RESUMEN
BACKGROUND: Intravenous immunoglobulin G (IVIG) is used to treat blood-type incompatibility hemolytic disease of newborns (BTHDN). Although IVIG's efficacy for treating BTHDN has been challenged, as an updated systematic review suggests, IVIG could significantly reduce exchange transfusions. We conducted a mail-in questionnaire survey to ascertain actual use of IVIG for BTHDN in Japan. METHODS: The survey, conducted in 2014, included infants born between January 1, 2009, and December 31, 2013. Questionnaires were sent to the heads of neonatal intensive care units (NICUs) at perinatal centers of the Japan Neonatologist Association. RESULTS: A total of 195 centers (64.6%) responded to the questionnaire. During the study period, 170 centers (87.2%) reported incidences of BTHDN. Among these centers, there were 1726 diagnosed cases of BTHDN in neonates. Of these cases, 419 infants were treated with IVIG in 127 centers, representing approximately 74.7% of all centers. After the exclusion of cases with missing data and those where consent for data usage was not obtained, a total 916 infants were included in this study. Of these, 219 (23.9%) were treated with IVIG after phototherapy, and 187 (20.4%) of these infants did not require further blood exchange transfusion. The IVIG dosages ranged from 40 to 1200 mg/kg/dose, but the majority were between 500 and 1000 mg/kg/dose, with a median of 800 mg/kg/dose. About 20% of the infants treated with IVIG showed late-onset anemia and required treatment. Adverse events were reported in less than 1% of infants. CONCLUSIONS: For the treatment of BTHDN, IVIG administration was widely used in NICUs in Japan without severe adverse events.
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Eritroblastosis Fetal , Ictericia Neonatal , Ictericia , Femenino , Humanos , Lactante , Recién Nacido , Eritroblastosis Fetal/epidemiología , Eritroblastosis Fetal/terapia , Inmunoglobulinas Intravenosas , Japón/epidemiología , Ictericia/inducido químicamente , Ictericia/tratamiento farmacológico , Ictericia Neonatal/epidemiología , Ictericia Neonatal/terapia , Estudios Retrospectivos , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: This non-randomized intervention study aimed to evaluate the effect of supplementing infant formula with biotin on biotin metabolism and on development. METHODS: We enrolled healthy Japanese infants (n = 84) and assigned them to groups offered Formula A (total biotin, 0.5 µg/100 kcal) or Formula B (total biotin, 2.4 µg/100 kcal) until they were 6 months of age, and completed an additional follow up to age 36 months. Urinary biotin concentrations were measured at 1 and 6 months, and were compared among breast-fed, Formula A-fed, and Formula B-fed infants at each age. In a follow-up subgroup analysis, we compared scores on the Ages and Stages Questionnaire, version 3 (ASQ-3), from 9 to 36 months among infants continuously fed Formula A, Formula B, or breastmilk. RESULTS: No adverse events occurred during the intervention period. At 1 month, urinary biotin concentrations were highest in Formula B-fed infants and lowest in Formula A-fed infants. At 6 months, Formula B-fed infants retained higher biotin levels than Formula A-fed and breast-fed infants. Both differences were statistically significant (P < 0.05). The breast-fed, Formula A-fed, and Formula B-fed groups had similar ASQ scores at 9-36 months. CONCLUSIONS: Biotin supplementation of infant formula contributed to improving biotin status in formula-fed infants. The results support the official approval of the use of biotin in infant formula by the government of Japan in 2014.
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Biotina , Fórmulas Infantiles , Lactante , Femenino , Humanos , Preescolar , Japón , Lactancia Materna , Suplementos DietéticosAsunto(s)
Síndromes Mielodisplásicos , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Femenino , Humanos , Recién Nacido , Madres , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/terapia , Trombocitopenia/diagnóstico , Trombocitopenia/etiologíaRESUMEN
Neonatal disseminated herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity; yet, the pathophysiology remains unclear. Here, we report a male infant with disseminated HSV type 1 (HSV-1) infection, complicated by hemophagocytic lymphohistiocytosis (HLH) and multiple organ failure. The infant, born at 39 weeks of gestation by normal delivery, developed fever (38.5ËC) with the high serum C-reactive protein levels on the 1st day of life, and exhibited tachypnea on the 3rd day. On the 5th day of life, the patient received mechanical ventilation and was transferred to our neonatal ICU. Real-time PCR for HSV-1 DNA revealed an extremely high serum concentration (1.0 × 109 copies/µL), and he was diagnosed with HSV-1 infection. Acyclovir (ACV) and corticosteroid pulse therapies with methylprednisolone were started. Continuous hemodiafiltration (CHDF) using cytokine-absorbing hemofilters was also initiated because of renal failure. These therapies, however, failed to control the disease, and the patient died on the 41st day of life. The dose of ACV on CHDF might not be adequate, although we could not measure the serum ACV concentrations. After the patient's death, we measured his serum cytokine concentrations taken four times during the clinical course. Serum concentrations of interleukin (IL)-6, IL-10, IL-1ß, and interferon (IFN)-γ were elevated at the time of admission and were remarkably decreased by 10 days after treatment. In particular, the concentrations of IL-1ß and IFN-γ were lower than the measurable ranges. It is therefore important to measure serum cytokine concentrations in real time to prevent excessive immune suppression.
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Herpes Simple/virología , Linfohistiocitosis Hemofagocítica/complicaciones , Complicaciones Infecciosas del Embarazo/virología , Índice de Severidad de la Enfermedad , Carga Viral , Adulto , Estudios de Casos y Controles , Citocinas/sangre , Resultado Fatal , Femenino , Herpes Simple/sangre , Humanos , Lactante , Recién Nacido , Linfohistiocitosis Hemofagocítica/sangre , Masculino , Complicaciones Infecciosas del Embarazo/sangreAsunto(s)
Displasia Broncopulmonar , Mucopolisacaridosis II , Síndrome de Dificultad Respiratoria del Recién Nacido , Recién Nacido , Humanos , Displasia Broncopulmonar/complicaciones , Displasia Broncopulmonar/diagnóstico , Recien Nacido Prematuro , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Síndrome de Dificultad Respiratoria del Recién Nacido/etiologíaRESUMEN
Background: Antiviral-resistant herpes simplex virus type 1 (HSV-1) has been recognized as an emerging clinical problem among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A prospective observational study was conducted at a hematological center over a 2-year period. Oropharyngeal swab samples were serially collected each week from 1 week before and up to 100 days after HSCT and were tested for virus isolation. The HSV-1 isolates were tested for sensitivity to acyclovir (ACV). The prognosis of patients with ACV-resistant (ACVr) HSV-1 and the genetic background of the ACVr HSV-1 isolates were assessed. Results: Herpes simplex virus type 1 was isolated in 39 of 268 (15%) HSCT patients within 100 days after transplantation. Acyclovir-resistant HSV-1 emerged in 11 of these 39 patients (28%). The 100-day death rates of HSCT patients without HSV-1 shedding, those with only ACV-sensitive HSV-1 shedding, and those with ACVr HSV-1 shedding were 31%, 39%, and 64%, respectively. Patients with HSV-1, including ACVr HSV-1, shedding showed a significantly higher mortality rate. Relapsed malignancies were a significant risk factor for the emergence of ACVr HSV-1. Acyclovir resistance was attributable to viral thymidine kinase and DNA polymerase mutations in 6 and 5 patients, respectively. Conclusions: Herpes simplex virus type 1, including ACVr HSV-1, shedding was associated with poorer outcome in HSCT patients, even if HSV disease did not always occur. Patients with relapsed malignancies were at especially high risk for the emergence of ACVr HSV-1.
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Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Farmacorresistencia Viral , Trasplante de Células Madre Hematopoyéticas/mortalidad , Herpes Simple/tratamiento farmacológico , Herpesvirus Humano 1/efectos de los fármacos , Adolescente , Adulto , Anciano , ADN Polimerasa Dirigida por ADN/genética , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Simple/virología , Herpesvirus Humano 1/aislamiento & purificación , Humanos , Japón , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/virología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Tasa de Supervivencia , Timidina Quinasa/genética , Adulto JovenRESUMEN
Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days.
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Vacunas Antirrábicas/inmunología , Virus de la Rabia/inmunología , Rabia/inmunología , Vacunación/métodos , Potencia de la Vacuna , Animales , Peso Corporal/inmunología , Embrión de Pollo , Femenino , Humanos , Ratones , Rabia/mortalidad , Rabia/virología , Análisis de Supervivencia , Tasa de Supervivencia , Factores de Tiempo , Vacunas de Productos Inactivados/inmunología , Pérdida de Peso/inmunologíaAsunto(s)
Cardiomiopatías , Insuficiencia Cardíaca , Neoplasias Cardíacas , Rabdomioma , Esclerosis Tuberosa , Everolimus/uso terapéutico , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/tratamiento farmacológico , Humanos , Rabdomioma/complicaciones , Rabdomioma/diagnóstico , Rabdomioma/tratamiento farmacológicoRESUMEN
Tetraploidy is characterized by the presence of four complete sets of chromosomes in an individual. Full tetraploidy is usually considered lethal. To date, only ten live-births with the condition have been reported. Trisomy 18 without neonatal intensive treatment is also known to be fatal. We report a female newborn who had mosaicism with near-tetraploidy and trisomy 18 (94,XXXX,+18,+18/47,XX,+18). She had features of conditions. The most plausible mechanism of the formation was a failure of cytoplasmic cleavage at the first division of the zygote. The longer survival of the patient compared with the 10 previously reported live-births with non-mosaic tetraploidy may be due to the dominance of the trisomy cells. We suggest that non-tetraploid cells, even when trisomic for chromosome 18, might contribute to longer survival in comparison to non-mosaic tetrapolid patients.
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Anomalías Múltiples/genética , Cromosomas Humanos Par 18/genética , Mosaicismo , Trisomía/genética , Anomalías Múltiples/fisiopatología , Análisis Citogenético , Femenino , Humanos , Recién Nacido , Tetraploidía , Trisomía/fisiopatología , Síndrome de la Trisomía 18RESUMEN
Among the tick-borne orbiviruses (genus Orbivirus, family Reoviridae), 36 serotypes are currently classified within a single virus species, Great Island virus. In this study, we report the first characterization of a tick-borne orbivirus isolated from the tick Ixodes turdus in Japan, which we identified as a new member of the species Great Island virus. The virus isolate, designated Muko virus (MUV), replicated and induced cytopathic effects in BHK-21, Vero E6, and CCL-141 cells and caused high mortality in suckling mice after intracerebral inoculation. Full genome sequence analysis showed that MUV shared the greatest phylogenetic similarity with Tribec virus in terms of the amino acid sequences of all viral proteins except for outer capsid protein 1 (OC1; VP4 of MUV). Analysis of genome segment 9 in MUV detected an uninterrupted open reading frame that overlaps with VP6 (Hel), which putatively encodes a molecular and functional equivalent of NS4 from Great Island virus. Our study provides new insights into the geographic distribution, genetic diversity, and evolutionary history of the members of the species Great Island virus.
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Vectores Arácnidos/virología , Ixodes/virología , Orbivirus/genética , Orbivirus/aislamiento & purificación , Infecciones por Reoviridae/virología , Animales , Línea Celular , Genoma Viral , Humanos , Japón , Ratones , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Orbivirus/clasificación , Filogenia , Proteínas Virales/genéticaRESUMEN
Rabies is a viral disease transmitted through bites from rabid animals and can be prevented by vaccines. Clinically used rabies vaccines are prepared from inactivated rabies viruses grown in cell cultures or embryonated eggs. In Japan and across the world, tests that confirm complete inactivation, such as the in vivo suckling mouse assay, in which suckling mice are intracerebrally inoculated with vaccine products, are required for quality control. In this study, we developed a novel cell-based immunofluorescence assay that does not require mice for testing rabies vaccine inactivation for human use. The sensitivity of this cell-based in vitro assay was 5.7 times that of the in vivo suckling mouse assay, with a detection limit of one focus forming units per ml of test sample. This newly developed in vitro assay may replace the established in vivo suckling mouse assay for confirming viral vaccine inactivation.
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Vacunas Antirrábicas/química , Vacunas de Productos Inactivados/química , Animales , Animales Lactantes , Línea Celular , Cricetinae , Humanos , Técnicas In Vitro , RatonesRESUMEN
The 22q11.2 deletion syndrome has many complications; one of them is immunodeficiency. However, the time of onset and the degree of immunodeficiency can vary. We report a case of a preterm infant with congenital cytomegalovirus infection complicated with 22q11.2 deletion syndrome and immunological abnormalities. Ultrasonography revealed pulmonary atresia, ventricular septal defect, major aortopulmonary collateral artery, and thymic hypoplasia. His serum chemistry tests on admission revealed immunoglobulin G, A, and M levels of 1,547 mg/dL, 70 mg/dL, and 274 mg/dL, respectively. A surface antigen analysis of the peripheral lymphocytes using flow cytometry revealed the following: relatively low CD4-positive T-cell levels (18.1%; 1,767/µL), very high CD8-positive T-cell levels (58.9%; 5,751/µL), and CD4/CD8 ratio of 0.31. The level of T-cell receptor excision circles was relatively low at 17.5 copies/µL. After birth, the CD8-positive T-cell level began to gradually decrease, whereas the CD4/CD8 ratio began to increase. Thrombocytopenia, neutropenia, and skin petechiae were observed on admission. However, the condition improved. Treatment for congenital cytomegalovirus infection was not provided due to the absence of viremia. Unfortunately, the patient died suddenly on the 158th day of life, and the cause of death was unknown. To the best of our knowledge, no association between 22q11 deletion syndrome and cCMV has been described in the recent medical literature. According to the calculation, around one newborn infant who have both 22q11 deletion syndrome and cCMV infection will be born each year in Japan. Healthcare providers should pay more attention to this medical situation in the future.
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Infecciones por Citomegalovirus , Síndrome de DiGeorge , Cardiopatías Congénitas , Atresia Pulmonar , Lactante , Humanos , Recién Nacido , Síndrome de DiGeorge/complicaciones , Recien Nacido Prematuro , Infecciones por Citomegalovirus/complicacionesRESUMEN
The binding ratio of palmitic acid (PA) at the sn-2 position of triacylglycerols in infant formulas is lower than that in breast milk, resulting in higher levels of fecal PA. Even if the ratio is increased to 40-50%, fecal PA levels in formula-fed infants remain higher than those in breast-fed infants. In Japan, infant formulas with 50% or more of PA bound to sn-2 (high sn-2 PA milk) are commercially available; however, their effects on PA excretion have not been investigated. Therefore, this observational study aimed to preliminarily evaluate whether the feeding volume of high sn-2 PA milk is significantly associated with fecal total/soaped PA levels in newborns. Infant formulas were classified as high (≥50% of PA bound to sn-2) or low sn-2 (<50%) PA milk. Associations between feeding volume of high or low sn-2 PA milk and fecal PA levels were evaluated using multiple regression analysis models. The results showed that the feeding volume of low sn-2 PA milk was positively associated with fecal total/soaped PA levels, while there was no significant association between those of high sn-2 PA milk and fecal total/soaped PA levels. Our preliminary study suggests that high sn-2 PA milk may reduce increased fecal PA levels in formula-fed newborns.
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Heces , Fórmulas Infantiles , Ácido Palmítico , Triglicéridos , Humanos , Fórmulas Infantiles/química , Heces/química , Ácido Palmítico/análisis , Triglicéridos/análisis , Triglicéridos/química , Recién Nacido , Femenino , Masculino , Fenómenos Fisiológicos Nutricionales del Lactante , Leche Humana/química , JapónRESUMEN
Meconium, a non-invasive biomaterial reflecting prenatal substance accumulation, could provide valuable insights into neonatal health. However, the comprehensive protein profile of meconium across gestational ages remains unclear. Here, we conducted an extensive proteomic analysis of first meconium from 259 newborns across varied gestational ages to delineate protein composition and elucidate its relevance to neonatal diseases. The first meconium samples were collected, with the majority obtained before feeding, and the mean time for the first meconium passage from the anus was 11.9 ± 9.47 h. Our analysis revealed 5370 host-derived meconium proteins, which varied depending on sex and gestational age. Specifically, meconium from preterm infants exhibited elevated concentrations of proteins associated with the extracellular matrix. Additionally, the protein profiles of meconium also exhibited unique variations depending on both specific diseases, including gastrointestinal diseases, congenital heart diseases, and maternal conditions. Furthermore, we developed a machine learning model to predict gestational ages using meconium proteins. Our model suggests that newborns with gastrointestinal diseases and congenital heart diseases may have immature gastrointestinal systems. These findings highlight the intricate relationship between clinical parameters and meconium protein composition, offering potential for a novel approach to assess neonatal gastrointestinal health.
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Edad Gestacional , Aprendizaje Automático , Meconio , Proteómica , Humanos , Meconio/metabolismo , Recién Nacido , Femenino , Masculino , Proteómica/métodos , Recien Nacido Prematuro/metabolismo , Enfermedades Gastrointestinales/metabolismo , Cardiopatías Congénitas/metabolismo , Embarazo , Proteoma/metabolismoRESUMEN
Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.
RESUMEN
A neonate with herpes simplex virus 1 encephalitis was treated with intravenous acyclovir. During the course of therapy, the infection became intractable to the treatment and a mutation in the viral thymidine kinase gene (nucleotide G375T, amino acid Q125H) developed. This mutation was demonstrated in vitro to confer acyclovir resistance.
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Aciclovir/farmacología , Antivirales/farmacología , Farmacorresistencia Viral , Encefalitis por Herpes Simple/diagnóstico , Herpes Simple/diagnóstico , Herpesvirus Humano 1/aislamiento & purificación , Complicaciones Infecciosas del Embarazo/diagnóstico , Aciclovir/uso terapéutico , Sustitución de Aminoácidos , Antivirales/uso terapéutico , ADN Viral/química , ADN Viral/genética , Encefalitis por Herpes Simple/virología , Herpes Simple/virología , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/genética , Humanos , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Mutación Missense , Complicaciones Infecciosas del Embarazo/virología , Análisis de Secuencia de ADN , Timidina Quinasa/genéticaRESUMEN
Reports on the birth of infants weighing <300 g are quite rare and little is known about the best practices in treating such micropreemies. Therefore, we report here on three cases of low birthweight infants weighing <300 g, of whom two infants survived. The birthweights and gestational ages were ranging 279-293 g and 22 + 6/7 - 23 + 6/7 weeks, respectively. All the infants had severe fetal growth restriction and prematurity. The infant in case 1 died of hepatic rupture, perhaps due to birth trauma, which emphasized the need for less invasive obstetric procedures including en caul delivery. The infant in case 2 managed to survive through severe prematurity secondary to hydrops fetalis. However, complications followed soon as tracheal granulation tissue was formed with neurodevelopmental impairment. The infant in case 3 was born recently and her clinical course was less remarkable without severe complications, despite having the least gestational age and birthweight among the three patients. The improved care protocols for extremely low birthweight infants over these years through experiential learning including that with cases 1 and 2 may have ensured the better outcome of case 3. Accumulating evidence and recording the experience of such cases with continuous constructive discussion can contribute to better outcomes and appropriate parental counseling for extremely small babies in the future.
RESUMEN
Pulmonary hypoplasia is a rare entity in a fetus with imperforate anus. The fetus was diagnosed with high-type imperforate anus with rectourethral fistula based on the dilated fetal bowel and the presence of bowel calcification at 19 weeks of gestation. As gestation advanced, fetal ultrasonography demonstrated development of pulmonary hypoplasia, progressive bowel dilation, and persistent oligohydramnios from 28 weeks of gestation despite a fluid-filled bladder without hydroureter or hydronephrosis. To prevent further worsening of pulmonary hypoplasia caused by thoracic compression due to bowel dilation and oligohydramnios, a male neonate was delivered by cesarean section at 32 weeks of gestation. The neonate showed respiratory failure requiring full respiratory support. Although a catheter did not pass through the urethra into the bladder at birth, cystourethrography revealed the patency of fistula and stenosed lower urinary tract. Prenatal and postnatal findings strongly suggested that the meconium in the colon might have passed into the urethra in the penis, resulting in the physical blockage of urine outflow to the amniotic space which leads urine flow from the bladder to the colon through the fistula, which resulted in subsequent oligohydramnios and bowel dilation. To the best of our knowledge, this is the first case report of a fetus with imperforate anus developing pulmonary hypoplasia possibly due to urethral obstruction.
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We report the one case of sepsis caused by Bifidobacterium breve administered as probiotic therapy. Probiotics can be a potential cause of an invasive disease and should be used with care in vulnerable patients.
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Infecciones por Bifidobacteriales/etiología , Bifidobacterium/aislamiento & purificación , Hernia Umbilical/cirugía , Cuidados Posoperatorios/efectos adversos , Probióticos/efectos adversos , Sepsis/etiología , Antibacterianos/uso terapéutico , Infecciones por Bifidobacteriales/tratamiento farmacológico , Infecciones por Bifidobacteriales/microbiología , Femenino , Humanos , Recién Nacido , Cuidados Posoperatorios/métodos , Embarazo , Probióticos/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
Ion Torrent next-generation sequencing (NGS) technology was applied to study the mode of emergence of acyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1 (HSV-1) in patients with hematopoietic stem cell transplantation (HSCT) by quantitatively detecting mutations in the viral thymidine kinase (vTK) gene in the HSV-1 isolates recovered from HSCT patients. All of the mutations detected with the Sanger sequencing method in the vTK genes of HSV-1 isolates were also detected with the NGS assay. Furthermore, different mutations, which conferred ACV resistance and were not detected with the Sanger sequencing method, were also detected in a quantitative manner by using the NGS assay. The approach described here is applicable to studying the emergence process of vTK gene mutation-associated ACVr HSV-1 more in detail than the Sanger method. The NGS assay makes it possible to make a diagnosis of vTK gene mutation-associated ACVr HSV-1 infections at the early stage, which the ratio of ACVr HSV-1 is much lower than that of ACV-sensitive (ACVs) HSV-1.