Search

s Background Pneumocystis pneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality. Methods This is a retrospective, five-year study was conducted in a medical center, enrolling patients diagnosed with PCP, who received a chest computed tomography (CT) scan. The radiological findings and medical records of all participants were reviewed carefully by 2 independent doctors. Univariable and multivariable analysis was performed to identify radiological predictors for pulmonary coinfection and clinical risk factors for poor prognosis. Results A total of 101 participants were included, of which 39 were HIV-infected and 62 were non-HIV-infected. In multivariable analysis, radiologic predictors on chest CT for coinfection with bacteria pneumonia included lack of ground glass opacity (adjusted odds ratio [aOR], 6.33; 95% confidence interval [CI], 2.03-19.77; p = 0.001) and presence of pleural effusion (aOR, 3.74; 95% CI, 1.27-10.99; p = 0.017). Predictors for fungal pneumonia included diffuse consolidation (adjusted OR, 6.27; 95% CI, 1.72-22.86; p = 0.005) and presence of pleural effusion (adjusted OR, 5.26; 95% CI, 1.44-19.17; p = 0.012). A significantly higher in-hospital mortality was associated with older age, recent corticosteroid exposure, cytomegalovirus coinfection, and acute respiratory failure. Conclusion Early identification of pulmonary coinfections in PCP using radiological features on the CT scans, will enable appropriate treatment which is crucial to improve the prognosis.

Background: The detection and treatment of latent tuberculosis infection (LTBI) is a key step in eliminating tuberculosis (TB), but information on safety and on treatment interruption in elderly LTBI patients remains limited. Methods: This multicenter prospective observational study included individuals with LTBI who underwent preventive therapy. Incidents of systemic adverse reactions (SARs) and treatment interruption rates in an elderly group (≥60 years old) and a young group (

Yu-Ting Tseng,1,2 Pei-Yun Chou,1 Ming-Hong Tai,2,3 Chia-Yen Dai,4– 6 Susan Shin-Jung Lee,1,7 Yao-Shen Chen,1,7 Hung-Chin Tsai,1,3,7,8,* Yen-Hsu Chen2,6,9– 13,* 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; 4Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 5Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 8Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 9Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Sepsis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center of Tropical Medicine and Infectious Diseases, Kaohsiung Medical University, Kaohsiung, Taiwan; 12Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan; 13Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Hung-Chin TsaiDivision of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanEmail hctsai1011@yahoo.com.twYen-Hsu ChenGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanEmail infchen@gmail.comBackground: The Jarisch–Herxheimer reaction (JHR) is an inflammatory reaction that can occur after treatment for syphilis. The mechanism of JHR is unknown. The level of C-reactive protein (CRP) increases during infection and inflammation. We hypothesized that CRP may be involved in the JHR in syphilitic patients at initial syphilis infection and also through interactions with benzathine penicillin-induced phagocytosis.Methods: This prospective cohort study enrolled syphilitic adult patients with/without JHR between July 2018 and October 2020. Serum samples before and after the administration of the first dose of benzathine penicillin were obtained. The serum level of CRP was determined by ELISA. The Kruskal–Wallis test was used to compare the levels of CRP in different groups, and the Wilcoxon signed-rank test was used to compare changes in CRP before and after benzathine penicillin treatment.Results: Twenty-nine syphilitic patients and three control groups (10 men who have sex with men (MSM) taking pre-exposure prophylaxis, 10 HIV-infected patients without syphilis, and 12 HIV-infected patients with previous syphilis) were enrolled. All 29 syphilitic patients were MSM, and 21 patients (72%) were infected with HIV. Overall, 41% (12/29) of the patients developed the JHR. The active syphilis groups had significantly higher serum levels of CRP (median 11,761 ng/mL, IQR 2986– 19,061 ng/mL). There were no significant differences in the serum levels of CRP before or after benzathine penicillin treatment. The 12 patients with the JHR had significantly higher CRP levels before benzathine penicillin treatment (16,262 ng/mL [IQR 12,033– 26,150 ng/mL] vs 3489 ng/mL [IQR 924– 160,640] ng/mL, p = 0.0059, 95% CI 4002– 17,098 ng/mL, area under the curve 0.799, 95% CI 0.632– 0.966, sensitivity 1, specificity 0.647, with a CRP cut-off value of 4569.32 ng/mL).Conclusion: A high baseline CRP level can predict the occurrence of the JHR in syphilitic patients treated with benzathine penicillin.Keywords: C-reactive protein, Jarisch-Herxheimer reaction, syphilis

Background: In Southeast Asia, Japanese encephalitis (JE) is an important cause of viral encephalitis which may cause severe neurological sequelae. JE affects mostly children; therefore, clinical presentations and prognosis of adult JE patients are seldom addressed. This study aimed to describe the clinical characteristics and prognostic factors for the outcome of adult JE patients. Methods: Medical records of adult JE patients with acute encephalitis syndrome during 2001–2018 from five medical centers in southern Taiwan were reviewed. Clinical characteristics, brain images, and prognostic factors for outcomes were analyzed. Patients were divided into the good outcome (GO) group and poor outcome (PO) group according to their Glasgow Coma Scale (GCS) scores (GCS >8 vs. ≤ 8) at discharge. Results: Sixty-eight patients (men, 61.8%; median age, 50 years) were included. Summer is the epidemic season, and the number of cases peaked in June. The most common symptoms at initial presentation were altered consciousness and fever (both 94.1%), followed by headache (51.4%). The most commonly involved brain regions were thalamus (55.7%) and basal ganglion (37.7%). The median GCS score at nadir was 8, and the median time from onset to nadir was five days. Fifty-two patients were included in the GO group, while 16 were included in the PO group. On multivariate analysis, flaccidity, rigidity, and elevated CSF protein level were identified as independent prognostic factors for PO. Conclusion: Initial clinical presentations of abnormal muscle tone including flaccidity, rigidity and high CSF protein levels are independent prognostic factors for PO in adult JE patients. Keywords: Adult, Japanese encephalitis, Outcome, Prognostic factor

Purpose The role of pathogenic Escherichia coli colonization in asymptomatic pregnant women is not well understood. The purpose of this work was to determine the prevalence, antimicrobial susceptibility, and neonatal outcomes of pathogenic E. coli colonization in pregnant women. Patients and methods A total of 137 women from southern Taiwan with singleton pregnancies were enrolled between March 2016 and June 2017. The women were prospectively screened for E. coli colonization in the rectovaginal region during prenatal examination. The exclusion criteria are twin pregnancy of the mother and major anomaly of the neonate. All E. coli isolates were identified as either pathogenic or commensal strains, and their susceptibility to various antimicrobials was investigated. Clinical data of the infants were retrieved from their medical records. Results Results showed that 35.8% of asymptomatic pregnant women had pathogenic E. coli colonization in the rectovaginal region. Neonates born to such mothers showed significant morbidities, including hospitalization (OR= 3.74, 95% CI= 1.18~11.87), hyperbilirubinemia (OR= 2.81, 95% CI= 1.24~6.38), and gastrointestinal symptoms (OR= 5.53, 95% CI= 1.39~21.94). Maternal colonization with pathogenic E. coli at rectoanal site was a risk factor for neonatal hyperbilirubinemia after Benjamini-Hochberg (BH) adjustment (52% vs 24%, adjusted P= 0.048). Conclusion The prevalence of pathogenic E. coli colonization in Taiwanese asymptomatic pregnant women was high, and the neonates born to colonized mothers exhibited potential neonatal morbidities. Larger studies are necessary to confirm these findings.

Background: The incidence of non-tuberculous mycobacterial (NTM) infections of the skin, soft tissue, and musculoskeletal system (SSTI) has increased over the past two decades, however, re...

Background: This study aimed to investigate the frequency of sequence type (ST) 131 strains and outcome of cirrhotic patients with bloodstream infections (BSIs) caused by extended-spectrum beta-lactamase-producing Escherichiacoli (ESBLEC) and non-extended-spectrum beta-lactamase-producing Escherichiacoli (NESBLEC). Methods: The incidence of ST 131 strains, hospital stay, and 30-day re-admission/mortality were compared between 51 ESBLEC and 51 NESBLEC bacteremic patients with cirrhosis. Results: ST 131 strains were found in 35.3% of the ESBLEC group and 0% of the NESBLEC group (p &lt, 0.001). Mean hospital stay was 26.5 days in the ESBLEC group and 17.1 days in the NESBLEC group (p = 0.006). Thirty-day re-admission rates were 11.8% in the ESBLEC group and 5.9% in the NESBLEC group (p = 0.5). ST 131 strains were associated with 30-day re-admission (odds ratio: 4.5, 95% confidence interval: 1.1&ndash, 18.9). Thirty-day mortality rate was 31.4% in the ESBLEC group and 23.5% in the NESBLEC group (p = 0.4). Conclusion: In patients with cirrhosis, the ESBLEC BSIs group had a higher frequency of ST 131 strains and longer hospital stay than the NESBLEC BSIs group with similar 30-day re-admission/mortality. ST 131 strains were associated with 30-day re-admission.

Nontuberculous mycobacterial infections and colonization are becoming more prevalent worldwide. Mycobacterium abscessus complex (MABC) is one of the predominant pathogens capable of a wide spectrum of infections, with 50% of infections involving the lungs. The decision to commence treatment is determined according to the severity of the disease, risk of progressive disease, presence of comorbidities, and goals of treatment. MABC is resistant to standard antituberculous agents and has variable drug susceptibility across different geographical locations, therefore, antibiotic susceptibility testing of all clinically significant isolates is crucial for selecting a treatment strategy. Pulmonary infections due to MABC is difficult to cure using the currently recommended regimens from the American Thoracic Society and British Thoracic Society. Macrolides are the cornerstone of treatment, but the efficacy of macrolide-based chemotherapy may be compromised by resistance. Despite the introduction of new drugs for treatment, treatment outcomes remain unsatisfactory. The combination of surgical resection of limited lung disease regions with a multidrug, macrolide-based therapy offers the optimal chance of achieving clinical cure of the disease. This review focuses on medical treatment of MABC–lung disease and the efficacy of new agents, such as clofazimine, amikacin inhalation therapy, tigecycline and linezolid, for treating MABC–lung disease.

Background/Purpose: The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. This study investigated the clinical features and bacteriology of pediatric patients with ESBL-producing E. coli bacteremia and compared their characteristics with those of adult patients. Methods: Clinical and laboratory data from all of the 41 patients aged ≤18 years diagnosed with E. coli bacteremia were collected over 5 years. Patients aged >18 years diagnosed with E. coli bacteremia, matched 1:1 for calendar time, were enrolled as the adult group. All E. coli isolates were tested for their blaCTX-M group and sequence type 131 (ST131). A novel seven-single nucleotide polymorphism-based clonotyping test was applied to detect the septatypes of each isolate. Results: In the adult group, patients with ESBL-producing E. coli bacteremia had more previous hospitalizations and antimicrobial agent use than did those with non-ESBL-producing E. coli bacteremia, but these differences were not found in pediatric group. In the pediatric group, the proportion of isolates producing CTX-M group 9 was higher than that in the adult group (85.7% vs. 42.9%; p

Hung-Chin Tsai,1–3 I-Tzu Chen,1 Susan Shin-Jung Lee,1,2 Yao-Shen Chen1,2 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan Purpose: Sparse data are available on the prevalence of resistance among HIV-1-infected patients with virological failure to a single-tablet regimen (STR). This study aimed to evaluate the prevalence of HIV genotypic drug resistance in HIV-1-infected patients with virological failure to STRs in southern Taiwan. Patients and methods: This retrospective study investigated drug resistance in patients with virological failure to STR from January 2016 to September 2017. Antiretroviral resistance mutations were defined using the 2017 International AIDS Society-USA HIV drug resistance algorithm, and drug resistance was compared using the HIVdb program of the Stanford University HIV Drug Resistance Database. Variables between resistance and non-resistance groups were compared. Results: Thirty-nine HIV-1-infected patients with treatment failure were tested for resistance, of whom 89% were infected by men who have sex with men. Subtype B HIV-1 strains were found in 90% of the patients. Eight patients were treatment naïve and initiated STRs, while 31 patients experienced treatment failure after switching to STRs. Eighty-seven percent of the patients harbored any of four classes of resistance (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors (PIs), and integrase strand transfer inhibitors). The prevalence rates of nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, PI, and integrase strand transfer inhibitor resistance were 72%, 82%, 10%, and 3%, respectively. Patients with PI resistance were more likely to respond to treatment with a non-tenofovir disoproxil fumarate/emtricitabine/efavirenz-based STR (P=0.004) and a longer duration of antiretroviral therapy (101 months [72.0–123.3] vs 11 months [7–44], P=0.007). There were no associations between different STRs and transmission risk factors, HIV subtype, duration of antiretroviral therapy, and resistance to tenofovir disoproxil fumarate. Conclusion: A high rate of antiretroviral drug resistance was found in the patients who failed STR treatment. The presence of PI resistance in these patients represented an inappropriate switch from a multiple tablet regimen to an STR. These findings should remind clinicians that detailed drug resistance history and close monitoring are mandatory after switching to an STR. Keywords: HIV, single-tablet regimen, drug resistance, treatment failure, antiretroviral therapy

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform β and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 β, γ, e, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

BackgroundThe risk of tuberculosis (TB) is higher in human immunodeficiency virus (HIV)-infected patients and intravenous drug users (IDUs). We determined the prevalence and risk factors of latent TB infection (LTBI) in individuals with or without HIV infection, including IDUs, in a country with a low HIV prevalence, an intermediate TB burden, and a high Bacillus Calmette-Guérin (BCG) vaccine coverage using two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST).MethodsFor this prospective, cross-sectional study, HIV-infected and -uninfected patients from a regional hospital and medical center in Taiwan were enrolled. Results of the two IGRAs [QuantiFERON-TB Gold (QFT-G) and QuantiFERON-TB Gold In-Tube (QFT-GIT)] and the TST were compared. Risk factors for positivity were analyzed.ResultsWe recruited 233 patients [198 (85%) men; mean age, 39.4 years]. Most patients (74%) were BCG vaccinated. The prevalence of LTBI was estimated to be 22.8% by TST, 15.9% by QFT-G, and 20.6% by QFT-GIT. HIV-infected individuals had fewer positive QFT-GIT [7.0% vs. 28.6%, p

Hand hygiene (HH) is considered to be the most simple, rapid, and economic way to prevent health care-associated infection (HAI). However, poor HH compliance has been repeatedly reported. Our objective was to evaluate the impact of implementing the updated World Health Organization (WHO) multimodal HH guidelines on HH compliance and HAI in a tertiary hospital in Taiwan.We conducted a before-and-after interventional study during 2010-2011. A multimodal HH promotion campaign was initiated. Key strategies included providing alcohol-based handrub dispensers at points of care, designing educational programs tailored to the needs of different health care workers, placement of general and individual reminders in the workplace, and establishment of evaluation and feedback for HH compliance and infection rates.Overall HH compliance increased from 62.3% to 73.3% after 1 year of intervention (P .001). The rate of overall HAI decreased from 3.7% to 3.1% (P .05), urinary tract infection rate decreased from 1.5% to 1.2% (P .05), and respiratory tract infection rate decreased from 0.53% to 0.35% (P .05). This campaign saved an estimated $940,000 and 3,564 admission patient days per year.The WHO multimodal HH guidelines are feasible and effective for the promotion of HH compliance and are associated with the reduction of HAIs.

Executive Summary: Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia. Keywords: Pneumonia, Guidelines, Treatment, Taiwan

The 14-3-3 proteins are cerebrospinal fluid (CSF) markers of neuronal damage during infectious meningitis and Creutzfeldt-Jakob disease. Little is known about dynamic changes in the individual isoforms in response to parasitic eosinophilic meningitis. The purposes of this study were to determine the 14-3-3 protein isoform patterns, examine the kinetics and correlate the severity of blood brain barrier (BBB) damage with the expressions of these markers in mice with eosinophilic meningitis. Mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and sacrificed every week for 3 consecutive weeks after infection. The Evans blue method and BBB junctional protein expressions were used to measure changes in the BBB. Hematoxylin and eosin staining was used to analyze pathological changes in the mice brains following 1-3 weeks of infection with A. cantonensis. The levels of 14-3-3 protein isoforms in serum/CSF and brain homogenates were analyzed by Western blot, and immunohistochemistry (IHC) was used to explore the different isoform distributions of 14-3-3 proteins and changes in BBB junctional proteins in the mice brain meninges. Dexamethasone was injected intraperitoneally from the seventh day post infection (dpi) until the end of the study (21 dpi) to study the changes in BBB junctional proteins. The amounts of Evans blue, tight junction and 14-3-3 protein isoforms in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. There were significant increases in 14-3-3 protein isoforms β and γ in the CSF in the second and third weeks after infection compared to the controls and first week of infection, which were correlated with the severity of BBB damage in brain histology, and Evans blue extravasation. Using IHC to assess the distribution of 14-3-3 protein isoforms and changes in BBB junctional proteins in the mice brain meninges, the expressions of isoforms β, γ, e, and θ and junctional proteins occludin and claudin-5 in the brain meninges increased over a 3-week period after infection compared to the controls and 1 week after infection. The administration of dexamethasone decreased the expressions of BBB junctional proteins occludin and claudin-5 in the mice brain meninges. Our findings support that 14-3-3 proteins β and γ can potentially be used as a CSF marker of neuronal damage in parasitic eosinophilic meningitis caused by A. cantonensis.

Background The epidemiology and impact of hepatitis δ virus (HDV) on hepatic outcomes and virological and immunological responses to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) patients coinfected with hepatitis B virus (HBV) in northern Taiwan have been reported. However, the epidemiology and impact of HDV infection in HIV–HBV coinfection patients in southern Taiwan remains uncertain. Methods In this cohort study, a total of 64 HIV patients coinfected with HBV were identified between January 1, 2009 and May 30, 2012. The seroprevalence of anti-HDV antibodies, HDV genotyping, clinical manifestations and hepatic outcomes were compared between the patients with and without HDV coinfection, and laboratory examinations and hepatic outcomes were recorded. Results Among the 64 HIV patients coinfected with HBV, seven were seropositive for HDV (10.9%). There were no statistically significant differences in risk factors for acquiring HIV infection. During a median observation period of 27.8 months, the adjusted hazard ratio of HDV and HBV genotype (type B vs. non-type B) on hepatitis flare-ups were 62.132 ( p = 0.04) and 0.028 ( p = 0.01), respectively. All seven patients had genotype II and were HDV viremic. The phylogenetic tree analysis and clinical history evaluation did not identify any clusters of HDV infection. Conclusion HDV infection resulted in higher rate of hepatitis flare-ups, but it did not have a statistical significance on HIV progression and immunological response to HAART. Whether higher rate of HDV viremia has worse impact on the hepatic outcomes requires further investigation.

Background Dengue fever is an important arboviral disease. The clinical manifestations vary from a mild non-specific febrile syndrome to severe life-threatening illness. The virus can usually be detected in the blood during the early stages of the disease. Dengue virus has also been found in isolated cases in the cerebrospinal fluid, urine, nasopharyngeal sections and saliva. In this report, we describe the isolation of dengue virus from the upper respiratory tract of four confirmed cases of dengue. Methods We reviewed all laboratory reports of the isolation of dengue virus from respiratory specimens at the clinical microbiology laboratory of the Kaohsiung Veterans General Hospital during 2007 to 2015. We then examined the medical records of the cases from whom the virus was isolated to determine their demographic characteristics, family contacts, clinical signs and symptoms, course of illness and laboratory findings. Results Dengue virus was identified in four patients from a nasopharyngeal or throat culture. Two were classified as group A dengue (dengue without warning signs), one as group B (dengue with warning signs) and one as group C (severe dengue). All had respiratory symptoms. Half had family members with similar respiratory symptoms during the period of their illnesses. All of the patients recovered uneventfully. Conclusions The isolation of dengue virus from respiratory specimens of patients with cough, rhinorrhea and nasal congestion, although rare, raises the possibility that the virus is capable of transmission by the aerosol route among close contacts. This concept is supported by studies that show that the virus can replicate in cultures of respiratory epithelium and can be transmitted through mucocutaneous exposure to blood from infected patients. However, current evidence is insufficient to prove the hypothesis of transmission through the respiratory route. Further studies will be needed to determine the frequency of respiratory colonization, viable virus titers in respiratory secretions and molecular genetic evidence of transmission among close contacts., Author summary Dengue virus is rarely identified in respiratory specimens. We retrospectively identified four patients with dengue fever who had the virus isolated from their nose or throat. All the patients had respiratory signs or symptoms. Half had family members who also had respiratory symptoms. Further studies are needed to evaluate the possibility of respiratory transmission of this virus.

Background/PurposeHuman immunodeficiency virus (HIV) and syphilis coinfection is a common phenomenon. A percentage of neurosyphilis cases is asymptomatic in HIV-infected patients. The diagnosis of neurosyphilis is more difficult because of the alteration of cerebrospinal fluid (CSF) presentation by the HIV itself. The CSF levels of the degradation products of nitric oxide (NO; e.g., nitrate and nitrite) are reportedly elevated in animals and patients with bacterial meningitis. We hypothesized that an elevated CSF nitrite concentration may be present in patients coinfected with HIV and neurosyphilis.MethodsThis cohort study was conducted from January 2007 to June 2008. Forty patients were enrolled and included seven patients in the control group and 33 HIV-infected patients with or without syphilis. Nitrite levels in the serum and the CSF were measured by using the Griess assay.ResultsThe CSF nitrite levels were significantly higher in HIV-infected patients with neurosyphilis, compared to the control group or patients with HIV infection only or patients with HIV and syphilis coinfection (p = 0.026). The CSF nitrite levels were correlated with the CSF white blood cell counts (Spearman correlation test, r2 = 0.324; p

Angiostrongylus cantonensis is the main causative agent of human eosinophilic meningitis in Southeast Asia and the Pacific Islands. A previous study demonstrated that the 14-3-3β protein is a neuropathological marker in monitoring neuronal damage in meningitis. Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infection. However, the mechanism by which steroids act in eosinophilic meningitis is unknown. We hypothesized that the beneficial effect of steroids on eosinophilic meningitis is partially mediated by the down-regulation of 14-3-3β protein expression in the cerebrospinal fluid (CSF). In this animal study, we determined the dynamic changes of 14-3-3β protein in mice with eosinophilic meningitis. The 14-3-3β protein in serum and CSF was increased in week 2 and 3 after infections. Dexamethasone administration significantly decreased the amounts of CSF 14-3-3β protein. By developing an in-house ELISA to measure 14-3-3β protein, it was found that the amounts of 14-3-3β protein in the CSF and serum increased over a three-week period after infection. There was a remarkable reduction of 14-3-3β protein in the CSF after 2 weeks of dexamethasone treatment. In conclusion, the administration of corticosteroids in mice with eosinophilic meningitis decreased the expression of 14-3-3β protein in the CSF.

The potential mechanisms for blood–brain barrier damage and the diagnosis of neurosyphilis in HIV patients co-infected with syphilis (HIV-S) are unclear. The aim of the study was to determine the expression of CXCL2 in the serum and cerebrospinal fluid (CSF) of HIV-S patients. A total of 34 HIV patients and 7 controls were enrolled in a HIV clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of CXCL2 were determined by ELISA. Neurosyphilis was defined as a CSF white blood cell count of ≧20 cells/μl or a reactive CSF Venereal Disease Research Laboratory (VDRL). Demographics and medical histories were collected. All the patients with HIV-S were males. Most (80 %) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≧1:32. The medium age was 37 (range 21–68) years. The medium CD4 T cell counts at the time of the diagnosis of syphilis were 299 (range 92–434) cells/μl. Eight patients (24 %) had neurosyphilis based on a reactive CSF VDRL test (n = 5) or increased CSF white blood cell counts of ≧20 cells/μl (n = 3). The concentrations of CSF CXCL2 were significantly higher in patients with HIV and neurosyphilis as compared to HIV with syphilis, HIV, and controls (p = 0.012). There were no significant differences in serum concentrations between the four groups. There was a correlation between CSF CXCL2 concentrations with neurosyphilis (p = 0.017), CSF white blood cell count (p = 0.001), and CSF protein levels (p = 0.005). The CSF level of CXCL2 can be used to distinguish those with or without neurosyphilis in HIV infected patients.

Background Cellulitis is a common infectious disease. Although blood culture is frequently used in the diagnosis and subsequent treatment of cellulitis, it is a contentious diagnostic test. To help clinicians determine which patients should undergo blood culture for the management of cellulitis, a diagnostic scoring system referred to as the Bacteremia Score of Cellulitis was developed. Methods Univariable and multivariable logistic regression analyses were performed as part of a retrospective cohort study of all adults diagnosed with cellulitis in a tertiary teaching hospital in Taiwan in 2013. Patients who underwent blood culture were used to develop a diagnostic prediction model where the main outcome measures were true bacteremia in cellulitis cases. Area under the receiver operating characteristics curve (AUC) was used to demonstrate the predictive power of the model, and bootstrapping was then used to validate the performance. Results Three hundred fifty one cases with cellulitis who underwent blood culture were enrolled. The overall prevalence of true bacteremia was 33/351 cases (9.4 %). Multivariable logistic regression analysis showed optimal diagnostic discrimination for the combination of age ≥65 years (odds ratio [OR] = 3.9; 95 % confidence interval (CI), 1.5–10.1), involvement of non-lower extremities (OR = 4.0; 95 % CI, 1.5–10.6), liver cirrhosis (OR = 6.8; 95 % CI, 1.8–25.3), and systemic inflammatory response syndrome (SIRS) (OR = 15.2; 95 % CI, 4.8–48.0). These four independent factors were included in the initial formula, and the AUC for this combination of factors was 0.867 (95 % CI, 0.806–0.928). The rounded formula was 1 × (age ≥65 years) + 1.5 × (involvement of non-lower extremities) + 2 × (liver cirrhosis) + 2.5 × (SIRS). The overall prevalence of true bacteremia (9.4 %) in this study could be lowered to 1.0 % (low risk group, score ≤1.5) or raised to 14.7 % (medium risk group, score 2–3.5) and 41.2 % (high risk group, score ≥4.0), depending on different clinical scores. Conclusions Determining the risk of bacteremia in patients with cellulitis will allow a more efficient use of blood cultures in the diagnosis and treatment of this condition. External validation of this preliminary scoring system in future trials is needed to optimize the test. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1907-2) contains supplementary material, which is available to authorized users.

Objectives This study was designed to determine the susceptibility of clinical isolates of multidrug-resistant (MDR) and non-MDR Mycobacterium tuberculosis to sulfamethoxazole, trimethoprim and trimethoprim/sulfamethoxazole over a 12 year period in Taiwan. Patients and methods We examined a total of 117 clinical isolates of M. tuberculosis collected from Southern Taiwan, 116 from 1995 to 2006 and an extensively drug-resistant (XDR) isolate in 2009. These included 28 isolates susceptible to all four first-line agents, 52 MDR isolates and 36 isolates with a mixed combination of drug resistance patterns other than MDR and 1 XDR isolate. Results Sulfamethoxazole inhibited 80% growth of all 117 isolates regardless of their susceptibility to the first-line agents at an MIC(90) of 9.5 mg/L. The concentration required to inhibit 99% growth was 38 mg/L. There were no significant changes in the MIC(50) or MIC(90) of sulfamethoxazole over a 12 year period. All 117 isolates were resistant to trimethoprim at >8 mg/L. The combination of trimethoprim/sulfamethoxazole at a ratio of 1:19 had no additive or synergistic effects. Conclusions Sulfamethoxazole inhibited the growth of clinical isolates of M. tuberculosis at achievable concentrations in plasma after oral administration. Susceptibility to sulfamethoxazole remained constant over a 12 year period. Trimethoprim was inactive against M. tuberculosis and trimethoprim/sulfamethoxazole provided no additional activity. Although the current and prior studies demonstrate that sulfamethoxazole is active against M. tuberculosis the search needs to continue for more active, lipid-soluble sulphonamides that are better absorbed into tissues and have improved therapeutic efficacy.

Accurately differentiating tuberculous pleurisy from lung cancer is important for disease management but difficult using conventional laboratory methods. This study assessed the value of adenosine deaminase (ADA) and interferon gamma (IFN-γ) for differentiating the two conditions in a region of Taiwan with a high prevalence of tuberculosis. The study population comprised patients with lymphocytic exudative pleural effusions: tuberculous (n=24) and malignant (n=42). Mean levels of ADA and IFN-γ in pleural fluid, measured with commercial standardized kits, were significantly higher for tuberculous than for malignant pleurisy (p

Angiostrongylus cantonensis also known as the rat lungworm, is prevalent in the Pacific Islands and southeast Asia and is the most common cause of eosinophilic meningitis in humans. Although frogs and toads are known as paratenic hosts of A. cantonensis, they are rarely reported as the infectious source of human angiostrongyliasis. We report a case of encephalitis caused by Angiostrongylus cantonensis after eating raw frogs mixed with wine as a health supplement. Prednisolone at a dose of 1 mg/kg/day was prescribed for 14 days successfully. We advise that travelers and residents of endemic areas should avoid eating raw frogs and a public caution on the danger of eating raw wild animal products or the whole animal is recommended to alleviate such accidental infection.

Cellulomonas spp. are often believed to be of low virulence and have never been reported as a pathogen causing human disease before. We report the first case of endocarditis caused by Cellulomonas and complicated with osteomyelitis of the lumbar spine in a 78-year-old woman. General weakness and aggravated lower back pain followed by sudden-onset of fever and chills were the major presentation. The diagnosis of infective endocarditis in this case was definitely using the Duke criteria. The magnetic resonance imaging of the lumbar spine revealed infective spondylodisciitis at an early stage. After a full course of antibiotics treatment, the patient's fever subsided but her lower back pain persisted. A slow clinical response to appropriate antimicrobial agents was characteristic of Gram-positive bacillary endocarditis.

To quantitate cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase 9 (MMP-9) in adult patients with Klebsiella pneumoniae meningitis and to correlate levels of MMP-9 with parameters of intrathecal inflammation and analyze the kinetic changes of MMP-9. In a prospective cohort study, levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP-1) concentrations were measured in the CSF of six adult patients with meningitis and 11 controls. MMP-9 and TIMP-1 were detected in all of the six patients at presentation and follow up lumbar puncture. CSF levels of MMP-9 (6.71+/-7.29 ng/ml) and TIMP-1(454.3+/-242.9 ng/ml) were higher in patients than in the control group (0.07+/-0.11 ng/ml and 27.14+/-39.34 ng/ml, respectively). Levels of MMP-9 correlated with CSF concentrations of protein, cell count and lactate. Repeated lumbar punctures showed that levels of MMP-9 decrease during clinical recovery, although the levels of MMP-9 in the CSF are variable because of the small number of cases. The relative change in gelatin zymography is comparable to the changes of MMP-9 levels found in ELISA. MMP-9 levels in CSF may be a useful tool in follow-up in patients with K. pneumoniae meningitis.

Reports of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates carrying Panton-Valentine leukocidin (PVL) gene that causes infective endocarditis in injection drug users (IDUs) with human immunodeficiency virus (HIV) infection are rare in the English language literature. We present a case of CA-MRSA infective endocarditis with bilateral septic lung emboli in a previously healthy 45-year-old IDU. This case suggests that PVL gene-positive CA-MRSA should be considered as a potential pathogen in IDUs with infective endocarditis.

We describe a patient with Mycobacterium marinum tenosynovitis associated with a fish spine injury acquired at a gambling fishing pond in southern Taiwan and identify the source of the infection. M. marinum was isolated from fishing ponds and underground water and wastewater at the site. The isolates shared the same pulsed-field gel electrophoresis pattern as the patient. M. marinum was not detected in 54 samples obtained from 27 fish. Mycobacterium gordonae was isolated from 24 samples collected from the fish. Mycobacterium abscessus was isolated from 3 fish samples (Lateolabrax japonicus 1 and Sciaenops ocellatus 2). M. abscessus and M. gordonae were isolated from all water samples. This investigation provides strong evidence that the predisposing factor for the M. marinum infection was with a fish spine injury acquired at a gambling fishing pond. The source of the infection was the contaminated pond water.

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of vascular endothelial growth factor in eosinophilic meningitis, vascular endothelial growth factor was measured in the cerebrospinal fluid (CSF) and blood of 9 patients with eosinophilic meningitis in a cohort study. VEGFCSF was detected in 8 (90%) of 9 eosinophilic meningitis patients (range, 45-2190 pg/mL) at presentation. The mean VEGFCSF at presentation, 1 week, and 2 weeks after admission was 568 pg/mL, 751 pg/mL, and 1031 pg/mL, respectively. There was an association between VEGFCSF, CSF protein, white cell count, and eosinophil counts. The VEGFSERUM fluctuated during the 6-month follow-up period. These results indicate that vascular endothelial growth factor may be associated with blood-brain barrier disruption in patients with eosinophilic meningitis.

Background The risk factors, microbial etiology, differentiation, and clinical features of purulent and non-purulent cellulitis are not well defined in Taiwan. Methods We conducted a retrospective cohort study of hospitalized adults with cellulitis in Taiwan in 2013. The demographic characteristics, underlying diseases, clinical manifestations, laboratory and microbiological findings, treatments, and outcomes were compared for patients with purulent and non-purulent cellulitis. Results Of the 465 patients, 369 had non-purulent cellulitis and 96 had purulent cellulitis. The non-purulent group was significantly older (p = 0.001) and was more likely to have lower limb involvement (p

Background Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the most effective therapeutic agent for Pneumocystis jirovecii pneumonia (PJP) in patients with AIDS. The major drawback is the frequent occurrence of adverse reactions (ADRs).The current study was designed to determine the frequency and risk factors for TMP/SMX-related ADRs among patients with PJP and AIDS. Methods A retrospective study was conducted in adult patients with PJP and AIDS who were admitted to the Veterans General Hospital in, Kaohsiung, Taiwan between January 2006 and December 2011. Charts were reviewed to determine the effect of age, risk behaviors, severity of illness, viral load, CD4 cell counts, use of corticosteroids, and dosage and duration of TMP/SMX on ADRs during hospitalization. Patients who received TMP/SMX for ≤ 5 days or with an incomplete medical record were excluded. Multivariate logistic regression was used to calculate the hazard ratio (HR) for ADRs. Results Fifty two of 75 patients with PJP and AIDS met the study criteria. Of these patients, 21/52 (40.3%) developed an ADR. Among the 21 patients who suffered an ADR, skin rash was noted in 10 (47.6%), liver function impairment in nine (42.9%), elevated creatinine in eight (38.1%), fever in four (19%), and gastrointestinal symptoms in three (14.3%). Most of the ADRs occurred within the 1 st 2 weeks of TMP/SMX therapy. Cox proportional hazards analysis revealed that a daily dose of TMP/SMX of ≥ 16 mg/kg (HR, 3.8; 95% confidence interval, 1.40–10.35; p = 0.009) and age 34 years (HR, 4.30; 95% confidence interval, 1.52–12.14; p = 0.006) were independently associated with ADRs. Conclusion We found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.

The human immunodeficiency virus type 1 (HIV-1) epidemic in Taiwan is rapidly escalating because of an increasing number of injection drug users (IDUs). A molecular epidemiological study of HIV-1-infected IDUs in Taiwan was conducted from January 2004 to April 2005. Of the 131 HIV-1-positive specimens collected all contained detectable sequences including 105 from the C2-V3 region of env and 87 from the protease and reverse transcriptase genes of pol. Phylogenetic analysis of these sequences indicated that 128 individuals harbored CRF07_BC which resembles the dominant strains circulating among IDUs in China. Twenty-three individuals had a history of travel to the southwest provinces of China and shared needles or apparatuses there. This suggests that CRF07_BC might have been transmitted from China into Taiwan thereby causing an outbreak among IDUs in Taiwan. This is the first report in the English literature of the appearance of HIV-1 CRF07_BC in Taiwan. These provide information relevant to the development of antiviral therapy and vaccine in Taiwan and may assist public health workers in the prevention of HIV-1 spread. (authors)

Invasive aspergillosis is a devastating infection in immunocompromised hosts. The lung is the most common site of primary infection, and the central nervous system is the most common secondary site of invasive disease. Invasive aspergillosis in autoimmunopathies treated with corticosteroids has rarely been reported in the literature. Herein, we report the case of a 48-year-old female patient with idiopathic thrombocytopenic purpura complicated with fatal invasive pulmonary and cerebral aspergillosis. She had been given 1,016 g intravenous amphotericin B empirically for lung infection during a previous admission. At presentation, she had fever, cough, and shortness of breath for 4 weeks. Chest radiography revealed a huge cavity over the left upper lung field. Bronchoscopic biopsy and culture showed Aspergillus species. She was initially treated with intravenous amphotericin B (0.9 mg/kg/day), and intravenous hydrocortisone for her idiopathic thrombocytopenic purpura. However, deterioration of consciousness occurred 12 days after hospitalization. Computed tomography of the brain showed ring-like cystic mass lesions in the right side basal ganglion. Stereotactic aspiration of the brain revealed Aspergillus species. Her condition exacerbated despite combination treatment with high-dose amphotericin B (1.2 mg/kg/day) and itraconazole (400 mg/day). She died 24 days after admission. This case suggests that treatment with corticosteroids and premature discontinuation of antifungal drugs bear the risk of fatal cerebral involvement in patients with invasive pulmonary aspergillosis.

The most common cause of eosinophilic meningitis is the rat lungworm Angiostrongylus cantonensis a parasite that is endemic in the southeast Asian and Pacific regions. Outbreaks of eosinophilic meningitis associated with drinking raw vegetable juice are rarely reported, even in regions of endemic infection. We performed a cohort study among Taiwanese with eosinophilic meningitis who drank raw vegetable juice within three months of the onset of the outbreak. Clinical manifestations, laboratory examinations, and outcomes were prospectively followed. Five native Taiwanese met the case definition of eosinophilic meningitis. Specific antibodies to A. cantonensis were detected in the serum of five of the patients and in the cerebrospinal fluid (CSF) of four of the patients. Central nervous system manifestations included headache (n = 5 [100%]), Brudzinski's sign/stiff neck (n = 5 [100%]), hyperesthesia/paresthesias (n = 5 [100%]), and cranial nerve palsy (n = 1 [20%]). Laboratory findings included peripheral (n = 5 [100%]) and CSF eosinophilia (n = 4 [80%]), transient increases in the white blood cell count (n = 1 [20%]), and in serum levels of creatine kinase (n = 1 [20%]). Meningeal enhancement, as well as high signal intensity, at the subcortical white matter on T2 weighted and fluid attenuated inversion recovery images were observed on magnetic resonance imaging in four patients. There were three episodes of relapse during treatment and all resolved with after a lumbar puncture and/or administration of steroids. At the 12-month follow up, all five patients had recovered without neurologic sequelae. Risk factors identification showed that consumption of raw vegetable juice was associated with illness (Pearson correlation test r = 0.867, P = 0.01). There was association between the presence of raw vegetable juice and CSF eosinophilia (Spearman's correlation test r = 0.816, P = 0.004).

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis worldwide. Human infection occurs after ingestion of the worms in raw snails or fish that serve as intermediate hosts. Two outbreaks of central nervous system infection with A. cantonensis occurred in Kaoshiung, Taiwan, during 1998 and 1999 among Thai laborers who ate raw snails. A detailed clinical studies of 17 of these patients was conducted, including study of 13 patients who underwent magnetic resonance imaging (MRI) scans of the brain. The MRI scans revealed high signal intensities over the globus pallidus and cerebral peduncle on T1-weighted imaging, leptomeningeal enhancement, ventriculomegaly, and punctate areas of abnormal enhancement within the cerebral and cerebellar hemisphere on gadolinium-enhancing T1 imaging, and a hyperintense signal on T2-weighted images. There was a significant correlation between severity of headache, cerebrospinal fluid (CSF) pleocytosis, and CSF and blood eosinophilia with MRI signal intensity in T1-weighted imaging (P < 0.05). Eosinophilic meningitis produced by A. cantonensis needs to added to the list of causes of hyperintense basal ganglia lesions found on T1-weighted MRI scans in tropical countries.

type 2 monomicrobial NF, classically caused by Streptococcus pyogenes (group A β-hemolytic streptococci), with or without concomitant infection with Staphylococcus aureus; and type 3 NF, gas gangrene caused by Clostridium perfringens. Monomicrobial NF caused by Vibrio vulnificus and Aeromonas hydrophila, which often occur in patients with underlying liver disease [4, 5], and fungal NF have been added as separate entities. In this issue of Clinical Infectious

Background The prevalence of patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is higher in Taiwan than in Western countries. This study aimed to analyze the frequency and risk factors for highly active antiretroviral therapy (HAART)-related liver toxicity in patients co-infected with HIV and HCV with advanced liver fibrosis in Taiwan. Methods This retrospective cohort study included 228 HAART-experienced and HAART-naive patients who were co-infected with HIV and HCV from January 2013 to December 2013 in Taiwan. Transaminase elevation (TE) was defined by grades. Fibrosis 4 score and aspartate-to-platelet ratio index were used to evaluate liver fibrosis. Cox proportional hazard regression model was used to analyze the risk factors for time to TE events. Results A total of 228 patients were included. Only two episodes (1.28%) of high-grade TE were observed. The overall prevalence rate of TE was 16%, and the incidence was 1.38 cases/100 patient-months. Two predictive factors of TE were the initiation of HAART during the study period and CD4 cell count less than 350 cells/mm 3 . Subgroup analysis showed that HAART improved liver fibrosis status in patients who had advanced liver fibrosis at baseline ( p = 0.033). Conclusion The frequency of HAART-related TE in HIV and HCV co-infected patients in Taiwan was much lower than that observed in previous studies. Pre-existing advanced liver fibrosis had no influence on the frequency of TE. The use of HAART showed benefits on liver fibrosis progression in patients with underlying advanced liver fibrosis.

Purpose To describe two outbreaks of Angiostrongylus cantonensis infection that occurred in Kaohsiung, Taiwan, during 1998 and 1999, and to characterize the source of the outbreaks and the clinical manifestations of the disease. Subjects and methods We performed a retrospective cohort study among Thai laborers with eosinophilic meningitis who ate raw snails ( Ampullarium canaliculatus ), as well as an environmental surveillance of larvae in snails. Results We enrolled 17 Thai laborers in whom severe headache and eosinophilia developed within 4 to 23 days after eating raw snails. Twelve (71%) developed eosinophilic meningitis. Third-stage larvae were found in the cerebrospinal fluids of 2 patients and in all 12 tested snails. Specific antibodies to A. cantonensis were detected in serum from 16 of the patients and in cerebrospinal fluid from 5 of the patients. Central nervous system manifestations included headache (n = 17 [100%]), fever (n = 11 [65%]), Brudzinski's sign/stiff neck (n = 11 [65%]), hyperesthesia (n = 3 [18%]), cranial nerve palsy (n = 2 [12%]), diplopia (n = 2 [12%]), and ataxia (n = 1 [6%]). Laboratory findings included peripheral eosinophilia (n = 15 [88%]) and cerebrospinal fluid eosinophilia (n = 12 [71%]); elevated immunoglobulin (Ig) E levels (n = 13 [100%]); and transient increases in white blood cell count (n = 7 [41%]) and in serum levels of creatine kinase (n = 7 [41%]), transaminase (n = 3 [18%]), and lactate dehydrogenase (n = 2 [12%]). The severity of illness and eosinophilia were correlated with the number of ingested snails. Meningeal and basal ganglion enhancement was noted on magnetic resonance imaging in several patients. Treatment with mebendazole combined with glucocorticosteroids appeared to shorten the course of the infection, but not the number of relapses. The eosinophil count fell to normal within 3 months, but IgE levels remained elevated for as long as 6 months. All patients recovered with minimal neurologic sequelae. Conclusion Eosinophilic meningitis caused by A. cantonensis should be considered in patients who have headache or central nervous system manifestations after eating raw snails.

To the Editor: The influenza A pandemic (H1N1) 2009 virus has spread globally since it first appeared in Mexico in April 2009. This third influenza pandemic since the Spanish influenza pandemic of 1918 (1) has caused at least 400,000 infections within 6 months; estimated mortality rate is 1.2% (2). Emergence of oseltamivir resistance in the pandemic (H1N1) 2009 virus is a rising challenge to global control of the pandemic. So far, 39 oseltamivir-resistant pandemic (H1N1) 2009 viruses have been reported worldwide (3). Among the 32 resistant strains reported in October 2009, a total of 13 (41%) were associated with postexposure chemoprophylaxis and 16 (50%) were from samples of patients receiving oseltamivir (3). We report rapid emergence of resistance (H275Y mutation) in a patient, 4 days after early treatment with standard doses of oseltamivir for pandemic (H1N1) 2009 pneumonia. On September 1, 2009, a 20-year-old man with mental retardation consulted the emergency department of Kaohsiung Veterans General Hospital after 1 day of fever, sore throat, and nonproductive cough. A rapid diagnostic antigen test (Quick Vue Influenza test; Quidel, San Diego, CA, USA) showed the man to be positive for influenza A. He was hospitalized for bilateral pneumonitis and treated with oseltamivir (75 mg 2×/day for 5 days), ampicillin/sulbactam, and erythromycin. However, a progressive increase in bilateral perihilar interstitial infiltration developed on the third day, accompanied by increasing dyspnea. Influenza A pandemic (H1N1) 2009 virus was isolated from the patient’s nasopharyngeal secretions on days 1 and 4 by using MDCK cells. After DNA sequence analysis of the neuraminidase gene, the mutation of H275Y was not found in the first isolate, but sequence analysis of the second isolate detected mixed populations (C/T) in the 823-nt position of the neuraminidase gene. Only a single pattern (T) was found from the cultured viruses, indicating a mixed quasispecies of oseltamivir-resistant and -susceptible viruses emerging after 4 days of oseltamivir treatment. The oseltamivir-resistant viruses become dominant in the cell culture–propagated viruses. Chan et al. reported a similar case in which the original clinical specimens contained a mixed population of variants, and oseltamivir-resistant viruses become dominant after the passage in MDCK cells (4). On his 9th day in the hospital, the patient was intubated because of acute respiratory distress syndrome (Figure) and given levofloxacin. Urine samples were negative for Pneumococcus and Legionella spp. antigens. The patient improved and was extubated on hospital day 16. Figure Radiograph (anteroposterior view) of patient with acute respiratory distress syndrome and oseltamivir-resistant pandemic (H1N1) 2009 virus. Paired serologic test results were negative for Mycoplasma pneumoniae and Legionella spp. antibody; however, immunoglobulin G for Chlamydia pneumoniae increased 4-fold. By 37 days after illness onset, clinical signs and symptoms resolved and bilateral lineoreticular infiltration was reduced. On August 8, 2009, Taiwan had the most devastating typhoon (Typhoon Morakot) in 50 years. The patient reported here had stayed in a typhoon evacuation camp for 1 week before his influenza signs and symptoms developed. Although 4 sporadic cases of pandemic (H1N1) 2009 infections were reported from the same camp, none of the isolated viruses harbored the H275Y mutation in the neuraminidase gene. No evidence of virus transmission was found among healthcare personnel, family members, and camp members who had been in close contact with the patient. Oseltamivir has been recommended by the US Centers for Disease Control and Prevention for the treatment of infection caused by pandemic (H1N1) 2009 virus (5). The first 2 cases of oseltamivir resistance of pandemic H1N1 (2009) virus were reported in August 2009 (6). For these cases, oseltamivir-resistant virus was isolated on days 11 and 23 after the initial isolation of oseltamivir-susceptible viruses, for each patient, respectively. In contrast, in the case reported here, resistance to oseltamivir developed rapidly, after only 4 days of treatment. In severe cases of pandemic (H1N1) 2009 infections, mortality rates are highest for patients who are pregnant

Hepatocyte growth factor (HGF) is a member of the angiogenic growth factor family, which exerts a variety of effects on epithelial, endothelial, and neuronal cells by binding to the c-MET receptor tyrosine kinase. It was reported that HGF attenuates cerebral ischemia-induced increase in permeability of the blood-brain barrier (BBB) and decreases in expression of tight junction proteins in cerebral vessels of rats. Studies on the localization of the c-Met/HGF receptor in the rat brain and the interaction with HGF after brain injuries show that HGF plays an important role as a neurotrophic factor in the brain. To assess the role of HGF in patients with eosinophilic meningitis, a retrospective, cohort study was conducted to measure the dynamic changes of HGF in the cerebrospinal fluid (CSF) and blood of nine patients with eosinophilic meningitis. The mean HGF(CSF) at presentation, 1 week, 2 weeks, and 3 weeks after admission was 539 pg/mL, 540 pg/mL, 376 pg/mL, and 279 pg/mL, respectively. The mean level of HGF(CSF) at presentation (539 +/- 242 pg/mL) and 1 week after admission (540 +/- 213 pg/mL) was significantly higher than in controls (162 +/- 207 pg/mL)(P = 0.02 and P = 0.01, respectively). The CSF/blood ratio of HGF at presentation (0.61) was higher when compared with physiologic situations in uninfected individuals (0.51). The levels of HGF in CSF were not correlated with the amount of CSF cells or proteins. All patients recovered without neurologic sequelae. These results indicate that high concentrations of HGF in the CSF occur in eosinophilic meningitis, and may have a role in protecting against endothelial injury and reducing BBB dysfunction.

The formation of an aortic aneurysm caused by infection with Mycobacterium tuberculosis is rare. In a recent review of the English literature from 1945 to 1999 only 41 cases of tuberculous mycotic aneurysm of the aorta were identified. In this report we present our experience with one such patient and a brief review of the English language literature. An 80-year-old man was admitted to our hospital because of a one-week history of recurrent upper gastrointestinal bleeding. During this period upper gastrointestinal panendoscopy had failed to show active bleeding. Only a 2-cm linear ulcer with white base over the high body of the stomach was detected. He was given blood transfusions and a proton pump inhibitor. Eight years before admission he had had pneumonia of the right middle lobe. Bronchoscopic biopsy had revealed chronic granulomatous inflammation. Sputum mycobacterial culture was negative and he was treated with intravenous penicillin and erythromycin. Four years before admission he had experienced fever abdominal pain and jaundice. An abdominal computerized tomography scan done at that time was negative for an abdominal aneurysm. (excerpt)

Pyogenic liver abscess is an uncommon complication of intra-abdominal or biliary tract infection and is usually a polymicrobial infection associated with high mortality and high rates of relapse. However, over the past 15 years, we have observed a new clinical syndrome in Taiwan: liver abscesses caused by a single microorganism, Klebsiella pneumoniae. We reviewed 182 cases of pyogenic liver abscess during the period September 1990 to June 1996; 160 of these cases were caused by K. pneumoniae alone, and 22 were polymicrobial. When patients with K. pneumoniae liver abscess were compared with those who had polymicrobial liver abscess, we found higher incidences of diabetes or glucose intolerance (75% vs. 4.5%) and metastatic infections (11.9% vs. 0) and lower rates of intra-abdominal abnormalities (0.6% vs. 95.5%), mortality (11.3% vs. 41%), and relapse (4.4% vs. 41%) in the former group. Liver abscess caused by K. pneumoniae is a new clinical syndrome that has emerged as an important infectious complication in diabetic patients in Taiwan.

Background The risk of healthcare workers (HCWs) acquiring tuberculosis (TB) infection is high. We determined the prevalence of latent TB infection (LTBI) in HCWs with a high Bacille Calmette-Guerin (BCG) vaccine coverage in an intermediate TB burden country by using an interferon-gamma release assay [QuantiFERON-TB Gold (QFT-G)] and by using the tuberculin skin test (TST). Risk factors associated with a positive test were determined. Methods This prospective cross-sectional study enrolled HCWs from a medical center in Taiwan. Participants were grouped into workers without exposure (Group 1) and workers who self-reported a history of TB exposure (Group 2). All participants completed a questionnaire to collect demographic information and risk factors for acquiring TB. The QFT-G test and the TST were administered and risk factors for a positive test were analyzed. Results We recruited 193 HCWs [149 (77.2%) female workers] with a mean age of 35.6 years. All were BCG-vaccinated. The prevalence of LTBI was 88.8% (based on the TST) and 14.5% (based on the QFT-G test). There was no difference between HCWs with and without known exposure to TB. Agreement between the tests was poor (i.e., the kappa value was less than 0.05). Multivariable logistic regression showed that only the QFT-G test was associated with age (35 years or greater) (adjusted OR, 2.53; p = 0.03). Conclusion By using the QFT-G test or TST, this study found a similar prevalence of LTBI in HCWs with and without known exposure to TB. This suggests that in intermediate TB burden countries exposure to TB may occur within the hospital and within the community. Compared to the TST, the QFT-G test was correlated better with age, which is a known risk factor for latent TB infection.

Background Angiostrongylus cantonensis is a parasite endemic in the Southeast Asian and Pacific regions. Humans are incidentally infected either by eating uncooked intermediate hosts or by consuming vegetables containing the living third-stage larvae. The 14-3-3β protein is a cerebrospinal fluid (CSF) marker of neuronal damage during the development of Creutzfeldt-Jakob disease. In addition, increased 14-3-3β protein is also found in CSF from patients with a variety of neurological disorders. The goal of this study is to determine the roles of serum/CSF14-3-3β protein in patients with eosinophilic meningitis. Methods In a cohort study among nine Thai laborers with eosinophilic meningitis due to eating raw snails (Pomacea canaliculata), we examined the CSF weekly while patients were still hospitalized and followed up the serum for 6 months. The levels of 14-3-3β protein in CSF were analyzed by western blot and an in-house 14-3-3β enzyme-linked immunosorbent assay (ELISA) measurement was established and tested in an animal model of eosinophilic meningitis. Results The elevated 14-3-3β level was detected in the CSF from eight out of nine (81%) patients After 2 weeks of treatment, all patients showed a declined level or cleared of 14-3-3β protein in the CSF. By developing an in-house ELISA for measurement of 14-3-3β protein, it was found that the serum 14-3-3β level was significantly increased in patients during initial visit. . This finding was consistent to the animal experiment result in which there was severe blood brain barrier damage three weeks after infection and increased 14-3-3β protein expression in the CSF and serum by western blot and in house ELISA. After treatment, the serum 14-3-3β level in meningitis patients was rapidly returned to normal threshold. There was a correlation between initial CSF 14-3-3β level with severity of headache (r = 0.692, p = 0.039), CSF pleocytosis (r = 0.807, p = 0.009) and eosinophilia (r = 0.798, p = 0.01) in the CSF of patients with eosinophilic meningitis (Spearman’s correlation test). Conclusions The serum 14-3-3β concentrations may constitute a useful marker for blood brain barrier damage severity and follow up in patients with eosinophilic meningitis caused by A. cantonensis.

Head-up tilt testing has proved to be useful in provocation of neurocardiogenic syncope. The purpose of this study was to examine whether simply assuming an upright posture by standing can be an alternative to the head-up tilt testing for diagnosis of neurocardiogenic syncope. Eighty-four patients with recurrent unexplained syncope and 22 normal volunteers were recruited into the study. Forty-seven patients with syncope and all normal volunteers received the standing test. Thirty-seven of the patients with syncope received head-up tilt testing (90 degrees). All subjects lay down for 5 minutes and then assumed an upright posture until syncope or presyncope occurred or until a maximum of 10 minutes was reached in each stage of the test. The tests included four stages: baseline and infusion of 1, 2, or 3 micrograms/min isoproterenol in each of the successive stages. Five subjects could not tolerate the procedure, and further testing was terminated. Overall, the standing test was positive in 83% of the patients with syncope, and its specificity was 74%. The head-up tilt testing was positive in 75% of the patients with syncope. The duration of assuming an upright posture before occurrence of syncope or presyncope was significantly longer in the syncope-tilting group in the third stage (p < 0.01) and the fourth stage (p < 0.05) compared with the syncope-standing group. However, the curves of the time course for cumulative positive rates were not significantly different (p = 0.0739) in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Tuberculosis (TB) is the leading cause of death in HIV/AIDS. The incidence of active TB is 30 times higher in HIV-infected persons. Treatment of latent TB infection (LTBI) is pivotal to the control of TB. We aim to determine the positive predictive value of an interferon-gamma release assay, QuantiFERON-TB GOLD test (QFT), for incident active TB in HIV-infected persons.

HIV-infected individuals are at higher risk for acquiring HDV. We sought to study the prevalence, genotypes, and associated risk factors causing HDV infection in HIV-infected individuals from an area with high prevalence of hepatitis B virus infection.

Angiostrongylus cantonensis is a parasite endemic in the Southeast Asian and Pacific regions. Humans are incidentally infected either by eating uncooked intermediate hosts or by consuming vegetables containing the living third-stage larvae. Reports on brain magnetic resonance imaging (MRI) findings and how they correlate with clinical features are limited in the literature. In this retrospective study, we investigated the brain MR features of eosinophilic meningitis caused by human infection with A. cantonensis. A detailed clinical study of 26 of these patients was conducted. The brain MRI findings were nonspecific, ranging from normal (n=1), leptomeningeal enhancement (n=21), hyperintense signal lesions (n=11) on T2-weighted MRI and nodular enhancing lesions in gadolinium-enhanced T1W1 (n=1). There was an association between the presence of brain MRI high signal intensities with peripheral eosinophilia (p=0.02), cerebrospinal fluid (CSF), eosinophil count ≥10%, and the presence of CSF antibodies to A. cantonensis (p=0.01). The patients with leptomeningeal enhancement in brain MRI tended to be younger and predominantly men (p=0.03). The time from onset of symptom to spinal tapping or brain MRI studies did not have an effect on the presence of brain MRI abnormalities. The brain MRI findings did not add any additional importance to the clinical evaluation of patients with eosinophilic meningitis in this series. Further studies are required to clarify the role of brain MRI in eosinophilic meningitis.