Asymptomatic Cytomegalovirus Infection Research Articles

Rapid Shell Vial Culture and Tissue Histology Compared With Serology for the Rapid Diagnosis of Cytomegalovirus Infection in Liver Transplantation

Sixty-six patients who had undergone 78 liver transplantations, with no detectable cytomegalovirus (CMV) infection before transplantation, were studied to assess the value of CMV serology compared with the rapid detection of the virus in shell vial cell cultures or histology for the diagnosis of (1) the first evidence of infection, (2) symptomatic disease, and (3) asymptomatic infection. Of 28 evaluable patients, shell vial cell culture assay and histologic findings provided the first evidence of CMV infection earlier in 22 (79%) or at the same time as the serologic response in 5 (18%). Serologic results yielded the first indication of CMV infection in only 1 of these 28 patients (3%). Of 17 evaluable transplantations in 15 patients in whom symptomatic invasive disease developed, shell vial culture or histology provided a laboratory diagnosis of CMV infection earlier or at the same time as serologic responses in 16 (94%). Similarly, shell vial culture or histology provided evidence of CMV infection in 10 of 11 patients (91%) who had asymptomatic CMV infection and remained asymptomatic. Urine surveillance cultures yielded the first evidence of CMV infection in 14 of 19 patients who initially had an asymptomatic infection, of which 6 became symptomatic. Culturing of the blood with use of the rapid shell vial technique showed that viremia preceded CMV organ involvement in 7 of 10 patients. We recommend culture by the shell vial assay as the most rapid and sensitive method of determining CMV infection in liver transplant patients.

Cytomegalovirus infection complicating immunosuppressive treatment.

Two case reports in this issue of the Journal describe remarkably similar clinical presentations. The patients (a 37 year old woman1 with systemic lupus erythematosus and a 49 year old man2 with glomerulonephritis and pulmonary haemorrhage) presented with lung involvement which improved after immunosuppressive therapy was instituted. The patients were maintaoned on lower doses of immunosuppressives and remained stable. Once their condition was under control, episodes of severe haemoptysis occurred four weeks and six weeks after initial presentation. Investigation of both patients lead to lung biopsy which revealed inclusion bodies within the lung suggestive of cytomegalovirus (CMV) infection. One patient survived while the other died. The authors discuss whether the immunosuppression given might have reactivated CMV or whether the virus was transmitted by blood transfusion. They also discuss the pathogenesis of CMV infection of the lung. Cytomegalovirus is a common infectious agent which is well adapted to hosts with normal immune responses. However, in immunosuppressed patients, latent virus can reactivate to lead to dissemination of infection and ultimately life-threatening disease. Such reactivations are the usual means by which CMV affects bone marrow transplant3'4 and acquired immune deficiency syndrome (AIDS) patients5 in whom pre-existing immunity confers little protection. In renal transplant patients, most reactivations of virus are asymptomatic while primary infections (transmitted with the donor kidney) are frequently life-threatening.6 Re-infection of patients with pre-existing antibody also occurs7 and disease can develop in a proportion. The virus can also be transmitted by blood transfusion and the serological status of the donor (seropositive) and of the recipient (seronegative) represent markers of susceptibility to CMV spread by blood transfusion.8 The pathogenesis of the various clinical conditions caused by CMV is not completely understood. Involvement of the retina and gastrointestinal tract for example, appears to be mediated by active virus replication. In contrast, CMV can be detected readily in urine and saliva, without the accompaniment of symptoms.3'9-11 In the mouse model of CMV, the development of CMV pneumonitis requires a host immune response which can be suppressed by continued administration of cyclophosphamide12 while the presence of graft versus host disease13 can turn an asymptomatic CMV infection into one with fatal outcome. What lessons can be learned from these case reports which could ultimately benefit patients? Since CMV is the single commonest cause of death in bone marrow transplant patients14 and is a major cause of mortality and morbidity in renal transplant patients,15 16 physicians caring for such individuals should already be following standard protocols to detect this virus. Those caring for other groups of immunosuppressed patients may be stimulated by the two case reports to follow such guidelines, the principles of which are straightforward. First, when a patient presents with a clinical condition which may require therapeutic immunosuppression, his antibody status to CMV should be determined. The absence of antibody indicates that he is seronegative and so not infected with this virus and every attempt should be made to give him only blood products which have been shown to lack antibodies to CMV. The presence of antibody within the patient does not indicate immunity in the protective sense but is a marker for latent CMV infection which may reactivate under the influence of immunosuppressive drugs.15 Second, once immunosuppression has been administered, serology has no further diagnostic role to play since it is absurd to assume that such patients will be able to mount appropriate immune

Evaluation of a prescreening blood donor program for prevention of perinatal transfusion-acquired cytomegalovirus (CMV) infection.

The purpose of this study was to evaluate the efficacy of a prescreened CMV seronegative blood donor group in preventing transfusion-acquired CMV infection in premature infants in the perinatal period. Group 0 donors with known CMV seronegative status were recruited to supply blood to the neonatal intensive care nurseries. One hundred and twenty-seven low birth weight infants born of CMV seronegative mothers remained seronegative when blood for transfusion was screened for CMV antibody. Twenty two infants shared six units of CMV seropositive blood due to technical errors or poor sensitivity of the test kit in the initial phase of the study. Fifteen of these patients were in the study group. One infant died of immaturity at four weeks of age and two of the remaining 14 showed asymptomatic CMV infection. Another infant who received granulocyte concentrates from CMV seropositive donors had symptomatic CMV infection. Throughout the 24 month study period, blood supply to the ICN was adequate and timely. The donor seroconversion rate was 0.7% per annum. Only one infant was exposed to the risk of CMV infection due to donor seroconversion. We conclude that the prescreening donor program is a sensible and efficient approach for providing CMV seronegative blood in neonatal transfusion therapy.

A clinical pathologic study of hearing loss in congenital cytomegalovirus infection

Cytomegalovirus (CMV) infection is currently reported as the most common cause of congenital viral induced deafness. However, few systematic studies of the audiovestibular sequelae of this infection are present in the literature. A clinical pathologic study was conducted from 1976 to 1982 to evaluate this. Fifty-two pairs of infant and children's temporal bone studied demonstrated no evidence of CMV endolabyrinthitis even in the single case with evidence of extensive congenital CMV infection. Over 2,000 umbilical cord sera were screened to detect asymptomatic CMV infection with an incidence of 0.38% (and slightly greater than 1% when extrapolated to correct for the sensitivity of the method of detection) in a central Pennsylvania study population. No sensorineural abnormalities were detected in five asymptomatic children and 30 control children. However, three out of six (50%) infants, symptomatic at birth and followed to a mean age of 5.5 years, showed significant and progressive sensorineural loss and vestibular deficits.

Diagnosis of severe fetal cytomegalovirus infection from amniotic fluid in the third trimester of pregnancy

rr~~~~ ARE, at present, two reports in the literature describing the isolation of cytomegalovirus (CMV) from amniotic fluid, obtained during pregnancy by means of amniocentesis.’ In both cases there was a severe CMV infection of the mother with an asymptomatic infection in the neonate. We present a case in which CMV was recovered from the amniotic fluid at 32 weeks of amenorrhea in a woman with an asymptomatic CMV infection, who was eventually delivered of an infant with a severe congenital CMV syndrome. A 19-year-old, Caucasian, primigravid woman was admitted at 30 weeks of pregnancy with the diagnosis of insufficient fetal growth. The course of pregnancy had been uneventful and, in particular, there was no history of malaise or fever during pregnancy. The uterus was about the size of a 28 weeks’ pregnancy with a single fetus in cephalic position. The biparietal diameter of the fetal head as measured by ultrasound was 6.8 cm, being far below the fifth percentile of the usual standard curve, and the fetal chest area was with 40 sq cm on the fifth percentile of our reference curve. The routine laboratory tests revealed no abnormalities, except for a slightly elevated serum bilirubin concentration (18 pmoles/L). On serologic screening for infections, the complement-fixation

Asymptomatic cytomegalovirus infection in children with leukemia.

Forty-two children with acute leukemia were studied to determine the incidence and course of cytomegalovirus infection. Five patients excreted the virus in the urine, saliva, or both. Three others had complement-fixing antibodies to cytomegalovirus. There was no clinical evidence of infection. The incidence of infection did not differ from that found in other studies in nonleukemic and leukemic children.

Cytomegalovirus Infection In Patients Receiving Long-Term Hemodialysis

To the Editor.— In their communication ( 212 :1350, 1970), Siddiqui et al reported that causes of death in patients receiving long-term hemodialysis were intracranial hemorrhage, convulsive disorders of unknown etiology, hyperkalemia, infection, and others. Attention was concentrated on bacterial infection, but viral infection, especially cytomegalovirus (CMV) infection, must be considered, as in the case of a 13-year-old boy who suffered from chronic glomerulonephritis and was treated by hemodialysis from January 1970 onward. Complement-fixing antibody titers against CMV rose significantly in November. At that time, serum transaminase levels were elevated, but no clinical illness was seen. Immunofluorescent antibody titers to Epstein-Barr virus were not changed and Australia antigen was negative throughout the period of hemodialysis. Elevation of serum transaminase levels in this case was thought to be due to CMV infection. It is known that asymptomatic CMV infection may follow blood transfusion. 1,2 Since the report by Hanshaw et al, 3

Studies of cytomegalovirus infection in newborn infants.

Histological examinations of post mortem specimens, virus isolation and the indirect immunofluorescent test for cytomegalovirus macroglobulin were carried out in newborn infants. The most reliable method for a diagnosis of congenital cytomegalovirus infection in newborn infants was virus isolation, but the detection of cytomegalovirus IgM antibody by indirect immunofluorescent method could be used for a diagnosis of asymptomatic cytomegalovirus infection.

Asymptomatic cytomegalovirus infection following blood transfusion in tumor surgery

Asymptomatic cytomegalovirus infection following blood transfusion in tumor surgery

Asymptomatic Cytomegalovirus Infection Following Blood Transfusion in Tumor Surgery

Forty-one patients who underwent whole blood transfusion during aggressive surgical excision of solid tumors were followed up prospectively for evidence of active cytomegalovirus (CMV) infection. Fourfold or greater elevation in complement-fixing antibody titers developed in 13 (32%) of the patients within 8 to 16 weeks after surgery. Cytomegalovirus was isolated from one of these patients. The incidence of antibody rise correlated best with volume of blood received, but it did not appear to be related to either the time of storage of transfused blood or the type of operative procedure performed. No clinical illness could be attributed to CMV infection in these patients.