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Herpesvirus infection of eye and brain in HIV infected patients.

OBJECTIVES: To compare histological with genome detection methods for diagnosis of herpesvirus infection in eye and brain of HIV infected patients undergoing necropsy and to correlate these findings with both antemortem clinical findings and postmortem evidence of extraocular herpesvirus infection, especially in the CNS. METHODS: A prospective study of 31 consecutive HIV infected patients undergoing necropsy. In life 11 patients had been assessed by an ophthalmologist because of ocular symptoms. Ocular and brain samples were examined for herpesviruses by conventional histological methods and by nested polymerase chain reaction (nPCR) for all eight human herpesviruses; evidence of extraneural herpesvirus infection was sought by histological methods. RESULTS: Although only 12 out of 31 patients (39%) had antemortem clinical evidence of ocular or CNS herpesvirus associated disease, herpesviruses were detected by nPCR in eye and brain from 26 (84%) patients; six patients had more than one herpesvirus infection. There was concordance between ocular and CNS findings in 15 of 19 patients (79%) with CMV infection. 17 of 31 patients (55%) had extraocular or CNS CMV infection at necropsy. Genome detection using nPCR was superior to histological methods for diagnosis of ocular and CNS herpesvirus infection. CONCLUSION: Herpesvirus infection of eye and brain was a frequent finding at necropsy in this group of HIV infected patients; almost a fifth were co-infected by more than one herpesvirus. This was more than twice the incidence predicted from clinical evidence before death. Genome detection using nPCR was superior to histological methods for diagnosis of ocular and CNS herpesvirus infection.

Adult↗

Herpesvirus infection of inflammatory cells in human periodontitis.

Human cytomegalovirus (HCMV) and Epstein-Barr virus type 1 (EBV-1) are frequently detected in human periodontitis lesions. However, no information is available on the types of gingival cells infected by herpesviruses. The present study determined the presence of herpesviruses in polymorphonuclear neutrophils, monocytes, macrophages and T and B lymphocytes in biopsies of periodontitis lesions from 20 adults. A nested polymerase chain reaction method was employed to detect HCMV, EBV-1, EBV-2, human herpes virus-6 and herpes simplex virus (HSV) in periodontal tissue biopsy and in gingival cell fractions separated by immunomagnetic cell sorting. Tissue specimens from 18 (90%) and cell fractions from 14 (70%) patients demonstrated herpesviruses. Periodontitis-derived monocytes and macrophages revealed HCMV in cell fractions from 11 (55%) patients and HSV in cells from 1 (5%) patient. T lymphocytes harbored HCMV in cell fractions from 4 (20%) patients and HSV in cell fractions from 4 (20%) patients. B lymphocytes showed EBV-1 in cell fractions from 9 (45%) patients. Periodontal polymorphonuclear neutrophils demonstrated no herpesviruses. This study suggests that HCMV mainly infects periodontal monocytes, macrophages and less frequently T lymphocytes and that EBV-1 infects periodontal B lymphocytes. The possible etio-pathologic significance of periodontal herpesvirus infection is discussed.

Adult↗

Comparison of the therapeutic effects of five antiviral agents on cutaneous herpesvirus infection in guinea pigs.

Cutaneous herpesvirus infection of guinea pigs has been evaluated as a model for testing antiviral compounds. Six infected sites on each animal can be used independently for local treatment. The severity of the infection has been graded in a score system. The cumulative scores during infection and the time to healing can be used to determine antiviral effects. The effects of adenine arabinoside, cytosine arabinoside, iododeoxyuridine, ribavirin and phosphonoacetic acid on the cutaneous infection was compared. Phosphonoacetic acid was the only compound with a good therapeutic activity against herpesvirus infection, causing a reduction of both the cumulative score and the time to healing. Phosphonoacetic acid was skin irritating at 2 per cent, but at 1 per cent, which still had a good therapeutic activity, skin irritation was seen only occasionally.

Animals↗

Human herpesvirus infection in children with fever and maculopapular rash.

Fever with maculopapular rash is a common problem in children. Infection with human herpesviruses is one of the common etiologies in fever with rash. The aim of this study has been to examine patients presenting with fever and maculopapular rash without respiratory symptoms for human herpesviruses infection by using multiplex nested-polymerase chain reaction. A descriptive and prospective study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand from June 2000 to December 2001. One hundred patients, 43 boys and 57 girls, aged between 2 months and 14 years were recruited. Human herpesvirus 6 (HHV6) was the most common (24%) whereas HHV7, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were present in 9%, 3% and 2% of the patients, respectively. Four percent of the patients simultaneously harbored HHV6 and HHV7. Only one patient had CMV, HHV6 and HHV7. Patients with HHV7 had a mean age of 4.5 years, whereas those with HHV6 had a mean age of 1.6 years. HHV6 and HHV7 were commonly found as causes of fever and maculopapular rash without respiratory symptoms. Co-infection with different herpesviruses can be found in the same patient.

Adolescent↗

Antivirals for the treatment of herpesvirus infections.

Agents available to treat herpesvirus infections include idoxuridine, trifluridine, vidarabine and acyclovir for the topical treatment of herpetic eye infections; vidarabine and acyclovir for the systemic (intravenous) treatment of herpes encephalitis; acyclovir for the topical and systemic (oral) treatment of genital herpes; acyclovir for the systemic (intravenous, oral) treatment of HSV or varicella-zoster (VZV) infections in immunosuppressed patients; brivudin for the systemic (oral) treatment of HSV-1 or VZV infections in immunosuppressed patients; and ganciclovir and foscarnet for the systemic (intravenous) treatment of cytomegalovirus (CMV) retinitis in AIDS patients. Brivudin is also effective in the treatment of herpetic eye infections that no longer respond to idoxuridine, trifluridine, vidarabine or acyclovir; and foscarnet is effective in the treatment of infections with acyclovir-resistant, thymidine kinase-deficient (TK-) HSV or VZV mutants. Other antiviral agents considered for use in herpesvirus infections include brovavir, penciclovir (and its prodrug famciclovir), desciclovir (a prodrug of acyclovir), bishydroxymethylcyclobutylguanine (BHCG) and, in particular, 1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). The latter is more active than either acyclovir or ganciclovir in the chemotherapy and prophylaxis of various HSV-1, HSV-2, TK- HSV, VZV or CMV infections in animal models.

Acyclovir↗

Ocular herpesvirus infections.

BACKGROUND: More than 50 herpesviruses have been discovered and, of these, humans are the only natural hosts for seven. Human herpesvirus infections are widespread and are a common cause of ocular pathology involving the anterior and/or posterior segment of the eye. Eye infection can occur during the primary infection or may be due to reactivation of the virus from a latent state and may be relatively mild or may be severe and threaten the health of the globe. CONCLUSIONS: Given the prevalence and importance of herpesvirus infection, this paper reviews the biological aspects as well as the systemic and ocular manifestations of these infections.

Eye Infections, Viral↗

Herpesvirus infections in the acquired immune deficiency syndrome.

Herpesvirus infections were studied in persons with or at risk for the acquired immune deficiency syndrome (AIDS). The infections diagnosed were as follows: patients with AIDS, cytomegalovirus (CMV) in 34 of 34, Epstein-Barr virus (EBV) in 33 of 34, herpes simplex viruses (HSV) in eight of 34, and varicella zoster virus in four of 34; patients with chronic lymphadenopathy syndrome, CMV in eight of nine and EBV in nine of nine; in healthy homosexual men, CMV in five of 13 and EBV in seven of eight. Cytomegalovirus infections were frequently related to disease and death. Herpesvirus infections are frequent causes of serious diseases in AIDS. The prevalence of EBV and CMV infections in AIDS and the chronic lymphadenopathy syndrome may be the result of an important interaction between these viruses and the cause of AIDS.

Acquired Immunodeficiency Syndrome↗

Effect of multiple herpesvirus infections on the progression of HIV disease in a cohort of HIV seroconverters.

The effects of herpesviruses infection on the progression of HIV disease remain controversial, with some studies showing accelerated progression and others showing no effect. Furthermore, the effect of concurrent infection with more than one herpesvirus on the progression of HIV disease has never been investigated. To this end, the rates of progression of HIV disease were determined after stratifying for the presence of up to five different herpesvirus infections. The study population consisted of 359 HIV-infected persons for whom the date of seroconversion was estimated (part of the Italian Seroconversion Study). One serum sample from each participant was tested for antibodies to five herpesviruses: HSV-2, CMV, HHV-6, HHV-7, and HHV-8. Univariate analysis showed that HSV-2 and HHV-8 were significantly associated with progression to AIDS, yet when adjusting for age at HIV seroconversion and for the presence of the other herpesvirus infections, only HHV-8 infection showed a significant association. The age-adjusted risk of progression to AIDS with Kaposi's sarcoma increased with the number of herpesvirus infections and was significant in individuals with four infections. The risk of progression to AIDS without Kaposi's sarcoma also increased with the number of infections, although not significantly. Similar results were found when considering CD4+ cell count <200 x 10(6) cells/L as the endpoint. Concurrent infection with more than one herpesvirus does not appear to have a significant effect on the course of HIV disease, except for the known association between HHV-8 and Kaposi's sarcoma. However, even after excluding Kaposi's sarcoma from the AIDS-defining endpoints, a slightly increased risk for participants with four herpesvirus infections remained.

AIDS-Related Opportunistic Infections↗

Vertically transmitted herpesvirus infections.

The importance of recognizing perinatally acquired herpes simplex virus infections is now well understood and recently, increased attention has been devoted by clinicians to the problem of perinatally acquired cytomegalovirus infections. Less commonly, other members of the herpesvirus family may also be transmitted from mother to infant in the perinatal period, causing disease. Future developments of the management of herpesvirus infections will include greater roles for antiviral therapies and vaccines. Expanded use of oral nucleoside antiviral therapies in pregnancy has engendered uncertainty in how best to screen, monitor, and treat women at risk of transmitting the infection. Vaccines against herpesviruses have progressed in clinical trials, and the imminent licensing of such vaccines will further complicate clinical management decisions. As potential therapeutic agents become available, better understanding and recognition of risk factors, and awareness of the clinical presentation of perinatally acquired herpesvirus infections, will be required to maximize satisfactory pregnancy outcomes.

Antiviral Agents↗

Herpesvirus infections in persons infected with human immunodeficiency virus.

Herpesviruses are among the most common causes of infections of humans. Viruses in this family share the unique biological property of being able to establish latency and to recur. Furthermore, chronic excretion of virus is not uncommon. In the immunocompromised host, including persons with human immunodeficiency virus (HIV) infection, herpesvirus disease can be particularly severe, resulting in chronic, persistent, active infection and, in some cases, life-threatening disease. The most pathogenic of the herpesviruses in patients with AIDS include herpes simplex viruses, human cytomegalovirus, and varicella-zoster virus. Disease caused by Epstein-Barr virus, particularly opportunistic malignancies, has been recognized. A new herpesvirus that is associated with Kaposi's sarcoma was recently described. On the other hand, disease caused by human herpesviruses 6 and 7 in persons infected with HIV remains to be unequivocally recognized. Prevention of exposure to herpesviruses, disease, and recurrence requires different measures than those for some of the other opportunistic infections in HIV-infected patients; this is because herpesvirus disease develops in most of these individuals as a result of reactivation rather than primary infection. Thus, approaches to the prevention and control of herpesvirus infections must be individualized according to both the type of virus as well as the type of infection (i.e., primary or recurrent). We discuss recommended measures for the prevention and control of these infections.

HIV Infections↗

Chronic antigenic stimulation, herpesvirus infection, and cancer in transplant recipients.

An increased incidence of malignancy has been reported in transplant recipients. The pathogenesis of this increase was originally attributed to immunosuppressive therapy. However, not all tumours are increased in proportion to their occurrence in the general population-75% of reported tumours are lymphorproliferative or carcinoma of the skin, lip, or cervix. This cannot be explained by impaired immunosurveillance, and alternative hypotheses must be considered. 90% of transplant recipients develop clinical or serological evidence of herpesvirus infection. Herpesviruses have been implicated in the pathogenesis of lymphorproliferative tumours and carcinoma of the skin and cervix. They can remain in latent form and be reactivated by allogeneic stimulation and/or immunosuppression. These viruses localise to skin, cervix, and neural tissue-i.e., exactly those sites where cancer develops in transplant patients. Herpesvirus infections in association with the presence of an allogeneic graft in an immunosuppressed patient may be responsible for the increased incidence of both lymphoproliferative tumours and carcinoma of the skin, lip, and cervix in the transplant recipient.

Antibodies, Viral↗

[Alpha herpesvirus infections in AIDS patients].

Alpha-herpesvirus infections by herpes simplex virus and varicella-zoster virus among HIV-infected patients were summarized. These infections were occurred in a high frequency and shown to be extensive lesions, prolonged virus excretion from the lesions, generalized infection, and uncommon diseases as compared these of with immunocompetent patients. Acyclovir-resistant viruses appeared. These evidences supplied the profound understanding of the pathogenesis and new subjects in the field of herpesvirus infection. Recent introduction of HAART against HIV and the appropriate use of anti-herpesvirus drugs, however, reduced the development of severe infection, and provided successful treatment, respectively.

AIDS-Related Opportunistic Infections↗

Specific diagnostic methods for herpesvirus infections of the central nervous system: a consensus review by the European Union Concerted Action on Virus Meningitis and Encephalitis.

BACKGROUND: Herpesvirus infections of the central nervous system are often severe but are fortunately rare. The incidence of these infections has however, increased in recent years as a consequence of an increase in the number of immune-compromised individuals. New diagnostic procedures have improved our ability to diagnose these infections and herpesviruses may yet be implicated as the cause of further neurological diseases with no known aetiology. Methodological standards for selection and evaluation of patient materials are essential to the provision of reliable diagnosis, yet few studies have addressed this important issue. OBJECTIVES: To describe and define methodological standards and reference methodology for diagnosis of herpesvirus infections of the CNS. STUDY DESIGN: Information gathered by literature review. RESULTS: Only for herpes simplex encephalitis is there sufficient data to allow the definition of reference methodology. Good methodological standards exist but few studies have adhered to these standards. As methods for the detection of specific intrathecal antibody synthesis are well established yet under-used in diagnostic virology, the principle of these measurements is reviewed in some detail. CONCLUSIONS: Herpesvirus infections of the CNS are of increasing importance. High quality, multi-centre studies are needed to establish the value of the new diagnostic test procedures if further improvement in the diagnostic sensitivity and specificity of these procedures is to be achieved.

Brain↗

Continuous infusion of high-dose acyclovir for serious herpesvirus infections.

Thirteen patients with herpesvirus infections who were unresponsive to at least 72 h of intermittent acyclovir administration received high-dose continuous infusion. Steady-state concentrations were maintained at between 20 and 98 mumol/liter. Of 12 patients who had continuous infusion for greater than 5 days, 7 (58%) resolved their infections, as determined by clinical and virologic parameters, suggesting that continuous infusion may succeed in some patients who do not respond to conventional therapy.

Acyclovir↗

Herpesvirus infection of seborrheic keratoses.

We present three examples of patients with seborrheic keratoses complicated by necrotizing herpesvirus infection. Two patients had localized cutaneous herpetic infections, and the third patient had a generalized cutaneous herpesvirus infection. Two of the lesions were thought to be squamous cell carcinoma. The third was clinically identified as inflamed seborrheic keratosis. Herpesvirus infection was not clinically suspected in two of the patients. The histologic changes were similar in all cases. Epidermal proliferation was accompanied by hyperkeratosis and pseudo horn cyst formation. Extensive keratinocyte necrosis was present along with balloon degeneration of keratinocytes, herpetic viral inclusions, and multinucleated giant cells. Viral lesions of molluscum contagiosum and human papillomavirus have been observed in benign skin proliferations. Nevertheless, we were unable to find descriptions of herpesvirus involvement in seborrheic keratosis in a Medline search. Necrotic seborrheic keratoses should be carefully examined for the possibility of herpesvirus infection, a condition that may be improved by prompt medical intervention as demonstrated in one of our cases.

Aged↗

Herpesvirus infection of the respiratory tract in patients with alcoholic hepatitis.

Respiratory herpesvirus infections have rarely been described in alcoholics. We report four cases of severe respiratory herpesvirus infections in patients with alcoholic liver disease. Two were related to Herpes Simplex Virus and two to Cytomegalovirus. Both chronic alcoholism and severe liver disease induce immunosuppression, which might account for these unusual herpesvirus infections of the respiratory tract. These cases suggest that infections with herpesviruses should be considered in patients with alcoholic liver disease and pulmonary or tracheobronchial disease unresponsive to standard antibiotic therapy. Bronchoscopy, viral culture, and serological tests appear warranted, particularly given the existence of specific therapy.

Adult↗