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.

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.).

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.

Pyronaridine-artesunate versus mefloquine plus artesunate for malaria.

BACKGROUND: Pyronaridine-artesunate is an artemisinin-based combination therapy under evaluation for the treatment of Plasmodium falciparum and P. vivax malaria. METHODS: We conducted a phase 3, open-label, multicenter, noninferiority trial that included 1271 patients between 3 and 60 years of age from Asia (81.3%) or Africa (18.7%) with microscopically confirmed, uncomplicated P. falciparum malaria. Patients underwent randomization for treatment with a fixed-dose combination of 180 mg of pyronaridine and 60 mg of artesunate or with 250 mg of mefloquine plus 100 mg of artesunate. Doses were calculated according to body weight and administered once daily for 3 days. RESULTS: Pyronaridine-artesunate was noninferior to mefloquine plus artesunate for the primary outcome: adequate clinical and parasitologic response in the per-protocol population on day 28, corrected for reinfection with the use of polymerase-chain-reaction (PCR) genotyping. For this outcome, efficacy in the group receiving pyronaridine-artesunate was 99.2% (743 of 749 patients; 95% confidence interval [CI], 98.3 to 99.7) and that in the group receiving mefloquine plus artesunate was 97.8% (360 of 368 patients; 95% CI, 95.8 to 99.1), with a treatment difference of 1.4 percentage points (95% CI, 0.0 to 3.5; P=0.05). In the intention-to-treat population, efficacy on day 42 in the group receiving pyronaridine-artesunate was 83.1% (705 of 848 patients; 95% CI, 80.4 to 85.6) and that in the group receiving mefloquine plus artesunate was 83.9% (355 of 423 patients; 95% CI, 80.1 to 87.3). In Cambodia, where there were 211 study patients, the median parasite clearance time was prolonged for both treatments: 64 hours versus 16.0 to 38.9 hours in other countries (P<0.001, on the basis of Kaplan-Meier estimates). Kaplan-Meier estimates of the recrudescence rate in the intention-to-treat population in Cambodia until day 42 were higher with pyronaridine-artesunate than with mefloquine plus artesunate (10.2% [95% CI, 5.4 to 18.6] vs. 0%; P=0.04 as calculated with the log-rank test), but similar for the other countries combined (4.7% [95% CI, 3.3 to 6.7] and 2.8% [95% CI, 1.5 to 5.3], respectively; P=0.24). Elevated levels of aminotransferases were observed in those receiving pyronaridine-artesunate. Two patients receiving mefloquine plus artesunate had seizures. CONCLUSIONS: Fixed-dose pyronaridine-artesunate was efficacious in the treatment of uncomplicated P. falciparum malaria. In Cambodia, extended parasite clearance times were suggestive of in vivo resistance to artemisinin. (Funded by Shin Poong Pharmaceutical Company and the Medicines for Malaria Venture; ClinicalTrials.gov number, NCT00403260.).

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.

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.

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.

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.

In vivo parasitological measures of artemisinin susceptibility.

Parasite clearance data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low (n=14,539), moderate (n=2077), and high (n=2083) levels of malaria transmission across the world were analyzed to determine the factors that affect clearance rates and identify a simple in vivo screening measure for artemisinin resistance. The main factor affecting parasite clearance time was parasite density on admission. Clearance rates were faster in high-transmission settings and with more effective partner drugs in artemisinin-based combination treatments (ACTs). The result of the malaria blood smear on day 3 (72 h) was a good predictor of subsequent treatment failure and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100,000 parasites/microL given the currently recommended 3-day ACT who have a positive smear result on day 3 is <3%; that is, for n patients the observed number with a positive smear result on day 3 does not exceed (n + 60)/24.

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.

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.

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 relationship between the haemoglobin concentration and the haematocrit in Plasmodium falciparum malaria.

BACKGROUND: Malaria is a very important cause of anaemia in tropical countries. Anaemia is assessed either by measurement of the haematocrit or the haemoglobin concentration. For comparisons across studies, it is often necessary to derive one measure from the other. METHODS: Data on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries, to assess the haemoglobin/haematocrit relationship at different time points in malaria. Using a linear random effects model, a conversion equation for haematocrit was derived based on 3,254 measurements from various time points (ranging from day 0 to day 63) from 1,810 patients with simultaneous measurements of both parameters. Haemoglobin was also estimated from haematocrit with the commonly used threefold conversion. RESULTS: A good fit was obtained using Haematocrit = 5.62 + 2.60 * Haemoglobin. On average, haematocrit/3 levels were slightly higher than haemoglobin measurements with a mean difference (+/- SD) of -0.69 (+/- 1.3) for children under the age of 5 (n = 1,440 measurements from 449 patients). CONCLUSION: Based on this large data set, an accurate and robust conversion factor both in acute malaria and in convalescence was obtained. The commonly used threefold conversion is also valid.

Seroepidemiology and serological follow-up of anti-leptospiral IgG in children in Southern Vietnam.

A follow-up study was conducted with 23 months interval to investigate the seroepidemiology and persistence of Leptospira IgG antibodies among healthy children in Binh Thuan province, Southern Vietnam. Sera from 262 children (7-13 years of age) were collected and analysed with a commercially available enzyme-linked immunosorbent assay (ELISA) for Leptospira IgG. Seroconversion was observed in 10.4% (22 of 211, 95% CI: 5.6-26.7) of the children, of whom 18 (8.5%) had probably and four (1.9%) had certainly been exposed to Leptospira. Based on the reduction of sero-negatives of 1.9% among children who have been certainly exposed, the annual seroconversion rate, a measure of the incidence rate of Leptospira infections, corresponds to 0.99% (95% CI: 0.39-2.52). In 61% (31 of 51, 95% CI: 47.1-73.0) of the children with past-infection, Leptospira IgG antibodies remain detectable after 2 years. Data from this study indicate that IgG antibody responses against Leptospira may persist at least for 2 years in children without manifestations of leptospirosis. Results of study uncover the true incidence of leptospirosis infection, the dynamics of waxing and waning antibody concentrations and points at a larger burden of clinically non-significant Leptospira infections in Southern Vietnam. This also indicates background reactivity for serological testing and thus serological result of a single serum sample must be carefully interpreted.

Incidence of primary dengue virus infections in Southern Vietnamese children and reactivity against other flaviviruses.

OBJECTIVE: To study the incidence of asymptomatic primary dengue infections among children and reactivity against other flaviviruses. METHODS: A total of 216 children, who had no dengue-specific IgG antibodies during a serosurvey in 2003 were re-examined 23 months later to determine if seroconversion had occurred. Dengue-specific IgG was demonstrated with enzyme-linked immunosorbent assay (ELISA) and reactivity patterns against other flaviviruses were assessed by using immunofluorescence assay (IFA). RESULTS: Sixty-six children had seroconverted for dengue virus-specific IgG; the true annual incidence of primary dengue was thus 17.3% (95% CI: 13.8-21.4). Japanese Encephalitis virus (JEV)-specific IgG antibodies were detected by IFA among three (4.6%) samples that showed seroconversion in the dengue ELISA, because of cross-reactivity. CONCLUSION: Our findings highlight the high incidence of dengue among Vietnamese children; JEV infections are rare. The true annual incidence of dengue can be estimated with a single cross-sectional seroprevalence survey.