Genotype distribution, viral load and clinical characteristics of infants with postnatal or congenital cytomegalovirus infection.

BACKGROUND: Congenital cytomegalovirus infection is a leading cause of long-term sequelae. Cytomegalovirus is also frequently transmitted to preterm infants postnatally, but these infections are mostly asymptomatic. A correlation between cytomegalovirus genotypes and clinical manifestations has been reported previously in infants with congenital infection, but not in preterm infants with postnatal infection. OBJECTIVES: The main objective of this study was to investigate cytomegalovirus genotype distribution in postnatal and congenital cytomegalovirus infection and its association with disease severity. METHODS: Infants admitted to the neonatal intensive care unit of the University Medical Center Utrecht, The Netherlands between 2003-2010 and diagnosed with postnatal or congenital cytomegalovirus infection were included. Classification of cytomegalovirus isolates in genotypes was performed upon amplification and sequencing of the cytomegalovirus UL55 (gB) and UL144 genes. Clinical data, cerebral abnormalities, neurodevelopmental outcome and viral load were studied in relation to genotype distribution. RESULTS: Genotyping results were obtained from 58 preterm infants with postnatal cytomegalovirus infection and 13 infants with congenital cytomegalovirus infection. Postnatal disease was mild in all preterm infants and all had favourable outcome. Infants with congenital infection were significantly more severely affected than infants with postnatal infection. Seventy-seven percent of these infants were symptomatic at birth, 2/13 died and 3/13 developed long-term sequelae (median follow-up 6 (range 2-8) years). The distribution of cytomegalovirus genotypes was comparable for postnatal and congenital infection. UL55 genotype 1 and UL144 genotype 3 were predominant genotypes in both groups. CONCLUSIONS: Distribution of UL55 and UL144 genotypes was similar in asymptomatic postnatal and severe congenital CMV infection suggesting that other factors rather than cytomegalovirus UL55 and UL144 genotype are responsible for the development of severe disease.

Urine viral load and correlation with disease severity in infants with congenital or postnatal cytomegalovirus infection.

BACKGROUND: A correlation between cytomegalovirus (CMV) load in urine and severity of disease in congenitally infected infants has previously been reported. CMV load in postnatally infected infants has not been studied before. OBJECTIVE: To investigate CMV load in urine of infants with postnatal or congenital infection and correlate this with clinical symptoms of CMV disease and cerebral abnormalities. STUDY DESIGN: Infants admitted to our NICU between July 2000 and February 2010, and diagnosed with congenital or postnatal CMV infection were included. Clinical symptoms of CMV infection, cranial ultrasonography (cUS) and magnetic resonance imaging (MRI) findings were evaluated. CMV urine loads of postnatally infected infants were analyzed and compared with CMV urine loads of congenitally infected infants. RESULTS: Seventeen infants with congenital CMV infection and 45 infants with postnatal CMV infection were included. Thirteen/17 (76%) congenitally infected infants had clinical symptoms of CMV infection at birth and 11/17 (65%) had cerebral abnormalities diagnosed by neuro-imaging. None of the four asymptomatic infants had cerebral abnormalities. Of the postnatally infected infants 43/45 (96%) did not develop any clinical symptoms of CMV infection, but in 23/45 (51%) cerebral abnormalities such as lenticulostriate vasculopathy and germinolytic cysts were identified. The median CMV load in postnatally infected infants was significantly lower than in congenitally infected infants (1.0×10(5)copies/ml versus 8.5×10(6)copies/ml, p<0.001, respectively). CONCLUSIONS: CMV load in urine is significantly lower in infants with postnatal CMV infection than in infants with congenital CMV infection irrespective of clinical symptoms of CMV infection or cerebral abnormalities.

Development of cystic periventricular leukomalacia in newborn infants after rotavirus infection.

We describe 5 preterm and 3 term infants who presented with seizures during rotavirus infection within 6 weeks after birth. Six of these infants developed late-onset cystic periventricular leukomalacia. Four of the preterm infants had neurodevelopmental delay, and 4 (near) term infants had normal early outcome.

The role of cranial ultrasound and magnetic resonance imaging in the diagnosis of infections of the central nervous system.

Imaging data concerning infection of the central nervous system (CNS) in neonates are usually confined to small groups of infants. We have reviewed the imaging findings in 96 preterm and full-term infants admitted to our neonatal intensive care unit over a 15 year period. Neuro-imaging, especially cranial ultrasound (CUS) and magnetic resonance imaging (MRI) provided useful information; CUS allows the early and later detection of calcification, germinolytic and parenchymal cysts, ventricular dilatation and strands and ependymal abnormality; diffusion weighted imaging (DWI) is especially useful in the acute stage of bacterial and viral infections, while conventional MRI helps in the detection of neocortical dysplasia in CMV infection and defining cerebellar abnormality.

Inflammatory mediators for the diagnosis and treatment of sepsis in early infancy.

Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls. Group II was divided into subgroups IIa, systemic enterovirus infection, and IIb, no enterovirus infection. Enterovirus was identified by real-time (RT) polymerase chain reaction (PCR) and/or by culture in blood and cerebrospinal fluid (CSF). The positive predictive values of IL-6, IL-8, and PCT (78%, 72%, and 83%, respectively) were better than that of CRP (63%) in the diagnosis of neonatal sepsis. After 48 h of antibiotic treatment, IL-6 and IL-8 levels significantly decreased and PCT stabilized in clinically recovered patients, suggesting that these markers may be useful in distinguishing patients in which antibiotic treatment may be discontinued. Among infants of subgroup IIa, 80%-90% had normal values of IL-6, IL-8, and PCT, whereas CRP was increased in 40%. In conclusion, IL-6, IL-8, and PCT are better parameters than CRP in the diagnosis and follow-up of neonatal sepsis due to coagulase-negative staphylococci (CoNS) and in the exclusion of bacterial infection among those with enteroviral infection among febrile infants presenting from home.

Clinical and epidemiologic characteristics of viral infections in a neonatal intensive care unit during a 12-year period.

BACKGROUND: The incidence of viral infections in patients treated in the neonatal intensive care unit (NICU) is not well-known. We summarized the data of all patients with laboratory-confirmed viral infections admitted at the NICU of our hospital during the period of 1992-2003. OBJECTIVES: To determine the incidence of viral infections among infants hospitalized in a NICU, the associated clinical manifestations and their outcome. METHODS: Retrospective analysis of epidemiologic, virologic and clinical data from infants with proven viral infection. The diagnosis viral infection was confirmed by positive viral culture and/or polymerase chain reaction from clinical samples. RESULTS: Viral infection was confirmed in 51 of 5396 infants (1%) admitted to the NICU; 20 (39%) had an enterovirus and parechovirus (EV/PEV) infection, 15 (29%) a respiratory syncytial virus (RSV) infection, 5 (10%) a rotavirus infection, 3 (6%) a cytomegalovirus (CMV) infection, 2 (4%) an adenovirus infection, 2 (4%) a parainfluenza virus infection, 2 (4%) a herpes simplex virus infection, 1 (2%) a rhinovirus infection and 1 (2%) a rubella virus infection. Three of the infants presented at birth with symptomatic rubella virus, CMV or herpes simplex virus infection. RSV infection developed mostly in hospitalized infants (60%), and 93% of infections occurred during the winter (November-March). The clinical presentations of EV/PEV disease were sepsis-like illness, prolonged seizures in term infants and gastrointestinal disease in preterm infants. RSV, parainfluenza virus, rhinovirus and CMV caused respiratory disease, predominantly in preterm infants. Gastrointestinal disease was seen only in preterm infants with adenovirus, rotavirus or EV/PEV infection. Mortality and serious sequelae were high in patients infected with EV/PEV (10 and 15%, respectively). CONCLUSIONS: The incidence of viral infection in the NICU was 1%. Enteroviral infections were the most frequently diagnosed infections, occurred often in term infants born at home and presented with sepsis-like illness or seizures. Preterm infants hospitalized from birth mainly developed gastrointestinal disease caused by rotavirus and adenovirus infection or respiratory disease caused by RSV, parainfluenza and CMV infection. Enteroviruses were responsible for the highest mortality and development of serious sequelae.