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.

A high incidence of rash has been reported in HIV-1 patients who received the anti-retroviral drug nevirapine. In addition, several studies have suggested that polymorphisms of human leukocyte antigen (HLA) genes may play important roles in nevirapine-induced rash. The aim of the present study was to evaluate the effects of different HLA-C alleles on rash associated with nevirapine in patients who started highly active anti-retroviral therapy (HAART) containing nevirapine in Thailand.

Dengue is a mosquito-borne disease that has spread to >100 countries and is caused by the dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. DENV comprises 4 serotypes (DENV-1 to -4), and each serotype is further divided into distinct genotypes. In India, it is reported that all 4 serotypes of DENV co-circulate. Although Bangladesh is a neighboring country of India, very few reports have published DENV sequence data for the country, especially after 2012. To understand the current distribution of DENV genotypes in Bangladesh, we determined the nucleotide sequences of envelope regions obtained from 58 DENV-positive patients diagnosed at Apollo Hospitals Dhaka during the period between September 2017 and February 2018. We found 5 DENV-1, 47 DENV-2, and 6 DENV-3 serotypes. A phylogenetic analysis of the obtained viral sequences revealed that DENV-3 genotype I was present instead of DENV-3 genotype II, which was predominant in Bangladesh between 2000 and 2009. Furthermore, we found two distinct lineages of the Cosmopolitan genotype of DENV-2, one of which was closely related to strains from Southeast Asia and has never been reported previously in Bangladesh. These results indicated that DENVs in Bangladesh have increased in genotypic diversity and suggest that the DENV genotypic shift observed in other Asian countries also might have been taking place in Bangladesh.

Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864–882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2–specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.

Background: Cytochrome P450 2B6(CYP2B6)metabolizes efavirenz and nevirapine, the major core antiretroviral drugs for HIV in Thailand. Rifampicin, a critical component of tuberculosis (TB) therapy is a potent inducer of CYP enzyme activity. Polymorphisms ofCYP2B6andCYP3A4are associated with altered activity of hepatic enzyme in the liver and pharmacokinetics resulting in treatment efficacy. This study aimed to investigate whetherCYP2B6orCYP3A4polymorphisms had effects on plasma efavirenz and nevirapine concentrations when co-administered with rifampicin in HIV/TB co-infected Thai adults.Results: We studied 124 rifampicin recipients with concurrent HIV-1/TB coinfection, receiving efavirenz (600 mg/day) (n = 65) or nevirapine (400 mg/day) (n = 59) based antiretroviral therapy (ART). The frequencies of GG, GT and TT genotypes ofCYP2B6-G516T were 38.46%, 47.69% and 13.85% in efavirenz group and 44.07%, 52.54% and 3.39% in nevirapine group, respectively. The mean 12-hour post-dose plasma efavirenz concentration in patients with TT genotype at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation (10.97 ± 2.32, 13.62 ± 4.21 and 8.48 ± 1.30 mg/L, respectively) were significantly higher than those with GT (3.43 ± 0.29, 3.35 ± 0.27 and 3.21 ± 0.22 mg/L, respectively) (p < 0.0001) or GG genotypes (2.88 ± 0.33, 2.45 ± 0.26 and 2.08 ± 0.16 mg/L, respectively) (p < 0.0001). Likewise, the mean 12-hour post-dose plasma nevirapine concentration in patients carrying TT genotype at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation (14.09 ± 9.49, 7.94 ± 2.76 and 9.44 ± 0.17 mg/L, respectively) tended to be higher than those carrying GT (5.65 ± 0.54, 5.58 ± 0.48 and 7.03 ± 0.64 mg/L, respectively) or GG genotypes (5.42 ± 0.48, 5.34 ± 0.50 and 6.43 ± 0.64 mg/L, respectively) (p = 0.003, p = 0.409 and p = 0.448, respectively). Compared with the effects ofCYP2B6-516TT genotype, we could observe only small effects of rifampicin on plasma efavirenz and nevirapine levels. After 12 weeks of both drug regimens, there was a trend towards higher percentage of patients withCYP2B6-TT genotype who achieved HIV-1 RNA levels <50 copies/mL compared to those with GT or GG genotypes. This is the first report to demonstrate the effects ofCYP2B6G516T polymorphisms on plasma efavirenz and nevirapine concentrations when co-administered with rifampicin in HIV/TB co-infected Thai adults.Conclusions: CYP2B6-TT genotype had impact on plasma efavirenz and nevirapine concentrations, while rifampicin co-administration had only small effects.

Dengue virus (DENV) infections have unpredictable clinical outcomes, ranging from asymptomatic or minor febrile illness to severe and fatal disease. The severity of dengue infection is at least partly related to the replacement of circulating DENV serotypes and/or genotypes. To describe clinical profiles of patients and the viral sequence diversity corresponding to non-severe and severe cases, we collected patient samples from 2018 to 2022 at Evercare Hospital Dhaka, Bangladesh. Serotyping of 495 cases and sequencing of 179 cases showed that the dominant serotype of DENV shifted from DENV2 in 2017 and 2018 to DENV3 in 2019. DENV3 persisted as the only representative serotype until 2022. Co-circulation of clades B and C of the DENV2 cosmopolitan genotype in 2017 was replaced by circulation of clade C alone in 2018 with all clones disappearing thereafter. DENV3 genotype I was first detected in 2017 and was the only genotype in circulation until 2022. We observed a high incidence of severe cases in 2019 when the DENV3 genotype I became the only virus in circulation. Phylogenetic analysis revealed clusters of severe cases in several different subclades of DENV3 genotype I. Thus, these serotype and genotype changes in DENV may explain the large dengue outbreaks and increased severity of the disease in 2019.