604 CYTOMEGALOVIRUS INFECTION AND RENAL TRANSPLANTATION
SIR,-Some highly contentious statements have been made about the clinical manifestations of cytomegalovirus (c.M.v.) infection, highlighted by Simmons" report of 8 fatal cases. Reviews of these papers, including your editoriaI,2 have accepted much of this work without criticism. For instance, Betts et aI.3 report "5 individuals [with c.M.v. infections] who were very ill with prolonged fever, pneumonia and elevated SGOT levels", but they confess "on occasion, it was difficult to differentiate these symptoms and signs from rejection (5 patients), azathioprine induced hepatic disease (2 patients), lobar pneumonia and leucocytosis (2 patients)". We suggest that such differentiation is impossible. Your editorial states that for the diagnosis of c.M.v. infection "immunofluorescent tests are greatly preferable to the less sensitive complement-fixation (c.F.) test". The studies on c.M.v. cited were based almost exclusively on the c.F. test. To assess more fully the place of c.M.v. infection in the renaltransplant recipient we have followed up prospectively our patients since May, 1977. Between May, 1977, and December, 1978, we did sixty-eight transplants on 63 patients. 41 patients, with functioning grafts, have been followed up for more than 15 weeks. Sera were examined, by an immunofluorescent method (i.F.) for IgG and IgM antibodies to the antigen of c.M.v. strain AD169, weekly for 2 months and then every 1-3 weeks. TABLE
I-IgG
TITRES IN FIRST WEEK AFTER TRANSPLANTATION
than 12 months and their titres have all fallen to 2 of the 35 "responders" had only a brief four-fold rise and have since fallen to titres of < 1/8. These 8 patients are the only ones whose titres have returned to consistently low levels. As a group they had few rejection episodes and less than average amounts of prednisolone. Infection has not been a problem, but they may be a subgroup whose humoral system is in some way defective. This group may tolerate excessive immunosuppression less well and be more susceptible to overwhelming opportunistic infection. It is possible that Simmons’ fatal cases of "c.M.v. infection" belong to this subgroup of non-responders. (6 of this group were HLA-B12; only 5 of the other 33 responders were B12.) Only 1 patient in the study period had any symptoms which seemed likely to be due to c.M.v. (remittent fever for 2 weeks) and 1 possibly had an episode of left-ventricular failure due
up for
more
1/8. Furthermore,
to
myocarditis.
In summary, the failure to detect c.M.v. antibody preoperatively does not exclude previous c.M.v. infection. At least 90% of our population have evidence of a previous infection, so primary infection is likely to be uncommon. Thus previous reports of c.M.v. infection transmitted by donor kidney or fresh bloodtransfusion must be interpreted with great caution. Vaccination against c.M.v. would seem to have little to offer our patients; donor kidneys are difficult enough to obtain without our being expected to find "seronegative" donors. Renal Unit and Department of Clinical Virology,
Guy’s Hospital, London SE1 9RT
GUY NEILD TREVOR SOUTHEE
ORAL Rh TREATMENT FOR SEVERELY IMMUNISED MOTHERS
Only 7 of the 63patients (11%), in the first week after transplantation, had an IgG titre of less than 1/8 (table i). This suggests that at least 89% of this population had had a previous c.mt.v. infection. Previous studies, with c.F. tests, have found that 30-70% of transplant recipients have preoperative titres of < 1/8. Postoperative seroconversion has often been equated with evidence of primary infection; a four-fold rise from a preoperative titre of 1/8 indicates either secondary infection or, reactivation of a latent virus. We have so far been both specific IgG titres (by I.F.) and c.F. titres on preoperative samples in 35 patients (table n). (In our normal blood-donor population 33% have IgG
SIR,-Some highly contentious statements have been made about the clinical manifestations of cytomegalovirus (c.M.v.) infection, highlighted by Simmons" report of 8 fatal cases. Reviews of these papers, including your editoriaI,2 have accepted much of this work without criticism. For instance, Betts et aI.3 report "5 individuals [with c.M.v. infections] who were very ill with prolonged fever, pneumonia and elevated SGOT levels", but they confess "on occasion, it was difficult to differentiate these symptoms and signs from rejection (5 patients), azathioprine induced hepatic disease (2 patients), lobar pneumonia and leucocytosis (2 patients)". We suggest that such differentiation is impossible. Your editorial states that for the diagnosis of c.M.v. infection "immunofluorescent tests are greatly preferable to the less sensitive complement-fixation (c.F.) test". The studies on c.M.v. cited were based almost exclusively on the c.F. test. To assess more fully the place of c.M.v. infection in the renaltransplant recipient we have followed up prospectively our patients since May, 1977. Between May, 1977, and December, 1978, we did sixty-eight transplants on 63 patients. 41 patients, with functioning grafts, have been followed up for more than 15 weeks. Sera were examined, by an immunofluorescent method (i.F.) for IgG and IgM antibodies to the antigen of c.M.v. strain AD169, weekly for 2 months and then every 1-3 weeks. TABLE
I-IgG
TITRES IN FIRST WEEK AFTER TRANSPLANTATION
than 12 months and their titres have all fallen to 2 of the 35 "responders" had only a brief four-fold rise and have since fallen to titres of < 1/8. These 8 patients are the only ones whose titres have returned to consistently low levels. As a group they had few rejection episodes and less than average amounts of prednisolone. Infection has not been a problem, but they may be a subgroup whose humoral system is in some way defective. This group may tolerate excessive immunosuppression less well and be more susceptible to overwhelming opportunistic infection. It is possible that Simmons’ fatal cases of "c.M.v. infection" belong to this subgroup of non-responders. (6 of this group were HLA-B12; only 5 of the other 33 responders were B12.) Only 1 patient in the study period had any symptoms which seemed likely to be due to c.M.v. (remittent fever for 2 weeks) and 1 possibly had an episode of left-ventricular failure due
up for
more
1/8. Furthermore,
to
myocarditis.
In summary, the failure to detect c.M.v. antibody preoperatively does not exclude previous c.M.v. infection. At least 90% of our population have evidence of a previous infection, so primary infection is likely to be uncommon. Thus previous reports of c.M.v. infection transmitted by donor kidney or fresh bloodtransfusion must be interpreted with great caution. Vaccination against c.M.v. would seem to have little to offer our patients; donor kidneys are difficult enough to obtain without our being expected to find "seronegative" donors. Renal Unit and Department of Clinical Virology,
Guy’s Hospital, London SE1 9RT
GUY NEILD TREVOR SOUTHEE
ORAL Rh TREATMENT FOR SEVERELY IMMUNISED MOTHERS
Only 7 of the 63patients (11%), in the first week after transplantation, had an IgG titre of less than 1/8 (table i). This suggests that at least 89% of this population had had a previous c.mt.v. infection. Previous studies, with c.F. tests, have found that 30-70% of transplant recipients have preoperative titres of < 1/8. Postoperative seroconversion has often been equated with evidence of primary infection; a four-fold rise from a preoperative titre of 1/8 indicates either secondary infection or, reactivation of a latent virus. We have so far been both specific IgG titres (by I.F.) and c.F. titres on preoperative samples in 35 patients (table n). (In our normal blood-donor population 33% have IgG
