The present study aimed to determine the impact of pneumococcal conjugate vaccine (PCV) on the incidence of invasive pneumococcal disease (IPD) in children, and on the distribution of the serotype, genotype, and the antimicrobial susceptibility of Streptococcus pneumoniae isolates at a regional center in Kobe, Japan. We retrospectively analyzed 89 children (92 episodes of IPD) who were admitted to Kobe City, Nishi-Kobe Medical Center between 2002 and 2018. The IPD episodes comprised non-meningitis bacteremia (n=86) and meningitis (n=6), including 3 cases with recurrence of IPD. The 17-year study period was divided as period I (pre-vaccine era, 2002-2010；n=63), period II (PCV7 era, 2011-2013；n=15), and period III (PCV13 era, 2014- 2018；n=14). The median annual number of IPD cases was 7.0 (95% confidence interval [CI]：4.0-10.0), 5.0 (95% CI：3.6-5.2), and 2.8 (95% CI：0.4-5.2) in periods I, II, and III, respectively. In comparison with period I, the incidence rate ratio (IRR) based on the number of annual IPD cases was 0.71 (95% CI：0.40-1.27, p=0.24) in period II and 0.40 (95% CI：0.22-0.72, p=0.002) in period III. The IRR based on the IPD incidence/number of in-patients in comparison with period I was reduced to 0.61 (95% CI：0.34-1.08, p=0.082) in period II and 0.32 (95% CI：0.18-0.58, p＜0.001) in period III. The trend of the incidence of meningitis IPD was similar to that of overall IPD. The number of IPD cases abruptly decreased in 2012, one year after PCV7 introduction,and thereafter has remained constant. This phenomenon was markedly different to the 2-step reduction in reaction to PCV7 and subsequent higher-valent PCV introduction which occurred in the US and many European countries. This discrepancy may be attributable to differences in the interval of the introduction of the two kinds of PCV and differences in the prevalent serotype distribution in the pre-vaccine era. Vaccine coverage rate of the serotyped isolates were 78%, 36%, and 0% for PCV7 and 95%, 43%, and 0% for PCV13 in periods I, II, and III, respectively. The penicillin susceptibility has also changed；penicillin-susceptible S. pneumoniae accounted for 27%, 47%, and 57% of the isolates, while penicillin-resistant S. pneumoniae for 30%,33%, and 0% in periods I, II, and III, respectively. The predominant serotypes in periods II and III included 24F and 15A (4 strains each) and 15B and 15C (3 strains each). Notably, there has been no serotype of the 19 A strain, a prevalent serotype which has been replaced in other regions in Japan and Western countries. All 4 strains of 15A-sequence type 63 exhibited multidrug resistance, and appropriate use of antimicrobial agents is necessary for limiting the spread of new resistant strains. In conclusion, our study showed the impact of PCV introduction on both the clinical and microbiological findings of childhood IPD at a regional center in Japan, and it provided important epidemiological information on this serious infection.

Vaccine adverse events are reported following immunization as vaccine adverse reactions in Japan. Vaccine adverse events are inevitable because vaccines induce protective immunity to reduce the severity of infection through the stimulation of innate immunity. Vaccine adverse events are registered by the Ministry of Health, Labour and Welfare (Committee of evaluation of vaccine adverse events). We analyzed the data reported as severe adverse events and death in the meeting from Apr. 2013 to Feb. 2018). Some data reported form licensure to 2018.The incidence of serious adverse events following immunization with measles and rubella combined (MR), measles, rubella, mumps, and zoster monovalent vaccines was 0.51-1.91/100,000 doses and five cases of death after MR, one after mumps, and three after zoster vaccination, were reported during five years. That following, DTaP-IPV，IPV，Hib，PCV, Japanese Encephalitis vaccines was ≦2.03/100,000 doses and 44 deaths were reported following simultaneous administration of Hib and PCV. The main reason for death was sudden infant death syndrome (SIDS)：some were unidentified in infants,and those in the elderly were respiratory and cardiovascular diseases. Vaccine adverse events were reported as adverse reactions (causal relationship to vaccination) and vaccine adverse events are discriminated from adverse reactions.

Serum (1→3)-β-D-glucan (BDG) measurement is a useful tool for the diagnosis of invasive fungal infections (IFIs), and is often used. On the other hand, contamination of BDG and nonspecific reactions by the kit can cause false positives. Three BDG measurement kits, Fungitec G test MKII, Fungitec G test ES, and β-glucan test Wako, are available in Japan. However, not only their method of quantification but also their cutoff levels for the diagnosis of IFI are different. To clarify the difference between each kit and verify the causes of false positives, we measured and compared serum BDG levels using these kits.
Measures of diagnostic accuracy varied somewhat among the kits, but the areas under the receiver operating characteristic curves of the kits were not significantly different. The results of the cluster analysis suggested that the cause of false positives varies depending on the kit.
Although the difference between each kit in diagnosis of invasive fungal infection is small, we should interpret the results of BDG tests considering the characteristics of each kit.

Background and Objective：Streptococcus agalactiae (group B streptococcus, GBS) is one of the important pathogens of invasive neonatal infections that results frequently in a poor prognosis in cases following onset. The polysaccharide capsule present on the GBS surface is a key pathogenic factor and the majority of the cases originate from serotypes Ia, Ib, or III. The GBS infection in neonates arises mostly during the delivery through the birth canal. For this reason, GBS colonization screening of mothers is already conducted routinely for late pregnancy in Japan. However, cultivation tests require several days without the serotype identification until the results are reported. We therefore applied the “Cycleave PCR GBS Detection Kit” and “GBS Capsular Typing Kit” that were constructed as research reagents to identify GBS and its capsular serotype, on samples obtained from pregnant women；these results were compared with those of the culture.
Subjects and Methods：We investigated vaginal/anal swab samples collected from late pregnancy who were asked to participate in the study at multiple maternity hospitals. The 500 samples were collected during the 4-month period starting July 1, 2017. Cultivation tests were carried out as routine laboratory work and another PCR was performed in accordance with the manufacturersʼ protocols. GBS serotypes identified by the PCR were Ia, Ib, and III.
Results：The number of GBS-positive samples were 84 (16.8%) with PCR and 76 (15.2%) with culture. Of those samples, ten were positive with PCR but negative with culture. The PCR method was superior with a sensitivity of 97.4% and specificity of 97.6%. Of the 74 samples that were positive according to both methods,56.8% were serotyped with PCR (Ia [n=9], Ib [n=12], and III [n=21]), but 47.3% were serotyped into these three types with the serum agglutination method. The required time from initiation of PCR testing to report of results was 2.5 hours.
Conclusion：GBS identification and the serotyping with PCR was clearly superior compared with the culture method from the perspective of sensitivity, specificity, and rapidity. Application of the PCR method described here for GBS screening in pregnant women and the neonates will be highly useful in the clinical setting.

A 73-year-old Japanese man was admitted with edema of the limbs for 3 days. He was diagnosed with complete atrioventricular block. He underwent permanent pacemaker implantation and had a central venous catheter inserted into the right internal jugular vein. On day 8 of hospitalization, he had fever and his catheter was pulled out. The blood and catheter cultures were examined. On day 10, his blood culture yielded Candida sp. and liposomal amphotericin B was initiated. On day 12, the catheter tip culture was positive for Candida sp. Because of anemia, lower gastrointestinal endoscopy was performed, which revealed rectal cancer. On day 21, the permanent pacemaker was changed to a temporary pacemaker. Fluconazole was added to liposomal amphotericin B. On days 38 and 41, blood cultures remained positive for Candida sp.,which was identified as Yarrowia lipolytica using a polymerase chain reaction assay. Transesophageal echocardiography was performed, but vegetation was not observed. On day 52, he died. Y. lipolytica colonizes the human skin and feces and is poorly pathogenic. In recent years, case reports of immunocompromised and critically ill patients have increased, and catheter-related bloodstream infections have been particularly reported. Appropriate management of Y. lipolytica fungemia is controversial. Some patients with catheterrelated bloodstream infections by Y. lipolytica have been treated only with catheter removal without systemic antifungal therapy, but many patients have been treated with amphotericin B, fluconazole, or echinocandins.

A 60-year-old man who had fever and a productive cough was hospitalized with hypoxemia. His chest radiography and CT scan showed multiple nodular lesions and cavities in the left lung and a large amount of pleural effusion on the right side. Culture of pleural fluid and blood yielded Campylobacter gracilis. He was treated with thoracic drainage and intravenous administration of meropenem (MEPM) (1g every 8hours) to which C. gracilis was susceptible. His general status improved gradually, and he became afebrile on the 42nd hospital day.
However, in the course of these treatments, he developed incomplete paralysis on his left side and had the right femoral pain. Contrast-enhanced CT scan showed a ring- enhanced coin lesion, 22mm in diameter, in his right thalamus, and two ring-enhanced lesions in his right iliopsoas. Positive blood culture of C. gracilis suggested these lesions as abscesses. Then, MEPM was increased from 1g to 2g every 8hours. He was discharged from the hospital in a good condition when these abscesses became smaller and stable after completion of a 59-day course of therapy with MEPM.

We report herein on a case of a 71-year-old female who recovered from Japanese spotted fever (JSF) without tetracycline (TC) treatment. In late September 2015, she suffered from a high fever of 38℃ and appetite loss after mountain hiking. In 2 days, she had rash over her whole body suspected to be due to viral infection. Her blood test showed thrombocytopenia, moderate inflammation, and mild liver dysfunction. She was admitted to in our hospital with intravenous drip infusions of 1.5-2.0L/day, and her general condition was improved on Day 3 of admission. Her serum IgG/IgM levels of anti-JSF were elevated from negative on Day 17 to 1：5,120/1：2,560 on Day 61, indicating the diagnosis of JSF. Our literature search found 2 cases that recovered from JSF without TC and 4 fatal cases and suggested that maintaining renal function by early admission is necessary to obtain a favorable outcome of JSF.