{"title":"Clinical and immunological considerations in Epstein-Barr virus-associated diseases.","authors":"J Andersson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Despite the fact that nucleoside analogues, such as aciclovir and ganciclovir, and DNA-polymerase inhibitors, such as foscarnet, have a proven antiviral effect on oropharyngeal-Epstein-Barr virus (EBV) replication, they have been unable to show any effect on the severity or duration of infectious mononucleosis (IM), a condition for which there is currently no established treatment. Clinical symptoms may be due to an EBV-induced polyclonal humoral, as well as cellular, immunoreactivity with limited pathology caused by viral replication itself. However, despite an extensive immune response, 90% of tested IM patients (n = 36) had a spontaneous outgrowth of in vivo EBV-infected B-lymphocytes at onset of disease, indicating lack of specific EBV-restricted cellular cytotoxicity at this time. Establishment of an EBV-specific T-lymphocyte response occurred 90-180 days after onset of disease (human leukocyte antigen-restricted cytotoxicity against EBV-infected B-cells). Thus, development of a specific cytotoxic response was a gradual and slow process. Assessment of cytokine pattern, at the single cell level, was performed by immunocytochemical technique and by enzyme-linked immunosorbent assay. This revealed an increased production of interleukin (IL)-2, interferon (IFN)-gamma, IL-6 and tumour necrosis factor (TNF) beta in all IM patients. Those with disseminated disease were characterized by lack of IFN-gamma production. This loss was selective since in vitro stimulation with superantigen, such as streptococcal pyrogenic exotoxin A, induced a normal response. These patients lacked signs of EBV-specific T-cell cytotoxicity in vitro. Treatment with intravenous or subcutaneous IFN-gamma, 1.5 MU every second day, in combination with intravenous immunoglobulin G (0.5 g/kg three times per week) and oral aciclovir, 800 mg 5 times daily, has shown promising results in some patients. Cytokine production in tonsil tissue in 4 patients with fulminant IM and respiratory tract obstruction showed a concomitant expression of IL-2, IFN-gamma, IL-6, TNF beta, transforming growth factor (TGF) beta 1-3, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-4 IL-1alpha, IL-beta and TNF alpha. The number of IL-2, IFN-gamma, IL-6 and TNF beta producing cells was significantly higher compared to tonsil tissue obtained from children with tonsillar hypertrophy. Thus, IM is associated with extensive local cytokine production. It is suggested that this extensive cytokine production is closely involved in the pathology of IM and that patients with atypical IM have a dysregulation in the cytokine network. However, the mechanism by which EBV-infected B-lymphocytes triggers this cytokine cascade is still unknown. These findings show the need for evaluation of patients with immunodeficiency and EBV-induced lymphoproliferative disorders and perhaps the introduction of new immunoregulatory treatment strategies.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"100 ","pages":"72-82"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19826020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antiviral drugs in development for herpes zoster.","authors":"A P Fiddian","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Until recently aciclovir has been the only licensed drug for the treatment of herpes zoster. A number of new drugs have emerged over the past few years which offered the potential for improved efficacy or ease of administration. With the completion of the first efficacy trials for each of these agents it has become apparent that, whilst less frequent dosing can he accomplished, it is not easy to significantly improve on the efficacy of aciclovir. Increasing age, the presence of prodromal pain and more severe pain at presentation have, however, been found to predispose to a longer duration of pain. Taking cessation of pain as the single most important parameter, at least for the older immunocompetent population as a whole, only valaciclovir has, to date, been shown to be superior to standard therapy with aciclovir. This review utilises primarily intent-to-treat data to illustrate the relative efficacy of the different therapies.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"100 ","pages":"51-4"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20109057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Herpes simplex virus and pregnancy.","authors":"M Forsgren, G Malm","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although herpes simplex virus (HSV) infections are common in pregnant women, they are rarely serious. The complication, however, is viral transmission to the infant and morbidity and mortality in neonatal herpes remains considerable, in spite of the availability of antiviral therapy. Early recognition and treatment of the infected child is of the utmost importance to inhibit viral replication and thus limit the severity of the disease. Moreover, prevention is the ultimate challenge. Unfortunately, in many cases this is not achievable since the infection in the mother and child often presents without typical herpes symptoms. This was illustrated in a follow-up study of neonatal herpes in Sweden. In nearly half of the cases of neonatal herpes, neither mother nor child had typical herpes symptoms. The herpes simplex virus type 2 (HSV-2) infections were more often atypical or asymptomatic in nature in the mother and child than the HSV-1 infections. Outcome was more serious in HSV-2 infections, and a large proportion of children with this type did not have skin lesions. Neonatal herpes transmitted from recurrent maternal infection had a long incubation period (mean 14 days) and was often localized to the brain. Disease due to primary infection was disseminated, with a mean incubation time of 6 days. Preventive strategies are discussed. In the majority of cases, clinical recognition of risk factors for transmission in the mother--a prerequisite for preventive measurements --is not possible.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"100 ","pages":"14-9"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20110509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neurological complications in herpes zoster.","authors":"L Flamholc","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This paper discusses the complications associated with herpes zoster, with emphasis on its neurological manifestations. These complications, which are particularly prevalent in elderly and immunodeficient patients, include focal muscle paralysis, contralateral hemiplegia, myelitis, cranial nerve palsies and meningoencephalitis. A causative relationship with herpes zoster in many of these syndromes is probably more common than previously suspected due to difficulties in diagnosis and lack of awareness among clinicians. Zoster sine herpete-- reactivation of varicella zoster virus without rash--is associated with a spectrum of neurological disease and, for obvious reasons, is particularly difficult to diagnose. The polymerase chain reaction could be a valuable tool in overcoming these diagnostic problems, especially in patients without characteristic eruptions, allowing the early initiation of effective antiviral therapy.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"100 ","pages":"35-40"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20110514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibiotics, cytokines, and endotoxin: a complex and evolving relationship in gram-negative sepsis.","authors":"D L Horn, S M Opal, E Lomastro","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Compelling experimental evidence now exists that antimicrobial agents induce the release of endotoxin from Gram-negative bacteria during the process of bacteriolysis. Different antimicrobial classes, particularly those which act upon the outer membrane of bacteria, vary in the amount of free endotoxin released from Gram-negative organisms. Despite this in vitro evidence, clinically important consequences of antibiotic-induced endotoxin release have yet to be consistently documented. Complexities in the host-pathogen interactions during actual infection with Gram-negative bacteria may account for the difficulties in demonstrating this phenomena in vivo. This brief review analyses these interactions and defines clinical settings where antibiotic-induced endotoxin release may prove to be clinically relevant.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"101 ","pages":"9-13"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20015749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T H The, A P van den Berg, M C Harmsen, W van der Bij, W J van Son
{"title":"The cytomegalovirus antigenemia assay: a plea for standardization.","authors":"T H The, A P van den Berg, M C Harmsen, W van der Bij, W J van Son","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Its high diagnostic accuracy, rapidity, quantitative nature and technical simplicity have made the cytomegalovirus (CMV) antigenaemia assay one of the cornerstone methods for diagnosis and management of active CMV infection in immunocompromised patients. Many technical variations have been introduced in an effort to optimize the assay. Now, standardization of the assay and quality control are becoming of increasing importance. In this review we first discuss the nature and origin of the CMV antigens in distinct blood cells during active CMV infection. Further, some of the most important technical variations of the assay are considered and a proposal for standardization is made to indicate how quality control might be achieved. Acceptance of these proposals by the international community would be an important step forward, e.g. towards multicentre antigenaemia-directed intervention studies.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"99 ","pages":"25-9"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19644141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Update (1995) on clinical trials of antiviral therapy and prophylaxis for AIDS-related cytomegalovirus disease.","authors":"M A Jacobson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>An overview of the current state of antiviral therapy and prophylaxis for opportunistic cytomegalovirus (CMV) disease in 1995 is provided, focusing primarily on therapeutic trials for AIDS-related CMV retinitis. Retinitis is the most common serious CMV end-organ disease in AIDS; and it is the one for which clinical end-points can be measured most objectively and precisely. Standard antiviral chemotherapy for CMV retinitis consists of chronic intravenous treatment with either ganciclovir or foscarnet, each of which significantly delays loss of vision compared to no treatment. New agents such as HPMPC and new treatment strategies such as intravitreal ganciclovir may be more effective than standard treatment in delaying time to retinitis progression but are associated with serious toxicity problems. Preliminary data from a placebo-controlled trial of oral ganciclovir suggest that this agent reduces the risk of developing CMV end-organ disease by 50%; however, the implications of oral ganciclovir prophylaxis for development of antiviral drug resistance are unknown.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"99 ","pages":"96-9"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19644727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The pharmacokinetics of meropenem.","authors":"G L Drusano, M Hutchison","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Meropenem is a new carbapenem antibiotic which differs chemically from imipenem/cilastatin by having a 1-beta-methyl substitution, providing it with excellent intrinsic stability to human renal dehydropeptidase-I. In addition, an altered 2' side chain enhances its anti-pseudomonal activity. The drug has one identified metabolite, a beta-lactam ring-opened form which is devoid of microbiological activity, as would be expected. The parent compound displays linear pharmacokinetics over a dose range of 250 mg to 2 g. The terminal half-life is approximately 1 hour and the plasma clearance is approximately 15.5 L/h/70 kg. The plasma concentrations after a 1 g dose show a trough concentration (8 hours) of slightly greater than 0.25 mg/L. The renal route is the major clearance pathway for this drug and its metabolite, with renal clearance accounting for approximately 70% of the plasma clearance and there being approximately 70% of an administered dose recovered in the urine as intact parent compound over 12 hours. When combined with metabolite, over 90% of administered radiolabel is recovered in the urine over this 12 hour period. As expected, renal functional impairment alters the clearance of meropenem, but the alteration is predictable. Hepatic functional impairment does not alter drug disposition and no dosing alterations are required here. In summary, meropenem's disposition is similar to that seen for imipenem/cilastatin, except that no renal dehydropeptidase-I inhibitor is required. When evaluated against the background of its excellent profile of in vitro activity, it is clear that this is a drug of great promise which should be extensively evaluated in clinical trials of seriously ill patients with nosocomial infections.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"96 ","pages":"11-6"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18658359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Drug-resistant mycobacterium tuberculosis; some data from Sweden, Estonia and Ethiopia.","authors":"S E Hoffner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Drug-resistant tuberculosis is a threat not only to the estimated 50 million people in the world carrying resistant strains, but also to the success of national TB control programmes. In Sweden, multidrug-resistant (MDR) tuberculosis comprises around 1% of the isolated strains. Isoniazid resistance is found in 7% of strains and resistance to other drugs in < 3%. Of patients with resistant TB 70% are born outside Scandinavia. Preliminary data from Estonia show that close to 20% of the strains are resistant to each of the drugs isoniazid, rifampicin and streptomycin. MDR is seen in around 16%. In a study in Ethiopia isoniazid resistance was found in 46% and MDR in 11% among treatment failures and relapse cases.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"98 ","pages":"17-8"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19833376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}