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• The Japanese immunization law was revised in October 2020. • Rotavirus vaccines are now included in the Japanese National Immunization Program. • Rules on vaccine intervals have been withdrawn. • The Japan Pediatric Society Vaccine Information Statement was published in 2018. • Concerns remain regarding the Japanese immunization program. The Japanese immunization program has made considerable progress since 2009: several new vaccines have been introduced and most are included in the National Immunization Program (NIP). In October 2020, the Japanese law on immunization was revised, which resulted in a few laudable achievements. First, rotavirus vaccines were added to the NIP, 10 years after their introduction, and noteworthy studies of vaccine effectiveness and the incidence of intussusception in Japanese children were published. Second, rules on vaccine intervals—which had been a longstanding concern—were withdrawn. In addition to this revision of the law, the Japanese version of the Vaccine Information Statement (VIS) was released by the Japan Pediatric Society in 2018. The VIS provides useful caregiver information on general immunization concepts and individual vaccines. Further challenges for the Japanese immunization program include (1) administering a booster dose of pertussis-containing vaccine to preschool children or teenagers, (2) reestablishing the active recommendation for human papilloma virus vaccines, (3) adding the mumps and influenza vaccines to the NIP, and (4) ensuring optimal dosing of seasonal influenza vaccines. During the current coronavirus disease 2019 (COVID-19) pandemic, vaccination rates among children have been decreasing in many countries. In Japan, vaccination rates have been stable in infants, but declining among toddlers and school-aged children, despite public awareness of the need for timely administration of vaccines during the pandemic. Clearly, further action is needed if we are to adequately protect children living in Japan from vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan. This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups. We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01). The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood. [ABSTRACT FROM AUTHOR]

Intradermal (ID) injection is an alternate route that enhances vaccine immunogenicity and decreases vaccine dose. Regular immunization usually starts at age 2 months, and the limited immune capacity of neonates and young infants makes them vulnerable to infection. Successful ID vaccine delivery in this population requires knowledge of skin thickness. Although skin thickness has been evaluated in infants aged 2 months or older, no comparable data are available for neonates, including preterm neonates. This prospective observational study used ultrasonography to assess skin thickness in 70 neonates (35 full-term and 35 preterm neonates) at deltoid, suprascapular, and thigh sites. The measurements were compared in relation to anatomical site, between full-term and preterm infants, and with skin thickness values for children aged 2 months or older, which were collected in our previous study using the same measurement technique. In full-term neonates, skin was significantly thicker at the suprascapular site than at the deltoid and thigh sites (P < 0.05); in preterm neonates, skin was significantly thicker at the suprascapular site than at the thigh site (P < 0.05). Skin thickness values at all three sites were significantly lower in preterm neonates than in full-term neonates (P < 0.05). As compared with skin thickness values for infants aged 2 months, values for full-term neonates were significantly lower for the deltoid and suprascapular sites (P < 0.001). Skin thickness values for neonates were affected by prematurity and were significantly lower than those for infants aged 2 months. These findings are important in the design of ID injection devices for neonates and young infants. [ABSTRACT FROM AUTHOR]

The Japanese immunization program has made considerable recent progress. The introduction of several new vaccines, especially foreign-produced vaccines, and the inclusion of important new vaccines in the National Immunization Program (NIP) are closing the “vaccine gap”, i.e., the delay in the Japanese immunization program relative to programs in other developed countries. Major progress in the Japanese immunization program since 2014 includes (1) elimination of measles in March 2015, (2) introduction of a varicella vaccine as a routine immunization in the NIP in October 2015, and (3) introduction of hepatitis B virus vaccines as routine immunizations in the NIP in October 2016. Despite these promising developments, important issues remain. First, the government withdrew the active recommendation for human papilloma virus vaccines temporarily in 2013. The withdrawal has continued and unresolved despite new scientific evidence confirming the safety of these vaccines. Second, a few important voluntary vaccines, including vaccines for mumps and rotavirus, have not been included in the NIP since their introduction to Japan. Finally, there are concerns related to a shortage of mandatory domestic vaccines, which was caused by a natural disaster in the area where a vaccine-producing factory was located. Additionally, the manufacturer included unauthorized additives in some vaccine products with falsifying the production-process records. To avoid problems related to vaccine shortages, essential vaccines need to be stockpiled, and the future vaccine needs for children should to be discussed. New initiatives must continue to close the vaccine gap, as this will protect children living in Japan from vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Background Perinatal immunization education is important for improving the immunization outcomes of infants; however, the content of educational materials used at each perinatal period has not been carefully evaluated. We hypothesized that stepwise education offered at different perinatal periods would improve infant immunization status and enhance maternal immunization knowledge. Methods In this cluster-randomized controlled trial, pregnant women were recruited from nine obstetric sites in Niigata, Japan. The intervention group received a stepwise, interactive education intervention (prenatally, postnatally, and 1 month after birth). The control group received a leaflet containing general information on immunization. Infant immunization status was evaluated at 6 months of age, and maternal immunization knowledge was evaluated by a written survey after each intervention. Results Among 188 study participants, 151 (80.3%) replied to the final post-intervention survey. At 6 months of age, the percentage of children who completed three doses of inactivated polio, diphtheria, tetanus toxoid, and acellular pertussis (DTaP-IPV) vaccine was higher in the intervention group than in the control ( p = 0.04); however, no differences between groups were observed for the Haemophilus influenzae type b (Hib) ( p = 0.67) or 13-valent pneumococcal conjugate (PCV13) vaccines ( p = 0.20). The duration to the completion of the third dose of the DTaP-IPV, Hib, and PCV13 vaccines was shorter in the intervention group than in the control ( p = 0.03, p < 0.01, and p < 0.01, respectively). Furthermore, maternal knowledge scores exhibited significantly greater improvement in the intervention group over time compared with those of the control group ( p = 0.02). Conclusions Stepwise perinatal immunization education improved immunization schedule adherence for required vaccines and improved maternal immunization knowledge. [ABSTRACT FROM AUTHOR]

Background Accurate, standardized information on childhood immunization is not available in Japan. We investigated current practices in perinatal childhood immunization education in the community and the needs and interest for such education among Japanese mothers. Methods This cross-sectional, descriptive study evaluated pregnant and postnatal women at four institutions in Niigata, Japan from May through July 2014. Data were collected using questionnaires inquiring about demographics, immunization education received, intent to receive childhood vaccines, and needs regarding information on childhood immunization. Results Questionnaires were distributed to 300 women, and 116 (38.6%) were returned; 70 (59.6%) of the respondents were pregnant women and 46 (40.3%) were postnatal women. Fourteen (20%) of the 70 pregnant women reported receiving some form of immunization education; in contrast, 34 (73.9%) of 46 postnatal women had received such education within 1 month of delivery. The rates of respondents who felt that the information was insufficient were high: 78.6% among pregnant women and 52.9% among postnatal women. Pregnant women reported that the most important information was general concepts of immunization; in contrast, postnatal women desired more-detailed information, e.g., on immunization scheduling. Conclusions Japanese women do not receive sufficient perinatal immunization education. The information needed during the prenatal and postnatal periods differs. Thus, educational approaches may need to provide carefully targeted information. [ABSTRACT FROM AUTHOR]

As compared with standard intramuscular and subcutaneous vaccines, intradermal (ID) vaccines elicit a more potent immune response in both adults and children, with equivalent dosage or antigen dose sparing. Recently, various devices for ID injection have been developed; the length of needles ranges in 0.6–1.5 mm. However, skin thickness must be measured to determine optimal needle length for ID vaccines. Use of ID vaccines in infants and children is appealing because children require more vaccines than do adults; however, information on skin thickness in infants and children is limited. We used ultrasound echography to measure skin thickness in Japanese infants aged 2 months ( n = 78) and adolescents aged 13–15 years ( n = 82). Mean (range) deltoid and suprascapular skin thickness was 1.67 mm (1.16–2.39 mm) and 1.83 mm (1.24–2.60 mm), respectively, in infants and 1.81 mm (1.25–3.00 mm) and 2.43 mm (1.51–3.95 mm), respectively, in adolescents. Among infants who underwent re-measurement of skin thickness at age 6 months ( n = 11), mean deltoid skin thickness (1.84 mm) was significantly greater than at age 2 months (1.60 mm) ( P < 0.001). In contrast, no significant difference was observed in suprascapular skin thickness (1.79 mm vs. 1.67 mm, respectively; P = 0.17). Gender was not associated with skin thickness in either age group. Skin thickness was positively correlated with body weight in adolescents ( r = 0.43, P < 0.001 in deltoid region; r = 0.30, P = 0.01 in suprascapular region). In conclusion, this is the first study to evaluate skin thickness in different age groups of children, including at age 2 months. Skin thickness gradually increased from age 2 months to age 13–15 years, but no consistent trend was noted in analysis stratified by measurement site, gender, or age. These findings suggest that an appropriate length of ID device needle for infants and children is likely to be less than 1.2 mm and a special device with shorter length of needle is warranted for infants and children. [ABSTRACT FROM AUTHOR]

Abstract: The “vaccine gap” is a term which has been used in Japan to indicate that the current immunization program is behind compared to the programs in other developed countries. The current national immunization program (NIP) which was established under the Japanese Immunization Law includes only six vaccines (eight targeted diseases), and the rest of available vaccines have been categorized as voluntary vaccines, which require out-of-pocket expense in order for the patients to receive them. This has led the vaccination rates for the voluntary vaccines remaining low, and the incidence of the target diseases remaining high. In addition, there are a few domestic rules that exist for immunizations including (1) subcutaneous injection is the standard method of vaccination, (2) the thigh is not considered to be the common site of vaccination in infants, and (3) the intervals of administration of inactivated and live vaccines are strictly determined by law. Along with the “vaccine gap” and the domestic rules, some movements to improve our current NIP are underway; including increased calls to change the NIP from civilians and professionals, the establishment of a group by the representatives from 13 medical professional societies asking the government to consider the immunization policy a “national policy” and seeking the establishment of a new and reorganized national immunization technical advisory group (NITAG). In addition, the Vaccination Subcommittee of Health Sciences Council was formed in the government to reform the current Immunization Law and NIP, which established a new national program for three voluntary vaccines funded by a temporary budget. We hope these new movements will fill the “vaccine gap” and that the NITAG will help ensure that vaccine policy becomes a national policy, and will provide necessary vaccinations without out-of-pocket expense to protect children in Japan from vaccine preventable diseases. [Copyright &y& Elsevier]

The article presents a study which examines the effect of P-glycoprotein (ABCB1) genetic variants and cytochrome P450 (CYP) on nelfinavir pharmacokinetics and virologic response to highly active antiretroviral therapy (HAART) in HIV-1-infected children. Researchers perform genomic DNA assay among HIV-1-infected children using real-time polymerase chain reaction (PCR). Results show that nelfinavir pharmacokinetics and response to HAART in children are changed by CYP2C19 genotypes.

The article focuses on the analysis of CYP2B6-G516T polymorphisms in HIV-infected children who are receiving highly active antiretroviral therapy containing efavirenz (EFV). The impact of CYP2B6-G516T polymorphisms on EFV concentrations may be different in children because of differences in liver maturation and drug dosage.

Abstract: The destabilization of vesicles caused by interactions between lipid bilayers and proteins was studied by direct, real-time observation using high-intensity dark-field microscopy. We previously reported that talin, a cytoskeletal submembranous protein, can reversibly open stable large holes in giant liposomes made of neutral and acidic phospholipids. Talin and other proteins belonging to the band 4.1 superfamily have the FERM domain at their N-terminal and interact with lipid membranes via that domain. Here, we observed that band 4.1, ezrin and moesin, members of the band 4.1 superfamily, are also able to open stable holes in liposomes. However, truncation of their C-terminal domains, which can interact with the N-terminal FERM domain, impaired their hole opening activities. Oligomeric states of ezrin affected the capability of the membrane hole formation. Phosphatidylinositol bisphosphate (PIP2), which binds to the FERM domain and disrupts the interaction between the N and C termini of the band 4.1 superfamily, down-regulates their membrane opening activity. These results suggest that the intermolecular interaction plays a key role in the observed membrane hole formation. [Copyright &y& Elsevier]

The associations between human immunodeficiency virus type 1 (HIV-1) intracellular DNA and immunological markers were analyzed longitudinally for children with sustained, undetectable RNA levels while receiving highly active antiretroviral therapy (HAART) for >2 years. When DNA levels reached a plateau at week 104 of therapy, in contrast to findings for adults, there was no correlation between the CD4+:CD8+ ratio and DNA levels (r = -0.02; P = .95), and naive CD4+CD45RA+ lymphocytes predominated. These data suggest that the increased proportion of naive lymphocytes found in children are less susceptible to HIV-1 infection than are the memory lymphocytes that dominate immune reconstitution in adults. [ABSTRACT FROM AUTHOR]

Examines the persistence of HIV type 1 DNA in peripheral blood mononuclear cells in children. Usefulness of HIV-1 DNA as a marker for virus suppression; Effect of antiretroviral therapy on HIV-1 DNA levels; Median half-life of intracellular HIV-1 DNA.

Discusses the morphological changes of the liposomes. How liposomes can be visualized; Observation of liposomes; Detailed information on liposomes.

Introduction: Bronchopulmonary dysplasia (BPD) is associated with neurodevelopmental outcomes of preterm infants, but its effect on brain growth in preterm infants after the neonatal period is unknown. This study aimed to evaluate the effect of severe BPD on brain growth of preterm infants from term to 18 months of corrected age (CA). Methods: Sixty-three preterm infants (42 with severe BPD and 21 without severe BPD) who underwent magnetic resonance imaging at term equivalent age (TEA) and 18 months of CA were studied by using the Infant Brain Extraction and Analysis Toolbox (iBEAT). We measured segmented brain volumes and compared brain volume and brain growth velocity between the severe BPD group and the non-severe BPD group. Results: There was no significant difference in brain volumes at TEA between the groups. However, the brain volumes of the total brain and cerebral white matter in the severe BPD group were significantly smaller than those in the non-severe BPD group at 18 months of CA. The brain growth velocities from TEA to 18 months of CA in the total brain, cerebral cortex, and cerebral white matter in the severe BPD group were lower than those in the non-severe BPD group. Conclusion: Brain growth in preterm infants with severe BPD from TEA age to 18 months of CA is less than that in preterm infants without severe BPD. [ABSTRACT FROM AUTHOR]

The underlying disease was ultimately diagnosed as XL-EDA-ID because of the decreased NEMO activity (up to 20% of wild-type NEMO) assessed by NF- B luciferase reporter assay of the D311E variant [[4]]. Conical incisors are one of the keys to identifying I IKBKG i variants in boys with unusually severe infections, even when such patients do not have other clinical manifestations of ectodermal dysplasia [[2]]. Although NF- B activation by NEMO involvement is essential in the ectodysplasin/ectodysplasin receptor signaling pathway, residual NEMO activity of 20-50% might be enough for the dental development. [Extracted from the article]

Data are limited on the incidence of coronavirus disease 2019 (COVID-19) reinfection in children. This population-based cohort study in Niigata, Japan from January to November 2022 demonstrated the incidence of reinfection was 1337/48 099 (2.8%), and the hazard ratio for reinfection in vaccinated children was 0.29 (95% confidence interval, 0.20–0.40). [ABSTRACT FROM AUTHOR]

• Mumps is still endemic in Japan because mumps vaccination is voluntary. • We clarified several parental factors associated with mumps vaccination. • Our study also highlights the importance of clear explanations of mumps vaccine. Mumps is still endemic in Japan because mumps vaccination is voluntary. In this study, we investigated associations of parental socioeconomic status, family structure, and knowledge/belief about mumps and mumps vaccine with parental decision to vaccinate their children. We also evaluated effectiveness of a campaign based on survey results. We conducted a cross-sectional survey of parents with children aged 1–6 years attending preschools or kindergartens in Tokamachi City, Japan. We assessed the association of parental factors with their decision to vaccinate their children using multivariable logistic regression analyses. We designed a campaign based on the survey results, and compared the number of annual vaccinations at Tokamachi Hospital per the child population aged 1–6 years in Tokamachi City before and after the campaign using a trend test. In total, 1391 of 1617 (86%) eligible parents completed the survey. Among these parents, 229 (16%) vaccinated their children. In multivariable analyses, higher parental education [odds ratio (OR) = 2.21; 95% CI, 1.59–3.08; P < 0.001], greater knowledge about mumps and the mumps vaccine (OR = 1.88; 95% CI, 1.60–2.21; P < 0.001), and living without grandparents (OR = 1.44; 95% CI, 1.05–1.99; P = 0.024) were significantly associated with parental decision to vaccinate their children. The number of annual vaccinations per the child population significantly increased following the campaign (P < 0.001). Our study showed several sociodemographic factors significantly associated with mumps vaccination. Further research is needed to examine the relevance of our findings to the uptake of other voluntary vaccines among children. [ABSTRACT FROM AUTHOR]

Neonatal gonorrhea, caused by Neisseria gonorrhoeae , is an uncommon but important disease to prevent because its complications, such as gonococcal ophthalmia neonatorum causes blindness if untreated. Neonatal gonococcal nasopharyngitis is a rare, but important clinical manifestation to suspect gonococcal infection in a neonate. Herein we report a case of neonatal gonococcal nasopharyngitis, presented with purulent nasal discharge. A full-term male neonate without perinatal complications developed purulent eye discharge on the 7th day of life. N. gonorrhoeae was isolated from the eye discharge culture; however, he did not receive the standard regimen. Subsequently, he presented to our hospital with fever and nasal discharge on the 20th day of life. N. gonorrhoeae was also isolated from nasal discharge and nasopharyngeal swabs without any evidence of chlamydia or syphilis. He received intravenous cefotaxime until disseminated gonococcal infection was ruled out and was discharged without any sequelae. Rhinorrhea in newborns requires consideration of mother-to-child transmission of various microorganisms, not only common respiratory viruses, but also rare, serious preventable infections such as gonorrhea or syphilis. Along with the recent syphilis patients on the rise in Japan, gonorrhea is an important disease to recognize, and the incidence could increase. Clinical manifestations of neonatal gonococcal infections, including nasopharyngitis, need to be recognized to suspect the diagnosis and initiate appropriate treatment to prevent serious complications. [ABSTRACT FROM AUTHOR]

We report a case of myelomeningocele in an infant whose mother was exposed to efavirenz during the first 16 weeks of pregnancy. Although the true risk for myelomeningocele with the use of efavirenz early in pregnancy is still unknown, the findings in humans are consistent with those observed in primates and suggest that efavirenz is a potent teratogen. Thus, we suggest that efavirenz only be prescribed for women of childbearing potential when no other comparable antiretroviral options are available.Journal of Perinatology (2005) 25, 555–556. doi:10.1038/sj.jp.7211343; published online 9 June 2005 [ABSTRACT FROM AUTHOR]

Early-onset sepsis (EOS) is a serious and fatal illness in neonates, Group B Streptococcus and Escherichia coli are major causative pathogens. We report a case of EOS and pneumonia caused by E. coli in a preterm neonate with multiple pneumatoceles and lung abscesses. A male neonate weighing 1670g was delivered at 33 6/7 weeks' gestation by a mother with clinical chorioamnionitis. He showed respiratory distress soon after birth and developed septic shock. He was intubated and mechanical ventilation was started. E.coli was detected in blood culture obtained from both the patient and his mother. He developed multiple pneumatoceles and lung abscesses. Surgical drainage was complicated, cefotaxime was thus continued until day 74. Pneumatoceles and lung abscesses are complications of neonatal pneumonia, rarely reported by E. coli. Multiple lung abscesses in our patient are distinct from single abscesses in previous case studies of neonatal lung abscesses. We speculate that bacteremia along with pneumatoceles led to multiple lung abscesses in our patient. These complications require long-term antibiotic therapy, to minimize morbidity and mortality, and should thus be considered when managing EOS caused by E. coli. [ABSTRACT FROM AUTHOR]

Human parechoviruses (HPeVs) are RNA viruses that have characteristics similar to those of enteroviruses and usually cause mild respiratory or gastrointestinal symptoms. Human parechovirus type 3 (HPeV3), first reported in 2004, is exceptional because it can provoke sepsis and meningoencephalitis leading to neurological sequelae, and even death, in neonates and young infants. Pediatricians and researchers are increasingly aware that HPeV3 is responsible for serious disease in neonates and young infants. Retrospective studies and several reports of epidemics of HPeV3 infection have provided data on epidemiology, clinical symptoms and signs, laboratory findings, and outcomes. However, the pathogenesis of HPeV3 infection remains unclear, which explains the lack of specific antiviral therapy and effective prevention measures. Maternal antibodies are important in protection against severe HPeV3-related disease, and this may be a clue regarding its pathogenesis. HPeV3 epidemics are likely to continue, and because the clinical manifestations of HPeV3 are severe, determining the pathogenesis of HPeV3 infection and establishing specific antiviral therapies are important goals for future research. [ABSTRACT FROM AUTHOR]

Aim This study was aimed at examining the effects of treatment with rituximab, a chimeric monoclonal antibody against the protein CD20, in a B-lymphocyte independent adriamycin-induced rat model of nephrotic syndrome. Rituximab is an emerging rescue therapy used in patients with complicated nephrotic syndrome and, therefore, we sought to elucidate the apparent B-lymphocyte independent mechanism underlying its anti-proteinuric effect. Methods Adriamycin-induced nephropathy was established in Wistar rats by intravenously injecting 10 mg/kg of adriamycin, which were then treated with rituximab or purified human IgG weekly and euthanized on day 28. Proteinuria, glomerular expression of sphingomyelin phosphodiesterase acid-like 3b protein, and podocyte-related proteins were examined using immunofluorescence staining and a reverse transcription-polymerase chain reaction. Results Rituximab treatment of rats with adriamycin-induced nephropathy significantly reduced urinary protein excretion 14 to 28 days after induction of disease, compared with those treated with purified normal human IgG. Furthermore, rituximab treatment also prevented the reduction of glomerular nephrin and podocin expression on day 28. Double-immunofluorescence staining revealed that after in vivo administration, rituximab was bound to the glomeruli, which also expressed synaptopodin or sphingomyelin phosphodiesterase, acid-like 3b. Moreover, sphingomyelin phosphodiesterase, acid-like 3b expression was significantly decreased on day 28 of adriamycin-induced nephropathy, which was also prevented by rituximab. Conclusions This study demonstrated that rituximab directly affected glomerular podocytes and ameliorated proteinuria in adriamycin-induced nephropathy in rats. Furthermore, protection of podocyte function by rituximab may be mediated by direct modulation of a sphingomyelin phosphodiesterase, acid-like 3b-dependent mechanism. [ABSTRACT FROM AUTHOR]

Parechovirus-A3 (PeV-A3), first reported in 2004 in Japan, is an emerging pathogen that causes sepsis and meningoencephalitis in neonates and young infants. Although PeV-A3 has been identified worldwide, its epidemiological characteristics differ by region. To investigate the molecular evolution and epidemiology of PeV-A3, we performed genetic analyses of 131 PeV-A3 strains from the years 1997–2019 in Niigata, Japan. During 2016–2019, annual numbers remained steady, in contrast to the PeV-A3 epidemic interval of every 2–3 years that was observed in Japan from 2006. Bayesian evolutionary analysis of the complete viral protein 1 region revealed alternate dominant clusters during years of PeV-A3 epidemics. The branch including the oldest and first isolated PeV-A3 strains in Japan has been disrupted since 2001. The year of PeV-A3 emergence was estimated to be 1991. Continuous surveillance with genetic analyses of different regions will improve understanding of PeV-A3 epidemiology worldwide. [ABSTRACT FROM AUTHOR]

Timothy syndrome (TS) is a rare pleiotropic disorder associated with long QT syndrome, syndactyly, dysmorphic features, and neurological symptoms. Several variants in exon 8 or 8a of CACNA1C, a gene encoding the α-subunit of voltage-gated Ca2+ channels (Cav1.2), are known to cause classical TS. We identified a p.R412M (exon 9) variant in an atypical TS case. The aim of this study was to examine the functional effects of CACNA1C p.R412M on CaV1.2 in comparison with those of p.G406R. The index patient was a 2-month-old female infant who suffered from a cardio-pulmonary arrest in association with prolonged QT intervals. She showed dysmorphic facial features and developmental delay, but not syndactyly. Interestingly, she also presented recurrent seizures from 4 months. Genetic tests identified a novel heterozygous CACNA1C variant, p.R412M. Using heterologous expression system with HEK-293 cells, analyses with whole-cell patch-clamp technique revealed that p.R412M caused late Ca2+ currents by significantly delaying CaV1.2 channel inactivation, consistent with the underlying mechanisms of classical TS. A novel CACNA1C variant, p.R412M, was found to be associated with atypical TS through the same mechanism as p.G406R, the variant responsible for classical TS. [ABSTRACT FROM AUTHOR]

Background Infantile central nervous system infections (CNSIs) can be life-threatening and cause severe sequelae. However, the causative microorganism remains unknown in >40% of patients with aseptic infections. This study aimed to analyze the metagenome for detection of pathogens and the transcriptome for host immune responses during infection in a single cerebrospinal fluid (CSF) sample using 2 different next-generation sequencing (NGS) platforms, Nanopore and Illumina. Methods Twenty-eight CNSIs patients (<12 months) were enrolled, and 49 clinical samples (28 CSF and 21 blood) were collected. The DNA extracted from all 49 samples was sequenced using the Illumina sequencer for the detection of pathogens. Extracted RNA was obtained in sufficient quantities from 23 CSF samples and subjected to sequencing on both Nanopore and Illumina platforms. Human-derived reads subtracted during pathogen detection were used for host transcriptomic analysis from both Nanopore and Illumina sequencing. Results RNA metagenomic sequencing using both sequencing platforms revealed putative viral pathogens in 10 cases. DNA sequencing using the Illumina sequencer detected 2 pathogens. The results of Nanopore and Illumina RNA sequencing were consistent; however, the mapping coverage and depth to the detected pathogen genome of Nanopore RNA sequencing were greater than those of Illumina. Host transcriptomic analysis of Nanopore sequencing revealed highly expressed genes related to the antiviral roles of innate immunity from pathogen-identified cases. Conclusions The use of Nanopore RNA sequencing for metagenomic diagnostics of CSF samples should help to elucidate both pathogens and host immune responses of CNSI and could shed light on the pathogenesis of these infections. [ABSTRACT FROM AUTHOR]

Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. The primary strategy for immunizing transplant recipients is to deliver all potential vaccines prior to transplantation. However, time constraints limit the number of vaccines that may be delivered. In such cases, the administration of live attenuated vaccines that are contraindicated after transplantation should be prioritized. Simultaneous vaccination is also encouraged to maximize the number of vaccines delivered. Immunity induced by both inactivated and live vaccines wane after transplantation. The limited but available evidence suggests that immunization using inactivated vaccines in transplant recipients is both effective and safe. An increasing number of studies also suggest that once patients are under minimal immunosuppression, live attenuated vaccines may be given effectively and safely. The need for serologic monitoring and booster immunizations remain issues for future research. [ABSTRACT FROM AUTHOR]

Herpes zoster caused by reactivation of latent varicella-zoster virus (VZV) usually develop in later adulthood. In the pediatric population, herpes zoster is unusual, and involvement of pharyngolaryngeal lesion and cranial nerves is rare. Here, we report a 14-year-old boy who was diagnosed with laryngeal herpes zoster (LHZ), and developed subsequent cranial nerve symptoms suspected of vagus neuropathy. This case provides additional evidence that children can develop LHZ and subsequent cranial nerve symptoms. LHZ should be considered if a pediatric patient with a history of varicella, has unilateral throat pain, with or without cranial nerve symptoms. [ABSTRACT FROM AUTHOR]

Background: Acute lower respiratory infection (ALRI) remains the leading cause of death in children worldwide, and viruses have been the major cause of ALRI. In Myanmar, ALRI is associated with high morbidity and mortality in children, and detailed information on ALRI is currently lacking.Methods: This prospective study investigated the viral aetiologies, clinical manifestations, and outcomes of ALRI in hospitalised children aged 1 month to 12 years at the Yankin Children Hospital, Yangon, Myanmar from May 2017 to April 2019. The sample size was set to 300 patients for each year. Two nasopharyngeal swabs were obtained for the patients with suspected viral ALRI; one for rapid tests for influenza and respiratory syncytial virus (RSV), and the other for real-time PCR for the 16 ALRI-causing viruses. Pneumococcal colonization rates were also investigated using real-time PCR. Clinical information was extracted from the medical records, and enrolled patients were categorised by age and severity for comparison.Results: Among the 5463 patients admitted with a diagnosis of ALRI, 570 (10.4%) were enrolled in this study. The median age of the patients was 8 months (interquartile range, 4-15 months). The most common symptoms were cough (93%) and difficulty in breathing (73%), while the most common signs of ALRI were tachypnoea (78%) and chest indrawing (67%). A total of 16 viruses were detected in 502 of 570 patients' samples (88%), with RSV B (36%) and rhinovirus (28%) being the most commonly detected. Multiple viruses were detected in 221 of 570 samples (37%) collected from 570 patients. Severe ALRI was diagnosed in 107 of 570 patients (19%), and RSV B and human rhinovirus were commonly detected. The mortality rate was 5%; influenza virus A (29%) and RSV B (21%) were commonly detected, and stunting and lack of immunization were frequently observed in such cases. Additionally, 45% (259/570) of the patients had pneumococcal colonization.Conclusions: Viral ALRI in hospitalised children with a median of 8 months has significant morbidity and mortality rates in Myanmar. RSV and rhinovirus were the most commonly detected from nasopharyngeal swabs, while influenza virus and RSV were the most frequently associated with fatal cases. [ABSTRACT FROM AUTHOR]

Objectives: To determine if providing perinatal immunization education positively changes the immunization status of infants, influences the infant immunization knowledge, attitudes and beliefs of mothers and affects the intent to vaccinate children in Japan where immunization education is limited. Methods: Pregnant women were recruited from three sites in Tokyo, Japan and were assigned to two intervention (pre- or postnatal education) groups and a control group. The immunization status of infants was assessed and a written survey was performed before and after the intervention. Results: Among 119 study participants, 106 subjects replied to the post-survey. The intervention groups (34.3%) had higher immunization rates in infants at three months of age than the control group (8.3%) (P=0.005); however, no differences were observed between the prenatal (29.4%) and postnatal groups (38.9%) (P=0.40). The percentage of women intended to vaccinate their infants was higher in the intervention groups (61.4%) compared to the control group (33.3%) (P=0.01). The improvement in score for basic knowledge was higher in the intervention groups, particularly in the prenatal group (mean±S.D.: 3.4±1.8) compared to the control (1.9±1.9) (P=0.003). Conclusions: Perinatal immunization education improved the immunization status of infants, increased the women's knowledge on immunization and intention to vaccinate their infants. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to examine the seroprevalence of human T-lymphotropic virus (HTLV)-I among pregnant women at our institution in Tokyo, Japan, which is a non-endemic area, and to investigate the results of Western blotting among pregnant women who had obtained positive results from a screening test. Material and Methods: The seroprevalence of HTLV-I was retrospectively reviewed in 11 352 pregnant women who gave birth at the National Center for Child Health and Development in Tokyo, Japan, between 2002 and 2009. For the screening test, a chemiluminescent enzyme immunoassay was performed followed by a confirmatory Western blot test. Results: The overall positive rate for the screening test was 0.33% (37/11 352). Western blot testing was performed in 36 of these 37 cases. Only nine patients (25%) were positive for HTLV-I by Western blot testing, seven patients (19%) were indeterminate, and 20 patients (56%) were negative. Conclusions: In this study (carried out in a non-endemic area), the percentage of patients with a positive result from the screening test who were confirmed to be true carriers was significantly low, differing from endemic areas. [ABSTRACT FROM AUTHOR]

Efavirenz, a nonnucleoside reverse transcriptase inhibitor, is a highly effective and widely prescribed antiretroviral agent. It is recommended as first-line treatment of human immunodeficiency virus (HIV) infection. The standard dose of efavirenz is 600 mg/day; however, adverse central nervous system effects limit its use. Few data citing use of efavirenz at lower doses have been published. We describe a 35-year-old man with HIV infection whose virologic suppression was maintained after 18 months of treatment with efavirenz 400 mg/day. Genetic testing for cytochrome P450 (CYP) 2B6 showed that the patient was a heterozygous variant; patients with this polymorphism tend to have higher plasma efavirenz concentrations and slower plasma efavirenz clearance (prolonged elimination half-lives). Therapeutic drug monitoring also supported the dose reduction in this patient. Even with the 400-mg dose, the patient's plasma trough concentrations exceeded the upper limit of the therapeutic range. However, as he remained completely asymptomatic with this dose, no further dose reduction was necessary. This case report provides evidence that reduced efavirenz doses may be effective in the treatment of HIV infection. In addition, this case demonstrates that pharmacogenetic and pharmacokinetic testing combined with therapeutic drug monitoring may be used to guide reduced-dose, efavirenz-based therapy. [ABSTRACT FROM AUTHOR]

The heat transfer mechanism of multiple impinging jets with gas–solid suspensions has been investigated experimentally and numerically. By heat transfer experiments, the effects of nozzle Reynolds number, solid loading ratio, distance from jet exit to impingement surface, spacing between jets and solid particle characteristics on the heat transfer coefficient were cleared. In the case of using graphite particles, the heat transfer coefficient enhancement as against single phase flow are found all over the heat transfer surface. While, in the case of using glass beads particles, the heat transfer coefficient is decreased compared with single phase flow. Numerical simulation were also performed by using Yokomine et al.''s model in which both turbulence augmentation and suppression due to particles can be taken into account. In the case of graphite particle, particles flow near the heat transfer surface with making belt-shaped dense region after impingement and its heat capacity and function of turbulence augmentation are used effectively. When the glass beads are used, particles are scattered after impingement and turbulent kinetic energy near the heat transfer surface is decreased. [Copyright &y& Elsevier]

The coronavirus disease 2019 (COVID-19) pandemic has greatly affected daily life. COVID-19 often causes asymptomatic or mild disease in children; however, delayed routine childhood immunization is a concern, as it could increase the risk of vaccine-preventable disease. No study has evaluated the status of childhood vaccinations in Japan during the COVID-19 pandemic. This retrospective observational study evaluated the number of vaccine doses administered to children in 4 Japanese cities (2 cities in the Tokyo metropolitan area and 2 cities far from Tokyo) during the period from 2016 to 2020. Vaccine doses administered between January and September 2020 during the COVID-19 pandemic were compared, by month, with those given during 2016–2019. Age-stratified demographic data were collected to determine whether factors other than change in the child population over time affected vaccination trends. In all cities the decrease in vaccine doses administered was most apparent in March and April 2020, i.e., just before or coincident with the declaration of a nationwide COVID-19 emergency on April 7, 2020. The decrease started as early as February in the Tokyo metropolitan area. As child age increased, the decrease became more apparent. Before the lift of national emergency on May 25, catch-up of the vaccination was observed in all age groups in all cities. Vaccine doses persistently increased in older age groups but not in infants. The overall vaccination trends did not differ significantly among the 4 cities. The COVID-19 pandemic significantly affected routine childhood immunization in Japan. Thus, a nationwide electronic surveillance system and announcements for guardians to encourage timely routine immunization are warranted. [ABSTRACT FROM AUTHOR]

The nucleolus serves a multifaceted role encompassing not only rRNA transcription and ribosome synthesis, but also the intricate orchestration of cell cycle regulation and the modulation of cellular senescence. G-patch domain containing 4 (GPATCH4) stands as one among the nucleolar proteins; however, its functional significances remain still unclear. In order to elucidate the functions of GPATCH4, we examined the effects of its dysfunction on cellular proliferation, alterations in nucleolar architecture, apoptotic events, and cellular senescence. Through experimentation conducted on cultured neuroblastoma SH-SY5Y cells, the reduction of GPATCH4 caused inhibition of cellular proliferation, concurrently fostering escalated apoptotic susceptibilities upon exposure to high-dose etoposide. In the realm of nucleolar morphology comparisons, a discernible decline was noted in the count of nucleoli per nucleus, concomitant with a significant expansion in the area occupied by individual nucleoli. Upon induction of senescence prompted by low-dose etoposide, GPATCH4 knockdown resulted in decreased cell viability and increased expression of senescence-associated markers, namely senescence-associated β-galactosidase (SA-β-GAL) and p16. Furthermore, GPATCH4 dysfunction elicited alterations in the gene expression profile of the ribosomal system. In sum, our findings showed that GPATCH4 is a pivotal nucleolar protein that regulates nucleolar morphology and is correlated with cell viability. • GPATCH4 reduction inhibited cell proliferation and increased apoptotic sensitivity. • GPATCH4 knockdown reduced the nucleolar number and increased the size of each. • GPATCH4 reduction enhanced senescence-associated markers such as SA-β-GAL and p16. • GPATCH4 plays a role in nucleolus morphology and correlates with cell viability. [ABSTRACT FROM AUTHOR]

• Umbilical cord arteritis (UCA) is associated with brain injury in preterm neonates. • Preterm neonates with UCA have high G-CSF, IL-1β, and IL-6 levels in cord blood. • Very preterm neonates with UCA have high G-CSF levels in cord blood. • G-CSF levels in cord blood could be an optimal predictor for UCA. The study aimed 1) to evaluate the association between the presence or absence of umbilical cord arteritis (UCA) and the cord blood cytokine levels, and 2) morbidity and mortality of preterm neonates; and 3) to identify predictive markers for UCA of preterm neonates. In this single-center retrospective observational cohort study, preterm neonates born at gestational age (GA) < 36 weeks were categorized pathologically according to the severity of intrauterine inflammation; those without UCA as Group 1, those with UCA as Group 2, and those without any intrauterine inflammation as Group 3 (control), and subgroup analyses classified by their GA were performed. We compared morbidity and mortality, and eight representative cytokine levels in cord blood samples between the groups. Subsequently, receiver operating characteristics (ROC) curves for UCA diagnosis for each cytokine were created, and values of areas under the curve (AUC) were calculated to determine the optimal predictive markers. In total, 105 patients (36, 58, and 11 in Groups 1, 2, and 3, respectively) were included. Multivariate logistic analysis revealed that patients with UCA had higher incidence of brain injury (Odds Ratio [OR] = 8.53, P = 0.0049, 95% Confidence Interval [CI]: 1.91 – 38.0), at term equivalent age in the subgroup analysis with GA < 32 weeks. Although the median value of cord blood granulocyte colony-stimulating factor (G-CSF) was significantly higher in Group 2 than in Group 1 or 3, only the G-CSF level was found to be high in the subgroup analysis with GA < 32 weeks. For UCA diagnosis, the AUC values of G-CSF were the highest among eight cytokines including interleukin 6 (IL-6). These findings were similar in the subgroup analysis with GA < 32 weeks. Preterm neonates, especially born at GA < 32 week, had higher morbidity from brain injury in the group with UCA. The cord blood G-CSF level was highly accurate for predicting UCA and could thus be used as an optimal biomarker. [ABSTRACT FROM AUTHOR]

Recently, efforts have been made to fill a so-called "vaccine gap" between Japan and other countries; however, more work remains. Concerns about adverse events following immunization (AEFI) resulted in an historically passive approach to policy making in the National Immunization Program (NIP). For example, reports of AEFI following human papillomavirus vaccine (HPVV) in 2013 led the Japanese government to withdraw its proactive recommendations, resulting in a sharp drop in HPVV coverage rate to less than 1.0%. In this report, we review key historical incidents that led to the current immunization system in Japan, compare it to that in the United States, and discuss strategies for improving the Japanese immunization system. By strengthening existing policies and programs, such as National Immunization Technical Advisory Groups and AEFI reporting, compensation laws, and immunization education, the remaining vaccine gap in Japan could be filled. [ABSTRACT FROM AUTHOR]

Background: The strategy to eradicate polio is based on preventing infection by immunizing all children until the world is polio‐free. However, data regarding efficacy of polio‐containing vaccination in immunocompromised patients such as LT recipients are limited. Methods: We conducted an observational study at the largest pediatric transplant center in Japan from January 2011 to January 2015. LT recipients were enrolled after transplantation, and those who had completed the Japanese polio vaccination program were eligible for the study. Patients' demographics were collected from their medical records. Antibody titers against poliovirus serotypes 1‐3 were measured using the neutralization test at the routine follow‐up visits after enrollment. Factors associated with seropositivity against each type of poliovirus were evaluated. Results: Sixty‐four patients who had received the complete polio vaccination series were enrolled in the study. Of these, 37 patients had received all series of polio‐containing vaccination before LT. Median age of the patients was 75 months. Their underlying diseases included the following: 40 (63%) with cholestatic liver diseases and 11 (17%) with metabolic disorders. After a median interval of 43 months after LT, seropositivity rates against poliovirus 1, 2, and 3 were 93.8% (60/64), 92.2% (59/64), and 54.7% (35/64), respectively. Among 32 patients who had received only oral polio vaccine (OPV), seropositivity against poliovirus 3 was particularly low (25.0%). No factors associated with seropositivity against each type of poliovirus were identified. Conclusions: In the LT recipients, seropositivity for poliovirus 3 was low, suggesting a need for additional inactivated polio‐containing vaccination after LT, especially for patients who had received only OPV. [ABSTRACT FROM AUTHOR]

Background: Parechovirus (PeV)-A3 and enteroviruses (EV) are the most common viruses causing sepsis and meningoencephalitis in neonates and young infants. Clinical manifestations of PeV-A3 infection are more severe than those of EV infection, and no pleocytosis with a positive polymerase chain reaction (PCR) result for PeV-A3 in cerebrospinal fluid (CSF) are characteristic findings. We hypothesized that innate immune responses to PeV-A3 and EV are distinct in serum and CSF.Methods: We evaluated 22 cytokines/chemokines in serum and CSF from PeV-A3- or EV-infected patients younger than 4 months in Niigata, Japan, from 2015 through 2018. Infection was diagnosed with real-time PCR followed by sequencing. Febrile neonates and infants with sepsis-like syndrome who had negative bacterial culture and viral PCR for both PeV-A and EV were also included (non-PeV-A/EV patients).Results: Among 192 febrile patients, we evaluated 16 PeV-A3-infected, 15 EV-infected, and 8 non-PeV-A/EV patients. Serum pro-/anti-inflammatory cytokine/chemokine levels were higher in PeV-A3-infected patients than in EV-infected patients (P < .02). Although most cytokine/chemokine were elevated in CSF from EV-infected patients, levels were low or undetectable in PeV-A3-infected and non-PeV-A/EV patients (P < .001).Conclusions: Distinct cytokine/chemokine patterns in serum and CSF may explain the different clinical manifestations of PeV-A3-infected and EV-infected neonates and young infants. [ABSTRACT FROM AUTHOR]

Objectives: One of the reasons as to why chimeric antigen receptors (CAR)‐T cell therapy for malignancies other than CD19‐ or BCMA‐positive tumors has yet to produce remarkable progress is the paucity of targetable antigens. NKp44 is only expressed by activated natural killer cells and detects a variety of transformed cells, while it reportedly does not react with normal tissues. The aim of this study is to develop CAR‐T cell that can target multiple types of tumor cells. Methods: We created a series of novel CAR constructs in first‐generation (1G) and second‐generation (2G) CAR format with the extracellular immunoglobulin‐like domain of NKp44 (NKp44‐CAR). Results: Transduction of the best 1G construct into human primary T cells led to specific cytotoxic effects and cytokine secretion upon encountering multiple types of neoplastic cells including AML, T‐ALL and childhood solid tumors. Replacement of the extracellular hinge domain of NKp44 with that of CD8α resulted in diminished CAR function. The 1G NKp44‐CAR‐T cells exhibited significantly better tumor control in long‐term co‐culture assays compared with activated NK cells, as well as with NK cells transduced with identical NKp44‐CAR. T cells transduced with the best 2G‐CAR construct with 4‐1BB co‐stimulatory domain proliferated at significantly higher levels upon single antigen exposure and showed significantly better tumor control compared with the 1G‐CAR and 2G‐CAR with CD28 co‐stimulatory domain. Conclusions: NKp44‐based CAR endows T cells with NK cell‐like anti‐tumor specificity. The CAR gene created in this study will be useful for the development of novel gene‐modified T‐cell immunotherapy. [ABSTRACT FROM AUTHOR]

Febrile neonates and young infants presenting with seizure require immediate evaluation and treatment. Herein we experienced two young infants with parechovirus-A3 (PeV-A3) encephalitis, initially presented with focal seizure suspecting herpes simplex virus (HSV) encephalitis. We have experienced 2 infantile cases, initially presented with focal seizure. At presentation, HSV encephalitis was strongly suspected and empiric acyclovir therapy was started; however, serum and/or cerebrospinal fluid (CSF) PCR for HSV were negative. Instead, serum and/or CSF PCR for parechovirus-A was positive. PeV-A3 infection was confirmed by genetic sequence analyses. Both cases required multiple anticonvulsant therapy and intensive care for intractable seizure. Diffusion-weighted imaging of brain magnetic resonance imaging (MRI) showed distinct findings; high-intensity lesions in the gray matter of parietal and occipital lobes in Case 1, and bilateral decreased diffusion of the deep white matter and corpus callosum in Case 2. We have followed two cases more than four years; Case 1 developed epilepsy, has been on an anticonvulsant to control her seizure. Case 2 has significant neurodevelopmental delay, unable to stand or communicate with language. PeV-A3 encephalitis needs to be in differential diagnosis when neonates and young infants present with focal seizure, mimicking HSV encephalitis. Special attention may be necessary in patients with PeV-A3 encephalitis given it could present with intractable seizure with high morbidity in a long-term. [ABSTRACT FROM AUTHOR]

In this article the author talks about the changes in laboratory findings in parechovirus-A infection in neonates and infants. Topics discussed include neonates and infants whose serum samples were positive for PeV-A when tested with the polymerase chain reaction (PCR) method at Nagano Red Cross Hospital, Japan, between July and October 2014, and patients received corticosteroids and intravenous immunoglobulin therapy during hospitalization.

A community outbreak of human influenza A(H1N1)pdm09 virus strains was observed in Myanmar in 2017. We investigated the circulation patterns, antigenicity, and drug resistance of 2017 influenza A(H1N1)pdm09 viruses from Myanmar and characterized the full genome of influenza virus strains in Myanmar from in-patients and out-patients to assess the pathogenicity of the viruses. Nasopharyngeal swabs were collected from out-patients and in-patients with acute respiratory tract infections in Yangon and Pyinmana City in Myanmar during January-December 2017. A total of 215 out-patients and 18 in-patients infected with A(H1N1)pdm09 were detected by virus isolation and real-time RT-PCR. Among the positive patients, 90.6% were less than 14 years old. Hemagglutination inhibition (HI) antibody titers against A(H1N1)pdm09 viruses in Myanmar were similar to the recommended Japanese influenza vaccine strain for 2017–2018 seasons (A/Singapore/GP1908/2015) and WHO recommended 2017 southern hemisphere vaccine component (A/Michigan/45/2015). Phylogenetic analysis of the hemagglutinin sequence showed that the Myanmar strains belonged to the genetic subclade 6B.1, possessing mutations of S162N and S164T at potential antigenic sites. However, the amino acid mutation at position 222, which may enhance the severity of disease and mortality, was not found. One case with no prior history of oseltamivir treatment possessed H275Y mutated virus in neuraminidase (NA), which confers resistance to oseltamivir and peramivir with elevated IC50 values. The full genome sequence of Myanmar strains showed no difference between samples from in-patients and out-patients, suggesting no additional viral mutations associated with patient severity. Several amino acid changes were observed in PB2, PB1, and M2 of Myanmar strains when compared to the vaccine strain and other Asian strains. However, no mutations associated with pathogenicity were found in the Myanmar strains, suggesting that viral factors cannot explain the underlying reasons of the massive outbreak in Myanmar. This study reported the first detection of an oseltamivir-resistant influenza virus in Myanmar, highlighting the importance of continuous antiviral monitoring and genetic characterization of the influenza virus in Myanmar. [ABSTRACT FROM AUTHOR]