Studies of Cytomegalovirus Infection in Renal Allograft Recipients: I. Virus Isolation

Abstract

A prospective study of cytomegalovirus (CMV) infections has been carried out in 28 renal graft recipients. The protocol called for frequent blood and urine sampling during the first year after transplantation, but death or graft loss caused earlier termination in nearly half the patients. In this material 5/7 (71%) susceptible patients developed primary infections and 20/21 experienced a secondary infection (95%). Viruria was detected in 79% and viremia in 43%. The type of blood cell responsible for the viremic phase was studied by separating the blood cells on a density gradient. The polymorphonuclear cell fraction was the most common source of virus but virus could also be recovered from the mononuclear cell fraction. As some samples that were freeze-thawed repeatedly never yielded virus, it would appear that viable cells are needed for virus isolation. In both primary and secondary infections isolation of CMV from blood cells often preceded the isolation of CMV from urine. Among variables tested for a possible relationship to the occurrence of CMV viremia the only one to display such an association was the time at which rejection episodes occurred. In 19/28 such episodes recorded in 19 patients there was a temporal relationship to viremia (p less than 0.03). Seven of the patients experienced clinical symptoms suggestive of CMV infection as fever, cough, myalgia, arthralgia, chest pain and pneumonia. Laboratory signs included elevated amino acid transferase levels, leukopenia and thrombocytopenia and a specific anti-CMV antibody response.

A Prospective Randomized Trial Comparing Sequential Ganciclovir-High Dose Acyclovir to High Dose Acyclovir for Prevention of Cytomegalovirus Disease in Adult Liver Transplant Recipients

“…exerts an immunosuppressant effect that increuea the incidence of other opportunistic infections (21 >o.a tients with tissue invasive disease. This is in contrast to previous reports in which viremia was associated with virtually all cases of CMV disease (22) and suggests that both antiviral agents may in fact influence the recovery rate of CMV from blood samples obtained during CMV disease. The multivariate analysis identified the use of high dose acyclovir alone and donor-seropositivelrecipient-seronegative combinations as risk factors for development of both CMV infection and CMV disease.…”

Serum Antibodies to Individual Cytomegalovirus Structural Polypeptides in Renal Transplant Recipients during Viral Infection

“…However the production of IgM antibody detected by IB in all seroconverted sera was usually delayed with respect to the appearance of IgG seroconversion revealed either by conventional serological procedures or by IB. This finding may account for some of the controversial data present in the literature (5,8,14) on the production of IgM antibody in CMV reinfections or reactivations.…”

Disseminated cytomegalovirus infection. Molecular analysis of virus and leukocyte interactions in viremia.

“…Hence, viremia has been a major focus of intensive investigation. Most studies of separated cell populations have shown CMV to be associated primarily with polymorphonuclear leukocytes (9,10,(16)(17)(18)(19)(20). However, CMV has also been shown to be carried in lesser amounts or less frequently by mononuclear cells (10,(16)(17)(18)(19)(20)22).…”

“…These findings have been confirmed in one instance by electron microscopy (21). However, data also exist to suggest that the virus may be carried in lesser amounts or less frequently by mononuclear cells (10,(16)(17)(18)(19)(20)22). Advances in molecular hybridization technology have now made it feasible to detect CMV genetic material in peripheral blood leukocytes with viral DNA probes (21,23,24).…”

“…Thus far, studies of separated cell populations using virus culture indicate that most of the infectious virus is associated with polymorphonuclear leukocytes (9,10,(16)(17)(18)(19)(20). These findings have been confirmed in one instance by electron microscopy (21).…”