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Objective The present study was undertaken to evaluate the safety and efficacy of intravenous (IV) golimumab in patients with active psoriatic arthritis (PsA) through 1 year. Methods GO-VIBRANT was a phase III, randomized, placebo-controlled trial of 480 adults with active PsA. Patients were randomized to receive IV placebo (n = 239) or golimumab 2 mg/kg (n = 241) at weeks 0, 4, and every 8 weeks, with placebo crossover to golimumab at weeks 24, 28, and every 8 weeks thereafter. Efficacy through week 52 was assessed using the American College of Rheumatology (ACR) ≥20%, 50%, or 70% improvement criteria (ACR20/50/70), and the Psoriasis Area and Severity Index ≥75% improvement criteria (PASI75). Radiographic progression was measured using the PsA-modified Sharp/van der Heijde score (SHS). Adverse events (AEs) were monitored through week 60. Results The primary and major secondary end points through week 24 were achieved. At week 52, 76.8% of patients in the golimumab group and 77.0% in the placebo-crossover group achieved an ACR20 response, 58.1% and 53.6%, respectively, achieved an ACR50 response, and 38.6% and 33.9%, respectively, achieved an ACR70 response. Among patients with ≥3% body surface area affected, 71.9% in the golimumab group and 60.6% in the placebo-crossover group achieved a PASI75 response at week 52. Mean change from baseline in total SHS at week 52 was -0.5 in the golimumab group and 0.8 in the placebo-crossover group. Through week 60, 50.9% of all golimumab-treated patients had ≥1 AE, and 5.2% had ≥1 serious AE. There were no opportunistic infections, 2 malignancies, and 1 death in patients treated with golimumab. Conclusion Sustained improvements in joint and skin disease in patients with PsA were maintained through 1 year in the GO-VIBRANT study. No new safety signals for IV golimumab were identified.

It is a great pleasure to contribute a few words of introduction to this Special Issue of MDPI’s Diseases entitled “Recent Studies of Arthropod-, Bat-, and Rodent-Borne Viruses: A Theme Issue in Honor of Professor Charles H [...]

Purpose Radiology-trained nurse practitioners (NPs) may perform image-guided medical renal biopsies with computed tomography (CT). This study evaluates the procedural differences and diagnostic success between biopsies performed by NPs compared to radiologists. Data sources A retrospective study was performed on patients who underwent nontargeted, CT-guided renal biopsy between 2009 and 2014. Provider type (NP or radiologist), number of core specimens obtained, sedation medication dose, CT dose index (CTDI), and diagnostic success were recorded. Categorical and continuous variables were analyzed using χ2 and Student's two-tailed t-test, respectively, comparing NPs with radiologists. Conclusions A total of 386 patients were included; radiologists performed 215 biopsies and NPs performed 171 biopsies. There was no significant difference in diagnostic success, amount of tissue harvested (number of cores), radiation dose, or sedation dosage between NPs and radiologists performing CT-guided renal biopsies. Only 4% were nondiagnostic (n = 7, radiologists; n = 9, NPs; p = .325). Overall mean number of cores obtained was 3.7, mean CTDI was 176.5 mGy, mean fentanyl dose was 86.3 μg, and mean midazolam was dose 1.54 mg without a statistically significant difference between provider types. Implications for practice NPs perform image-guided medical renal biopsies in a similar fashion to radiologists with respect to diagnostic success, amount of tissue harvested, total radiation dose exposure, and administration of sedation.

A 65-year-old woman presented to our rheumatology clinic with pain and swelling of multiple joints of her hands. After a thorough evaluation, she was diagnosed with rheumatoid arthritis and was started on hydroxychloroquine therapy. A week later, she presented to our clinic with an acute condition and reported that after taking hydroxychloroquine for a few days she developed multiple rashes, most prominent at skin folds around her breasts, neck, axillae and buttocks. The rashes were characteristic of inverse psoriasis. Hydroxychloroquine was discontinued and the patient was started on methotrexate therapy that resulted in resolution of her rashes in a week.

This chapter presents morphologic and morphogenetic characterizations for the virus family as a whole, and uses these characterizations for informal subgrouping of the family. The term "rhabdovirus" emerged after it was found that the unusual bullet-shaped morphology of vesicular stomatitis virus was shared with other viruses, such as rabies and sigma viruses. Thin-section electron microscopy must be considered secondary to negative contrast methods in elucidation of viral morphology per se, but with the rhabdoviruses the techniques are complementary. Rhabdovirus assembly is usually associated with the accumulation of extra nucleoprotein strands within host cell cytoplasm. Early in infection the strands may be undetectable by electron microscopy because of their narrow diameter and dispersion in cytosol. Electron microscopy has been used for the presumptive identification of laboratory (vaccine) strains of rabies virus in circumstances where vaccine-associated disease had to be distinguished from natural disease.

Purpose The aim of this study was to determine the rate of detection of unsuspected pregnancies after the implementation of mandatory point-of-care urine pregnancy testing before hysterosalpingography (HSG). Methods At the authors' institution, HSGs are scheduled to occur during days 8 to 12 of the menstrual cycle. Upon arrival in the radiology department, all women undergo point-of-care urine pregnancy testing before HSG (at a cost of $1.25 per test). Urine pregnancy test results were retrospectively reviewed. Results Four hundred ten women (mean age, 25.9 years; range, 22-50 years) underwent point-of-care urine pregnancy testing before HSG between October 2010 and July 2012. Study indications were infertility evaluation (90.7% [372 of 410]) and tubal patency assessment after placement of tubal occlusive devices (9.3% [38 of 410]). Two positive urine pregnancy test results (0.5%) were recorded. One positive result was deemed a false-positive because the patient had received an intramuscular injection of β–human chorionic gonadotropin before the scheduled HSG, and follow-up laboratory testing showed declining β–human chorionic gonadotropin levels. The second positive result was a true-positive, and the patient was determined to be 4.5 weeks pregnant on the date of the scheduled HSG. Conclusions One of 410 women presenting for HSG was found to have an unsuspected early pregnancy, which was detected with a point-of-care urine pregnancy test. Consideration should be given to routine pregnancy testing of women before HSG because scheduling on the basis of menstrual cycle dates can be unreliable.

Objective To compare the efficacy of tanezumab versus placebo for reducing pain and improving physical function in patients with osteoarthritis (OA) of the hip. Methods This was a 32-week, randomized, double-blind, placebo-controlled, phase III trial. Patients with baseline Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively, and patient's global assessment of OA as “fair,” “poor,” or “very poor” were treated at baseline and weeks 8 and 16. Coprimary efficacy end points were change from baseline to week 16 in WOMAC Pain and Physical Function subscales and patient's global assessment, analyzed using analysis of covariance. Adverse events (AEs) were monitored throughout. Results Patients (n = 621) were randomized 1:1:1:1 to treatment with intravenous tanezumab 2.5 mg, 5 mg, or 10 mg or placebo. Each tanezumab group showed significant improvement for the 3 coprimary end points versus placebo (P ≤ 0.001 for all). AE incidence ranged from 55% to 58% across tanezumab groups versus 44% for placebo. Safety findings were similar to those previously reported. The tanezumab OA clinical program was temporarily placed on hold because of AEs leading to joint replacement. Total joint replacements were reported in 8 patients: 1 in the 10 mg, 2 in the 5 mg, 2 in the 2.5 mg, and 3 in the placebo group. A total of 9 joints were replaced (8 hips [7 index joints] and 1 shoulder). Conclusion Our findings indicate that tanezumab provides superior pain relief and improvement in physical function and patient's global assessment versus placebo in patients with painful hip OA, and is generally well tolerated.

Parvoviruses target the dividing cells of the bone marrow, gut, and the developing fetus. Human B19 parvovirus is associated with a very common exanthematous disease of children as well as aplastic crises in hydrops fetalis and chronic hemolytic anemia. The newly recognized bocaviruses within the family Parvoviridae are linked to respiratory infections and gastroenteritis. The single-stranded DNA genome is the smallest among DNA viruses but replicates via a unique “rolling circle” mechanism and a complexity of splicing and transfer events to produce viral proteins.

The family Flaviviridae includes many viruses of medical importance, for example, the arthropod-transmitted dengue, yellow fever, West Nile and Japanese encephalitis viruses. Recently, Zika virus has become of global public health importance. Hepattitis C virus within the genus Hepacivirus is a major cause of chronic liver disease and hepatocellular carcinoma. Vaccines are available for yellow fever, Japanese encephalitis and West Nile viruses. The treatment of hepatitis C virus infection through the use of antivirals is showing considerable promise. All flaviviruses contain a positive sense single-stranded RNA genome, divided into structural and non-structural protein coding regions.

Hepatitis B is one of the world’s major unconquered diseases. Over 300 million people are chronic carriers of the virus, and a significant minority of these go on to develop cirrhosis or cancer of the liver from which over a million die each year. It is estimated that up to 2 billion people have been exposed to this virus at some time in their life. Reliable diagnostic procedures and vaccines have been available for several decades. Despite the availability of vaccines, however, there are still more than 600,000 deaths each year. Owing to the large number of chronically infected individuals, however, it will take several generations before such implementation has a significant impact on the incidence of chronic liver disease and related hepatocellular carcinoma. Antiviral therapy of hepatitis B is now having a significant impact on preventing patients progressing to chronic liver disease. Hepatitis delta virus is dependent upon the presence of hepatitis B virus and co-infection can lead to severe liver disease. Unique among all human viruses, the hepatitis delta viral genome acts as a satellite virus, with an RNA genome possessing many of the properties of ribozymes.

Of the more than 175 viruses of vertebrates, invertebrates and plants within the family Rhabdoviridae, only rabies virus represents a significant infection risk to humans: vesicular stomatitis and a few others are only occasional, zoonotic diseases. Containing a negative sense single-stranded RNA genome, the virions have a distinctive bullet shape. Transmission is invariably through the bite of a rabid animal. The virus ascends to the brain through peripheral nerve fibers to cause extensive damage to the brain parenchyma. Human infection with rabies virus is almost invariably fatal. Post-exposure prophylaxis involves administering hyperimmune globulin and a course of vaccine. Cell culture-based vaccines are available.

With the exception of rubella, most togaviruses exist in well-defined geographical areas where mosquito vectors and host species determine the extent of virus survival and spread to humans. Important zoonotic pathogens include the three equine encephalitis viruses of the Americas. Chikungunya virus is now widely recognized as a significant cause of febrile illness accompanied by arthralgia. More serious complications have been observed in recent years. In contrast rubella is endemic worldwide: although a mild childhood exanthema, infection of non-immune pregnant woman can result in serious congenital malformations. For this reason, extensive vaccination is practiced among infants using the measles/mumps/rubella vaccine. All togaviruses contain a positive sense RNA genome expressed through the generation of full-length and sub-genomic mRNA transcripts.

Arenaviruses have evolved closely with a number of animal hosts that act as reservoirs of infection. Regarded as important zoonotic pathogens, the risk of transmission of each virus to humans relates to the nature of the infection in each rodent host: rodents usually undergo a persistent, asymptomatic infection accompanied by the shedding of virus throughout the life of the animal. The family Arenaviridae includes some of the most lethal hemorrhagic fevers known—Lassa, Lujo, Argentine, Bolivian, Venezuelan, and Brazilian hemorrhagic fevers. The risk of human infection through contact with virus-laden rodent excreta closely corresponds to rodent population dynamics, animal behavior, and changes in agricultural practice. Viruses unusually contain non-functional host ribosomes. The replication cycle involves an ambisense coding strategy similar to that of the bunyaviruses.

Two major forms of immune defense are activated once a virus has breached a natural barrier to entry, innate and adaptive immunity. This chapter deals with the innate immune response, a mechanism that operates immediately to limit tissue injury and prevent the spread of virus to adjacent, healthy cells, the so-called “bystander” effect. Innate immunity is of broad specificity, modulated largely by the secretion of an extensive array of signaling molecules that collectively form local inflammatory responses. Almost all viruses have developed elaborate strategies to circumvent host innate immunity. Some viruses use the host innate response as a vital part of the replication cycle, for example by taking advantage of innate responses the number of cell surface viral receptors may increase or use of an expanded endoplasmic reticulum for virus assembly.

An accurate virus diagnosis invariably requires laboratory testing of clinical specimens for the presence of virus, viral antigens, or specific antibodies. The past few decades have seen a major revolution in the operation of virus diagnostic laboratories and in their role in clinical patient management. Virus isolation has been largely replaced by sensitive nucleic acid detection assays and the measurement of specific antibodies at a very high level of sensitivity and specificity.

Viral infections can be classified as either transient or persistent , and within each of these categories an infection may be either localized (that is, confined to the epithelial surface where the virus initially enters), or systemic (that is, spreading more generally throughout body compartments, usually via the bloodstream). Under normal circumstances most common human infections typically lead to one of these four possible scenarios, transient local, systemic persistent infection, etc., depending on the virus. The outcome may be dependent upon age, variation among wild-type viruses, and whether or not the individual is immunosuppressed. Chronic infection caused by herpesviruses, viral hepatitis viruses B and C, and HIV represents the vast proportion of infections confronting the virologist.

Epidemiology is the study of the distribution, the dynamics, and the determinants of diseases in populations. The risk of virus infection and/or clinical disease is determined by characteristics both of the virus, and the levels of innate and acquired resistance in the community. Virus transmission is affected by behavioral, environmental, and ecological factors. Knowledge of these factors contributes to evidence-based policy decisions as to how best to control and prevent virus diseases. Considerable use of genome sequencing of isolates now provides useful information as to the identification of outbreak sources as well as informing the design and testing of candidate vaccines.

Emerging viral diseases now represent a major concern worldwide with the appearance of a new virus, or the re-emergence of a previously recognized virus with altered epidemiology and properties, occurring almost annually. Prominent examples in the last years include the sudden crossing of H5N1 avian influenza virus into humans in 1995, the unexpected West African outbreak of Ebola virus in 2014, the appearance of the Middle East respiratory syndrome related to the SARS virus first recognized in 2003, and the more recent epidemic of Zika virus in the Americas. These are just a few examples representing the constantly evolving relationship between pathogen and host, a process of evolution accelerated by population growth, climatic changes, and human activities.

Extracellular virus consists of the viral genome surrounded by a protective coat of protein; the resulting nucleocapsid may be surrounded by an outer lipid envelope in which viral proteins are embedded. Viral proteins confer specificity as to the range and type of host cell that may be infected. The assembly of spherical particles follows the principles of cubic symmetry with individual asymmetrical proteins clustered into symmetrical structures grouped around the cubic axis of symmetry to form an icosahedron. X-ray diffraction studies have revealed how viral proteins expose ligands important for the recognition of host cell receptors and the properties of antigenic variants. The properties of viral proteins determine temperature sensitivity and resistance to environment and chemical factors.

The taxonomy of viruses represents a unique classification system that recognizes boundaries among at first sight a continuum of properties. Genome sequencing has brought into sharp debate the origin of viruses, with RNA viruses perhaps having a separate evolutionary lineage. The criteria adopted for assessing the causal linkage between virus and disease deviates from those normally adopted for bacterial diseases and reflects those unique properties that underlie the principles of virus classification.

Pathogenesis encompasses all the sequence of events accompanying acute and persistent infections. It includes entry of the virus into the body, multiplication and spread, the development of tissue damage, and the production of an immune response; the latter may contribute to the pathology of an infection. It includes the appearance of clinical signs and symptoms, the eventual resolution of the infection and, in most cases, virus elimination. Understanding viral disease pathogenesis requires knowledge of each of the stages of infection and an awareness of the underlying mechanisms. There may be variation from individual to individual in the severity and/or the duration of these events, but a sound working knowledge of a typical sequence associated with each infection is crucial in both making an accurate diagnosis and recommending the appropriate treatment.

Vaccination is one of the most effective intervention measures known to medical science. Apart from the eradication of smallpox and the near eradication of poliomyelitis, the incidence of major childhood diseases has declined dramatically in developed countries through the implementation of childhood immunization programs. However, effective vaccination protocols require a political will that is often lacking in many countries. Vaccines against diseases such as hepatitis B and certain papillomaviruses will make inroads into the prevalence of human cancer induced by these viruses. The introduction of vaccines against some viruses such as HIV, hepatitis C virus and others, has proved remarkably difficult, however, and a plethora of newer technologies have been investigated.

Coronaviruses possess a distinctive morphology, the name being derived from the outer fringe, or “corona” of embedded envelope protein. Members of the family Coronaviridae cause a broad spectrum of animal and human diseases. Uniquely, replication of the RNA genome proceeds through the generation of a nested set of viral mRNA molecules. Until 2003, coronaviruses attracted little interest beyond causing mild upper respiratory tract infections. This changed dramatically in 2003 with the zoonotic SARS-CoV and the more recent emergence of MERS-CoV has confirmed the coronaviruses as significant causes of severe respiratory disease.

The chapters in this textbook deal with those viruses causing human disease, and the various modes of replication, transmission, and disease-causing processes that contribute to a particular clinical presentation. This final chapter focuses on each of the major clinical syndromes and outlines the contribution of particular viruses to each one, thereby serving as a pointer to elsewhere among earlier chapters where more specific information can be found. These virus–disease associations have been presented in tabular form for ease of reference.

The overwhelming majority of viruses within the family Bunyaviridae do not cause human disease. Notwithstanding, there are several bunyaviruses of considerable public health importance. The Bunyaviridae is the largest virus family, with more than 350 member viruses and it is likely that more will become recognized as significant human pathogens in the years to come. Members of the family Bunyaviridae show common features both regarding the nature of the virions and in biological properties. Nearly all of the viruses are arboviruses, maintained in arthropod–vertebrate–arthropod cycles that have considerable specificity with regard to both arthropod vectors and vertebrate reservoir hosts. This specificity is the basis for the usually narrow geographical and ecological niches occupied by each virus. The important exception is the hantaviruses, which are transmitted in vertebrate–vertebrate cycles without arthropod vectors; however, the hantaviruses also share with other bunyaviruses exquisite specificity as to vertebrate reservoir hosts and narrow ecological niches.

It is now accepted that as many as one-fifth of all human cancers may result from virus infection. Viral oncology owes much to the observations over 100 years ago that viruses may cause tumors in animals. Over 50 years later, detailed epidemiological and molecular studies have confirmed some retroviruses, hepadnaviruses, herpesviruses, and papillomaviruses as major causes of human cancers. The mechanisms of viral oncogenesis are complex, differing from virus to virus. As noted elsewhere, considerable advances have been made in developing vaccines against several viruses oncogenic for humans, notably some papilloma and hepatitis B viruses.

Herpesviruses are ubiquitous among all vertebrate species. Most usually cause asymptomatic infections except in the very young and the immunocompromised. All persist indefinitely within the nucleus of infected cells. Major human herpetic infections include herpes simplex, varicella-zoster and Epstein-Barr viruses together with cytomegalovirus. Recent years have revealed three other human herpesviruses, two (HHV-6 and HHV-7) cause mild infections; HHV-8 is linked to Kaposi’s sarcoma, a marker for AIDS. The double-stranded herpesvirus genome codes for most of the enzymes required for replication. Herpes simplex infection was one of the first to be successfully treated by antiviral chemotherapy and vaccines are available against varicella-zoster virus: indeed the latter are now steadily being incorporated into childhood immunization programs.

Understanding the molecular events accompanying virus replication is essential for the proper understanding and control of all virus diseases. The virus replication cycle generates new viral genomes and proteins in sufficient quantities to ensure propagation of the viral genome; this requires that the extracellular viral genome is protected from enzymatic degradation and can be introduced into further target cells for further rounds of replication. The initial recognition between virus and host is more complex than originally supposed and may involve more than one cellular receptor. A critical first intracellular step is the generation of viral mRNA by one of a limited number of strategies first described by David Baltimore. Lacking ribosomes, viruses have no means of producing protein and are reliant on the host cell for protein synthesis. Viral proteins are often modified by host cell glycosylation during or after virus assembly. Temporal regulation of intracellular events is critical in all but the very simplest of viruses, and some form of suppression of the host innate immune response is common to nearly all human viruses. Infected cells often produce non-infectious particles with incomplete genomes, and these defective interfering particles may play a role in pathogenesis. Understanding these processes will open up a range of targets for the development of novel therapies.

The foundations of the science of medical virology are intertwined with the other life sciences, particularly microbiology and infectious diseases. Medical virology has a relatively brief history, spanning just over a century, but it is crowded with intriguing discoveries, stories of immense personal courage and numerous practical applications, many of which have had an overwhelmingly positive benefit on humankind. Its origins involved the replacement of centuries-old beliefs and theories with discoveries borne out of rigorous scientific investigation. Targeted prevention and control strategies could only be developed and implemented once the concept of the specificity of disease causation had been accepted, namely that infectious diseases are caused not by some common miasma (a mysteriously poisonous substance), but rather by specific agents. In a wider sense, the microbial sciences have played a pivotal role in the development of medical thought, particularly in applying scientific rigor in understanding pathological processes. Advances in understanding of infectious agents have led to improvements in human health and well-being that arguably have exceeded the contribution of any other branch of science. Indeed, many workers in this field have been awarded the Nobel Prize in Physiology or Medicine in recognition of their achievements.