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Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14 - CD16 + ) and NK cells (CD56 + CD16 - ) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chancharoenthana, Kamolratanakul, Ariyanon, Thanachartwet, Phumratanaprapin, Wilairatana and Leelahavanichkul.)

Delayed plasma leakage recognition could lead to improper fluid administration resulting in dengue shock syndrome, subsequently, multi-organ failure, and death. This prospective observational study was conducted in Bangkok, Thailand, between March 2018 and February 2020 to determine predictors of plasma leakage and develop a plasma leakage predictive score among dengue patients aged ≥15 years. Of 667 confirmed dengue patients, 318 (47.7%) developed plasma leakage, and 349 (52.3%) had no plasma leakage. Multivariate analysis showed three independent factors associated with plasma leakage, including body mass index ≥25.0 kg/m2 (odds ratio [OR] = 1.784; 95% confidence interval [CI] = 1.040-3.057; P = 0.035), platelet count <100,000/mm3 on fever days 3 to 4 (OR = 2.151; 95% CI = 1.269-3.647; P = 0.004), and aspartate aminotransferase or alanine aminotransferase ≥100 U/l on fever days 3 to 4 (OR = 2.189; 95% CI = 1.231-3.891; P = 0.008). Because these three parameters had evidence of equality, each independent factor was weighted to give a score of 1 with a total plasma-leak score of 3. Higher scores were associated with increased plasma leakage occurrence, with ORs of 2.017 (95% CI = 1.052-3.869; P = 0.035) for score 1, 6.158 (95% CI = 2.914-13.015; P <0.001) for score 2, and 6.300 (95% CI = 2.419-16.407; P <0.001) for score 3. The area under the receiver operating characteristics curves for predicting plasma leakage was good (0.677 [95% CI = 0.616-0.739]). Patients with a plasma-leak score ≥1 had high sensitivity (88.8%), and those with a plasma-leak score of 3 had high specificity (93.4%) for plasma leakage occurrence. This simple and easily accessible clinical score might help physicians provide early and timely appropriate clinical dengue management in endemic areas., Competing Interests: The authors declare that they have no competing interests.

The implementation of a laboratory information system (LIS) at the Hospital for Tropical Diseases in Thailand provides valuable medical resources, particularly for dengue. Hematocrit (Hct), which is often derived from hemoglobin (Hgb), is important in the diagnosis and management of dengue. This study aimed to evaluate the Hct value obtained from the LIS automated analyzer. We prospectively enrolled 163 hospitalized adults with dengue, for whom 1,141 real-time complete blood count (CBC) results were obtained via a hematology analyzer and updated in the LIS database. The median (interquartile range (IQR)) duration of analytic turnaround times (TATs) was 40.0 (30.0-53.0) minutes. Linear regression analysis indicated a significant relationship between Hgb and Hct with a coefficient of determination (Pearson's R 2 ) of 0.92 at red blood cell distribution width (RDW) ≤18, but Pearson's R 2 decreased to 0.78 at RDW >18. The Hct calculated from the three-fold conversion method and from the analyzer had a Pearson's R 2 of 0.92. At Hgb <12 g/dl and ≥16 g/dl, a greater difference between the two Hct values was observed, with median (IQR) differences of -0.8% (-1.9%-0.2%) and 0.8% (-0.1%-1.7%), respectively ( P value <0.05). In conclusion, the Hgb and Hct of patients with dengue were highly correlated at RDW ≤18. The Hct calculated from the three-fold conversion method and from the analyzer had an excellent relationship, except when the Hgb was <12 g/dl or ≥16 g/dl. Apart from routine CBC evaluation, the LIS could help for accurate data collection in clinical research and development., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Duangjai Sahassananda et al.)

Background: Out-of-hospital cardiac arrest is an emergency that requires immediate management to save lives. However, some predictive scores for the immediate outcomes of patients with out-of-hospital cardiac arrest are difficult to use in clinical practice., Aims: This study aimed to identify predictors of sustained return of spontaneous circulation and to develop a predictive score., Methods: This prospective observational study evaluated sustained return of spontaneous circulation among out-of-hospital cardiac arrest patients in a Thai emergency department between July 2014 and March 2018. The baseline characteristics and prehospital and hospital findings were analysed., Results: Of 347 patients, 126 (36.3%) had sustained return of spontaneous circulation and 20 (5.8%) were discharged. Witnessed arrest (odds ratio = 2.9, 95% confidence interval 1.3-6.2), time from arrest to chest compression <15 min (odds ratio = 3.0, 95% confidence interval 1.3-7.0) and chest compression duration <30 min (odds ratio = 15.6, 95% confidence interval 8.7-28.0) predicted sustained return of spontaneous circulation; these were developed into the WATCH-CPR (Witnessed Arrest, Time from arrest to CHest compression-CPR duration) score. A score of ≥2 was optimal for predicting sustained return of spontaneous circulation, which provided an area under the receiver operating characteristic of 0.775 (95% confidence interval 0.724-0.825) and a sensitivity of 72.2% (95% confidence interval 63.4-79.6%) and specificity of 76.0% (95% confidence interval 69.8-81.4%)., Conclusions: The factors including witnessed arrest, time from arrest to chest compression and chest compression duration were developed as the WATCH-CPR score for predicting sustained return of spontaneous circulation among patients with out-of-hospital cardiac arrest., (© 2020 John Wiley & Sons Ltd.)

Background: Liposuction is the most common aesthetic surgical procedure performed globally. Some of the patients with normal weight who seek liposuction may suffer from body dysmorphic disorder (BDD). Leptin, which is mainly produced by adipose tissue, may be associated with this condition. The aim of this study was to determine the prevalence of BDD and leptin levels in patients with normal weight seeking liposuction., Methods: Thirty-two nonobese women who sought liposuction were matched with 32 healthy volunteers by age and body mass index. Blood biochemistry, leptin levels, and BDD-Yale-Brown Obsessive-Compulsive Scale (BDD-YBOCS) questionnaires were evaluated and compared between the groups., Results: Patients who underwent liposuction had significantly higher median (interquartile range) of total BDD-YBOCS scores than healthy volunteers [25 (22-27) versus 12 (8-20); P < 0.001]. Overall, 28 (87.5%) patients had total BDD-YBOCS scores of >20, whereas 10 (31.5%) volunteers had scores of >20. Patients with total BDD-YBOCS scores of >20 had significantly lower levels of serum leptin [12.43 (7.15-16.98) ng/ml versus 15.57 (9.59-22.28) ng/ml; P = 0.043]., Conclusions: Patients who underwent liposuction had a significantly higher total score of BDD-YBOCS than healthy volunteers matched by sex, age, and body mass index. Subjects with higher BDD-YBOCS scores had significantly lower serum leptin levels., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction: Factors predictive for death from snake envenomation vary between studies, possibly due to variation in host genetic factors and venom composition. This study aimed to evaluate predictive factors for death from snake envenomation in Myanmar., Methods: A prospective study was performed among adult patients with snakebite admitted to tertiary hospitals in Yangon, Myanmar, from May 2015 to August 2016. Data including clinical variables and laboratory parameters, management, and outcomes were evaluated. Multivariate regression analysis was performed to evaluate factors predictive for death at the time of presentation to the hospital., Results: Of the 246 patients with snake envenomation recruited into the study, 225 (92%) survived and 21 (8%) died during hospitalization. The snake species responsible for a bite was identified in 74 (30%) of the patients; the majority of bites were from Russell's vipers (63 patients, 85%). The independent factors predictive for death included 1) duration from bite to arrival at the hospital >1 h (odds ratio [OR]: 9.0, 95% confidence interval [CI]: 1.1-75.2; P=0.04); 2) white blood cell counts >20 ×10 3 cells·μL -1 (OR: 8.9, 95% CI: 2.3-33.7; P=0.001); and 3) the presence of capillary leakage (OR: 3.7, 95% CI: 1.2-11.2; P=0.02). A delay in antivenom administration >4 h increases risk of death (11/21 deaths)., Conclusions: Patients who present with these independent predictive factors should be recognized and provided with early appropriate intervention to reduce the mortality rate among adults with snake envenomation in Myanmar., (Copyright © 2018 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Severe dengue is more prevalent in adults than in children. Our objectives were to determine the clinical presentations of dengue in adults and to identify predictive factors for severe dengue. A retrospective cohort study was performed in adults with dengue, as confirmed by a positive NS1 antigen test result. Patients were classified as with non-severe or severe dengue. A total of 357 patients were enrolled; 45.4% were men, with a median (interquartile range [IQR]) age of 27.9 (21.8-43.5) years. Of all patients, 28.3% had warning signs and 10.6% had severe dengue. Patients with severe dengue were significantly older (35.1 [26.2-50.6] vs. 26.7 [21.7-43.3] years, P = 0.010), immunocompromised (7.9% vs. 0.9%, P = 0.018), and had cough (29% vs. 16%, P = 0.046), hepatomegaly (10.5% vs. 3.1%, P = 0.050), impaired consciousness (5.3% vs. 0%, P = 0.011) or higher (IQR) alanine aminotransferase (ALT) level (151 [57-295] vs. 66 [37-114] U/L, P = 0.008). By multivariate analysis, having cough (odds ratio [OR], 8.07; 95% confidence interval [CI], 2.51-30.16, P = 0.001) and ALT>120 U/L (OR, 3.51; 95% CI, 1.11-11.14, P = 0.033) were predictors of severe dengue. Early recognition of risk variables may be important for healthcare providers to appropriately manage dengue patients.

Background: The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost., Methods: This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts. Part 1 consisted of a randomised, double-blind, placebo-controlled trial done over 18 months. We randomly assigned (2:1) healthy Thai adults aged 18-49 years with a computer generated randomisation sequence (blocks of six) to receive either two intranasal doses (0·25 mL per nostril) of LAIV H5N2 (101 participants) or placebo (51 participants) 21 days apart. For part 2, an open-label trial was done in which previously vaccinated participants (40 from LAIV H5N2 group and 20 placebo) were given one intramuscular dose (0·5 mL) of H5N1 booster vaccine. Participants, investigators, and site-study workers were blinded from randomisation. Immune responses after subsequent immunisation were evaluated using haemagglutination-inhibition and microneutralisation assays and circulating follicular T-helper cells and plasmablast cells were measured in serum and whole blood. The trials are registered with ClinicalTrials.gov, numbers NCT01841918 and NCT02229357., Findings: Between Feb 4, 2013, and Feb 28, 2013, 256 individuals were screened, of whom 152 participants were enrolled in part 1 of this study. LAIV H5N2 vaccine was well tolerated. Viral shedding was detected in only six (6%) of 101 participants in the vaccine group 1 day after the first vaccination and in and two (2%) of 98 participants in the group after the second vaccination. There was no serious adverse event in both groups. 51 (50%) of 101 participants in the vaccine group and 28 (55%) of 51 in the placebo group reported at least one adverse event. 80 (84%) of 95 events in the vaccine group and 32 (78%) of 43 events in the placebo groups were reportedly suspected adverse events, probably related to the vaccine; however, most were mild in nature. After two doses of vaccine, 13 (13%) of 100 participants in the vaccine group had an increase in haemagglutination-inhibition titre of more than four-fold and four (4%) of 100 vaccinees developed a rise in neutralisng antibody titre of more than four-fold. 1 year later, after a booster with an inactivated H5N1 vaccine (part 2), 39 (98%) of 40 participants who had previously been vaccinated with LAIV H5N2 had an increase in haemagglutination-inhibition titre of greater than four-fold as early as day 7 compared with three (15%) of 20 participants in the placebo group. Peak geometric mean titre (GMT) for haemagglutination-inhibition antibodies in the previously LAIV H5N2 vaccinated group (566·89 [95% CI 436·97-735·44]) were significantly higher than among those who previously received placebo (25·49 [11·82-54·96]; p<0·0001). The peak GMT by neutralising antibody assay in the H5N2 vaccinated group (1395·85 [1040·79-1872·03]) was also significantly higher than that observed in the placebo group (17·41 [9·05-33·48]; p<0·0001). Importantly, higher cross-reactive haemagglutination-inhibition antibody titres against H5N1 (clades 1, 2.1.3.2, and 2.3.4) were detected in the LAIV H5N2 experienced group than the naive group (p<0·0001)., Interpretation: Our data suggest that LAIV vaccination induces long-lasting memory immune responses. The limitation of this study was that part 2 was designed as a proof-of-concept study by contrast with part 1., Funding: WHO., (Copyright © This is an Open Access article published under the CC BY 3.0 IGO license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: Snakebite-related acute kidney injury (AKI) is a common community-acquired AKI in tropical countries leading to death and disability. The aims of this study were to (1) determine the occurrence of snakebite-related AKI, (2) assess factors at presentation that are associated with snakebite-related AKI, and (3) determine the outcomes of patients with snakebite-related AKI., Methods: We conducted a prospective observational study of patients with snake envenomation at the three academic tertiary care hospitals in Yangon, Myanmar between March 2015 and June 2016. Patient data including baseline characteristics, clinical and laboratory findings, hospital management, and outcomes were recorded in a case report form. A stepwise multivariate logistic regression analysis using a backward selection method determined independent factors significantly associated with AKI., Results: AKI was observed in 140 patients (54.3%), the majority of whom were AKI stage III (110 patients, 78.6%). AKI occurred at presentation and developed during hospitalization in 88 (62.9%) and 52 patients (37.1%), respectively. Twenty-seven patients died (19.3%), and 69 patients (49.3%) required dialysis. On multivariate logistic regression analysis, (1) snakebites from the Viperidae family (odds ratio [OR]: 9.65, 95% confidence interval [CI]: 2.42-38.44; p = 0.001), (2) WBC >10 × 10 3 cells/μL (OR: 3.55, 95% CI: 1.35-9.34; p = 0.010), (3) overt disseminated intravascular coagulation (OR: 2.23, 95% CI: 1.02-4.89; p = 0.045), (4) serum creatine kinase >500 IU/L (OR: 4.06, 95% CI: 1.71-9.63; p = 0.001), (5) serum sodium <135 mmol/L (OR: 4.37, 95% CI: 2.04-9.38; p < 0.001), (6) presence of microscopic hematuria (OR: 3.60, 95% CI: 1.45-8.91; p = 0.006), and (7) duration from snakebite to receiving antivenom ≥2 h (OR: 3.73, 95% CI: 1.48-9.37; p = 0.005) were independently associated with AKI. Patients bitten by Viperidae with normal renal function who had serum sodium <135 mmol/L had a significantly higher urine sodium-to-creatinine ratio than those with serum sodium ≥135 mmol/L (p < 0.001)., Conclusions: Identifying factors associated with snakebite-related AKI might help clinicians to be aware of snakebite patients who are at risk of AKI, particularly patients who demonstrate renal tubular dysfunction after Viperidae bites.

Background: Currently, there are no biomarkers that can predict the incidence of dengue shock and/or organ failure, although the early identification of risk factors is important in determining appropriate management to reduce mortality. Therefore, we sought to determine the factors associated with dengue shock and/or organ failure and to evaluate the prognostic value of serum procalcitonin (PCT) and peripheral venous lactate (PVL) levels as biomarkers of dengue shock and/or organ failure., Methodology/principal Findings: A prospective observational study was conducted among adults hospitalized for confirmed viral dengue infection at the Hospital for Tropical Diseases in Bangkok, Thailand between October 2013 and July 2015. Data, including baseline characteristics, clinical parameters, laboratory findings, serum PCT and PVL levels, management, and outcomes, were recorded on pre-defined case report forms. Of 160 patients with dengue, 128 (80.0%) patients had dengue without shock or organ failure, whereas 32 (20.0%) patients developed dengue with shock and/or organ failure. Using a stepwise multivariate logistic regression analysis, PCT ≥0.7 ng/mL (odds ratio [OR]: 4.80; 95% confidence interval [CI]: 1.60-14.45; p = 0.005) and PVL ≥2.5 mmol/L (OR: 27.99, 95% CI: 8.47-92.53; p <0.001) were independently associated with dengue shock and/or organ failure. A combination of PCT ≥0.7 ng/mL and PVL ≥2.5 mmol/L provided good prognostic value for predicting dengue shock and/or organ failure, with an area under the receiver operating characteristics curve of 0.83 (95% CI: 0.74-0.92), a sensitivity of 81.2% (95% CI: 63.6-92.8%), and a specificity of 84.4% (95% CI: 76.9-90.2%). Dengue shock patients with non-clearance of PCT and PVL expired during hospitalization., Conclusions/significance: PCT ≥0.7 ng/mL and PVL ≥2.5 mmol/L were independently associated with dengue shock and/or organ failure. The combination of PCT and PVL levels could be used as prognostic biomarkers for the prediction of dengue shock and/or organ failure., Competing Interests: All authors have declared that no competing interests exist in this study. Roche Diagnostics (Thailand) Ltd. provided Elecsys BRAHMS PCT as a gift for this study. All authors have declared that the Roche Diagnostics (Thailand) Ltd. had no role in study design, data collection and/or analysis, the decision to publish, or preparation of the manuscript.

Few previous studies have monitored hemodynamic parameters to determine the physiological process of dengue or examined inferior vena cava (IVC) parameters to assess cardiac preload during the clinical phase of dengue. From January 2013 to July 2015, we prospectively studied 162 hospitalized adults with confirmed dengue viral infection using non-invasive cardiac output monitoring and bedside ultrasonography to determine changes in hemodynamic and IVC parameters and identify the types of circulatory shock that occur in patients with dengue. Of 162 patients with dengue, 17 (10.5%) experienced dengue shock and 145 (89.5%) did not. In patients with shock, the mean arterial pressure was significantly lower on day 6 after fever onset (P = 0.045) and the pulse pressure was significantly lower between days 4 and 7 (P<0.05). The stroke volume index and cardiac index were significantly decreased between days 4 and 15 and between days 5 and 8 after fever onset (P<0.05), respectively. A significant proportion of patients with dengue shock had an IVC diameter <1.5 cm and IVC collapsibility index >50% between days 4 and 5 (P<0.05). Hypovolemic shock was observed in 9 (52.9%) patients and cardiogenic shock in 8 (47.1%), with a median (interquartile range) time to shock onset of 6.0 (5.0-6.5) days after fever onset, which was the median day of defervescence. Intravascular hypovolemia occurred before defervescence, whereas myocardial dysfunction occurred on the day of defervescence until 2 weeks after fever onset. Hypovolemic shock and cardiogenic shock each occurred in approximately half of the patients with dengue shock. Therefore, dynamic measures to estimate changes in hemodynamic parameters and preload should be monitored to ensure adequate fluid therapy among patients with dengue, particularly patients with dengue shock.

Background: Dengue is the most common mosquito-borne viral disease in humans. However, the sensitivities of warning signs (WSs) for identifying severe dengue in adults are low, and the utility of lactate levels for identifying severe dengue in adults has not been verified. Therefore, we aimed to evaluate the diagnostic accuracy of using peripheral venous lactate levels (PVL), as well as WSs established by the World Health Organization, for identifying severe dengue., Methods: We prospectively evaluated individuals hospitalized for dengue who were admitted to the Hospital for Tropical Diseases in Thailand between May 2013 and January 2015. Blood samples to evaluate PVL levels were collected at admission and every 24 h until the patient exhibited a body temperature of <37.8 °C for at least 24 h. Data were recorded on a pre-defined case report form, including baseline characteristics, clinical parameters, and laboratory findings., Results: Among 125 patients with confirmed dengue, 105 (84.0%) patients had non-severe dengue, and 20 (16.0%) patients had severe dengue. The presence of clinical fluid accumulation as a WS provided high sensitivity (75.0%, 95% confidence interval [CI]: 50.9-91.3%) and specificity (90.5%, 95% CI: 83.2-95.3%). The PVL level at admission was used to evaluate its diagnostic value, and receiver operating characteristic curve analysis revealed an area under the curve of 0.84 for identifying severe dengue. At the optimal cutoff value (PVL: 2.5 mmol/L), the sensitivity and specificity were 65.0% (95% CI: 40.8-84.6%) and 96.2% (95% CI: 90.5-99.0%), respectively. A combined biomarker comprising clinical fluid accumulation and/or PVL of ≥2.5 mmol/L provided the maximum diagnostic accuracy for identifying severe dengue, with a sensitivity of 90.0% (95% CI: 68.3-98.8%) and a specificity of 87.6% (95% CI: 79.8-93.2%)., Conclusions: Clinical fluid accumulation and/or PVL may be used as a diagnostic biomarker of severe dengue among adults. This biomarker may facilitate early recognition and timely treatment of patients with severe dengue, which may reduce dengue-related mortality and hospital burden.

Background: Dengue is the most common mosquito-borne viral disease in humans. Recently, there has been an epidemic shift of dengue from mainly affecting children to affecting more adults with increased severity. However, clinical factors associated with severe dengue in adults have varied widely between studies. We aimed to identify the clinical factors associated with the development of severe dengue according to the World Health Organization (WHO)'s 2009 definition., Methods: We conducted a prospective study of adults with dengue admitted to the Hospital for Tropical Diseases in Bangkok, Thailand, from October 2012 to December 2014. Univariate and stepwise multivariate logistic regression analyses were performed., Results: Of the 153 hospitalized patients with confirmed dengue viral infections, 132 (86.3 %) patients had non-severe dengue including dengue without warning signs (7 patients, 5.3 %) and dengue with warning signs (125, 94.7 %). The rest (21, 13.7 %) had severe dengue including severe plasma leakage (16, 76.2 %), severe organ involvement (16, 76.2 %), and severe clinical bleeding (8, 38.1 %). Using stepwise multivariate logistic regression, clinical factors identified as independently associated with the development of severe dengue were: (1) being >40 years old (odds ratio [OR]: 5.215, 95 % confidence interval [CI]: 1.538-17.689), (2) having persistent vomiting (OR: 4.817, CI: 1.375-16.873), (3) having >300 cells per μL of absolute atypical lymphocytes (OR: 3.163, CI: 1.017-9.834), and (4) having lactate levels ≥2.0 mmol/L (OR: 7.340, CI: 2.334-23.087). In addition, increases in lactate and absolute atypical lymphocyte levels corresponded with severe dengue (p < 0.05)., Conclusions: Our study identified several clinical factors independently associated with the development of severe dengue among hospitalized adults with dengue. This can aid in the early recognition and prompt management of at-risk patients to reduce morbidity and mortality.

There are limited data available on the risk factors for multidrug-resistant tuberculosis (MDR-TB). Therefore, we here conducted a retrospective matched case-control study among adults with pulmonary TB who received treatment at the Central Chest Institute of Thailand (CCIT) between January 2007 and December 2013, in order to determine the risk factors associated with MDR-TB among patients with pulmonary TB. We identified 145 patients with pulmonary MDR-TB (cases) and 145 patients with drug-sensitive pulmonary TB (controls). Multivariate analysis identified the independent risk factors for MDR-TB as follows: (1) ≥ 2 episodes of prior pulmonary TB (odds ratio [OR] 39.72, 95% confidence interval (95% CI) 7.86-200.66), (2) duration of illness > 60 days (OR 3.08, 95% CI 1.52-6.22), (3) sputum acid fast bacilli smear 3+ (OR 13.09, 95% CI 4.64-36.91), (4) presence of lung cavities (OR 3.82, 95% CI 1.89-7.73), and (5) presence of pleural effusion (OR 2.75, 95% CI 1.06-7.16). Prior pulmonary TB management with a non-category I regimen (P = 0.012) and having treatment failure or default as treatment outcomes (P = 0.036) were observed in a higher proportion among patients with MDR-TB. Particular characteristics of lung cavities, including the maximum diameter ≥ 30 mm (P < 0.001), the number of cavities ≥ 3 (P = 0.001), bilateral involvement (P < 0.001), and ≥ 2 lung zones involved (P = 0.001) were more commonly observed in patients with MDR-TB. In conclusion, these clinical factors and chest radiographic findings associated with MDR-TB among patients with pulmonary TB may help physicians to provide proper management of cases for prevention of the development and spread of MDR-TB in future.

Malaria is a common parasitic disease in tropical countries, causing one to two million deaths every year. To establish the new biomarker, we analyzed plasma miRNAs obtained from 19 malaria patients and 19 normal subjects, using reverse transcription-based quantitative polymerase chain reaction (RT-qPCR). The average levels of plasma miR-451 and miR-16 were significantly lower in malaria patients, (8.9-fold; p <0.001 and 10.4-fold; p = 0.01, respectively). The levels of other abundant miRNAs in plasma (miR-223, miR-226-3p) did not change significantly in malaria patients. Our data suggest that plasma miR-451 and miR-16 are relevant biomarkers for malaria infection., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In tuberculosis endemic areas, patients with sputum positive for acid-fast bacilli (AFB) are usually diagnosed and treated for pulmonary tuberculosis. The diagnosis of nontuberculous mycobacteria (NTM) lung disease is often ascertained only after lung disease progression occurs, increasing the risk of severe morbidity and mortality. We conducted a matched case-control study among a prospective cohort of 300 patients with newly diagnosed AFB-positive sputum in Thailand during 2010-2012. We compared clinical and laboratory parameters and outcomes among patients with pulmonary tuberculosis, NTM lung disease and NTM colonization. A mycobacterial culture was performed in all patients. Ten patients with NTM lung disease were compared to 50 patients with pulmonary tuberculosis and 10 patients with NTM colonization. The presence of diabetes mellitus or human immunodeficiency virus infection, were associated with NTM lung disease (p = 0.030). Patients with NTM lung disease had a significantly lower body weight prior to treatment (p = 0.021), a higher body weight change from baseline (p = 0.038), and were more likely to have cavitations on chest radiograph (p = 0.033) than those with NTM colonization. In tuberculosis endemic areas, mycobacterial identification should be performed among patients with impaired immune function. NTM lung disease treatment should be considered in patients with NTM sputum isolates who have a history of significant weight loss or cavitations on chest radiography.

Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU) admission of patients with severe falciparum malaria among hospitalized adults in Southeast Asia. A total of 255 patients with falciparum malaria in the Hospital for Tropical Diseases in Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients with severe malaria (cases) and 151 patients with non-severe malaria (controls). Patients with falciparum malaria with following clinical and laboratory characteristics on admission (1) referrals, (2) no prior history of malaria, (3) body temperature of >38.5°C, (4) white blood cell counts >10×10(9)/µL, (5) presence of schizonts in peripheral blood smears, and (6) albumin concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05). Among patients with severe malaria, patients who met ≥3 of the 2010 WHO criteria had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission. Multivariate analysis identified the following as independent associated factors for severe malaria requiring ICU admission; (1) ethnicity of Thai [odds ratio (OR) = 3.601, 95% confidence interval (CI) = 1.011-12.822] or Myanmar [OR = 3.610, 95% CI = 1.138-11.445]; (2) referrals [OR = 3.571, 95% CI = 1.306-9.762]; (3) no prior history of malaria [OR = 5.887, 95% CI = 1.354-25.594]; and (4) albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802-28.759]. Our findings are important for the clinical management of patients with malaria because it can help early identification of patients that could develop severe malaria and require ICU admission. Early identification and the timely initiation of appropriate treatments may well improve the outcomes and reduce the mortality of these patients.

A retrospective study was conducted by reviewing medical records of 323 adult patients hospitalized with dengue infection at the Hospital for Tropical Diseases, Bangkok, Thailand between 2006 and 2010 in order to determine factors associated with severe clinical manifestations of dengue. Of 323 patients, 95 (29.4%) had dengue fever (DF) and 228 (70.6%) had DHF, which were categorized as grade I (67 patients, 29.4%), grade II (62 patients, 27.2%), grade III (95 patients, 41.7%) and grade IV (4 patients, 1.8%) following 1997 WHO definitions. Using the revised 2009 WHO definitions, 233 patients (72.1%) had non-severe dengue infection and 90 patients (27.9%) had severe dengue infection. Of the 233 patients with non-severe dengue infection, 193 (82.8%) were classified as having non-severe dengue infection with warning signs and 40 (17.2%) were classified as having non-severe dengue infection without warning signs. Using stepwise multivariate logistic regression analysis, having a hematocrit >2% above the reference range [odds ratio (OR) 3.235; 95% confidence interval (CI) 1.807-5.793] or having an alanine aminotransferase level >120 IU/l (OR 1.896; 95% CI 1.018-3.531) were associated with having DHF grades II-IV, whereas female gender (OR 2.042; 95% CI 1.143-3.648) or having a mean arterial pressure <80 mmHg (OR 2.275; 95% CI 1.302-3.975) were associated with severe dengue. These findings may help clinicians to determine patients at risk for severe manifestations of dengue infection, which could lead to proper management of these cases.

A retrospective study was conducted by reviewing 459 medical records of adult treatment naive HIV patients who received a fixed dose combination of GPO-VIR-S (stavudine, lamivudine and nevirapine) or GPO-VIR-Z (zidovudine, lamivudine and nevirapine) at Ramathibodi Hospital in Bangkok, Thailand during 2002-2009 following Thai National Treatment Guideline for adults with HIV. The aim of this study was to assess the association between the baseline CD4 cell count and outcome. The median CD4 cell count at baseline, 6, 12 and 102 months were 102 cells/microl, 213 cells/microl, 274 cells/microl and 423 cells/microl. The virologic response (p=0.327), virologic rebound (p=0.626), adverse effects of anti-retroviral therapy (ART) (p=0.976), switching to other ART (p=0.245), occurrence of immune reconstitution inflammatory syndrome (IRIS) (p>0.05) and occurrence of drug resistance (p=0.952) were not significantly associated with baseline CD4 count. The Kaplan-Meier estimate showed the median time (95% CI) to achieve virologic response was 10.4 (9.8-11.0) months and the median time to achieve virologic rebound was 30.0 (21.6-38.4) months after initiation of ART. Analysis showed the median time to achieved virologic response (p=0.401) and virologic rebound (p=0.562) were not significantly associated with the baseline CD4 count. This study shows the outcome after onset of ART did not vary by baseline CD4 cell count.

There are limited data on the application of the RIFLE criteria among patients with severe malaria. This retrospective study was conducted by reviewing 257 medical records of adult hospitalized patients with severe falciparum malaria at the Mae Sot General Hospital, Tak province in the northern part of Thailand. The aims of this study were to determine the incidence of acute renal failure (ARF) in patients with severe falciparum malaria and its association with RRT as well as in-hospital mortality. Using the WHO 2006 criteria, ARF was the second most common complication with incidence of 44.7% (115 patients). The requirement for RRT was 45.2% (52 patients) and the in-hospital mortality was 31.9% (36 patients). Using the RIFLE criteria, 73.9% (190 patients) had acute kidney injury (AKI). The requirement for RRT was 11.6% (5 patients) in patients with RIFLE-I and 44.9% (48 patients) in patients with RIFLE-F. The in-hospital mortality gradually increased with the severity of AKI. The requirement for RRT (P < 0.05) and the in-hospital mortality (P < 0.05) were significantly higher in ARF patients with severe falciparum malaria using both criteria. In conclusion, the RIFLE criteria could be used for diagnosing AKI and predicting outcomes in patients with severe malaria similar to the WHO 2006 criteria.

We conducted a retrospective study of patients with severe falciparum malaria to determine factors associated with malarial acute renal failure (MARF). We reviewed 262 medical records of adults hospitalized with severe falciparum malaria in Thailand from 2004 to 2008. The incidence of MARF in our study population was 44% (115/262); 75% (86/115) of these had MARF on admission and 25% (29/115) developed MARF during hospitalization. The majority of MARF patients presented in a hypercatabolic state (62%, 68/109) and were non-oliguric (48%, 55/115) or oliguric (44%, 51/115). Forty-six percent of MARF patients (53/115) required renal replacement therapy for a median duration of 4.5 days. Patients with MARF had significantly higher complication rates (p < 0.001), longer duration of hospitalization (p < 0.001) and a higher case fatality rate (p = 0.001). Using stepwise multiple logistic regression analysis by backward selection method, factors associated with MARF were advanced age [odds ratios (OR); 95% confidence intervals (CI) 1.037 (1.011-1.063), p = 0.005], being, referred from another hospital [2.876 (1.447-5.714), p = 0.003], an elevated total bilirubin level [(1.168 (1.101-1.241), p < 0.001], requiring inotropic drugs [4.879 (2.255-10.557), p < 0.001] and developing a hospital acquired infection [3.425; 1.406-8.343, p = 0.007]. Clinicians should be aware of these factors associated with MARF.

Hemorrhage is an important complication in dengue infection, but early predictors of clinically significant bleeding are undefined. This study aimed to determine clinical factors on admission associated with Type I bleeding, defined as gastrointestinal bleed, hematuria and menorrhagia, among adult patients with dengue infection. We carried out a retrospective study among 277 patients aged >15 years with serologically-confirmed dengue infection admitted to the Hospital for Tropical Diseases, Bangkok, Thailand during 2006-2009. Female gender (p<0.001), vomiting (p=0.05), severe thrombocytopenia (platelet count < 25 x 10(9)/l; p=0.007), high absolute lymphocyte count (ALC >500; p=0.05) and high aspartate aminotransferase level (AST >200; p=0.02) were significantly associated with hemorrhage on univariate analysis. Multivariate analysis revealed variables associated with bleeding were female gender [odds ratio (OR) 14.5; 95% confidence interval (CI) 0.16-0.56, p<0.001], thrombocytopenia (OR 4.7; 95%CI 0.13-0.9, p=0.03) and ALC >500 (OR 5.7; 95%CI 1.17-4.99, p=0.02). These data identify patients at high risk for developing clinically significant bleeding with dengue infection.

The Leptospira immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) has been recommended for the rapid diagnosis of leptospirosis in endemic areas. We conducted a retrospective case-control study of 218 patients (109 leptospirosis cases confirmed by Leptospira culture and/or microscopic agglutination test and 109 control patients with acute febrile illness) to evaluate the diagnostic accuracy of a commercial IgM ELISA (Panbio) in northeast Thailand. Paired serum samples taken on admission and at least 10 days after the onset of symptoms were tested. Using the cutoff value recommended by the manufacturer (11 Panbio units), sensitivity and specificity of IgM ELISA on paired sera were 90.8% and 55.1%. A receiver operating characteristic curve was used to determine the optimal cutoff value. This was 20 Panbio units, which gave a sensitivity and specificity of 76.1% and 82.6%, respectively, on paired sera. We conclude that using either cutoff value, the accuracy of IgM ELISA is limited in our setting.

Generic fixed dose combination stavudine (d4T), lamivudine (3TC) and nevirapine (NVP), named GPO-VIR is recommended in the HIV treatment guidelines for Thailand. The long term effectiveness and adverse effects of this drug combination for the treatment of HIV were evaluated in an ambispective study at Bamrasnaradura Infectious Diseases Institute, Nonthaburi Province, Thailand from March 2002 to January 2006. A total of 152 adult treatment naive HIV patients who had received at least 12 months of GPO-VIR were enrolled. The median (IQR) CD4 cell count increased from 23 (8-94) cells/microl at baseline to 126 (38-180), 136 (98-189), 199 (141-255) and 334 (243-414) cells/microl at 3, 6, 12 and 24 months (p < 0.001), respectively. The median (IQR) percentage of body weights increased from baseline by 3.0% (0.3-6.3), 6.2% (2.2-9.3), 7.3% (3.9-10.9) and 8.1% (3.4-11.9) at 3, 6, 12 and 24 months, respectively and then remained at a plateau until the end of the 3-year study. The occurrence of new opportunistic infections decreased significantly (p < 0.001) with GPO-VIR treatment. Drug resistance occurred in 5 cases (3.3%) with a median (IQR) time of 18.0 (16.5-32.5) months to occurrence. Adverse effects included hypercholesterolemia (43.2%), lipodystrophy (35.5%), hypertriglyceridemia (25%), hypertension (13.1%), peripheral neuropathy (11.9%), hyperlactatemia (2.6%) and lactic acidosis (1.3%). Thirty-six patients (27%) switched from GPO-VIR to other anti-retroviral drugs regimens due to lipodystrophy. This study showed GPO-VIR had clinical and immunological benefits, but one-third of patients had adverse effects.

Cerebral venous sinus thrombosis has been reported to be associated with various systemic illnesses and infections, including severe malaria. We report here a 43 year-old Thai male presenting with fever and seizures. He was diagnosed as and treated for severe falciparum malaria. After gaining consciousness he developed focal neurological signs and evidence of increased intracranial pressure. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the brain revealed a mid-superior sagittal sinus thrombosis with venous infarction. Investigations for other infections and thrombophilia were negative. The patient denied anticoagulant treatment. The clinical status and radiologic findings improved gradually. Physicians who care for malaria patients need to be aware of this rare complication when a malaria patient presents with focal neurological signs.

In a retrospective study of 1415 patients aged 15 and over, we determined the incidence of clinically important hyponatraemia and hypokalaemia in adults with uncomplicated malaria. On admission, serum concentrations of sodium (135-145 mmol/L) and potassium (3.5-5.0 mmol/L) were found outside these reference ranges in 81% of patients. Severe hypokalaemia (K+ <3.0 mmol/L) and severe hyponatraemia (Na+ <125 mmol/L occurred in 4.4% and 0.6% of the patients, respectively. For hypokalaemia (43%) and hyponatraemia (37%), hypovolaemia, blood urea to creatinine ratio and high serum glucose (>100 mg/dL) were all independent factors (P < 0.001). Other independent predictors for hypokalaemia were Plasmodium vivax infection, female gender; and for hyponatraemia, P. falciparum infection, male gender, concentrations of G-6-PD and serum bicarbonate.

To determine the efficacy, safety and tolerability of an alternative short-course, artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum malaria, we compared Artequick--a fixed-dosed combination of artemisinin (80 mg), piperaquine (400 mg), and primaquine (4 mg), per tablet--with a standard regimen of artesunate-mefloquine. A total of 130 patients were randomly assigned to treatment with an orally administered, once-daily, 3-day regimen of either Artequick (Group A: 3.2 mg/Kg/day of artemisinin, 16 mg/Kg/day of piperaquine, and 0.16 mg/Kg/day of primaquine) or artesunate-mefloquine (Group B: artesunate, 4 mg/Kg/day, with mefloquine, 8 mg/Kg/day). Patients receiving each regimen had a rapid clinical and parasitological response. All treatments were well tolerated, and no serious adverse effects occurred. No significant differences were found in fever- and parasite-clearance times between the two study groups. The 28-day cure rates were similarly high, at 98.5% and 100%, in groups A and B, respectively. We conclude that Artequick was as effective and well tolerated as artesunate-mefloquine and could be used as an alternative treatment for multidrug-resistant Plasmodium falciparum malaria in Southeast Asia.

In acute uncomplicated falciparum malaria, there is a continuum from mild to severe malaria. However, no mathematical system is available to predict uncomplicated falciparum malaria patients turning to severe malaria. This study aimed to devise a simple and reliable model of Malaria Severity Prognostic Score (MSPS). The study was performed in adult patients with acute uncomplicated falciparum malaria admitted to the Bangkok Hospital for Tropical Diseases between 2000 and 2005. Total 38 initial clinical parameters were identified to predict the usual recovery or deterioration to severe malaria. The stepwise multiple discriminant analysis was performed to get a linear discriminant equation. The results showed that 4.3% of study patients turned to severe malaria. The MSPS = 4.38 (schizontemia) + 1.62 (gametocytemia) + 1.17 (dehydration) + 0.14 (overweight by body mass index; BMI) + 0.05 (initial pulse rate) + 0.04 (duration of fever before admission) - 0.50 (past history of malaria in last 1 year) - 0.48 (initial serum albumin) - 5.66. Based on the validation study in other malaria patients, the sensitivity and specificity were 88.8% and 88.4%, respectively. We conclude that the MSPS is a simple screening tool for predicting uncomplicated falciparum malaria patients turning to severe malaria. However, the MSPS may need revalidation in different geographical areas before utilized at specific places.

Background: Patients on dialysis are at high risk of acquiring viral hepatitis infections. However, there were only few data from Thailand. The aim of the present study was to assess the prevalence, incidence and associated risk factors of viral hepatitis infections among dialysis patients., Methods: A retrospective study was conducted to evaluate 5179 medical records of dialysis patients from the Thailand Renal Replacement Therapy Registry., Results: In 2002, the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were 6.3% (n = 2454) and 4.8% (n = 2167), respectively. HBV and HCV seroprevalence became 6.5% (n = 2585) and 4.3% (n = 2399) in 2003. The incidence of HBV and HCV infections were 1.5 and 2.4 cases per 1000 patient-years, respectively. Logistic regression analysis showed that age and gender were significant risk factors for HBV infection, but not for HCV infection., Conclusion: In Thailand, it was not uncommon for dialysis patients to acquire viral hepatitis infections. However, our prevalence is similar to reports from some other South-East Asian countries.

Chloroquine remains the drug of choice for the treatment of vivax malaria in Thailand. Mixed infections of falciparum and vivax malaria are also common in South-East Asia. Laboratory confirmation of malaria species is not generally available. This study aimed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs. From June 2004 to May 2005, 98 patients with Plasmodium vivax were randomly treated with either artemether-lumefantrine (n = 47) or chloroquine (n = 51). Both treatments were followed by 15 mg of primaquine over 14 days. Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups. The cure rate was 97.4% for the artemether-lumefantrine treated group and 100% for the chloroquine treated group. We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated, as effective as chloroquine and primaquine, and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out.

Liver function tests were performed in 61 vivax, 54 malariae and 15 ovale malaria patients who were admitted to Bangkok Hospital for Tropical Diseases between 2001 and 2004. The objective of the study was to evaluate changes in hepatic biochemical indices before and after treatment with artemisinin derivatives. On admission and prior to treatment, hepatic dysfunction was found among the 3 groups. Serum liver function tests and physical examinations were performed weekly during the 28-day follow-up period. Initially elevated serum bilirubin and diminished albumin returned to normal within 2 weeks of treatment. Serum alkaline phosphatase and aminotransferases returned to within normal limits within 3 weeks. We conclude that patients with Plasmodium vivax, P. malariae and P. ovale infections had slightly elevated serum bilirubin, aminotransferase and alkaline phosphatase levels, and hypoalbuminemia. These minor abnormalities returned to normal within a few weeks after treatment with therapies based on artemisinin derivatives.

We conducted a study to compare the safety and tolerability of anti-relapse drugs elubaquine and primaquine against Plasmodium vivax malaria. After standard therapy with chloroquine, 30 mg/kg given over 3 days, 141 patients with P. vivax infection were randomized to receive primaquine or elubaquine. The 2 treatment regimens were primaquine 30 mg once daily for 7 days (group A, n = 71), and elubaquine 25 mg once daily for 7 days (group B, n = 70). All patients cleared parasitemia within 7 days after chloroquine treatment. Among patients treated with primaquine, one patient relapsed on day 26; no relapse occurred with elubaquine treatement. Both drugs were well tolerated. Adverse effects occurred only in patients with G6PD deficiency who were treated with primaquine (group A, n = 4), whose mean hematocrit fell significantly on days 7, 8 and 9 (P = 0.015, 0.027, and 0.048, respectively). No significant change in hematocrit was observed in patients with G6PD deficiency who were treated with elubaquine (group B, n = 3) or in patients with normal G6PD. In conclusion, elubaquine, as anti-relapse therapy for P. vivax malaria, was as safe and well tolerated as primaquine and did not cause clinically significant hemolysis.

Peripheral gangrene, characterized by distal ischemia of the extremities, is a rare complication in patients with falciparum malaria. Patients with this complication have generally undergone early amputation of the affected areas. In this report, we describe 3 adult Thai patients presented at the Hospital for Tropical Diseases, Bangkok, with high grade of fever ranged 6-9 days, jaundice, acute renal failure, respiratory failure, alteration of consciousness and shock. Two patients had gangrene developed at the lower extremities on day 1 of hospitalization and 1 patient had gangrene developed on day 3. Blood smears revealed hyperparasitemia with Plasmodium falciparum. These patients were diagnosed as having severe malaria with peripheral gangrene. The resolution of gangrene was successfully achieved by treatment with artesunate and conservative treatment in 2 of 3 cases.