This is a case of a four-month-old female infant who presented with clinical manifestations of congenital rubella syndrome (CRS) — bilateral cataracts, poorly-dilating pupils, microcorneas, salt and pepper retinopathies seen after cataract extractions, bilateral sensorineural hearing loss, patent ductus arteriosus, microcephaly, history of blueberry spots and low birth weight, and positive serum IgM and IgG tests for rubella. The patient’s mother also had prenatal rubella infection. However, the patient also presented with additional set of clinical findings not seen in recent patients with CRS and not commonly reported in literature: visual acuities of poor to no dazzle, bilateral choroidal thickening on ocular ultrasound that spontaneously resolved, optic nerve inflammation that became atrophic, vessel tortuosities seen after cataract extractions, bilateral subependymal cysts with lenticulostriate vasculopathy in basal ganglia, basal ganglia hyperintensity suggestive of calcification, and jaundice. These findings plus the overlapping clinical manifestations with CRS and the positive IgM and IgG for cytomegalovirus (CMV) made us consider a congenital CMV co-infection. CRS already causes significant childhood morbidity. Getting co-infected with CMV in utero worsens morbidity and makes management more difficult. This case presented a congenital co-infection of rubella and CMV and discussed the added challenges in their diagnosis and management.
Rubella Syndrome, Congenital ; Cytomegalovirus Infections ; Coinfection

Congenital cytomegalovirus (CMV) infection (cCMV) is challenging to differentiate from congenital rubella syndrome (CRS) clinically. Virus detection and serological tests are needed. However, they are often not readily available or are expensive. This is a case of a five-month-old male with bilateral cataracts. He was jaundiced at birth and started having seizure episodes at one month of age. He was also diagnosed with right inguinal hernia and had abnormal bilateral hearing tests. Both eyes were noted to have leukocoria at two months of age. There was dazzle on both eyes and sclerae were anicteric. Examination revealed dense cataracts on both eyes, but their ocular ultrasound results were essentially normal. Due to the bilateral hearing loss and bilateral cataracts, CRS was initially considered despite the absence of heart abnormality since there were reported CRS cases without the complete triad. However, possible coinfection or another disease was considered due to the presence of jaundice, seizures, and hernia, which were never seen in our previous CRS patients nor were reported in the literature. The patient underwent cataract extraction on both eyes without intraocular lens implantation (IOL) as recommended for CRS cataracts to prevent severe inflammation. TORCH (TOxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex) test was negative for rubella but positive for CMV. As such, the patient would have benefitted from early IOL implantation. The patient was then referred to a national medical center for possible treatment. However, since the patient already tested negative for CMV polymerase chain reaction (PCR) there, systemic antiviral therapy was no longer initiated. This case presented the challenge of clinically differentiating cCMV and CRS.
Cytomegalovirus Infections ; Rubella Syndrome, Congenital ; Hearing Loss ; Jaundice

Infantile osteopetrosis is a rare congenital disorder caused by abnormal bone resorption. Patients with osteopetrosis can have severe anemia, thrombocytopenia, hepatosplenomegaly, rickets, visual impairment, and deafness. Cytomegalovirus also can cause a congenital infection with anemia, thrombocytopenia, hepatosplenomegaly, and calcifications in the brain. We report a 38-day-old infant with severe hepatosplenomegaly, thrombocytopenia, hypocalcemia, and growth failure. Real time polymerase chain reaction detected cytomegalovirus in the plasma. Skeletal radiography revealed generalized bone sclerosis. He was diagnosed with osteopetrosis along with cytomegalovirus infection. Only the test for mutation of the CLCN7 gene, representing the most common and heterogeneous form of osteopetrosis, was available, and the result was negative. With supportive care and antiviral treatment, severe thrombocytopenia due to the cytomegalovirus infection almost normalized despite the possible immunosuppression caused by osteopetrosis. We present the first report of an infant who suffered from osteopetrosis and CMV infection which was successfully treated by long term antiviral agent therapy.
Anemia ; Bone Resorption ; Brain ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Deafness ; Humans ; Hypocalcemia ; Immunosuppression ; Infant ; Infant, Newborn* ; Osteopetrosis* ; Plasma ; Radiography ; Real-Time Polymerase Chain Reaction ; Rickets ; Sclerosis ; Thrombocytopenia ; Vision Disorders

OBJECTIVETo evaluate the clinical application value of throat swab nested PCR for detecting active congenital human cytomegalovirus (HCMV) infection in neonates.

METHODSThe throat swabs and umbilical cord blood specimens from 51 neonates were collected for nested PCR assay for HCMV glycoprotein B (gB) gene. Moreover, 18 of them were subjected to a pp65 antigen test.

RESULTSThe sensitivity and specificity of throat swab nested PCR for HCMV gB gene were 67% and 75%, respectively, and the positive and negative predictive values were 57% and 82%, respectively.

CONCLUSIONSThroat swab nested PCR assay for HCMV gB gene is non-invasive, rapid, and highly sensitive for HCMV detection and holds promise as an excellent screening technology for detecting active congenital HCMV infection in neonates.

Cytomegalovirus Infections ; congenital ; diagnosis ; Fetal Blood ; virology ; Humans ; Infant, Newborn ; Phosphoproteins ; blood ; Polymerase Chain Reaction ; methods ; Viral Envelope Proteins ; genetics ; Viral Matrix Proteins ; blood

Cytomegalovirus infection is extremely common in the population, especially for newborns. Congenital CMV infection may cause central nervous system damage and other related diseases, thus potentially harmful. At home and abroad, some related research had been carried out on the incidence of disease, and a variety of detection methods had been developed. In this paper, the current situation of congenital cytomegalovirus infection and detection method is reviewed.
Antibodies, Viral ; blood ; Cytomegalovirus ; isolation & purification ; Cytomegalovirus Infections ; congenital ; diagnosis ; DNA, Viral ; blood ; Female ; Humans ; Infant, Newborn ; Polymerase Chain Reaction ; Pregnancy

OBJECTIVETo explore the cost-effectiveness of the diagnosis of congenital cytomegalovirus (CMV) infection by fluorescent quantitative polymerase chain reaction (FQ-PCR) in neonates.

METHODSSerum CMV immunoglobulin M (CMV-IgM) and CMV-IgG were detected using ELISA in 610 neonates aged less than 14 days. CMV DNA content was detected by FQ-PCR. The cost-effectiveness analysis was then performed.

RESULTSThe positive rate of FQ-PCR in neonates with positive CMV-IgM was 42.9% (15/35), while, 2.9% (16/547) in neonates with positive CMV-IgG. The mean logarithm values of CMV DNA in neonates with positive CMV-IgM were higher than those in neonates with positive CMV-IgG (5.79±1.24 vs 4.11±0.87; P<0.01). The costs of the diagnosis of CMV infection by FQ-PCR were 256 RMB/case in neonates with positive CMV-IgM, and 3 760 RMB/case in neonates with positive CMV-IgG.

CONCLUSIONSThe CMV DNA content in neonates with positive CMV-IgM is higher than that in neonates with positive CMV-IgG. Diagnosis of congenital CMV infection by FQ-PCR in neonates with positive CMV-IgG is not suitable for large scale epidemiological survey because of high cost-effectiveness ratio.

Antibodies, Viral ; urine ; Cytomegalovirus Infections ; congenital ; diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Fluorescence ; Humans ; Immunoglobulin G ; urine ; Immunoglobulin M ; urine ; Infant, Newborn ; Male ; Polymerase Chain Reaction ; economics ; methods

OBJECTIVETo evaluate the efficacy and safety of ganciclovir therapy for congenital cytomegalovirus (CMV) infection in newborn infants.

METHODSThe randomized controlled trials (RCTs) and quasi-RCTs on ganciclovir therapy for congenital CMV were reviewed in the following electronic databases: PubMed (January 1988 to January 2009), EMbase (January 1988 to January 2009), the Cochrane library (Issue 3, 2003 and Issue 1, 2009), the Chinese Journals Full-text Database (January 1994 to January 2009), the Chinese Biological Medical Disc (January 1994 to January 2009) and the Chinese Medical Current Contents (January 1994 to January 2009). Quality assessment, data extraction, and meta analysis were performed.

RESULTSTen papers were included. Meta analysis showed that the ganciclovir therapy increased the improvement rate (91.4% vs 34.0%; p<0.01) and led CMV infection indexes to become negative in more patients (87.6% vs 15.3%; p<0.01) and decreased incidence of hearing disturbance (4.7% vs 37.2%; p<0.01) as compared with the non-ganciclovir therapy control group. The incidence of the ganciclovir-therapy-related side effects was low.

CONCLUSIONSGanciclovir treatment may increase the improvement rate and the rate of CMV infection indexes becoming negative, and decrease incidence of hearing disturbance, with few side effects, in newborn infants with CMV infection. However the supporting evidence is not strong due to few trials and more high-quality research is needed.

Antiviral Agents ; therapeutic use ; Cytomegalovirus Infections ; complications ; congenital ; drug therapy ; Follow-Up Studies ; Ganciclovir ; therapeutic use ; Hearing Disorders ; etiology ; Humans ; Infant, Newborn

OBJECTIVETo investigate the variability of human cytomegalovirus (HCMV) UL138 open reading frame (ORF) in clinical strains.

METHODSHCMV UL138 ORF was amplified by polymerase chain reaction (PCR) and PCR amplification products were sequenced directly, and the data were analyzed in 19 clinical strains.

RESULTSUL138 ORF in all 30 clinical strains was amplified successfully. Compared with that of Toledo strain, the nucleotide and amino acid sequence identities of UL138 ORF in all strains were 97.41% to 99.41% and 98.24% to 99.42%, respectively. All of the nucleotide mutations were substitutions. The spatial structure and post-translational modification sites of UL138 encoded proteins were conserved. The result of phylogenetic tree showed that HCMV UL138 sequence variations were not definitely related with different clinical symptoms.

CONCLUSIONHCMV UL138 ORF in clinical strains is high conservation, which might be helpful for UL138 encoded protein to play a role in latent infection of HCMV.

Amino Acid Sequence ; Cytomegalovirus ; classification ; genetics ; Cytomegalovirus Infections ; congenital ; genetics ; Humans ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; Protein Structure, Secondary ; Sequence Alignment ; Viral Proteins ; chemistry ; genetics

PURPOSE: To observe changes in audiology, intellectual development, behavior development, and physical growth during systematic follow-up of infants with asymptomatic congenital human cytomegalovirus (HCMV) infection. MATERIALS AND METHODS: Fifty-two infants diagnosed with asymptomatic congenital HCMV infection from July 2003 to July 2007 served as the infection group, and 21 healthy infants served as the control group. All infants were confirmed to have HCMV infection by Fluorescent Quantative polymerase chain reaction (FQ-PCR). In both the infection and control groups, the neonates and infants at 3 months, 6 months, and 1 year of age underwent examinations. RESULTS: 1) 20 items of National Black Nurses Association (NBNA) scores of neonates 12-14 days after birth in 2 groups were 38.3 +/- 1.95 and 38.5 +/- 2.29, without significant differences. 2) Auditory test: 50 ears of 25 cases in the infection group showed abnormal auditory thresholds in V waves with an abnormal rate of 14%, while no abnormalities were found in 21 cases in the control group. 3) Mental and psychomotor development index scores in the control group (107.49 +/- 11.31 and 107.19 +/- 10.98) were compared with those in 41 asymptomatically infected infants at 1 year of age (107.21 +/- 9.96 and 108.31 +/- 11.25), and no statistically significant difference was noted. CONCLUSION: 1) An elevated threshold in the V wave was present in asymptomatically infected infants, but could not be detected through otoacoustic emission (OAE) screening. 2) Either in the neonatal or infant periods, asymptomatic congenital HCMV infection did not have a significant influence on nervous behavior or on physical and intellectual development.
Auditory Threshold ; *Child Development ; Cytomegalovirus Infections/*complications/congenital ; Female ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Male ; Neuropsychological Tests ; Psychomotor Performance

OBJECTIVEGanciclovir is a first-line drug for treatment of cytomegalovirus (CMV) infection. However, some ganciclovir treatment-related side-effects can be found. This study aimed to compare the efficacy and side effects of relatively low and high doses of ganciclovir in the treatment of neonatal congenital CMV infection.

METHODSOne hundred and sixty-seven neonates with congenital CMV infection were randomly assigned to high-dose (n=79) and low-dose ganciclovir groups (n=88). The high-dose ganciclovir group was injected with ganciclovir of 7.5 mg/kg in the inducement phase and of 10 mg/kg in the maintaining phase. The low-dose ganciclovir group was injected with ganciclovir of 5 mg/kg in the inducement and the maintaining phases. The efficacy and side effects were observed in the two groups.

RESULTSAfter treatment the clinical symptoms and signs were obviously improved in both groups. CMV-IgM became negative in 93.8% of neonates in the high-dose ganciclovir group and 93.1% of neonates in the low-dose ganciclovir group (P>0.05). CMV-DNA became negative in 80.8% of neonates in the high-dose ganciclovir group and in 86.7% in the low-dose ganciclovir group (P>0.05). The low-dose ganciclovir group had lower incidence of side effects than the high-dose ganciclovir group: vomiting 2.3% vs 11.4%; anemia 8.0% vs 20.3%; reduction of neutrophilic granulocytes 5.7% vs 16.5%; increase in platelet count 8.0% vs 18.9% (P<0.05).

CONCLUSIONSLow-dose ganciclovir has the same clinical efficacy to high-dose ganciclovir for treatment of neonatal congenital CMV infection, but fewer side effects occur in the low-dose group.

Antiviral Agents ; administration & dosage ; Cytomegalovirus Infections ; congenital ; drug therapy ; DNA, Viral ; analysis ; Dose-Response Relationship, Drug ; Female ; Ganciclovir ; administration & dosage ; adverse effects ; Humans ; Infant, Newborn ; Male