Associations between human cytomegalovirus infection and type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: Multiple studies have reported a potential contribution of human cytomegalovirus (HCMV) to the pathogenesis of type 1 diabetes and post-transplantation diabetes. However, the association between HCMV and type 2 diabetes mellitus (T2DM) remains unclear. In this paper, we employ the meta-analysis approach to investigate the potential correlation between HCMV infection and T2DM. METHOD: The data of our study were collected from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure and WAN FANG databases from inception to November 2022. Using the Review Manager V.5.4 software, the meta-analysis was performed. RESULTS: A total of 18 139 patients from 22 studies were included in our analysis. In the Asian subgroup, the patients with T2DM group had a significantly higher frequency of HCMV infection and older age compared with the healthy group. In the European, the frequency of HCMV infection in the T2DM was lower than the healthy group, although this difference was not statistically significant. After adjusting for demographic factors, the adjusted OR of T2DM for risk of by HCMV status was not found to be significant (adjusted OR=1.19, 95% CI=0.88 to 1.62, p>0.05). Additionally, T2DM with vasculopathy had a significantly higher rate of HCMV infection compared with those without vasculopathy (OR=1.87, 95% CI=1.24 to 2.83, p<0.05). Among T2DM with HCMV infection, there were significant increases in fasting blood glucose levels and the proportion of CD8+ T lymphocytes. Conversely, fasting blood insulin levels, the proportion of CD4+ T lymphocyte and the CD4+/CD8+ ratio were significantly decreased compared with the healthy group. CONCLUSION: At present, the available evidence does not provide a clear understanding of whether there is a significant association between T2DM and HCMV infection. Additionally, T2DM with HCMV infection exhibited significantly worse blood glucose regulation and immune markers, as well as a higher frequency of vasculopathy. PROSPERO REGISTRATION NUMBER: CRD42022342066.

The Association Between Cytomegalovirus and Disability by Race/Ethnicity and Sex: Results From the Health and Retirement Study.

Recent studies have documented a decline in the overall prevalence of disability in the United States; however, racial/ethnic and sex disparities continue to persist. Cytomegalovirus (CMV) infection, a socially patterned exposure, may be a key mechanism in understanding these previously documented disparities. Using data from a nationally representative study, the 2016 Health and Retirement Study, we employed Poisson log-binomial models to estimate the prevalence of disability in a comparison of CMV-seropositive and -seronegative adults and investigated effect modification by race/ethnicity and sex. Among the 9,029 participants (55% women; mean age = 67.4 years), 63% were CMV-seropositive and 15% were disabled. CMV seropositivity was highest among non-Hispanic Black (88%) and Hispanic (92%) adults as compared with non-Hispanic White adults (57%). We found evidence for effect modification in the association between CMV and disability by sex but not race/ethnicity. While the 95% confidence intervals in the fully adjusted models included the null value, in comparison with seronegative women, our results suggest a greater prevalence of disability among CMV-seropositive women (prevalence ratio = 1.16, 95% confidence interval: 0.97, 1.38) but not among men (prevalence ratio = 0.85, 95% confidence interval: 0.69, 1.06). Results provide initial support for the hypothesis that CMV may be an important determinant of sex disparities in disability.

Herpesvirus encephalitis diagnosed by polymerase chain reaction at the National Institute of Neurology of Mexico.

The frequency of central nervous system infections due to herpesvirus have been studied in various populations; however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis; polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502; in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

Clinical Features and Diagnosis of Anterior Segment Inflammation Related to Cytomegalovirus in Immunocompetent African, Asian, and Caucasian Patients.

Objective: To report the clinical features and treatment outcomes in immunocompetent patients with anterior segment inflammation (ASI) related to human cytomegalovirus (HCMV) depending on their ethnic origin.Material and Methods: Multicenter retrospective study of 38 patients with at least one test, either HCMV-positive PCR or GWc.Results: Features of Posner-Schlossman syndrome were observed in 50% of the eyes, Fuchs heterochromic iridocyclitis in 13% of the eyes, chronic nonspecific anterior uveitis in 21% of the eyes, and corneal endotheliitis in 18% of the eyes. PCR and GWc were positive for HCMV in 50% and 96.2% of the eyes, respectively. Glaucoma was diagnosed in 50% of eyes. Treatment was oral valganciclovir in about half of the patients. Other treatments were intravenous ganciclovir and/or ganciclovir topical ointment and/or intravitreal ganciclovir.Conclusions: No obvious association of specific clinical features with individual ethnicity could be identified. We found a high rate of glaucoma in all ethnic groups. There was a delay in diagnosis and specific treatment of HCMV in most patients.

Stillbirth Associated With Infection in a Diverse U.S. Cohort.

OBJECTIVE: To better characterize infection-related stillbirth in terms of pathogenesis and microbiology. METHODS: We conducted a secondary analysis of 512 stillbirths in a prospective, multisite, geographically, racially and ethnically diverse, population-based study of stillbirth in the United States. Cases underwent evaluation that included maternal interview, chart abstraction, biospecimen collection, fetal autopsy, and placental pathology. Recommended evaluations included syphilis and parvovirus serology. Each case was assigned probable and possible causes of death using the INCODE Stillbirth Classification System. Cases where infection was assigned as a probable or possible cause of death were reviewed. For these cases, clinical scenario, autopsy, maternal serology, culture results, and placental pathology were evaluated. RESULTS: For 66 (12.9%) cases of stillbirth, infection was identified as a probable or possible cause of death. Of these, 36% (95% CI 35-38%) were categorized as a probable and 64% (95% CI 62-65%) as a possible cause of death. Infection-related stillbirth occurred earlier than non-infection-related stillbirth (median gestational age 22 vs 28 weeks, P=.001). Fetal bacterial culture results were available in 47 cases (71%), of which 35 (53%) grew identifiable organisms. The predominant species were Escherichia coli (19, 29%), group B streptococcus (GBS) (8, 12%), and enterococcus species (8, 12%). Placental pathology revealed chorioamnionitis in 50 (76%), funisitis in 27 (41%), villitis in 11 (17%), deciduitis in 35 (53%), necrosis in 27 (41%), and viral staining in seven (11%) cases. Placental pathology found inflammation or evidence of infection in 65 (99%) cases and fetal autopsy in 26 (39%) cases. In infection-related stillbirth cases, the likely causative nonbacterial organisms identified were parvovirus in two (3%) cases, syphilis in one (2%) case, cytomegalovirus (CMV) in five (8%) cases, and herpes in one (2%) case. CONCLUSION: Of infection-related stillbirth cases in a large U.S. cohort, E coli, GBS, and enterococcus species were the most common bacterial pathogens and CMV the most common viral pathogen.

Evaluation of infectious risk and outcomes in the hmong renal transplant population.

BACKGROUND: Hmong ethnicity has been associated with infection, particularly fungal. The risk of infection after transplant in the Hmong population is unknown. METHODS: Observational study of adult renal transplant (RTX) recipients between 1/1/1994 and 12/31/2015. Primary objective was to identify infectious risk in the Hmong RTX population as compared to non-Hispanic whites (NHW). Secondary objective was to evaluate transplant outcomes. RESULTS: There was a total of 2599 patients in the study window; 95 Hmong, 2504 NHW. The Hmong population had significantly fewer bacterial and fungal infections at 1 and 3 years (Bacterial: Hmong 21.7%, 32.4% vs NHW 36.9%, 46.7%, P = .004; Fungal: Hmong 3.3%, 5.7% vs NHW 12.7%, 16.6%, P = .0005) and improved graft and patient survival at 1, 5, and 10 years (Graft: Hmong 92.6%, 78.4%, 61.9% vs NHW 90.7%, 72.2%, 48.5%, P = .006; Patient: Hmong 97.8%, 94.5%, 83.3% vs NHW 95.3%, 82.1%, 62.1% P < .001). Spectrum of bacterial infection was similar, but with significantly more Staphylococcal infection in the NHW population. Blastomycoses were the major fungal pathogen in Hmong (2/3, 67%) vs Candida in NWH (77%). When minimally adjusted for PRA and age, rates of bacterial infection (HR 0.69, 95% CI 0.48-0.99, P = .047), fungal infection (HR 0.39, 95% CI 0.17-0.87, P = .02), and mortality (HR 0.5, 95% CI 0.28-0.88, P = .02) were more favorable in the Hmong population. When analyzed in a stepwise Cox proportional hazards model; Hmong ethnicity was not a significant risk factor for graft failure, rejection, CMV, BK, or fungal infection after RTX and was associated with reduced risk of bacterial infection (HR 0.61, 95% CI 0.4-0.9, P = .02) and mortality (HR 0.51, 95% CI 0.27-0.96, P = .04). CONCLUSIONS: Despite concern regarding infective risk in the Hmong population, infection after RTX is no higher than NHW comparator. In all analyses, the Hmong population has equal or better outcomes. It does not appear variance in standard infection prophylaxis is necessary for the Hmong population after RTX.

Attitudes of U.S. Hispanic and non-Hispanic women toward congenital CMV prevention behaviors: a cross sectional study.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection. The only way to protect against congenital CMV infection is to practice CMV prevention behaviors. CMV seroprevalence rates are high in Hispanic women. It is unknown whether communication strategies should differ by ethnicity. The purpose of this study was to understand differences between U.S. Hispanic and non-Hispanic women's attitudes toward CMV prevention behaviors and examine the relationship between perceived subjective norms and these attitudes. METHODS: This was a cross-sectional study using an online panel. Participants were U.S. women of childbearing age. The dependent variable was attitude toward practicing CMV prevention behaviors, specifically avoiding sharing cups, food, and utensils with a child and not kissing a child on the lips. RESULTS: Among 818 women (50% Hispanic), 16.8% of Hispanic women and 9.7% of non-Hispanic women (p = 0.002) reported familiarity with CMV. Attitudes toward CMV prevention through avoiding sharing behaviors (M Hispanic = 5.55 vs. M non-Hispanic  = 5.20; p = 0.002) and not kissing a child on the lips (M Hispanic = 4.80 vs. M non-Hispanic = 4.21; p = 0.001) were positive for both ethnicities, but higher for Hispanic women. Hispanic women (M = 5.11) reported higher perceived behavioral control for avoiding kissing a child on the lips than non-Hispanic women (M = 4.63; p = 0.001). Hispanic women who were U.S. born or spoke English primarily more frequently kissed a child on the lips or engaged in sharing behaviors. Additionally, those who spoke Spanish mostly held more positive attitudes toward not kissing on the lips. Significant predictors for more positive attitudes toward CMV prevention behaviors were associated with perceived subjective norms, perceived behavioral control and pre-survey participation in risk behaviors. CONCLUSIONS: Hispanic women have more positive attitudes toward CMV prevention behaviors than non-Hispanic women, however in regression models other factors are more important predictors of positive attitudes than ethnicity. In developing strategies to encourage women to practice CMV prevention behaviors, a focus on further understanding and increasing subjective norms and perceived control over those behaviors may be warranted.

Racial and Ethnic Differences in the Prevalence of Congenital Cytomegalovirus Infection.

OBJECTIVE: To evaluate the impact of race and ethnicity upon the prevalence and clinical spectrum of congenital cytomegalovirus infection (cCMV). STUDY DESIGN: From 2007 to 2012, 100 332 infants from 7 medical centers were screened for cCMV while in the hospital. Ethnicity and race were collected and cCMV prevalence rates were calculated. RESULTS: The overall prevalence of cCMV in the cohort was 4.5 per 1000 live births (95% CI, 4.1-4.9). Black infants had the highest cCMV prevalence (9.5 per 1000 live births; 95% CI, 8.3-11.0), followed by multiracial infants (7.8 per 1000 live births; 95% CI, 4.7-12.0). Significantly lower prevalence rates were observed in non-Hispanic white infants (2.7 per 1000 live births; 95% CI, 2.2-3.3), Hispanic white infants (3.0 per 1000 live births; 95% CI, 2.4-3.6), and Asian infants (1.0 per 1000 live births; 95% CI, 0.3-2.5). After adjusting for socioeconomic status and maternal age, black infants were significantly more likely to have cCMV compared with non-Hispanic white infants (adjusted prevalence OR, 1.9; 95% CI, 1.4-2.5). Hispanic white infants had a slightly lower risk of having cCMV compared with non-Hispanic white infants (adjusted prevalence OR, 0.7; 95% CI, 0.5-1.0). However, no significant differences in symptomatic cCMV (9.6%) and sensorineural hearing loss (7.8%) were observed between the race/ethnic groups. CONCLUSIONS: Significant racial and ethnic differences exist in the prevalence of cCMV, even after adjusting for socioeconomic status and maternal age. Although once infected, the newborn disease and rates of hearing loss in infants are similar with respect to race and ethnicity.

Unexpected role of the human cytomegalovirus contribute to essential hypertension in the Kazakh Chinese population of Xinjiang.

Human cytomegalovirus (HCMV) infection, chronic inflammation and oxidative stress, the renin-angiotensin system (RAS), endothelial function, and DNA methylation play roles in the pathogenesis of essential hypertension (EH); however, the mechanism by which HCMV predisposes patients to hypertension remain unclear. Our group previously demonstrated an association between EH and HCMV infection in Kazakh Chinese. Here, we investigated the relationship between HCMV infection and other clinicopathological features in 720 Kazakh individuals with or without hypertension (n=360 each; age: 18-80). Multiple linear and logistic regression analyses were used to determine the associations between HCMV infection, clinical characteristics, and EH. Notably, patients with EH, particularly those with HCMV infection, exhibited a marked increase in tumor necrosis factor-α (TNF-α) and 8-hydroxy-2-deoxyguanosine (8-OHDG) levels, but a decrease in endothelial nitric oxide synthase (eNOS) and renin levels. Similarly, elevated TNF-α and 8-OHDG levels were independent predictors of increased HCMV antibody titers, whereas eNOS and renin were negatively correlated with the latter. Moreover, serum angiotensin-converting enzyme (sACE, ACE) methylation was increased, whereas 11-ß hydroxysteroid dehydrogenase 2 (HSD11ß2; HSD3B2) methylation was decreased in patients with EH who were also infected with HCMV. A positive correlation between HSD3B2 methylation and HCMV IgG titer and blood pressure was additionally observed, whereas angiotensin-converting enzyme (ACE) methylation was inversely correlated with blood pressure. Collectively, these data indicate that HCMV may contribute to EH development in the Kazakh Chinese by increasing TNF-α and 8-OHDG levels, suppressing eNOS and renin, and manipulating HSD3B2 and ACE methylation.

Risk factors and clinical outcomes of pediatric liver transplant recipients with post-transplant lymphoproliferative disease in a multi-ethnic Asian cohort.

BACKGROUND: We aimed to evaluate clinical characteristics, risk factors, and disease outcomes for liver transplant recipients (LTR) with post-transplant lymphoproliferative disease (PTLD) at our center. METHODS: Retrospective review of data of all pediatric LTR (1991-2015) was conducted. RESULTS: The overall incidence of PTLD was 16.4% (18/110), the majority (13/18) were early lesions, while 3/18 were polymorphic/monomorphic PTLD. The risk factors significant on univariate analysis were as follows: mean age (years) at transplant (1.66 vs 4.76, P = .006); age <2 years at transplant (odds ratio [OR] 3.53 [95% confidence interval [CI]: 1.16-10.73], P = .026); cytomegalovirus (CMV) primary infection (OR 11.39 [95% CI: 3.44-37.7], P < .001); recipient CMV seronegativity (OR 7.50 [95% CI: 2.02-27.78], P = .003); presence of CMV end-organ disease (OR 4.00 [95% CI: 1.22-13.16], P = .022); Chinese ethnicity; and higher mean duration of intravenous ganciclovir prophylaxis. In multivariate analysis, CMV primary infection (OR 5.22 [95% CI: 1.25-21.87], P = .024), CMV seronegativity (OR 5.91 [95% CI: 1.13-30.90, P = .035]), and having acute cellular rejections (ACR) prior to PTLD (OR 5.53 [95% CI: 1.43-21.48, P = .013]) were significant risk factors for PTLD, with the latter two factors having a synergistic effect in increasing PTLD risk in a stratified analysis. The final multivariate model in predicting the risk of PTLD, utilizing CMV primary infection, recipient CMV seronegativity, and ACR before PTLD as predictive variables, was statistically significant (likelihood ratio chi square statistic = 25.18, P < .0001 with df = 3). CONCLUSIONS: We report a unique clinicopathologic and risk factor profile in our cohort-early lesion PTLD accounts for the majority and the incidence of monomorphic PTLD remains low. In addition, we show a synergism between CMV naivety and ACR on PTLD risk, a higher prevalence of gastrointestinal manifestations, and a lack of significant association with Epstein-Barr virus seronegativity.

Association between high cytomegalovirus antibody titers and blood pressure in the adult Kazakh and Han Chinese populations.

BACKGROUND: Human cytomegalovirus (CMV) has been linked to the pathogenesis of elevated arterial blood pressure (BP). Our study aimed to determine the association between anti-CMV titers and arterial BP in the Kazakh and Han Chinese populations. MATERIAL AND METHODS: Kazakh and Han (n = 800 each) (age, ≥18 years) subjects from Xinjiang, China were examined for anti-CMV immunoglobulin (Ig)G titers using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The highest anti-CMV titer tertiles determined within gender and ethnicity groups were compared against the two lower tertiles and seronegative samples. RESULTS: Multivariate linear regression analysis revealed that anti-CMV titers were independent determinants for elevated systolic (p = 0.006) BP in Kazakh women and inversely associated with systolic (p = 0.004) and mean arterial (p = 0.019) BP in Han women. CONCLUSION: The association between CMV infection and/or resulting immune response and BP elevation differed by sex and ethnicity. In Kazakh women, they were associated with elevated BP and the opposite was true among Han women.

Cytomegalovirus infection and atherosclerosis risk: A meta-analysis.

Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta-analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta-analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non-atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG-based HCMV tests, IgM-based tests, PCR-based tests, and pp65-based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09-4.51), 8.92(95%CI 3.17-25.11), 6.75 (95%CI 3.50-13.02), and 5.72(95%CI 1.51-21.58), respectively. The meta-analysis results showed that HCMV infection is significant connected with an increased risk for AS.

Enhancement of cytokine-driven NK cell IFN-γ production after vaccination of HCMV infected Africans.

Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK-cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure. In contrast to populations with lower prevalence of HCMV infection, no significant enhancement of NK-cell responses (IFN-γ, CD107a, CD25) occurred after in vitro re-stimulation of post-vaccination NK cells with TIV or DTPiP antigens compared to pre-vaccination baseline cells. However, both vaccinations resulted in higher frequencies of NK cells producing IFN-γ in response to exogenous IL-12 with IL-18, which persisted for up to 6 months. Enhanced cytokine responsiveness was restricted to less differentiated NK cells, with increased frequencies of IFN-γ+ cells observed within CD56bright CD57- , CD56dim CD57- NKG2C- and CD56dim CD57- NKG2C+ NK-cell subsets. These data suggest a common mechanism whereby different vaccines enhance NK cell IFN-γ function in HCMV infected donors and raise the potential for further exploitation of NK cell "pre-activation" to improve vaccine effectiveness.

Geographic Disparities in Cytomegalovirus Infection During Pregnancy.

BACKGROUND: Cytomegalovirus (CMV) is the most common infectious cause of fetal malformations and childhood hearing loss. CMV is more common among socially disadvantaged groups, and it clusters geographically in poor communities. We conducted a geospatial analysis of chronic and primary CMV infection among pregnant women around Durham, NC. METHODS: We performed a geospatial analysis of subjects from an ongoing study of CMV infection among pregnant women using geographic information systems and spatial statistics. Subjects were categorized on the basis of results of their CMV immunoglobulin G avidity testing as seronegative, seropositive, or primary infection. We used generalized additive models to analyze the spatial distributions of individuals who fell into each category and to control for confounders such as race and age. We used a generalized estimating equation to correlate community-level variables with CMV status. RESULTS: Of 3527 pregnant women aged 15 to 59 years, 93.4% were either white or black. CMV seropositivity was significantly more common among non-Hispanic white subjects than among minority subjects (odds ratio, 3.76 [95% confidence interval, 3.25-4.34]). We identified a cluster in which women had elevated odds of CMV seropositivity in the urban neighborhoods of Durham. Cases of primary CMV infection were more common in areas with higher-than-average CMV seroprevalence. Neighborhood median family income was associated inversely with the prevalence of chronic CMV. CONCLUSIONS: We found a high prevalence of CMV seropositivity in urban low-income neighborhoods among pregnant women, particularly among racial and ethnic minorities. Seronegative pregnant women from these communities might be at heightened risk for primary CMV infection.

In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia.

It is widely suspected, yet controversial, that infection plays an etiologic role in the development of acute lymphoblastic leukemia (ALL), the most common childhood cancer and a disease with a confirmed prenatal origin in most cases. We investigated infections at diagnosis and then assessed the timing of infection at birth in children with ALL and age, gender, and ethnicity matched controls to identify potential causal initiating infections. Comprehensive untargeted virome and bacterial analyses of pretreatment bone marrow specimens (n = 127 ALL in comparison with 38 acute myeloid leukemia cases in a comparison group) revealed prevalent cytomegalovirus (CMV) infection at diagnosis in childhood ALL, demonstrating active viral transcription in leukemia blasts as well as intact virions in serum. Screening of newborn blood samples revealed a significantly higher prevalence of in utero CMV infection in ALL cases (n = 268) than healthy controls (n = 270) (odds ratio [OR], 3.71, confidence interval [CI], 1.56-7.92, P = .0016). Risk was more pronounced in Hispanics (OR=5.90, CI=1.89-25.96) than in non-Hispanic whites (OR=2.10 CI= 0.69-7.13). This is the first study to suggest that congenital CMV infection is a risk factor for childhood ALL and is more prominent in Hispanic children. Further investigation of CMV as an etiologic agent for ALL is warranted.

Analysis of the shedding of three ß-herpesviruses DNA in Polish patients subjected to allogeneic hematopoietic stem cell transplantation: Six-year follow up.

BACKGROUND: Infections with human ß-herpesviruses are common worldwide and are still frequent in patients after hematopoietic stem cell transplantation. Some data suggest that HHV-6 and HHV-7 could take part in CMV reactivation from latency and/or progression of CMV disease in immunosupressed patients. OBJECTIVES: The aims of this study were: (1) to summarise retrospectively the results of ß-herpesviruses DNA detection in a large group of adult allogeneic haematopoietic stem cell transplant recipients; and (2) to find a potential correlation between viruses belonging to this subfamily. STUDY DESIGN: AlloHSCT recipients (N=142) were examined in the early post-transplant period (median=89 days). The presence of CMV, HHV-6 and HHV-7 was confirmed through detection and quantification of viral DNA, isolated from 1679 sera samples. RESULTS: CMV DNA alone was detected in 23.9% of patients, while single HHV-6 and HHV-7 were detected in 14.8% and 9.9% of individuals, respectively. The reactivation of more than one virus was identified in 31% of analysed patients. In cases of concurrent infection, HHV-7 was detected at the same time as HHV-6, and both of them were usually reactivated before CMV. The kinetics of virus reactivation and measured viral load may suggest a potential role of HHV-6 and HHV-7 as co-factors in CMV reactivation. CONCLUSIONS: The observed kinetics of virus reactivation may strongly suggest a potential role of HHV-6 and/or HHV-7 as co-factors of CMV reactivation. The co-infection with these ß-herpesviruses could predispose patients after hematopoietic stem cell transplantation to a longer and more severe CMV infection.

Determinants of Ethnic Differences in Cytomegalovirus, Epstein-Barr Virus, and Herpes Simplex Virus Type 1 Seroprevalence in Childhood.

OBJECTIVE: To identify whether there are ethnic differences in cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus type 1 (HSV-1) seroprevalence rates in children at 6 years of age, and when present, to evaluate how these differences can be explained by sociodemographic and environmental factors. STUDY DESIGN: This study was embedded within a multi-ethnic population-based prospective cohort study. Serum IgG levels against CMV, EBV, and HSV-1 were measured by enzyme-linked immunosorbent assay in 4464 children (median age 6.0 years). Information on demographics and characteristics were assessed by questionnaires. Herpesvirus seroprevalences between Surinamese-Creole, Surinamese-Hindustani, Turkish, Moroccan, Cape Verdean Antillean, and Native Dutch children were compared. RESULTS: Non-Western ethnicity was an independent risk factor for CMV (aOR, 2.16; 95% CI 1.81-2.57), EBV (1.76; 1.48-2.09), and HSV-1 seropositivity (1.52; 1.39-1.66). Among the ethnic groups, CMV seroprevalences ranged between 29% and 65%, EBV between 43% and 69%, and HSV-1 between 13% and 39%. Low family net household income, low maternal educational level, crowding, and lifestyle factors explained up to 48% of the ethnic differences in HSV-1 seroprevalences, and up to 39% of the ethnic differences in EBV seroprevalences. These factors did not explain ethnic differences in CMV seroprevalences. CONCLUSIONS: Socioeconomic position and factors related to lifestyle explain only a part of the large ethnic differences in EBV and HSV-1 seroprevalences, whereas they do not explain ethnic differences in CMV seroprevalences in childhood.

Racial differences in allogeneic hematopoietic cell transplantation outcomes among African Americans and whites.

The impact of race on outcome has been identified in a number of cancers, with African Americans having poorer survival compared with whites. We conducted a study to investigate the association of race with allogeneic hematopoietic cell transplant (HCT) outcomes. We identified 789 patients (58 African Americans and 731 whites) who underwent allogeneic HCT for hematologic disorders. There were no significant differences between African Americans and white patients in gender, performance status or comorbidity score. However, African Americans were younger than whites (median 40 years versus 47 years, P=0.003) and were more likely to be in remission at HCT (74% versus 57%, P=0.011), to have an HLA-mismatched donor (36% versus 14%, P<0.001), to have positive donor or recipient CMV serostatus (90% versus 69%, P<0.001) and to have received a cord blood transplant (21% versus 6%, P<0.001). In univariate analysis, African Americans had worse overall survival (OS) (HR 1.41, P=0.026) compared with whites, with no significant differences in acute or chronic GvHD, non-CMV infection or relapse. However, after adjusting for several transplant and disease-related factors in multivariate analysis, the OS difference between African Americans and whites became nonsignificant (HR 1.27, P=0.18). These results suggest that race in and of itself does not lead to worse survival post HCT.

Human cytomegalovirus (CMV) UL97 D605E mutation has a higher prevalence in infants with primary CMV infection compared with transplant recipients with CMV recurrence.

Mutations in the UL97 gene are a major mechanism of human cytomegalovirus (CMV) resistance to gancyclovir (GCV). Some mutations may show different regional distributions. To analyze UL97 mutations in Chinese people, we scanned the UL97 gene fragment among virus isolates from 27 infants as well as blood samples from 28 solid organ transplant (SOT) and 42 bone marrow transplant (BMT) recipients with active CMV infections as defined by DNAemia or PP65 antigenemia. Only a known GCV-resistant mutation M406V was found in a BMT recipient. However, the D605E mutation was identified in 18 of 27 (66.7%) infants as well as 11 of 28 (39.3%) SOT and 17 of 42 (40.5%) BMT recipients. It was significantly different between the infants and transplant recipients (P < .05). So far, the influence of D605E mutation on GCV-resistance is controversial. In this study, 18 D605E mutants, 9 wild type (WT) isolates, and AD169 controls cultured in fibroblasts were tested for phenotypic drug resistance using a plaque reduction assay. The dose of GCV required for 50% inhibition of plaque formation (IC50) was 1.20 ± 0.67 µmol/L (D605E), 1.71 ± 0.64 µmol/L (WT), and 1.43 ± 0.70 µmol/L (AD169), respectively. This small difference could be caused by analytical error. We concluded that the UL97 D605E mutation showed a different prevalence between infants with primary CMV infection and transplant recipients with CMV recurrence. However, it was not related to a resistant phenotype to GCV.

Perinatal outcomes following the ultrasound diagnosis of echogenic bowel: an Australian perspective.

INTRODUCTION: The aim of this study was to describe the association between fetal echogenic bowel (FEB) diagnosed during the second trimester and adverse perinatal outcomes in an Australian antenatal population. METHODS: A retrospective analysis of ultrasound scans was performed between March 1, 2004 and March 1, 2009 at The Royal Women's Hospital, Melbourne, Vic., Australia. Cases reported as having FEB on second trimester ultrasound were included. Medical records of each case were reviewed and information concerning additional investigations and perinatal outcomes were extracted. RESULTS: A total of 66 cases were identified in our database. Three patients (5%) were excluded from further analysis as they were lost to follow-up, leaving 63 (95%) cases in this series. Thirty-two fetuses (52%) underwent karyotyping via amniocentesis, 5 (16%) of which were found to have chromosomal defects. Maternal serology for cytomegalovirus (CMV) was performed in 49 (78%) cases. Investigations indicated a total of 5 women who had CMV infection during their pregnancy. Thirty-three pregnancies (53%) were tested for cystic fibrosis (CF) and 1 baby was confirmed to have CF postnatally. Among the 50 liveborn infants, 3 cases of fetal growth restriction were apparent. Overall, 42 of the 50 liveborn infants (84%) and 67% of the entire cohort of 63 patients with a midtrimester diagnosis of FEB had a normal short-term neonatal outcome. CONCLUSION: This study reiterates the increased prevalence of aneuploidy, CMV, CF and fetal growth restriction in pregnancies complicated by the midtrimester sonographic finding of FEB. However, reassuringly, 67% of cases with ultrasound-detected echogenic bowel in the second trimester had a normal short-term neonatal outcome in this multiethnic Australian population.