Detection of modified measles and super-spreader using a real-time reverse transcription PCR in the largest measles outbreak, Yamagata, Japan, 2017 in its elimination era.

We aimed to verify the effectiveness of real-time reverse transcription (rRT) polymerase chain reaction (PCR) for detecting cases of modified measles (M-Me) and for predicting super-spreader candidates through the experience of a measles outbreak dominated by M-Me in Yamagata, Japan, during March-April 2017. We applied rRT-PCR to specimens from 35 cases of M-Me, nine cases of typical measles (T-Me) and nine cases of prodromal stage of T-Me (P-Me). From rRT-PCR among the M-Me cases, peripheral blood mononuclear cells (PBMC) showed the highest positive rate (80.0%), followed by throat swab (48.6%), urine (33.3%) and serum (3.1%). The negative result of PBMC in M-Me cases was recovered by the result of a throat swab. In specimens of PBMC, throat swab and urine, M-Me group showed the significantly higher cycle of threshold (i.e., lower viral load) in the rRT-PCR than T-Me and P-Me groups, respectively. Furthermore, three super-spreaders in T-Me or P-Me showed an extremely low cycle of threshold in their throat swab specimens. rRT-PCR using PBMC and throat swab might be helpful for clinical management and measles control by certain detection of M-Me cases and by predicting super-spreading events resulting from measles cases with the high viral load.

Meteorological factors affecting scrub typhus occurrence: a retrospective study of Yamagata Prefecture, Japan, 1984-2014.

Climate change, by its influence on the ecology of vectors might affect the occurrence of vector-borne diseases. This study examines the effects of meteorological factors in Japan on the occurrence of scrub typhus, a mite-borne zoonosis caused by Orientia tsutsugamushi. Using negative binomial regression, we analysed the relationships between meteorological factors (including temperature, rainfall, snowfall) and spring-early summer cases of scrub typhus in Yamagata Prefecture, Japan, during 1984-2014. The average temperature in July and August of the previous year, cumulative rainfall in September of the previous year, snowfall throughout the winter, and maximum depth of snow cover in January and February were positively correlated with the number of scrub typhus cases. By contrast, cumulative rainfall in July of the previous year showed a negative relationship to the number of cases. These associations can be explained by the life-cycle of Leptotrombidium pallidum, a predominant vector of spring-early summer cases of scrub typhus in northern Japan. Our findings show that several meteorological factors are useful to estimate the number of scrub typhus cases before the endemic period. They are applicable to establish an early warning system for scrub typhus in northern Japan.

Epidemic myalgia and myositis associated with human parechovirus type 3 infections occur not only in adults but also in children: findings in Yamagata, Japan, 2014.

We previously reported an association between human parechovirus type 3 (HPeV3) and epidemic myalgia with myositis in adults during summers in which an HPeV3 outbreak occurred in children. However, this disease association has not yet been reported elsewhere. We have since continued our surveillance to accumulate data on this disease association and to confirm whether myalgia occurs in children as well as adults. Between June and August 2014, we collected 380 specimens from children with infectious diseases. We also collected clinical specimens from two adult and three paediatric patients suspected of myalgia. We then performed virus isolation and reverse-transcription-PCR using the collected specimens. We detected HPeV3 in 26 children with infectious diseases, which we regarded as indicating an outbreak. We also confirmed HPeV3 infection in all patients suspected of myalgia. In particular the symptoms in two boys, complaining of myalgia and fever, closely matched the criteria for adult myalgia. Based on our findings from 2008, 2011 and 2014, we again urge that clinical consideration be given to the relationship between myalgia and HPeV3 infections during HPeV3 outbreaks in children. Furthermore, our observations from 2014 suggest that epidemic myalgia and myositis occur not only in adults but also in children.

Carcinoma of the external auditory canal: histological and treatment groups.

OBJECTIVE: Evaluation of the clinical and pathological factors associated with the treatment and outcomes of external auditory canal (EAC) carcinomas. METHODOLOGY: A retrospective review of clinical and pathological analysis was performed on 23 patients who were histologically diagnosed with EAC carcinomas and treated at Hamamatsu University hospital. We evaluated the clinical staging, treatment methods, pathological diagnosis (particularly squamous cell carcinoma, SCC), and patient outcomes. Main outcome measures include staging, treatment procedures, pathological features, and estimated survival rates. RESULTS: The 5-year overall survival (OS) of study participants was 75.2% and the 10-year OS was 60.2% using the Kaplan-Meier method. The prognosis for SCC was poor compared with other carcinomas (p= 0.0462). The prognoses for SCC patients after treatment with surgery alone and after postoperative radiotherapy or chemoradiotherapy were significantly better than for patients with unresectable tumours (p = 0.0004 and p = 0.0001, respectively). There was no significant difference among the four tumour stage groups. Information about patients' survival status was obtained after a median follow-up period of 57.5 months (range, 7-151 months). CONCLUSION: Our survival analysis data for carcinoma of the EAC demonstrates that SCC and unresectable cases are associated with poor outcomes. Outcomes for patients with operable disease more closely parallel the survival curves of patients with advanced stage T4 disease. Patients with SCC should be strictly categorized as cases with severe disease.

Human metapneumovirus infection among family members.

The transmission of human metapneumovirus (hMPV) among family members is not well understood. We identified 15 families in which multiple members were diagnosed with hMPV infection by real-time PCR in 2008 and 2010. Index patients ranged in age from 2 years to 11 years (median 5 years), and all 15 index cases were children who attended primary school, kindergarten, or nursery school. Contact patients ranged in age from 2 months to 46 years (median 6 years). Excluding five adult cases, contact patients were significantly younger than index patients (P = 0·0389). Of the 12 contact children, seven (58%) were infants who were taken care of at home. The serial interval between the onset of symptoms in an index patient and the onset of symptoms in a contact patient was estimated to be 5 days. These results suggest that the control of school-based outbreaks is important for preventing hMPV infection in infants.

Interventional radiology for hepatic artery complications soon after living donor liver transplantation in a neonate.

Early hepatic artery complications after liver transplantation in children, having undergone LDLT, can directly affect graft and recipient outcomes, making early diagnosis and treatment essential. In the past, laparotomy (thrombectomy or reanastomosis) was generally employed to treat early hepatic artery complications. Recently, favorable outcomes of IR have been reported. In children, however, the number of such reports is small. To the best of our knowledge, there is no published report on IR applied to neonates with early hepatic artery complications. We recently succeeded in safely using IR for a neonate with early hepatic artery complications after LDLT and obtained a favorable outcome. This case is presented herein.

Hepatic artery reconstruction with the jejunal artery of the Roux-en-Y limb in pediatric living donor liver re-transplantation.

When re-anastomosis and re-transplantation becomes necessary after LDLT, arterial reconstruction can be extremely difficult because of severe inflammation and lack of an adequate artery for reconstruction. Frequently, the recipient's HA is not in good condition, necessitating an alternative to the HA. In such cases, the recipient's splenic artery, right gastroepiploic artery or another vessel can be safely used for arterial reconstruction. There have, however, been few reports on using the jejunal artery. Herein, we report our experience with arterial reconstruction using the jejunal artery of the Roux-en-Y limb as an alternative to the HA. A three-yr-old girl who had developed graft failure due to early HA thrombosis after LDLT required re-transplantation. At re-transplantation, an adequate artery for reconstruction was lacking. We reconstructed the artery by using the jejunal artery of the Roux-en-Y limb, as we judged it to be the most appropriate alternative. After surgery, stent was deployed because hepatic blood flow had reduced due to kinking of the anastomosed site, and a favorable outcome was obtained. In conclusion, when an alternative to the HA is required, using the jejunal artery is a feasible alternative.

Living donor liver transplantation from an asymptomatic mother who was a carrier for ornithine transcarbamylase deficiency.

Liver transplantation (LT) has been adopted as a radical treatment for ornithine transcarbamylase deficiency (OTCD), yielding favorable outcomes. Despite the fact that it is an inheritable disease, a blood relative who is heterozygous for the disorder must sometimes be used as a liver donor for living donor LT. There is ongoing discussion regarding the use of heterozygous donors, however, to our knowledge, no cases where donation was determined based on the Ornithine transcarbamylase (OTC) activity before LT have been reported. Between May 2001 and April 2011, 17 patients were indicated for living donor LT because of OTCD at our facility. There were three cases with heterozygous donor candidate (17.6%). All heterozygous candidates underwent a liver biopsy to measure their OTC activity before LT and made efforts to secure the safety of the both donor and recipient. Two of 3 candidates had headaches sometimes, and their activity was less than 40%, and thus they were not employed as the donor. One candidate with 104.4% activity was employed, yielding favorable outcomes. Our current experience supported the effectiveness of our donation criteria, however it is necessary to collect sufficient data on a large number of patients to confirm the safety of the procedure.

Pediatric liver retransplantation from living donors can be considered as a therapeutic option for patients with irreversible living donor graft failure.

Liver retransplantation (re-LT) is required in patients with irreversible graft failure, but it is a significant issue that remains medically, ethically, and economically controversial, especially in living donor liver transplantation (LDLT). The aim of this study was to evaluate the outcome, morbidity, mortality, safety and prognostic factors to improve the outcome of pediatric living donor liver retransplantation (re-LDLT). Six of 172 children that underwent LDLT between January 2001 and March 2010 received a re-LDLT and one received a second re-LDLT. The overall re-LDLT rate was 3.5%. All candidates had re-LDLT after the initial LDLT. The overall actuarial survival of these patients was 83.3% and 83.3% at one and five yr, respectively. These rates are significantly worse than the rates of pediatric first LDLT. Vascular complications occurred in four patients and were successfully treated by interventional radiologic therapy. There were no post-operative biliary complications. One case expired because of hemophagocytic syndrome after re-LDLT. Although pediatric re-LDLT is medically, ethically, and economically controversial, it is a feasible option and should be offered to children with irreversible graft failure. Further investigations, including multicenter studies, are therefore essential to identify any prognostic factors that may improve the present poor outcome after re-LDLT.

Living donor liver transplantation for ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency, the most common urea cycle disorder, causes hyperammonemic encephalopathy and has a poor prognosis. Recently, LT was introduced as a radical OTCD treatment, yielding favorable outcomes. We retrospectively analyzed LT results for OTCD at our facility. Twelve children with OTCD (six boys and six girls) accounted for 7.1% of the 170 children who underwent LDLT at our department between May 2001 and April 2010. Ages at LT ranged from nine months to 11 yr seven months. Post-operative follow-up period was 3-97 months. The post-operative survival rate was 91.7%. One patient died. Two patients who had neurological impairment preoperatively showed no alleviation after LT. All patients other than those who died or failed to show recovery from impairment achieved satisfactory quality-of-life improvement after LT. The outcomes of LDLT as a radical OTCD treatment have been satisfactory. However, neurological impairment associated with hyperammonemia is unlikely to subside even after LT. It is desirable henceforth that more objective and concrete guidelines for OTCD management be established to facilitate LDLT with optimal timing while avoiding the risk of hyperammonemic episodes.

Living donor liver transplantation for neonates using segment 2 monosubsegment graft.

The prognosis of liver transplantation for neonates with fulminant hepatic failure (FHF) continues to be extremely poor, especially in patients whose body weight is less than 3 kg. To address this problem, we have developed a safe living donor liver transplantation (LDLT) modality for neonates. We performed LDLTs with segment 2 monosubsegment (S2) grafts for three neonatal FHF. The recipient age and body weight at LDLT were 13-27 days, 2.59-2.84 kg, respectively. S2 or reduced S2 grafts (93-98 g) obtained from their fathers were implanted using temporary portacaval shunt. The recipient portal vein was reconstructed at a more distal site, such as the umbilical portion, to have the graft liver move freely during hepatic artery (HA) reconstruction. The recipient operation time and bleeding were 11 h 58 min-15 h 27 min and 200-395 mL, respectively. The graft-to-recipient weight ratio was 3.3-3.8% and primary abdominal wall closure was possible in all cases. Although hepatic artery thrombosis occurred in one case, all cases survived with normal growth. Emergency LDLT with S2 grafts weighing less than 100 g can save neonates with FHF whose body weight is less than 3 kg. This LDLT modality using S2 grafts could become a new option for neonates and very small infants requiring LT.

Determination of Lycopene Concentration in Fresh Tomatoes by Spectrophotometry: A Collaborative Study.

BACKGROUND: Lycopene has been the object of considerable research attention recently, and the effects of the intake of lycopene, or of tomato products, have been studied in various ways. In Japan, interest in the health-promoting function of food components has increased. OBJECTIVE: Developing a method to determine lycopene contents in tomato that meets the Japanese Agricultural Standard (JAS). METHOD: In the proposed JAS method, the test sample consists of fresh tomatoes; a hexane-acetone mixture is utilized as the extraction solvent. A collaborative study was conducted to evaluate the interlaboratory performance of the method. RESULTS: Ten laboratories participated and analyzed six test materials characterized by a lycopene content between 39 and 170 mg/kg as blind duplicates. After removing statistical outliers, RSDr ranged from 1.2 to 3.0% and RSDR ranged from 2.4 to 4.2%. The HorRat values were calculated and found to be in the 0.26-0.49 range. CONCLUSIONS: The method for determining the lycopene content in tomato was evaluated by means of a collaborative study, and the reproducibility of this method was found to be acceptable. HIGHLIGHTS: Intended for standardization in Japan, a method to determine lycopene content in tomato has been developed and shown to have acceptable precision in a collaborative study.

Identification of 11 novel mutations in USH2A among Japanese patients with Usher syndrome type 2.

Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 2 (USH2) is the most common type of USH and is frequently caused by mutations in USH2A, which accounts for 74-90% of USH2 cases. This is the first study reporting the results of scanning for USH2A mutations in Japanese patients with USH2. In 8 of 10 unrelated patients, we identified 14 different mutations. Of these mutations, 11 were novel. Although the mutation spectrum that we identified differed from that for Caucasians, the incidence of mutations in USH2A was 80% for all patients tested, which is consistent with previous findings. Further, c.8559-2A>G was identified in four patients and accounted for 26.7% of mutated alleles; it is thus a frequent mutation in Japanese patients. Hence, mutation screening for c.8559-2A>G in USH2A may prove very effective for the early diagnosis of USH2.

[Gastrointestinal hemorrhage induced by percussive ventilator in an infant with chronic lung disease complicated after surgery for corrected transposition of the great arteries].

A newborn patient (birth weight 2,332 g) with corrected transposition of the great arteries developed chronic lung disease due to a severe heart failure and post operative several complications. We applied intrapulmonary percussive ventilation (IPV) to the patient. IPV improved oxygenation concomitant with the improvement of respiratory condition and chest X-ray finding. However, the patient suffered from upper gastrointestinal bleeding 15 days after initiation of IPV therapy. The bleeding was healed several days after temporal termination of IPV, but recurred with resuming IPV therapy. The patient was irritable throughout the IPV therapy, and thus gastrointestinal bleeding of the patient could be due to stress induced by IPV therapy. IPV may be useful for the management of respiratory disturbance, often observed in low birth weight patients with congenital heart defects. However, gastrointestinal bleeding may occur and should be considered as a possible complication associated with IPV therapy.

Nosocomial Mycobacterium tuberculosis transmission by brief casual contact identified using comparative genomics.

This paper reports a case of nosocomial transmission of Mycobacterium tuberculosis by brief casual contact. Routine variable number tandem repeat typing in Yamagata Prefecture, Japan found that M. tuberculosis clinical isolates from two patients showed indistinguishable genotypes. The patients had an epidemiological relationship of sharing a waiting room in a hospital on the same day. As comparative genomics detected only two single nucleotide variants between the isolates, it was concluded that recent tuberculosis transmission occurred in the waiting room. These results indicate that the physical separation of infectious tuberculosis patients is an essential control measure for preventing unpredictable nosocomial transmission by casual contact.

A case of laboratory cross-contamination of Mycobacterium tuberculosis identified using comparative genomics.

BACKGROUND: Two false-positive tuberculosis (TB) cases in Yamagata Prefecture, Japan, 2016. OBJECTIVE: To report the effectiveness of comparative genomics of Mycobacterium tuberculosis for identification of cross-contamination cases. DESIGN: Case report of laboratory cross-contamination. RESULTS: Beginning with detection of an identical genotype in two M. tuberculosis strains using variable number of tandem repeat typing, we suspected M. tuberculosis cross-contamination of specimens collected in a mycobacteriology laboratory based on epidemiological investigations. This suspicion was confirmed using comparative genomics of the two M. tuberculosis strains and a strain from an epidemiologically unrelated specimen from the same batch as the two strains in the mycobacteriology laboratory. All strains had an identical genomic sequence with no single nucleotide variants. CONCLUSION: Comparative genomics, which offers the highest discrimination power, is a potent tool for identifying laboratory cross-contamination using epidemiological investigations.

Transition of Spleen Volume Long After Pediatric Living Donor Liver Transplantation for Biliary Atresia.

PURPOSE: After undergoing the Kasai procedure for biliary atresia (BA), most patients develop severe splenomegaly that tends to be improved by liver transplantation. However, fluctuations in splenic volume long after transplantation remain to be elucidated. PATIENTS AND METHODS: Seventy-one consecutive patients who had undergone pediatric living donor liver transplantation (LDLT) for BA were followed up in our outpatient clinic for 5 years. They were classified into 3 groups according to their clinical outcomes: a good course group (GC, n = 41) who were maintained on only 1 or without an immunosuppressant, a liver dysfunction group (LD, n = 18) who were maintained on 2 or 3 types of immunosuppressants, and a vascular complication group (VC, n = 11). Splenic and hepatic volumes were calculated by computed tomography in 464 examinations and the values compared before and after the treatment, especially in the VC group. RESULTS: Splenic volume decreased exponentially in the GC group, with splenic volume to standard spleen volume ratio (SD) being 1.59 (0.33) 5 years after liver transplantation. Splenic volume to standard spleen volume ratios were greater in the VC and LD groups than in the GC group. Patients in the VC group with portal vein stenosis developed liver atrophy and splenomegaly, whereas those with hepatic vein stenosis developed hepatomegaly and splenomegaly. Interventional radiation therapy tended to improve the associated symptoms. CONCLUSIONS: Fluctuations in splenic volume long after pediatric LDLT for BA may reflect various clinical conditions. Evaluation of both splenic and hepatic volumes can facilitate understanding clinical conditions following pediatric LDLT.

Antibody Drug Treatment for Steroid-Resistant Rejection After Pediatric Living Donor Liver Transplantation: A Single-Center Experience.

BACKGROUND: Antibody drugs have been used to treat steroid-resistant rejection (SRR) after liver transplantation. Although anti-thymocyte globulin has been used for SRR after liver transplantation in place of muromonab-CD3 since 2011 in Japan, the effectiveness of anti-thymocyte globulin after pediatric living-donor liver transplantation (LDLT) has not yet been reported. The aim of this study was to evaluate the effectiveness of antibody drug treatment for SRR after pediatric LDLT in our single center. METHODS: Between May 2001 and December 2013, 220 pediatric LDLTs were performed. Initial immunosuppression after LDLT included tacrolimus and methylprednisolone therapy. Acute rejection was diagnosed by use of a liver biopsy and the administration of steroid pulse treatment, and SRR was defined as acute rejection refractory to the steroid pulse treatment. RESULTS: Acute rejection and SRR occurred in 74 (33.6%) and 16 patients (7.3%), respectively. The graft survival rates of non-SRR and SRR were 92.4% and 87.5%, respectively (P = .464). The median concentration of alanine aminotransferase before and after the administration of antibody drug was 193.5 mU/mL (range, 8-508) and 78 mU/mL (range, 9-655), respectively (P = .012). The median rejection activity index before and after the administration of antibody drugs was 5 (range, 2-9) and 1 (range, 0-9), respectively (P = .004). After antibody drug treatment, 12 patients had cytomegalovirus infections, 2 patients had Epstein-Barr virus infections, 3 patients had respiratory infections, and 1 patient had encephalitis. The cause of death in 1 patient with SRR was recurrence of infant fulminant hepatic failure. CONCLUSIONS: Antibody drug treatment for SRR after pediatric LDLT is safe and effective.

Endotoxin Metabolism Reflects Hepatic Functional Reserve in End-Stage Liver Disease.

BACKGROUND: The hepatic clearance of endotoxin (Et) may reflect hepatic functional reserve and ischemic injury to hepatocytes. Therefore, we examined the relationships between Et activity (EA) and the metrics Pediatric End-Stage Liver Disease (PELD)/Model of End-Stage Liver Disease (MELD) score and alanine transaminase (ALT) levels in the postoperative period. METHODS: We performed 8 living-donor liver transplantations (LDLTs) for biliary atresia at our center from April 2012 to December 2012. EA was measured by means of an Et activity assay (EAA) in samples collected from a vein 1 day before LDLT, from the portal vein during the intraoperative anhepatic phase, from an artery 1 hour after reperfusion, from an artery on postoperative day (POD) 1, and from an artery or vein at PODs 7 and 14. RESULTS: EAs generally remained at low levels. EA at the reperfusion period was significantly lowest. The correlation coefficient for the preoperative MELD/PELD score and the EAA was 0.837, and the corresponding P value was .009; thus, there was a significant relationship between the preoperative MELD/PELD score and the EAA. The correlation coefficients for ALT at POD 1 and EA during the anhepatic phase, at 1 hour after reperfusion, and at POD 1 were 0.64, 0.43, and 0.38, respectively, and the P values for these correlations were .08, .67, and .34. Thus, we observed that ALT and EA generally tended to be somewhat directly correlated, but no significant relationships between these 2 metrics were observed. CONCLUSIONS: Endotoxin metabolism reflects the hepatic functional reserve capacity of end-stage liver disease.

The relevance of an elevation in the plasma vasopressin levels to the pathogenesis of Meniere's attack.

An elevation of plasma vasopressin levels has been frequently observed in Meniere's disease patients. However, little is known regarding the mechanism behind this elevation. The plasma vasopressin levels and plasma osmolality were therefore determined in 18 diagnosed Meniere's disease patients and 20 patients with other types of vertigo, who required admission for severe vertigo attacks. All participants were given questionnaires regarding their clinical and psychological status, including their stress levels and depression status, to evaluate environmental stress events. The plasma vasopressin levels of Meniere's disease patients in the acute phase (4.1 +/- 1.37 pg/ml) were significantly higher compared with with those of other vertigo patients in the acute phase (2.1 +/- 0.41 pg/ml) (P < 0.01). The average plasma osmolality of the Meniere's disease group was higher than that of the other vertigo patients group (P < 0.05). No significant difference in reported stress levels, depression status and prevalence of primary headache between the groups was observed. The plasma vasopressin showed no significant correlation with the patients' clinical data (occurrence of emesis or nausea, prevalence of primary headache, depression status and stress). No correlation between the plasma vasopressin and the plasma osmolarity was observed in the Meniere's disease group. These results suggest that the elevation of plasma vasopressin in the acute phase of Meniere's disease is therefore related to the pathogenesis of Meniere's attacks, and the results obtained may provide helpful information for distinguishing between Meniere's disease and other various inner ear diseases.