Soluble LR11 as a Novel Biomarker in Acute Kawasaki Disease.

BACKGROUND: Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.Methods and Results: 106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0-24.9 ng/mL) than in controls (11.9 ng/mL, 10.4-14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7-16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity. CONCLUSIONS: sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.

Skin thickness in neonates: Implications for intradermal vaccination.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Skin thickness in young infants and adolescents: Applications for intradermal vaccination.

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 1.2mm and a special device with shorter length of needle is warranted for infants and children.

Effectiveness of oseltamivir treatment among children with influenza A or B virus infections during four successive winters in Niigata City, Japan.

Oseltamivir has been used for treatment of influenza A and B infections, but recent reports documented that it was less active against the latter. We compared the effectiveness of oseltamivir in children between laboratory confirmed influenza A and B over 4 influenza seasons from 2001 to 2005 in a pediatric clinic in Japan. Among 1,848 patients screened, 299 influenza A and 209 influenza B patients were administered oseltamivir (treated groups), and 28 influenza A and 66 influenza B patients were assigned as non-treated groups. The duration of fever, defined as period when patients had the maximum temperature higher than 37.5 degrees C in three-time measurements in a day after the clinic visit, was evaluated among the four groups. In uni-variate analysis, the duration of fever was shorter for treated group than non-treated for influenza A (1.8 +/- 0.9 days vs 2.6 +/- 1.3 days, p < 0.01), but it was not significant for influenza B (2.4 +/- 1.3 days vs 2.8 +/- 1.2 days, p = 0.9). The fever duration was longer in treated influenza B than A patients (p < 0.01). Multi-variate analysis indicated younger age (< 6 years old) and higher body temperature at the clinic visit prolonged the duration of fever. Adjusted average duration of fever indicated that oseltamivir was effective for both types, but more effective on influenza A, and the benefit increased for younger children. Our data provide evidence that oseltamivir is beneficial for influenza infections, but the effectiveness is differed by type and age.

Peak rotavirus activity shifted from winter to early spring in Japan.

BACKGROUND: Since 1910, there have been many studies on acute gastroenteritis in children in Japan. These diseases, namely Kasei-shoni-kolera (pseudocholera infantum) or banshu-otosho (late autumn vomiting disease), are historically known to occur in the cooler season with a peak in November or December. Earlier we confirmed their causation by rotaviruses but found peaks in January or February from 1974 to 1981. The aim of the present study was to confirm the temporal shift in peak rotavirus activity. METHODS: Under the National Epidemiological Surveillance of Infectious Diseases program from 1983 through 2003, rotavirus positive patients 0-3 years old and clinically diagnosed with "infantile vomiting and diarrhea" at sentinel clinics were examined. Fecal samples were screened by electron microscopy and/or using commercial latex agglutination kits at prefectural/municipal Public Health Institutes, and we determined the trend for the "peak" month during 21 seasons. RESULTS: Peak rotavirus activity shifted gradually from January to March during the 21 consecutive seasons. The mean duration from December to the peak month (mean beginning peak duration) of the rotavirus season significantly varied among 3 periods of 7 consecutive seasons (1.7 +/- 0.5 months in 1982/1983-1988/1989, 2.3+/-0.8 months in 1989/1980-1995/1996, and 3.1 +/- 0.7 months in 1996/1997-2002/2003, respectively; P = 0.0026 by 1-way analysis of variance). This time series shift in the peak rotavirus infection was statistically significant (P = 0.0003 for trend). CONCLUSION: Our findings confirmed that the temporal trend in peak rotavirus activity in Japan has shifted gradually from winter to early spring for unknown reasons.

Molecular epidemiology of respiratory syncytial virus infections among children with acute respiratory symptoms in a community over three seasons.

To study the molecular epidemiology of respiratory syncytial virus (RSV) in a community, children with acute respiratory symptoms at a pediatric outpatient clinic in Niigata, Japan, were analyzed over three seasons from November 2001 to July 2004. Of 499 nasopharyngeal aspirate specimens, 185 (37.1%) were RSV positive, and only 8 (4.5%) of 177 patients were shown by the reverse transcription (RT)-PCR method to be reinfected. RSV infection occurred beginning in the early winter, and the rates declined in the spring. The predominant subgroup changed from A to B and returned to A over the three seasons. Phylogenetic analysis also revealed that multiple genotypes cocirculated each year, with genotype GA5 of subgroup A predominating in the 2001-2002 and the 2003-2004 seasons. A new genotype of subgroup B (named BA, according to the nomenclature for viruses) with a 60-nucleotide insertion in the second variable region of the attachment glycoportein protein was predominant as an emerging strain in the 2002-2003 season, but this was not associated with new epidemiological or clinical features, unlike the cases of disease caused by other genotypes in the other seasons. In conclusion, our molecular analysis of RSV confirms that multiple genotypes cocirculate each year and that the genotype predominating may shift with the season. Support for determination of the genotype by RT-PCR as an effective tool for characterization of RSV circulation patterns in the community is provided.

Geographic and temporal trends in influenzalike illness, Japan, 1992-1999.

From 1992 to 1999, we analyzed >2.5 million cases of influenzalike illness (ILI). Nationwide influenza epidemics generally lasted 3-4 months in winter. Kriging analysis, which illustrates geographic movement, showed that the starting areas of peak ILI activity were mostly found in western Japan. Two spreading patterns, monotonous and multitonous, were observed. Monotonous patterns in two seasons featured peak ILI activity that covered all of Japan within 3 to 5 weeks in larger epidemics with new antigenic variants of A/H3N2. Multitonous patterns, observed in the other five seasons, featured peak ILI activity within 12 to 15 weeks in small epidemics without new variants. Applying the kriging method allowed better visualization and understanding of spatiotemporal trends in seasonal ILI activity. This method will likely be an important tool for future influenza surveillance in Japan.

Frequency of amantadine-resistant influenza A viruses during two seasons featuring cocirculation of H1N1 and H3N2.

In two influenza seasons during which H1N1 and H3N2 cocirculated, resistance was more frequent in H3N2 strains than in H1N1 strains after amantadine treatment. Predominant amino acid substitutions in M2 protein occurred at position 31 (serine to asparagine) in H3N2 strains and at position 27 (valine to alanine) in H1N1 strains.

The effectiveness of influenza vaccine against influenza a (H3N2) virus infections in nursing homes in Niigata, Japan, during the 1998-1999 and 1999-2000 seasons.

OBJECTIVE: To evaluate the effectiveness of influenza vaccines against influenza-like illness (ILI) among nursing home residents. DESIGN: Prospective, nonrandomized, cohort study. SETTING: Nine nursing homes during the 1998-1999 influenza season and 11 nursing homes during the 1999-2000 influenza season in Niigata Prefecture, Japan. PARTICIPANTS: Six hundred ninety-nine residents and 440 healthcare workers (HCWs) during the first season, and 930 residents and 517 HCWs during the second season, with vaccination rates ranging from 0% to 97.7%. RESULTS: Overall, ILI decreased from 24.3% during the 1998-1999 season to 8.8% during the 1999-2000 season. Multivariate analysis adjusted for several factors, including gender, age, underlying diseases, and resident and HCW vaccination rates, failed to demonstrate clear individual protection of residents (relative risk [RR], 1.42; P = .2 for the first season; RR, 0.95; P = .9 for the second season). However, vaccination rates of 60% or greater for residents and HCWs reduced the risk of ILI, and also could prevent outbreaks during the 2 seasons. Highly impaired activities of daily living and chronic respiratory diseases were significantly associated with increased ILI. CONCLUSIONS: A high vaccination rate for both residents and HCWs may reduce the risk of ILI and institutional outbreaks in nursing homes.