Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections.
BACKGROUND
Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients.


METHODS
The CMV doubling time of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥ 18,200 IU/mL) were explored using mathematical simulation.


RESULTS
The overall median doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load at diagnosis, compared to 1.4% and 4.3% if the doubling time varies as observed in our cohort. Consistently, 1.9% of recipients screened weekly had a high diagnostic virus load.


CONCLUSIONS
Screening intervals can be extended to 10 days in cohorts with comparable CMV doubling time, whereas shorter than 7 days is required in cohorts with shorter doubling times to maintain pre-emptive screening quality.
Centre for Health and Infectious Disease Research (CHIP), Department of Infectious Diseases and Rheumatology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
I P
IP
Lodding
Department of Hematology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
H
H
Sengeløv
Department of Hematology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark ; Department of Hematology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
C
C
da Cunha-Bang
Department of Cardiology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
M
M
Iversen
Department of Surgery C, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
A
A
Rasmussen
Department of Cardiology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
F
F
Gustafsson
Centre for Health and Infectious Disease Research (CHIP), Department of Infectious Diseases and Rheumatology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
J G
JG
Downing
Centre for Health and Infectious Disease Research (CHIP), Department of Infectious Diseases and Rheumatology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
J
J
Grarup
Department of Clinical Microbiology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
N
N
Kirkby
Centre for Health and Infectious Disease Research (CHIP), Department of Infectious Diseases and Rheumatology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
C M
CM
Frederiksen
Research Department of Infection and Population Health, University College of London (UCL), Royal Free Hospital Rowland Hill Street London NW3 2PF, United Kingdom.
A
A
Mocroft
Department of Nephrology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
S S
SS
Sørensen
Centre for Health and Infectious Disease Research (CHIP), Department of Infectious Diseases and Rheumatology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
J D
JD
Lundgren
D000328:Adult; D015331:Cohort Studies; D003198:Computer Simulation; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000821:virology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014180:Transplantation; D014779:Virus Replication
Cytomegalovirus; Doubling time; Haematopoietic stem cell transplantation; PCR; Pre-emptive treatment; Solid organ transplantation