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Background: Internationally established guidelines mention pharmacological prophylaxis for all hospitalized COVID-19 patients. However, there are concerns regarding the efficacy and safety of anticoagulants. This study investigated the associations between thrombosis/bleeding risk scores and clinical outcomes. Methods: We conducted a retrospective review of adult patients admitted to two hospitals between 2021 and 2022. We analyzed clinical data, laboratory results, low molecular weight heparin (LMWH) use, thrombosis, bleeding, and 30-day survival. Results: Of the 160 patients, 69.4% were female, and the median age was 59 years. The rates of thrombotic complications and mortality were 12.5% and 36.3%, respectively. LMWH prophylaxis was administered to 73 of the patients (45.6%). The patients with high Padua prediction scores (PPS) and high IMPROVEVTE scores had a significantly higher risk of venous thromboembolism (VTE) compared to those with low scores (30.8% vs. 9.0%, p = 0.006 and 25.6% vs. 7.7%, p = 0.006). Similarly, elevated IMPROVEVTE and IMPROVEBRS scores were associated with increased mortality (hazard ratios of 7.49 and 6.27, respectively; p < 0.001). Interestingly, LMWH use was not associated with a decreased incidence of VTE when stratified by risk groups. Conclusions: this study suggests that COVID-19 patients with high thrombosis and bleeding risk scores have a higher mortality rate. [ABSTRACT FROM AUTHOR]

Objective: Mistake in diagnosis. Background: A rapid investigation of dengue viral infection is needed for physicians who manage patients with suspected dengue infection. The nonstructural protein 1 (NS1) test kit is commonly used to diagnose patients with acute febrile illness in dengue-endemic countries, although this test kit can yield false-positive results. The Dengue NS1 test kit mostly relies on cross-reaction among febrile illness patients with other viral infections rather than malignancies. Case Report: A 52-year-old male patient presented with 3 days of fever, intermittent gum bleeding, weight loss, and mucocutaneous bleeding. He was transferred to a second hospital with acute febrile illness. Both dengue NS1 antigen test kits were positive from the 2 hospitals where he was previously treated. Fever and cytopenia persisted, and then the dengue RT-PCR test was performed to establish the cause of illness. A peripheral blood smear was reviewed and showed blast cells. A bone marrow examination was done to test for the compatibility of lymphoblastic leukemia. The flow cytometry test showed B cells ALL with Philadelphia-positive chromosome. Finally, the result of the dengue RT-PCR test was negative. Conclusions: Our patient presented with fever and viral-like illness, but he was finally diagnosed with Ph+ ALL. We demonstrated the first case of false-positive dengue NS1 antigen in a Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) patient. Moreover, we reviewed the literature to gather information on false-positive results using the dengue NS1 test kit. The dengue NS1 test kit is useful and produces reliable clinical findings, especially in patients with hematological malignancies. [ABSTRACT FROM AUTHOR]

Abtract 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. [ABSTRACT FROM AUTHOR]

Background: It was hypothesized that glucose-6-phosphate dehydrogenase (G6PD) deficiency confers a protective effect against malaria infection, however, safety concerns have been raised regarding haemolytic toxicity caused by radical cure with 8-aminoquinolines in G6PD-deficient individuals. Malaria elimination and control are also complicated by the high prevalence of G6PD deficiency in malaria-endemic areas. Hence, accurate identification of G6PD deficiency is required to identify those who are eligible for malaria treatment using 8-aminoquinolines. Methods: The prevalence of G6PD deficiency among 408 Thai participants diagnosed with malaria by microscopy (71), and malaria-negative controls (337), was assessed using a phenotypic test based on water-soluble tetrazolium salts. High-resolution melting (HRM) curve analysis was developed from a previous study to enable the detection of 15 common missense, synonymous and intronic G6PD mutations in Asian populations. The identified mutations were subjected to biochemical and structural characterisation to understand the molecular mechanisms underlying enzyme deficiency. Results: Based on phenotypic testing, the prevalence of G6PD deficiency (< 30% activity) was 6.13% (25/408) and intermediate deficiency (30–70% activity) was found in 15.20% (62/408) of participants. Several G6PD genotypes with newly discovered double missense variants were identified by HRM assays, including G6PD Gaohe + Viangchan, G6PD Valladolid + Viangchan and G6PD Canton + Viangchan. A significantly high frequency of synonymous (c.1311C>T) and intronic (c.1365-13T>C and c.486-34delT) mutations was detected with intermediate to normal enzyme activity. The double missense mutations were less catalytically active than their corresponding single missense mutations, resulting in severe enzyme deficiency. While the mutations had a minor effect on binding affinity, structural instability was a key contributor to the enzyme deficiency observed in G6PD-deficient individuals. Conclusions: With varying degrees of enzyme deficiency, G6PD genotyping can be used as a complement to phenotypic screening to identify those who are eligible for 8-aminoquinolines. The information gained from this study could be useful for management and treatment of malaria, as well as for the prevention of unanticipated reactions to certain medications and foods in the studied population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Emergence and rapid spread of influenza H1N1 virus prompted health authorities to develop a safe and effective influenza vaccine for domestic use. The Thai Government Pharmaceutical Organization (GPO) with technical support from Russia through WHO had prepared a pandemic live attenuated vaccine (PLAIV) using ca-ts attenuated candidate strain A/17/CA/2009/38 (H1N1) for Thais. Methods: Each participant received two doses of intranasal H1N1 vaccine or placebo 21 days apart. All were followed up at 7, 21, 42 and 60 days after first immunization. Blood was drawn for hemagglutination inhibition (HAI) assay from all participants at days 1, 21, 42, and 60 after first immunization. A subset of 40 participants aged 19–49 years was randomly selected for nasal washing at days 1, 21, 42, and 60 to assess IgA using direct enzyme-linked immunosorbent assay (ELISA) along with serum HAI and microneutralization (MN) assay determination. Results: A total of 363 subjects aged 12–75 years were randomized into 2 groups (271 vaccinees:92 placebos). Almost all AEs were mild to moderate. Local reactions were stuffy nose (22.3%), runny nose (25.1%), scratchy throat (27.2%) and sore throat (19.3%). Systemic reactions included headache (21.7%), myalgia (13.8%), fatigue (16.8%) and postnasal drip (19.9%). On day 60, HAI seroconversion rates for vaccine:placebo group were 30.3:6.0 for ITT and 29.4:5.1 for PP analysis. Children showed highest seroconversion rate at 44, but it decreased to 39.4 when all 3 assays (HAI, MN assay and ELISA) from subgroup analysis were considered. Conclusion: The vaccine candidate is safe. The use of more than one assay may be needed for evaluation of immune response because live attenuated vaccines could effectively induce different kinds of responses. Different individuals could also mount different kinds of immune response, even to the same antigen. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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 R2) of 0.92 at red blood cell distribution width (RDW) ≤18, but Pearson's R2 decreased to 0.78 at RDW >18. The Hct calculated from the three-fold conversion method and from the analyzer had a Pearson's R2 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. [ABSTRACT FROM AUTHOR]

Three patients diagnosed with severe COVID‐19 pneumonia received treatment with hydroxychloroquine combined with lopinavir, ritonavir, and favipiravir. Two patients diagnosed early, received tocilizumab when the pneumonia became severe and survived. The thrid patient was diagnosed late and received tocilizumab when the disease progressed to acute respiratory distress syndrome, and died. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 >10×109/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. [ABSTRACT FROM AUTHOR]

Circulating microRNAs (miRNAs) are useful biomarkers of hemolysis. Since blood cells are the main origins of circulating miRNAs, we evaluated blood cell-related pre-analytical modification of the miRNA signatures during blood drawing and serum processing. The levels of miRNA before and after ex vivo blood drawing were analyzed with the reverse transcriptase-based polymerase chain reaction method. Furthermore, the changes of miRNA signatures caused by different time-lag between blood drawing and serum preparation by 24 h were evaluated. Finally, we compared the miRNA levels between leftover samples and samples of hemolytic diseases. Blood drawing procedure induced increments of red blood cell (RBC)-related miRNAs (miR-451a, miR-486) about 2-fold. One hour standing of blood samples before serum separation induced almost the same increases in RBC-related miRNAs. To test the clinical usefulness of miR-451a as a biomarker of hemolytic diseases, we analyzed miRNAs of samples from 10 normal subjects, 30 leftover samples in the clinical laboratory, and 20 samples from patients with hemolytic diseases. Serum miR-451a significantly increased in patients with hemolytic anemia more than the levels of pre-analytical modification. In conclusion, the pre-analytical modification of serum miRNAs did not disturb the usefulness of RBC-derived miRNAs as biomarkers of hemolytic diseases. [ABSTRACT FROM AUTHOR]

• The first report comparing the stability of three different G6PD sample types (normal controls, heterozygous females and deficient individuals) under different storage conditions. • Specimens with normal G6PD activity, both EDTA blood and DBS, can be stored at −20 °C for up to 1 year under controlled conditions. • Blood samples from heterozygous females can be stored as DBS at −20 °C under controlled conditions for up to 1 year. • G6PD activity in G6PD deficient samples significantly decreased over 1 year of storage. Accurate measurement of glucose-6-phosphate dehydrogenase (G6PD) activity is critical for malaria treatment as misclassification of G6PD deficiency could cause serious harm to patients. G6PD activity should be assessed in blood samples on the day of collection. Otherwise, specimens should be stored under suitable conditions to prevent loss of G6PD activity. Here, we assessed stability and integrity of G6PD testing in samples from normal controls, heterozygous females, and G6PD deficient individuals using water-soluble tetrazolium salts (WST-8) assay. Specimens were stored as ethylenediaminetetraacetic acid (EDTA) whole blood and dried blood spots (DBS) at various temperatures (37 °C, room temperature, 4 °C and -20 °C) and under different humidity conditions (with and without desiccant). G6PD normal samples were stable for up to 1 year when stored at -20 °C under controlled conditions, with 85% and 91% G6PD activity in EDTA whole blood and DBS in the presence of desiccant, respectively. Specimens from heterozygous females showed greater G6PD activity when stored as DBS, with 85% enzyme activity after 1 year of storage at -20 °C under controlled conditions in the presence of desiccant. G6PD deficient samples rapidly lost enzyme activity in all storage conditions tested. However, the reduction in G6PD enzyme activity in G6PD deficient samples did not interfere with G6PD classification. Samples stored under suitable conditions for G6PD testing will allow accurate measurement of enzyme activity, prevent misclassification of G6PD deficiency and enable safe and effective use of antimalarial drugs such as primaquine and tafenoquine. [ABSTRACT FROM AUTHOR]