Human herpesvirus 6 reactivation is associated with cytomegalovirus infection and syndromes in kidney transplant recipients at risk for primary cytomegalovirus infection

A potential association between human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) following kidney transplantation was explored by retrospectively testing serial serum specimens for HHV-6 IgG and IgM antibody. HHV-6 reactivation occurred in 35 (66%) of 53 transplant recipients. Fungal or parasitic opportunistic infections, graft rejection or loss, and mortality were not associated with HHV-6 reactivation. HHV-6 reactivation was associated with primary CMV infection (P=.001) and CMV syndrome (P=.003) and with trends for CMV-related hepatitis (P=.095), CMV-related neutropenia (P=.104), and serious CMV disease (P=.085). After controlling for CMV immune globulin (CMVIG) prophylaxis, the association between HHV-6 reactivation and primary CMV infection and syndrome remained significant (P=.002 and 0.006, respectively). The reduction in CMV syndrome among those receiving CMVIG prophylaxis remained significant (P=.007) after controlling for HHV-6 reactivation. HHV-6 reactivation in kidney transplant recipients at risk for primary CMV infection is associated with CMV infection and CMV-related disease, and these effects are independent of CMVIG prophylaxis.     

Case of the month: May 1998--a patient with HIV infection and multiple cranial neuritis

A 36-year old male with a three year history of HIV infection and more recently, CMV retinitis, had several episodes of polyradiculitis with severe bilateral leg pain and urinary retention which resolved slowly over several months. He then presented with high fevers and severe dysphagia with dehydration. Examination showed oral thrush, dyarthric speech and mild memory impairment. Fundoscopic exam showed CMV retinitis and HIV retinopathy. Further examination revealed other cranial nerve signs and leg weakness. MRI scans showed several contrast enhancing abnormalities of cranial nerve roots. The patient died from massive barium aspiration. At autopsy the brain showed multiple CMV cranial neuritis, CMV polyradiculitis and CMV ventriculo-ependymitis. While spinal nerve root involvement by CMV may occur in up to 1% of AIDS patients, involvement of cranial nerves is unusual and CMV infection of multiple cranial nerves is distinctly rare.     

Lysozyme activity in cerebrospinal fluid. Studies in inflammatory and non-inflammatory CNS disorders

Lysozyme activity was measured in cerebrospinal fluid (CSF) from 114 patients with inflammatory (bacterial and serous meningitis, polyradiculitis, encephalitis) and non-inflammatory (multiple sclerosis, CNS tumors, cerebral vascular diseases) CNS diseases. Highly elevated values were found consistently in patients with bacterial meningitis. Elevated values were found also in patients with encephalitis, polyradiculitis, multiple sclerosis and CNS tumors, but a considerable overlapping between these groups and normal controls precludes the use of CSF lysozyme measurements as a diagnostic aid in the latter disease groups. Simultaneous measurements of lysozyme, albumin and IgG in CSF and serum suggested that the mechanism for increased CSF lysozyme values in bacterial meningitis is mainly a breakdown of the blood/brain barrier, whereas the increased CSF lysozyme values in the remaining groups of patients are more likely caused by production of lysozyme by cells within the meninges (neutrophilic granulocytes, monocytes?).     

Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome

An atypical virus, cytopathic for human and animal fibroblasts, was repeatedly cultured from a patient with chronic fatigue syndrome. Viral particles, suggestive of cytomegalovirus (CMV) were seen by electron microscopy. Infected cells did not, however, stain with antisera specific for CMV, herpes, simplex virus, or human herpes-virus-6. Polymerase chain reaction (PCR) assays for these viruses were also negative. Two distinct products of approximately 1.5 kilobase pairs were amplified from virally infected cells using the human T lymphotropic virus-II tax gene reactive primer, SK44, in low stringency PCR. Sequencing of one of the amplified products showed a region of highly significant partial homology with the UL34 gene of CMV. The sequence of the other PCR product did not correspond with CMV or any other virus. DNA was extracted from the material pelleted by ultracentrifugation of filtered culture supernatants. It migrated in agarose gels as a single band of approximately 20 kpb. The banded DNA was digested with EcoRI and cloned. A 2.2 kbp plasmid containing the CMV-related sequence identified within the PCR product was recovered. Sequencing of this plasmid extended the region of partial sequence homology with CMV to include a portion of the UL35 gene of CMV. Initial sequencing of additional plasmids has confirmed the partial relatedness to CMV. The data indicate a novel type of CMV-related "stealth" virus that is able to establish a clinically persistent human infection.     

Comparative study of cytomegalovirus (CMV) antigenemia assay, polymerase chain reaction, serology, and shell vial assay in the early diagnosis and monitoring of CMV infection after renal transplantation

BACKGROUND: Early diagnosis of cytomegalovirus (CMV) infection, which is an important cause of morbidity and mortality in renal transplant recipients, remains of great importance. This prospective study was performed in kidney transplant recipients to determine the diagnostic value of the CMV antigenemia assay in comparison with polymerase chain reaction (PCR), serology, and shell vial assay. METHODS: Seventy-five consecutive renal transplant recipients were enrolled in this study and monitored by both antigenemia assay and serology. The initial 34 of the 75 patients were subjected to PCR and shell vial assay. RESULTS: Antigenemia, PCR, and shell vial assay became positive before the onset of CMV-related symptoms in 31/34 (89%), 13/16 (81%), and 2/16 (13%), respectively. None of the 34 patients who had symptomatic CMV disease showed a significant increase in IgG or IgM before the onset of symptoms. Antigenemia and PCR assays turned positive, 7 and 11 days (median), respectively, before the onset of clinical symptoms. Serology and shell vial assay became positive 21 and 25 days (median), respectively, after the onset of CMV-related clinical symptoms. To examine the clinical value of these assays, "good correlation" was defined based on the correlation between the clinical course and the results of the assays. Good correlation with the antigenemia assay was observed in 33 (96%) out of 34 renal transplant recipients who recovered from their CMV disease after ganciclovir therapy. Only one of 16 (7%) patients showed good correlation by shell vial assay, whereas PCR and serology did not show a good correlation. Consequently, antigenemia was considered the best way to monitor CMV infections after kidney transplantation. CONCLUSIONS: Only the CMV antigenemia assay can be successfully employed after renal transplantation for the early diagnosis and extensive monitoring of active CMV infection.     

Reversible neurological complications in chronic alcohol abuse with hypophosphatemia

Severe hypophosphatemia is rare, usually affecting chronic alcoholics and patients under total parenteral nutrition. The most important clinical features are rhabdomyolysis and neurological deficits. The latter may take various forms and can affect the peripheral as well as the central nervous system. Symptoms of polyradiculitis with progressive paresis or cerebellar symptoms such as dysarthria, dysphagia and ataxia are frequent manifestations. Rarely, hypophosphatemia can cause confusional states, epileptic seizure or coma. The differential diagnosis includes Guillain-Barré polyradiculitis, diffuse encephalopathy, Wernicke encephalopathy and central pontine myelinolysis. We describe the neurological signs in a female chronic alcoholic who developed severe ataxia and tetraparesis after a week's course of parenteral, phosphate-free nutrition. Complete recovery occurred after adequate substitution of phosphate.     

Strategies for the prevention of cytomegalovirus disease after marrow transplantation

The purposes of this review are to examine the epidemiology of disease due to cytomegalovirus (CMV) in recipients of autologous and allogeneic marrow transplants and to compare different antiviral regimens used for the prevention of such disease in recipients of allogeneic marrow transplants, with an emphasis on ganciclovir. In seven studies, ganciclovir reduced the incidence of CMV infection and disease after allogeneic marrow transplantation. In one study mortality after transplantation was reduced because of a decreased rate of CMV-related death among ganciclovir-treated patients. Ganciclovir was effective when given to all CMV-seropositive patients (prophylaxis) or to patients who were considered at high risk for CMV disease on the basis of a positive surveillance culture (early treatment). The effectiveness of ganciclovir for the prevention of CMV infection and disease is limited by drug-induced neutropenia. Experience with other antiviral agents, such as foscarnet, has been limited. Initial studies of the adoptive transfer of CMV-specific CD8+ cytotoxic T cells have been conducted. In short, ganciclovir is currently effective for the prevention of CMV disease in allogeneic marrow transplant recipients, but its usefulness is limited by neutropenia. Future studies must be aimed at confining the toxicity of ganciclovir to patients at the highest risk for CMV disease.     

Fulminant cerebello-brainstem encephalitis with polyradiculitis following probable Epstein-Barr virus infection]

Epstein-Barr virus (EBV) infection is occasionally accompanied by acute neurological impairment. The pathogenesis of neurological manifestations with EBV infection consists of primary inflammations of EBV infection, and secondary immunologic reactions. However, their clinical course and prognosis are usually favorable. Here we report a patient with fulminant neurological involvement in association with EBV infection. The patient was a 44-year-old man. One morning he developed ataxic gait and speech following flu-like symptoms. He noticed double vision in the afternoon. He had disturbance of consciousness, bilateral ptosis with mydriasis, opthalmoplegia, facial diplegia, bulbar palsy, and weakness of muscles in extremities and respiratory system on the next day. He required mechanical ventilatory support for a month. His symptoms began to improve gradually two weeks after the onset. Two month later, neurological examinations disclosed severe cerebellar ataxia of the four extremities and ocular movement, cerebellar speech, and moderate weakness in his limbs. Moderate cerebellar ataxia and diminished deep tendon reflexes remained for 8-months. Although he had no physical manifestations of infectious mononucleosis, DNA of EBV was identified in the cerebrospinal fluid (CSF) by the polymerase chain reaction method. From these results, we diagnosed his condition as a cerebello brainstem encephalitis with polyradiculitis associated with EBV infection. The cell counts and protein content of CSF gradually normalized in the early stage of his illness, but CSF protein increased again, and had the peak of 275 mg/dl in about one month. In spite of normalized CSF cell counts, his neurological symptoms persisted. CT scan and MRI studies of the brain and the spinal cord were repeated, but demonstrated no significant abnormalities. Clinical course and CSF findings revealed that his fulminant neurological symptoms were most likely produced by the secondary immunologic reactions following the primary inflammations by EBV infection.     

The correlation between symptomatic CMV infection and CMV antigenemia in heart allograft recipients

Previous studies have demonstrated that CMV-specific antigens detected from peripheral blood leukocytes correlate with active CMV infection in transplant patients. However, the clinical diagnosis of CMV infection is difficult, and the significance of a positive blood finding is unclear, while CMV antigenemia and viremia may also occur in asymptomatic patients. To investigate the clinical significance of CMV antigenemia after heart transplantation, 68 heart allograft recipients were monitored weekly. Altogether 501 blood specimens were analyzed. CMV was demonstrated in blood leukocytes by a monoclonal antibody and immunoperoxidase staining, and the antigenemia level was expressed as CMV positive cells/50,000 leukocytes. CMV antigenemia occurred in 28/68 patients, and 12 of them developed a symptomatic infection. Of all blood specimens 88/501 were CMV positive, and 30 of them related to the clinical manifestation of CMV. When antigenemia level exceeded > 100/50,000, a significant correlation between antigenemia and CMV-related clinical manifestation was reached (P < 0.001). Of the 28 antigenemia positive patients 16 never developed any clinical signs of CMV infection. Their maximal antigenemia level was low (median 23, range 30-90) compared with those with clinical manifestation (median 500, range 30-1000) (P < 0.002). In conclusion, high antigenemia levels (> 100/50,000) correlate with clinical manifestations of CMV infection. Patients with lower levels (< 100/50,000) do not necessarily ever develop a symptomatic infection. Quantitative monitoring of CMV antigenemia may, thus, be helpful in the clinical diagnosis of CMV infection in heart transplant patients.     

Evaluation of Murex CMV DNA hybrid capture assay for detection and quantitation of cytomegalovirus infection in patients following allogeneic stem cell transplantation

Murex hybrid capture DNA assay (HCS) is a solution hybridization antibody capture assay for detection and quantitation of cytomegalovirus (CMV) DNA in leukocytes. To determine whether CMV HCS is sensitive enough to initiate and monitor antiviral therapy after allogeneic stem cell transplantation (SCT), 51 consecutive SCT recipients were prospectively screened for the appearance of CMV infection by HCS, PCR, and culture assays from blood samples. Preemptive antiviral therapy was initiated after the second positive PCR result in all patients, as previously reported, and HCS was not considered for clinical decision making. A total of 417 samples were analyzed. Of these, 21 samples were found to be positive by PCR and HCS, 88 samples were PCR positive but HCS negative, and 308 were negative by both assays. Concordance of results between PCR and HCS and between HCS and blood culture was observed in 78.9 and 95.9% of the samples assayed, respectively. PCR was found to be more sensitive than HCS, and HCS was more sensitive than the blood culture assay (P < 0.0001). Four patients with symptomatic CMV infection were PCR positive prior to the onset of CMV-related symptoms, whereas HCS detected CMV DNA in three patients prior to and one at onset of CMV disease. The numbers of genomes per milliliter of blood were higher in patients with symptomatic CMV infection than in those with asymptomatic CMV infection (P = 0.06). None of the HCS-negative patients developed CMV disease. Thus, all patients with CMV disease were correctly identified by HCS; however, the lower sensitivity limit of the HCS assay may still be insufficient to allow diagnosis of CMV infection early enough to prevent CMV disease in patients following allogeneic SCT.     

Maximum rate of change in oesophageal pressure assessed from unoccluded breaths: an option where mouth occlusion pressure is impractical

A nested polymerase chain reaction (PCR) assay was used to determine the levels of cytomegalovirus (CMV) genomes in cells of CSF from 19 patients with AIDS and 12 human immunodeficiency virus type I (HIV-1) seronegative individuals with various neurologic disorders. Five AIDS patients had autopsy-proven CMV encephalitis (CMVE) and 14 patients had no evidence of CMV-related CNS manifestations. CSF cells from AIDS patients with confirmed CMVE harbored viral genomes at a median value of 3,333/10(5) cells (range, 1,667 to 5,333/10(5) cells; mean, 3,558/10(5) cells) compared with a median value of 125/10(5) cells (range, 9 to 1,000/10(5) cells; mean, 281/10(5) cells) for AIDS patients with CMV-unrelated symptoms and a median value of 1.9/10(5) cells (range, 0 to 562/10(5) cells; mean, 52/10(5) cells) for HIV-1 seronegative control subjects. A subset of CSF samples was assessed using a modified single round amplification PCR with a detection limit of 500 viral copies. CMV DNA was detected in all four specimens from AIDS patients with proven CMVE, in two of five AIDS patients without CMVE, and in none of five seronegative control subjects. Quantitation of CMV genomes in CSF cells is indicative of latent or productive CMV infection and is a reliable means for diagnosis of CMVE in patients with AIDS. Detection of a cutoff value of cellular CMV genomes by means of nonquantitative PCR may identify patients at risk for CMV infection of the CNS.     

Impact of high-dose oral acyclovir prophylaxis on cytomegalovirus (CMV) disease in CMV high-risk renal transplant recipients

Recent studies showed contradictory results concerning the efficacy of oral acyclovir in the prevention or amelioration of cytomegalovirus (CMV) disease after renal transplantation (TX). This study evaluated the incidence and severity of CMV disease within the first year after TX in high-risk renal transplant recipients (CMV-seropositive donor, seronegative recipient) treated prophylactically with oral acyclovir (800 to 3200 mg/day) over a period of 12 wk (ACY, N = 22), compared with high-risk patients randomly assigned as controls (CO, N = 10). Follow-up for CMV infection included serological determination of CMV-specific immunoglobulin G and immunoglobulin M antibodies, antigen detection in peripheral blood leukocytes (PP 65), shell vial culture (blood), and virus isolation/early antigen detection (urine). Severity of CMV disease was quantified by a scoring system for CMV-related symptoms. Nine patients (40.1%) in the acyclovir group and four patients (40%) in the control group developed CMV disease. Neither severity (ACY, 11.4 versus CO; 12.5 points score), nor duration of disease (ACY, 21 days; CO, 22 days), nor transplant function at the end of the observation period differed significantly. The onst of CMV disease was not delayed significantly in acyclovir-treated patients compared with controls (ACY, 47 +/- 34 days versus CO, 27 +/- 14 days after TX, not significant). Our results show no beneficial effect of oral acyclovir prophylaxis in CMV high-risk renal transplant recipients.     

N-nitroso compounds and man: sources of exposure, endogenous formation and occurrence in body fluids

BACKGROUND: An outbreak of seven cases of hepatitis A (HA) occurred in a day-care center. Five of the cases were children attending the center, one was a nurse and one was the mother of a child. It is probable that the first case with HA was a male child infected by an unknown source. METHODS AND RESULTS: Human immunoglobulin (HIG) was administered to both children and staff at the center following which there were no new cases of infection among in-center contacts. However, a new case of HA among household contacts developed 3 weeks following the treatment of in-center contacts. CONCLUSIONS: The outbreak may have been prevented if the sibling (case 2) of the source case of infection (case 1) had been given HIG as soon as infection had been confirmed. Additionally, the data suggest that HIG for prevention of HA should be given not only to children but also to their parents.     

Endoscopic bladder repair during total modified laparoscopic hysterectomy. A case report

A case of abdominal mycobacterial infection mimicking acute appendicitis in a human immunodeficiency virus (HIV) infected patient is reported. The case illustrates the unusual aetiology of an acute abdomen in this population and the report reviews the aetiology of surgical abdominal pain in HIV infection and discusses the management of abdominal mycobacterial infections.     

Rapid detection cytomegalovirus pneumonia in recipients of bone marrow transplant: evaluation and comparison of five survey methods for bronchoalveolar lavage fluid

To detect cytomegalovirus-associated interstitial pneumonia (CMV-IP) in recipients of BMT in its earliest stage, five CMV methods were assessed for their usefulness using bronchoalveolar lavage fluid as the test specimen. Of the 43 cases enrolled in the study, PCR was positive in 12 cases, shell vial in eight, culture in eight and cytology in three. There were no positive cases in in situ hybridization. Based on this result, the 43 cases were classified into four groups: Group 1, three cases: positive in PCR, shell vial and cytology; Group 2, five cases: positive in PCR and shell vial; Group 3, four cases: positive only in PCR; and Group 4, 31 cases: negative in all CMV tests. Cases in Group 1 were judged as having the highest risk of overt CMV-IP. They were successfully treated with a combination of ganciclovir and immunoglobulin. Group 2 was diagnosed as having active CMV infection and ganciclovir monotherapy was effective for these patients. Groups 3 and 4 were not given anti-CMV therapy, but they were free from CMV-related manifestations throughout the study. The sensitivity and specificity of each survey method for the detection of Groups 1 and 2 were 1.0 and 0.89 in PCR, 1.0 and 1.0 in shell vial, 0.88 and 1.0 in culture, and 0.38 and 1.0 in cytology. Similarly, the positive and negative predictive values were 0.67 and 1.0 in PCR, 1.0 and 1.0 in shell vial, 1.0 and 0.97 in culture, and 1.0 and 0.88 in cytology. Thus, CMV survey on bronchoalveolar fluid was thought to be useful in detecting post BMT CMV-IP in its earliest stage.     

Anesthesia in early surgery and endovascular therapy for aneurysmic subarachnoid hemorrhage]

This article describes a case of infectious mononucleosis (IM) in a 16-year-old female adolescent who presented with fever, sore throat, cervical lymphadenopathy and genital ulcerations. Initially, this patient was thought to have herpes simplex viral infection secondary to the characteristic multiple genital ulcers. Seven cases (including this case) have reported an association between Epstein-Barr virus (EBV) infection and genital ulcerations. IM as a cause of genital ulcerations should be included in the differential diagnosis.     

Fetal Candida infection associated with an intrauterine contraceptive device

Fetal Candida infection is rarely described but is often associated with a retained intrauterine contraceptive device (IUCD). A case of abortion due to Candida infection in a patient wearing an IUCD is reported.     

Remission of Ménétrier's disease after a prolonged period with therapeutic eradication of Helicobacter pylori

We report here a case of Ménétrier's disease (MD) that required a prolonged period for remission after eradication therapy of Helicobacter pylori (HP). The appropriate time needed to judge the efficacy of the eradication therapy for HP infection in an MD case is discussed.     

Pediatric tuberculosis: problems in diagnosis and issues in management

The diagnosis of infection and disease due to Mycobacterium tuberculosis in infants and children presents many clinical challenges. The distinction of infection from disease (tuberculosis) in children is often unclear. There is difficulty in obtaining positive microbiological confirmation of infection in sputum, gastric, tracheal, or bronchial aspirates and in other body fluids in infants and children. Isoniazid is effective in the treatment of infection and prevention of progression of infection to clinical disease. Approximately 50% of children with primary tuberculosis are asymptomatic and are diagnosed as a result of contact investigation. Children become infected from exposure to an adult or adolescent with contagious pulmonary tuberculosis. The results of drug susceptibility tests in the source case in contact with an exposed child can guide the antituberculous chemotherapy. Chemotherapy regimens for treatment of pediatric tuberculosis have become shorter and more intensive with a marked increase in directly observed therapy (DOT).     

Poncet's disease and papulonecrotic tuberculid in a patient infected with the human immunodeficiency virus

We report the case of a 27-year-old patient with the human immunodeficiency virus (HIV) infection who presented with a 2-week history of crops of painful, red papules over the trunk and extremities, together with a sterile, symmetric polyarthritis involving the small and large joints. Histologic study of a skin biopsy specimen demonstrated features of papulonecrotic tuberculid. Analytical and microbiologic studies ruled out tuberculous infection. Both the synovial and the skin processes were considered to be an immune response secondary to Mycobacterium tuberculosis infection. Specific treatment was established, and there was marked improvement in both the skin and joint symptoms. This case illustrates the complex relationship between the host and the HIV, suggesting an immune dysregulation cause for both the synovial and the skin lesions.