Scandinavian journal of infectious diseases. Supplementum最新文献

Varicella zoster virus (VZV) can cause disease in the central nervous system (CNS) during both primary infection and reactivation. Rapid and adequate diagnosis of VZV have previously been hampered by the shortcomings of standard virological methods, such as isolation and serology. Earlier reported cases of CNS manifestations of VZV infection have, therefore, mostly been noted in connection with, or shortly after, onset of vesicular rash. Several studies have recently been described of cases of VZV-induced CNS disease occurring as the only sign of viral reactivation, with the diagnosis aided by polymerase chain reaction (PCR) amplification and other methods of genome detection. A prospective study was performed using PCR on cerebrospinal fluid (CSF) and brain samples received for routine diagnosis of possible VZV infection during a 2-year period. Samples from 8 (7 from CSF, 1 from brain) of the 260 patients investigated (3.1%) were found to be positive for VZV-DNA. All 8 had a presumed reactivated VZV infection according to serological and clinical analysis. Their CNS manifestations ranged from meningitis to severe encephalitis, and only in 3 of these patients was a vesicular rash present. Thus, VZV-DNA detection in the CSF was an unexpected finding for the clinician and, in 2 cases, antiviral treatment with aciclovir was initiated only because of the PCR evidence of CNS infection. VZV should be considered as a possible causative agent of infection in patients with CNS disease of suspected viral origin, even in the absence of skin manifestations. Rapid diagnosis by PCR amplification of VZV-DNA from CSF might allow for early and adequate antiviral treatment.

Varicella zoster virus (VZV) is the causative agent of chickenpox (varicella) and shingles (zoster). The study of latency and reactivation has been hampered by the fact that the virus is strictly human and grows to low titres in tissue culture. Molecular biology techniques have opened a new era of VZV research. The site of VZV latency was determined to be sensory ganglia by Southern blotting and later by PCR technology. It was also demonstrated that the entire virus genome is present in the latently infected ganglia and that VZV is latent in multiple ganglia along the entire human neuraxis. Since the amount of latent VZV per cell is very low, the question of which cell type is involved in VZV latency could not be conclusively settled by the use of traditional in situ hybridization studies. However, we have now demonstrated the presence of latent VZV DNA in neurons only, by using a more sensitive method which employs a combination of in situ PCR and in situ hybridization. The transcriptional activity of VZV during latency is still not completely clear. Ganglia are small and the total amount of latent VZV is low, therefore conventional methods to detect latent VZV have proved limited. Nevertheless, the detection of a latent transcript from the SalI C region of the virus was demonstrated by Southern hybridization of cDNA synthesized from RNA isolated from latently-infected ganglia. Further studies have localized this transcript to the open reading frame of VZV gene 21. The study of VZV latency and reactivation has, until now, been dependent on the investigation of post mortem human tissue. However, simian varicella virus seems to be the simian counterpart to human VZV. The 2 viruses exhibit DNA homology as well as similarities in clinical, virological, and immunological features. Further studies of VZV infections may open new and possibly unpredictable opportunities in varicella virus research.

The array of diagnostic tools now available allows not only precise serological determination of past exposure to cytomegalovirus (CMV) infections but also identification of CMV components in blood during viraemia--predictive of CMV disease. Sensitive and rapid identification of CMV components from infected organs from biopsies and body fluids, such as cerebrospinal fluid and bronchoalveolar lavage fluid, is also possible. The polymerase chain reaction (PCR) has become a highly sensitive and specific diagnostic tool that now also can he applied in a quantitative or semiquantitative manner. Non-PCR methods, which amplify the signal rather than DNA itself, are also available as quantitative tests. The antigenaemia assay was the first quantitative measure of CMV load during viraemia. It is useful in the surveillance of CMV in transplant patients as well as for drug efficacy monitoring, and is the method of choice in many laboratories. The use of modern diagnostic tools and subsequent treatment with an appropriate antiviral drug should reduce the number of lethal CMV cases to a minimum.

High levels of resistance to extended-spectrum cephalosporins have been reported in the Western Pacific area but data on the prevalence of extended-spectrum beta-lactamases (ESBLs) is more scanty. 370 Hong Kong blood culture isolates of Enterobacteriaceae isolated in the years 1990 and 1995 were evaluated for resistance to 15 antibiotics and the presence of ESBLs. 1995 isolates showed increased levels of resistance for beta-lactams, trimethoprim, ciprofloxacin and aminoglycosides. The proportion of E. coli harbouring ESBLs was 1/61 (1.6%) in 1990 and 2/77 (2.6%) in 1995. The prevalence in Klebsiella spp. rose from 1/36 (2.8%) in 1990 to 5/49 (10.2%) in 1995. ESBLs were found most frequently in Enterobacter spp. and were present in 7/29 (24.1%) of 1990 isolates and 5/22 (22.7%) of 1995 isolates. ESBLs may not be detectable in routine susceptibility testing and appropriate screening methods such as double disc screening tests are necessary to accurately determine ESBL prevalence.

Genital herpes causes considerable psychological and psychosexual morbidity. The most common emotional responses are depression, anguish, anger, diminution in self-esteem and hostility towards the person believed to be the source of the infection. These emotional problems appear to be worse in women than in men. The psychological morbidity in patients with first episode genital herpes is statistically significantly greater than that occurring in non-herpes patients attending sexually transmitted disease clinics. It was previously believed that stressful life events could precipitate recurrences. However, recent studies suggest that ongoing recurrences cause the emotional stress rather than vice versa. There is some evidence that premorbid personality may effect recurrence rates, but an equally plausible explanation is that frequent recurrences adversely affect personality. Long-term aciclovir suppression significantly reduces the psychological morbidity associated with recurrent genital herpes, over at least the period of treatment. Cognitive coping strategies and social support from a partner appear to assist with adjustment. Improving a patient's problem-solving skills, and long-term aciclovir therapy should form an integral part of the long-term management of recurrent genital herpes.

It is well recognized clinically that herpesviruses can cause disease in AIDS patients once human immunodeficiency virus (HIV) has precipitated marked immunosuppression. However, in addition to this opportunistic relationship, there is evidence to suggest that herpesviruses could increase the pathogenicity of HIV by acting as cofactors. Experiments in vitro have shown that several herpesviruses can activate HIV gene expression or alter the cellular tropism of HIV through a variety of mechanisms (antigen presentation, cytokine release, pseudotype formation, CD4 cell surface upregulation, Fc receptor formation, transactivation). Studies of human autopsy material have shown that some herpesviruses (particularly cytomegalovirus, human herpes virus 6 and herpes simplex virus) are found frequently in AIDS patients. If such herpesviruses act as cofactors in vivo, then their inhibition by aciclovir could explain why a survival benefit has been reported from the use of this drug in two double-blind, placebo-controlled randomized trials.

Herpes simplex encephalitis (HSE) is a life-threatening condition with high mortality as well as significant morbidity in survivors. In most cases herpes simplex virus type 1 (HSV-1) is responsible for the diseases, however, the type 2 virus (HSV-2) is involved in 4-6% of cases. Primary HSV infection is identified in only one-third of patients with HSE. The majority of cases are recorded in adults with recurrent HSV infection who are already seropositive for HSV at the onset of symptoms, but only 6-10% of these patients have a history of labial herpes. Acute focal, necrotizing encephalitis with inflammation and swelling of the brain tissue are consistent features of the pathology of HSE. HSV-induced cytolysis certainly damages neurones, oligodendrocytes and astrocytes, but the role of cellular and humoral immunopathology is important. A complex network of cytokines seems to be active in regulating the local immune response and inflammation during and after HSE. Brain biopsy, serological analysis of intrathecal HSV antibodies and detection of HSV-DNA in the cerebrospinal fluid (CSF) are all useful techniques to confirm the aetiology of HSE. Neurodiagnostic tests which support a presumptive diagnosis of HSE include: CSF analysis, electroencephalography, computer-assisted tomography and magnetic resonance imaging. Although aciclovir is the treatment of choice in HSE, mortality and morbidity still remain problematic. Long-term follow-up indicates that intrathecal cellular and humoral activation persist in HSE.

The susceptibility of 140 Acinetobacter spp. isolated from blood cultures of patients from the Prince of Wales Hospital, Hong Kong, from 1990 to 1994 to 23 antimicrobial agents was studied by an agar dilution method. Resistance to most of the beta-lactams, aminoglycosides and fluoroquinolones tested was high, being 11%-92%. Only amikacin, imipenem and meropenem were reliably active against this organism. Most of the isolates produced cephalosporinases with very high pIs while 33% produced beta-lactamases with pI ranges of 5.2-8.7.

beta-Lactams are the largest antibiotic family, but are readily compromised by resistance. The result has been a cat-and-mouse game between chemists and bacteria, with the compounds repeatedly modified to overcome emergent resistance. With penicillins, it is possible to obtain spectrum, or beta-lactamase stability, but difficult to combine both. In general, it is better to protect a labile penicillin with an inhibitor, though this strategy is limited by the absence of good inhibitors of AmpC beta-lactamases. Combining spectrum and beta-lactamase stability proved easier with cephalosporins, but it is difficult to cover enterobacteria, anaerobes, non-fermenters and staphylococci with a single compound, and enterococci are consistently resistant. Carbapenems allow the broadest spectrum of available beta-lactams. Less equal or predictable than initial spectrum is how rapidly resistance emerges. This point is especially important pertinent to beta-lactamases; PBP changes compromise all beta-lactams. Spread of plasmidic beta-lactamases destroyed the utility of penicillin G against staphylococci and that of anti-gram-negative penicillins against enterobacteria. Resistance to 'beta-lactamase-stable' cephalosporins has recently spread in enterobacteria, mediated by hyperproduction of AmpC beta-lactamases and extended-spectrum TEM and SHV types. Carbapenems were launched shortly after 3rd-generation cephalosporins, but beta-lactamase-mediated resistance has emerged more slowly. Nevertheless, recent reports of zinc carbapenems in gram-negative bacteria from Japan are disturbing.