Cytomegalovirus Infection in Ireland

Abstract

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.

Role of Immunogenetics in the Outcome of HCMV Infection: Implications for Ageing

“…However, in the previously quoted study [6], the presence of HLA-B8 allele had a protective effect for developing HCMV infection after kidney transplantation. It is intriguing that in a study performed on HCMV infection in Ireland, HLA-A1, HLA-B8 alleles were associated with HCMV seronegativity [5]. These alleles are carried by the 8.1 ancestral haplotype, i.e., an evolutionarily highly conserved haplotype, known to influence cytokines production with decreased type 1 responses in contrast to type 2 ones.…”

“…The transmission occurs via saliva, urine, breastfeeding, placenta, sexual intercourse, blood and organ transplants. In transplanted patients, immunosuppressive drugs can increase the risk of infection and complications [4,5,6,7].…”

Severe Symptomatic Primary CMV Infection in Inflammatory Bowel Disease Patients with Low Population Seroprevalence

“…Indeed, the seroprevalence of CMV amongst Irish-born women engaged in antenatal care has been reported to be amongst the lowest in the world [ 14 ] (30%, compared to almost 90% in women tested in Ireland but born elsewhere). In addition, the CMV seroprevalence in Irish solid organ transplant donors was 33.4% (range 22–48% per annum) over the time period 1990–2013 [ 15 ]. Consequently, the seroprevalence of CMV reported in our IBD cohort, estimated at 30%, is in keeping with the data from previous Irish studies.…”

Sex-Associated Differences in Cytomegalovirus Prevention: Prophylactic Strategy is Potentially Associated With a Strong Kidney Function Impairment in Female Renal Transplant Patients

“…However, the differences in outcome with regard to other criteria, including renal function and other viral (re)activations is largely unclear. Interestingly, there is evidence of sex differences in both ganciclovir pharmacokinetics and the anti-CMV immune response ( Villacres et al, 2004 ; Perrottet et al, 2009 ; Di Benedetto et al, 2015 ; Hassan et al, 2016 ; Stranzinger et al, 2016 ; Fleck-Derderian et al, 2017 ; Momper et al, 2017 ; Lindemann et al, 2018 ). Thus, female patients have been shown to have a faster ganciclovir clearance, and distinct anti-CMV immunological profiles, e.g., higher number of IL-21 secreting anti-CMV T cells ( Villacres et al, 2004 ; Perrottet et al, 2009 ; Di Benedetto et al, 2015 ; Momper et al, 2017 ; Lindemann et al, 2018 ).…”