In situ hybridization analysis for cytomegalovirus in chronic villitis

Chronic villitis with villous lymphoplasmacytic, histiocytic infiltrate and stromal necrosis may have various etiologies. Infection with cytomegalovirus (CMV) is a frequent cause of such villitis, but the nuclear and cytoplasmic inclusions diagnostic of CMV are often not apparent. In this study placentas with chronic villitis were analyzed for CMV DNA by means of in situ hybridization. Of the eight cases of chronic villitis studied, three demonstrated inclusions diagnostic of CMV infection. On in situ hybridization, three additional cases had detectable CMV DNA. CMV was detected in endothelial, histiocytic, and fibroblastic cells and occasionally in the trophoblast. In cases with characteristic CMV inclusions, CMV DNA was often present in cells that lacked inclusions. CMV DNA was not detected in unremarkable placental tissue obtained from normal deliveries. It is concluded that CMV is commonly found in lymphoplasmacytic and histiocytic villitis and that in situ analysis for CMV is a rapid, easy, and sensitive way to detect the virus in placentas.     

Distribution of human herpesvirus 6 and varicella-zoster virus in organs of a fatal case with exanthem subitum and varicella

The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV) was examined in autopsy samples from a fatal case with both virus infections. A 9-month-old boy developed convulsive seizures followed by macular skin rashes, rapidly progressed to brain death, and died 15 days after the onset, when signs of varicella were noted. An isolation of HHV-6 from blood and evaluation of antibody activities to various viral agents including HHV-6 were performed before his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from tissues or organs; (ii) detection of both virus antigens in tissues or organs by an indirect immunofluorescent assay using monoclonal antibodies to both viruses; (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a nested polymerase chain reaction assay; and (iv) endonuclease digestion of amplified products of HHV-6 DNA for differentation of variants A and B. Human herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and plasma obtained at the eruptive stage but present only in PBMC 15 days after, indicating the primary infection with HHV-6, although the virus was not isolated from the same blood sample and a significant rise in the antibody titers to HHV-6 was not observed. Both virus antigens and DNA were detected in various tissues or organs obtained at autopsy, but only VZV was isolated from these samples, suggesting disseminated infection with both viruses in an infant. All the amplified products of HHV-6 DNA were variant B. Among the findings for the distribution of virus antigens, it was noteworthy that HHV-6 antigen was demonstrated in the endothelial cells of small vessels in the frontal lobe of the brain. There was no evidence of HHV-7 infection. These data indicate that the primary HHV-6 infection closely followed by the primary VZV infection had the potential hazard of an unexpected and apparently life-threatening event, in which disseminated infections with both viruses were noted in multiple tissues or organs including the brain.     

Differentiating inherited human herpesvirus type 6 genome from primary human herpesvirus type 6 infection by means of dried blood spot from the newborn screening card

To differentiate active human herpesvirus type 6 (HHV-6) infection from inherited HHV-6 (iHHV-6), we analyzed dried blood spots from archived newborn screening cards in 3 patients with high HHV-6 DNA copy numbers. Two patients were positive for HHV-6 DNA as neonates suggesting iHHV-6. In 1 patient, the absence of HHV-6 DNA excluded iHHV-6.     

Absence of associations between influenza-associated encephalopathy and human herpesvirus 6 or human herpesvirus 7

BACKGROUND: Influenza-associated encephalopathy is a severe complication of influenza virus infection, but its pathogenesis is unknown. It was recently suggested that the neurologic complications of influenza, including encephalopathy, are associated with human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7).AIM To confirm or refute the association between influenza-associated encephalopathy and HHV-6 or HHV-7. METHODS: Cerebrospinal fluid and serum from 25 patients with central nervous system complications of influenza (18 patients with encephalopathy and 7 patients with febrile convulsions) were investigated. The specimens were examined by real time polymerase chain reaction (PCR) and nested PCR for HHV-6 and HHV-7 DNA. RESULTS: In the cerebrospinal fluid samples neither HHV-6 DNA nor HHV-7 DNA was detected by real time PCR or nested PCR. HHV-6 DNA was detected in a single serum sample from a patient with febrile convulsions. CONCLUSION: In our study there was no association with HHV-6 or HHV-7 in most patients with central nervous system complications of influenza.     

Usefulness of diffusion-weighted MRI in human herpesvirus-6 encephalitis

We report a patient with human herpesvirus-6 (HHV-6) encephalitis diagnosed by diffusion-weighted magnetic resonance imaging (DW-MRI). A previously healthy 10-month-old girl developed acute encephalopathy. HHV-6 DNA was detected in her cerebrospinal fluid during the acute phase of the disease by polymerase chain reaction. The patient demonstrated cortical diffusion abnormalities in affected brain parenchyma, partially as the initial or most sensitive sign of encephalitis that could be detected not by conventional MRI but by DW-MRI. Serial imaging showed that the diffusion abnormality DW-MRI returned to normal after 45 days. CONCLUSION: DW-MRI may be a valuable tool for early detection and diagnosis of HHV-6 encephalitis and is more sensitive than conventional MRI to detect a subtle edematous change in the brain.     

Primary human herpesvirus 6 infection in liver transplant recipients

We detected primary human herpesvirus 6 (HHV-6) infection in 5 infants who received living related liver transplantation from their HHV-6 seropositive mothers. Primary HHV-6 infection was confirmed by demonstrating the seroconversion of HHV-6 antibodies with an immunofluorescence assay, by the isolation of the virus, or both. Seroconversion of HHV-6 immunoglobulin G antibody was demonstrated in all 5 recipients. HHV-6 was isolated from 3 of the 5 recipients between 2 and 3 weeks after transplantation. Moreover, the virus genome was detected in plasma by polymerase chain reaction in 4 of the 5 recipients during the same period. Although the 5 recipients had pyrexia at the time of primary HHV-6 infection, none of the recipients had a skin rash after defervescence. Clinical symptoms disappeared without specific antiviral treatment in all but 1 of the recipients.     

Transfer of human herpesvirus 6 and 7 antibodies from mothers to their offspring

Placental transfer of maternal human herpesvirus (HHV) 6 and HHV 7 antibodies to infants was examined simultaneously in 69 paired plasma samples by an indirect immunofluorescence assay. All the mothers had antibodies to both viruses. The mean HHV 6 and HHV 7 antibody titers of infants were significantly higher than those of the mothers. The mean ratio of cord blood antibody titer to the maternal titer for both viruses was 1.89, suggesting active transport by placenta.     

Extranodal rosai-dorfman disease presenting as a solitary mass with human herpesvirus 6 detection in a pediatric patient

ABSTRACT In Rosai-Dorfman disease (RDD), exclusive extranodal involvement with lesions limited to the kidneys is very uncommon and has been described only in adult patients. Occasionally, human herpesvirus 6 (HHV-6) has also been detected in RDD tissue samples. We present the case of a 7-year-old boy referred to our center presenting a single solid mass in the right kidney measuring 3.4?cm, detected both on contrast computed tomography and magnetic resonance imaging. Surgical excision was successfully completed, and the pathology report informed characteristic histopathology and immmunohistochemistry features of RDD. Human herpesvirus 6 was detected and amplified by polymerase chain reaction, as well as by immunohistochemistry. We discuss imaging and histology-based differential diagnoses in the pediatric age group. Although RDD is a rare histiocytic disorder of unknown etiology and pathogenesis, the presence of HHV-6 observed in this case supports the possibility of an abnormal immunologic response linked to viral presence.     

Mollaret's meningitis due to human herpesvirus 6 in an adolescent

We report the first pediatric case of Mollaret meningitis in an adolescent female with acute lymphoblastic leukemia in remission. This patient had signs and symptoms consistent with meningitis, with three episodes over a 3-month period. Human herpesvirus 6 (HHV-6) was identified during her last episode from polymerase chain reaction assay of a cerebrospinal fluid specimen. She was treated successfully with foscarnet, after which HHV-6 was undetectable in her cerebrospinal fluid.     

Invasion by human herpesvirus 6 and human herpesvirus 7 of the central nervous system in patients with neurological signs and symptoms

METHODS—A total of 43 children with neurological signs and symptoms were enrolled in the study. All children were suspected of having meningitis, and lumbar punctures were performed. Human herpesvirus 6 (HHV-6) and HHV-7 DNA was detected in cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) by nested polymerase chain reaction.
RESULTS—Most patients had detectable serum antibody to both HHV6 and 7. HHV6 DNA was detected in PBMC of 15 patients and in CSF cell pellet of seven. Corresponding figures for HHV7 were 28 and 6.2/7, and 5/6 with CSF viral DNA also had it in PBMC, respectively. No viral DNA was detected in CSF supernatants. The seven HHV6 CSF viruses were all variant B.
CONCLUSION—These data suggest that HHV-7 may invade the CNS.

     

Mononucleosis-like illness in an infant associated with human herpesvirus 6 infection

Illnesses resembling mononucleosis, hematologically characterized by atypical lymphocytosis in the peripheral blood, are caused by other viral infections as well as by a primary Epstein-Barr virus infection. Human herpesvirus 6, a newly isolated member of the herpesvirus group, can also cause a mononucleosis-like illness. Illness associated with human herpesvirus 6 infection mostly occurs in immunocompetent adults. We observed a 3 month old infant who presented with marked atypical lymphocytosis and liver dysfunction. We examined serum samples to detect viral antibodies related to mononucleosis-like illness. Only the titers of antibody against human herpesvirus 6 were elevated. Primary human herpesvirus 6 infection cannot only cause exanthem subitum or present in an inapparent form but can also cause an illness like mononucleosis, even in an infant.     

Invasion by human herpesvirus 6 and human herpesvirus 7 of the central nervous system in patients with neurological signs and symptoms.

METHODS: A total of 43 children with neurological signs and symptoms were enrolled in the study. All children were suspected of having meningitis, and lumbar punctures were performed. Human herpesvirus 6 (HHV-6) and HHV-7 DNA was detected in cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) by nested polymerase chain reaction. RESULTS: Most patients had detectable serum antibody to both HHV6 and 7. HHV6 DNA was detected in PBMC of 15 patients and in CSF cell pellet of seven. Corresponding figures for HHV7 were 28 and 6.2/7, and 5/6 with CSF viral DNA also had it in PBMC, respectively. No viral DNA was detected in CSF supernatants. The seven HHV6 CSF viruses were all variant B. CONCLUSION: These data suggest that HHV-7 may invade the CNS.     

Low level of mosaicism in atypical Prader Willi syndrome: detection using fluorescent in situ hybridization

Prader Willi syndrome (PWS) most commonly is due to paternal micro-deletion of 15q11-q13. Although PWS is not a rare condition, mosaic micro-deletion cases are reported rarely. FISH using PWS micro-deletion probe is the most useful method to detect deletion including mosaicism. In this report we describe a female child with clinical features of atypical PWS and FISH analysis showing mosaicism for deletion in the PWS critical region. This is first mosaic deletion case of PWS from Indian subcontinent.     

Fatal encephalitis/encephalopathy in primary human herpesvirus-6 infection.

An encephalitic illness with a fatal outcome occurred in a 9 month old girl with virologically confirmed exanthem subitum. Human herpes-virus-6 (HHV-6) DNA was found in the cerebrospinal fluid at the acute stage of the disease by the polymerase chain reaction, but the virus antigen was not detected in her brain tissue. This suggests that HHV-6-induced encephalitis/encephalopathy may be due to a non-infectious process.     

Five cases of thrombocytopenia induced by primary human herpesvirus 6 infection

Abstract Five patients suffering from exanthem subitum with thrombocytopenia were confirmed as primary human herpesvirus 6 (HHV-6) infection by serological test. All cases had thrombocytopenia during the acute phase of exanthem subitum. The clinical features of these cases were benign, and all recovered without any specific treatment. Moreover. 4 of the 5 cases showed a mild elevation of hepatic transaminase during the same period, and other viral infections including cytomegalovirus, Epstein-Barr virus, and human herpesvirus 7 were ruled out in these patients. It was speculated that direct inhibition of platelet production by the virus or cytokine induced by the virus-infected cells was the mechanism of the thrombocytopenia induced by primary HHV-6 infection.