ABSTRACT
BACKGROUND: Congenital human cytomegalovirus (cCMV) infection can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Ganciclovir and valganciclovir (GCV/VGCV) improve long-term audiologic and neurodevelopmental outcomes for patients with cCMV infection; however, antiviral drug resistance has been documented in some cases. Long-read sequencing can be used for the detection of drug resistance mutations. The objective of this study was to develop full-length analysis of UL97 and UL54, target genes with mutations that confer GCV/VGCV resistance using long-read sequencing, and investigate drug resistance mutation in patients with cCMV infection. METHODS: Drug resistance mutation analysis was retrospectively performed in 11 patients with cCMV infection treated with GCV/VGCV. UL97 and UL54 genes were amplified using blood DNA. The amplicons were sequenced using a long-read sequencer and aligned with the reference gene. Single nucleotide variants were detected and replaced with the reference sequence. The replaced sequence was submitted to a mutation resistance analyzer, which is an open platform for drug resistance mutations. RESULTS: Two drug resistance mutations (UL54 V823A and UL97 A594V) were found in one patient. Both mutations emerged after 6 months of therapy, where viral load increased. Mutation rates subsided after cessation of GCV/VGCV treatment. CONCLUSIONS: Antiviral drug resistance can emerge in patients with cCMV receiving long-term therapy. Full-length analysis of UL97 and UL54 via long-read sequencing enabled the rapid and comprehensive detection of drug resistance mutations.
Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Drug Resistance, Viral , Antiviral Agents/therapeutic use , Child , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/drug therapy , Drug Resistance, Viral/genetics , Ganciclovir/therapeutic use , Humans , Mutation , Retrospective Studies , Valganciclovir/therapeutic useABSTRACT
Cytomegalovirus (CMV) is the most common cause of congenital infection. Pneumonitis is considered to be a rare manifestation although congenital CMV infection presents with various non-specific findings. Ganciclovir and valganciclovir are beneficial for improving neurodevelopmental sequelae and hearing outcomes of congenital CMV infection; however, treatment response evaluation is not well reported. We report a female case of congenital CMV infection presenting with pneumonitis, meningoencephalitis, and chorioretinitis. She was treated with intravenous ganciclovir for 6 weeks, and clinical features improved. Measurement of the CMV genome load by real-time polymerase chain reaction assay was performed during treatment. After the administration of ganciclovir, the CMV genome was not detected in the blood and levels decreased gradually in the urine. Physicians should consider the possibility of congenital CMV infection in neonates who present with respiratory distress. Furthermore, measurement of the CMV genome load in blood and urine may be useful for evaluating treatment response.
Subject(s)
Antiviral Agents/administration & dosage , Cytomegalovirus Infections/drug therapy , Cytomegalovirus/isolation & purification , Drug Monitoring/methods , Ganciclovir/administration & dosage , Pneumonia/drug therapy , Viral Load , Administration, Intravenous , Adult , Blood/virology , Chorioretinitis/congenital , Chorioretinitis/drug therapy , Chorioretinitis/pathology , Chorioretinitis/virology , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/pathology , Cytomegalovirus Infections/virology , DNA, Viral/blood , DNA, Viral/urine , Female , Humans , Infant, Newborn , Meningoencephalitis/congenital , Meningoencephalitis/drug therapy , Meningoencephalitis/pathology , Meningoencephalitis/virology , Pneumonia/congenital , Pneumonia/pathology , Pneumonia/virology , Real-Time Polymerase Chain Reaction , Urine/virologyABSTRACT
For the first time in 16 years, a food-borne outbreak of typhoid fever due to Salmonella enterica serotype Typhi was reported in Japan. Seven patients consumed food in an Indian buffet at a restaurant in the center of Tokyo, while one was a Nepali chef in the restaurant, an asymptomatic carrier and the implicated source of this outbreak. The multiple-locus variable-number tandem repeat analysis showed 100% consistency in the genomic sequence for five of the eight cases.
