Viral infections in renal allograft recipients treated with long-term immunosuppression.

Thirty-nine renal allograft recipients who had received continuous immunosuppression for six to 13 years were examined clinically and virologically for evidence of past or present viral infection. Twenty-five had common warts, usually on the hands. In most the warts had appeared about one year after transplantation; once present, they never disappeared. Six patients had had a zoster rash from two months to four years after transplantation. None had had jaundice, and there was no change in the frequency of colds or non-specific fibrile illness. Four patients had no cytomegalovirus complement-fixing antibodies throughout the observation period; in the other 35 the antibody titre had risen appreciably during the first three to four months after transplantation. Antibody titres were high (mean 64) at follow-up, being only slightly lower than the highest titres achieved during the immediate postoperative period. None of the patients had had symptomatic cytomegalovirus infection, and in only two was the virus isolated from the urine at follow-up; the titres were extremely low. No changes occurred in the frequency of herpes simplex eruptions. Although all patients had herpes simplex humoral antibody, none excreted the virus. Although cytomegalovirus antibody titres were high, virus excretion was rare, indicating that chronic cytomegalovirus infection in these patients is immunologically well controlled.     

HLA-DRw6 as a risk factor for active cytomegalovirus but not for herpes simplex virus infection after renal allograft transplantation.

To study genetically determined susceptibility to cytomegalovirus and herpes simplex virus infections in patients given renal transplants a prospective study was performed of 68 consecutive patients receiving their first cadaveric kidney allograft. The recipients positive for HLA-DRw6 showed a significantly increased incidence of active cytomegalovirus infection as early as the 10th week after transplantation (p less than 0.05). No relation with other human leucocyte antigens was found, nor did a correlation exist between HLA typing and the incidence of herpes simplex virus infections. Furthermore, recipients positive for HLA-DRw6 with secondary cytomegalovirus infections excreted infectious virus more often (p less than 0.01) and showed more clinical symptoms (p less than 0.01) than a comparable group of recipients negative for HLA-DRw6. These observations may have practical implications for the treatment of patients who have had renal transplant operations.     

Diagnosis of HIV-Associated Oral Lesions in Relation to Early versus Delayed Antiretroviral Therapy: Results from the CIPRA HT001 Trial

Oral mucosal lesions that are associated with HIV infection can play an important role in guiding the decision to initiate antiretroviral therapy (ART). The incidence of these lesions relative to the timing of ART initiation has not been well characterized. A randomized controlled clinical trial was conducted at the GHESKIO Center in Port-au-Prince, Haiti between 2004 and 2009. 816 HIV-infected ART-naïve participants with CD4 T cell counts between 200 and 350 cells/mm³ were randomized to either immediate ART initiation (early group; N = 408), or initiation when CD4 T cell count was less than or equal 200 cells/mm³ or with the development of an AIDS-defining condition (delayed group; N = 408). Every 3 months, all participants underwent an oral examination. The incidence of oral lesions was 4.10 in the early group and 17.85 in the delayed group (p-value <0.01). In comparison to the early group, there was a significantly higher incidence of candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex in the delayed group. The incidence of oral warts in delayed group was 0.97 before therapy and 4.27 post-ART initiation (p-value <0.01). In the delayed group the incidence of oral warts post-ART initiation was significantly higher than that seen in the early group (4.27 versus 1.09; p-value <0.01). The incidence of oral warts increased after ART was initiated, and relative to the early group there was a four-fold increase in oral warts if ART was initiated following an AIDS diagnosis. Based upon our findings, candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex indicate immune suppression and the need to start ART. In contrast, oral warts are a sign of immune reconstitution following ART initiation.     

Detection of herpes simplex virus by DNA-DNA hybridization method]

Eight recombinant clones were obtained by insertion of BamHI fragments of herpes simplex type I viral DNA into a vector plasmid pUC19o. Of the obtained clones 5 were found to hybridize with herpes simplex type I and 2 viral DNA while 3 clones revealed a positive reaction with the Vero cells DNA. A constructed DNA-probe possessing the highest level of activity was selected for further studies. The probe is a BamHI fragment of herpes simplex type I viral DNA labelled with 32P dTTP. Probe sensitivity in blot hybridization is 10 pg for identification of type I viral DNA and 50 pg for type 2 viral DNA. The DNAs of cytomegalovirus and herpes zoster virus do not show positive signals with the probe. The increased sensitivity of the used dot hybridization as compared with biological or IEA antigen identification of the virus was confirmed with the clinical material from 59 patients with the different clinical manifestations of the herpes viral infection.     

Temozolomide-related infections: review of the literature

Temozolomide (TMZ) is an alkylating, antineoplastic agent which is being used to treat cases of refractory anaplastic astrocytoma, newly-diagnosed glioblastoma multiforme and metastatic melanoma. TMZ causes lymphopenia and T-cell dysfunction in most of the patients. Related to this toxicity several opportunistic infections have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 36 previously reported cases of infection related to TMZ. The median age of the cases was 55 years (range 33-73). The most frequently experienced infections were mucocutaneous candidiasis (n=11; 28.2%), herpes zoster (n=5; 12.8%), herpes simplex virus (n=4; 10.2%), cytomegalovirus (CMV) (n=5; 12.8%), pneumocystis carinii pneumonia (PCP) (n=3; 7.6%), hepatitis B virus (HBV) (n=2; 5.1%) and others (n=9; 23%). Mortality rates were 28.5% (n=4/14) in patients with reported outcome. In this survey, about one third of the TMZ-related severe infections resulted in death. Patients treated with TMZ are at increased risk for opportunistic viral and bacterial infection. Therefore, close monitoring of patients receiving TMZ for opportunistic infections should be carried out.     

Use of acyclovir in the prevention of herpes infections after allogenic bone marrow grafts

In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.     

Ocular herpes:the pathophysiology,management and treatment of herpetic eye diseases

Herpesviruses are a prominent cause of human viral disease, second only to the cold and influenza viruses. Most herpesvirus infections are mild or asymptomatic. However, when the virus invades the eye, a number of pathologies can develop and its associated sequelae have become a considerable source of ocular morbidity. The most common culprits of herpetic eye disease are the herpes simplex virus(HSV), varicella zoster virus(VZV), and cytomegalovirus(CMV). While primary infection can produce ocular disease, the most destructive manifestations tend to arise from recurrent infection. These recurrent infections can wreck devastating effects and lead to irreversible vision loss accompanied by a decreased quality of life, increased healthcare usage, and significant cost burden. Unfortunately, no method currently exists to eradicate herpesviruses from the body after infection. Treatment and management of herpes-related eye conditions continue to revolve around antiviral drugs, although corticosteroids, interferons, and other newer therapies may also be appropriate depending on the disease presentation. Ultimately, the advent of effective vaccines will be crucial to preventing herpesvirus diseases altogether and cutting the incidence of ocular complications.     

Ocular herpes: the pathophysiology,management and treatment of herpetic eye diseases

Herpesviruses are a prominent cause of human viral disease, second only to the cold and influenza viruses. Most herpesvirus infections are mild or asymptomatic. However, when the virus invades the eye, a number of pathologies can develop and its associated sequelae have become a considerable source of ocular morbidity. The most common culprits of herpetic eye disease are the herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV). While primary infection can produce ocular disease, the most destructive manifestations tend to arise from recurrent infection. These recurrent infections can wreck devastating effects and lead to irreversible vision loss accompanied by a decreased quality of life, increased healthcare usage, and significant cost burden. Unfortunately, no method currently exists to eradicate herpesviruses from the body after infection. Treatment and management of herpes-related eye conditions continue to revolve around antiviral drugs, although corticosteroids, interferons, and other newer therapies may also be appropriate depending on the disease presentation. Ultimately, the advent of effective vaccines will be crucial to preventing herpesvirus diseases altogether and cutting the incidence of ocular complications.     

Failure to demonstrate concomitant antibody changes to viral antigens other than Epstein-Barr virus (EBV) during or after infectious mononucleosis

A search for antibody rises to viral antigens other than to Epstein-Barr virus, the causative agent, has been carried out in serial serum samples from 82 patients with infectious mononucleosis (IM). Fourfold or greater rises in titer rarely occurred and did did not cluster in time. No rises occurred to cytomegalovirus, only 1.2 percent to herpes simplex virus, and 8.5 percent to varicella zoster virus. Rises to measles antibody were found in 7.5 percent of patients and to rubella in 10.4 percent; these may represent natural infections or immunizations. A few patients also showed rises to respiratory viruses but there was no apparent connection to IM.     

Detection of herpes simplex and varicella zoster viruses in clinical specimens using direct immunofluorescence and cell culture assays

Patients (33 in toto) with a clinical diagnosis of herpes infections (simplex, zoster or chickenpox) were investigated for the presence of herpes simplex virus (HSV) and varicella zoster virus (VZV) in skin samples, using direct immunofluorescence and cell culture assays. Five patients with nonherpetic vesiculobullous disorders were included as negative controls. Of the 33 patients, nineteen (57.6%) were positive for HSV or VZV and fourteen (42.4%) were negative. Five controls were all negative for HSV or VZV. Of the nineteen positive patients, HSV was isolated from eight (42.1%) patients, by both direct immunofluorescence and cell culture assays. VZV was isolated from eleven (57.9%) patients, eleven (100%) by direct immunofluorescence assay, and six (54.5%) by cell culture assays. HSV was isolated from one patient clinically diagnosed as chickenpox (VZV), but otherwise the positive laboratory results were concordant with the clinical diagnosis. For epidemiological studies, atypical cases and immunocompromised patients the clinical diagnosis should be confirmed in the laboratory.     

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised,double blind,placebo controlled trial.

OBJECTIVES--To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN--Randomised, double blind, placebo controlled trial. SUBJECTS--74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES--Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS--The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION--Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.     

Comparison of several ELISA tests for detecting the presence of IgG and IgM against herpes simplex viruses

Four enzyme-linked immunosorbent assays designated test 1 (ETI-HSVK-G 1/2); test 2 (ETI-HSVK-M 1/2); test 3 (ETI-HSVK-G 2), and test 4 (BioElisa HSV2 IgG) were studied to evaluate different stages of herpes simplex virus (HSV) infection. Samples (50 sera and 14 cerebrospinal fluid) were included in four groups. Group 1 consisted of samples from patients with primary HSV infections; group 2 comprised samples from patients with recurrent HSV infections; group 3 were samples nonreactive to HSV; and group 4 were samples from patients with infections by other herpes viruses (4a, chickenpox; 4b, herpes zoster; and 4c, infectious mononucleosis by Epstein-Barr virus). The percentages of agreement between tests 1 and 2 were 100 and 72.1%, respectively. The total diagnostic values of tests 1 and 2 were: 100 and 50% sensitivity, respectively; and 100 and 89% specificity, respectively. Few positive results for HSV-2 infection were found, and so, tests 3 and 4 were not evaluated. The results of tests 3 and 4 for a chickenpox patient, and a herpes zoster patient were not in agreement.     

Identification of viruses in the urine of renal transplant recipients by cytomorphology

This study was designed to reassess the cytomorphology of viral infections in urinary cells obtained from renal transplant patients and to examine the association, if any, between these cytologic changes and the transplant rejection. A total of 2,354 cytologic specimens obtained from 91 renal transplant recipients was evaluated. A combination of techniques, including cellulosic filters, immunofluorescence, hemagglutination inhibition and electron microscopy, was utilized. Cytologic observations were correlated with the patient's clinical history. Thirty-eight patients revealed cytologic evidence of viral infections (herpes simplex, cytomegalovirus and papovavirus). These viral infections had distinct cytomorphology. Cytomegalovirus infection may manifest as intracytoplasmic, orangeophilic inclusions, in addition to the classical intranuclear inclusion. In the majority of renal transplant patients there appeared to be no relationship between the viral infection and the renal transplant rejection episodes.     

National Lupus Hospitalization Trends Reveal Rising Rates of Herpes Zoster and Declines in Pneumocystis Pneumonia

Objective

Infection is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE). Therapeutic practices have evolved over the past 15 years, but effects on infectious complications of SLE are unknown. We evaluated trends in hospitalizations for severe and opportunistic infections in a population-based SLE study.

Methods

Data derive from the 2000 to 2011 United States National Inpatient Sample, including individuals who met a validated administrative definition of SLE. Primary outcomes were diagnoses of bacteremia, pneumonia, opportunistic fungal infection, herpes zoster, cytomegalovirus, or pneumocystis pneumonia (PCP). We used Poisson regression to determine whether infection rates were changing in SLE hospitalizations and used predictive marginals to generate annual adjusted rates of specific infections.

Results

We identified 361,337 SLE hospitalizations from 2000 to 2011 meeting study inclusion criteria. Compared to non-SLE hospitalizations, SLE patients were younger (51 vs. 62 years), predominantly female (89% vs. 54%), and more likely to be racial/ethnic minorities. SLE diagnosis was significantly associated with all measured severe and opportunistic infections. From 2000 to 2011, adjusted SLE hospitalization rates for herpes zoster increased more than non-SLE rates: 54 to 79 per 10,000 SLE hospitalizations compared with 24 to 29 per 10,000 non-SLE hospitalizations. Conversely, SLE hospitalizations for PCP disproportionately decreased: 5.1 to 2.5 per 10,000 SLE hospitalizations compared with 0.9 to 1.3 per 10,000 non-SLE hospitalizations.

Conclusions

Among patients with SLE, herpes zoster hospitalizations are rising while PCP hospitalizations are declining. These trends likely reflect evolving SLE treatment strategies. Further research is needed to identify patients at greatest risk for infectious complications.     

Long term effects of exposure to viral infections in utero.

An analysis was conducted of the major findings of a long term follow up study of 3076 subjects who were exposed to viral infections in utero and who at the time of analysis were up to 40 years of age. Mortality and morbidity were compared with those in a control population matched for sex and date and area of birth. An excess of cancers (16 cases against seven) appeared to be clustered among those exposed to herpes viruses (varicella or cytomegalovirus). There was evidence of an increased risk of diabetes among those exposed to mumps during the first trimester (four cases among 128 subjects against none in 148 controls). The most surprising finding was a decrease of diseases of the skin and subcutaneous tissue and of the nervous system among subjects exposed to antenatal varicella zoster infection. The mechanism for the association may include production of fetal anti-idiotype antibodies in response to transplacentally acquired maternal autoantibodies.     

Varicella zoster virus reactivation during or immediately following treatment of tegumentary leishmaniasis with antimony compounds

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.     

The study of markers of herpes virus infections in myocardial ischemia

A group of patients with ischemic heart disease (IHD), who underwent surgical aorta-coronary vascular shunting, was examined in this investigation. Low titers of HSV-1 specific IgG were detected in all patients, the obtained values being consistent with similar data obtained in healthy subjects of the same age. Negative PCR of HSV-I DNA in blood and biopsy results were obtained. None of the patients demonstrated typical clinical pattern of infectious disease caused by herpes simplex virus. These data are evidence of the absence of the HSV-1 correlation with coronary atherosclerosis in patients with the IHD diagnosis. The significance of HCMV specific IgG titers and HCMV DNA detected in blood plasma in 87.7% cases is probably attributed to existence of connection of HCMV infection markers revealing in patient' blood with IHD diagnosis and coronary atherosclerosis. Besides, the HCMV DNA presence in biopsy taken from myocardium or vascular wall with lesion is revealed in 100% cases. The cytomegalovirus markers in tissue lesions with the help of specific antiserums marked to HSMV recombinant proteins are also revealed in 100% cases. This fact indicates the connection between pathological atherosclerotical process in IHD and cytomegalovirus infection.     

Epidemiology of herpes zoster. The herpes zoster patient as a source of infection with chickenpox

The authors analyse the inpatient findings accumulated from 2,179 observations on herpes zoster cases for 10 years. The clinico-epidemiological characterization of herpes zoster patients as the potential source of chickenpox infection is presented. The clinical data speak for the droplet transfer of the agent (varicella zoster virus) in this infection, which has permitted the formulation of exact practical recommendations of quarantine and isolation measures in the focus of herpes zoster.     

Infections in pregnancy: highlights from the collaborative perinatal project

The longitudinal study of approximately 60,000 pregnant women was conducted at 14 major medical centers throughout the United States. Clinical data was obtained under prescribed protocols for each of the study women throughout their pregnancy, at delivery, and through the postpartum period. The children were followed with uniform examinations from birth through seven years of age. In addition blood samples were taken from the pregnant women at registration, every two months through pregnancy, at delivery, and six weeks postpartum. Cord blood samples were also taken from the children during the last half of the study. We have used this material from the Collaborative Perinatal Project for the investigation of the role of infections in the production of damage to the fetus and newborn. The frequency of clinically recognizing infection during pregnancy was determined and geographic variation was demonstrated. Serological tests were used to document certain diseases. The frequency of confirmed clinical cases per 10,000 were: rubella, 8; rubeola, 0.6; mumps, 10; varicella-zoster, 5. The epidemiology and clinical findings associated with infections were studied using serological methods. This has provided data on the frequencies of infections such as cytomegalovirus, herpes simplex, mumps, rubeola, respiratory syncytial virus, and others. The study of abnormal pregnancies and matched controls is in progress using serological techniques. A number of specific studies have been reported on infections including rubella, neonatal meningitis, cytomegalovirus, maternal urinary tract infections, and toxoplasmosis. Further testing is now in progress employing more sophisticated laboratory methods and more complete data analysis.