Yu-Tzu Tseng

Causes, clinical symptoms, and outcomes of infectious diseases associated with hemophagocytic lymphohistiocytosis in Taiwanese adults

BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is an uncommon but a potentially life-threatening condition. Few systematic reviews have been published on the clinical manifestations, causes, and indicators for prognosis of HLH caused by infections. METHODS We retrospectively reviewed the medical records of patients diagnosed with HLH documented by bone marrow study at a teaching hospital between 2000 and 2007. HLH was defined according to the HLH-2004 diagnostic guidelines, which include fever; splenomegaly; cytopenia; hypertriglyceridemia; hypofibrinogenemia; and hemophagocytosis evident on pathological examination of bone marrow, spleen, or lymph node tissue; low or absent natural killer cell activity; hyperferritinemia; and high serum levels of soluble CD25. The demographic characteristics, clinical presentations, laboratory results, and final outcomes were recorded. The cause of HLH was diagnosed by microbiological, pathological, serological, and molecular biological methods. RESULTS Among the studied patients, 66 had HLH because of noninfectious causes and 30 because of infections. Compared with patients with HLH related to noninfectious causes, those with HLH related to infections had lower mortality (70% vs. 47%, p=0.03). The most common causative pathogens causing HLH were virus (41%), mycobacteria (23%), bacteria (23%), and fungi (13%), in that order of frequency. Clinical presentations of HLH were variable and included fever (90%), tachypnea (83%), tachycardia (80%), hepatosplenomegaly (40%), lymphadenopathy (27%), and altered consciousness (23%). Laboratory findings revealed thrombocytopenia in 93%, hyperferritinemia in 90%, elevated serum lactate dehydrogenase levels in 80%, anemia in 67%, and leukopenia in 60% of the patients. Fourteen patients (47%) died. In multivariate analysis, age more than 50 years (p=0.05; odds ratio [OR], 3.46; 95% confidence interval [CI], 1.00-15.73), fever not subsiding within 3 days of diagnosing HLH (p=0.003; OR, 2.38; 95% CI, 1.21-11.25), and occurrence of disseminated intravascular coagulation as a complication (p=0.009; OR, 3.22; 95% CI, 1.68-10.01) were found to be statistically significant indicators of mortality in patients with HLH. CONCLUSIONS The infectious diseases associated with HLH were diverse and resulted in a high mortality rate. Cases in which the patients were aged more than 50 years, developed DIC, and had persistent fever even after 3 days of being diagnosed with HLH showed poor prognosis.

Comparative effectiveness of two doses versus three doses of hepatitis A vaccine in human immunodeficiency virus–infected and -uninfected men who have sex with men†‡§

The purpose of this prospective cohort study was to compare the serologic response between human immunodeficiency virus (HIV)‐infected men who have sex with men (MSM) receiving two and three doses of hepatitis A virus (HAV) vaccine and HIV‐uninfected MSM receiving two doses of HAV vaccine. Between June 2009 and December 2010, 582 MSM aged 18 to 40 years who were seronegative for HAV were enrolled in the study. HIV‐infected MSM received either two doses of HAV vaccine (1,440 enzyme‐linked immunosorbent assay units) (n = 140) with the second dose given at week 24 or three doses (n = 225) with the second and third dose given at weeks 4 and 24, respectively, while HIV‐uninfected MSM (n = 217) received two doses. The primary endpoint was seroconversion at week 48. The geometric mean concentration (GMC) of anti‐HAV antibody was determined at weeks 48 and 72. At week 48, the seroconversion rate was 75.7%, 77.8%, and 88.5% in intention‐to‐treat analysis for two‐dose HIV‐infected, three‐dose HIV‐infected, and two‐dose HIV‐uninfected MSM, respectively. The GMC of anti‐HAV antibody at week 48 for three‐dose HIV‐infected MSM (2.29 ± 0.73 log10 mIU/mL) was significantly higher than that for two‐dose HIV‐infected MSM (1.94 ± 0.66; P < 0.01), but was lower than HIV‐uninfected MSM (2.49 ± 0.42; P < 0.01). Multivariate analysis revealed higher CD4 counts (adjusted odds ratio [AOR] for per 50 cells/μL increase, 1.13; 95% confidence interval [CI], 1.05‐1.21) and undetectable plasma HIV RNA load (AOR, 1.90; 95% CI, 1.10‐3.28) before HAV vaccination were predictive of seroconversion in HIV‐infected patients. Conclusion: Serologic response rate to three and two doses of HAV vaccine was similar in HIV‐infected MSM, which was lower than that in HIV‐uninfected MSM receiving two doses. HAV vaccination in HIV‐infected patients with a higher CD4 count and suppression of HIV replication increased the seroconversion rate. (HEPATOLOGY 2013)

Trends of transmitted drug resistance of HIV-1 and its impact on treatment response to first-line antiretroviral therapy in Taiwan

OBJECTIVES To determine the impact of transmitted drug resistance (TDR) of HIV-1 on treatment outcome in areas where routine testing for drug resistance mutations may not be available before combination antiretroviral therapy (cART) is initiated. METHODS Genotypic resistance assays were performed on HIV isolates from archived blood samples obtained from 1349 antiretroviral-naive HIV-1-infected patients in Taiwan from 2000 to 2010. Resistance mutations were interpreted with the use of the HIVdb program of the Stanford University HIV Drug Resistance Database. The genotypic sensitivity score (GSS) of the regimens prescribed was calculated. A matched case-control study was conducted to assess the impact of TDR on treatment outcomes. RESULTS The overall prevalence of TDR to any antiretroviral agent was 8.0%, declining from 12.3% in 2003-06 to 5.1% in 2007-10. In the matched case-control study, 31 patients with high- or intermediate-level resistance, 16 with low-level resistance and 89 controls were enrolled. Compared with regimens with GSS >2.5, initiation of regimens with GSS ≤2.5 was associated with a higher treatment failure rate (39.3% versus 15.7%, P = 0.02) and shorter time to treatment failure (log-rank P < 0.001). In patients receiving regimens with GSS ≤2.5, protease inhibitor-based regimens were less likely to result in treatment failure, compared with non-nucleoside reverse-transcriptase inhibitor-based regimens (hazard ratio 0.26, 95% CI 0.06-1.12, P = 0.07). CONCLUSIONS In Taiwan the prevalence of TDR of HIV-1 strains declined and stabilized between 2007 and 2010. Receipt of antiretroviral regimens with GSS ≤2.5 was associated with poorer treatment responses than regimens with GSS >2.5.

Oropharyngeal Colonization of HIV-Infected Outpatients in Taiwan by Yeast Pathogens

ABSTRACT Among 234 isolates comprising 26 different Candida species colonizing the oropharynx of 181 (54.3% of 399 surveyed) HIV-infected outpatients, 27 (11.7%) were fluconazole resistant. Antibacterial treatment was associated with increased rates of yeast colonization, while antiretroviral therapy and pneumococcal vaccination protected patients from yeast colonization.

Empirical use of fluoroquinolones improves the survival of critically ill patients with tuberculosis mimicking severe pneumonia

IntroductionEmpirical use of fluoroquinolones may delay the initiation of appropriate therapy for tuberculosis (TB). This study aimed to evaluate the impact of empirical fluoroquinolone use on the survival of patients with pulmonary TB that mimicked severe community-acquired pneumonia (CAP) requiring intensive care.MethodsPatients aged >18 years with culture-confirmed pulmonary TB who presented as severe CAP and were admitted to the ICU were divided into fluoroquinolone (FQ) and nonfluoroquinolone (non-FQ) groups based on the type of empirical antibiotics used. Those patients with previous anti-TB treatment or those who died within 3 days of hospitalization were excluded. The primary end point was 100-day survival.ResultsOf the 77 patients identified, 43 (56%) were in the FQ group and 34 (44%) were in the non-FQ group. The two groups had no statistically significant difference in co-morbidities (95% vs. 97%, P > 0.99) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores (21.2 ± 7.1 vs. 22.5 ± 7.5, P = 0.46) on ICU admission. Overall, 91% and 82% of patients in the FQ and non-FQ groups, respectively, had sputum examinations for TB within 1 week of admission (P = 0.46), and results were positive in 7% and 15% (P = 0.47), respectively. For both groups, 29% received appropriate anti-TB therapy within 2 weeks after ICU admission. The 100-day mortality rate was 40% and 68% for the FQ and non-FQ groups, respectively (P = 0.02). By Cox regression analysis, APACHE score <20, no bacteremia during the ICU stay, and empirical fluoroquinolone use were independently associated with survival.ConclusionEmpirical use of fluoroquinolones may improve the survival of ICU patients admitted for pulmonary TB mimicking severe CAP.

Comparison of serologic responses to vaccination with one dose or two doses of 7-valent pneumococcal conjugate vaccine in HIV-infected adult patients.

BACKGROUND Vaccination with 7-valent pneumococcal conjugate vaccine (PCV) has been shown to decrease the incidence of recurrent invasive pneumococcal disease among HIV-infected adults in Africa. Longitudinal follow-up studies of serologic responses to different doses of 7-valent PCV are rarely performed in HIV-infected adult patients receiving combination antiretroviral therapy (cART). METHODS From October 2008 to June 2010, 115 CD4-matched pairs of HIV-infected patients aged ≥ 20 years who had no prior pneumococcal vaccination received one or two doses of 7-valent PCV. Anticapsular antibodies against 4 serotypes (6B, 14, 19F, and 23F) were examined at the 12th, 24th, 36th, and 48th week following vaccination. Significant antibody responses were defined as ≥ 2-fold increase in the IgG level plus a post-vaccination antibody level ≥ 1000 ng/ml. RESULTS The most common reported adverse effects were injection site soreness (19.3%) and pain (4.8%). Significant antibody response rate was highest for serotype 14, followed by 23F, 19F, and 6B in all of the four time points examined. At week 48, patients who received two doses of 7-valent PCV had a significantly higher response rate to serotype 6B (P=0.03) and 23F (P=0.01) than those who received one dose; moreover, the former group also had a higher response rate to at least one (P=0.03) and two serotypes (P=0.02) in intention-to-treat analysis than the latter group. CONCLUSIONS HIV-infected adult patients on cART who received two doses of 7-valent PCV achieved better serological responses to at least one serotype than those who received one dose during the 48 weeks of follow-up.

Etiology of pulmonary complications of human immunodeficiency virus-1-infected patients in Taiwan in the era of combination antiretroviral therapy: A prospective observational study

OBJECTIVES We aimed to investigate the etiology of pulmonary complications of human immunodeficiency virus-(HIV)-1-infected patients in Taiwan in the era of combination antiretroviral therapy (cART). METHODS From July 2009 to March 2012, a prospective observational study was conducted to identify the etiology of pulmonary complications in HIV-1-infected patients who sought HIV care at a university hospital in Taiwan. A stepwise diagnostic approach was adopted, which included radiography, serology, microbiology, bronchoscopy or video-assisted thoracoscopic surgery, and polymerase chain reaction assays for cytomegalovirus and Pneumocystis jirovecii. RESULTS During the study period, a total of 203 episodes of pulmonary complications that occurred in 190 patients with a mean CD4 count of 123 × 10(6) cells/L were analyzed. Thirty-eight episodes (18.7%) occurred in patients with a CD4 count >200 × 10(6) cells/L, 71 (35.0%) between 50 and 200 × 10(6) cells/L, and 94 (46.3%) <50 × 10(6) cells/L. Pneumocystis pneumonia accounted for more than half of the complications in patients with a CD4 count <200 × 10(6) cells/L. In patients with a CD4 count >200 × 10(6) cells/L, the etiology of pulmonary complications was diverse, with bacterial infections (47.4%) being the most common, followed by tuberculosis (15.8%) and lung edema (13.2%). Pneumocystosis and cytomegalovirus pneumonitis were seen mostly or exclusively in patients with a CD4 count <200 × 10(6) cells/L and were the leading causes of interstitial pneumonitis. On the other hand, empyema, legionellosis, and lung edema were more commonly seen in patients with a CD4 count >200 × 10(6) cells/L. CONCLUSIONS The etiology of pulmonary complications in HIV-1-infected patients was diverse and varied with the categories of CD4 counts. Pneumocystosis remained the leading cause of pulmonary complications in patients with lower CD4 counts in Taiwan in the cART era.

Incidence and risk factors of skin rashes and hepatotoxicity in HIV-infected patients receiving nevirapine-containing combination antiretroviral therapy in Taiwan

OBJECTIVES To retrospectively investigate the incidence of and factors associated with skin rashes and hepatotoxicity in HIV-infected patients who initiated combination antiretroviral therapy (cART) containing nevirapine plus two nucleos(t)ide reverse-transcriptase inhibitors. METHODS The medical records of HIV-infected adult patients who started nevirapine-containing cART and continued follow-up for ≥4 weeks were reviewed at two hospitals in Taiwan between 2000 and 2012. Clinical data obtained at baseline and during follow-up were collected and analyzed. RESULTS Of the 338 patients included in the analysis, 13.0% tested positive for hepatitis B virus surface antigen and 7.9% tested positive for anti-hepatitis C virus antibody. The incidence of rashes was 21.6% and of hepatotoxicity was 25.5%. On multiple logistic regression analysis, a two-fold or greater increase from the upper limit of normal levels of aminotransferases at baseline was associated with rashes (adjusted odds ratio (aOR) 3.74, 95% confidence interval (CI) 1.56-8.96); higher CD4 counts (aOR for per 50 cells/μl increase 1.51, 95% CI 1.12-2.03) and the concurrent use of trimethoprim/sulfamethoxazole (aOR 14.01, 95% CI 1.98-98.95) were associated with hepatotoxicity. CONCLUSIONS Abnormal liver function at baseline was significantly associated with skin rashes, while a higher CD4 count and the concurrent use of trimethoprim/sulfamethoxazole were associated with hepatotoxicity after the initiation of nevirapine-containing cART in HIV-infected Taiwanese patients.

Mycobacterium avium complex infection-related immune reconstitution inflammatory syndrome of the central nervous system in an HIV-infected patient: Case report and review

Disseminated Mycobacterium avium complex (MAC) infection involves the central nervous system (CNS) less frequently than tuberculosis, and MAC-related immune reconstitution inflammatory syndrome (IRIS) of the CNS in AIDS patients is even more rarely described. We report a case of MAC-related IRIS of the CNS in an HIV-infected patient who presented with meningoencephalitis and myelitis 2 months after discontinuation of antiMAC therapy, when he had achieved prolonged suppression of HIV replication and restoration of CD4 counts to >100 cells/μL for 1 year. Cases of MAC-related IRIS of the CNS reported in the literature are reviewed.

Demand and Predictors for Post-Discharge Medical Counseling in Home Care Patients: A Prospective Cohort Study

Rationale Post-discharge care is challenging due to the high rate of adverse events after discharge. However, details regarding post-discharge care requirements remain unclear. Post-discharge medical counseling (PDMC) by telephone service was set-up to investigate its demand and predictors. Methods This prospective study was conducted from April 2011 to March 2012 in a tertiary referral center in northern Taiwan. Patients discharged for home care were recruited and educated via telephone hotline counseling when needed. The patient’s characteristics and call-in details were recorded, and predictors of PDMC use and worsening by red-flag sign were analyzed. Results During the study period, 224 patients were enrolled. The PDMC was used 121 times by 65 patients in an average of 8.6 days after discharge. The red-flag sign was noted in 17 PDMC from 16 patients. Of the PDMC used, 50% (n = 60) were for symptom change and the rest were for post-discharge care problems and issues regarding other administrative services. Predictors of PDMC were underlying malignancy and lower Barthel index (BI). On the other hand, lower BI, higher adjusted Charlson co-morbidity index (CCI), and longer length of hospital stay were associated with PDMC and red-flag sign. Conclusions Demand for PDMC may be as high as 29% in home care patients within 30 days after discharge. PDMC is needed more by patients with malignancy and lower BI. More focus should also be given to those with lower BI, higher CCI, and longer length of hospital stay, as they more frequently have red flag signs.