Impact of different genotypes of CMV infection in neonates and infants

Transcription

1 Impact of different genotypes of CMV infection in neonates and infants The 2nd International Neonatology Association Conference Vienna, July th 2016 A. Kozakova 1, K. Kaluzova 1, J. Dornakova 1, K. Tabery 1, A. Briksi 2, J. Sumova 2, P. Chramostova 2, V. Novakova 2, K. Blahova 3, M. Zajac 2, M. Cerny 1,P. Hubacek 2

2 Approach Aim of the study was to find out various genotypes and clinical impact in Department of Neonatology in Czech Republic Focus / aim of the study 1 Understanding of CMV (cytomegalovirus) infection should clarify the impact of different CMV genotypes on patient s prognosis. We focused on survival, presence of severe complication, long-term effects. Based on the data we should use targeted therapy for each patient in the future. CMV genome is coded by double-stranded DNA, length approximately 230 kb consisting of the Unique Long (UL) and Unique Short (US) part. Human cytomegalovirus infection is dependent on the functions of structural glycoproteins B, O, N and H. Glycoprotein B and H are the most common. Glycoprotein B (gb) is coded by UL55 gene, which is important for virus entry into the cell. Glycoprotein H (gh) is coded by UL74 gene, which is a part of glycoprotein complex III and is involved in membrane fusion, cellular entry and spreading of the virus in the tissue. Streblov et al., 2006 in M. Reddehase Cohort was created between n = 592 biological samples tested for CMV infection whole blood samples, 94 urine samples, 42 other biological samples (mostly cerebrospinal fluid samples) CMV detection was performed by quantitative PCR technique

3 As scope of this conference focus group of 13 newborns was chosen out of the patient pool of this study Results: Group of newborns in our study 2 No. Preterm delivery Gestation age Weight (g) Length (cm) gb gh UL144 ccmv IUGR Microcephaly CNS calcification Hepatopathy Thrombocytopenia ND ND* ND* ND* No No No No 10 No Platelets at delivery Purpura Psychomotoric development Longterm effects (x10 9 /L) Dysharmonic developement with severe intellectual delay Age at evaluation (days) Central dysarthria, Growth retardation No ND* ND* ND* No No No No No 174 No M. Down No No Breech presentatio 3 1 B 42 Normal SNHL, Growth retardation treated with GH No B No No No No No ND (330) No Normal Pollen allergy No Breech presentatio n, ND CMV genotype Clinical symptoms 2 2 C No No ND (313) No Delayed - subsequently normalized C No No 88 Hemiparetic cerebral palsy (right-sided) 7 No B No No No 94 Hypermetrophy normalized, often repeated otitis - speech impediment, need for logopaedics Bilateral SNHL and speech impairment with dyslalia gravis, ADHD Sligth delay (for 4-6 weeks), but in 1 year after the 3 rd dose of polio vaccine-palsy-crawling in ADHD, microcytic anaemia normalized months, problems in gross motor skills (walking in 3 years) 8 No AB No No No No 297 No Normal No ND* ND* ND* No No No No 293 No Severe mental retardation Autism, permanent severe obstipation, multicystic dysplastic kidney 10 No ND* No No No No No ND No Normal No No ,3 1 A No 97 4th-83th day No Slight delay (6 months), problem with balance Strabismus ND 1 2 ND ND 1 1 ND No - at 37 WG No- at 32 WG ND* = sample not usable due to risk of demaged DNA (5,10,11 years old sample) or small positivity No No No No 168 No Normal No 717 No No No 81 6th-10th week No Delayed (6 months), hemiparetic cerebral palsy(left-sided) with slight central symptomatology Hemisyndrome left-sided 700 Majority of newborns were full term babies (62%) IUGR was detecteted in ¼ only CNS symptoms were very frequent (70%) Interestingly thrombocytopenia was very often (46%), opposite to purpura which was rare (23%) 2/3 patients had abnormal psychomotoric development Long-term effects were only observed in two patients (15%)

4 Variability of genotypes in focus group equally spread interestingly also the mixed infection genotype was observed in no more than one patient Results: Variability of genotypes in our group of 10 patients 3 2 patients 2 patients 1 patient 1 patient 1 patent 2 patients 1 patient

5 Two unusual cases were found during our study showing a postnatal infection found in preterm (#12) while a congenital infection in full term patient with serious defect of CNS without any disturbances in psychomotoric development (#11) Results: case reports 4 Case report of patient n. 12 Case report of patient n. 11 born 27+4 weeks of gestation (WG), birth weight 780g mother decompensated arterial hypertension, primary aldosteronism, gestational diabetes APGAR score IUGR, signs of bronchopulmonar dysplasia (surfactant administration 4 days ago delivery), hypotonia 37 WG- ventilary dysfunctions, development of pneumonia (6 days of ventilatory support, improved after ATB therapy) CMV IgG antibodies were positive at 37+5 WG interestingly negative PCR CMV in Guthrie card born 40+2 weeks of gestation, birth weight 2160g APGAR score congenital developmental defect of CNS at the US test in 31 WG (porencephaly, pachygyria, microgyria, hemosiderosis and calcification). local choroidal atrophy; neurologically hyperexcitative status and contractures in flex and slight asymetry in particular reflexes. CMV IgM antibodies were detected in cord blood. ganciclovir treatment (10 mg/kg/d) started at the age of 5 days and including valganciclovir (5 mg/kg/d) lasted for 76 days except of strabism, patient is recently without any neurological and developmental problems

6 Conclusion 5 Our study showed a frequently observed thrombocytopenia in the group CMV infected patients. This indicates that there might be a strong correlation between the number of thrombocytopenia and CMV infections. We therefore recommend that CMV infection should be routinely tested in the differential diagnosis of thrombocytopenia in neonate age. Due to the high variability of genotypes in our group of patients we couldn t observe any clear correlation between the specific genotype and clinical consequences. Further studies should be performed with a larger cohort of patients.