scholarly journals Prediction of poor neurological development in patients with symptomatic congenital cytomegalovirus diseases after oral valganciclovir treatment

2019 ◽  
Vol 41 (9) ◽  
pp. 743-750 ◽  
Author(s):  
Sachiyo Fukushima ◽  
Ichiro Morioka ◽  
Shohei Ohyama ◽  
Kosuke Nishida ◽  
Sota Iwatani ◽  
...  
2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S23-S23 ◽  
Author(s):  
Scott H James ◽  
Ra’Shun L Conner ◽  
David W Kimberlin ◽  
Richard Whitley ◽  
Mark N Prichard

Abstract Background A recently completed Phase 3 randomized, controlled, double-blind, multicenter study of infants with symptomatic congenital cytomegalovirus (CMV) disease receiving 6 months of oral valganciclovir (VGCV) therapy represents the largest such population in which to evaluate treatment-emergent antiviral resistance. The most common mechanism of CMV antiviral resistance occurs through mutations in the CMV UL97 gene that confer resistance to ganciclovir (GCV). Genotypic resistance analyses were performed on infants receiving 6 months of VGCV to assess the incidence of antiviral resistance due to UL97 sequence variants. Methods Resistance analyses were performed by conventional DNA sequencing of the UL97 gene at multiple time points. Following CMV DNA extraction from frozen whole blood specimens, the UL97 gene was amplified with a double nested polymerase chain reaction method and sequenced to identify polymorphisms and mutations that might confer GCV resistance. Results Forty-six infants with symptomatic CMV disease who received a 6-month course of VGCV underwent resistance analysis to identify UL97 sequence variants. In addition to a range of natural polymorphisms known to have no effect on antiviral susceptibility, 2 subjects developed UL97 mutations known to confer resistance to GCV (A594V and G598S detected in one subject; E596G detected in another), yielding an incidence of 4%. Each of these resistance mutations occurred in specimens collected after at least 4 months of antiviral therapy. As evaluated in the original Phase 3 trial, neither of these infants showed an improvement in hearing outcome. Conclusion The development of treatment-emergent UL97 resistance mutations was determined in a controlled study population of infants with congenital CMV disease receiving 6 months of VGCV. This targeted resistance analysis demonstrated an incidence approaching the total incidence of antiviral resistance for CMV disease in some immunocompromised populations, such as solid-organ transplant recipients. Further studies within this study population are warranted to elucidate the risk of emerging antiviral resistance and to assess clinical impact as well as the potential need for combination antiviral therapy. Disclosures All authors: No reported disclosures.


2008 ◽  
Vol 197 (6) ◽  
pp. 836-845 ◽  
Author(s):  
David W. Kimberlin ◽  
Edward P. Acosta ◽  
Pablo J. Sánchez ◽  
Sunil Sood ◽  
Vish Agrawal ◽  
...  

2011 ◽  
Vol 53 (2) ◽  
pp. 249-252 ◽  
Author(s):  
Takashi Imamura ◽  
Tatsuo Suzutani ◽  
Hiroshi Ogawa ◽  
Kimisato Asano ◽  
Mika Nomoto ◽  
...  

2021 ◽  
Vol 14 (7) ◽  
pp. e242712
Author(s):  
Ana Araújo Carvalho ◽  
Cláudia B Silva ◽  
Maria Luísa Martins ◽  
Gonçalo Cassiano Santos

Cytomegalovirus (CMV) infection is one of the preeminent congenital viral infections, and despite its potential morbidity, uncertainty about its physiopathology, prevention and treatment remains until now. We report a case of a dichorionic and diamniotic twin pregnancy in which only one of the fetus had signs of being affected. The first twin had prenatal diagnosis of intrauterine growth restriction and hyperechogenic bowel, attributable to CMV infection, while there was no evidence of infection of the second one. Prenatal treatment was done with maternal administration of valacyclovir and postnatal treatment of the infected newborn with oral valganciclovir with normal neurodevelopment assessment at 12 months corrected age. In this case, maternal CMV infection was not equally transmitted to both fetuses, suggesting that there may be intrinsic fetal and placental factors influencing both transmission and the clinical features of the infection.


2013 ◽  
Vol 57 (4) ◽  
pp. 356-360 ◽  
Author(s):  
K. Yeon Choi ◽  
B. Sharon ◽  
H.H. Balfour ◽  
K. Belani ◽  
T.C. Pozos ◽  
...  

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S600-S600
Author(s):  
Kathleen Murtagh ◽  
Jacquie Toia ◽  
Tonya Scardina ◽  
Anne H Rowley ◽  
Leena B Mithal

Abstract Background Congenital CMV (cCMV) is associated with sensorineural hearing loss and neurodevelopmental disabilities. Infants with symptomatic cCMV infection benefit from 6 months of oral valganciclovir (vGCV) therapy. Neutropenia, thrombocytopenia, and hepatotoxicity are adverse effects vGCV, for which we monitor. We observed a pattern that cCMV infants treated with vGCV developed an uptrend in platelets and/or thrombocytosis (platelet count >450,000/uL) while on therapy. This observation has not previously been reported. Methods Medical records and laboratory results from our multi-disciplinary cCMV clinic led by Infectious Diseases at Lurie Children’s Hospital were reviewed (2017-2020). Data included cCMV signs/symptoms, cCMV treatment prescribed, indication for ganciclovir/vGCV treatment, and complete blood count prior to, during, and post- vGCV therapy. Results Of 21 cCMV infants referred to clinic, 14 received >1 month of vGCV for symptomatic disease, 1 discontinued vGCV < 1 month due to perceived fussiness, and 1 was part of a clinical trial. Four infants were initially treated with ganciclovir for ≤1 month and transitioned to vGCV. Of the 14 patients treated with vGCV, 10 (71%) had sensorineural hearing loss (50% unilateral), 12 (86%) had central nervous system abnormalities (including cystic lesions on head ultrasound), 5 (36%) had thrombocytopenia, and 7 (50%) were intrauterine growth restricted [Table 1]. Eleven infants (79%) developed thrombocytosis. Thirteen infants (93%) had an uptrend in platelet count [not including normalization of initial thrombocytopenia (platelets < 150,000/uL)]. Figure 1 shows platelet counts by time with respect to vGCV treatment. Neutropenia (absolute neutrophil count < 500/uL) occurred in 1 patient that required temporary discontinuation of vGCV. Table 1 Figure 1 Conclusion We observed an interesting trend of rising platelet count and the development of thrombocytosis in the majority of our cCMV patients on vGCV. Platelet elevation associated with vGCV has not previously been described. This observation is limited by small number of patients and thrombocytosis is not a definitive association/adverse effect. With increasing use of vGCV and interest in its effect on bone marrow function, this observation is notable and warrants further study. Disclosures All Authors: No reported disclosures


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