Shared and unique antibody and B cell profiles in HIV-positive and HIV-negative individuals with cryptococcal meningoencephalitis.

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\rm{\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.

Unlike cryptococcal meningitis (CM) in HIV-positive individuals, there are no known biomarkers of risk in HIV-negative individuals and the diagnosis is often not suspected and delayed. This study identified non-T cells, including antibody and B cell CM-associated profiles that may guide cryptococcal antigen testing in HIV-negative individuals.

FTO-rs9939609 Polymorphism is a Predictor of Future Type 2 Diabetes: A Population-Based Prospective Study.

The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective study included 1443 nondiabetic subjects at baseline, and they were examined for developing T2D after 5-year follow-up. Cox proportional hazards model was used to evaluate the hazard ratio (HR) of rs9939609 to the future T2D in the models adjusted for the confounding factors including socio-economic status, lifestyle factors (smoking and drinking history, sporting habits, and leisure time), and clinical patterns (obese status, blood pressures, and dyslipidemia) at baseline. The area under receiver operating characteristic curve (AUC) was used to measure the power to predict individuals with T2D. The FTO-rs9939609 polymorphism was a significant predictor of future T2D in the model unadjusted, and it remained significant in the final model after adjustment for the confounding factors, showing an additive effect of the A-allele (HR = 1.35, 95% CI = 1.02-1.78, P = 0.036, AUC = 0.676). For normoglycemic subjects at baseline, the similar final adjusted model reported the increased HR per A-allele (HR = 1.50, 95% CI = 1.09-2.07, P = 0.012, AUC = 0.697). Five-year changes in BMI, waist circumference, and systolic blood pressure did not remove the contribution of rs9939609 to increased HR of T2D. The population attributable risk for risk genotype was 13.6%. In conclusion, the study indicates that the FTO-rs9939609 polymorphism is an important genetic predictor for future T2D in Vietnamese population.

Incidence and prediction nomogram for metabolic syndrome in a middle-aged Vietnamese population: a 5-year follow-up study.

PURPOSE: We aimed to determine the incidence and prediction nomogram for new-onset metabolic syndrome (MetS) in a middle-aged Vietnamese population. METHODS: A population-based prospective study was conducted in 1150 participants aged 40-64 years without MetS at baseline and followed-up for 5 years. Data on lifestyle factors, socioeconomic status, family diabetes history, and anthropometric measures were collected. MetS incidence was estimated in general population and subgroup of age, gender, and MetS components. A Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for MetS. A prediction nomogram was developed and checked for discrimination and calibration. RESULTS: During median follow-up of 5.14 years, the accumulate MetS incidence rate was 23.4% (95% CI: 22.2-24.7). The annual incidence rate (95% CI) was 52.9 (46.7-60.1) per 1000 person-years in general population and higher in women [56.6 (48.7-65.9)] than men [46.5 (36.9-59.3)]. The HRs (95% CI) for developing MetS were gender [females vs males: 2.04 (1.26-3.29)], advanced age [1.02 (1.01-1.04) per one year], waist circumference [1.08 (1.06-1.10) per one cm] and other obesity-related traits, and systolic blood pressure [1.02 (1.01-1.03) per one mmHg]. The prediction nomogram for MetS had a good discrimination (C-statistics = 0.742) and fit calibration (mean absolute error = 0.009) with a positive net benefit in the predicted probability thresholds between 0.13 and 0.70. CONCLUSIONS: The study is the first to indicate an alarmingly high incidence of MetS in a middle-aged population in Vietnam. The nomogram with simply applicable variables would be useful to qualify individual risk of developing MetS.

An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis.

Background: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential. Methods: Open label randomized controlled trial. Participants received standard care - amphotericin combined with fluconazole for the first 2 weeks - or standard care plus tamoxifen 300 mg/day. The primary end point was Early Fungicidal Activity (EFA) - the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031. Results: Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (-0.48log10 colony-forming units/mL/CSF control arm versus -0.49 tamoxifen arm, difference -0.005log10CFU/ml/day, 95% CI: -0.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation. Conclusions: High-dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed. Funding: The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.

Clinical Patterns and Risk Factors for Pneumonia Caused by Atypical Bacteria in Vietnamese Children.

OBJECTIVE: To investigate clinical characteristics and risk factors for atypical community-acquired pneumonia (CAP) in children. METHODS: Multiplex polymerase chain reaction and specific IgM determination were used to detect atypical bacteria in 661 hospitalized children aged 1-15 years with CAP. Clinical and epidemiological patterns were compared between typical and atypical CAP. RESULTS: Children in atypical CAP group manifested significantly lower rates of wheezing, bronchial rales, and interstitial pneumonia and showed higher rates of asthma history, headache, chest pain, and lobar pneumonia . Age group, season of disease onset, asthma history, duration of symptom onset to hospital admission, and radiological findings were the significant risk factors for atypical CAP on multivariate logistic regression analysis. CONCLUSIONS: The clinical characteristics and risk factors can be used to identify a child at high risk of atypical CAP.

The APOA5-rs662799 Polymorphism Is a Determinant of Dyslipidemia in Vietnamese Primary School Children.

Apolipoprotein A-V encoded by apolipoprotein 5 (APOA5) gene plays an important role in lipid metabolism, especially in the regulation of plasma triglycerol levels. The study aimed to evaluate the association of the APOA5-rs662799 polymorphism with dyslipidemia in Vietnamese children and the potential modification of obesity-related traits (body mass index, waist circumference, hip circumference, and waist-to-hip ratio) on this association. A case-control study was conducted with a total of 154 dyslipidemia cases and 389 controls at the age of 6 to 10 recruited at 31 primary schools in Hanoi city of Vietnam. Genotype for APOA5-rs662799 polymorphism was determined by the restriction fragment length polymorphism analysis. The association of APOA5-rs662799 polymorphism with dyslipidemia adjusting for age, sex, residence, and obesity-related traits was analyzed by binary logistic regression analysis. The results showed that in comparison with T/T and T/C carriers, the C/C carriers had a higher concentration of serum TAG in cases (p =0.049). Carriers of the C allele (C/C + T/C) had higher risk for developing dyslipidemia and hypertriglyceridemia than subjects with T/T genotype (odds ratio, OR = 1.7, p =0.0062 and OR = 1.6, p = 0.026, respectively). The association remained significant after adjusting for age, gender, residence, and obesity status (OR = 1.75, p = 0.006 and OR = 1.53, p = 0.049, respectively) or other obesity-related traits. The study suggested that the APOA5-rs662799 polymorphism may be a determinant of dyslipidemia and hypertriglyceridemia in Vietnamese children, independent of obesity-related traits.

Antimicrobial Resistance Profile and Molecular Characteristics of Staphylococcus aureus Isolates from Hospitalized Adults in Three Regions of Vietnam.

This study aimed to investigate antimicrobial resistance profile, multidrug resistance (MDR), and molecular characteristics of pathogenic Staphylococcus aureus isolates from hospitalized Vietnamese adults. Two hundred and twenty-three pathogenic S. aureus isolates were obtained from the hospitals located in 3 regions of Vietnam. The minimum inhibitory concentrations were determined to detect the antibiotic susceptibility of the isolates. The molecular characteristics of S. aureus isolates were investigated through antibiotic-resistant genes analysis, staphylococcal cassette chromosome mec typing, pulsed-field gel electrophoresis, and multilocus sequence typing. Substantial differences among the 3 regions were found in the prevalence rates of methicillin-resistant S. aureus (north: 48.6%, central: 58.7%, south: 78.9%) and MDR (north: 65.8%, central: 79.7%, and south: 84.2%). The prevalence rates of the genes tetK/M, aacA/aphD, ermA/B/C, and mecA increased substantially from north to south. ST188-SCCmecIV and ST239-SCCmecII isolates were most commonly found in the 2 largest clusters. ST188 predominance was observed in the largest cluster in methicillin-resistant and methicillin-sensitive S. aureus isolates, including SCCmecIII and SCCmecIVa, in fatal cases. Our results revealed a high occurrence of MDR and possible north-south trend in antibiotic resistance profile, MDR patterns, and frequency of antibiotic-conferring genes among S. aureus isolates. ST188 predominance raises concerns about the global importance of host-adapted ST188 in East Asian populations.

First Report on Association of Hyperuricemia with Type 2 Diabetes in a Vietnamese Population.

BACKGROUND: Uric acid is a powerful free-radical scavenger in humans, but hyperuricemia may induce insulin resistance and beta-cell dysfunction. The study aimed to evaluate the association between hyperuricemia and hyperglycemia, considering the confounding factors in a Vietnamese population. METHODS: A population-based cross-sectional study recruited 1542 adults aged 50 to 70 years to collect data on socioeconomic status, lifestyle factors, and clinical patterns. Associations between hyperuricemia and hyperglycemia (isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG-IGT, and type 2 diabetes (T2D)) were evaluated by multinomial logistic regression analysis in several models, adjusting for the confounding factors including socioeconomic status, lifestyle factors, and clinical measures. RESULTS: Uric acid values were much higher in IFG, IFG-IGT, and T2D groups compared to those in the normal glucose tolerance (NGT) group. The significant association of hyperuricemia with IFG, IFG-IGT, and T2D was found in the model unadjusted and remained consistently in several models adjusted for socioeconomic status, lifestyle factors, and clinical patterns. In the final model, the consistent hyperglycemia risk was found in total sample (OR = 2.23 for IFG, OR = 2.29 for IFG-IGT, and 1.75 for T2D, P ≤ 0.006) and in women (OR = 2.90 for IFG, OR = 3.96 for IFG-IGT, and OR = 2.49 for T2D, P < 0.001) but not in men. CONCLUSIONS: It is the first report in Vietnamese population suggesting the significant association of hyperuricemia with IFG, IFG-IGT, and T2D; and the predominant association was found in women than in men, taken into account the confounding factors.

A randomized open label trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis.

Background: Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with amphotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest. Where unavailable, guidelines recommend treatment with amphotericin and fluconazole, but this is less effective, with mortality rates of 40-50%. Faster rates of clearance of yeast from cerebrospinal fluid (CSF) are associated with better outcomes - improving the potency of antifungal therapy is likely to be an effective strategy to improve survival. Tamoxifen, a selective estrogen receptor modulator used to treat breast cancer, has anti-cryptococcal activity, appearing synergistic when combined in vitro with amphotericin, and fungicidal when combined with fluconazole. It is concentrated in the brain and macrophages, off-patent, cheap and widely available. We designed a randomized trial to deliver initial efficacy and safety data for tamoxifen combined with amphotericin and fluconazole. Method: A phase II, open-label, randomized (1:1) controlled trial of tamoxifen (300mg/day) combined with amphotericin (1mg/kg/day) and fluconazole (800mg/day) for the first 2 weeks therapy for HIV infected or uninfected adults with cryptococcal meningitis. The study recruits at Cho Ray Hospital and the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. The primary end point is Early Fungicidal Activity (EFA-the rate of yeast clearance from CSF), over the first two weeks of treatment. 50 patients will be recruited providing ≈80% and 90% power to detect a difference in the EFA of -0.11 or -0.13 log10CFU/ml/day, respectively. Discussion: The results of the study will inform the decision to proceed to a larger trial powered to mortality. The size of effect detectable has previously been associated with reduced mortality from this devastating disease. Particular side effects of interest include QT prolongation. Trial registration: Clinicaltrials.gov NCT03112031 (11/04/2017).

The Brain-Derived Neurotrophic Factor Val66Met Polymorphism, Delivery Method, Birth Weight, and Night Sleep Duration as Determinants of Obesity in Vietnamese Children of Primary School Age.

BACKGROUND: Obesity is a complex disease that involves both environmental and genetic factors in its pathogenesis. Several studies have identified multiple obesity-associated loci in many populations. However, their contribution to obesity in the Vietnamese population is not fully described, especially in children. The study aimed to investigate the association of obesity with Val66Met polymorphism in brain-derived neurotrophic factor (BDNF) gene, delivery method, birth weight, and lifestyle factors in Vietnamese primary school children. METHODS: A case-control study was conducted on 559 children aged 6-11 years (278 obese cases and 281 normal controls). The obesity of the children was classified using both criteria of International Obesity Task Force (IOTF, 2000) and World Health Organization (WHO, 2007). Lifestyle factors, birth delivery, and birth weight of the children were self-reported by parents. The BDNF genotype was analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Association was evaluated by multivariate logistic regression and cross-validated by the Bayesian model averaging method. RESULTS: The most significantly independent factors for obesity were delivery method (cesarean section vs. vaginal delivery, ß = 0.56, p = 0.007), birth weight (>3500 to <4000 g vs. 2500-3500 g, ß = 0.52, p = 0.035; ≥4000 g vs. 2500-3500 g, ß = 1.06, p = 0.015), night sleep duration (<8 h/day vs. ≥8 h/day, ß = 0.99, p < 0.0001), and BDNF Val66Met polymorphism (AA and GG vs. AG, ß = 0.38, p = 0.039). CONCLUSIONS: The study suggested the significant association of delivery method, birth weight, night sleep duration, and BDNF Val66Met polymorphism, with obesity in Vietnamese primary school children.

Association of apolipoprotein E polymorphism with plasma lipid disorders, independent of obesity-related traits in Vietnamese children.

BACKGROUND: The dyslipidemia associated with obesity plays a major role in the development of atherosclerosis and cardiovascular disease. Dyslipidemia in childhood can progress in adult stage. APOE is one of the most important genes that regulate plasma lipid transport and clearance. The study aimed to assess whether the common APOE polymorphism is associated with lipid profiles and dyslipidemia, and it could be modulated by obesity-related traits (body mass index, waist circumference, hip circumference, and waist-to-hip ratio) in Vietnamese children. METHODS: A case-control study was designed including 249 cases with dyslipidemia and 600 controls without dyslipidemia. Dyslipidemia is defined as elevated total or low-density lipoprotein (LDL) cholesterol levels, or low levels of high-density lipoprotein (HDL) cholesterol. Genotype for APOE polymorphism (rs7412 and rs429358) was determined by the polymerase chain reaction and restriction fragment length polymorphism method. The association of APOE genotypes with plasma lipid disorders was tested by binary logistic regression analysis, taking into account the confounding factors of age, sex, residence, province and obesity-related traits. RESULTS: In comparison with ε3/ε3 carriers, the ε4 carriers had the highest concentration of serum TC and LDL-C in cases and controls (P ≤ 0.001), while ε2 carriers had the lowest. Carriers without TT haplotype had higher serum TC than those with TT haplotype. The ε4 carriers had higher hypoalphalipoproteinemia risk than ε3/ε3 carriers (OR = 2.78, P = 0.02) before and after adjustment for age, gender, residence and obesity-related traits. CONCLUSIONS: The study suggested that the APOE genotype and haplotype significantly associated with plasma TC and LDL-C level in Vietnamese children. The association of APOE genotype with hypoalphalipoproteinemia was independent of obesity-related traits.

Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis.

BACKGROUND: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis. METHODS: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole. RESULTS: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites. CONCLUSIONS: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo. (Funded by the United Kingdom Department for International Development and others through the Joint Global Health Trials program; Current Controlled Trials number, ISRCTN59144167.).

Retraction: Pneumonia in Vietnamese Children Aged 1 to 15 years Due to Atypical Pneumonia Causative Bacteria: Hospital-Based Microbiological and Epidemiological Characteristics.

This article has been retracted by the authors under the agreement between the Editor-in-Chief, Masayuki Saijo and authors.

CDKN2A-rs10811661 polymorphism, waist-hip ratio, systolic blood pressure, and dyslipidemia are the independent risk factors for prediabetes in a Vietnamese population.

BACKGROUND: People with prediabetes are at greater risk for heart attack, stroke, kidney disease, vision problems, nerve damage and high blood pressure, compared to those without the disease. Prediabetes is a complex disorder involving both genetic and environmental factors in its pathogenesis. This cross-sectional study aimed to investigate the independent risk factors for prediabetes, considering the contribution of genetic factors (TCF7L2-rs7903146, IRS1-rs1801278, INSR-rs3745551, CDKN2A-rs10811661, and FTO-rs9939609), socio-economic status, and lifestyle factors. RESULTS: Among the candidate genes studied, the CDKN2A-rs10811661 polymorphism was found to be the most significant factor associated with prediabetes in the model unadjusted and adjusted for age, sex, obesity-related traits, systolic blood pressure, dyslipidemia, socio-economic status, and lifestyle factors. In the final model, the CDKN2A-rs10811661 polymorphism (OR per T allele = 1.22, 95 % CI = 1.04-1.44, P = 0.017), systolic blood pressure (OR per 10 mmHg = 1.14, 95 % CI = 1.08-1.20, P < 0.0001), waist-hip ratio (OR = 1.25, 95 % CI = 1.10-1.42, P < 0.0001), dyslipidemia (OR = 1.57, 95 % CI = 1.15-2.14, P = 0.004), and residence (OR = 1.93, 95 % CI = 2.82-4.14, P < 0.0001) were the most significant independent predictors of prediabetes, in which the power of the adjusted prediction model was 0.646. CONCLUSIONS: The study suggested that the CDKN2A-rs10811661 polymorphism, waist-hip ratio, systolic blood pressure, and dyslipidemia were significantly associated with the increased risk of prediabetes in a Vietnamese population. The studied genetic variant had a small effect on prediabetes.

Knowledge and associated factors towards type 2 diabetes among a rural population in the Red River Delta region, Vietnam.

INTRODUCTION: Knowledge about type 2 diabetes (T2D) and attitude towards the condition are known to affect compliance and play an important role in diabetes management. T2D knowledge is a prerequisite for individuals and communities to take action on control of the disease. METHODS: A cross-sectional study was designed to identify knowledge and related factors towards T2D, risk factors, complications, prevention and treatment of the disease. A total of 2580 subjects representative of the general population aged 40-64 years was recruited from a typical province of Red River Delta region, Vietnam. The trained surveyors interviewed subjects directly to collect data, using a structured questionnaire. To evaluate the overall knowledge of T2D, 14 questions were used to calculate the 100 points. Total knowledge score was classified into the following four categories: highly insufficient (≤25 points), insufficient (26-50 points), satisfactory (51-75 points), and highly satisfactory (>75 points). Association between inadequate knowledge (<50 points) and variables was evaluated using multivariate logistic regression. RESULTS: The highly insufficient, insufficient, satisfactory, and highly satisfactory levels of the overall knowledge were 75, 17.9, 6.8, and 0.3%, respectively. Of the total population, more than 65% thought that there is no cure for diabetes, and more than 90% did not know the essential combination of drugs, diet, and physical activity in T2D treatment. Less than 10% of the population understood the concept of T2D, its risk factors, complications, approaches to prevention and treatment. The rural-urban difference of T2D knowledge was found in rates of understanding at least one risk factor (34.8% vs 63%), all the three methods for T2D prevention (1.7% vs 10.3%), and three combined approaches for T2D treatment (8.9% vs 16.4%). Age, residence, educational level, and occupation were the most significant factors associated with inadequate knowledge. CONCLUSIONS: The study shows a low level of diabetes knowledge among the general population aged 40-64 years in the Red River Delta, and significantly lower awareness in rural areas compared with urban areas. The limited awareness has indicated the urgent need for communication and education to improve the T2D knowledge of the Vietnamese population on risk factors, serious level, complications, prevention and treatment, taking into account the age, residence, educational level, and occupation of the subjects.

First report on prevalence and risk factors of severe atypical pneumonia in Vietnamese children aged 1-15 years.

BACKGROUND: Atypical pathogens such as Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila are increasingly recognized as important causes of community acquired pneumonia (CAP) worldwide. Such etiological data for Vietnam is scarce and clinical doctors lack accurate information on which to base their diagnosis and treatment of pneumonia. This study identifies the prevalence and risk factors of severe community acquired pneumonia due to these atypical pathogens (severe-ApCAP) in children aged 1-15 years with CAP in a pediatric hospital in Hanoi, Vietnam. METHODS: 722 hospitalized children with CAP were recruited for detecting those atypical pathogens, using multiplex PCR and ELISA. Clinical and epidemiological data were collected. Multivariate logistic-regression analyses were performed to evaluate the associations of potential risk factors with severe-ApCAP. RESULTS: Among 215 atypical pathogen-positive CAP cases, 45.12% (97/215) were severe-ApCAP. Among the severe-ApCAP group, 55.67% (54/97) cases were caused by pure atypical pathogens and 44.33% (43/97) resulted from a co-infection with typical respiratory pathogens. M. pneumoniae was the most common, with 86.6% cases (84/97) in the severe-ApCAP group, whereas C. pneumoniae and L. pneumophila were less frequent (6.19% and 7.22%, respectively). The highest rate of severe-ApCAP was in children younger than two years (65.98%). The differences related to age are statistically significant (P = 0.008).The factors significantly associated with severe-ApCAP were age (OR = 0.84, 95% CI = 0.75-0.93, P = 0.001), co-infection with typical bacteria (OR = 4.86, 95% CI = 2.17-10.9, P < 0.0001), co-infection with respiratory viruses (OR = 4.36, 95% CI = 1.46-13.0, P = 0.008), respiratory/cardiac system malformation (OR = 14.8, 95% CI = 1.12-196, P = 0.041) and neonatal pneumonia (OR = 11.1, 95% CI = 1.06-116, P = 0.044). CONCLUSIONS: Severe-ApCAP presented at a significant rate in Vietnamese children. More than 50% of severe-ApCAP cases were associated with pure atypical pathogen infection. M. pneumoniae appeared most frequently. The highest rate of severe-ApCAP was in children younger than two years. Younger age and co-infection with typical bacteria or viruses were the most significant risk factors, while respiratory/cardiac system malformation and neonatal pneumonia were additional potential risk factors, associated with severe-ApCAP in Vietnamese children.

CryptoDex: a randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial.

BACKGROUND: Cryptococcal meningitis (CM) is a severe AIDS-defining illness with 90-day case mortality as high as 70% in sub-Saharan Africa, despite treatment. It is the leading cause of death in HIV patients in Asia and Africa.No major advance has been made in the treatment of CM since the 1970s. The mainstays of induction therapy are amphotericin B and flucytosine, but these are often poorly available where the disease burden is highest. Adjunctive treatments, such as dexamethasone, have had dramatic effects on mortality in other neurologic infections, but are untested in CM. Given the high death rates in patients receiving current optimal treatment, and the lack of new agents on the horizon, adjuvant treatments, which offer the potential to reduce mortality in CM, should be tested.The principal research question posed by this study is as follows: does adding dexamethasone to standard antifungal therapy for CM reduce mortality? Dexamethasone is a cheap, readily available, and practicable intervention. METHOD: A double-blind placebo-controlled trial with parallel arms in which patients are randomised to receive either dexamethasone or placebo, in addition to local standard of care. The study recruits patients in both Asia and Africa to ensure the relevance of its results to the populations in which the disease burden is highest. The 10-week mortality risk in the control group is expected to be between 30% and 50%, depending on location, and the target hazard ratio of 0.7 corresponds to absolute risk reductions in mortality from 30% to 22%, or from 50% to 38%. Assuming an overall 10-week mortality of at least 30% in our study population, recruitment of 824 patients will be sufficient to observe the expected number of deaths. Allowing for some loss to follow-up, the total sample size for this study is 880 patients. To generate robust evidence across both continents, we aim to recruit roughly similar numbers of patients from each continent. The primary end point is 10-week mortality. Ethical approval has been obtained from Oxford University's Tropical Research Ethics Committee (OxTREC), and as locally mandated at each site. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN59144167 26-July-2012.

Metabolic syndrome among a middle-aged population in the Red River Delta region of Vietnam.

BACKGROUND: Metabolic syndrome (MetS) is a clustering of metabolic risk factors for cardiovascular diseases and type 2 diabetes. The study aimed to estimate the prevalence of MetS, its components, and their associations among rural middle-aged population in Vietnam. METHODS: A cross-sectional study with a representative sample (n = 2443) was conducted to collect data on demographic, socioeconomic, anthropometric, lifestyles, plasma glucose, and lipid profile. The age- and sex-adjusted prevalences of MetS and its components were calculated using the direct standardization. Associations of risk factors with MetS were evaluated using logistic regression, taken into account the confounding factors. RESULTS: The total age- and sex-adjusted prevalence (95% CI) of MetS was 16.3% (14.0 - 18.6). The most frequent component of MetS was high triglycerides (43.2%), followed by low HDL-C (42.0%), elevated blood pressure (29.2%), high plasma glucose (14.3%), and central obesity (12.3%). Of the total population, only 17.6% did not have any component of MetS and more than 40% had at least two MetS components. The association of MetS with residence, age, body mass index, marital status, and siesta time per day was statistically significant in univariate analysis and replicated in multivariate analysis. CONCLUSION: The MetS prevalence and its components are common and major public health burden in the middle-aged adults in Vietnam. Habitants living in urban, being never-married, having an increase in age, BMI, and siesta time per day are significantly associated with MetS, and they should be paid much more attention for screening and implementing preventive activities.

Association of the common FTO-rs9939609 polymorphism with type 2 diabetes, independent of obesity-related traits in a Vietnamese population.

Type 2 diabetes (T2D) is a complex disorder resulting from both genetic and environmental factors in its pathogenesis. A case-control study was designed with subjects recruited from a general population to investigate whether the association between T2D and the common T>A polymorphism (rs9939609) in fat mass and obesity associated (FTO) gene is mediated by obesity-related measurements, considering the contribution of socio-economic status and lifestyle factors. The significant association between the FTO rs9939609 polymorphism and T2D was first observed in the model unadjusted (OR per A allele=1.61, 95% CI=1.06-2.44, P=0.024). It remained consistently replicated in the final model after adjustments for sex, age, systolic blood pressure, socio-economic status, lifestyle factors, and obesity-related measurements (body mass index, waist-hip ratio, body fat percentage, and body adiposity index), showing an increased T2D risk with an additive effect of the alleles (ORs per A allele=1.80-1.92, 95% CI=1.09-3.19, P<0.05). The FTO-rs9939609 polymorphism, systolic blood pressure, and waist-hip ratio were the most significant independent predictors for T2D, in which the power of the adjusted prediction model was 0.769. In conclusion, the study suggested that the FTO-rs9939609 polymorphism was significantly associated with the increased risk of T2D, independent of obesity-related measurements in a Vietnamese population.