Two large randomized multinational efficacy trials (ZOE-50 and ZOE-70) showed that the novel herpes zoster subunit vaccine (HZ/su) candidate containing varicella-zoster virus glycoprotein E (gE) and the AS01B adjuvant system reduced the risk of herpes zoster (HZ) and post-herpetic neuralgia (PHN) by more than 90%. We conducted a descriptive subgroup analysis in subjects enrolled in Japan in these studies and evaluated the results.
Participants received two doses of HZ/su or a placebo (assigned in a 1：1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against HZ was assessed in participants aged ≧50 years in ZOE-50 and in a pooled analyses of participants aged ≧70 years from ZOE-70 and ZOE-50. Vaccine efficacy against PHN was also assessed as a co-primary endpoint. Safety was assessed in all subjects and reactogenicity was assessed in a subgroup of participants. Humoral and cell mediated immunogenicity (CMI) were assessed in the respective subset for which blood samples were collected.
A total of 577 participants from ZOE-50 and 511 participants from ZOE-70 were enrolled in Japan, with a total of 1,042 included in the efficacy analysis (561 and 481 subjects, respectively). Overall vaccine efficacy against HZ in 561 adults ≧50 years was 81.4% (95% confidence interval [CI]：14.9-98.0%). In the pooled analysis of all Japanese ZOE-50 and ZOE-70 participants ≧70 years (N=608), vaccine efficacy against HZ was 92.4% (95% CI：69.4-99.1%). As no PHN event was observed in the HZ/su group, the vaccine efficacy against PHN was 100% (95% CI：-58.7-100%). Vaccine efficacy against HZ and PHN remained high throughout 4 years of the study period. Robust humoral and CMI responses were observed and persisted throughout the study period in HZ/su recipients. Solicited reports of injection-site and systemic reactions within 7 days after injection were statistically significantly more frequent among HZ/su recipients than among placebo recipients. The frequency of serious adverse events, potential immune-mediated diseases, and deaths in the HZ/su recipients was similar to the placebo recipients and no statistically significant difference was found.
Based on above results, it can be concluded that HZ/su has demonstrated high efficacy as well as robust immunogenicity in the Japanese sub-population, in line with the results observed in the global studies. In terms of safety, no meaningful differences were detected between the Japanese population and the global population. HZ/su seems to be a valuable vaccine in Japanese elderly people.
Skin and soft infections (SSTIs) comprise a diverse group of bacterial infections. In many patients with nonprulent SSTIs, bacterial pathogens tends to remain unknown because direct detection of the organism by blood and puncture culture is difficult. Although β-hemolytic Streptococcus (BHS) is believed to be the primary cause of cellulitis, this has been proved only by serological investigation and therapeutic response. On the other hand, community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is most widely detected by bacteriological investigation in purulent SSTIs in recent years.
Cellulitis is distinct from purulent SSTIs, and guidelines by the Infectious Diseases Society of America do not recommend CA-MRSA coverage for cellulitis as initial management, except for severe cases. Despite this, broad-spectrum antibiotics including anti-MRSA drugs are haphazardly prescribed due to physiciansʼ concerns over the uncertainty of the established pathogen of cellulitis, which has led to the ominous emergence of bacterial resistance.
The aim of this prospective investigation was to evaluate the contribution of BHS to the etiology of cellulitis in our hospital, and we considered the necessity of antibiotics targeting CA-MRSA. BHS was considered as the pathogen in 59.4% (60 cases) of 101 patients. There was no need for MRSA-covering antibiotics in all 101 cases.
We have evaluated the performance among four brands of immunochromatography (IC) assay kits,available in the market in Japan, for detection of norovirus antigen and compared with Real Time PCR (RTPCR) assays. The four brands used were ImmunoCatch-Noro (A Kit, EIKEN CHEMICAL Co., Ltd., Tokyo,Japan), Quick Chaser-Noro (B Kit, MIZUHO MEDY Co., Ltd., Saga, Japan), GE test Noro Nissui (C Kit, NISSUI PHARMACEUTICAL Co., Ltd., Tokyo, Japan), and Quick Navi-Noro2 (D Kit, DENKA SEIKEN Co., Ltd.,Tokyo, Japan). The results from the RT-PCR analysis of 69 suspected cases of norovirus infection identified 6 cases of Genogroup I (GI) and 22 cases of Genogroup II (GII) infection, whereas one case among them had a mixed infection of both GI and GII. The virus titers of the positive samples varied from 1.54×101 to 3.14× 108copies/μL. The genotypes identified were as follows：GI, GI.1 (1 case each), GI.2 (3 cases), and GI.3 (2 cases)；GII, GII.2 (1 case each), GII.4 (7 cases), GII.13 (2 cases), and GII.17 (12 cases). The positive concordance rates between the IC assay kits and the Real Time RT-PCR were as follows：A, 59.3%；B, 51.9%；C,51.9%；and D, 48.1%. On the other hand, the negative concordance rates were as follows：A, 97.6%；B, 100 %；C, 100%；and D, 97.6%. There was good agreement among the kits in norovirus detection as assessed with the κ coefficient. GII.P17_GII.17/Kawasaki308, known to be weakly-reactive for norovirus antigen assay kits, was detected in 12 cases；however, the samples with a virus titer of 104 to 105copies/μL or less tended to test false-negative. The sensitivity of detection, which is a limitation of norovirus antigen assay kits, as well as the reaction specificity of the assay should be of consideration in the use of IC assay kits in the clinical environment.
We evaluated a new immunochromatographic assay (ICA) for the detection of hepatitis B surface antigen (HBsAg) (Alere HBsAg；Alere Medical Co., Ltd) using 275 serum and 40 whole blood (EDTA) samples screened in our hospital. Five seroconversion panels and a reference panel according to the WHO International Standard for HBsAg were also tested. The performance of the ICA was compared with that of the conventional ICA (ICA2), chemiluminescent enzyme immunoassay (quaitative CLEIA), and chemiluminescent assay (quantitative CLIA). The sensitivity of the ICA in 54 HBV DNA positive specimens with a RTPCR (TaqMan assay) was 98.1% (53/54), better than the ICA2 -92.6%- (50/54) and the CLEIA -96.3%- (52/54),and equivalent to the CLIA -98.1%-(53/54) . The specificity in 221 HBV DNA negative specimens was 100%,better than the ICA2 -99.5%-(220 /221), and equivalent to the CLEIA and CLIA. The ICA indicated a detectability superior to the ICA2 and CLEIA, and equivalent to the CLIA in the seroconversion panels. The limit of detection of the assay was calculated as 0.1IU/mL based on the results of the CLIA assay with the seroconversion panels. This assay using an avidin-biotin format demonstrated to show an excellent sensitivity and specificity in the clinical specimens and the panels. We conclude that this simple and rapid assay with a capability for whole blood sample application is suitable and applicable for use in risk mana gement in patients with resolved HBV infection as well as in emergency and resource-limited settings.
A 79-year-old woman with diffuse large B-cell lymphoma (DLBCL), who had undergone R-DeVIC therapy, was admitted to our hospital because of cellulitis. After the cellulitis was healed, she was treated with the oral administration of etoposide for DLBCL.
On day 22, she was administered ceftriaxone for bacteremia accompanied by high fever；when blood culture was positive for Helicobacter cinaedi. On day 28, infectious enteritis due to Clostrid- ium difficile with bloody stool appeared, and H. cinaedi was detected in the intestinal mucosa obt-ained by colonoscopy. Histopathological examination revealed gram-negative bacteria with a log spiral structure that is characteristic of H.cinaedi.
The presence of bowel lesions needs to be confirmed, when H. cinaedi bacteremia recurs.
A 57-year-old male, who was nearly drowned by a tsunami following the East Japan Great Earthquake in March 2011, was referred to the vascular surgery team and infectious disease consultation of Tohoku University Hospital in October 2014, for a rapidly enlarging aneurysm of the abdominal aorta. The patient, who was previously healthy, developed pneumonia and a pulmonary abscess shortly after surviving the tsunami. He became disoriented 3 months later, MRI showed a brain abscess, and drainage with a ventriculoperitoneal shunt was performed. He developed an abscess of thoracic wall in January 2012 and itraconazole was administered. Forty-two months after the tsunami, a CT scan revealed rapidly enlarging aneurysm of the abdominal aorta, suggesting a mycotic aneurysm, and the patient was referred to our hospital. The aneurysm was surgically removed and replaced with a Y-graft. Although blood culture and culture of the aneurysm removed showed no specific finding, pathological specimens showed necrotizing granulomatous inflammation, filled with filamentous fungi, which was genetically identified as Aspergillus fumigatus.We presume that A. fumigatus, usually unlikely to cause invasive infection in immunocompetent hosts, had been inhaled on the occasion of near-drowning, which caused bloodstream infection, involving the brain, soft tissue,and the abdominal aorta. This is, to our knowledge, the first report of a mycotic aneurysm of the aorta in a tsunami survivor caused by filamentous fungi.
Fifteen to 42 cases of leptospirosis have been reported each year in Japan, mostly from Okinawa prefecture, and no case has been found in Hokkaido prefecture. We report herein on a case of leptospirosis encountered in a non-epidemic region (Hokkaido prefecture). A 14-year-old male presenting with persistent fever, headache, conjunctival injection and rash was admitted to our hospital on the 8th day of illness. He also complained of bilateral calf muscle pain and general malaise. We initially suspected him of having Kawasaki disease and administered intravenous immunoglobulin (2g/kg/dose) with oral aspirin (2,000mg/day) on the day of admission, but the symptoms did not resolve. We asked him his history again, and it was revealed that he had a hamster die on the same day of his admission. Considering leptospirosis, we started oral doxycycline (200mg/day) on the 13th day of illness and his symptoms rapidly improved following the treatment. We tested with PCR (for flaB gene), bacterial culture (with EMJH broth) and the microscopic agglutination test (MAT) for Leptospira on the 13th day of illness but the result of all tests was negative. Oral doxycycline was continued for 14 days. He was discharged from our hospital on the 22nd day of illness. We performed an MAT again on the 63rd day of illness and the test was positive for the Leptospira interogans serovar Copenhageni. In our case, the source of Leptospira was not clearly demonstrated because we could not examine the dead hamster microbiologically, but we assume the possibility of transmission from the hamster. In conclusion, it is important that, in patients who complain of fever and bilateral calf muscle pain following contact with rodents, leptospirosis must be considered even if they had not visited region where Leptospira in endemic.