Kuan-Sheng Wu

Clinical manifestations of eosinophilic meningitis caused by Angiostrongylus cantonensis: 18 years’ experience in a medical center in southern Taiwan

BACKGROUND With the improvement of public health, eosinophilic meningitis associated with Angiostrongylus cantonensis infection is now seldom reported in Taiwan. Eosinophilic meningitis typically occurred sporadically in children. This study aims to analyze the clinical manifestations and change in the contemporary epidemiology of eosinophilic meningitis in Taiwan. METHODS This is a retrospective study of patients diagnosed with eosinophilic meningitis at Kaohsiung Veterans General Hospital, from December 1991 to September 2009. The demographic characteristics, clinical presentations, laboratory data, radiographic imaging, and treatment and clinical outcome were analyzed. A PubMed search with the keywords of eosinophilic meningitis, A cantonensis, and Taiwan was performed to retrieve cases of eosinophilic meningitis caused by A cantonensis since 1960. RESULTS Thirty-seven patients were diagnosed to have eosinophilic meningitis during a period of 18 years. The median age was 32 years (range, 2-80 years). Ninety five percent (35/37) of the patients were adults. The median incubation period was 10.5 days (range, 3-80 days). Most of the patients presented with headache (29, 78%), fever (25, 68%), and 11(30%) had hyperesthesia. Patients with hyperesthesia had longer incubation period (55 vs. 7 days, p=0.004), lower serum immunoglobulin E levels (127.5 vs. 1295 IU/mL, p<0.001), and longer duration between symptom onset and spinal taps (14 vs. 5 days, p=0.011). Three patients presented initially with lymphocytic meningitis, and eosinophilia only appeared on a second lumbar puncture. Magnetic resonance imaging of the brain disclosed leptomeningeal enhancement (17/26, 65%) and increased signal intensity (10/26, 38%) on T2-weighted and fluid-attenuated inversion recovery images. There were eight relapses and two patients died. No sequela was noted except in one 2-year-old toddler, who had weakness of both lower limbs. CONCLUSIONS The epidemiology of eosinophilic meningitis has changed during the past two decades in Taiwan and occurs mainly in adults in the setting of outbreaks. Hyperesthesia; repeated lumbar puncture in cases with lymphocytic meningitis of uncertain cause; and a detailed history, including food consumption, are important to establish an accurate diagnosis.

Non-nosocomial healthcare-associated infective endocarditis in Taiwan: an underrecognized disease with poor outcome

BackgroundNon-nosocomial healthcare-associated infective endocarditis (NNHCA-IE) is a new category of IE of increasing importance. This study described the clinical and microbiological characteristics and outcome of NNHCA-IE in Taiwan.MethodsA retrospective study was conducted of all patients with IE admitted to the Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan over a five-year period from July 2004 to July 2009. The clinical and microbiological features of NNHCA-IE were compared to those of community-acquired and nosocomial IE. Predictors for in-hospital death were determined.ResultsTwo-hundred episodes of confirmed IE occurred during the study period. These included 148 (74%) community-acquired, 30 (15%) non-nosocomial healthcare-associated, and 22 (11%) nosocomial healthcare-associated IE. Staphylococcus aureus was the most frequent pathogen. Patients with NNHCA-IE compared to community-acquired IE, were older (median age, 67 vs. 44, years, p < 0.001), had more MRSA (43.3% vs. 9.5%, p < 0.001), more comorbidity conditions (median Charlson comorbidity index [interquartile range], 4[2-6] vs. 0[0-1], p < 0.001), a higher in-hospital mortality (50.0% vs. 17.6%, p < 0.001) and were less frequently recognized by clinicians on admission (16.7% vs. 47.7%, p = 0.002). The overall in-hospital mortality rate for all patients with IE was 25%. Shock was the strongest risk factor for in-hospital death (odds ratio 7.8, 95% confidence interval 2.4-25.2, p < 0.001).ConclusionsNNHCA-IE is underrecognized and carries a high mortality rate. Early recognition is crucial to provide optimal management and improve outcome.

Higher rate of hepatitis events in patients with human immunodeficiency virus, hepatitis B, and hepatitis D genotype II infection: A cohort study in a medical center in southern Taiwan

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.

Prevalence and associated factors for HIV-1 transmitted drug resistance in voluntary clients for counseling and testing in Southern Taiwan

BACKGROUND According to the World Health Organization, HIV-transmitted drug resistance (TDR) is increasing. We analyzed voluntary counseling test data from a hospital in Southern Taiwan to investigate the TDR pattern in Southern Taiwan, the potential relationship between sexual behavior and HIV transmission, and HIV drug-resistant strain transmission. METHODS Genotypic resistance assays were performed on treatment-naïve HIV patients recruited from voluntary counseling testing (VCT) in Southern Taiwan from 2007 to 2011. Drug resistance-associated mutations were interpreted with Stanford University HIV Drug Resistance Database HIVdb program. Socio-demographics and sexual activity were recorded from the VCT questionnaire. Logistic regression analysis was used to analyze the risk factors for TDR, and a phylogenetic tree was constructed to elucidate the pattern of HIV drug-resistant strains. RESULTS Among the 161 treatment-naïve HIV-infected patients, most were men who reported having sex with men. The overall TDR rate was 10.6%. Patients with a history of sexually transmitted diseases had a 7.8-fold higher risk of becoming infected with genotypic resistant strains. CONCLUSION In Southern Taiwan, the HIV TDR rate was 10.6% among those receiving VCT. Our findings suggest that sexual behavior may play an important role in HIV drug-resistant strain transmission.

A nationwide covert observation study using a novel method for hand hygiene compliance in health care

HighlightsA novel covert observation method and reporting system was developed.The novel covert observation method is feasible for large‐scale observation.Overall hand hygiene compliance by covert observation is low in Taiwan.Hand hygiene compliance increases significantly with an increase in the number of indications within 1 hand hygiene opportunity. Background: Evaluation and feedback is a core hand hygiene (HH) improvement strategy. The covert observation method avoids observation bias inherent to the overt method. The aim of the study was to observe HH compliance by a novel covert method in a real‐world setting. Methods: We conducted a 2‐year, nationwide, prospective, observational study in teaching hospitals across Taiwan. Medical students and students who may have contact with patients in their careers were recruited as participants. A novel, shorthand notation method for covert observation was used. Observation results were reported through a study website. Results: There were a total of 25,379 HH opportunities covertly observed by 93 observers. Overall HH compliance was 32.0%. Health care workers had the highest HH compliance for indication 4 (42.6%), and the lowest for indication 5 (21.7%). Overall handrubbing percentage was high, reaching 83.6%. The HH compliance increased significantly with an increase in the number of indications within 1 HH opportunity (P < .001). Conclusions: The overall HH compliance by the covert observation method was low. An innovative shorthand notation method facilitated covert observation, and website reporting was demonstrated to be feasible for large‐scale observation.

High rate of HIV-1 drug resistance in treatment failure patients in Taiwan, 2009–2014

Background Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy. Objectives This study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy. Materials and methods Data from the Veterans General Hospital Surveillance and Monitor Network for the period 2009–2014 were analyzed. Plasma samples from patients diagnosed with virologic failure and an HIV-1 RNA viral load >1000 copies/mL were analyzed by the ViroSeq™ HIV-1 genotyping system for drug susceptibility. Hazard ratios (HRs) for drug resistance were calculated using a Cox proportional hazard model. Results From 2009 to 2014, 359 patients were tested for resistance. The median CD4 count and viral load (log) were 214 cells/μL (interquartile range [IQR]: 71–367) and 4.5 (IQR: 3.9–5.0), respectively. Subtype B HIV-1 strains were found in 90% of individuals. The resistance rate to any of the three classes of antiretroviral drugs (NRTI, NNRTI, and PI) was 75.5%. The percentage of NRTI, NNRTI, and PI resistance was 58.6%, 61.4%, and 11.4%, respectively. The risk factors for any class of drug resistance included age ≤35 years (adjusted HR: 2.30, CI: 1.48–3.56; p<0.0001), initial NNRTI-based antiretroviral regimens (adjusted HR: 1.70, CI: 1.10–2.63; p=0.018), and current NNRTI-based antiretroviral regimens when treatment failure occurs (odds ratio: 4.04, CI: 2.47–6.59; p<0.001). There was no association between HIV-1 subtype, viral load, and resistance. Conclusion This study demonstrated a high level of resistance to NRTI and NNRTI in patients with virologic failure to first-line antiretroviral therapy despite routine viral load monitoring. Educating younger men who have sex with men to maintain good adherence is crucial, as PI use is associated with lower possibility of drug resistance.

Elevated cerebrospinal fluid nitrite level in human immunodeficiency virus-infected patients with neurosyphilis

BACKGROUND/PURPOSE Human 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. METHODS This 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. RESULTS The 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, r(2) = 0.324; p < 0.001). There was no significant difference between different groups in serum nitrite levels. CONCLUSION Marked elevation of CSF nitrite level was observed in HIV-infected patients with neurosyphilis.

Identifying heterogeneity in the Hawthorne effect on hand hygiene observation: a cohort study of overtly and covertly observed results

BackgroundObservation and feedback are core strategies of hand hygiene (HH) improvement. Direct overt observation is currently the gold standard method. Observation bias, also known as the Hawthorne effect, is a major disadvantage of this method. Our aim was to examine the variation of the Hawthorne effect on HH observation in different healthcare groups and settings.MethodsA prospective cohort study was performed in a tertiary teaching hospital during a 15-month period. Up to 38 overt observers (82% nurses) and 93 covert observers (81% medical students) participated in HH observation. The HH events observed overtly were matched for occupation, department, observation time, and location with those observed covertly. The data of matched pairs were then analysed to detect possible Hawthorne effects on different variables.ResultsA total of 31,522 HH opportunities were observed (4581 overtly, 26,941 covertly). There were 3047 matched pairs after 1:1 matching of overt and covert observations. The overall HH compliance was higher with overt observation than with covert observation (78% vs. 55%, p < 0.001). The Hawthorne effect was nearly three times larger in nurses (30 percentage points) than in physicians (11 percentage points) and was significantly greater in outpatient clinics (41 percentage points) than in intensive care units (11 percentage points). The magnitude of the Hawthorne effect varied among healthcare worker occupations and observation locations (p values both < 0.001) but not among departments, observation times, or HH indications.ConclusionsHeterogeneity in the Hawthorne effect may influence the interpretation of overt observations and prevent the correct identification of target populations with poor HH compliance. Therefore, directly observed HH compliance may not be an adequate performance indicator for infection control.

HIV-1 integrase strand-transfer inhibitor resistance in southern Taiwan

The use of antiretroviral therapy has reduced rates of mortality and morbidity in patients with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS). However, transmission of drug-resistant strains poses a challenge to control the spread of HIV-1. Primary resistance to integrase strand-transfer inhibitors (INSTIs) is rare despite their increased use. The prevalence of transmitted drug resistance (TDR) to INSTIs was 0.9% in northern Taiwan. This study was to analyse the prevalence and risk factors of TDR to INSTIs in southern Taiwan. In this study, we enrolled antiretroviral treatment-naïve HIV-1-infected subjects who underwent voluntary counselling and testing from 2013 to 2016 in southern Taiwan. Genotypic drug resistance, coreceptor tropism (CRT) and INSTI resistance were determined. Logistic regression was used to analyse the risk factors for INSTI polymorphic substitution. Sequences were obtained from 184 consecutive individuals, of whom 96.7% were men who have sex with men and 3.3% were heterosexual. Of the patients, 10% (19/183) had hepatitis B and 33.3% (61/183) had syphilis infection. Subtype B HIV-1 strains were found in 96.1% of the patients. Fifteen patients (8.4%, 15/178) harboured nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors or protease inhibitors resistance. CCR-5 coreceptors were used by 71.4% (130/184) of the patients. None of the patients had INSTI resistance-associated mutations, however 16 patients had INSTI polymorphic substitutions, and they were associated with a higher HIV viral load (p = 0.03, OR 2.4, CI 1.1–5.3) and syphilis infection (p = 0.03, OR 3.7, CI 1.1–12.0). In conclusion, no signature INSTI resistance-associated mutations were detected in our cohort. Continued monitoring of TDR to INSTI is needed due to the increased use of INSTIs.

Ocular Manifestations of Human Immunodeficiency Virus Infection at a Tertiary Referral Center in Taiwan

ABSTRACT Purpose: To investigate the prevalence and characteristics of ocular manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in patients treated at a tertiary referral center in Taiwan during a time of highly active antiretroviral therapy (HAART) Materials and Methods: A retrospective cohort study in Taiwan was performed between January 2006 and July 2016. Ocular examination and systemic information were recorded from the HIV-infected patients. Results: 1242 patients with HIV/AIDS were identified. Ninety patients had ophthalmic records, and HIV-related ocular manifestations were reported in 57 patients. The most prevalent ocular manifestations were cytomegalovirus (CMV) retinitis, ocular syphilis, and HIV microvasculopathy. Mean CD4 count was significantly lower in patients with HIV-related ocular manifestations compared to those without. Conclusion: We found that lower CD4 count, especially <200 cells/μL, was a significant factor for detecting HIV-related ocular manifestations. Comprehensive ophthalmic screening in high-risk group is helpful for early diagnosis and prompt treatment of sight-threatening ocular complications.