Airway hyperresponsiveness and inflammation in Japanese patients with human immunodeficiency virus 1 infection.

INTRODUCTION: Despite the growing population of long-term survivors with human immunodeficiency virus 1 (HIV) exhibiting asthma-like features worldwide, the pathogenesis underlying airway hyperresponsiveness (AHR) and airway inflammation remains unclear. We aimed to investigate AHR and airway inflammation in an HIV-infected Japanese population. METHODS: Of 94 Japanese participants, 10 HIV-infected participants with asthma were excluded from the study. We compared the characteristics of HIV-infected (n = 34) and non-HIV-infected participants (n = 50). Eosinophilic, neutrophilic, mixed (eosinophilic and neutrophilic), and paucigranulocytic airway inflammatory phenotypes were classified based on induced sputum characteristics. RESULTS: The prevalence of AHR in HIV-infected participants (32.4%) was significantly higher than that in their non-HIV-infected counterparts (10.0%) (P = 0.0213). The multivariate nominal logistic regression analysis revealed HIV as an independent risk factor for AHR. HIV-infected participants were significantly more likely to have a neutrophilic airway inflammatory phenotype than non-HIV-infected participants (P = 0.0358). Furthermore, HIV-infected participants with AHR demonstrated a significant correlation between AHR levels and the percentage of sputum neutrophils (r = -0.65, P = 0.0316). The percentage of sputum neutrophils was negatively associated with the blood CD4 cell count (r = -0.66, P = 0.0266). CONCLUSIONS: We observed the high prevalence of AHR and neutrophilic airway inflammatory phenotype in Japanese participants with stable HIV infection. Our findings provide insight into the mechanisms of AHR and may facilitate the development of novel treatment for individuals with AHR and HIV infection.

A small fragmented P protein of respiratory syncytial virus inhibits virus infection by targeting P protein.

Peptide-based inhibitors hold promising potential in the development of antiviral therapy. Here, we investigated the antiviral potential of fragmented viral proteins derived from ribonucleoprotein (RNP) components of the human respiratory syncytial virus (HRSV). Based on a mimicking approach that targets the functional domains of viral proteins, we designed various fragments of nucleoprotein (N), matrix protein M2-1 and phosphoprotein (P) and tested the antiviral activity in an RSV mini-genome system. We found that the fragment comprising residues 130-180 and 212-241 in the C-terminal region of P (81 amino acid length), denoted as P Fr, significantly inhibited the polymerase activity through competitive binding to the full-length P. Further deletion analysis of P Fr suggested that three functional domains in P Fr (oligomerization, L-binding and nucleocapsid binding) are required for maximum inhibitory activity. More importantly, a purified recombinant P Fr displayed significant antiviral activity at low nanomolar range in RSV-infected HEp-2 cells. These results highlight P as an important target for the development of antiviral compounds against RSV and other paramyxoviruses.

Biofilm-Forming by Carbapenem Resistant Enterobacteriaceae May Contribute to the Blood Stream Infection.

Bloodstream infection (BSI) due to carbapenem-resistant Enterobacteriaceae (CRE) has a high mortality rate and is a serious threat worldwide. Ten CRE strains (eight Enterobacter cloacae, one Klebsiella pneumoniae and one Citrobacter freundii) were isolated from the blood of nine patients, a percentage of whom had been treated with indwelling devices. The steps taken to establish cause included minimum inhibitory concentration (MIC) tests, a pulsed-field gel electrophoresis (PFGE), biofilm study, a multiplex PCR for resistant genes of carbapenemases and extended-spectrum beta-lactamases (ESBLs), and plasmid incompatibility typing. All strains showed a tendency toward resistance to multiple antibiotics, including carbapenems. Frequently isolated genes of ESBLs and carbapenemases include blaTEM-1 (four strains), blaSHV-12 (four strains) and blaIMP-1 (six strains). A molecular analysis by PFGE was used to divide the XbaI-digested genomic DNAs of 10 CRE strains into eight patterns, and the analysis showed that three E. cloacae strains detected from two patients were either identical or closely related. The biofilm production of all CRE strains was examined using a microtiter biofilm assay, and biofilm growth in continuous flow chambers was observed via the use of a confocal laser scanning microscope. Our study indicates that biofilm formation on indwelling devices may pose a risk of BSI due to CRE.

Invasive meningococcal disease due to a non-capsulated Neisseria meningitidis strain in a patient with IgG4-related disease.

BACKGROUND: Invasive Meningococcal Disease (IMD) is a rare and critical disease in Japan. Most of these cases are caused by capsulated Neisseria meningitidis strains. Non-capsulated (non-typable) strains are considered relatively low-pathogenic and can colonize in the nasopharynx of healthy children and young adults. As far as could be ascertained, only twelve IMD cases due to non-capsulated strains have been reported in the literature. No clear risk factors could be identified in a literature review (unknown or immunocompetent, seven cases; C6 deficiency, three cases). CASE PRESENTATION: We report a Japanese male taxi driver with bacteremia and meningitis due to non-capsulated N. meningitidis. He had a fever and shaking chills. Ceftriaxone was administered, and the patient finally recovered. During the clinical course, relative adrenal insufficiency occurred and was treated with hydrocortisone. A hidden co-morbidity, immunoglobulin G4 (IgG4)-related disease, was revealed in the past surgical history (a resection of bilateral orbital tumors), which included symptoms (swelling lachrymal glands and lymph nodes), elevated IgG4, immunoglobulin E, and hypocomplementemia. He recovered finally and no recurrence was observed. CONCLUSIONS: Our IMD case is the first reported in Japan, where IMD is not considered pandemic. The patient had a history of IgG4-related disease, although we could not establish a clear relationship between the patient's IMD and co-morbidity. A collection of further clinical cases might establish the risk factors and characteristics of IMD that could be caused by this neglected pathogen, non-capsulated N. meningitidis.

Integration of DPC and clinical microbiological data in Japan reveals importance of confirming a negative follow-up blood culture in patients with MRSA bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is one of the commonest and most life-threatening of all infectious diseases. The morbidity and mortality rates associated with MRSA bacteremia are higher than those associated with bacteremia caused by other pathogens. A common guideline in MRSA bacteremia treatment is to confirm bacteremia clearance through additional blood cultures 2-4 days after initial positive cultures and as needed thereafter. However, no study has presented statistical evidence of how and to what extent confirming a negative follow-up blood culture impacts clinical outcome. We present this evidence for the first time, by combining clinical microbiological data of blood cultures and the DPC administrative claims database; both had been systematically accumulated through routine medical care in hospitals. We used electronic medical records to investigate the clinical background and infection source in detail. By analyzing data from a university hospital, we revealed how survival curves change when a negative follow-up blood culture is confirmed. We also demonstrated confirmation of a negative culture is significantly associated with clinical outcomes: there was a more than three-fold increase in mortality risk (after adjusting for clinical background) if a negative blood culture was not confirmed within 14 days of the initial positive blood culture. Although we used data from only one university hospital, our novel approach and results will be a basis for future studies in several hospitals in Japan to provide statistical evidence of the clinical importance of confirming a negative follow-up blood culture in bacteremia patients, including those with MRSA infections.

[A Case of Vibrio vulnificus Infection Improved with Conservative Treatment in Kagoshima].

We herein report on a case of Vibrio vulnificus infection that was improved by conservative treatment in Kagoshima, Japan. A 75-year-old Japanese woman with liver cirrhosis presented to our hospital with shaking chill and right lower leg pain. Her blood culture was positive for V. vulnificus, and bullae had newly appeared on the right leg. Further history taking revealed that she had eaten some raw seafood before admission. She recovered following administration of antibiotics and small incisions in the lesion. West Japan (especially, the northern parts of Kyushu island) is well known as an endemic area of V. vulnificus infection: however, some cases had been reported in other areas in Japan. When clinicians treat cellulitis with risk factors, we should consider the possibility of V. vulnificus infection, even in a non-endemic area. Taking blood culture and early administration of appropriate antibiotics may contribute to conservative cure of some case of V. vulnificus infection.

Drug-induced liver injury associated with high-dose ceftriaxone: a retrospective cohort study adjusted for the propensity score.

PURPOSE: Ceftriaxone has been recognized as a well-tolerated drug; however, in some instances, liver dysfunction occurs after using high-dose ceftriaxone. We aimed to assess the incidence of liver injury due to high-dose ceftriaxone and to determine whether there is a dose-dependent risk of liver injury with this drug. METHODS: We conducted a retrospective cohort study of hospitalized adult patients treated with ceftriaxone at a tertiary care hospital from January 2012 to October 2013. We collected demographic and clinical data by reviewing their medical records. The incidence of liver injury based on biochemical criteria, defined as a primary outcome, was compared between patients treated with high-dose ceftriaxone (4 g/day) and those treated with a normal dose of ceftriaxone (2 g/day) for ≥5 consecutive days. A propensity score for the use of high-dose ceftriaxone was calculated from five factors. RESULTS: We identified 37 patients treated with high-dose ceftriaxone and 434 patients treated with a normal dose of ceftriaxone. Among these 471 patients, 15 patients (3.2 %) experienced liver injury, of whom six patients (6/37, 16.2 %) had received high-dose ceftriaxone and nine patients (9/434, 2.1 %) had received normal doses of ceftriaxone. In the multivariate analysis adjusted for the propensity score, high-dose ceftriaxone was independently associated with liver injury (odds ratio, 7.23; 95 % confidence interval, 2.01-26.0). CONCLUSIONS: The present study revealed that high-dose ceftriaxone was associated with a significantly higher incidence of liver injury compared with the normal-dose regimen. Therefore, clinicians should carefully observe for signs of liver injury after high-dose ceftriaxone use.

Nosocomial Native Valve Endocarditis due to Methicillin-Susceptible Staphylococcus aureus in a Patient with Psoriatic Arthritis.

Nosocomial infective endocarditis is a relatively rare, but critical disease. A Japanese man in his 80s with psoriatic arthritis that was being treated with prednisolone was admitted for dyspnea. The first diagnosis was healthcare-associated pneumonia, and piperacillin/tazobactam was started. The patient's blood culture was negative at the time of admission. During the treatment, acute kidney injury occurred due to the use of antibiotics. Hemodialysis was performed via a central venous catheter in the internal jugular vein. After treatment of pneumonia, the patient experienced a sudden onset of fever accompanied by a loss of consciousness. Blood cultures from the peripheral vein and the central venous catheter were positive for methicillin-susceptible Staphylococcus aureus. A transthoracic echocardiography revealed stringy strands of vegetation attached to the native mitral valve. Magnetic resonance imagings also showed a shower of emboli to the brain. Ceftriaxone and vancomycin were administered; however, the patient died following a massive cerebral infarction. Instances of in-hospital mortality from nosocomial endocarditis are higher than the rates of community-acquired endocarditis. Clinicians should pay close attention to risk factors for nosocomial infective endocarditis. These risk factors include long-term indwelling vascular devices, psoriatic arthritis and corticosteroid therapy.

Typhoid Vaccination among Japanese Travelers to South Asia and the Factors Associated with Compliance.

Objective In 2010, candid advice concerning the low rate of typhoid vaccination among Japanese travelers was received from Nepal. Recently, progressive Japanese travel clinics have encouraged Japanese travelers to be vaccinated against typhoid fever in conjunction with officially approved vaccines, such as hepatitis A vaccine. We herein report the status of typhoid vaccinations for Japanese travelers to the most endemic area (South Asia) and describe the factors associated with compliance. Methods In the travel clinic at Kurume University Hospital, we used the following criteria to retrospectively extract the records of new pre-travel Japanese clients between January 2011 and March 2015: hepatitis A vaccine administered, traveling to South Asian countries, and ≥2 years of age. We first summarized the participants and then divided them into typhoid-vaccinated and typhoid non-vaccinated groups for a comparative analysis. Results This study included 160 clients. A majority (70.0%) of these clients traveled for business. The duration of trips was long (≥1 month) (75.0%), and India was a popular destination (90.6%). A comparative study between the vaccinated group (n=122) and the non-vaccinated group (n=38) revealed that the two factors most positively associated with typhoid vaccination were business trips [adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 1.42-9.06] and coverage by a company/organization payment plan (aOR 7.14, 95% CI 2.67-20.3). Conclusion The trend toward typhoid vaccination among Japanese travelers to South Asia with pre-travel consultation is correlated with business trips and coverage by a company/organization payment plan. If problems concerning the cost of vaccines were resolved, more travelers would request typhoid vaccination.

The co-existence of Lemierre's syndrome and Bezold's abscesses due to Streptococcus constellatus: A case report.

RATIONALE: The ancient infectious diseases, Lemierre's Syndrome and Bezold's Abscesses are rare. PATIENT CONCERNS: A 70-year-old Japanese woman with a 15-year history of Parkinson's disease was referred to our hospital due to fever, occipital headache and bilateral shoulder pain that had continued for three months. She had been prescribed prednisolone due to a diagnosis of polymyalgia rheumatica. DIAGNOSES: A blood culture revealed bacteremia of Streptococcus constellatus. In addition, computed tomography revealed Bezold's abscesses and Lemierre's syndrome. INTERVENTIONS: We administered ceftriaxone for 31 days, followed by oral amoxicillin. OUTCOMES: The patient recovered and the abscesses improved. LESSONS: This case underscores the importance of blood culture tests and cross-referencing with radiological imagings in the diagnoses of these rare critical infectious diseases that mimic polymyalgia rheumatica.

Disseminated Mycobacterium intracellulare infection with multiple abscesses on extremities in a woman with chronic corticosteroid therapy.

A 78-year-old Japanese woman with rheumatoid arthritis was admitted to our hospital due to fever. She had been prescribed prednisolone and bucillamine. Computed tomography revealed abscesses on extremities. M. intracellulare was cultured from her calcaneus osteomyelitis, and this result pointed to a disseminated mycobacterial infection. We drained the abscesses and found M. intracellulare. We started antimycobacterial agents, but the patient died finally. Disseminated mycobacterial infection is rare but critical, and the possibility of such an infection in an immunocompromised patient should be a prime consideration when choosing appropriate drugs and surgical approaches.

Hepatitis B Vaccination Status among Japanese Travelers.

This study clarified the characteristics of travelers who received hepatitis B vaccinations. Subjects were 233 Japanese travelers who visited our clinic prior to travel. We summarized the characteristics of the clients and performed two comparative studies: first, we compared a hepatitis B-vaccinated group with an unvaccinated group; second, we compared a group that had completed the hepatitis B vaccine series with a group that did not complete the series. The hepatitis B vaccine was administered to 152 clients. Factors positively associated with the hepatitis B vaccination (after adjusting for age and sex) included the following: travel for business or travel as an accompanying family member; travel to Asia; travel for a duration of a month or more; and, inclusion of the vaccine in a company or organization's payment plan. Meanwhile, factors negatively associated with the vaccination were travel for leisure or education, and travel to North America or Africa. Among 89 record-confirmed cases, only 53 completed 3 doses. The completion rate was negatively associated with the scheduled duration of travel if it was from a month to less than a year (after adjusting for age and sex). The present study provides a basis for promoting vaccination compliance more vigorously among Japanese adults.

Mycobacterium conceptionense Bloodstream Infection in a Patient with Advanced Gastric Carcinoma.

A 65-year-old Japanese male farmer with advanced gastric adenocarcinoma and multiple hepatic metastases was admitted to our hospital. Blood culture results were positive on day 5, and Gram-positive rods were detected. According to the results of Ziehl-Neelsen staining and a cultured colony of this bacterium, we suspected a mycobacterial infection. Suspecting a rapidly growing mycobacterium (RGM), we started multidrug therapy with levofloxacin, clarithromycin, and ethambutol, and the patient recovered from the bloodstream infection. Further gene examination (16S rRNA, hsp65, and sodA) revealed an isolate of Mycobacterium conceptionense. M. conceptionense was first identified as an RGM in 2006. Among previous case reports of M. conceptionense infections, bone and soft tissue infections in hosts with a disorder of the normal structure (e.g., surgical sites) were dominant. We report the characteristics of M. conceptionense infection in this first Japanese case report and a review of the literature.

A Retrospective Analysis of Drug Fever Diagnosed during Infectious Disease Consultation.

OBJECTIVE: To clarify the current situation concerning drug fever (DF) in Japan, we retrospectively analyzed patients undergoing infectious disease consultation at our institution. METHODS: Between April 2014 and May 2015, we extracted the records of DF patients from among 388 patients who had obtained infectious disease consultations in Kurume University Hospital. We reviewed their medical charts and summarized the characteristics of DF. RESULTS: This study included the records of 16 patients. Clinical signs (relative bradycardia, the duration of the drug administration before becoming febrile, and the interval between the discontinuation of a drug and the alleviation of a fever), and laboratory tests (varied white blood cell count, low level of C-reactive protein, and a mild elevation of transaminases) were compatible with those from previous reports. Among the drug-confirmed cases, five involved the use of glycopeptides (vancomycin: 3, teicoplanin: 2), which were considered to be uncommon causes, and the another five cases involved the use of ß-lactams. In addition, the procalcitonin levels were either negative or low (≤0.25 ng/mL) in 10 of the 11 procalcitonin-measured cases. CONCLUSION: Our findings demonstrated that glycopeptides, similar to ß-lactams, may be the origin of DF. Furthermore, procalcitonin may be helpful in the diagnosis of DF, but only in combination with other detailed examinations.

Post-Travel Consultations in a Regional Hub City Hospital, Japan.

OBJECTIVE: To clarify the characteristics of post-travel consultation services in Japan, particularly in the provinces, we analyzed our post-travel patients in the travel clinic of Kurume University Hospital located in Kurume City (a regional hub City in southwestern Japan). METHODS: Sixty post-travel patients visited our clinic between April 2008 and October 2014 and participated in this study: 55 were Japanese and five were foreign. We summarized and compared the characteristics of the patients after dividing the Japanese participants into long-term travelers (>14 days) and short-term travelers (≤14 days). The foreign travelers were described in a separate analysis. RESULTS: Of the 55 Japanese travelers, the mean age (± standard deviation) was 37.3 ± 16.3 years, and 36 patients (65%) were men. Southeast Asia was the major destination (30/55, 55%), and business was stated as the major reason for travel (16/55, 29%). Post-exposure rabies prophylaxis (16/55, 29%) was the most common purpose for the consultations. There were 34 participants (62%) who were classified as short-term travelers. Fewer of the short-term travelers stated receiving pre-travel consultations compared with long-term travelers (11% vs. 79%, p=0.0002). The five foreign travelers included one dengue fever patient and two malaria patients. CONCLUSION: Most post-travel Japanese patients visited our clinic were short-term travelers who had not received any pre-travel consultation. One of the most common complaints, post-exposure rabies prophylaxis, could have been avoided to some extent by appropriate pre-travel consultations. The results of this study suggest that pre-travel consultations should therefore be encouraged for both long- and short-term travelers.

An HIV-infected Pregnant Woman Treated with the Long-term Administration of Antiretroviral Therapy Including Raltegravir.

A 27-year-old HIV-infected pregnant Japanese woman was admitted to our hospital at gestational week 14. The patient's HIV viral load was 71,000 copies/mL, and her CD4 cell count was 147 cells/mm(3). Zidovudine, lamivudine, and lopinavir/ritonavir were administered at gestational week 18. Because the viral load increased to 222,000 copies/mL at the initiation of antiretroviral therapy, we added raltegravir. The decrease in the viral load was satisfactory, and a caesarean delivery was performed. Although the plasma concentration of raltegravir in the neonate was significantly high (2,482 ng/mL), no adverse event was confirmed. There was no evidence of the mother-to-child transmission of HIV.

Four Cases of Autochthonous Dengue Infection in Japan and 46 Imported Cases: Characteristics of Japanese Dengue.

OBJECTIVE: A dengue outbreak occurred in Japan 2014. We investigated the characteristics of dengue infection among Japanese. METHODS: We investigated the medical charts retrospectively. Patients The study participants are patients who came to our clinic between 2008 and 2014. RESULTS: We investigated 4 domestic cases and 46 imported cases of Japanese with laboratory confirmation of dengue. Major symptoms were fever (100%), rash (86%), fatigue (84%), headache (81%), joint pain (66%), muscle pain (49%), and bleeding (6%). A late rash that appeared near the time of fever resolution was observed in 37 cases (74%). A total of 38/43 (88%) cases had low WBC count (<3,500 /µL) during the febrile period, 42/48 (88%) cases had a low platelet (PLT) count (<130×10(3)/µL), and 44/50 (88%) cases had a C-reactive protein (CRP) <2.0 mg/dL. CONCLUSION: Patients with a high fever, late rash, fever-associated leukopenia, low PLT count, low CRP, and elevated aminotransferases are generally suspected of having a dengue infection.