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Leptospirosis can cause a high mortality rate, especially in severe cases. This multicenter cross-sectional study aimed to examine both host and pathogen factors that might contribute to the disease severity. A total of 217 leptospirosis patients were recruited and divided into two groups of non-severe and severe. Severe leptospirosis was defined by a modified sequential organ failure assessment (mSOFA) score of more than two or needed for mechanical ventilation support or had pulmonary hemorrhage or death. We found that leptospiremia, plasma neutrophil gelatinase-associated lipocalin (pNGAL), and interleukin 6 (IL-6) at the first day of enrollment (day 1) and microscopic agglutination test (MAT) titer at 7 days after enrollment (days 7) were significantly higher in the severe group than in the non-severe group. After adjustment for age, gender, and the days of fever, there were statistically significant associations of baseline leptospiremia level (OR 1.70, 95% CI 1.23–2.34, p = 0.001), pNGAL (OR 9.46, 95% CI 4.20–21.33, p

BackgroundThe 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.MethodsWe 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.ResultsNinety-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%).ConclusionsAlmost 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.

Biomarkers to predict the severity of leptospirosis are still lacking. This study aimed to identify and validate microRNAs in patients with severe leptospirosis, that could potentially be used as biomarkers for predicting an unfavorable outcome. Serum samples were collected from participants with definite diagnosis of leptospirosis. The participants were divided into two groups, non-severe and severe leptospirosis, as defined by the Specific Organ Sequential Organ Failure (SOFA) Score of more than two in any organ. Microtranscriptome analysis was performed using the NanoString miRNA Expression Assay. The expression level of candidate miRNAs was then validated by quantitative RT-PCR. Based on the NanoString, the microtranscriptome profile of the severe group was significantly different from that of the non-severe group. Upregulation of miR155-5p, miR362-3p, miR502-5p, miR601, miR1323, and miR630 in the severe group were identified, and further investigated. A total of 119 participants were enrolled in the validation cohort. Serum miR155-5p and miR630 levels were significantly higher in the severe group compared to the non-severe group. The combined use of miR155-5p or miR-630 with serum bicarbonate levels had an AUC of 0.79 (95%CI; 0.69–0.89, p, Author summary Leptospirosis is a zoonotic disease of global importance, particularly in the tropics, including Thailand. The mortality rate could be as high as 40%. These patients often developed kidney failure, liver failure, or cardiopulmonary failure, and require a high level of care. Nevertheless, the mortality rate can be reduced to 5% if prompt intensive care is provided. Predicting those at risk of developing severe disease is challenging. However, biomarkers to predict severe leptospirosis are still lacking. Our data provided the first evidence that microtranscriptome profiles of severe leptospirosis were different from the non-severe group. This data provides the first evidence that the microtranscriptome profiles of patients with severe leptospirosis were different from the non-severe group. Serum miR155-5p and miR630 levels might be novel biomarkers for identifying severe leptospirosis.

Background Leptospirosis, a global zoonotic infectious disease, has various clinical manifestations ranging from mild self-limiting illness to life-threatening with multi-organ damage, including liver involvement. This study was aimed at identifying circulating microRNAs (miRNAs) as novel biomarkers for predicting severe liver involvement in patients with leptospirosis. Methods In a discovery set, 12 serum samples of patients with anicteric and icteric leptospirosis at initial clinical presentation were used for miRNA profiling by a NanoString nCounter miRNA assay. In a validated cohort, top candidate miRNAs were selected and further tested by qRT-PCR in serum samples of 81 and 16 individuals with anicteric and icteric leptospirosis, respectively. Results The discovery set identified 38 significantly differential expression miRNAs between the two groups. Among these, miR-601 and miR-630 were selected as the top two candidates significantly up-regulated expressed in the icteric group. The enriched KEGG pathway showed that these miRNAs were mainly involved in immune responses and inflammation. In the validated cohort, miR-601 and miR-630 levels were significantly higher in the icteric group compared with the anicteric group. Additionally, these two miRNAs displayed good predictors of subsequent acute liver failure with a high sensitivity of 100%. On regression analysis, elevated miR-601 and miR-630 expression were also predictive of multi-organ failures and poor overall survival. Conclusion Our data indicated that miRNA expression profiles were significantly differentiated between the icteric and anicteric groups. Serum miR-601 and miR-630 at presentation could potentially serve as promising biomarkers for predicting subsequent acute liver failure and overall survival in patients with leptospirosis.

Background Rapid diagnostic tests (RDTs) have become widely used in low-resource settings for leptospirosis diagnostic. This study aims to evaluate the diagnostic performance of the five commercially available RDTs to detect human IgM against Leptospira spp. in Thai population. Methodology/Principal findings Ninety-nine serum samples from Leptospirosis suspicious patients were tested with five RDTs, including Medical Science Public Health, Leptocheck-WB, SD bioline, TRUSTline, and J.Mitra. The case definition was based on MAT, qPCR, and culture results. Diagnostic accuracy was determined based on the first day of enrollment in an overall analysis and stratified according to days post-onset of fever. The five RDTs had overall sensitivity ranging from 1.8% to 75% and specificity ranging from 52.3% to 97.7%. Leptocheck-WB had high sensitivity of 75.0%. The sensitivity of five RDTs increased on days 4–6 post-onset of fever, while the specificity of all tests remained relatively stable at different days post-onset of fever. Conclusions/Significance The tested RDTs showed low sensitivity. Therefore, based on the present study, five commercially available RDTs might not be an appropriate test for acute leptospirosis screening in the Thai population., Author summary Leptospirosis is an important zoonosis, especially in the tropics. Rapid diagnostic tests (RDTs) have become widely used in low-resource settings for leptospirosis diagnostics. In this study, we evaluated the diagnostic performance of five commercially available RDTs in Thai population. The overall sensitivity ranged from 1.8% to 75%, and specificity was 52.3% to 97.7%. Leptocheck-WB had the highest sensitivity of 75.0%. The sensitivity of five RDTs increased on days 4–6 post onset of fever, while the specificity of all tests remained relatively stable at different days post onset of fever. Based on these results, RDTs showed low sensitivity and might not be an appropriate test for acute leptospirosis screening in the Thai population.

Background Interferon-gamma inducible protein 10 (IP-10) plays an important role in the clinical outcome of chronic hepatitis B (CHB). This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) G-201A of the IP-10 gene and treatment response to pegylated interferon (PEG-IFN) in patients with hepatitis B e antigen (HBeAg)-positive CHB. Methods We retrospectively analysed data of patients with HBeAg-positive CHB treated with PEG-IFN for 48 weeks. Virological response (VR) was defined as HBeAg clearance and HBV DNA Results Among 107 patients, VR was achieved in 45 (42.1%) patients. Hepatitis B surface antigen (HBsAg) clearance and decline (Conclusions Data from this study demonstrated for the first time that IP-10 polymorphism is independently associated with treatment response to PEG-IFN in patients with HBeAg-positive CHB.

Background Vitamin D, a potent immune-modulator, has been linked to the pathogenesis of chronic hepatitis B (CHB). This study was aimed at investigating the association between single nucleotide polymorphisms (SNPs) in vitamin-D-related genes and treatment response to pegylated interferon (PEG-IFN) in patients with CHB. Methods A total of 275 Thai patients (122 hepatitis B e antigen [HBeAg]-positive and 153 HBeAg-negative CHB) treated with 48-week PEG-IFN were recruited. Virological response (VR) at 48 weeks post-treatment was defined as HBeAg seroconversion plus HBV DNA Results The distribution of TT, CT and CC genotypes of rs4646536 in this cohort was 21.8%, 46.2% and 32.0%, respectively. There was no difference in its distribution according to HBeAg status. In HBeAg-positive CHB, patients with TT genotype, compared with non-TT genotype, achieved higher VR (53.3% versus 31.5%; P=0.032) and hepatitis B surface antigen (HBsAg) clearance (20.0% versus 5.4%; P=0.016). In HBeAg-negative CHB, the corresponding figures were 60.0% versus 30.9% ( P=0.003) and 16.7% versus 5.7% ( P=0.045), respectively. Patients with TT genotype had more rapid HBsAg decline than those with non-TT genotype. However, SNPs rs2228570 and rs7041were not associated with VR and HBsAg clearance. Logistic regression analysis demonstrated that SNP rs4646536 and baseline HBsAg level were independent predictors of VR in both HBeAg-positive and HBeAg-neg-ative CHB. Conclusions Our data suggest that SNP rs4646536 in the CYP27B1 gene is a predictive factor of response to PEG-IFN therapy in Thai patients with CHB.

The single nucleotide polymorphism (SNP) ss469415590 in the interferon lambda-4 (IFNL4) gene has recently been reported to have an association with treatment response in chronic hepatitis C. However, any importance of the SNP in association with response to pegylated interferon (PEG-IFN) therapy in patients with chronic hepatitis B (CHB) is unclear. We retrospectively analyzed data for Thai patients with CHB treated with PEG-IFN for 48 weeks. Virological response (VR) for HBeAg-positive CHB was defined as HBeAg seroconversion plus HBV DNA level

Combining peginterferon (PEG-IFN) and a potent nucleoside/nucleotide analogue might improve treatment response in patients with chronic hepatitis B (CHB). The aims of this study were to compare the efficacy of PEG-IFN alpha-2b with or without entecavir in HBeAg-negative CHB and to investigate predictors of response. A total of 126 treatment-naive patients were randomly assigned to receive monotherapy (n = 63) or combination therapy (n = 63) for 48 weeks. Virological response (VR) was defined as HBV DNA level