“Cytomegalovirus disease” in renal allograft recipients: Is human herpesvirus 7 a co-factor for disease progression?

Abstract

Fifty-six renal allograft recipients were studied prospectively for 3 months or longer after transplant. The polymerase chain reaction (PCR) was used to screen peripheral blood leucocyte (PBL) specimens for CMV, human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7) DNA (DNAemia) in 67 healthy controls and in serial (fortnightly) PBL specimens from the 56 allograft recipients. None of the healthy controls had detectable CMV DNAemia, although HHV6 and HHV7 DNAemia was found in 7% and 9% of individuals respectively. In contrast, DNAemia due to CMV, HHV6 and HHV7 was found in 50%, 36% and 39% of patients respectively, at some time during the post-transplant period. Of the 28 patients who had CMV DNAemia, eight developed "CMV disease". The risk of progression to "CMV disease" was increased in patients with concurrent DNAemia to all three viruses (relative risk 3.7; 95% CI 1.3-10.5). The relative risk of "CMV disease" for patients with concurrent CMV and HHV7 was also increased (RR = 3.5; 95% CI = 1.1-11.6), while the association between CMV and HHV6 was inconclusive (RR = v2.1; 95% CI = 0.7-6.6). The first 26 patients recruited to the study also had serial serum samples tested for antibody responses to the three viruses. "CMV disease" was associated with rising antibody titres to HHV7 (Fisher's exact test, P = 0.02), and weakly so with HHV6 (P = 0.07). It is concluded that in patients with CMV DNAemia, concurrent infection/reactivation HHV7 (and possibly HHV6) is associated with an increased risk of progression to "CMV disease".

Detection of Human Herpesvirus 7 DNA by Loop-Mediated Isothermal Amplification

“…Primary HHV-7 infection usually has a benign and self-limited clinical course but can in rare instances cause several severe complications (16,18). Furthermore, although the clinical features of HHV-7 reactivation remain obscure, several manifestations, including fatality due to viral reactivation, have been reported for organ transplant recipients (3,5,8,12,17,21). It is therefore important to establish a reliable rapid diagnostic procedure for the detection of active HHV-7 infection.…”

The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation

“…The principal indirect effect of HHV-6 and HHV-7 infection in association with organ transplantation results from their potential to exacerbate CMV infection and disease 32,[43][44][45][46] and their influence on the occurrence of other opportunistic infections such as invasive fungal disease. 33,34 These indirect effects of HHV-6 and HHV-7 infection are partly influenced by their impact on the host immune system.…”

Management of cytomegalovirus infection after liver transplantation

“…33,34 In addition to pharmacological agents, pretransplantation and posttransplantation events that contribute to further enhance immunosuppression and/or the reactivation of latent CMV infection in the transplant recipient have been identified. For example, in liver transplant recipients, CMV disease occurring later in the posttransplantation period may be noted in association with fulminant hepatitic failure, 25 recurrent hepatitis C virus infection, HHV-6 and HHV-7 infection, 35,36 and retransplantation for acute rejection. 11…”