In a prospective study of 148 children from urbanized southern Finland 3 were found to be congenitally and 48 perinatally infected with cytomegalovirus (CMV), while 6 developed "late" infection during the first year of life. During pregnancy and the first year after delivery 23 of the mothers had no CMV antibodies; none of the children of these seronegative mothers developed any type of CMV infection. Fresh blood exchange transfusions did not increase the risk of CMV infection. The data support the hypothesis that the mother is the source of perinatal CMV infection. Children with a low birthweight not due to prematurity, and first children seem to run a greater risk of acquiring perinatal CMV infection. If the child is breast fed up to the age of 2 months the risk seems to be increased. Perinatal CMV infection gave rise to no symptoms or signs and had no effect on growth or on motor and psychosocial development during the first year of life.
Sequential specimens from nine allograft recipients were examined by using a variety of methods to detect primary cytomegalovirus (CMV) infection as rapidly as possible posttransplantation. Sera were examined for immunoglobulin G (IgG) and IgM antibodies by immunoblotting, enzyme immunoassay, and immunofluorescence and also by complement fixation, latex agglutination, and an immunofluorescence test for antibody to CMV early antigen. Urine and occasionally blood, tissue, and other specimens were centrifuged onto cell cultures to enhance CMV infectivity. Eight of the nine patients showed laboratory evidence of primary CMV infection, and CMV was isolated from seven of the eight: in no case was virus isolated before seroconversion had become evident. However, serological tests differed in their abilities to detect antibody response to CMV infection in different patients; while immunoblotting, latex agglutination, and enzyme immunoassay for IgG antibodies generally detected seroconversion before complement fixation, this was not invariably the case. At present, optimal laboratory detection of CMV infections in these patients can be achieved only by a combination of serological methods and virus isolation.
Sera were obtained at intervals from 172 hospital employees for measurement of cytomegalovirus (CMV) complement fixation (CF) and indirect hemagglutination antibody. No fourfold rises or falls in titer were seen over a 19- to 27-month period among 71 employees with initially positive CMV CF titers. The concurrence rate between the CMV CF and the indirect hemagglutination antibody tests in identifying seronegative personnel was 96%. Five seroconversions were identified during an average follow-up period of 15 to 17 months per person among 65 pediatric nurses whose CMV CF titers had initially been less than 1:8. No seroconversions were seen during an average follow-up period of 29 months per person among 27 hospitad little patient contact. The rate of acquisition of CMV infections in seronegative pediatric nurses was 4.1 to 7.7% per year. Sera from 9 of the 172 employees studied (5.2%) gave inconsistent results at the lower limits of the CF test.
BACKGROUND--New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS--Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS--Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS--CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment.
AIMS--To study the association between cytomegalovirus (CMV) excretion and interstitial pneumonitis in allogeneic bone marrow transplant (BMT) recipients, with reference to donor and recipient CMV antibody response. METHODS--The incidence of CMV excretion was prospectively studied in 62 allogeneic bone marrow transplantations performed on adults and children. All recipients received CMV seronegative blood products. Prophylaxis with high dose acyclovir and CMV immune globulin was given to high risk patients (donor or recipient, or both, CMV seropositive). RESULTS--CMV excretion was detected in eight of 26 (31%) high risk patients but in only one of 36 low risk patients (donor and recipient both CMV seronegative). Five of the eight (63%) excretors in the high risk category developed CMV, of whom four (80%) belonged to the seropositive recipient/seronegative donor group, and included the three CMV seropositive recipients whose CMV complement fixation antibody titres were 64 or greater before transplantation. CONCLUSIONS--These findings suggest that there is a subgroup of patients at especially high risk of developing CMV.
This study investigated the incidence of acquired cytomegalovirus (CMV) infection in very low birth weight infants (VLBWI) given CMV seropositive blood, and sought to determine whether filtering and irradiation of blood products could help prevent CMV infection and the time required to clear passively-derived anti-CMV IgG among 80 VLBWI transfused with filtered-irradiated blood, 20 VLBWI transfused with nonfiltered-nonirradiated blood and 26 nontransfused VLBWI. CMV IgG and IgM values were obtained from all blood products prior to transfusions, and from VLBWI at birth until the infants became seronegative. Urine was obtained for CMV culture at birth and every 3-4 weeks until 12 weeks after the final transfusion. The incidence of CMV IgG seropositivity among the 126 infants at birth and the blood products given were 96% and 95%, respectively. The incidence of acquired CMV infection was 4/100 (4%) in the transfused group: 2/80 (2.5%) and 2/20 (10%) in the filtered-irradiated and nonfiltered-nonirradiated transfusion groups, respectively. Approximately 9-10 months elapsed to clear passively acquired CMV IgG. The irradiation and filtering of the blood products did not seem to decrease the transfusion-related CMV infection rate in Korea among VLBWI, however, further validation is recommended in a larger cohort of infants.
Cytomegalovirus; Blood Transfusion; Infant, Very Low Birth Weight
Transfusion-acquired cytomegalovirus (CMV) infections should be prevented in seronegative immunocompromised patients by providing blood products from donors who are also seronegative. Latex agglutination was investigated as a simple and rapid method for detecting antibody against CMV. Latex beads were coated with CMV antigen, incubated for 8 min at room temperature with 25 microliter of sera, and examined for agglutination. The sensitivity and specificity of latex agglutination was compared with that of indirect hemagglutination (IHA, Cetus Corp., Emeryville, Calif.) and enzyme immunoassay (EIA) with sera from 604 random blood donors or patients. Of 327 serum samples shown to be seronegative by EIA and IHA, 327 had a latex agglutination titer of less than 1:4 (specificity, 100%). Of 236 serum samples with detectable antibody by EIA and IHA, 228 had a latex agglutination titer of 1:4 or greater (sensitivity, 97%). Plasma collected with EDTA, heparin, or citrate was satisfactory for latex agglutination. Latex agglutination results correlated quantitatively with those of EIA, and the test also detected fourfold or greater rises in antibody with paired sera from six patients with posttransfusion CMV infections. Latex agglutination is a sensitive and specific assay that is rapid and simple to perform and should be effective in selecting seronegative blood donors to prevent posttransfusion CMV infections in seronegative recipients.
The precise role of cytomegalovirus (CMV) infection in contributing to outcomes in critically ill immunocompetent patients has not been fully defined.
Studies in which critically ill immunocompetent adults were monitored for CMV infection in the intensive care unit (ICU) were reviewed.
CMV infection occurs in 0 to 36% of critically ill patients, mostly between 4 and 12 days after ICU admission. Potential risk factors for CMV infection include sepsis, requirement of mechanical ventilation, and transfusions. Prolonged mechanical ventilation (21 to 39 days vs. 13 to 24 days) and duration of ICU stay (33 to 69 days vs. 22 to 48 days) correlated significantly with a higher risk of CMV infection. Mortality rates in patients with CMV infection were higher in some but not all studies. Whether CMV produces febrile syndrome or end-organ disease directly in these patients is not known.
CMV infection frequently occurs in critically ill immunocompetent patients and may be associated with poor outcomes. Further studies are warranted to identify subsets of patients who are likely to develop CMV infection and to determine the impact of antiviral agents on clinically meaningful outcomes in these patients.
Cytomegalovirus (CMV) is the most common congenital viral infection, occurring in 0.4%–2.3% of all live births. The clinical manifestations of CMV are multiorgan involvement. Currently, the numbers of studies of hepatic CMV infection in immunocompetent infants are insufficient and little information exists in the medical literature about the hepatic manifestations and complications of CMV.
Patients and Methods:
Nine infants diagnosed with hepatic CMV infection were included in the study. The diagnosis was based on the presence of IgM anti-CMV antibodies titer in serum and detection of CMV-DNA in blood. The authors identified clinical characteristics, biochemical characteristics, immunologic markers, and the outcome of hepatic CMV with or without treatment.
Jaundice was the most common clinical feature of CMV infection in infancy (100%). Hepatic abnormalities in the form of cholestasis (defined as a serum conjugated bilirubin concentration greater than 17.1 μmol/L or greater than 20% of the total serum bilirubin) were found in all patients (100%), hepatitis (77%), hypoalbuminemia (55%), elevated alkaline phosphatase, and gamma-glutamyltransferase (77%). Other findings showed hepatosplenomegaly (44%), thrombocytopenia (22%) and low birth weight (11%) The treatment of hepatic CMV infection was indicated in 66% and was not indicated in 33%. Both of them had resolved cholestasis and hepatitis.
Jaundice and cholestasis were the most common clinical features of hepatic CMV infections. Hepatic CMV infection in young infants is often a self-limited illness that does not require antiviral therapy. Most of the patients with hepatic CMV infection had a favorable outcome.
Alanine aminotransferase; cytomegalovirus; polymerase chain reaction
In a prospective study, 139 serial blood samples from 15 transplant recipients were assessed for the presence of cytomegalovirus (CMV) by virus isolation (CMV viremia) and by direct staining of CMV antigens (CMV Ag) in blood leukocytes (CMV antigenemia). CMV was isolated from 23 samples, whereas CMV Ag was detected in 44 specimens. All positive samples were from a total of nine patients who were diagnosed as having active CMV infections. In seven patients, active CMV infections were diagnosed by virus isolation from blood and urine and by a significant rise of CMV-specific antibodies. In these patients, 21 of the 23 blood samples which were positive for CMV by cell culture were also positive by direct CMV Ag detection. Moreover, CMV Ag were detected in 23 of the 116 culture-negative samples. Twenty of these samples were from the acute phase of infection in the same seven patients. The remaining three CMV Ag-positive specimens were from the other two patients, from whom CMV was not isolated but who had serological evidence of concomitant active CMV infections. These results suggest that direct detection of CMV Ag in peripheral blood leukocytes is as specific as and more sensitive than current isolation techniques. Furthermore, by its sensitivity and inherent rapidity the antigen detection test proved to be the earliest diagnostic marker of active CMV infection in eight of the nine patients. Finally, it was shown that monoclonal antibodies to CMV immediate early antigens are a prerequisite for demonstration of CMV antigenemia.
Little is known about cytomegalovirus (CMV) infection after face transplantation, since only two of the 11 cases of face transplantation reported worldwide have documented a CMV infection after transplantation. Herein, we present the first report of a composite-tissue face allotransplant recipient at high risk for CMV infection (D+/R− [CMV serpositive donor positive/CMV seronegative receptor]) undergoing preemptive treatment. Preemptive treatment was safe and effective for controlling CMV infection and thus promoting early acquisition of a CMV-specific immune response that protected the patient from late-onset CMV disease.
Despite antiviral prophylaxis, a high percentage (over 90%) of heart transplant patients experience active cytomegalovirus (CMV) infection, diagnosed by detection of viral DNA in peripheral blood polymorphonuclear leukocytes within the first few months posttransplantation. Viral DNA was detected in mononuclear cells prior to detection in granulocytes from CMV-seropositive recipients (R+) receiving a heart from a CMV-seropositive donor (D+). Based on assessment of systemic infection in leukocyte populations, both R+ subgroups (R+/D− and R+/D+) experienced a greater infection burden than the R−/D+ subgroup, which was aggressively treated because of a higher risk of acute CMV disease. Despite widespread systemic infection in all at-risk patient subgroups, CMV DNA was rarely (<3% of patients) detected in transplanted heart biopsy specimens. The R+ patients more frequently exceeded the 75th percentile of the CMV DNA copy number distribution in leukocytes (110 copies/105 polymorphonuclear leukocytes) than the R−/D+ subgroup. Therefore, active systemic CMV infection involving leukocytes is common in heart transplant recipients receiving prophylaxis to reduce acute disease. Infection of the transplanted organ is rare, suggesting that chronic vascular disease attributed to CMV may be driven by the consequences of systemic infection.
Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+)-patients with D(+) or D(-) donors.
We prospectively evaluated 73 consecutive KT-patients [48 R(+), 25 D(+)R(-)] undergoing routine testing for CMV replication as part of a preemptive strategy. We compared CMV-specific interferon-γ (IFN-γ) responses of CD4+CD3+ lymphocytes in peripheral blood mononuclear cells (PBMC) using three different antigen preparation (CMV-lysate, pp72- and pp65-overlapping peptide pools) using intracellular cytokine staining and flow cytometry.
Median CD4+ and CD8+T-cell responses to CMV-lysate, pp72- and pp65-overlapping peptide pools were lower in D(+)R(-) than in R(+)patients or in non-immunosuppressed donors. Comparing subpopulations we found that CMV-lysate favored CD4+- over CD8+-responses, whereas the reverse was observed for pp72, while pp65-CD4+- and -CD8+-responses were similar. Concurrent CMV replication in R(+)-patients was associated with significantly lower T-cell responses (pp65 median CD4+ 0.00% vs. 0.03%, p = 0.001; CD8+ 0.01% vs. 0.03%; p = 0.033). Receiver operated curve analysis associated CMV-pp65 CD4+ responses of > 0.03% in R(+)-patients with absence of concurrent (p = 0.003) and future CMV replication in the following 8 weeks (p = 0.036). GCV-resistant CMV replication occurred in 3 R(+)-patients (6.3%) with pp65- CD4+ frequencies < 0.03% (p = 0.041).
The data suggest that pp65-specific CD4+ T-cells might be useful to identify R(+)-patients at increased risk of CMV replication. Provided further corroborating evidence, CMV-pp65 CD4+ responses above 0.03% in PBMCs of KT patients under stable immunosuppression are associated with lower risk of concurrent and future CMV replication during the following 8 weeks.
AIM—To time the onset
of cytomegalovirus (CMV) infection in patients (n=39) with CMV
associated neonatal cholestasis by analysing CMV DNA on Guthrie cards
sampled at 3 days of age.
was diagnosed by serology/urine isolation or by CMV DNA detection
(polymerase chain reaction) in liver biopsy specimens. In order to time
the infection dry blood filter paper discs were punched out from stored
Guthrie cards. After phenol-chloroform extraction CMV DNA was detected
by nested polymerase chain reaction.
RESULTS—All cards from
control children (n=8) with congenital CMV tested positive; none of the
negative controls (n=4) did so. Two of 39 cholestatic infants were CMV
DNA positive; their mothers had serological signs compatible with
infection during the second half of the pregnancy. All other
cholestatic infants tested negative.
was not detected in most of the children using Guthrie cards,
suggesting that infection developed at or soon after birth.
In a series of 61 consecutive patients undergoing heart, heart and lung, and lung transplantation, 24 patients were known to be cytomegalovirus (CMV) antibody negative on the day of transplantation. Enzyme linked immunosorbent assays (ELISA) for CMV IgG were performed on donor samples on the day of operation. In 16 of the 24 susceptible patients the test was negative and the only preventive measure taken was the use of blood and blood products from CMV-antibody negative blood donors. None of these patients acquired primary infection with CMV. In another six patients the donor serum was found to contain CMV specific IgG, and in these patients, including one heart and lung transplant recipient, prophylaxis with CMV specific hyperimmune globulin was given. All six patients developed CMV IgM antibodies and in five there was an associated but clinically mild illness. None of these patients required treatment. In the remaining two patients ELISA tests on the donor sera gave equivocal results and hyperimmune globulin was withheld. Both patients developed primary CMV infection of greater severity than those given hyperimmune globulin and one required treatment. Reference tests confirmed that the donor sera contained CMV antibodies. Primary CMV infection in susceptible patients after heart transplantation can be avoided by the use of screened blood and blood products where the organ donor is seronegative to CMV and it can be improved by the use of prophylactic hyperimmune globulin where the donor is CMV antibody positive.
The role of specific cell-mediated immune responses in human cytomegalovirus (CMV) infections was studied by an in vitro lymphocyte transformation test, using a whole blood culture. CMV-induced in vitro lymphocyte proliferation was mainly dependent on the presence of sensitized T-cells. Three of five seronegative patients with B-cell deficiency showed positive lymphocyte responses to CMV antigen. In contrast, a patient with ataxia-telangiectasia who was shedding the virus in urine did not show a cellular response to either CMV or phytohemagglutinin. Age-related differences were found in the CMV lymphocyte transformation test. The responses were generally low (P less than 0.025) in infants and higher in older children and adults. CMV lymphocyte transformation responses were lower in 15 children who were excreting CMV in urine when tested than in 17 seropositive children who were not excreting the virus.
To determine the incidence of active cytomegalovirus (CMV) infection after organ transplantation and its relationship with the immune system, 55 renal and 14 cardiac transplant recipients were closely monitored for active CMV infection (expression of CMV immediate early antigen in granulocytes--antigenemia--and positive cultures) and immune parameters. All 19 CMV-seronegative recipients with seronegative donors remained seronegative, showing that no CMV transmission occurred by leukocyte-depleted blood products. Primary CMV infection occurred in 4 of 11 (36%) patients with positive donors and was symptomatic in 1 (9%) patient. Active CMV infection was found in 29 of 39 (74%) seropositive patients and was symptomatic in 3 (8%) patients. CMV antigenemia was always the first indication of active CMV infection (antigenemia, on average, at day 45 +/- 15; immunoglobulin G rise at day 71 +/- 36; and positive cultures at day 70 +/- 17). Cellular immunity, as measured by lymphocyte proliferation (LPT), proved to be of importance in the prevention of active CMV infection, as 14 of 15 patients with negative LPT obtained active CMV infections with antigenemia and positive cultures, whereas 1 of 10 patients with positive LPT did so (P less than 0.0001).
Human cytomegalovirus (CMV) is a ubiquitous deoxyribonucleic acid virus that commonly infects a majority of individuals at some time during their life. Although most of these CMV infections are asymptomatic, certain patient groups are at risk to develop serious illness. Understanding the epidemiology of this virus is a key element in the development of strategies for preventing CMV disease. However, a number of features of this virus complicate such understanding. Following infection, CMV can remain latent, with subsequent reactivation; the factors controlling latency and reactivation and those factors which determine whether a CMV infection will be symptomatic are unknown. CMV disease can be acquired by natural routes, including horizontal and vertical transmission. Due to the ubiquity of CMV, the delineation of CMV transmission by these natural routes is complicated by the myriad of possible sources. Moreover, concerns over the risk of CMV transmission to the seronegative pregnant female have been raised in relation to preventing CMV transmission. By using molecular biologic techniques, much knowledge has been gained regarding the transmission of CMV disease by natural routes; however, a number of questions remain unanswered. The transmission of CMV infection by natural routes is therefore reviewed and the issues are highlighted. Primary infection, reactivation, and reinfection are the types of active CMV infections that can occur in an immunocompromised patient. In addition to natural routes of infection, introduction of presumably latently infected organs and requirements for multiple blood transfusions increase potential exposure to CMV in the immunocompromised patient. Understanding the epidemiology of CMV infections in the immunocompromised patient is difficult and in some instances controversial due to the complexity and interdependency of a number of factors which lead to CMV infection. In an immunocompromised individual, a major risk factor in developing overt CMV-related disease is associated with the serological status of an organ donor, the recipient, and the blood product given to these patients. In addition, a large body of inferential data supports the transmission of CMV by blood products or organs from seropositive donors; however, the mechanisms by which transmission occurs remain unclear. The possible sources and mechanisms of transmission of CMV infections in the immunocompromised host are reviewed. Lastly, strategies for the ultimate prevention of CMV disease are discussed in light of the epidemiology of CMV infections. To date, these strategies have included use of CMV-seronegative blood products or organs, antiviral agents, and vaccines.(ABSTRACT TRUNCATED AT 400 WORDS)
Immunoglobulin G antibody to human cytomegalovirus (CMV)-specific early antigens (EA-Ab) was determined by the immunoperoxidase antibody technique in several cases of congenital, primary, and reactivated CMV infections. Mothers of congenitally infected infants and a group of leukemic children and pregnant women were also studied. In 11 cases of congenital infection, CMV EA-Ab was always associated with CMV excretion whether immunoglobulin M antibody was present or not. Nine mothers of congenitally infected infants had CMV EA-Ab for several months after delivery, but association with CMV elimination was not established when urine and/or saliva were tested for virus isolation. In all nine cases of primary CMV infection, CMV EA-Ab was present, and in five its detection was associated with CMV isolation. In one case, disappearance of EA-Ab occurred when virus excretion ceased. In five cases of reactivated CMV infections, a consistent association between CMV EA-Ab and virus isolation was found. Six of 31 leukemia children had CMV EA-Ab, and virus was isolated from 3 of these. Four of 28 pregnant women showed EA-Ab in their serum, but tests for isolation were not done. These data suggest that CMV EA-Ab is not a marker of a current primary CMV infection, as previously reported, but a marker of an active CMV replication which can take place in primary as well as in congenital and reactivated CMV infections.
The factors that regulate cytomegalovirus (CMV) excretion from the genitourinary tract are poorly understood. To assess the role of cell-mediated immunity in such excretion, a CMV-specific mononuclear blastogenesis assay was used to study a predominantly lower-socioeconomic-status population of 92 healthy nonpregnant adolescent women who also had CMV complement-fixing antibody titers and viral cultures of cervix, urine, saliva, and blood performed. Eighteen were studied more than once. No blood cultures were positive and no seroconversions were noted. There was no significant difference for frequency or degree of systemic CMV-specific blastogenesis between the 20 who were culture positive and the 41 who were seropositive but culture negative, although 40% of the culture-positive group and 27% of the seropositive, culture-negative group lacked CMV-specific blastogenesis. One of 31 seronegative subjects displayed CMV-specific blastogenesis. No systematic deficits were noted in any groups or individuals for E rosette number or mitogen response, though some isolated significant differences among groups for mitogen responses existed. Local CMV excretion in the study population was not related to systemic CMV-specific mononuclear blastogenesis.
Sixteen episodes of cytomegalovirus (CMV) disease occurred in 10 of 41 children undergoing intestinal transplantation from 1990 to 1995. Stratification of CMV disease by donor (D)/recipient (R) serological status was as follows: 3 of 8, D+/R−; 3 of 9, D+/R+; 4 of 9, D−/R+; and 0 of 15, D−/R−. Treatment resulted in resolution of CMV disease in 93.3% of episodes. No deaths attributable to CMV disease occurred in this series. CMV in D+/R− children resulted in more extensive and persistent disease. However, patient and graft survival rates were similar in the different D/R subgroups and between children with and without CMV disease. Cumulative dose of steroid boluses (relative risk [RR]. 1.59; 95% confidence interval [CI]. 1.14–2.21) and history of steroid recycles (RR, 2.72; 95% CI, 1.21–6.13) were associated with CMV disease. These results suggest that although CMV-associated morbidity in pediatric intestinal transplant recipients was substantial, it was not associated with an increased rate of mortality or graft loss, even among high-risk D+/R− patients.
Altogether 54 children exposed prenatally to maternal cytomegalovirus (CMV) infection were followed up in a prospective study. Nine had congenital infection with CMV and 37 escaped congenital infection; in 8 congenital CMV could not be confirmed. The birthweight of children with congenital CMV was significantly lower than that of both controls and those who escaped congenital infection. Intrauterine infection was not clinically suspected in any of the children with congenital CMV, although two had head circumferences less than the third centile. Subsequently one child with congenital CMV developed marked psychomotor retardation, and one, in whom congenital CMV was not confirmed, showed mild developmental delay. Speech and language ability was significantly impaired in children with congenital CMV compared with controls and those who escaped congenital infection, suggesting that subtle damage may have occurred. The incidence of intrauterine transmission of CMV after exposure to infection in the first trimester was 20% and in the third trimester 40%, but no congenital infections resulted from exposure in the second trimester. The severity of congenital infection was not related to the time of exposure in utero. Our findings suggest that the risk to an individual fetus from maternal infection in early gestation is so low that termination of pregnancy cannot be recommended; screening of women for primary CMV infection in pregnancy seems therefore to have limited value.
Cytomegalovirus (CMV) and herpes simplex virus (HSV) are common viruses that can affect critically ill patients who are not immunocompromised. The aim of this study was to determine whether the identification of CMV and/or HSV in mechanically ventilated critically ill patients suspected of having pneumonia was associated with an increased mortality.
Prospective epidemiological study.
Medical intensive care unit of a tertiary medical center.
Ninety-three patients with suspected pneumonia.
Patients with suspected pneumonia had bronchoalveolar lavage and blood samples taken to confirm the diagnosis. Antigenemia was used to detect CMV in the blood. Bronchoalveolar lavage samples were submitted to testing using quantitative real-time Polymerase Chain Reaction.
Measurements and Main Results
We identified 22 patients with a CMV infection, 26 patients with an HSV infection and 45 patients without CMV or HSV infection (control group). Mortality at day 60 was higher in patients with a CMV infection than in patients from the control group (55% vs. 20%, P<0.01). Mortality at day 60 was not significantly increased in the group with HSV infection. Duration of ICU stay and ICU mortality were significantly higher in patients with CMV infections when compared to patients from the control group, whereas ventilator free days were significantly lower in patients with CMV infections when compared to patients from the control group.
In critically ill patients, a CMV infection is associated with an increased mortality. Further interventional studies are needed to evaluate whether treatment could improve the prognosis.
Although opportunistic infections like cytomegalovirus (CMV) are common sequelae of end-stage AIDS, the immune events leading to CMV reactivation in human immunodeficiency virus (HIV)-infected individuals are not well defined. The role of cellular and humoral CMV-specific immune responses in immune control of latent CMV infection was evaluated prospectively in a cohort of 11 simian immunodeficiency virus (SIV)-infected CMV-seropositive rhesus macaques, 6 of whom had histologic evidence of CMV disease at death. Macaques with CMV disease differed from macaques without CMV disease in having significantly higher levels of plasma SIV RNA and CMV DNA and significantly lower titers of anti-CMV binding antibodies (Abs) at the time of death. A significant decline in anti-CMV Abs and CMV-specific CD4+ and CD8+ T lymphocytes over time was observed in the macaques with CMV disease, but not in the macaques without CMV disease. Reduction in CMV-specific CD8+ T lymphocytes and anti-CMV neutralizing Abs was significantly correlated with a decline in CMV-specific CD4+ T lymphocytes. Although declines in CMV-specific T lymphocytes alone were sufficient for reactivation of low-level CMV viremia, high-level viremia (>1,000 copies of CMV DNA per ml of plasma) was observed when anti-CMV neutralizing and binding Abs had also declined. Thus, the occurrence of CMV reactivation-associated disease in AIDS is associated with suppression of both cellular and humoral CMV-specific immune responses. The underlying mechanism may be a dysfunction of memory B and CD8+ T lymphocytes associated with SIV-induced impairment of CMV-specific CD4+ T-cell help.
Cell-mediated immune responses in 27 infants and children with cytomegalovirus (CMV) infection acquired between birth and 1 year of age were compared with responses in 13 children who had neonatal herpes simplex virus (HSV) infection. Infection was asymptomatic in 25 of 27 CMV-infected children; the 13 patients with HSV infection were all ill as newborns. The median age when studied was 46 months for children infected with CMV and 24 months for those infected with HSV. We measured lymphocyte transformation responses (LTRs) to CMV antigens in the former group and to HSV type 1 (HSV-1) (and in six cases to HSV-2) in the latter group, with the results expressed as a stimulation index. Based on the results in seropositive and seronegative adult control subjects, stimulation indexes of greater than or equal to 3 were considered indicative of a positive LTR. Among the CMV-infected children, a positive LTR was observed in 0 to 13 assays performed before 1 year of age, 3 of 8 assays performed between 1 and 4 years of age, and 9 of 15 assays performed over 4 years of age. In contrast, a positive LTR to HSV-1 was seen in 15 to 18 assays performed in children under 1 year of age and in 14 of 16 assays performed in survivors of neonatal HSV infection older than 1 year. Six HSV-2-infected patients were tested simultaneously 13 times with HSV-1 and HSV-2 antigens. Those patients under 6 months of age responded similarly to each antigen, whereas those who were older had significantly higher LTRs to HSV-2. Children with CMV infection that was acquired early had persistently diminished specific LTRs. In contrast, after neonatal HSV infection, LTRs to HSV were present even in infancy and became more specific for the infecting type with increasing age.