Comparison of antibody responses before and after booster doses with the Pfizer-BioNTech or Oxford-AstraZeneca vaccines in healthcare workers in Thailand.

The severe acute respiratory syndrome 2 (SARS-CoV-2) has spread rapidly worldwide, not only causing significant morbidity and mortality but also dramatically increasing health care spending. To manage this in Thailand, healthcare workers first received two doses of the CoronaVac vaccine followed by a booster vaccine with either BNT162b2 vaccine (Pfizer-BioNTech; PZ) or ChAdOx1 nCoV-19 vaccine (Oxford-AstraZeneca; AZ). Given that the difference in anti-SARS-CoV-2 levels following vaccination may vary depending on the vaccine and on demographic characteristics, we measured the antibody response after the second CoronaVac dose and after the booster with either the PZ or AZ vaccine. Our results in 473 healthcare workers show that the variation in antibody response to the full CoronaVac dose depends on demographic characteristics such as age, gender, body mass index, and underlying disease. After receiving a booster dose, anti-SARS-CoV-2 levels were significantly higher in participants who received the PZ vaccine than in people who received the AZ vaccine. Overall, however, receiving a booster dose of either the PZ or AZ vaccine promoted strong antibody responses, even in the old and those with obesity or diabetes mellitus. In conclusion, our results support the use of a booster vaccination program after full vaccination with the CoronaVac vaccine. This approach effectively enhances immunity against SARS-CoV-2, especially in clinically vulnerable groups and healthcare workers.

Vascular leakage in dengue hemorrhagic Fever is associated with dengue infected monocytes, monocyte activation/exhaustion, and cytokines production.

The vascular leakage was shown by the increment of hematocrit (Hct), dengue viral infected monocyte, monocyte status, and cytokines production in patients infected with dengue virus. Dengue viral antigens were demonstrated in monocytes (CD14+) from peripheral blood mononuclear cells. The increased levels of Hct, interleukin- (IL-) 10, and tumor necrosis factor-alpha (TNF-α) were detected in dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) patients as compared with other febrile illnesses (OFIs). The highest levels of Hct and IL-10 were detected in DSS patients as compared with other groups (P < 0.05) especially on one day before and after defervescence. The unstimulated and lipopolysaccharide- (LPS-) stimulated monocytes from DSS patients showed the significantly decreased of intracellular IL-1ß and TNF-α. In addition, the lowest level of mean fluorescence intensity (MFI) of CD11b expression on monocytes surface in DSS patients was also demonstrated. Furthermore, the negative correlations between IL-10 levels and intracellular IL-1ß and MFI of CD11b expression in unstimulated and LPS-stimulated monocytes were also detected. Nevertheless, not only were the relationships between the prominent IL-10 and the suppression of intracellular monocyte secretion, namely, IL-1ß, TNF-α, demonstrated but also the effect of vascular leakage was observed.

Tumour necrosis factor gene polymorphism in dengue infection: association with risk of bleeding.

BACKGROUND: A single nucleotide polymorphism located at the promoter -308A of tumour necrosis factor-alpha (TNF-α) gene may affect transcription and increase cytokine production, leading to the severe manifestation of dengue virus infection. AIM: To study the association of the TNF-α -308A allele and the severity of patients with dengue infection. METHODS: 112 patients suspected of having dengue infection and 106 normal controls were enrolled in the study. Mean (SD) age was 10.4 (3.6) years. In all, 19 and 82 patients were diagnosed with dengue fever (DF) and dengue haemorrhagic fever (DHF), respectively, while 11 were diagnosed with other febrile illnesses (OFIs). They were tested for the polymorphisms at the promoter -308 position of the TNF-α gene and their TNF-α levels were measured. RESULTS: In the patients with dengue infection (14/202, 6.9%) with OFIs (1/22, 4.5%) and in normal controls (17/212, 8.0%), the frequency of the TNF-α -308A allele was not significantly different. Moreover, no statistically significant difference was found in patients with various clinical manifestations of dengue infection involving DF (5.3%, 2/38), DHF grade I (5.0%, 2/40), DHF grade II (9.5%, 4/42), DHF grade III (2.5%, 1/40) and DHF grade IV (11.9%, 5/42). However, patients with dengue infection and significant bleeding manifestations, apart from petechiae and ecchymosis, tended to have a higher frequency of the TNF-α -308A allele (11.8%, 9/76) than those without significant bleeding manifestations (5/126, 4.0%) (P = 0.056). The levels of TNF-α were additionally measured in 67 patients but the results failed to demonstrate a functional effect in the transcriptional rate of the TNF-α -308A allele. CONCLUSION: In patients with dengue infection there is an association between the TNF-α -308A allele and the risk of bleeding. The test may be used as one of the predictors of the severity of dengue infection.

Alteration of cytokines and chemokines during febrile episodes associated with endothelial cell damage and plasma leakage in dengue hemorrhagic fever.

BACKGROUND: The leakage of plasma during febrile episodes in dengue-infected patients is a severe condition leading to dengue shock syndrome. Alteration of cytokines/chemokines is suspected to be a major cause of endothelial cell damage in these patients. The study was designed to demonstrate the alteration of cytokines and chemokines in dengue-infected patients during febrile episodes. METHODS: The blood samples from 164 patients with dengue fever, dengue hemorrhagic fever and other febrile illnesses were collected daily from the day of hospitalization until discharge and also in the convalescent stage. The levels of cytokines/chemokines were determined using a sandwich chemiluminescent immunoassay, and the hematological parameters were examined by the ADVIA hematological analyzer. RESULTS: Two patterns of cytokines/chemokines alteration were detected at different time points during the febrile episode. The increased factors included interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, interferon-γ and monocyte chemoattractant protein-1 whereas IL-1ß, IL-2, vascular endothelial growth factor and epidermal growth factor were decreased. Several cytokines were correlated with disease severity especially in dengue hemorrhagic fever/dengue shock syndrome patients. CONCLUSIONS: The alteration in the cytokine/chemokine kinetics during a febrile episode can be used as a predictor for severe dengue infection. The increased and decreased levels at different time points can indicate the disease progression related to vascular leakage in dengue hemorrhagic fever/dengue shock syndrome patients.

Laboratory predictors of dengue shock syndrome during the febrile stage.

The clinical manifestations of dengue hemorrhagic fever (DHF) consist of three successive stages: febrile, toxic and convalescent. The toxic stage is the critical period, which may manifestas circulatory disturbance or even profound shock in some patients. We attempted to determine predictors for the risk of dengue shock syndrome (DSS) during the febrile stage. One hundred one children with acute febrile illness were enrolled in the study, with a mean age of 11 years old. The diagnosis included dengue fever (DF) 21 cases, DHF grade I 30 cases, DHF grade II 33 cases, DHF grades III and IV 10 cases; children with other febrile illnesses (OFI) 7 cases were used as controls. Complete blood counts, coagulation tests, von Willebrand factor antigens (VWF:Ag) and ristocetin cofactor activity (VWF:Rcof) were determined daily during hospitalization and 2-4 weeks after discharge from the hospital. The results revealed any one of the following abnormal laboratory findings during the febrile stage served as a predictor for risk of DSS: increase in hematocrit > 25%, a platelet count < 40,000/microl, an activated partial thromboplastin time >44 seconds, a prothrombin time >14 seconds, a thrombin time >16 seconds or a VWF:Ag or VWF:Rcof > 210%. The relative risk ranged from 4.8 to 10.9. Simple laboratory investigations with complete blood count, coagulation test or the more sophisticated von Willebrand factor, are helpful in predicting the risk for DSS during the febrile stage.

Early diagnosis of dengue virus infection by detection of dengue viral antigen in peripheral blood mononuclear cell.

BACKGROUND: An essential requirement related to treatment of dengue-infected patients is a rapid and accurate detection of dengue virus during febrile stage of the disease. OBJECTIVE: The study examined using direct immunofluorescence staining the presence of dengue viral antigen in peripheral blood mononuclear cells (PBMCs). METHODS: Four hundred forty-five blood samples from 164 patients with dengue fever, dengue hemorrhagic fever, and other febrile illnesses were collected daily from the day of admission until discharge and also at convalescent stage. Blood smear was stained with fluorescein isothiocyanate-conjugated polyvalent dengue antiserum and examined under a fluorescent microscope. Dengue infection was confirmed by virus isolation and/or dengue-specific IgM and IgG enzyme linked immunosorbent assay test. RESULTS: Dengue viral antigens were found in most PBMC samples of dengue infected patients collected on the day before defervescence and continued until 2 to 3 days afterward. The number of dengue viral antigen positive PBMCs was highest in patients with dengue shock syndrome. Sensitivity and specificity of this method during the febrile stage was 93.8% (95% confidence interval: 88.8%-98.9%) and 100%, respectively. The positive and negative predictive values were 100% and 69.0%, respectively. CONCLUSION: Detection of dengue viral antigen in direct PBMC smear provides a useful and rapid technique for early diagnosis of dengue virus infection.

A study of seven rule-based algorithms for the interpretation of HIV-1 genotypic resistance data in Thailand.

Since the free therapy program was started by the Thai government, the number of patients infected by HIV-1 with access to antiretroviral drugs has increased. The selection of effective interpretation algorithms for antiretroviral drug resistance has become even more important for clinical management. In this retrospective study, the level of agreement was evaluated in 721 antiretroviral-therapy failing HIV-1 subjects. Regarding genetic diversity, about 89% was recognized as non-B variants (CRF01_AE). The level of complete concordant interpretation score in all seven algorithms was recognized in non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) (67%), but not in nucleoside reverse transcriptase inhibitors (NRTIs) (52%). Over 10% of the major discordance score with TRUGENE was revealed in didanosine (Agence Nationale de Recherches sur le SIDA[ANRS]; Detroit Medical Centre [DMC]), abacavir (ANRS; Centre Hospitalier de Luxembourg [CHL]), and also with delavirdine, indinavir and amprenavir (Grupo de Aconselhamento Virológico [GAV]). A good to excellent agreement range of kappa scores was detected for most antiretroviral drugs. However, poor agreement with the TRUGENE system (k<0.40) was seen in the ANRS system with didanosine, abacavir and lopinavir; GAV system in indinavir and amprenavir; and DMC system in ritonavir. These might be an option for resource limited countries when selecting the use of a low cost or free algorithm interpretation, which has excellent agreement as the U.S. Food and Drug Administration (FDA)-approved TRUGENE commercial system.

Elevated soluble thrombomodulin in the febrile stage related to patients at risk for dengue shock syndrome.

BACKGROUND: Children with dengue hemorrhagic fever (DHF) are at risk to develop dengue shock syndrome (DSS) for which neither marker has been demonstrated. OBJECTIVE: The study was designed to investigate the markers of vascular endothelial cell injuries and dysfunction that might be used as early predictors of the subsequent manifestation of DSS. METHODS: The blood samples from 111 patients with dengue fever, DHF and other febrile illness (OFI) were collected daily from the day of admission until discharge and at convalescent stage. The sample from the day of defervescence was defined as day 0, 1 day before defervescence was defined as day -1 and so on. Also, 1 day after defervescence was defined as day +1 and so on. RESULTS: Increased soluble thrombomodulin (sTM) was demonstrated in dengue-infected patients via an enzyme-linked immunosorbent assay. Patients with DSS (DHF grades III and IV) had higher concentrations of sTM than those with dengue fever, DHF grade I, II and OFIs from day -3 until day +2. Increased circulating endothelial cells were detected from day 0 until day +2 in DSS patients as compared with other groups. In addition, increased soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and soluble E-selectin were also found in dengue virus-infected patients as compared with OFIs. CONCLUSION: Blood sTM may be useful as an early predictor of DSS in dengue infected patients in the febrile stage. However, a further evaluation in a large prospective series is needed.