Serum Galactomannan: A Predictor of Poor Outcomes in Peritoneal Dialysis Patients With Fungal Peritonitis.

Introduction: The potential value of serum galactomannan index (GMI) in monitoring treatment response in patients with fungal peritonitis who are receiving peritoneal dialysis (PD) was assessed in the present study. Methods: The study included all Thailand fungal PD-related infectious complications surveillance (MycoPDICS) DATA study participants who had timely PD catheter removal and availability of both baseline and ≥2 subsequent serum GMI measurements after starting antifungal therapy (if available). Serum GMI was assessed by direct double-sandwich enzyme-linked immunosorbent assay with reference to positive and negative control samples. Comparisons of categorical variables among groups were analyzed by Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous variables. Mortality outcomes were analyzed by survival analyses using Kaplan-Meier curves with Log-rank test. Results: Seventy-six (46%) of 166 participants from 21 PD centers between 2018 and 2022 were included. The median age was 58 (50-65) years, and a half of the patients (50%) had type II diabetes. Nineteen (25%) and 57 (75%) episodes were caused by yeast and mold, respectively. Death occurred in 11 (14%) patients at 3 months, and no differences were observed in demographics, laboratories, treatment characteristics, or in baseline serum GMI between those who died and those who survived. Serum GMI progressively declined over the follow-up period after the completion of treatment. Patients who died had significantly higher posttreatment serum GMI levels and were more likely to have positive GMI after treatment. Conclusion: Serum GMI is an excellent biomarker for risk stratification and treatment response monitoring in patients on PD with fungal peritonitis.

Serum Cortisol as a Biomarker of Severe Dengue.

Dengue infection presents a wide range of clinical symptoms. Serum cortisol is known as a severity predictor of serious infection but is not yet clearly understood in dengue infection. We aimed to investigate the pattern of cortisol response after dengue infection and evaluate the possibility of using serum cortisol as the biomarker to predict the severity of dengue infection. This prospective study was conducted in Thailand during 2018. Serum cortisol and other laboratory tests were collected at four time points: day 1 at hospital admission, day 3, day of defervescence (DFV) (4-7 days post-fever onset), and day of discharge (DC). The study recruited 265 patients (median age (IQR) 17 (13, 27.5)). Approximately 10% presented severe dengue infection. Serum cortisol levels were highest on the day of admission and day 3. The best cut-off value of serum cortisol level for predicting severe dengue was 18.2 mcg/dL with an AUC of 0.62 (95% CI, 0.51, 0.74). The sensitivity, specificity, PPV and NPV were 65.4, 62.3, 16 and 94%, respectively. When we combined serum cortisol with persistent vomiting and day of fever, the AUC increased to 0.76. In summary, serum cortisol at day of admission was likely to be associated with dengue severity. Further studies may focus on the possibility of using serum cortisol as one of the biomarkers for dengue severity.

Discovery and validation of circulating miRNAs for the clinical prognosis of severe dengue.

BACKGROUND: Early prognostic markers of severe dengue may improve case management and reduce dengue-related mortalities. This study aimed to identify circulating microRNAs (miRNAs) as biomarkers for predicting severe dengue. METHODOLOGY: Serum samples from dengue-infected patients were collected on the first day of admission. Patients were followed up for 14 days after admission to determine the final diagnosis. Participants were divided into non-severe and severe dengue, as defined by WHO 2009 criteria. Circulating microtranscriptome analysis was performed using NanoString miRNA Expression Assay. The expression level of candidate miRNAs were then validated by quantitative reverse transcription-PCR method. PRINCIPAL FINDINGS: The discovery cohort (N = 19) lead to the identification of 37 differentially expressed miRNAs between the two groups. Six up-regulated candidate miRNAs were selected and further validated in the larger cohort (N = 135). MiR574-5p and miR1246 displayed the highest diagnostic performance in discriminating between severe from non-severe dengue (ROC-AUC = 0.83). Additionally, miR574-5p and miR1246 had high sensitivity and high negative predictive value for detecting severe dengue. Multivariate analysis suggested that serum miR574-5p was an independent predictor of severe dengue (odds ratio 3.30, 95% CI 1.81-6.04; p<0.001). CONCLUSION: Our study indicated that circulating miRNAs, especially miR-574-5p and miR-1246, might be a promising diagnostic and prognostic biomarker for severe dengue upon hospital admission, especially when using these biomarkers on days 1 to 2 before the onset of severe dengue complications.

Dengue pre-vaccination screening test evaluation for the use of dengue vaccine in an endemic area.

BACKGROUND: The dengue vaccine (Dengvaxia) is only recommended for individuals with prior dengue infection (PDI). This study aimed to perform a serosurvey to inform decision-making for vaccine introduction and identify appropriate target populations. We also evaluated the performance of the serological tests using plaque reduction neutralization test (PRNT) as a reference test in identifying PDI to determine suitability for pre-vaccination screening. METHODS: We enrolled 115 healthy individuals between 10 and 22 years of age living in the Ratchaburi province of Thailand. The serum samples were tested by PRNT to measure the prevalence and concentration of serotype-specific neutralizing antibodies. The performance of the IgG rapid diagnostic test (RDT, SD Bioline, Korea) and IgG enzyme-linked immunosorbent assay (ELISA, EUROIMMUN, Germany) in identifying PDI were evaluated by using PRNT as a reference method. RESULTS: Ninety-four (81.7%) individuals neutralized one or more dengue serotypes at a titer threshold greater than or equal to 10. Multitypic profiles were observed in 70.4% of the samples which increased to 91.9% in subjects aged 19-22. Among monotypic samples, the highest proportion was reactive against DENV-1 followed by DENV-2, DENV-3, and DENV-4. The highest anti-dengue antibody titers were recorded against DENV-1 and increased with age to a geometric mean NT50 titer (GMT) of 188.6 in the 19-22 age group. While both RDT and ELISA exhibited 100% specificity, RDT demonstrated low sensitivity (35%) with ELISA displaying much greater sensitivity (87%). CONCLUSIONS: Almost 80% of adolescents and youth in Ratchaburi province had already been exposed to one or more of the dengue virus serotypes. The dengue IgG RDT displayed low sensitivity and is likely not be suitable for dengue pre-vaccination screening. These results support the use of IgG ELISA test for dengue vaccination in endemic areas.