Yuta Aizawa

Role of Maternal Antibodies in Infants with Severe Diseases Related to Human Parechovirus Type 3.

Maternal antibodies may protect infants from severe illness caused by this pathogen.

Asymptomatic children might transmit human parechovirus type 3 to neonates and young infants.

BACKGROUND Human parechovirus type 3 (HPeV3) epidemics occur worldwide and can lead to severe disease in neonates and young infants. Little is known about the source of HPeV3 infection. OBJECTIVES To investigate the source of HPeV3 infection and the role of asymptomatic children in the families of infected children. STUDY DESIGN During a 2014 HPeV3 epidemic in Niigata, Japan, we analyzed (1) clinical information on sick contacts for 43 neonates and young infants with HPeV3-related disease diagnosed by PCR analysis of serum and/or cerebrospinal fluid and (2) stool samples from symptomatic and asymptomatic siblings/cousins of index patients. To confirm transmission, the P1 (VP0, VP3, and VP1) and 3D(pol) regions of HPeVs were sequenced and analyzed. RESULTS Sick contact with family members was confirmed for 51% (n=22) of patients. Among the 30 symptomatic family members, 67% (n=20) were siblings, 20% (n=6) were mothers, and 13% (n=4) were other relatives. Stool samples from symptomatic and asymptomatic siblings/cousins of 4 HPeV3-infected patients yielded positive results for HPeVs on PCR analysis. Furthermore, the P1 and 3D(pol) nucleotide sequences of family members were 100% identical to those of the respective index cases. CONCLUSIONS Identification of genetically identical virus from HPeV3-infected patients and asymptomatic children in their families suggests that the latter are a source of infection in neonates and young infants with HPeV3-related diseases.

Clinical utility of loop-mediated isothermal amplification for rapid diagnosis of Mycoplasma pneumoniae in children.

Loop-mediated isothermal amplification (LAMP) is a cost-effective and rapid method for identifying Mycoplasma pneumoniae (MP). We investigated the utility of the LAMP assay in diagnosing MP pneumonia among children in a clinical setting. In this prospective study, the cause of community-acquired pneumonia was evaluated in 111 patients for whom MP was the suspected pathogen. All participants were patients at a city hospital in Japan between April 2012 and September 2012. Throat swabs for the LAMP assay were obtained at admission, and paired serum samples to measure antibody titres to MP by particle agglutination were obtained at admission and during convalescence. Overall, 45 of 111 (41 %) patients had a fourfold or greater increase in MP titres and received a diagnosis of MP pneumonia. Among them, 43 (96 %) patients (median age, 9 years) were positive on the LAMP assay and had a fourfold or greater increase in MP titres. The median interval from fever onset to collection of throat swabs was 7 days (range, 4-10 days). As compared with paired serum titres, the LAMP assay enabled quicker diagnosis of MP (median interval, 13 vs. 7 days), thereby allowing early initiation of appropriate antimicrobial therapy.

Rhabdomyolysis Associated with Antimicrobial Drug-Resistant Mycoplasma pneumoniae

We describe a case of rhabdomyolysis in a patient infected with antimicrobial drug–resistant Mycoplasma pneumoniae The patient’s acute-phase serum levels of interleukin-18 and tumor necrosis factor–α were high, which suggests a pathogenic role for M. pneumoniae. In an era of increasing antimicrobial drug resistance, a system for rapidly identifying resistant M. pneumoniae would be beneficial.

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.

Human parechovirus type 3 infection: Cause of apnea in infants born prematurely.

Four infants born prematurely presented with multiple apnea episodes caused by human parechovirus type 3 (HPeV3) infection. All patients required oxygen supplementation, and one patient required mechanical ventilation. HPeV3 infection might be included in the differential diagnosis of apnea in neonates and young infants, especially those born prematurely.

Sustained pediatric antimicrobial stewardship program with consultation to infectious diseases reduced carbapenem resistance and infection-related mortality

OBJECTIVE The impact of pediatric antimicrobial stewardship programs (ASP) on antimicrobial resistance (AMR) remains largely unknown. This study aimed to evaluate the AMR for carbapenem of Gram-negative bacilli (GNB) and carbapenem use with infectious diseases consultation after the implementation of an ASP. METHODS This quasi-experimental study was conducted at Tokyo Metropolitan Childrens Medical Center in Japan. The pre- and post-intervention periods were April 2010 to September 2011 and October 2011 to March 2017, respectively. The pre-intervention phase consisted of consultations with the infectious diseases service alone. The ASP was implemented during the post-intervention phase. The carbapenem resistance rates of GNB were calculated. The correlation between carbapenem resistance rates and carbapenem day of therapy (DOT) was examined. The outcome metrics were compared by average length of hospitalization, all-cause mortality, and infection-related mortality. RESULTS A positive correlation was observed between the carbapenem resistance rate in Pseudomonas aeruginosa and DOT (0.76, p=0.04). The carbapenem resistance rate in P. aeruginosa (p<0.01) and DOT (p<0.01) decreased significantly in the post-intervention period. The length of hospitalization (p<0.01) and infection-related mortality (p=0.05) decreased in the post-intervention period. CONCLUSIONS A sustained ASP with additional consultation with the infectious disease service reduced carbapenem use and resistance in P. aeruginosa, leading to favorable outcomes in terms of length of hospitalization and infection-related mortality.

Intradermal vaccination for infants and children

ABSTRACT Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children.

Sibling visits and viral infection in the neonatal intensive care unit

Sibling visits to the neonatal intensive care unit (NICU) are a part of family‐centered care, which is now being increasingly endorsed as a positive development in patient care. Sibling visits, however, pose a risk of viral infection, and hence many NICU in Japan impose strict limits on the practice. The aim of this study was therefore to assess whether sibling visits to the NICU are related to an increase in the nosocomial viral infection rate.

Parvovirus B19: A Cause of Sepsislike Syndrome in an Infant

This is the first case report of an infant who presented with a sepsislike illness caused by PB19. Parvovirus B19 (PB19) is an important human pathogen that results in a wide spectrum of clinical outcomes, from mild, self-limiting erythema infectiosum in immunocompetent children and arthralgia in adults to lethal cytopenia in immunocompromised patients and intrauterine fetal death. However, there have been few reports of PB19 infection in neonates or young infants (aged 28–90 days), and no previous reports contained descriptions of PB19 infection as a cause of sepsislike syndrome in this age group. We report a case of sepsislike syndrome caused by PB19 infection in a 56-day-old infant whose mother had polyarthralgia at the time of his admission. PB19 infection was diagnosed on the basis of positive polymerase chain reaction results for PB19 DNA in the serum and cerebrospinal fluid. Positive immunoglobulin M and negative immunoglobulin G for PB19 suggested acute infection. He was admitted to the ICU because of poor peripheral circulation, but fully recovered without antibiotic administration. After excluding other possible pathogens, PB19 should be suspected as a cause of sepsislike syndrome in young infants, especially those who have close contact with PB19-infected individuals.