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Corticosteroids are widely used to treat severe COVID-19, but in immunocompromised individuals, who are susceptible to persistent infection, long term corticosteroid use may delay viral clearance. We present a case of prolonged SARS-CoV-2 infection in a man with significantly impaired B-cell immunity due to non-Hodgkin lymphoma which had been treated with rituximab. SARS-CoV-2 shedding persisted, despite treatment with remdesivir. Viral sequencing confirmed the persistence of the same viral strain, ruling out the possibility of reinfection. Although SARS-CoV-2 IgG, IgA and IgM remained negative throughout the treatment period, after reduction of the corticosteroid dose, PCR became negative. Long-term corticosteroid treatment, especially in immunocompromised individuals, may result in suppression of cell-mediated immunity and prolonged SARS-CoV-2 infection.

We herein report a 67-year-old kidney transplant patient who died of COVID-19. He was treated with hydroxychloroquine and azithromycin and received mechanical ventilation that temporarily improved his respiratory status. Despite our efforts, however, he later developed respiratory failure and died 43 days after the disease onset. The autopsy revealed prominent organization of alveoli and alveolar ducts, with a massive accumulation of macrophages in the lungs. A few severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-positive cells were detected in the lung, suggesting delayed virus clearance owing to his long-term immunosuppressed state, leading to constant lung damage and ultimately respiratory failure.

This study aimed to describe characteristics and treatment outcomes of overseas-born pulmonary tuberculosis (PTB) patients in Japan, and identify the factors associated with “treatment non-success”. We conducted a retrospective analysis of overseas-born patients with drug-susceptible PTB using cohort data of PTB cases newly registered in the Japan tuberculosis (TB) surveillance system between 2009 and 2018. Overall, 9151 overseas-born PTB cases were included in this study, and 70.3% were aged 34 years old or younger. “Students of high school and higher” (28.6%) and “regular workers other than service related sectors” (28.5%) accounted for over half of the study population, and they have continued to increase. Overall, the treatment success rate was 67.1%. Transferred-out constituted the largest proportion (14.8%) among the treatment non-success rate (32.9%). Multiple logistic regression analysis revealed patients whose health insurance type was “others and unknown”, including the uninsured (adjusted OR (AOR) = 3.43: 95% Confidence Intervals (CI) 2.57–4.58), those diagnosed as TB within “one year” (AOR = 2.61, 95% CI 1.97–3.46) and “1–5 years” (AOR = 2.44, 95% CI 1.88–3.17) of arrival in Japan, and males (AOR = 1.34, 95% CI 1.16–1.54), which were the main factors associated with treatment non-success. These findings imply that Japan needs to develop TB control activities considering the increasing trends of overseas-born PTB patients, the majority of whom are young and highly mobile. There is a need to pay greater attention to overseas-born PTB patients diagnosed within a short duration after entering Japan, who may be socially and economically disadvantaged for their treatment completion.

INTRODUCTION: Among patients with coronavirus disease 2019 (COVID-19), the factors that affect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production remain unclear. This study aimed to identify such factors among patients convalescing from COVID-19. METHODS: This study comprised patients who had been diagnosed with COVID-19 between January 1 and June 30, 2020 and gave consent for anti-SARS-CoV-2 spike protein antibody measurement using enzyme-linked immunosorbent assay during their acute and/or convalescent phases. Factors related to elevated antibody titers and the relationship between the days from disease onset and the development of antibody titers were assessed. RESULTS: A total of 84 participants enrolled in the study. Nineteen participants had antibody titers measured during the convalescent phase only, and 65 participants had antibody titers measured during the acute and convalescent phases. The antibody titers peaked in weeks 5 and 6. The stepwise multivariate log-normal analysis revealed that male sex (P = 0.04), diabetes mellitus (P = 0.03), and high C-reactive protein levels during the disease course (P

Real-time reverse transcription polymerase chain reaction (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are occasionally repeated when clinicians suspect false-negative results, but the conditions under which repeated RT-PCR testing is warranted remain unclear. We evaluated the practice of repeat RT-PCR testing for SARS-CoV-2 in 45 patients who were retested after an initial negative PCR test. Of these, the diagnosis of coronavirus disease (COVID-19) was confirmed in four patients with typical chest computed tomography (CT) findings and in one patient without typical CT findings in whom the test result was strongly suspected to be false-positive. We recommend repeat RT-PCR testing only for patients with typical CT findings of COVID-19.

Objective To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B‐immobilized polystyrene column (PMX‐DHP) in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive pneumonia patients. Methods This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS‐CoV‐2‐positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio

Summary Background Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. Methods We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov , NCT04492475 . Findings Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87–1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3–7%) in the interferon beta-1a plus remdesivir group and 3% (2–6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69–2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. Interpretation Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. Funding The National Institute of Allergy and Infectious Diseases (USA).

An 83-year-old man was hospitalized for coronavirus disease 2019 (COVID-19) after a 10-day history of a persistent fever. Chest computed tomography showed extensive non-segmental ground glass opacity. Despite the initiation of lopinavir and ritonavir, respiratory failure progressed. Two days of polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) with adjunctive corticosteroid prevented his respiratory condition from worsening. For rapidly progressive COVID-19 cases, the early use of PMX-DHP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung.

Rationale No comprehensive analysis has previously been performed to evaluate the clinical aspects of and microbiological evidence associated with Mycobacteroides abscessus complex (MABC) infection in a region, such as Japan, with a low MABC incidence. Objectives This study aimed to clarify the clinicopathological characteristics of MABC, which included clinical relatedness to erm(41) sequevar, phenotype (as colony morphology and minimum inhibitory concentration), and genotype. Methods A total of 121 MABC patients (68 with M. abscessus subsp. abscessus and 53 with M. abscessus subsp. massiliense) were recruited into this retrospective clinical-biological study from tertiary hospitals in Japan between 2004 and 2014. Results Approximately 30% of MABC patients had a history of previous nontuberculous mycobacterium (NTM) disease. Furthermore, 24.8% of the patients had another concomitant NTM infection after they were diagnosed with MABC. Fewer than 10% of the patients in the M. abscessus group had T28C in erm(41). While we observed a higher conversion rate for M. massiliense than for M. abscessus (72.4% and 34.8%, respectively, p = 0.002), recurrence remained relatively common for M. massiliense (31.0%). In the M. abscessus patients, the MIC of clarithromycin (CLR) was significantly lower on day 3 in patients with a better treatment response than in refractory patients (The median MIC; 0.75 μg/ml v.s 2.0 μg/ml, p = 0.03). There was no significant relation between clinical manifestations and variable number of tandem repeat genotypes. Conclusions Because the history and simultaneous isolation of other NTM in MABC infection are relatively common, these information should be carefully translated into clinical actions. The evaluation of early CLR resistance in M. abscessus and the erm(41) functions should be important to improve the treatment strategy.

Background The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. Method We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. Results The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934–0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929–0.998) and T-SPOT (96.9%; 95% CI, 0.914–0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934–0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. Conclusions The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan.

Development of aspergilloma is common in cases with a fungus ball-like shadow in cavities due to old tuberculosis. Some reports have shown that blood clots tend to appear as a fungus ball-like shadow. A 71-year-old man with a history of pulmonary tuberculosis presented with a fungus ball-like shadow in an old cavity and hemoptysis. There was no evidence of aspergillus infection on various examinations. We confirmed a blood clot and aneurysm of an artery under direct vision by bronchoscopy. A lateral thoracic artery aneurysm was detected by angiography. Transcatheter arterial embolization was performed. After treatment, the artery aneurysm disappeared.

Background In Vietnam, a country with a high tuberculosis (TB) burden, health professionals in both TB-specialized and non-TB-specialized general hospitals have a high risk of acquiring TB. The aims of the present study were to clarify the difficulties in TB infection control at non-TB specialized hospitals and whether any associated risks of latent TB infection exist among health professionals in Vietnam. Methods We conducted a cross-sectional study in a national tertiary and general hospital of Hanoi, Vietnam. Participants were health professionals, including physicians, nurses, and other health professionals. We assessed difficulties in TB infection control by conducting a knowledge, attitude, and practice (KAP) survey. We also collected data on the results of tuberculin skin tests (TSTs) conducted during health check-ups for hospital staff to determine whether health professionals had latent TB infection or TB disease. KAP scores were compared among health professional groups (physicians vs. nurses vs. other health professionals). Factors influencing knowledge scores were evaluated using multiple regression analysis. Results A total 440 health professionals at the study site participated in the KAP survey, and we collected the results of TSTs from a total of 299 health professionals. We observed a high prevalence of latent TB infection (74.2%), especially among participants in the emergency department. Although participants had high KAP scores, some topics were less understood, such as symptoms and risks of TB, proper use of protective equipment such as N95 respirators, and preventing transmission by patients with confirmed or suspected TB. Factors influencing knowledge scores associated with TB were age, a belief that TB is the most important infectious disease, being a medical professional, having previously attended workshops or seminars, and knowing that Vietnam has a high burden of TB. Conclusion In a non-TB specialized hospital of Vietnam, we observed a risk of TB infection among health professionals and difficulties in properly controlling TB infection. Early awareness regarding patients with suspected TB, to apply proper measures and prevent transmission, and education regarding obtaining updated knowledge through scientific information are crucial to enhancing TB infection control in general hospitals of Vietnam.

Background The seasonality of pulmonary tuberculosis (TB) incidence may indicate season-specific risk factors that could be controlled if they were better understood. The aims of this study were to elucidate how the incidence of TB changes seasonally and to determine the factors influencing TB incidence, to reduce the TB burden in Japan. Methods We assessed the seasonality of newly notified TB cases in Japan using national surveillance data collected between 2007 and 2015. To investigate age and sex differences, seasonal variation was analyzed according to sex for all cases and then by stratified age groups (0–4, 5–14, 15–24, 25–44, 45–64, 65–74, and ≥ 75 years). We used Roger’s test to analyze the cyclic monthly trends in seasonal variation of TB incidence. Results A total of 199,856 newly notified TB cases (male, 62.2%) were reported over the past 9-year period. Among them, 60.6% involved patients aged ≥65 years. Overall, the peak months of TB incidence occurred from April to October, excluding September. In the analysis stratified by age group, a significant seasonal variation in TB cases was observed for age groups ≥15 years, whereas no seasonal variation was observed for age groups ≤14 years. For female patients aged ≥25 years, the peak TB epidemic period was seen from June to December, excluding November. Male patients in the same age groups exhibited declining TB incidence from September to March. Conclusions TB incidence exhibits seasonality in Japan for people aged > 15 years and peaks in summer to fall. Monthly trends differ according to age and sex. For age groups ≥25 years, cases in women showed longer peaks from June to December whereas cases in men declined from September to December. These results suggest that the seasonality of TB incidence in Japan might be influenced by health checkups in young adults, reactivation of latent TB infection with aging, and lifestyle habits in older adults. These findings can contribute to establishing the potential determinants of TB seasonality in Japan.

The management of macrolide-resistant Mycobacterium avium complex (MR-MAC) pulmonary disease is difficult and is thought to be analogous to that of multidrug-resistant tuberculosis (MDR-TB).This study aimed to clarify the cause of MR-MAC, to see how its management affected outcome, and to compare its prognosis with that of MDR-TB.The medical records of 102 consecutive cases with MR-MAC pulmonary disease at three tertiary hospitals for mycobacteriosis in metropolitan Tokyo and one in Aichi prefecture from 2005 to 2014 were reviewed. The data of 311 consecutive cases with MDR-TB were extracted from the medical data at Fukujuji Hospital.Of the 90 patients who met the criteria, 53 (58.9%) received inappropriate first-line treatment, and 28 (31.1%) deviated from the standard treatment because of the adverse effects of ethambutol. The survival rates for MR-MAC disease and MDR-TB were not significantly different (P = 0.6). Multivariate analysis showed that the combination of aminoglycoside and surgery resulted in the best treatment outcome (P = 0.02), although neither of the two factors reached significance by themselves. The continuation of clarithromycin and the addition of fluoroquinolones did not improve the outcome for the treatment of disease caused by MR-MAC.Inappropriate prescription patterns and deviations from the standard treatment because of adverse drug reactions appeared to be the main causes of macrolide resistance in this patient series. Drug sensitivity testing should be performed at diagnosis to identify macrolide resistance and patients who may benefit from other therapy.

Background Mycobacterium scrofulaceum is a well-known pathogen associated with cervical lymphadenitis in children. However, pulmonary M. scrofulaceum disease is a rare condition with unknown clinical features. The present study aimed to clarify the clinical features of pulmonary M. scrofulaceum disease described in recent cases and reports. Methods We reviewed the medical records of all adult patients with pulmonary M. scrofulaceum disease at Keio University Hospital and the National Center for Global Health and Medicine Center Hospital between 2001 and 2011. We also conducted a review of the PubMed database to identify additional cases of pulmonary M. scrofulaceum disease in adults. Results Our study identified 8 cases of pulmonary M. scrofulaceum disease at the 2 identified institutions during our study period. Most cases were diagnosed in middle-aged and elderly men with underlying pulmonary diseases such as chronic obstructive pulmonary disease and Mycobacterium avium complex lung disease, as well as those with a history of pulmonary tuberculosis. In contrast, most previously reported cases identified through our literature review had a history of dust inhalation or underlying silicosis. Three of 8 cases at our institutions and 20 of 23 cases from the literature were treated with combination therapies. Conclusions We conclude that in the recent histories of our institutions, pulmonary M. scrofulaceum disease has mainly occurred in patients with chronic pulmonary diseases. We further conclude that combination therapies that include clarithromycin might yield better patient outcomes.

We examined preserved medical charts of 470 Spanish influenza patients (8 with fatal cases) hospitalized at former army hospitals in Japan during 1919-1920. The following factors were associated with longer periods of hospitalization: adventitious discontinuous lung sounds, maximum respiration rate, continuation of high fever after hospital admission, and diphasic fever.

Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p

BACKGROUND: Pneumothorax is one of the most important complications after bronchoscopy. This study was conducted to determine the risk factors for post-bronchoscopy pneumothorax. METHODS: We retrospectively reviewed the medical records of 23 consecutive subjects who were diagnosed with iatrogenic pneumothorax after bronchoscopy between August 2010 and February 2014. Forty-six control subjects who did not develop pneumothorax after bronchoscopy were randomly selected. The factors affecting the occurrence of pneumothorax were determined by univariate and multivariate analyses. RESULTS: Among 991 patients who underwent bronchoscopy during the study period, 23 (2.3%) developed pneumothorax after bronchoscopy. Among these 23 subjects, 13 (57%) required chest tube drainage. Compared with the control group (46 randomly selected from 968 subjects who did not develop pneumothorax), the group that developed pneumothorax had a preponderance of women and had more target lesions located in the subpleural area (odds ratio [OR] 7.8, 95% CI 0.9–64), especially those that were close to the interlobular pleura (OR 5.1, 95% CI 1.6–16.1) and the left lung (OR 3.2, 95% CI 1.1–9.5). Multivariate analysis revealed that a subinterlobular pleural location of a lesion was a risk factor for pneumothorax (OR 4.8, 95% CI 1.1–20.4). CONCLUSIONS: Pneumothorax occurred significantly more frequently when bronchoscopy was performed for subinterlobular pleural lesions. Close attention and care should be taken during bronchoscopy, especially when target lesions are abutting the interlobular pleura.

A 63-year-old man was transferred to our hospital because of an exacerbation of asthma. His symptoms deteriorated even after increasing the dose of inhaled corticosteroids/long-acting beta2-adrenoceptor agonists (ICS/LABA). He had no chest pain and an electrocardiogram revealed ST elevation. A coronary angiogram revealed a reduced left ventricular function with an apical ballooning pattern without coronary stenosis. He was diagnosed with Takotsubo cardiomyopathy. Catecholamine elevation due to acute asthma and an overdose of ICS/LABA may be triggers of this disease. We should remember that Takotsubo cardiomyopathy is a complication of asthma and that catecholamine plays an important role in its onset, although it is essential for asthma treatment.

Background Avian influenza A (H5N1) in human presents a global pandemic threat, and preparedness is urgently required in high-risk countries. Methods A retrospective chart review was conducted on 8 patients with H5N1 infection (aged 2–30 years; 3 fatal) who were hospitalized in Bach Mai Hospital (BMH), Vietnam, or in affiliated hospitals with consultation by physicians in BMH between 2007 and 2010. Demographic background, chest radiographs, and clinical and laboratory data were evaluated to determine the critical issues in relation to clinical outcomes. Treatment of 4 patients with acute respiratory distress syndrome (ARDS) (2 fatal) was assessed for renal replacement therapy using continuous hemodiafiltration (CHDF), polymyxin B-immobilized (PMX) hemoperfusion, or their combination. Results Patients had direct contact with dead/sick poultry infected with H5N1 virus or lived in areas where H5N1 poultry outbreaks had been reported at the same time as their illness. Time to initiation of oseltamivir from symptom onset was 2–6 days for survivors and 7–9 days for non-survivors. All patients except one had infiltrative shadows on chest radiographs on admission. Patients with delayed treatment developed ARDS. Renal replacement therapy contributed to patient survival, with improvement of oxygenation and a dramatic decrease in serum cytokine levels if initiated earlier. Conclusions Understanding local H5N1 poultry outbreaks and chest radiography assist early diagnosis and initiation of antiviral treatment. Developing a network among local and tertiary care hospitals can reduce the time to initiation of treatment. CHDF and PMX hemoperfusion are possible candidates for effective treatment of ARDS with H5N1 if applied earlier.

Nontuberculous mycobacterial bone infections among human immunodeficiency virus (HIV)-negative patients are rare, although a few studies have described such infections. We retrospectively reviewed the medical and microbiological data of HIV-negative osteomyelitis cases caused by nontuberculous mycobacteria treated in our tertiary-care hospital over 14 years from January 1, 2000, to December 31, 2013. Three HIV-negative patients had contracted bone infections due to nontuberculous mycobacteria. All of the patients had at least 1 predisposing condition that led to the infections: idiopathic CD4-positive lymphocytopenia and/or anti-interferon-γ autoantibody syndrome.

Sputum conversion defined as 3 consecutive smear-negative sputum samples collected on different days is one of standard requirements for discontinuation of isolation for patients with smear-positive pulmonary tuberculosis (SPpTB). Sputum smear conversion is usually seen prior to culture conversion. However, in some patients, sputum smear tests are continuously positive for a long time. To discontinue isolation of the patients, culture conversion is required instead of smear conversion. Culture testing requires a long incubation period, which results in longer patient stay and isolation.To identify a more efficient definition of culture conversion, which will enable treating physicians to take the decision to discontinue isolation.The charts of patients with SPpTB admitted from September 2007 to March 2011 were reviewed. The recent definition of culture conversion is 3 subsequent culture-negative sputum specimens incubated for 6 weeks (3 CNs for 6 weeks) in liquid media. Treatment days and admission days were calculated based on the application of the new 3 definitions (3 CNs for 4 weeks, 2 CNs for 6 weeks, 2 CNs for 4 weeks).Of 301 patients, 224 were discharged after smear conversion; 77 were continuously smear-positive and were discharged after culture conversion. The median hospital stay was 56 days in patients discharged due to smear conversion and 107 days in patients discharged due to culture conversion, based on the recent definition. The numbers of treatment days needed for culture conversion were identical in most patients, regardless of definitions. At the time of reporting, all patients conformed to the new definitions and all the patients' sputum specimens were 3 CNs for 6 weeks except for one patient happened to be with 2 consecutive smear-negative specimens at an early phase of chemotherapy. The most efficient definition of culture conversion in this study was 2 CNs for 4 weeks. This enabled to shorten each patient's stay by 31 days and to lessen each patient's cost of hospitalization by about 4,900 dollars.Two subsequent CNs for 4 weeks of smear-positive sputum samples is enough to enable discontinuation of patient isolation and may thus shorten hospital stay.

The adverse effects of anti-tuberculosis agents is an important problem for treatment of tuberculosis. We report 2 possible cases of isoniazid-induced tenosynovitis. Case 1: A 49-year-old man with untreated diabetic mellitus presented with hypesthesia and difficulty grasping with his right hand 1 month after starting treatment of tuberculosis of the lung and pleuritis using isoniazid, rifampicin, ethambutol, and pyrazinamide. His symptoms were due to tenosynovitis, which was detected by magnetic resonance imaging. The clinical course and isoniazid challenge test revealed that the condition was related to isoniazid. After discontinuing isoniazid treatment, his symptoms gradually improved. Case 2: An 78-year-old man operated on for rectal cancer 3 weeks previously presented with edema and arthralgia of both hands 1 month after starting anti-tuberculosis treatment. His tuberculosis was diagnosed at preoperative screening tests for rectal cancer. Owing to a medical history of gout, pyrazinamide was discontinued. However, his symptoms did not improve. Magnetic resonance imaging revealed findings indicative of tenosynovitis. At the end of anti-tuberculosis treatment, his symptoms improved slightly within 6 months. Isoniazid-induced tenosynovitis and arthritis are rare adverse effects. However, they may be underestimated because the severity is variable. We suggest further investigations of the side effects of isoniazid using imaging techniques such as magnetic resonance imaging.

We report the case of a 71-year-old man with rheumatoid arthritis. Infliximab administration was started as treatment for rheumatoid arthritis in January 2009. As he showed a positive result for the tuberculin test, he was treated with isoniazid for 9 months. He was subsequently referred to our department in October 2011 with a right-sided pleural effusion. When thoracoscopy was performed under local anesthesia, white and red protruding lesions of various sizes were observed in the pleural cavity. A biopsy revealed fibrous granulation tissue, and tissue culture and all sensitivity tests were positive for Mycobacterium tuberculosis. Therefore, thoracoscopy is useful for not only diagnosis but also determining whether resistant tuberculosis is present.

BACKGROUND: In addition to clinical aspects and pathogen characteristics, people's health-related behavior and socioeconomic conditions can affect the occurrence and severity of diseases including influenza A(H1N1)pdm09. METHODOLOGY AND PRINCIPAL FINDINGS: A face-to-face interview survey was conducted in a hospital in Mexico City at the time of follow-up consultation for hospitalized patients with pneumonia due to influenza virus infection. In all, 302 subjects were enrolled and divided into two groups based on the period of hospitalization. Among them, 211 tested positive for influenza A(H1N1)pdm09 virus by real-time reverse-transcriptase-polymerase-chain-reaction during the pandemic period (Group-pdm) and 91 tested positive for influenza A virus in the post-pandemic period (Group-post). All subjects were treated with oseltamivir. Data on the demographic characteristics, socioeconomic status, living environment, and information relating to A(H1N1)pdm09, and related clinical data were compared between subjects in Group-pdm and those in Group-post. The ability of household income to pay for utilities, food, and health care services as well as housing quality in terms of construction materials and number of rooms revealed a significant difference: Group-post had lower socioeconomic status than Group-pdm. Group-post had lower availability of information regarding H1N1 influenza than Group-pdm. These results indicate that subjects in Group-post had difficulty receiving necessary information relating to influenza and were more likely to be impoverished than those in Group-pdm. Possible factors influencing time to seeking health care were number of household rooms, having received information on the necessity of quick access to health care, and house construction materials. CONCLUSIONS: Health-care-seeking behavior, poverty level, and the distribution of information affect the occurrence and severity of pneumonia due to H1N1 virus from a socioeconomic point of view. These socioeconomic factors may explain the different patterns of morbidity and mortality for H1N1 influenza observed among different countries and regions.

Background Awareness of individuals’ knowledge and predicting their behavior and emotional reactions is crucial when evaluating clinical preparedness for influenza pandemics with a highly pathogenic virus. Knowledge, attitude, and practice (KAP) relating to avian influenza (H5N1) virus infection among residents in communities where H5N1 patients occurred in Vietnam has not been reported. Methods and Principal Findings Face-to-face interviews including KAP survey were conducted in Bac Kan province, located in the northeast mountainous region of Vietnam. Participants were residents who lived in a community where H5N1 cases have ever been reported (event group, n = 322) or one where cases have not been reported (non-event group, n = 221). Data on emotional reactions of participants and healthcare-seeking behavior after the event in neighboring areas were collected as well as information on demographics and environmental measures, information sources, and KAP regarding H5N1. These data were compared between two groups. Higher environmental risk of H5N1 and improper poultry-handling behaviors were identified in the event group. At the time of the event, over 50% of the event group sought healthcare for flu-like symptoms or because they were scared. Awareness of the event influenced KAP scores. Healthcare-seeking behavior and attention to H5N1 poultry outbreaks diminished in the event group as time passed after the outbreak compared with the non-event group. Factors that motivated participants to seek healthcare sooner were knowledge of early access to healthcare and the risk of eating sick/dead poultry, and perception of the threat of H5N1. Conclusions Awareness of H5N1 patients in neighboring areas can provoke panic in residents and influence their healthcare-seeking behavior. Periodic education to share experiences on the occurrence of H5N1 patients and provide accurate information may help prevent panic and infection and reduce mortality. Local conditions should be taken into account when emphasizing the need for early access to healthcare.

Background Knowledge, clinical practice, and professional motivation of medical providers relating to H5N1 infection have an important influence on care for H5N1 patients who require early diagnosis and early medical intervention. Methods/Principal Findings Novel educational programs including training and workshops for medical providers relating to H5N1 infection in Vietnam were originally created and implemented in 18 provincial hospitals in northern Vietnam between 2008 and 2010. A self-administered, structured questionnaire survey was conducted in 8 provincial hospitals where both educational training and workshops were previously provided. A total of 326 medical providers, including physicians, nurses, and laboratory technicians who attended or did not attend original programs were enrolled in the survey. Knowledge, clinical attitudes and practice (KAP), including motivation surrounding caring for H5N1 patients, were evaluated. The study indicated a high level of knowledge and motivation in all professional groups, with especially high levels in laboratory technicians. Conferences and educational programs were evaluated to be the main scientific information resources for physicians, along with information from colleagues. The chest radiographs and the initiation of antiviral treatment in the absence of RT-PCR result were identified as gaps in education. Factors possibly influencing professional motivation for caring for H5N1 patients included healthcare profession, the hospital where the respondents worked, age group, attendance at original educational programs and at educational programs which were conducted by international health-related organizations. Conclusions Educational programs provide high knowledge and motivation for medical providers in Vietnam caring for H5N1 patients. Additional educational programs related to chest radiographs and an initiation of treatment in the absence of RT-PCR are needed. Networking is also necessary for sharing updated scientific information and practical experiences. These enhanced KAPs by educational programs and integrated systems among hospitals should result in appropriate care for H5N1 patients and may reduce morbidity and mortality.

Background Anti-viral treatment has been used to treat severe or progressive illness due to pandemic H1N1 2009. A main cause of severe illness in pandemic H1N1 2009 is viral pneumonia; however, it is unclear how effective antiviral treatment is against pneumonia when administered >48 hours after symptom onset. Therefore, we aimed to determine how time from symptom onset to antiviral administration affected the effectiveness of antiviral treatment against pneumonia due to pandemic (H1N1) 2009. Methods/Principal Findings A retrospective medical chart review of 442 patients was conducted in a hospital in Mexico. Subjects had tested positive for pandemic H1N1 2009 virus by real-time reverse-transcriptase-polymerase-chain-reaction and were administered oseltamivir. Median time from symptom onset to oseltamivir administration was 5.0 days (range, 0–43). 442 subjects, 71 (16.1%) had severe pneumonia which required mechanical ventilation, 191 (43.2%) had mild to moderate pneumonia, and 180 (40%) did not have pneumonia. Subjects were divided into four groups based on time to oseltamivir administration: ≤2, 3–7, 8–14, and >14 days. Severity of respiratory features was associated with time to treatment, and multivariate analysis indicated that time to oseltamivir administration was associated with severity of respiratory features. A proportional odds model indicated that 50% probability for occurrence of pneumonia of any severity and that of severe pneumonia in patients who would develop pneumonia reached at approximately 3.4 and 21 days, respectively, after symptom onset. Patients with a shorter time to oseltamivir administration were discharged earlier from the hospital. Conclusions Earlier initiation of oseltamivir administration after symptom onset significantly reduced occurrence and severity of pneumonia and shortened hospitalization due to pandemic H1N1 2009. Even when administered >48 hours after symptom onset, oseltamivir showed considerable potential for reducing pneumonia. Application of these results would benefit patients affected by future influenza pandemics.

We report 2 cases of household transmission of pneumococcal pneumonia in isolation, associated with pandemic influenza (H1N1) 2009. A Chinese-American family consisting of a 47-year-old woman and her 16- and 9-year-old sons came to Japan at the beginning of July 2009. The day after their arrival, the woman noticed a high fever in the eldest son. The following day, the other family members also developed high fevers. Real-time reverse transcription polymerase chain reaction (RRT-PCR) analysis confirmed pandemic influenza A (H1N1) 2009 infection in all family members. After diagnosis, all patients were given oseltamivir at another hospital. Subsequently, they were admitted to our hospital and placed in isolation in accordance with the Japanese Infectious Disease Law. At the time of admission, all family members were in a stable condition. However, on the day after admission, the mother complained of a productive cough. Upon further investigation, a CT scan showed a consolidation shadow in the right middle lung lobe. After isolating Streptococcus pneumoniae from her sputum culture, we diagnosed bacterial pneumonia due to S. pneumoniae. In addition, both of her sons also developed fever and cough, and sputum obtained from her elder son indicated S. pneumoniae infection. All 3 were treated with ampicillin and their symptoms improved over a period of a few days. Although the role of Streptococcus pneumoniae in cases of novel influenza A (H1N1) remains unclear, these bacteria may have been responsible for many complications during past pandemic and non-pandemic influenza cases. Use of the 23-valent pneumococcal polysaccharide vaccine should be considered as a potential way to prevent pneumococcal pneumonia during future influenza pandemics.

Although the incidence rate in Japan has been decreasing since the declaration of tuberculosis emergency in 1999, the reported tuberculosis cases among foreigners have been increasing year by year (from 5.1% in 2000 to 6% in 2003). As the number of foreign residents in Japan has been increasing every year, tuberculosis cases among them are also expected to increase.The aim of this study is to investigate and clarify clinical features of recent tuberculosis patients among foreigners.Fifty-two cases were analyzed, who were admitted to our hospital because of active tuberculosis from January 2004 to April 2007.Among total 52 cases, male was 29, female 23, and the mean age (SD) of the patients was 31.8 (+/- 8.8) years old. Their mother countries were China, Republic of Korea and so on. The cavitary lesions were found on chest X-ray in 54%, the drug resistant rate was 8.2%, and the treatment completion rate was 92%.Comparing with reports in the past, almost parameters about tuberculosis control have improved, for example the drug resistant rate was decreased and the treatment completion rate was increased. The promotion of DOTS strategy in Japan might be attributed to the improvement of these parameters. Because more immigrants from the developing countries are expected in near future, not only strengthening current DOTS strategy but also new countermeasures such as QFT-2G and Electronic-Nose Technology should be introduced into tuberculosis control of foreigners living in Japan to decrease tuberculosis incidence and improve treatment outcome by early detection and adherence to treatment.

Background Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear. Objective The relation between various infections and adult asthma exacerbations was investigated in clinical practice. Methods The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis. Results Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients. Conclusion Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation.

Background Pneumonia patients with wheezing due to influenza A(H1N1)pdm09 were frequently treated with systemic corticosteroids in Japan although systemic corticosteroid for critically ill patients with pneumonia caused by influenza A(H1N1)pdm09 has been controversial. Applicability of systemic corticosteroid treatment needs to be evaluated. Methods/Principal Findings We retrospectively reviewed 89 subjects who were diagnosed with influenza A(H1N1)pdm09 and admitted to a national hospital, Tokyo during the pandemic period. The median age of subjects (45 males) was 8 years (range, 0–71). All subjects were treated with antiviral agents and the median time from symptom onset to initiation of antiviral agents was 2 days (range, 0–7). Subjects were classified into four groups: upper respiratory tract infection, wheezing illness, pneumonia with wheezing, and pneumonia without wheezing. The characteristics of each group was evaluated. A history of asthma was found more frequently in the wheezing illness (55.6%) and pneumonia with wheezing (43.3%) groups than in the other two groups (p = 0.017). Corticosteroid treatment was assessed among subjects with pneumonia. Oxygen saturation was lower in subjects receiving corticosteroids (steroid group) than in subjects not receiving corticosteroids (no-steroid group) (p