Congenital Echovirus 11 Infection in a Neonate.

Neonates infected with enterovirus in utero would be fulminant at birth or develop symptoms within a few days. Echovirus 11 causes life-threatening hepatic necrosis with coagulopathy and adrenal hemorrhagic necrosis. The prognosis depends on the enterovirus serotype and the absence of serotype-specific maternal antibodies at the time of delivery. We describe a fatal neonatal case of congenital echovirus 11 infection.

Invasive Streptococcus oralis Expressing Serotype 3 Pneumococcal Capsule, Japan.

We report 2 adult cases of invasive disease in Japan caused by Streptococcus oralis that expressed the serotype 3 pneumococcal capsule and formed mucoid colonies. Whole-genome sequencing revealed that the identical serotype 3 pneumococcal capsule locus and hyl fragment were recombined into the genomes of 2 distinct S. oralis strains.

Subcutaneous abscess caused by Streptococcus pneumoniae serotype 28F in an infant: a case report.

BACKGROUND: Invasive pneumococcal disease (IPD) is defined by the detection of Streptococcus pneumoniae on culture from samples obtained from a normally sterile site. Pneumococcal conjugate vaccines (PCV) have been developed for the prevention of IPD that is caused by highly virulent serotypes. Despite the effective reduction of IPD caused by vaccine serotypes after the introduction of PCV, there has been a rapid increase in the incidence of IPD caused by non-vaccine serotypes, and serotype replacement has become a global issue. CASE PRESENTATION: We report a previously healthy 4-month-old girl presenting with a large subcutaneous abscess caused by S. pneumoniae, identified as non-vaccine serotype 28F. The patient had received routine vaccination, including PCV vaccination. After the incision and drainage of the subcutaneous abscess, the patient was treated with antibiotics. She was discharged on Day 7 of hospitalization without any residual sequelae. CONCLUSIONS: Subcutaneous abscess is a common pediatric skin and soft tissue infection, whereas pneumococcal subcutaneous abscesses are quite rare. As the pneumococcal serotype 28F caused a subcutaneous abscess, this serotype possibly has a high virulence. The incidence of IPD caused by non-vaccine serotypes, such as 28F, is expected to increase in the future. The consolidation of international data on pneumococcal serotypes is important for the development of novel PCV.

Long-term renal follow up of preterm neonates born before 35 weeks of gestation.

BACKGROUND: The hypothesis of the Developmental Origins of Health and Disease states that environmental factors during fetal and infantile life are risk factors for some chronic diseases in adulthood. Few studies, however, have confirmed this hypothesis early in childhood. Therefore, we assessed how premature birth and low-birthweight (LBW) affect the renal function of Japanese children. METHODS: This retrospective study surveyed 168 patients who were born before 35 weeks of gestation and were cared for at the present neonatal intensive care unit. Follow-up duration was >2 years. Serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) recorded in medical records were reviewed. RESULTS: The eGFR at 2 years of age was significantly correlated with birthweight and gestational age (P < 0.01). Approximately 10.7% of the children had low eGFR (<90 mL/min/1.73 m2 ) without clinical symptoms or abnormal urine examination. These children had high sCr on day 7 after birth (P < 0.01) and delayed recovery of these levels during the first month after birth. CONCLUSION: Premature gestational age and LBW directly affect renal function in young children. High sCr on day 7 after birth is a risk factor for chronic kidney disease in children. Careful follow up of renal function is therefore required for premature infants and infants with LBW beginning in early childhood to prevent renal dysfunction.

Increased community-acquired upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in children and the efficacy of flomoxef and cefmetazole.

BACKGROUND: Urinary tract infections caused by extended-spectrum beta-lactamase-producing bacteria are increasing worldwide. At our hospital, the number of pediatric patients hospitalized because of an upper urinary tract infection has dramatically increased since 2016. In total, 60.5% of urinary tract infections are caused by extended-spectrum beta-lactamase-producing Escherichia coli. Such a high prevalence of extended-spectrum beta-lactamase-producing E. coli has not been detected previously in Japan. Therefore, we evaluated the clinical and bacteriologic characteristics and efficacy of antibiotics against upper urinary tract infections caused by E. coli in children. METHODS: This retrospective study surveyed 152 patients who were hospitalized in the pediatric department of Shimane Prefectural Central Hospital because of upper urinary tract infections caused by E. coli. Medical records were reviewed to examine patient characteristics. O antigens, antibiotic susceptibility, gene typing, and pulse-field gel electrophoresis were studied at the Shimane Prefectural Institute of Public Health and Environmental Science. RESULTS: Urine sample analyses showed extended-spectrum beta-lactamase types such as CTX-M-9 and plural virulence genes. We changed the primary antibiotic treatment to flomoxef or cefmetazole to treat upper urinary tract infections caused by Gram-negative bacilli. After changing treatment, the time to fever alleviation was significantly shortened. CONCLUSION: Extended-spectrum beta-lactamase-producing E. coli should be suspected in community-acquired upper urinary tract infections. Therefore, when treating patients, it is necessary to focus on antibiotic susceptibility and the prevalence of extended-spectrum beta-lactamase-producing bacteria found in each area. Flomoxef and cefmetazole are useful primary treatments for upper urinary tract infections caused by extended-spectrum beta-lactamase-producing E. coli.

Fever Responses Are Enhanced with Advancing Age during Respiratory Syncytial Virus Infection among Children under 24 Months Old.

The most important risk factor for severe respiratory syncytial virus (RSV) infection is considered young age due to the immature immune system. The risk at young age is reported greater for RSV than for other respiratory infectious agents. Based on the strong association between young age and severity of RSV infection due to immature immunity, we aimed to assess whether there were any age-related differences in fever responses, as one clinical aspect of the immune response. In our observational study over two seasons (2014-2015 and 2015-2016), daily body temperatures of children under 3 years old with RSV infection were recorded from the first medical visit during the acute phase to defervescence. The body temperature records were analyzed among 171 children of four age groups (< 6, < 12, < 24 and ≥ 24 months), in terms of fever development, degrees of fever onset, the highest fever during the period, and fever duration. There were 54 patients in the group of < 6 months, 41 in the group of < 12 months, 58 in the group of < 24 months, and 18 in the group of ≥ 24 months. We thus found the correlation between age and fever responses under 24 months old; namely, the more the age advanced, the more frequently high and prolonged fever was experienced. Importantly, infants under 6 months old tend to show the suppressed fever responses. In conclusion, young infants with reduced fever response during RSV infection do not implicate less severity and needs attentive management.

Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes.

Streptococcus pneumoniae colonizes the nasopharyngeal mucus in healthy people and causes otitis media, pneumonia, bacteremia, and meningitis. In this study, we analyzed an S. pneumoniae strain that caused 7 repeated pneumonia episodes in an 80-month-old patient with cerebral palsy during a period of 25 months. A total of 10 S. pneumoniae strains were obtained from sputum samples, and serotype 6B was isolated from samples from the first 5 episodes, whereas serotype 6A was isolated from samples from the last 2. Whole-genome sequencing showed clonality of the 10 isolates with 10 single nucleotide polymorphisms (SNPs) in the genomes. Among these SNPs, one single point mutation in the wciP gene was presumed to relate to the serotype switching from 6B to 6A, and the other mutations in parC and gyrA were related to fluoroquinolone resistance. These results suggested that an S. pneumoniae strain, which asymptomatically colonized the patient's nasopharynx or was horizontally transmitted from an asymptomatic carrier, caused the repeated pneumonia events. Phenotypic variations in the capsule type and antimicrobial susceptibility occurred during the carrier state. Hyporesponsiveness to serotypes 6B and 6A of S. pneumoniae was found even after vaccination with the 7-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine. After an additional vaccination with the 13-valent pneumococcal conjugate vaccine, opsonic activities for both serotypes 6A and 6B significantly increased and are expected to prevent relapse by the same strain.

Risk factors for poor outcome in congenital cytomegalovirus infection and neonatal herpes on the basis of a nationwide survey in Japan.

BACKGROUND: Congenital cytomegalovirus (CMV) infection and neonatal herpes are major mother-to-child infections, and analyses of the important clinical issues, including risk factors for prognosis, are essential. METHODS: A secondary survey of congenital CMV infection and neonatal herpes was performed using questionnaires for cases reported in the primary survey between 2006 and 2008. RESULTS: Univariate analysis of 71 cases of congenital CMV infection showed that intrauterine growth restriction (IUGR) or other specific findings on fetal ultrasonography (US), microcephaly, intracranial calcification, disseminated intravascular coagulation, abnormal findings on computed tomography, and the use of i.v. gammaglobulin were all significantly correlated with poor outcome (death or severe sequelae). Multivariate analysis showed that only IUGR was significantly associated with poor outcome. Hearing impairment is one of the major abnormalities associated with congenital CMV infection. Automatic auditory brainstem response (automatic ABR) appeared to be useful for detection of hearing impairment in comparison with conventional ABR. Moreover, univariate analysis showed that specific fetal US or abnormal magnetic resonance imaging findings were correlated with sensorineural hearing loss. In 24 cases of neonatal herpes, fever and seizure were correlated with poor outcome on univariate analysis. All patients received acyclovir treatment, although substantial numbers of patients in severe clinical categories (disseminated or central nervous system diseases) received a low dose of acyclovir (<60 mg/kg per day). CONCLUSIONS: This secondary survey has identified the risk factors associated with outcome and important issues in diagnosis and treatment of two mother-to-child infections: congenital CMV and neonatal herpes, in Japan.

Clinicoepidemiologic status of mother-to-child infections: a nationwide survey in Japan.

We conducted a nationwide survey of the present status of 10 representative mother-to-child infections in Japan. Congenital syphilis, vertical human T-cell leukemia virus type 1 infection, congenital rubella and vertical HIV infection, for which effective preventative strategies have been established, were rare. Cytomegalovirus was the most common congenital pathogen in Japan, although most infants with congenital cytomegalovirus infection may remain undiagnosed.

Analysis of cases of severe respiratory failure in children with influenza (H1N1) 2009 infection in Japan.

Influenza (H1N1) 2009 occurred in Mexico in April 2009, quickly spread around the world, and was found in Japan in May. Many pediatric patients experienced encephalopathy, acute respiratory distress syndrome, and severe pneumonia. The subjects of this study were 31 pediatric patients who needed mechanical ventilation due to respiratory failure caused by influenza (H1N1) 2009 as reported to the Emergency Medical Information Center of the Japan Pediatric Society in Kanagawa Prefecture in Japan from August 1 to December 31, 2009. The diagnosis of influenza (H1N1) 2009 infection was based on positive results of a real-time polymerase chain reaction. No patient was diagnosed as having a bacterial infection. The average arterial PaO(2)/FiO(2) ratio was significantly decreased to 126. Atelectasis was revealed by chest X-ray in 90.3% of subjects. There was one plastic bronchitis patient. Anti-influenza drugs were used at an average of 14.9 h after onset. Five patients showed abnormal behavior as a complication of encephalopathy. We found that respiratory failure progressed rapidly. The type of respiratory failure was oxygenation failure. It was helpful to attempt to remove more sputum in these cases. Pediatric patients with respiratory failure from influenza (H1N1) 2009 should be carefully monitored for the onset of encephalopathy.

Superior mesenteric artery syndrome: risk factor for duodenal involvement in Henoch-Schönlein purpura.

BACKGROUND: The anatomical location of the third portion of the duodenum is between the superior mesenteric artery (SMA) and the abdominal aorta (AA). When the aorto-mesenteric angle (AMA) is small and the aorto-mesenteric distance (AMD) is short, the duodenum becomes tightly compressed between these two blood vessels. Severe compression can obstruct the duodenum, resulting in vomiting and abdominal pain. This clinical condition is termed superior mesenteric artery syndrome (SMA syndrome). The duodenum is frequently affected in Henoch-Schönlein purpura (HSP). The aim of the present study was to verify that duodenal anatomy mimicking SMA syndrome is a risk factor for duodenal involvement and abdominal pain in HSP. METHODS: A prospective case-control study involving 12 HSP patients compared with 48 age- and sex-matched children (controls) was conducted. Bowel abnormalities were defined as thickened wall >3 mm and paralytic ileus detected on ultrasound. AMA, AMD and obesity index (OI) were compared between the two groups on Mann-Whitney testing. The correlation between duodenal bowel abnormalities and SMA syndrome was examined using Fisher's exact test. RESULTS: AMA, AMD and OI were significantly smaller in the HSP patients (P < 0.001, 0.003 and 0.026, respectively). All HSP patients, but only 10 controls, met the ultrasound diagnostic criteria for SMA syndrome (100% vs 20.8%, P < 0.001). CONCLUSIONS: Duodenal compression by SMA against the AA, which mimics SMA syndrome, may lead to duodenal bowel abnormalities with abdominal pain in thin children with HSP.

ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms.

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.

Prevalence of beta-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae and Haemophilus influenzae type b strains obtained from children with lower respiratory tract infections.

The prevalence of strains with ampicillin (ABPC) resistance among Haemophilus influenzae strains isolated from the nasopharynx of children with lower respiratory tract infections has increased significantly during the 6 years from 2000, when it was 41.9%, to 2005, when it reached 60.1%. From 2002, the prevalence exceeded 50%, and the prevalence of beta-lactamase-nonproducing ABPC-resistant (BLNAR) strains with a minimum inhibitory concentration (MIC) of ABPC of over 4 microg/ml doubled, from 28.2% in 2002 to 54.7% in 2005. In H. influenzae strains obtained from the nasopharynx of children with lower respiratory tract infections between April 2004 and March 2006, identification of serotype b was defined, using the slide agglutination method. The frequency of isolation of H. influenzae type b (Hib) strains was then measured and the ABPC resistance conditions of the Hib strains were also evaluated. The frequency of the Hib strains was found to be 30 out of 479 strains, 6.3%. Of these 30 strains, BLNAR accounted for 53.3% (16 strains), approximately the same frequency of isolation as that of the BLNAR isolated from all H. influenzae strains during the same period. In Japan, the prevalence of BLNAR strains among clinically isolated H. influenzae strains has continued to increase, and the frequency of isolation of BLNAR strains among Hib strains has also continued to rise. As a countermeasure, attempts at improving resistance have been made through judicious antibiotic use, but concern that the choice of antibiotics for Hib meningitis may become complicated has sparked a keen interest in the introduction of Hib conjugate vaccine.

CD40 ligand gene and Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis syndrome of infants and young children. Although its etiology is largely unknown, epidemiological findings suggest that genetic factors play a role in the pathogenesis of KD. To identify genetic factors, affected sib-pair analysis has been performed. One of the identified peaks was located on the Xq26 region. A recent report of elevated expression of CD40 ligand (CD40L), which maps to Xq26, during the acute-phase KD, and its relationship to the development of coronary artery lesions (CAL) prompted us to screen for polymorphism of CD40L and to study the association of the gene to KD. A newly identified SNP in intron 4 (IVS4+121 A>G) is marginally over-represented in KD patients as compared to controls (109/602, 18.1 vs 111/737, 15.1%). When male KD patients with CAL were analyzed as a patient group, the SNP was significantly more frequent than in controls (15/58, 25.9%, vs 111/737, 15.1%, OR=2.0, 95% CI=1.07-3.66; P=0.030). Interestingly, this variation was extremely rare in a control Caucasian population (1/145, 0.7%). Our results suggest a role of CD40L in the pathogenesis of CAL and might explain the excess of males affected with KD.

[Mycoplasma pneumoniae infection in hospitalized children with acute pneumonia under the Mycoplasma epidemic].

Since October 2000, Mycoplasma pneumonia has been a recurring epidemic in Japan. To become clear the importance of Mycoplasma pneumoniae infection in children, we investigated cross-sectionally M. pneumoniae infection by serology in the hospitalized children age under seven years with acute pneumonia retrospectively reviewing pediatric patients of the four studies about lower respiratory tract infection which we had been treated during 2001 to 2003. Firstly, we found M. pneumoniae infection in 75 patients (33.8%) among a total of 222 patients with asthma exacerbation and acute pneumonia in 2001. Second, we had evaluated a total of 46 hospitalized children with acute pneumonia for M. pneumoniae infection in November 2002 and 18 patients (39.1%) were found. Thirdly, we found M. pneumoniae infection in 8 patients (34.8%) among 23 patients with respiratory syncitial virus and acute pneumonia age under two years during October 2002 to April 2003. Fourthly, we found M. pneumoniae infection in 19 patients (35.8%) among 53 patients with asthma exacerbation and acute pneumonia during January from June in 2003. Even only among the patients age under two years M. pneumoniae infection was found to be 24.3% (16/70), 27.8% (5/8), 34.8% (8/23) and 33.3% (7/21), respectively. These findings demonstrate that M. pneumoniae is common pathogen of acute pneumonia even in infants and young children under Mycoplasma epidemic. Not only typical bacteria and but also M. pneumoniae should be considered as important pathogens in the treatment of acute pneumonia in infants and young children under Mycoplasma epidemic.

[Efficacy of azithromycin as the empiric therapy in children with community-acquired pneumonia who were isolated macrolide resistant Streptococcus pneumoniae from nasopharynx].

Identification of pathogens in childhood community-acquired pneumonia (CAP) is not easy. However, it is believed that nasopharyngeal colonization of pathogenic bacteria leads to childhood CAP, so the etiology is inferred by the isolates obtained from nasopharynx of children with CAP. Among the pathogens of childhood CAP, Streptococcus pneumoniae (SP) is the most important agent and macrolides resistant SP (MRSP) is increasingly reported. We investigated the characterization of the mechanism of macrolide resistance in isolates of MRSP by the presence of the ermB gene or the mefA gene and clindamycin (CLDM) resistance. In addition, we also assessed the efficacy of azithromycin (AZM) in children with CAP who were isolated MRSP from nasopharynx. During a 6 month period between January and June in 2002, children with CAP who were treated with a 3 day regimen of AZM and isolated SP from nasopharynx were enrolled. Clinical outcome was based on assessment of fever on the fourth day of treatment. MIC measurements were obtained by broth microdilution and interpreted according to NCCLS criteria. 53 patients were enrolled and MRSP were isolated in 41 children. Of 41 MRSP isolates, 25 isolates were identified CLDM resistance. The AZM MIC90 of CLDM resistant MRSP isolates was 128 microg/ml. On the other hand, that of CLDM sensitive MRSP isolates was 8 microg/ml. However, AZM was effective in 20 children isolated CLDM resistant MRSP and 15 out of 16 children isolated CLDM sensitive MRSP. On this background, despite high rates of MRSP in Japan, AZM continues to be clinically effective for the treatment of childhood CAP.

[Evaluation of Streptococcus pneumoniae urinary antigen test in healthy children with nasopharyngeal pneumococcal carriage].

We evaluated the influence of colonization with pneumococci on the results of Streptococcus pneumoniae urinary antigen detection assay by testing 23 healthy children aged 1-3 years in one nursery. Nasopharyngeal swab specimens for culture and urine samples for antigen detection test were obtained. 7 of 12 children who were nasopharyngeal carriers of pneumococci had a positive result of the urine antigen test. 3 of 11 children without pneumococci in the nasopharynx also had a positive result of the urine antigen test, who were diagnosed as having acute pneumonia within one month before this study. Thus we found that 58.3% of the children with pneumococcal carriage and 27.3% of non-carriers had false-positive test results. This test is not likely to be useful for diagnosing the etiology of childhood acute pneumococcal pneumonia.