Cytomegalovirus Infection In Children Research Articles

Fulminant Hepatic Failure as a Risk Factor for Cytomegalovirus Infection in Children Receiving Preemptive Therapy After Living Donor Liver Transplantation

Cytomegalovirus (CMV) is one of the most common causes of infection after solid organ transplantation with symptomatic disease occurring at an incidence of 20% to 40% without preventative measures. Although CMV donor+/recipient - serostatus is well known to be a risk factor, there is little data about other risk factors for CMV infection in the setting of pediatric liver transplantation (LT). We hypothesized that fulminant hepatic failure (FHF) may be a risk factor for CMV infection given anecdotal reports of complications associated with FHF. We conducted medical chart review of children who underwent LT at a tertiary children's hospital in Tokyo between November 2005 and October 2015. We evaluated the risk factors, especially FHF, and prognosis for CMV infection under preemptive therapy. Three hundred thirty-seven living donor LT were analyzed. Underlying diseases were cholestatic liver disease (n = 172, 51%), metabolic disease (n = 59, 18%), and FHF (n = 51, 15%). Among 337 LT, 147 (44%) recipients developed CMV antigenemia. In multivariate analysis, FHF (odds ratio, 4.99; 95% confidence interval, 1.86-13.40; P = 0.001) and CMV serostatus were independent risk factors for developing CMV antigenemia. Positive donor serostatus was significantly associated with development of antigenemia within 1-year post-LT regardless of recipient serostatus (P <0.001). On the other hand, positive recipient status was associated with CMV antigenemia in the first 21 days (P <0.001). Only 12 (3.6%) of 337 children developed CMV disease. Fulminant hepatic failure was found to be a risk factor for CMV infection independent of CMV serostatus.

Host genetics and susceptibility to congenital and childhood cytomegalovirus infection: a systematic review.

AimTo summarize available evidence on the role of host genetics in the susceptibility to congenital and childhood cytomegalovirus (CMV) infections by conducting a systematic review of published studies.MethodsWe searched online databases (PubMed, Web of Science, Scopus and HuGe Navigator) for relevant studies with well-defined inclusion and exclusion criteria and assessed the risk of bias using novel Confounding-Selection-Information bias score (CSI).Results5105 studies were initially identified, but only 5 met all the inclusion criteria and were analyzed in detail. Polymorphisms of the toll-like receptors (TLRs) and mannose-binding lectin (MBL) genes were shown to have an impact on the CMV infection in infants. Polymorphisms of the TLR2 (rs3804100, rs1898830), TLR4 (rs4986791), and TLR9 (rs352140) were shown to have a role in congenital CMV infection. Low MBL levels were associated with CMV infection in Chinese individuals, a finding that was not replicated in Caucasians. The overall credibility of evidence was weak.ConclusionsBased on currently available very limited amount of evidence, it is uncertain whether congenital and childhood CMV infections are under host genetic control. Additional primary studies are needed with more specific research hypotheses that will enable gradual understanding of specific mechanisms of the CMV pathogenesis. More genetic studies in the future will facilitate better understanding of host susceptibility and likely enable novel preventative and curative measures.

Experience using recombinant interferon-alpha with taurine therapy of congenital cytomegalovirus infection in children

Cytomegalovirus (CMV) belongs to the most frequent causes of intrauterine infection and can cause birth defects and severe manifestations of the disease fatal. In most cases the infection is latent, but there is a high risk of developing late manifestations. For the prevention of vertical transmission of CMV infection are needed early prenatal diagnosis of infection in a pregnant woman with the definition of the extent of its activity and conduct of antiviral therapy. When intravenous anti-CMV immunoglobulin observed rapid clinical efficacy. However, the titer of circulating antibodies in the child’s body is rapidly reduced, determines the duration of the protective effect of the drug to 4-5 weeks. Since the suppository form of interferon-α with taurine has been used successfully in obstetric practice, we have examined its effectiveness in the treatment of 11 outpatient children aged 1 month to 3 years with congenital CMV infection, 3 of them received specific immunoglobulin baby immediately after birth. The drug was administered rectally by prolonged scheme for 3 months 2 times a day every 12 hours within 10 days, followed by 1 suppository 2 times a day every other day (3 times a week). The therapy in all children experienced rapid resolution of symptoms CMV: normalization of the size of lymph nodes, liver and spleen, blood count, serum ALT, urinalysis, as well as the disappearance of CMV DNA in blood and IgM antibodies to CMV infection after treatment. During 12 months of follow-up episodes of reactivation of CMV infection in any of the observed child is not mentioned.

Cytomegalovirus infection in children after bone marrow transplantation: Risk factors, clinical aspects and outcomes

Abstract Background and objectives Cytomegalovirus (CMV) infection remains the most common and potentially severe viral complication in patients given hematopoietic stem cell transplantation. The aim of this study was to determine the incidence, risk factors and outcomes of CMV infection in pediatric BMT unit. Material and methods This study was a retrospective analysis of clinical, laboratory and outcome data of 131 pediatric patients who underwent BMT. Results The mean age of the study population was 6.5 ± 4 years. Out of 131 pediatric patients, 85 were males (64.9%). Majority of patients had hematological disorder/malignancy ( n = 101; 77%) followed by solid tumors ( n = 30; 23%). Most of them received allogeneic transplant ( n = 92; 70.2%). CMV reactivation was observed in 38 (29%) patients; out of them, only ( n = 3; 2.3%) had clinical manifestation/organ involvement and most cases of CMV were resolved ( n = 35; 26.7%). Benign hematological disorder, conditioning regimen containing ATG, allogeneic BMT, graft-versus-host disease (GVHD) prophylaxis used and development of GVHD were identifiable risk factors in all patients, and lymphopenia 3 ( p = 0.047) was the only identifiable risk factors in allogeneic BMT patients associated with development CMV reactivation. Patients, who had CMV reactivation had significantly higher rate of GVHD (31.6% vs 15.1%; p = 0.031), however relapse rate (21% vs 25.8%) and mortality rate (22.5% vs 33.3%) in patients with CMV reactivation vs no CMV reactivation respectively were not statistically significant. Overall survival and event free survival of patients with and without CMV antigenemia were also comparable. Conclusions Antigenemia-guided pre-emptive strategy with ganciclovir was very affective and CMV reactivation tended not to affect the outcome in our study cohort.

Absence of cytomegalovirus infection in children with acquired immunodeficiency syndrome and distal sensory polyneuropathy

To investigate the role of cytomegalovirus (CMV) infection in the pathogenesis of peripheral neuropathy in children with acquired immunodeficiency syndrome (AIDS) a cross-sectional descriptive study was conducted on a sample of nine children. Plasma samples were tested for CMV DNA by two polymerase chain reaction assays (sensitivity limits of 400 and 10 copies/mls) respectively. While all nine were CMV seropositive all were negative for viremia in both assays. CMV would appear not to be involved in children with AIDS-associated sensory neuropathies. (J Pediatr Neurol 2004; 2(4): 219–223).

Surgical manifestations of gastrointestinal cytomegalovirus infection in children: Clinical audit and literature review

IntroductionGastrointestinal sequelae of cytomegalovirus are rare, usually associated with significant immune compromise, and carry a high morbidity and mortality. Gastrointestinal disease frequently requires surgical intervention for diagnosis and management. AimThe aim of the study is to evaluate the incidence, presentation and management of gastrointestinal cytomegalovirus disease in a pediatric population. MethodBetween January 2003 and June 2011, a retrospective folder review was conducted of all symptomatic children with proven CMV disease, presenting to the surgical service. Eligible patients were identified using the surgical, histopathology and serology databases. ResultsThirty-eight patients (1.8/1000 surgical admissions) were identified with a median presenting age of 5months (range 3days–12years). Esophagitis (n=18) and small bowel disease (n=16) predominated, but CMV was seen throughout the gastrointestinal tract. Risk factors included HIV infection (n=21, 55%) and recent gastrointestinal surgery or infection (n=10, 26%). Characteristic multiple jejunoileal perforations were seen in six patients. Compared to upper GIT disease, intestinal involvement was associated with younger age and doubled mortality. In HIV-infected children, median CD4 (%) was lower in intestinal compared to upper gastrointestinal disease. Morbidities included anastomotic breakdowns (5), anastomotic strictures (3), relook laparotomies (10), resistant esophageal strictures (5) and prolonged parenteral nutrition (5). Anti-CMV drugs were given in 63%. Overall mortality was 32% (12/38) and was associated with lower GIT disease. ConclusionInvasive CMV gastrointestinal disease in our children was predominantly HIV-associated, or followed a major lower gastrointestinal inflammatory insult in infants younger than 6months. Successful therapy requires a high index of suspicion of active CMV disease to allow early implementation of CMV viral load control and aggressive treatment of the underlying immune impairment. Multiple surgical interventions are often required for both tissue diagnosis and management of acute and chronic complications. CMV-viral-load-tailored anti-CMV therapy is supported by recent literature.

Cytomegalovirus viral and antibody correlates in young children.

BackgroundYoung, healthy children shedding cytomegalovirus (CMV) in urine and saliva appear to be the leading source of CMV in primary infection of pregnant women.FindingsWe screened 48 children 6 months – 5 years old for CMV IgG and measured levels of CMV IgG, IgM and IgG avidity antibodies, frequency of CMV shedding, and viral loads in blood, urine, and saliva. Thirteen of the 48 children (27%) were CMV IgG positive, among whom 3 were also CMV IgM positive with evidence of recent primary infection. Nine of the 13 seropositive children (69%) were shedding 102-105 copies/ml of CMV DNA in one or more bodily fluid. Among seropositive children, low IgG antibody titer (1:20–1:80) was associated with the absence of shedding (p = 0.014), and enrollment in daycare was associated with the presence of CMV shedding (p = 0.037).ConclusionsCMV antibody profiles correlated with CMV shedding. The presence of CMV IgM more often represents primary infection in children than in adults. Correlating antibodies with primary infection and viral shedding in healthy children adds to the understanding of CMV infection in children that can inform the prevention of CMV transmission to pregnant women.

Retrospective analysis of cytomegalovirus infection in children of Wuhu City

Objective To investigate the cytomegalovirus（ CMV） infection in children of Wuhu City. Methods Serum samples from children n=874 were tested for CMV-IgM using commercial ELISA kits. Re-sults The CMV-IgM detective rate of serum samples from 874 children was 4. 46%. The positive rate of CMV-IgM was 4. 89%（26/531cases）and 3. 79%（13/343 cases）in boys and girls,respectively. There was no signifi-cant difference in the positive rate of CMV-IgM between boys and girls（χ2 =0. 37,P〉0. 05）. The positive rate peaked in children at age of 〉6 months-1 year（10. 19%）. Clinical manifestations included liver dysfunction, neurological diseases,jaundice and pneumonia. Conclusion The positive rate of CMV-IgM in children in local district of Wuhu city is high,which should be given due attention. Key words: Cytomegalovirus; Infection; Children

Retrospective diagnosis of congenital cytomegalovirus infection in children with autism spectrum disorder but no other major neurologic deficit.

Congenital cytomegalovirus (CMV) infection can cause a variety of neurological deficits of delayed onset in infants who are asymptomatic at birth. The aim of this study was to investigate the prevalence of congenital CMV infection among children with autism spectrum disorder (ASD) in Nagasaki, Japan. Twenty-nine children with ASD who were born in Nagasaki and had no other major neurological deficits were recruited. Two of the patients were excluded due to significant perinatal events. The remaining 27 children were investigated retrospectively for congenital CMV infection by analyzing dried blood spot samples or dried umbilical cords for CMV DNA using real-time PCR. CMV DNA was detected in two (7.4%) of the 27 children. Neither of the patients had perinatal histories suggestive of congenital CMV disease or other neurological deficits, including hearing impairment and epilepsy. The severity of their autistic disorders varied considerably. The rate of congenital CMV infection in this study (two of 27 children with ASD), which was significantly (p=0.004) higher than the incidence of congenital CMV infection in Nagasaki (0.31%, 10/3230 live births), suggests the involvement of congenital CMV infection in a portion of children with ASD, although definite diagnosis was not obtained due to limited clinical data of the study subjects.

Seroprevalence of Cytomegalovirus infection in children aged 0-8 years in Nanjing

Objective To investigate the seroprevalence of Cytomegalovirus (CMV) infection and ages of the children in primary for better understanding the status of CMV infection in China with evidence-based medicine. Methods Total 837 children randomly selected from Nanjing Children's Hospital, from Jun.to Sep.in 2011, including 513 boys and 324 girls, aged from 1 day to 8 years, with mean age of 3.6 years old , were recruited.Serum samples were tested for CMV IgM, CMV IgG, and CMV IgG avidity index using commercial enzyme-linked immunosorbent assay kits. Results Of the total serum samples from 837 children, 690 cases were CMV IgG positive.The overall seroprevalence of CMV IgG was 82.4%, with 83.2% (427/513 cases) and 81.2% (263/324 cases) in boys and girls, respectively.There was no significant difference in the seroprevalence of CMV IgG between boys and girls (χ2=0.584, P=0.445). Of the 92 infants less than 6 months old, 86 cases were CMV IgG positive, and the positive rate was 93.5%.The prevalence gradually declined in infants after 7 months old, fell to the lowest level of 66.7% at age of 9 months, and then constantly maintained around 80.0% from 1 to 8 years old (χ2=15.4, P<0.001). CMV IgM in 352 serum samples were tested, and 23 (6.5%) cases were CMV IgM positive.The positive rate peaked in infants at age of 2-3 months (7/12 cases, 58.3%), then decreased over the age and none of the children older than 6 years were IgM positive (χ2=5.1, P<0.001). Furthermore, the CMV IgG avidity index assay was performed in all 23 cases of IgM positive indivi-duals to estimate the primary CMV infection rate.The results showed low avidity index (<30%) in 13 infants, the primary infection rate was 56.5% (13/23 cases). Most subjects with primary infection (n=7, 53.8%) were younger than 1 year old. Conclusions The current seroprevalence of CMV IgG in children in China was around 80.0%, lower than that in adults, and the primary CMV infection mostly occurred before 3 months of age. Key words: Cytomegalovirus; Seroprevalence; Primary infection; Child

Correlation of congenital cytomegalovirus infection in children with unilateral sensorineural hearing loss

Correlation of congenital cytomegalovirus infection in children with unilateral sensorineural hearing loss

Bilateral Subcapsular and Perinephric Hemorrhage as the Initial Presentation of Polyarteritis Nodosa

Polyarteritis nodosa is a systemic vasculitis of medium and small-sized arteries associated with aneurysm formation. Aneurysms may be complicated by thrombosis, rupture and hemorrhage. Kidney involvement in polyarteritis nodosa can rarely be complicated by Wunderlich syndrome which is characterized by acute onset of spontaneous, nontraumatic subcapsular and perirenal hematomas. A 22-year-old woman with mental retardation due to childhood cytomegalovirus infection presented with flank pain, weight loss and fever, and was found to have bilateral subcapsular and perinephric hematomas. Spontaneous bilateral renal hemorrhage as the initial manifestation of polyarteritis nodosa is rare, and it can be associated with delays in diagnosis and treatment.

A Universal Preemptive Therapy for Cytomegalovirus Infections in Children After Live-Donor Liver Transplantation

Cytomegalovirus (CMV) infection remains the most common and critical viral infection that occurs after liver transplantation (LT). The current set of guidelines recommends prophylaxis over a preemptive therapy for pediatric LT; however, the data regarding the optimal approach after LT in children are limited. We conducted a universal preemptive therapy for CMV infection in 113 children (median: 16 months) after live-donor LT at the largest pediatric LT center in Japan between November 2005 and August 2009. CMV-pp65 antigenemia was monitored weekly regardless of the subjects' CMV serostatus after LT, and ganciclovir therapy was initiated when CMV-pp65 antigenemia was positive. The overall success rate of LT was 91.7%. CMV-pp65 antigenemia became positive in 37 (33%) recipients, and the positivity with their CMV serostatus was as follows: donor (D)+/recipient (R)-: 62%, D+/R+: 36%, D-/R+: 11%, and D-/R-: 8%. Among the D+/R- (n=29) and D+/R+ (n=44) recipients, 38% (n=11) and 64% (n=28) recipients were able to avoid the use of ganciclovir, respectively. Human CMV disease was documented in six (5%) recipients, and they were successfully treated with ganciclovir without any sequelae. A universal preemptive therapy for CMV infection after live-donor LT was successful for reducing the use of antiviral agents and for controlling CMV infection and disease in children.

Congenital cytomegalovirus infection: the impact of cerebral cortical malformations

Cytomegalovirus has been suggested to have a teratogenous influence during the migration of neural cells from the ventricular zones to the cortex during the gestational period. The aim of this study was to investigate the prevalence of congenital cytomegalovirus infections in a cohort of children with neurological disability and cerebral cortical malformations recognized by neuroimaging. Twenty-six children with neurological disability and cerebral cortical malformations were investigated retrospectively for congenital cytomegalovirus infection by analysing the dried blood spot samples for cytomegalovirus deoxynucleic acid using qualitative polymerase chain reaction. CMV DNA in the dried blood spot samples was found in four out of 26 children. Two of these four had severe disabilities with mental retardation, autism, spastic cerebral palsy, epilepsy and deafness. A third child had epilepsy and unilateral cerebral palsy, while the fourth had a mild motor coordination dysfunction and hearing deficit. In our study, the number of congenital cytomegalovirus infections in children with cerebral cortical malformations was higher (4/26) than expected with reference to the birth prevalence (0.2-0.5%) of congenital cytomegalovirus infection in Sweden. We thus conclude that congenital cytomegalovirus infection should be considered in children with cortical malformations of unknown origin.

The HLA‐G 14 bp insertion/deletion polymorphism is a putative susceptible factor for active human cytomegalovirus infection in children

Human leukocyte antigen-G (HLA-G) expression is a potential factor for the pathogenesis of virus infection. A 14 bp insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene is involved in the stability of HLA-G mRNA and HLA-G protein expression. Therefore, the HLA-G 14 bp polymorphism might be involved in human cytomegalovirus (hCMV) infection. To test a possible association between the HLA-G 14 bp deletion/insertion polymorphism and the active hCMV infection, in this study, a total of 54 patients with active hCMV infection and 165 age- and sex-matched, unrelated, normal Chinese Han population were genotyped for the 14 bp insertion/deletion polymorphism. Association of 14 bp polymorphism with hCMV urine DNA copies and the odds ratio (OR) of the polymorphism as a risk factor for active hCMV infection were analyzed. Our results showed that the prevalence of -14 bp/ -14 bp genotype in active hCMV patients was markedly increased [P(c) = 0.00034, OR = 3.31, 95% confidence interval (CI): 1.77-6.18], and similar significance was also observed for the frequency of -14 bp allele (P c = 0.0023, OR = 2.24, 95% CI: 1.38-3.64) when compared with that of healthy controls. Furthermore, urine hCMV DNA copies in patients with the -14 bp/ -14 bp genotype were significantly higher than those in patients with the +14 bp/ +14 bp genotype (P = 0.041). Our findings support a potential role of HLA-G 14 bp insertion/deletion polymorphism as a susceptible factor for the active hCMV infection.

Cytomegalovirus infection in children undergoing hematopoietic stem cell transplantation in Chile

Cytomegalovirus (CMV) infection remains as an important cause of morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). Our aim was to assess the incidence, risk factors, and outcome related to CMV infection in children after HSCT in a developing country. From October 1, 1999, to December 31, 2005, we prospectively studied all patients admitted to the HSCT unit at Hospital Luis Calvo Mackenna in Santiago, Chile. Serologic studies before transplantation and weekly CMV infection surveillance (antigenemia or quantitative PCR) were routinely obtained. Patients with positive antigenemia or quantitative PCR received pre-emptive therapy with ganciclovir, and cases of unfavorable clinical evolution, persistent positive antigenemia, or quantitative PCR after 14 days of ganciclovir were treated with foscarnet. Ninety-seven patients received HSCT. Their median age was 8 years (range, 3 months to 24 years) and their overall survival was 67%. CMV reactivation was diagnosed in 26 patients. Of these, three developed CMV disease (two interstitial pneumonia, one hemorrhagic cystitis). One of the patients with pneumonia died. Risk factors identified were pre-transplant serologic status (positive recipient), acute and chronic graft versus host disease (GvHD), GvHD prophylaxis, and treatment with antithymocyte globulin. The rate and prognosis of CMV infection among children treated at our HSCT unit is similar to those reported from industrialized countries. These findings reflect adequate prevention and management of CMV infection within our program.

Acute acalculous cholecystitis of viral etiology—a rare condition in children?

Acute acalculous cholecystitis (AAC) comprises 5% to 10% of all cases of acute cholecystitis in adults and appears to be even less frequently diagnosed in children. The diagnosis of AAC is established upon some clinical, laboratory, and ultrasonographic findings, which may sometimes be ambiguous and confusing especially in children. Diagnostic difficulties may result in either delayed diagnosis or unnecessary surgical intervention. Acute cholecystitis owing to viral infectious factors is reported to be extremely rare. The aim of the article is to demonstrate 2 cases of AAC as a clinical presentation of both Epstein-Barr virus and cytomegalovirus infection in children.

Treatment of Enlarged Lymph Nodes in Children and Adolescents

Purpose:Cytomegalovirus(CMV) infection still remains as a major cause of morbidity and mortality after stem cell transplantation. In this study, we analyzed the results of antigenemia-guided pre- emptive therapy among children with allogeneic hematopoietic stem cell transplantation to determine the incidence and risk factors associated with CMV antigenemia, and evaluated the efficacy of the CMV antigenemia based preemptive therapy. Methods:We enrolled 213 pediatric patients following allogeneic hematopoietic stem cell transplantation(HSCT), at the Catholic HSCT center between October 1998 and December 2003. Pre-emptive ganciclovir was started when more than 5 CMV Ag-positive cells were detected in matched sibling HSCT, and when any Ag-positive cells were seen in unrelated allogenic HSCT. Results:CMV antigenemia was observed in 88(41.3 percent) of 213 patients on median day 28(day 11-99). In univariated analysis, use of unrelated donors(other than siblings), age of recipient(more than 5 years at transplant) at transplantation, the presence of recipient CMV-IgG before transplantation, TBI-based conditioning regimen and the presence of acute GvHD(grade ≥II) were the risk factors for positive CMV antigenemia. In multivariate analysis, unrelated bone marrow transplantation, positive recipient CMV serology and acute GvHD(grade ≥II) were the independent risk factors for positive CMV antigenemia. Conclusion:Risk factors of CMV infection in children were CMV serostatus of the recipient, the source of stem cells, and acute graft-versus-host disease. The pre-emptive therapy based on CMV antigenemia was effective in the prevention of CMV disease.

NO CMV DNA IN GUTHRIE CARDS FROM CHILDREN WHO LATER DEVELOPED ALL

An association of a viral infection in utero and development of acute lymphoblastic leukemia (ALL) has been suggested. Cytomegalovirus (CMV) has been reported as a leading agent of intrauterine infections resulting in some cases of congenital infections. The authors investigated the presence of prenatal CMV infection in children who later developed ALL. Guthrie cards were obtained from 48 children with ALL and 46 healthy children and were analyzed for the presence of CMV DNA by a real-time TaqMan PCR. CMV DNA was not detected in Guthrie cards from the children with ALL, from the control healthy children. The results show that prenatal CMV infection does not seem to be associated with later development of childhood ALL.

Immune Thrombocytopenic Purpura Associated with Acquired Cytomegalovirus Infection in Children

Immune Thrombocytopenic Purpura Associated with Acquired Cytomegalovirus Infection in Children