Late-onset CMV disease following CMV prophylaxis

Donnelly, C.; Kennedy, F. A.; Keane, Ciara; Schaffer, Kirsten; McCormick, Peter

doi:10.1007/s11845-009-0327-3

Cited by 8 publications

(19 citation statements)

References 13 publications

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“… 15 Dollard and colleagues 15 found that the overall prevalence of congenital CMV infection in industrialized countries is likely to be 0.6% to 0.7% which the authors state is more precise than the range of 0.2% to 2.5% often cited in the literature. Another study in agreement with our findings reported that the incidence of CMV infection and CMV disease were low in a cohort of Irish liver transplant recipients 16 compared with the published literature. 17 , 18 However, future studies in other countries are required to confirm this association and to address the strong selection pressure which HLA genes are under due to mechanisms such as selection, mutation, genetic drift but in particular migration.…”

Section: Discussionsupporting

confidence: 93%

Cytomegalovirus Infection in Ireland

et al. 2016

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Cytomegalovirus (CMV) infections occur worldwide and primary infection usually occurs in early childhood and is often asymptomatic whereas primary infection in adults may result in symptomatic illness. CMV establishes a chronic latent infection with intermittent periods of reactivation. Primary infection or reactivation associate with increased mortality and morbidity in those who are immunocompromised. Transplacental transmission may result in significant birth defects or long-term sensorineural hearing loss.We performed a study to determine the CMV seroprevalence and the association between HLA Class I alleles and frequency of CMV infection in Ireland. The presence of CMV IgG, a marker of previous CMV infection, was determined for a cohort of 1849 HLA typed solid organ transplant donors between 1990 and 2013. The presence of CMV IgG was correlated with HLA type.The CMV seroprevalence in solid organ transplant donors was 33.4% (range 22–48% per annum) over the time period 1990 to 2013. Multivariate logistic regression analysis showed that both age and HLA alleles were associated with CMV seropositivity. A significant and positive relationship between age and CMV seropositivity was observed (OR = 1.013, P < 0.001, CI [1.007, 1.019]). Chi-square analysis revealed that the female gender was independently associated with CMV seropositivity (P < 0.01). Seroprevalence in women of reproductive age (20–39 years) was significantly higher than men of the same age (37% vs 26%, P < 0.01). The frequencies of HLA-A1, HLA-A2, and HLA-A3 in our cohort were 40.8%, 48.8%, and 25.9%, respectively. Logistic regression analysis showed that the presence of HLA-A1 but not HLA-A2 or HLA-A3 was independently associated with CMV seronegativity (P < 0.01). Interestingly, individuals who co-expressed HLA-A2 and HLA-A3 alleles were significantly more likely to be CMV seropositive (P < 0.02). The frequencies of HLA-B5, HLA-B7, and HLA-B8 in our cohort were 6.1%, 31.2%, and 30.8%, respectively. The presence of the most common inherited haplotype in the Irish population, HLA-A1, B8 was significantly associated with CMV seronegativity (OR = 1.278, P < 0.001, CI [1.049, 1.556]).CMV seroprevalence is lower in Ireland compared with other countries. The high frequency of HLA-A1 in the Irish population may, in part, have a role in the reduced susceptibility to CMV infection.

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Section: Discussionsupporting

confidence: 93%

Cytomegalovirus Infection in Ireland

et al. 2016

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“…The use of prophylaxis against CMV infection has reduced the incidence of early CMV infection/disease in pediatric population. However, late CMV infection or disease post‐prophylaxis is an emerging problem in the pediatric population and is also well documented in adult LT recipients . The overall incidence of late CMV infection in our series was significantly higher at 10.5% in comparison with 6% reported by Honar et al.…”

Section: Discussioncontrasting

confidence: 59%

“…In most of the adult studies and in a retrospective review of 93 PLTR, D−R+ group was considered as a low‐risk group for acquiring CMV‐associated complications . The association between CMV infection and graft rejection after LT is well known . This association has been commonly reported in the high‐risk D+R− group after stopping prophylaxis .…”

Section: Discussionmentioning

confidence: 99%

“…The incidence of CMV infection in LT recipients varies between 23% and 85% with the highest rate in children, because considerable proportion of PLT recipients is CMV naive . Multiple adult studies have demonstrated the impact of late CMV infection on graft survival and morbidity in LT recipients . To our knowledge, there are no pediatric data available on late CMV infection‐ or disease‐associated complications in PLT recipients.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Late cytomegalovirus infection in children: High incidence of allograft rejection and hepatitis in donor negative and seropositive liver transplant recipients

Verma

Palaniswamy

Cremonini

et al. 2017

Pediatric Transplantation

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The complications and outcome associated with late CMV infection and disease on the graft are poorly characterized in PLT recipients. We studied the overall incidence, risk factors, and outcome of late CMV infection and disease (infection 6 months after transplant) in 180 PLT recipients admitted between 2008 and 2011 at the King's College Hospital. Antiviral prophylaxis of intravenous ganciclovir was given only to the D+R- group starting at day 7 post-transplant. The remaining groups (D-R+, D+R+, and D-R-) received pre-emptive therapy when they have CMV viremia above cut-off value and treatment for symptomatic CMV infection. The overall incidence of late CMV infection and disease was 9.4% (19/180) and 14.5% (19/130) in D+R-, D-R+, D+R- groups. The D-R+ group had the highest incidence of hepatitis (37.5%) and significantly increased incidence of CMV disease, and single and multiple acute rejection episodes when compared to the D+R- group, which received prophylaxis. The late CMV infection and disease in pediatric LT recipients was comparable to adult LT recipients despite variable duration of antiviral prophylaxis. Our results show that D-R+ group had highest rate of hepatitis and rejection episodes, associated with high morbidity, and should be considered for antiviral prophylaxis.

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“…For this systematic review and meta‐analyses, we included randomized controlled trials (RCTs) and observational studies in LTRs reporting on GCV or VGCV for UP and/or PE regardless of the language in which they were published. We excluded studies that used shell vial culture technique for CMV detection, as well as those reporting only on late CMD (beyond the first year of LT) .…”

Section: Methodsmentioning

confidence: 99%

Universal Prophylaxis or Preemptive Strategy for Cytomegalovirus Disease After Liver Transplantation: A Systematic Review and Meta-Analysis

Mumtaz

Faisal

Husain

et al. 2015

American Journal of Transplantation

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We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing cytomegalovirus (CMV) disease (CMD) among liver transplant recipients (LTRs). We performed an electronic search of MEDLINE, EMBASE and the Cochrane Database till December 2013. Studies that assessed UP or PE for preventing CMD in LTRs were included. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was CMD, secondary outcomes being acute cellular rejection (ACR), graft loss (GL) and mortality. Due to the heterogeneity of comparative studies, an indirect comparison was performed. Pooled incidence rates with 95% confidence interval (CI) are calculated for each outcome using a random-effects model. Thirty-two studies involving 2456 LTRs were included. The majority of the studies were of low risk of bias. Irrespective of donor/recipient CMV sero-status, CMD was 10% with UP (95% CI: 6-14; I 2 ¼ 87%; 16 studies, n ¼ 1581) and 7% with PE (95% CI: 3-10; I 2 ¼ 84%; 16 studies, n ¼ 875) (mean difference 2.6; 95% CI: À3.25 to 8.45, p ¼ 0.34). Likewise, ACR and mortality were similar with the two strategies. However, GL was significantly lower in the UP group, regardless of donor/recipient sero-status. In indirect comparison, the incidence of CMD, ACR and mortality in LTRs were similar with two strategies. Trials comparing the two strategies directly are needed.

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Late-onset CMV disease following CMV prophylaxis

Cited by 8 publications

References 13 publications

Cytomegalovirus Infection in Ireland

Cytomegalovirus Infection in Ireland

Late cytomegalovirus infection in children: High incidence of allograft rejection and hepatitis in donor negative and seropositive liver transplant recipients

Universal Prophylaxis or Preemptive Strategy for Cytomegalovirus Disease After Liver Transplantation: A Systematic Review and Meta-Analysis

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