The rapid diagnosis and clinical features of human herpesvirus 6

Department of Child Health, University of Glasgow, UK.
Journal of Infection (Impact Factor: 4.44). 04/1998; 36(2):161-5. DOI: 10.1016/S0163-4453(98)80006-6
Source: PubMed


Since human herpesvirus 6 (HHV6) was first linked with exanthem subitum in 1988 there has been increasing evidence that the morbidity associated with acute HHV6 infection may be more significant and variable. However, the clinical appreciation of HHV6 infection has been hampered by the lack of rapid and clinically useful diagnostic methods. In this prospective study of hospitalized febrile children under 3 years of age we compared three rapid viral diagnostic methods, (polymerase chain reaction assay (PCR), IgM serology and direct antigen detection), with conventional serology on paired serum samples. In addition, we documented the range of clinical features associated with acute HHV6 infection. Of 67 children recruited, 11 (16%) had evidence of acute HHV6 infection: six had detectable, specific, IgM; four were PCR positive; and one was PCR positive with IgM. Direct antigen testing on batched frozen samples detected no infections. Apart from high fever (median peak 38.5 degrees C), common features were non-specific. Two children had febrile convulsions and only one child had a non-specific rash. We conclude that rapid microbiological diagnosis at present requires two tests (IgM and PCR). HHV6 is a common cause of febrile illness in hospitalized infants with no rash and should be considered in their diagnosis.

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    • "However, HHV-6 is a ubiquitous infection that may be acute or latent, and establishing a link between HHV-6 and acute rash and fever illness remains a challenge because there is no gold-standard diagnostic test that can distinguish between latent infection and active viral repli- cation[33,34]. Viral isolation is the only test that can reliably distinguish between these 2 states; however, it lacks sensitivity and is not practical on a population basis[35]. We identified 3 school-based clusters of GAS. "
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    ABSTRACT: Few population-based studies of infectious etiologies of fever-rash illnesses have been conducted. This study reports on enhanced febrile-rash illness surveillance in Campinas, Brazil, a setting of low measles and rubella virus transmission. Cases of febrile-rash illnesses in individuals aged <40 years that occurred during the period 1 May 2003-30 May 2004 were reported. Blood samples were collected for laboratory diagnostic confirmation, which included testing for adenovirus, dengue virus, Epstein-Barr virus (EBV), enterovirus, human herpes virus 6 (HHV6), measles virus, parvovirus-B19, Rickettsia rickettsii, rubella virus, and group A streptococci (GAS) infections. Notification rates were compared with the prestudy period. A total of 1248 cases were notified, of which 519 (42%) had laboratory diagnosis. Of these, HHV-6 (312 cases), EBV (66 cases), parvovirus (30 cases), rubella virus (30 cases), and GAS (30 cases) were the most frequent causes of infection. Only 10 rubella cases met the rubella clinical case definition currently in use. Notification rates were higher during the study than in the prestudy period (181 vs 52.3 cases per 100,000 population aged <40 years). Stimulating a passive surveillance system enhanced its sensitivity and resulted in additional rubella cases detected. In settings with rubella elimination goals, rubella testing may be considered for all cases of febrile-rash illness, regardless of suspected clinical diagnosis.
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    ABSTRACT: To determine whether receipt of an investigational anti-CD3 monoclonal antibody (BC3) increased the risk of human herpesvirus 6 (HHV-6) reactivation and development of encephalitis in bone marrow transplant (BMT) recipients, persons who had and had not received BC3 were compared. Odds of HHV-6 reactivation were higher among BC3 recipients than among control patients (odds ratio, 2.5; 95% confidence interval [CI], 1.3–4.7). In addition, BC3 recipients were more likely than control patients to develop encephalitis (risk ratio [RR], 3.5; 95% CI, 1.3–9.5), and this association followed a BC3 dose-dependent relationship (P=.03, by Mantel-Haenszel χ2 test). In a multivariable model, HHV-6 reactivation and receipt of BC3 were associated with increased risk of encephalitis (RR, 5.4; 95% CI, 1.9–15.3, and RR, 3.3; 95% CI, 1.2–9.1, respectively). In conclusion, both HHV-6 reactivation and receipt of BC3 for prophylaxis of acute graft-versus-host disease independently increased the risk of encephalitis in allogeneic BMT recipients. Prospective studies to better define the relationship between HHV-6 reactivation and encephalitis in allogeneic BMT recipients are warranted.
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    ABSTRACT: Human herpes virus-6 (HHV-6) was first isolated in 1986. It has been shown to cause exanthema subitum and has been associated with various other diseases. HHV-6 infection is widespread, and more than 90% of the population have antibodies against HHV-6 at the age of 2 years. Once acquired, the virus remains latent in the body. This makes it difficult to draw any conclusions about a causal relationship between the demonstration of HHV-6 and a specific disease. This work was to develop a mu-capture HHV-6 IgM enzyme linked immuno sorbent assay (ELISA) for use in routine diagnosis and for wide scale patient population analysis. A mu-capture HHV-6 IgM ELISA was established. A total of 682 sera consisting of 585 sera from Danish blood donors and 97 sera from patients with autoimmune antibodies were analysed in the HHV-6 IGM ELISA. One hundred and ninety-two sera had earlier been analysed for total HHV-6 antibody content in a competitive ELISA, 94 sera were analysed for cytomegalovirus (CMV) IgM and 57 sera for Epstein Barr virus (EBV) antibodies, using different ELISA assays. The results for 12 primary infections with HHV-6 are also reported. A HHV-6 IgM optical density (OD)-ratio was calculated according to a constant positive control. An empirical cut off of 0.5 HHV-6 IgM OD-ratio was chosen (with regard to the 10 HHV-6 seroconverters), which resulted in a specificity of 97.5% of the HHV-6 IgM ELISA. Two of the three donor sera with HHV-6 IgM OD-ratios more than 1.05 had total HHV-6 antibody titers significantly above the group with IgM OD-ratios below 0.7 consisting with HHV-6 reactivation. There was no cross reactions to EBV or CMV IgM positive sera. The HHV-6 IgM ELISA seems valid to diagnose primary HHV-6 infection in particular in combination with the HHV-6 total antibody assay.
    No preview · Article · Sep 2002 · Journal of Clinical Virology
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