Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hemodynamics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.

: Exuberant inflammation manifesting as a “cytokine storm” has been suggested as a central feature in the pathogenesis of severe coronavirus disease 2019 (COVID-19). This study investigated two prognostic biomarkers, the high mobility group box 1 (HMGB1) and interleukin-6 (IL-6), in patients with severe COVID-19 at the time of admission in the intensive care unit (ICU). Of 60 ICU patients with COVID-19 enrolled and analyzed in this prospective cohort study, 48 patients (80%) were alive at ICU discharge. HMGB1 and IL-6 plasma levels at ICU admission were elevated compared with a healthy control, both in ICU nonsurvivors and ICU survivors. HMGB1 and IL-6 plasma levels were higher in patients with a higher Sequential Organ Failure Assessment (SOFA) score (> 10), and the presence of septic shock or acute kidney injury. HMGB1 and IL-6 plasma levels were also higher in patients with a poor oxygenation status (PaO₂/FiO₂ < 150 mm Hg) and a longer duration of ventilation (> 7 days). Plasma HMGB1 and IL-6 levels at ICU admission also correlated with other prognostic markers, including the maximum neutrophil/lymphocyte ratio, D-dimer levels, and C-reactive protein levels. Plasma HMGB1 and IL-6 levels at ICU admission predicted ICU mortality with comparable accuracy to the SOFA score and the COVID-GRAM risk score. Higher HMGB1 and IL-6 were not independently associated with ICU mortality after adjustment for age, gender, and comorbidities in multivariate analysis models. In conclusion, plasma HMGB1 and IL6 at ICU admission may serve as prognostic biomarkers in critically ill COVID-19 patients.

In recent decades, chikungunya virus (CHIKV) has become geographically widespread. In 2004, the CHIKV East/Central/South African (ECSA) genotype moved from Africa to Indian ocean islands and India followed by a large epidemic in Southeast Asia. In 2013, the CHIKV Asian genotype drove an outbreak in the Americas. Since 2016, CHIKV has re-emerged in the Indian subcontinent and Southeast Asia. In the present study, CHIKVs were obtained from Bangladesh in 2017 and Thailand in 2019, and their nearly full genomes were sequenced. Phylogenetic analysis revealed that the recent CHIKVs were of Indian Ocean Lineage (IOL) of genotype ECSA, similar to the previous outbreak. However, these CHIKVs were all clustered into a new distinct sub-lineage apart from the past IOL CHIKVs, and they lacked an alanine-to-valine substitution at position 226 of the E1 envelope glycoprotein, which enhances CHIKV replication in Aedes albopictus. Instead, all the re-emerged CHIKVs possessed mutations of lysine-to-glutamic acid at position 211 of E1 and valine-to-alanine at position 264 of E2. Molecular clock analysis suggested that the new sub-lineage CHIKV was introduced to Bangladesh around late 2015 and Thailand in early 2017. These results suggest that re-emerged CHIKVs have acquired different adaptations than the previous CHIKVs.

Severe dengue cases have been increasingly reported in Thailand, and the under-reporting of acute kidney injury (AKI) in cases of dengue viral infection has become an obstacle in obtaining an accurate description of the true nature and epidemiology of AKI. Because AKI may lead to patient morbidity and mortality, an early diagnosis is important in preventing its onset in dengue patients. This study aimed to determine the prevalence, clinical and laboratory characteristics, and associated factors of AKI among adult dengue patients. This retrospective study reviewed admission data from the medical records of adult dengue patients admitted to the Bangkok Hospital for Tropical Diseases between January 2012 and November 2017 and stratified these patients into AKI and non-AKI groups using the Kidney Disease Improving Global Outcomes criteria (KDIGO). A total of 1,484 patients were included in the study, with 71 categorized into the AKI group. The prevalence of AKI was 4.8%. In the AKI group, the predominant age range was 18–40 years (71.8%), with a female to male ratio of 1:2.7. These patients showed significantly (P < 0.05) higher proportions of altered consciousness, dyspnea, low mean arterial blood pressure, high-grade fever, major bleeding, severe thrombocytopenia, hypoalbuminemia, severe transaminitis, coagulopathy, metabolic acidosis, rhabdomyolysis, proteinuria, hematuria, and pyuria. Our study established that older age, male sex, diabetes mellitus, obesity, severe dengue, and coexisting bacterial infection were significant associated factors for AKI in dengue by multivariate analysis. A total of 10 (14.1%) patients with AKI received dialysis, among which 9 (12.7%) patients from the AKI group died. Our findings suggest that an awareness of AKI, its early diagnosis, and evaluation of clinical and laboratory characteristics of dengue patients will help clinicians to initiate appropriate therapy for dengue-associated AKI.

: The chikungunya virus is an arthritogenic arbovirus that has re-emerged in many tropical and subtropical regions, causing explosive outbreaks. This re-emergence is due to a genomic polymorphism that has increased the vector susceptibility of the virus. The majority of those infected with chikungunya virus exhibit symptoms of fever, rash, and debilitating polyarthralgia or arthritis. Symptoms can persist for weeks, and patients can relapse months later. Fatalities are rare, but individuals of extreme age can develop severe infection. Here, we describe the 2019 outbreak, the second-largest since the virus re-emerged in the Maldives after the 2004 Indian Ocean epidemic, in which a total of 1,470 cases were reported to the Health Ministry. Sixty-seven patients presenting at the main referral tertiary care hospital in the Maldives capital with acute undifferentiated illness were recruited following a negative dengue serology. A novel point-of-care antigen kit was used to screen suspected cases, 50 of which were subsequently confirmed using real-time reverse transcription–polymerase chain reaction. We describe the genotype and polymorphism of Maldives chikungunya virus using phylogenetic analysis. All isolates were consistent with the East Central South African genotype of the Indian Ocean lineage, with a specific E1-K211E mutation. In addition, we explored the clinical and laboratory manifestations of acute chikungunya in children and adults, of which severe infection was found in some children, whereas arthritis primarily occurred in adults. Arthritides in adults occurred irrespective of underlying comorbidities and were associated with the degree of viremia.

The hallmark of severe dengue infection is the increased vascular permeability and hemodynamic alteration that might be associated with an intestinal permeability defect. However, the mechanisms underlying the gastrointestinal-related symptoms of dengue are not well characterized. A prospective observational study was conducted on patients with dengue who were categorized according to: (i) febrile versus critical phase and (ii) hospitalized patients with versus without the warning signs to evaluate the gut barrier using lactulose-to-mannitol excretion ratio (LEMR). Serum endotoxins, (1→3)-β-D-glucan (BG), and inflammatory parameters were measured. A total of 48 and 38 patients were enrolled in febrile illness and critical phase, respectively, while 22 and 64 patients presented with or without the warning signs, respectively. At enrollment, a positive LEMR test was found in 20 patients (91%) with warning signs, regardless of phase of infection. Likewise, serum endotoxins and BG, the indirect biomarkers for leaky gut, prominently increased in patients who developed severe dengue when compared with the non-severe dengue (endotoxins, 399.1 versus 143.4 pg/mL (p < 0.0001); BG, 123 versus 73.8 pg/mL (p = 0.016)). Modest impaired intestinal permeability occurred in dengue patients, particularly those with warning signs, and were associated with endotoxemia and elevated BG. Thus, leaky gut syndrome might be associated with severity of dengue infection.