of highly immunosuppressed individuals. Although aspergillosis and candidiasis are among the most common invasive mycoses in such patients, there is evidence that the incidence of infectious diseases caused by Zygomycetes has risen significantly over the past decade. Patients with diabetes, malignancies, solid organ or bone marrow transplants, or iron overload and those receiving immunosuppressive agents, deferoxamine therapy, or broad-spectrum antimicrobial drugs are at highest risk for zygomycosis. This review details the emergence and importance of zygomycosis in current clinical practice and its manifestations and management. The etiologic species, pathogenesis and risk factors for zygomycosis are reviewed and updated. The clinical spectrum of zygomycosis is now broader, and it can be difficult to distinguish between mucormycosis and enthomophthoramycosis, both of which can manifest as disease ranging from a superficial infection to an angioinvasive infection with high mortality. Finally, the three-part treatment strategy (antifungal drugs, surgery, control of underlying diseases) is reviewed. Lipid formulations of amphotericin B are the antifungal agents of choice for treatment of zygomycosis. A novel antifungal triazole, posaconazole, has been developed and may become approved for treatment of zygomycosis. The clinical experience with adjunctive treatments like colony-stimulating factors, interferon-gamma, and hyperbaric oxygen therapy is still limited.     

Evaluation of a synthetic-peptide enzyme-linked immunosorbent assay for immunoglobulin M to human parvovirus B19.

A synthetic peptide corresponding to a part of the virus protein 1-virus protein 2 overlapping region of human parvovirus B19 was used in an indirect enzyme-linked immunosorbent assay. Antibodies of the immunoglobulin (Ig) M class were measured in serum samples from patients with erythema infectiosum and controls. In comparison with an IgM assay using native B19 viral antigen, the peptide antigen assay was 92% sensitive and 87% specific. B19 IgM reactivities were seen in a limited number of children with other viral diseases. Specific IgM reactivities to short synthetic viral peptides have previously been reported only with Epstein-Barr virus. Since other sources of viral antigen are limited, the peptide antigen assay may be a useful alternative for the diagnosis of B19-associated disease in human beings.     

Polymerase chain reaction as a diagnostic adjunct in herpesvirus infections of the nervous system

Polymerase chain reaction (PCR) is a powerful technique that allows detection of minute quantities of DNA or RNA in cerebrospinal fluid (CSF), vesicle and endoneurial fluids, blood, fresh-frozen, and even formalin-fixed tissues. Various infectious agents can be detected with high specificity and sensitivity, including bacteria, parasites, rickettsia and viruses. PCR analysis of CSF has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses (HHV), and has now replaced brain biopsy as the gold standard for diagnosis of herpes simplex virus (HSV) encephalitis. PCR analysis of both CSF and nervous system tissues has also broadened our understanding of the spectrum of disease caused by HSV-1 and -2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and HHV-6. Nonetheless, positive tissue PCR results must be interpreted cautiously, especially in cases that lack corroborating clinical and neuropathologic evidence of infection. Moreover, positive PCR results from tissues do not distinguish latent from productive (lytic) viral infections. In several neurological diseases, negative PCR results have provided strong evidence against a role for herpesviruses as the causative agents. This review focuses on the use of PCR tests to diagnose HSV and VZV infections of the nervous system.     

Epstein-Barr virus and human autoimmune diseases: possibilities and pitfalls

Epidemiologic studies suggest that human autoimmune disease involves both genetic and environmental components. Although a great deal has been learned about genetic components (i.e. histocompatibility antigens), little is known about the environmental factors. Because of its ubiquitous nature and ability to stimulate lymphoid responses, Epstein-Barr virus (EBV) has been examined as a potential candidate, particularly in rheumatoid arthritis and systemic lupus erythematosus. No convincing evidence has been produced that it plays a primary etiologic role in these disorders. Nevertheless, EBV or a related herpesvirus may play an indirect role in perpetuating the disorder or in the development of extra-articular manifestations such as Sj?gren's syndrome (an autoimmune disorder involving the salivary glands). Current data indicates increased EBV reactivation in some patients with autoimmune diseases, as evidenced by increased viral DNA in their saliva and increased number of circulating B-cells containing EBV in their blood. These patients also have modestly elevated anti-EBV antibody titers and altered antiviral T-cell responses, as measured by the ability to prevent outgrowth of autologous EBV infected B-cells. However, the relevance of these 'abnormalities' to pathogenesis remains unknown. It is hoped that new techniques such as polymerase chain reaction will provide new insights into these questions by allowing detection of viral DNA from tissue biopsies obtained early in the course of disease and by providing a method to identify viral isolates that do not grow well in vitro.