Extracellular vesicles as potential diagnostic markers for kidney allograft rejection.

Kidney transplantation is a highly effective treatment for end-stage kidney disease. However, allograft rejection remains a significant clinical challenge in kidney transplant patients. Although kidney allograft biopsy is the gold-standard diagnostic method, it is an invasive procedure. Since the current monitoring methods, including screening of serum creatinine and urinary protein, are not of sufficient sensitivity, there is a need for effective post-transplant monitoring to detect allograft rejection at an early stage. Extracellular vesicles are vesicles with a lipid bilayer that originate from different cell types in pathological and physiological conditions. The content of extracellular vesicles reflects the status of cells at the time of their production. This review comprehensively summarizes clinical, in vivo, and in vitro reports that highlight the potential of extracellular vesicles as diagnostic biomarkers for kidney allograft rejection. Clarification would facilitate differentiation between rejection and non-rejection and identification of the mechanisms involved in the allograft rejection. Despite increasing evidence, further research is necessary to establish the clinical utility of extracellular vesicles in the diagnosis and monitoring of allograft rejection in kidney transplant recipients. Using extracellular vesicles as non-invasive biomarkers for diagnosis of kidney allograft rejection could have tremendous benefits in improving patient outcomes and reduce the need for invasive procedures.

Comparative immunohistochemical analysis of inflammatory cytokines in distinct subtypes of Sweet syndrome.

Background: A dysregulated immune response has been implicated in Sweet syndrome (SS) pathogenesis; however, cytokine profiles across different conditions associated with SS - including adult-onset immunodeficiency (AOID) due to anti-interferon (IFN)-γ autoantibodies - remain unknown. Objective: To investigate alterations in inflammatory cytokines in skin lesions of distinct subtypes of SS. Methods: Skin biopsies were collected from 42 AOID- and 52 non-AOID-associated SS patients and 18 healthy controls. The comparative immunohistochemical study was conducted using monoclonal antibodies against interleukin (IL)-1ß, IL-6, IL-17, IFN-γ, and tumor necrosis factor-α on paraffin-embedded sections. The quantitative percentage positivity and intensity were calculated using computer-based image analysis. Results: The results showed stronger and more diffuse dermal immunoreactivity for IFN-γ and IL-17 in the AOID-associated (p < 0.001 and p < 0.001, respectively) and non-AOID-associated SS (p < 0.001 and p < 0.001, respectively) groups. However, no significant differences in the levels of these two cytokines were observed between the AOID- and non-AOID-associated SS groups. Increased expression of IFN-γ together with IL-17 was also noted in almost all subtypes among non-AOID-associated SS. Conclusions: These results demonstrate that IFN-γ and IL-17 are implicated in immunopathology of all SS subtypes, including AOID-associated SS, despite the presence of anti-IFN-γ autoantibodies.

Changes in atherosclerotic cardiovascular disease risk over time among people living with HIV.

OBJECTIVE: To describe changes in atherosclerotic cardiovascular disease (ASCVD) risk over time among people living with HIV (PLHIV). METHODS: We used data from the TREAT Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD). Five-year ASCVD risk was calculated using the D:A:D equation. Individuals were eligible for inclusion if they were aged ≥18 years, had started ART, had no previous history of ASCVD and had complete ASCVD risk factor data available within the first 5 years of ART initiation. RESULTS: A total of 3368 adults contributed data, 3221 were from TAHOD and 147 were from AHOD. The median age at ART initiation was 36 [IQR 31-43] years for TAHOD participants, and 42 [IQR 35-50] years for AHOD participants. Most TAHOD (70.4%) and AHOD (91.8%) participants were male. Overall, ASCVD risk increased from 0.84% (95% CI 0.81%-0.87%) at ART initiation to 1.34% (95% CI 1.29%-1.39%) after 5 years on ART. After adjusting for traditional and HIV-associated ASCVD risk factors, ASCVD risk increased at a similar rate among sub-populations defined by HIV exposure (heterosexuals, men who have sex with men, people who inject drugs), race/ethnicity (Caucasian and Asian) and nadir CD4 at ART initiation (<200 and ≥200 cells/mm3). CONCLUSIONS: These findings emphasize the growing burden of ASCVD risk among PLHIV and the need to develop interventions that are effective across a broad range of HIV sub-populations.

Reactive Neutrophilic Dermatoses in Adult-Onset Immunodeficiency due to Interferon-Gamma Autoantibody and Their Associated Factors.

BACKGROUND: Adult-onset immunodeficiency (AOID) due to interferon-gamma autoantibody is a rare, acquired immunodeficiency disease. Reactive neutrophilic dermatoses (RND), predominantly Sweet syndrome (SS), and generalized pustular eruption have been reported repeatedly. OBJECTIVES: The aims of this study were to describe the cutaneous manifestations in AOID patients and determine the incidence of RND and associated factors using a larger population size than have been previously reported. METHODS: A retrospective chart review of all confirmed AOID cases in Chiang Mai University Hospital from January 2006 to June 2020 was conducted. The demographics and characteristics of RND including type, onset, and laboratory information in every episode of cutaneous manifestations were collected. Generalized estimating equations of binary logistic regression were used to determine the indicators of RND. RESULTS: A total of 146 patients with confirmed AOID were identified. Of these, 57 cases (39%) developed at least one episode of RND. Thirteen cases (23%) of the patients experienced RND twice during the follow-up period. All recurrence of RND displayed the same cutaneous phenotype, with the exception of 2 cases who had both SS and generalized pustular eruption. Finally, 49 episodes of SS and 22 episodes of generalized pustular eruption were included in the analysis. All patients with RND had concomitant active opportunistic infections, of which most were non-tuberculous mycobacterium (NTM) infection. NTM infection (prevalence odds ratio [POR] 2.87), lymphadenopathy (POR 3.30) as well as lower serum alkaline phosphatase (ALP) level (POR 0.71 for every 100-unit increment in ALP) were found to be significantly associated with RND occurrence. CONCLUSIONS: 39% of our AOID patients experienced RND once during the course of the disease. Notable factors associated with RND occurrence were concomitant NTM infection, lymphadenopathy, and lower level of ALP.

The Prevalence and Risk Factors for Peripheral Arterial Disease in Adults Living With Human Immunodeficiency Virus.

Adult patients with human immunodeficiency virus (HIV) appear to be at high risk of cardiovascular disease (CVD). Peripheral arterial disease (PAD) is particularly concerning as it is associated with myocardial infarction and stroke. Nevertheless, the incidence of PAD is still unknown. The authors prospectively recruited HIV-infected patients from the outpatient clinic of the Department of Internal Medicine in our center. We assessed ankle-brachial index (ABI) using the VaSera system™ (Fukuda Denshi Co., Ltd). Patients were grouped into 3 ABI levels: an ABI ≤0.90 was considered abnormal and evidence of PAD, an ABI 1.0 to 1.40 was considered normal, and 0.91 to 0.99 was considered borderline. Cardiovascular risk factors were compared across all 3 levels of ABI and were analyzed using multivariate ordinal logistic regression. Eight hundred ninety-two patients were recruited. The mean age was 42.9 ± 10.0 years and 458 (51.4%) were males. There were 704, 149, and 39 patients in the normal, borderline, and abnormal ABI groups, respectively. The latter group of 39 patients was considered to have PAD, yielding a prevalence of 4.37% (95% confidence interval [CI] 3.21-5.93). Sex ratio, age, education levels, smoking rate, body mass index (BMI), blood pressure, prevalence of comorbidities with hypertension and coronary heart disease, median triglyceride level, reduced kidney function and HIV-1 RNA undetectable ratio, duration of HIV diagnosis, and duration on antiretroviral treatment were significantly different among 3 ABI subgroups. Independent risk factors associated with PAD were being female (odds ratio [OR]: 2.86; 95% CI: 1.94-4.22), being <30 years of age (OR: 4.66; 95% CI: 2.78-7.81), being overweight (BMI 25-25.9; OR: 0.39; 95% CI: 0.20-0.76), being obese (BMI: 30; OR: 3.53; 95% CI: 1.51-8.22), having a diastolic blood pressure ≥80 mmHg (OR: 0.50; 95% CI: 0.35-0.71), and having detectable HIV-1 RNA ≥20 copies/mL (OR: 1.85; 95% CI: 1.13-3.03). In conclusion, the prevalence of PAD in HIV-infected Thais was 4.37% in infected patients on therapy attending outpatient clinics. For this population, PAD appears to be relatively poorly correlated with traditional risk factors of CVD.

Hospital-Wide Protocol Significantly Improved Appropriate Management of Patients with Staphylococcus aureus Bloodstream Infection.

Background:Staphylococcus aureus bloodstream infection (SA-BSI) causes morbidity and mortality. We established a management protocol for patients with SA-BSI aimed at improving quality of care and patient outcomes. Methods: A retrospective pre−post intervention study was conducted at Maharaj Nakorn Chiang Mai Hospital from 1 October 2019 to 30 September 2020 in the pre-intervention period and from 1 November 2020 to 31 October 2021 in the post-intervention period. Results: Of the 169 patients enrolled, 88 were in the pre-intervention and 81 were in the post-intervention periods. There were similar demographic characteristics between the two periods. In the post-intervention period, evaluations for metastatic infections were performed more frequently, e.g., echocardiography (70.5% vs. 91.4%, p = 0.001). The appropriateness of antibiotic prescription was higher in the post-intervention period (42% vs. 81.5%, p < 0.001). The factors associated with the appropriateness of antibiotic prescription were ID consultation (OR 15.5; 95% CI = 5.9−40.8, p < 0.001), being in the post-intervention period (OR 9.4; 95% CI: 3.5−25.1, p < 0.001), and thorough investigations for metastatic infection foci (OR 7.2; 95% CI 2.1−25.2, p = 0.002). However, the 90-day mortality was not different (34.1% and 27.2% in the pre- and post-intervention periods, respectively). The factors associated with mortality from the multivariate analysis were the presence of alteration of consciousness (OR 11.24; 95% CI: 3.96−31.92, p < 0.001), having a malignancy (OR 6.64; 95% CI: 1.83−24.00, p = 0.004), hypoalbuminemia (OR 5.23; 95% CI: 1.71−16.02, p = 0.004), and having a respiratory tract infection (OR 5.07; 95% CI: 1.53−16.84, p = 0.008). Source control was the only factor that reduced the risk of death (OR 0.08; 95% CI: 0.01−0.53, p = 0.009). Conclusion: One-third of patients died. Hospital-wide protocol implementation significantly improved the quality of care. However, the mortality rate did not decrease.

Prevalence of Staphylococcus aureus nasal carriage and surgical site infection rate among patients undergoing elective cardiac surgery.

BACKGROUND: Nasal carriers of Staphylococcus aureus are at increased risk of postoperative surgical site infection. Nasal decolonization with mupirocin is recommended in patients undergoing cardiac surgery to reduce surgical site infection. These data are still lacking in Thailand. Therefore, the aim of this study was to determine the prevalence of S. aureus nasal carriage in Thai patients undergoing elective cardiac surgery. The association of surgical site infection and S. aureus nasal carriage was also examined. METHODS: This was a prospective cohort study of 352 patients who planned to undergo elective cardiac surgery. Nasal swab culture was performed in all patients preoperatively. RESULTS: Of 352 patients, 46 (13.1%) had a positive nasal swab culture for methicillin-sensitive S. aureus (MSSA) and one patient (0.3%) harbored a methicillin-resistant S. aureus (MRSA) strain. The incidence of superficial and deep surgical site infection was 1.3% and 0.3%, respectively. After multivariate analysis, S. aureus nasal carriage was independently associated with superficial surgical site infection (odds ratio 13.04, 95% confidence interval 1.28-133.27; P=0.03). CONCLUSIONS: The prevalence of MSSA and MRSA nasal carriage in Thai patients undergoing elective cardiac surgery was low. The incidence of surgical site infection was also very low in the population studied. Nevertheless, it was found that S. aureus nasal carriage increased the risk of superficial surgical site infection.

Cardiovascular disease incidence projections in the TREAT Asia HIV Observational Database (TAHOD).

BACKGROUND: We aimed to project the 10-year future incidence of cardiovascular disease (CVD) and model several intervention scenarios based on a multi-site Asian HIV-positive cohort. METHODS: Analyses were based on patients recruited to the TREAT Asia HIV Observational Database (TAHOD), consisting of 21 sites in 12 countries. Patients on triple antiretroviral therapy (ART) were included if they were alive, without previous CVD, and had data on CVD risk factors. Annual new CVD events for 2019-2028 were estimated with the D:A:D equation, accounting for age- and sex-adjusted mortality. Modelled intervention scenarios were treatment of high total cholesterol, low high-density lipoprotein cholesterol (HDL) or high blood pressure, abacavir or lopinavir substitution, and smoking cessation. RESULTS: Of 3,703 included patients, 69% were male, median age was 46 (IQR 40-53) years and median time since ART initiation was 9.8 years (IQR 7.5-14.1). Cohort incidence rates of CVD were projected to increase from 730 per 100,000 person-years (pys) in 2019 to 1,432 per 100,000 pys in 2028. In the modelled intervention scenarios, most events can be avoided by smoking cessation, abacavir substitution, lopinavir substitution, decreasing total cholesterol, treating high blood pressure and increasing HDL. CONCLUSIONS: Our projections suggest a doubling of CVD incidence rates in Asian HIV-positive adults in our cohort. An increase in CVD can be expected in any ageing population, however, according to our models, this can be close to averted by interventions. Thus, there is an urgent need for risk screening and integration of HIV and CVD programmes to reduce the future CVD burden.

The influence of age-associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV.

INTRODUCTION: Multiple comorbidities among HIV-positive individuals may increase the potential for polypharmacy causing drug-to-drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age-associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age-associated comorbidities on therapeutic outcomes of cART in HIV-positive adults in Asian countries. METHODS: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in-line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure. RESULTS: The incidence of virologic failure was 7.72/100 person-years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age-related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person-years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities. CONCLUSIONS: In our Asia regional cohort, age-associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.

Brief Report: Malignancies in Adults Living With HIV in Asia.

BACKGROUND: Hematological malignancies have continued to be highly prevalent among people living with HIV (PLHIV). This study assessed the occurrence of, risk factors for, and outcomes of hematological and nonhematological malignancies in PLHIV in Asia. METHODS: Incidence of malignancy after cohort enrollment was evaluated. Factors associated with development of hematological and nonhematological malignancy were analyzed using competing risk regression and survival time using Kaplan-Meier. RESULTS: Of 7455 patients, 107 patients (1%) developed a malignancy: 34 (0.5%) hematological [0.08 per 100 person-years (/100PY)] and 73 (1%) nonhematological (0.17/100PY). Of the hematological malignancies, non-Hodgkin lymphoma was predominant (n = 26, 76%): immunoblastic (n = 6, 18%), Burkitt (n = 5, 15%), diffuse large B-cell (n = 5, 15%), and unspecified (n = 10, 30%). Others include central nervous system lymphoma (n = 7, 21%) and myelodysplastic syndrome (n = 1, 3%). Nonhematological malignancies were mostly Kaposi sarcoma (n = 12, 16%) and cervical cancer (n = 10, 14%). Risk factors for hematological malignancy included age >50 vs. ≤30 years [subhazard ratio (SHR) = 6.48, 95% confidence interval (CI): 1.79 to 23.43] and being from a high-income vs. a lower-middle-income country (SHR = 3.97, 95% CI: 1.45 to 10.84). Risk was reduced with CD4 351-500 cells/µL (SHR = 0.20, 95% CI: 0.05 to 0.74) and CD4 >500 cells/µL (SHR = 0.14, 95% CI: 0.04 to 0.78), compared to CD4 ≤200 cells/µL. Similar risk factors were seen for nonhematological malignancy, with prior AIDS diagnosis showing a weak association. Patients diagnosed with a hematological malignancy had shorter survival time compared to patients diagnosed with a nonhematological malignancy. CONCLUSIONS: Nonhematological malignancies were common but non-Hodgkin lymphoma was more predominant in our cohort. PLHIV from high-income countries were more likely to be diagnosed, indicating a potential underdiagnosis of cancer in low-income settings.

Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia.

PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Hepatitis B Vaccination Induced TNF-α- and IL-2-Producing T Cell Responses in HIV- Healthy Individuals Higher than in HIV+ Individuals Who Received the Same Vaccination Regimen.

We investigated cytokine production and expression of degranulation marker CD107a after different strategies of hepatitis B virus (HBV) vaccination in human immunodeficiency virus-infected individuals, which were three doses of 20 µg (standard dose group), four doses of 20 µg (four doses group), or four doses of 40 µg (four double doses group), compared to standard dose vaccination in healthy controls. PBMCs collected at different time points were stimulated in vitro with recombinant hepatitis B surface antigen and analyzed by flow cytometry. There was an increase in TNF-α production of total and memory CD4+ T cells at 7 months after vaccination in healthy controls compared to the HIV+ group, which received the same standard vaccination regimen. An increase in the IL-2-producing memory CD4+ T cells in the healthy control group was also observed at 7 months after vaccination. No differences were observed between the healthy controls and both groups of four doses at any time point of study. These results suggest that the standard HBV vaccination schedule might induce better production of TNF-α and IL-2 from CD4+ T cells in healthy individuals. Modification of HBV vaccination schedule by increasing the frequency and/or dosage may improve the CMI response in HIV-infected individuals. This trial is registered with NCT1289106.

Characterization of anti-interferon-γ antibodies in HIV-negative immunodeficient patients infected with unusual intracellular microorganisms.

A major characteristic of immunodeficiency associated with life-threatening intracellular infection in adults is the presence of anti-interferon-γ antibodies. Although little is known about the mechanism underlying this syndrome, it is believed that the antibodies inhibit the activity of downstream signaling pathway of interferon-γ. In this study, the characteristics of these antibodies in patients who presented, or have a history of, intracellular infection and were positive to anti-interferon-γ antibodies were investigated. The antibodies exhibited mainly the IgG1 and the IgG4 subtypes and recognized the C-terminal of the interferon-γ linear epitope containing the KRKR motif, which is required for the biological activity of interferon-γ. The antibodies bound to recombinant interferon-γ with significantly lower avidity than antibodies to a recall antigen, tetanus toxoid, suggesting that the antibodies might have not undergone affinity maturation. The data from this study may provide fundamental information to better understand the properties of anti-interferon-γ antibodies, which can be useful for future studies. Impact statement An increase in the number of immunodeficient patients related to autoantibodies to interferon (IFN)-γ has been observed particularly in East Asian adults. These patients are often presented with opportunistic infections caused by intracellular pathogens, including non-tuberculous mycobacteria (NTM), Cryptococcus neoformans, Penicillium marneffei (now called Talaromyces marneffei), and non-typhoidal Salmonella spp. The mortality rate for this syndrome is relatively high with 32% patients dying at the median time of 25 months after diagnosis. Characterization of these autoantibodies may promote better understanding of the syndrome, an emerging health problem affecting East Asia populations and impeding their welfare and economic development.

Trends in first-line antiretroviral therapy in Asia: results from the TREAT Asia HIV observational database.

BACKGROUND: Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes. METHODS: Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥ 6 months were included. Predictors of treatment failure and treatment modification were assessed. RESULTS: Data from 4662 eligible patients was analysed. Patients started ART in 2003-2006 (n = 1419), 2007-2010 (n = 2690) and 2011-2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7-23.5] events per 100 patient/years in 2003-2006, 15.8 [14.9-16.8] in 2007-2010, and 11.6 [9.4-14.2] in 2011-2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33-0.81], p = 0.004 for 2011-2013 versus 2003-2006), older age (1.56 [1.19-2.04], p = 0.001 for ≥ 50 years versus <30 years), female sex (1.29 [1.11-1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06-1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28-20.54], p<0.001 for stavudine-based regimens versus tenofovir-based). CONCLUSIONS: The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.

Cryptococcal meningitis in HIV-infected patients at Chiang Mai University Hospital: a retrospective study.

Cryptococcal meningitis (CM) is a common central nervous system infection in HIV-infected patients. This study aimed to determine treatment outcomes among HIV-infected patients who had cryptococcal meningitis and to determine predictors of death. We conducted a retrospective cohort study among HIV-infected patients receiving care at Chiang Mai University Hospital from January 1, 2005 to December 31, 2010. We studied 79 patients; 45 (57.0%) were male and the mean age was 35.1 +/- 7.2 years. Eleven patients (13.9%) had previous opportunistic infection. The most common presenting symptoms were headache (63 patients, 79.8%), fever (49 patients, 62.0%), and altered consciousness (21 patients, 26.6%). The median CD4+ cell count was 20 cells/mm3 [Interquartile range (IQR) 10, 53]. The in-hospital, 90-day, and 1-year mortality rates were 24.1%, 32.4%, and 52.2%, respectively. The CM attributable in-hospital, 90-day and 1-year mortality rates were 13.9%, 20.3%, and 23.2%, respectively. Predictors associated with a 1-year mortality were a high cerebrospinal (CSF) cryptococcal antigen titer (> 1:10,000) [Odds Ratio (OR) =7.08, 95% confidence interval (CI): 1.62-31.00, p = 0.009], and altered consciousness at presentation (OR = 5.27; 95% CI: 1.16-24.05; p = 0.032). Cryptococcal meningitis is an important cause of death in HIV-infected patients. HIV-infected patients with a low CD4+ cell count, a headache, fever and altered consciousness should be investigated for CM and those with a high CSF cryptococcal antigen titer are at high risk for mortality.

Occupational exposure to blood and body fluids among healthcare workers in a teaching hospital: an experience from northern Thailand.

This retrospective study was conducted among healthcare workers (HCWs) in a tertiary care hospital to (i) determine the incidence of exposure to blood and/or body fluids, (ii) describe the characteristics of such exposures, and (iii) describe management after exposure. There were 1,611 episodes of occupational exposure between January 1, 2005 and December 31, 2010. Of those affected, 1,086 (67.4%) were women. The mean age was 27.6 ± 7.2 years. Nurses (483, 29.9%) were the HCWs most frequently exposed to blood and/or body fluids. The incidence was highest among physicians (11%/year). Percutaneous injury by hollow needles was the most common type of injury (576, 35.8%). Of the 1,611 episodes, 142 (8.8%) comprised HCWs being exposed to human immunodeficiency virus-positive sources. One hundred fifty-one HCWs (9.4%) were exposed to hepatitis B surface (HBs) antigen-positive sources. Sixty-one HCWs had indications for both hepatitis B virus (HBV) vaccine and hepatitis B immunoglobulin; 43 (70.5%) received both. Among the 266 HCWs who had no protective antibody against HBV and were exposed to HBs antigen-negative sources, only 1 (0.4%) received HBV vaccine. These findings suggest that guidelines for post-exposure management among HCWs exposed to HBs antigen-positive sources are not regularly followed. HBV immunization is necessary for all HCWs.

Streptococcus agalactiae in adults at Chiang Mai University Hospital: a retrospective study.

BACKGROUND: Infection caused by Streptococcus agalactiae, a Group B streptococcus, is an emerging disease in non-pregnant adults. This study describes the epidemiological, clinical, and microbiological characteristics of S. agalactiae infection in adult patients in northern Thailand. METHODS: A retrospective study was conducted between January 1, 2006 and December 31, 2009 at Chiang Mai University Hospital among patients aged ≥15 years, whose clinical specimens obtained from normally sterile sites grew S. agalactiae. RESULTS: One-hundred and eighty-six patients and 197 specimens were identified during the 4-year period. Among 186 patients, 82 were documented as having invasive infection; 42 patients were male (51.2%) with the mean age of 48.5 ± 19.4 years (range 17, 83). Fifty-three patients (64.6%) had underlying medical conditions; 17 patients (20.7%), 10 (12.2%), 8 (9.7%) had diabetes, chronic renal diseases, and malignancy, respectively. Among 40 patients (48.8%) with bloodstream infection, no other site of infection was determined in 29 (35.4%) patients. In the remaining 11 patients, 5 patients (6.1%), 5 (6.1%), and 1 (1.2%) had meningitis, arthritis, and meningitis with arthritis, respectively. Forty-two patients (51.2%) presented with localized infection, i.e., subcutaneous abscess (19 patients, 23.2%), chorioamnionitis (10 patients, 12.2%), urinary tract infection (5 patients, 6.1%), arthritis (3 patients, 3.7%), meningitis (2 patients, 2.4%), and spontaneous bacterial peritonitis, uveitis, and tracheobronchitis (1 patient each, 1.2%). The overall mortality was 14.6% (12 patients). CONCLUSIONS: S. agalactiae infection is a growing problem in non-pregnant patients, particularly in those with underlying medical conditions. Physicians should add S. agalactiae infection in the list of differential diagnoses in patients with meningitis and/or septicemia.

Epidemiology of adult candidemia at Chiang Mai University Hospital.

A retrospective study was conducted between July 1, 2004 and June 30, 2009 at Chiang Mai University Hospital among 138 patients with candidemia; 85 patients (61.6%) were male and the mean age was 57.7 +/- 19.4 years. Seventy-eight patients (56.5%) had underlying medical conditions. Candida albicans and non-albicans Candida were identified in 42 (30.4%) and 96 (69.6%) patients, respectively. Not being admitted to the ICU was the only factor associated with non-albicans candidemia (p = 0.018). Sixty patients (43.5%) had favorable outcomes. Factors independently associated with unfavorable outcomes included patients who were in the ICU (p = 0.025), were intubated (p < 0.001) or were on hemodialysis (p = 0.031); prior abdominal surgery was associated with a favorable outcome (p = 0.026). Candidemia is not a rare condition at this hospital. Early recognition and prompt empirical treatment are essential to improve outcomes of patients at risk for developing candidemia. Improvement of surveillance is crucial to recognizing emergence of highly resistant strains of Candida spp.

Diverse contexts of zoonotic transmission of simian foamy viruses in Asia.

In Asia, contact between persons and nonhuman primates is widespread in multiple occupational and nonoccupational contexts. Simian foamy viruses (SFVs) are retroviruses that are prevalent in all species of nonhuman primates. To determine SFV prevalence in humans, we tested 305 persons who lived or worked around nonhuman primates in several South and Southeast Asian countries; 8 (2.6%) were confirmed SFV positive by Western blot and, for some, by PCR. The interspecies interactions that likely resulted in virus transmission were diverse; 5 macaque taxa were implicated as a potential source of infection. Phylogenetic analysis showed that SFV from 3 infected persons was similar to that from the nonhuman primate populations with which the infected persons reported contact. Thus, SFV infections are likely to be prevalent among persons who live or work near nonhuman primates in Asia.