Human Herpesvirus-6 (HHV-6) Infection in Allogeneic Bone Marrow Transplant Recipients: Evidence of a Marrow-Suppressive Role for HHV-6 In Vivo

Summary:We investigated whether a causal relationship exists between human herpesvirus 6 (HHV-6) and skin rash resembling acute graft-versus-host disease (GVHD) following bone marrow transplantation (BMT). Isolation of HHV-6 was used to monitor active HHV-6 infection in this study. We analyzed 25 episodes of skin rash in 22 recipients. All recipients were seropositive for HHV-6 before BMT. The onset of skin rash started prior to 30 days post transplantation (group A) in 15 of 25 cases, but after that (group B) in the remaining 10 cases. Twenty-five skin tissue samples were obtained from 22 recipients. The HHV-6 genome was detected in four of 15 skin samples from group A, but not detected in those from group B. HHV-6 was isolated from 11 of 22 recipients around 2 to 3 weeks after BMT (range 14 to 28 days after BMT). HHV-6 was isolated at a time between 10 days before and after the onset of skin rash (skin rash-related viremia) in nine cases in group A. Meanwhile, no skin rash-related viremia was observed in group B. Of the four recipients with positive detection of HHV-6 genome in their skin tissue (group A), two had HHV-6 viremia at the same time. The association between the timing of HHV-6 infection and the onset of skin rash was analyzed statistically. HHV-6 viremia (skin rash-related viremia) was found in nine of 15 (60%) cases in group A, compared with none of 10 (0%) cases in group B. This difference was statistically significant (P = 0.008). Moreover, HHV-6 infection (skin rash-related viremia and/or positive detection of HHV-6 DNA in skin tissue) was demonstrated in 11 of 15 (73.3%) cases in group A, compared with none of 10 (0%) cases in group B (P = 0.001). Thus, this study suggests that HHV-6 may be involved in the development of skin rash in the first month after allogeneic BMT. Bone Marrow Transplantation (2001) 28, 77-81.

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confidence: 99%

Correlation between HHV-6 infection and skin rash after allogeneic bone marrow transplantation

Yoshikawa

Ihira

Ohashi

et al. 2001

“…5,6 HHV-6 infection has some association with chronic fatigue syndrome, 7 multiple sclerosis, 8,9 hepatitis, 10 meningoencephalitis, [11][12][13][14][15] thrombocytopenia, [15][16][17] and hemophagocytic syndrome. 5,7 HHV-7 also infects in infancy or early childhood and infects persistently throughout life.…”

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confidence: 99%

Inverse relationship between human herpesvirus-6 and -7 detection after allogeneic and autologous stem cell transplantation

Miyoshi

Tanaka‐Taya

Hara

et al. 2001

Summary:Human herpesvirus-6 (HHV-6) and -7 were analyzed in 25 and 18 patients with allogeneic (allo) and autologous (auto) stem cell transplantation (SCT), respectively, by weekly examination of viral DNA in peripheral mononuclear cells using semiquantitative PCR and serologic tests up to 12 weeks after SCT. HHV-6 DNA was detected in 29.6% and 27.9% of samples after allo-and auto-SCT, respectively. The proportions of HHV-6-DNA-positive samples increased in week 3 and 4 after allo-SCT, and in week 1 to 3 after auto-SCT. The frequency of HHV-7 DNA detection, however, was higher after auto-SCT (24.7%) than allo-SCT (12.8%) (P Ͻ 0.01). Antibody titer elevation was accompanied by HHV-6 infection in eight of 10 patients. That for HHV-7 was also frequently observed, but not associated with infection in the majority of patients. Five of six patients with Ͼ10 2 copies of HHV-6 DNA (/10 5 cells) on two consecutive occasions were allo-SCT recipients and three showed clinical episodes. Conversely, three of five patients with continuous reactivation of HHV-7 were auto-SCT recipients. Thus, the frequencies of HHV-6 and -7 DNA detection showed an inverse relationship comparing allo-and auto-SCT, suggesting a different mechanism may regulate HHV-6 and -7 reactivation. Bone Marrow Transplantation (2001) 27, 1065-1070. Keywords: HHV-6; HHV-7; stem cell transplantation; PCR; serology Human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) belong to ␤-herpesvirus subfamily. HHV-6 was first isolated from patients with immunodeficiency 1 and HHV-7 was isolated from a healthy adult. 2 It is now believed that HHV-6 and HHV-7 are causative agents of exanthem subitum and febrile illnesses in children. 3,4 HHV-6 infects persistently or latently after the primary infection in salivary glands, lymph nodes, T cells, monocytes/

“…[8][9]11,12,18 However, it has been documented that benign periodic HHV-6 reactivation occurs throughout the post-transplant period. In a study by Cone et al, 12 HHV-6 DNA was detected in PBMC by PCR in all 20 transplant patients and nine of 19 healthy control studies.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11][12][13] In this population, HHV-6 has reportedly been associated with skin rashes, graft-versus-host disease, pneumonitis, sinusitis, febrile episodes, graft failure, encephalitis and in some cases with a fatal outcome. 4 While serological methods are available for determining the presence of HHV-6 infection in healthy individuals, 14 such methods have limited utility in immunocompromised patients.…”

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confidence: 99%

The utility of plasma polymerase chain reaction for human herpes virus-6 among pediatric bone marrow transplant recipients: results of a pilot study

Allen

Tellier

Doyle

et al. 2001

Summary:We evaluated the utility of plasma polymerase chain reaction (PCR) for surveillance of human herpes virus 6 (HHV-6) infection among pediatric bone marrow transplant (BMT) recipients. We used a prospective, non-interventional design involving a study group and controls. BMT recipients and healthy controls were evaluated. BMT subjects had HHV-6 PCR done biweekly for 12 weeks post transplantation, while a single PCR test was done on controls. For the PCR assay, EDTA blood was collected and DNA extracted from whole blood and cell-free plasma using standard procedures. The PCR was first performed on DNA from whole blood and if a positive result was obtained, the test was repeated on the DNA from the plasma. Thirty BMT recipients (13 autologous and 17 allogeneic) were enrolled, on whom a total of 156 PCR tests were performed, while six tests were done on six healthy controls. The median age of BMT subjects was 6.2 years (range 0.5-17.5 years). The median age of the control subjects was 6.6 years (range 2-10 years). Among asymptomatic BMT patients who had PCR surveillance, the positivity rate was 3.3% (1/30) on whole blood and 0% (0/30) on plasma. None of the six healthy subjects had a positive PCR test on whole blood. During the period of the surveillance study, 14 patients had diagnostic evaluations for HHV-6 disease because of clinical symptoms. Two of these patients were diagnosed with disease associated with HHV-6 (graft failure and encephalitis) and had positive PCR tests on whole blood and plasma and whole blood and cerebrospinal fluid, respectively. We conclude that despite the fact that HHV-6 seropositivity rates are high among children, the frequency of HHV-6 plasma PCR positivity is low in pediatric BMT subjects who are asymptomatic for HHV-6 disease. Given that a positive test on plasma is consistent with active infection, this increases the utility of the PCR test as a