Use of Testing for West Nile Virus and Other Arboviruses.

In the United States, the most commonly diagnosed arboviral disease is West Nile virus (WNV) infection. Diagnosis is made by detecting WNV IgG or viral genomic sequences in serum or cerebrospinal fluid. To determine frequency of this testing in WNV-endemic areas, we examined the proportion of tests ordered for patients with meningitis and encephalitis at 9 hospitals in Houston, Texas, USA. We identified 751 patients (567 adults, 184 children), among whom 390 (52%) experienced illness onset during WNV season (June-October). WNV testing was ordered for 281 (37%) of the 751; results indicated acute infection for 32 (11%). Characteristics associated with WNV testing were acute focal neurologic deficits; older age; magnetic resonance imaging; empirically prescribed antiviral therapy; worse clinical outcomes: and concomitant testing for mycobacterial, fungal, or other viral infections. Testing for WNV is underutilized, and testing of patients with more severe disease raises the possibility of diagnostic bias in epidemiologic studies.

The demonstration of locally synthesized herpes simplex IgG antibodies in CSF by a Sepharose 4B linked enzyme immunoassay.

A newly developed peroxidase-linked immunoassay is described which is sensitive enough to quantify herpes simplex antibodies in serum and cerebrospinal fluid diluted to an IgG level of 1 mg/dl. Thus, a comparison of photometric signals allows the direct detection of specific antibodies which have been secreted by activated tissue B lymphocytes into the CSF compartment during the humoral immune phase of herpes simplex encephalitis. The technique utilizes urea-Triton-dissolved virus antigens covalently bound to Sepharose 4B pearls. A highly specific sandwich antibody was purified by immune absorption column chromatography and labelled in its protected state. In the majority of cases the antibody level increased around the 10th day, to reach its maximum a few days after. In some cases however the serum levels gradually rose over a period of several weeks. The antibody levels in the CSF increase uniformly at the same time, irrespective of the general immune response and soared up to higher than serum levels within a few days. Local antibody production may persist for years so that late diagnosis of herpes encephalitis becomes possible with a single side by side test of serum and CSF from the patient.

Herpes simplex retinitis.

Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infant. Clinically the disease appeared as whitish-yellow punctate lesions, perivascular cuffing, and hemorrhage. The antibody titer to herpes simplex rose from 1:8 on the day of admission to 1:256 on the day of death. Postmortem, intranuclear inclusion bodies that were typical of those found with herpesvirus were seen in the brain and retina. Viral particles consistent with those of herpesvirus were found by electron microscopy in the brain and in the inner-nuclear and ganglion-nerve fiber layers of the retina. This demonstrates the direct infectious nature of herpetic retinitis. Hematogenous spread of the virus to the retina is presumed.

Viral encephalitis.

Viral encephalitis represents an important source of morbidity and mortality worldwide. Numerous viruses possess neurovirulence, producing encephalitic disorders that usually consist of fever, headache, vomiting, altered consciousness, focal or generalized seizures, and motor dysfunction. Contemporary virologic methods frequently allow rapid and specific identification of viral pathogens, but the etiologic agent remains uncertain in 25% or more of encephalitis patients. Although acyclovir substantially reduces mortality and improves outcome for patients with herpes simplex virus encephalitis, supportive care remains the only therapy available for most patients with virus encephalitis.

Viral infections of the nervous system.

Neurotropic viruses cause a number of important infectious syndromes including encephalitis, myelitis, meningitis, and radiculopathy. In this review, the biology of conventional and unconventional viruses is examined. The host immune response to viruses is discussed, and patterns of viral pathogenesis are explained. The clinical features, laboratory findings, management of important viral infections, such as herpes simplex encephalitis and epidemic encephalitis, are presented. Post-infection syndromes, such as the Guillain-Barré syndrome, and chronic viral infections, such as those causing progressive multifocal leukoencephalopathy and subacute sclerosing panencephalitis, are discussed. Current knowledge concerning the nature of unconventional virus-like agents of the spongiform encephalopathies, including kuru and Creutzfeldt-Jakob disease, is summarized. Finally, viral infections of immunocompromised patients and the possible role of viruses in the newly described acquired immunodeficiency syndrome (AIDS) are examined.

The Gordon Wilson lecture: unique interactions between viruses, neurons and the immune system.

The increased susceptibility of young individuals to alphavirus encephalitis is likely to be linked to the ease with which immature neurons are induced to undergo apoptosis after infection. In the more mature individuals, virus infection of neurons may not lead to apoptosis and in the absence of an effective immune response persistent infection is established. The major mechanism by which alphavirus infection of neurons is controlled is by production and local secretion of antibody to the surface glycoproteins. Antibody acts synergistically with interferon to decrease intracellular virus replication but does not eliminate the infected cell or the viral RNA within the cell. Therefore, the immune response controls, but does not cure the infection, leading to a requirement for long-term local synthesis of antiviral antibody in the CNS. For the host persistent intracellular RNA and need for longterm control is probably a reasonable price to pay for a noncytolytic mechanism for control of neuronal viral infection.

Parotitis: clinical presentations and management.

Although mumps virus is the most common and, therefore, best known cause of parotitis, other causes are not infrequent and need to be distinguished from mumps. Knowledge of the various clinical presentations of parotitis and judicious use of a few ancillary tests will facilitate differential diagnosis.

[Von Economo-Cruchet lethargic encephalitis and its relation to HIV infection]. / L'encéphalite léthargique de von Economo-Cruchet et ses rapports avec l'infection HIV.

The AIDS epidemic is currently considered to be the first retroviral disease in humans. However, in the large volume of work on von Economo-Cruchet's encephalitis lethargica, the authors reveal a series of common points between both diseases. The progress of both diseases is identical at every stage, with neurotropism, premature psychological disorders, mononucleasic syndrome, similar somatic manifestations of the viral attack and terminal dementia. The anatomo-pathological and epidemiological data, along with the hypothesis that encephalitis lethargica is sexually transmitted, reinforce the idea of a relationship between the two diseases. The interest which would be aroused by the discovery of a viral origin of encephalitis lethargica and the resulting experimental elements seem to make it worthwhile leaving the question open in order to find a precise answer. We are calling on all our colleagues in basic research to seek a solution to what we think is an essential question.

[Viral encephalitis (etiology, pathogenesis, classification)]. / Virusnye éntsefality (osnovnye voprosy étiologii, patogeneza, klassifikatsii).

The existing classifications of viral encephalitis are based on mixed, heterogenous principles. The author on the grounds of comparing modern data, related to the etiology, pathogenesis, predilectiveness, gives his suggestions as to a new classification of viral encephalitis. This classification is structured according to the pathogenetical principles, with a consideration of the different variants of the dynamics and polymorphism of separate nozological forms, depending upon the interrelationships of the viral and the immunity factors.

[The clinico-laboratory characteristics of cases of diseases connected with viruses of the California encephalitis complex in the inhabitants of Moscow]. / Kliniko-laboratornaia kharakteristika sluchaev zabolevanii, sviazannykh s virusami kompleksa kaliforniiskogo éntsefalita, u zhitelei Moskvy.

To study the role of viruses of the California encephalitis virus complex (the family Bunyaviridae) in infectious pathology, 187 fever patients admitted to the Clinical Infectious Hospital in May-September 1986 were examined. In 10 of these patients the neutralization test revealed the presence of diagnostically significant changes in neutralizing antibodies (neutralization indices), which was indicative of the role played by Tahyna virus or other related viruses belonging to the California encephalitis virus complex in the etiology of the diseases. The analysis of the clinical picture showed that in all patients the disease took an acute course in its initial stage, starting with shivering and characterized by high fever, headache, pronounced toxicosis, the possibility of the formation of intracerebral hypertension and pneumonia.

Medical and molecular perspectives into a forgotten epidemic: encephalitis lethargica, viruses, and high-throughput sequencing.

The emergence of encephalitis lethargica (EL), an acute-onset polioencephalitis of unknown etiology as an epidemic in the years 1917-1925 is still unexplainable today. Questioned by the first descriptor of EL himself, Constantin von Economo, there has been much debate shrouding a possible role of the "Spanish" H1N1 influenza A pandemic virus in the development of EL. Previous molecular studies employing conventional PCR for the detection of influenza A virus RNA in archived human brain samples from patients who died of acute EL were negative. However, the clinical and laboratory characteristics of EL and its epidemiology are consistent with an infectious disease, and recently a possible enterovirus cause was investigated. With the rapid development of high-throughput sequencing, new information about a possible viral etiology can be obtained if sufficient specimens for analysis were still available today. Here, we discuss the implications of these technologies for the investigation of a possible infectious cause of EL from archived material, as well as a prospectus for future work for acquiring viral nucleic acids from these sources.