Publications by authors named "Chintana Chirathaworn"

43 Publications

Comparative genome characterization of Leptospira interrogans from mild and severe leptospirosis patients.

Genomics Inform 2021 Sep 30;19(3):e31. Epub 2021 Sep 30.

Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Leptospirosis is a zoonotic disease caused by spirochetes from the genus Leptospira. In Thailand, Leptospira interrogans is a major cause of leptospirosis. Leptospirosis patients present with a wide range of clinical manifestations from asymptomatic, mild infections to severe illness involving organ failure. For better understanding the difference between Leptospira isolates causing mild and severe leptospirosis, illumina sequencing was used to sequence genomic DNA in both serotypes. DNA of Leptospira isolated from two patients, one with mild and another with severe symptoms, were included in this study. The paired-end reads were removed adapters and trimmed with Q30 score using Trimmomatic. Trimmed reads were constructed to contigs and scaffolds using SPAdes. Cross-contamination of scaffolds was evaluated by ContEst16s. Prokka tool for bacterial annotation was used to annotate sequences from both Leptospira isolates. Predicted amino acid sequences from Prokka were searched in EggNOG and David gene ontology database to characterize gene ontology. In addition, Leptospira from mild and severe patients, that passed the criteria e-value < 10e-5 from blastP against virulence factor database, were used to analyze with Venn diagram. From this study, we found 13 and 12 genes that were unique in the isolates from mild and severe patients, respectively. The 12 genes in the severe isolate might be virulence factor genes that affect disease severity. However, these genes should be validated in further study.
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http://dx.doi.org/10.5808/gi.21037DOI Listing
September 2021

The role of leptospiremia and specific immune response in severe leptospirosis.

Sci Rep 2021 07 16;11(1):14630. Epub 2021 Jul 16.

Excellence Center for Critical Care Nephrology, Thai Red Cross Society, King Chulalongkorn Memorial Hospital, 1873, Rama 4 Rd., Lumphini, Pathumwan, Bangkok, 10330, Thailand.

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 < 0.001), and IL-6 (OR 2.82, 95% CI 1.96-4.07, p < 0.001) with the severity. In conclusion, a high leptospiremia, pNGAL, and IL-6 level at baseline were associated with severe leptospirosis.
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http://dx.doi.org/10.1038/s41598-021-94073-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285422PMC
July 2021

Rheumatic manifestations of Chikungunya virus infection: Prevalence, patterns, and enthesitis.

PLoS One 2021 22;16(4):e0249867. Epub 2021 Apr 22.

Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Chikungunya virus (CHIKV) is an arthropod-borne virus transmitted by mosquitoes of the genus Aedes. CHIKV infection causes various rheumatic symptoms, including enthesitis; however, these effects are rarely investigated. The aim of this study was to describe the rheumatic manifestations in CHIKV infection, estimate the prevalence of enthesitis in CHIKV-infected patients, and determine the factors associated with CHIKV-induced enthesitis. We conducted a prospective, observational study in patients with CHIKV infection confirmed by positive RT-PCR or IgM assay from October 2019 to March 2020. Patients with pre-existing inflammatory rheumatic diseases were excluded. A rheumatologist evaluated the demographic and clinical characteristics of the patients, including the number of inflamed joints, enthesitis sites, tendinitis, and tenosynovitis. The Leeds enthesitis index (LEI) and the Maastricht ankylosing spondylitis enthesis score (MASES) were used to evaluate enthesitis sites. Factors associated with enthesitis were determined using logistic regression analysis. One hundred and sixty-four participants diagnosed with CHIKV infection were enrolled. The mean (SD) age of the patients was 48.2 (14) years. The most common pattern of rheumatic manifestations was polyarthritis with or without enthesitis. Enthesitis was observed in 63 patients (38.4%). The most common site of enthesitis was the left lateral epicondyle as assessed by LEI and the posterior superior iliac spine as assessed by MASES. Multivariate analysis indicated that the number of actively inflamed joints and Thai-HAQ score at the initial evaluation were significantly associated with the presence of enthesitis. The main rheumatic manifestations of CHIKV infection were arthritis/arthralgia, with enthesitis as a prominent extraarticular feature. CHIKV infection can cause enthesitis at peripheral and axial sites. We found that enthesitis was associated with a high number of inflamed joints and reduced physical function. These results indicate that the assessment of enthesitis should be considered when monitoring disease activity and as a treatment response parameter in CHIKV-infected patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249867PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062098PMC
September 2021

Detection of SARS-CoV-2-specific antibodies via rapid diagnostic immunoassays in COVID-19 patients.

Virol J 2021 03 9;18(1):52. Epub 2021 Mar 9.

Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.

Background: Efficient monitoring and control of coronavirus disease 2019 (COVID-19) require access to diagnostic tests, and serological diagnostic testing is desirable. In the current study, antibodies were investigated in patients recently diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: Cross-sectional data were obtained from 245 patients in whom SARS-CoV-2 infection had been confirmed via real-time reverse transcriptase-polymerase chain reaction between March and October 2020. Serum samples were acquired between 2 and 60 days following the onset of COVID-19 symptoms or the first detection of SARS-CoV-2 in asymptomatic patients. All specimens were tested simultaneously using an IgM/IgG rapid diagnostic test (RDT), IgG nucleocapsid protein-based chemiluminescent microparticle immunoassay (CMIA), IgG, and IgA spike protein-based enzyme-linked immunosorbent assays (ELISAs). Blood donor samples obtained in 2018 were used as negative controls.

Results: The sensitivity and specificity of the RDT IgG were compared with the IgG immunoassays as standards. The RDT IgG exhibited 97.5% sensitivity and 89.4% specificity compared with a CMIA IgG, 98.4% sensitivity, and 78.8% specificity compared with an ELISA IgG. IgM, IgG, and IgA seropositivity rates were low between 1 and 2 weeks after COVID-19 symptom onset or the detection of SARS-CoV-2 RNA. IgM seropositivity rate began decreasing after 4 weeks, whereas IgG and IgA seropositivity rate remained at appreciable levels over the 8-week study period. No cross-reactivity with seasonal coronaviruses was detected.

Conclusions: IgG RDT alone or combined with molecular diagnostic tests may be useful for identifying recent SARS-CoV-2 infection.
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http://dx.doi.org/10.1186/s12985-021-01530-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942515PMC
March 2021

Large-scale outbreak of Chikungunya virus infection in Thailand, 2018-2019.

PLoS One 2021 10;16(3):e0247314. Epub 2021 Mar 10.

Department of Pediatrics, Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Between 2018 and 2019, the incidence of chikungunya was approximately 15,000 cases across 60 provinces in Thailand. Here, the clinical presentations in chikungunya, emergent pattern, and genomic diversity of the chikungunya virus (CHIKV) causing this massive outbreak were demonstrated. A total of 1,806 sera samples from suspected cases of chikungunya were collected from 13 provinces in Thailand, and samples were tested for the presence of CHIKV RNA, IgG, and IgM using real-time PCR, enzyme-linked immunoassay (ELISA), commercial immunoassay (rapid test). The phylogenetic tree of CHIKV whole-genome and CHIKV E1 were constructed using the maximum-likelihood method. CHIKV infection was confirmed in 547 (42.2%) male and 748 (57.8%) female patients by positive real-time PCR results and/or CHIKV IgM antibody titers. Unsurprisingly, CHIKV RNA was detected in >80% of confirmed cases between 1 and 5 days after symptom onset, whereas anti-CHIKV IgM was detectable in >90% of cases after day 6. Older age was clearly one of the risk factors for the development of arthralgia in infected patients. Although phylogenetic analysis revealed that the present CHIKV Thailand strain of 2018-2020 belongs to the East, Central, and Southern African (ECSA) genotype similar to the CHIKV strains that caused outbreaks during 2008-2009 and 2013, all present CHIKV Thailand strains were clustered within the recent CHIKV strain that caused an outbreak in South Asia. Interestingly, all present CHIKV Thailand strains possess two mutations, E1-K211E, and E2-V264A, in the background of E1-226A. These mutations are reported to be associated with virus-adapted Aedes aegypti. Taken together, it was likely that the present CHIKV outbreak in Thailand occurred as a result of the importation of the CHIKV strain from South Asia. Understanding with viral genetic diversity is essential for epidemiological study and may contribute to better disease management and preventive measures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247314PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946318PMC
August 2021

Effect of Gold Nanoparticles on the TLR2-Mediated Inflammatory Responses Induced by in TLR2-Overexpressed HEK293 Cells.

Nanomaterials (Basel) 2020 Dec 16;10(12). Epub 2020 Dec 16.

Nanomedicine Research Unit, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

infection can cause potential hazards to human health by stimulating inflammation, which is mediated mainly through the Toll-like receptor 2 (TLR2) pathway. Gold nanoparticles (AuNPs) are promising for medical applications, as they display both bioinert and noncytotoxic characteristics. AuNPs have been shown to have the ability to modify immune responses. To understand the in vitro immunomodulatory effect of AuNPs in a infection model, the activation of TLR2 expression was examined in HEK-Blue-hTLR2 cells treated with serovars and/or AuNPs (10 and 20 nm). The ability of AuNPs to modulate an inflammatory response induced by was examined in terms of transcript expression level modulation of three proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β and IL-6) using two-stage quantitative real-time reverse transcriptase PCR. The results revealed that the administration of 10 nm AuNPs could augment the -induced TLR2 signaling response and upregulate the expression of all three cytokine gene transcripts, whereas the 20 nm AuNPs attenuated the TLR2 activation and expression of proinflammatory cytokines. This indicates that AuNPs can modulate inflammatory parameters in infection and different-sized AuNPs had different immunomodulatory functions in this model.
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http://dx.doi.org/10.3390/nano10122522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765485PMC
December 2020

Endotoxemia and circulating bacteriome in severe COVID-19 patients.

Intensive Care Med Exp 2020 Dec 7;8(1):72. Epub 2020 Dec 7.

Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok, Thailand.

Background: When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19.

Methods: We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-β-D-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome.

Results: Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime.

Conclusions: Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.
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http://dx.doi.org/10.1186/s40635-020-00362-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719737PMC
December 2020

SARS-CoV-2 RNA shedding in recovered COVID-19 cases and the presence of antibodies against SARS-CoV-2 in recovered COVID-19 cases and close contacts, Thailand, April-June 2020.

PLoS One 2020 29;15(10):e0236905. Epub 2020 Oct 29.

Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although Thailand has been fairly effective at controlling the spread of COVID-19, continued disease surveillance and information on antibody response in recovered patients and their close contacts remain necessary in the absence of approved vaccines and antivirals. Here, we examined 217 recovered COVID-19 patients to assess their viral RNA shedding and residual antibodies against SARS-CoV-2. We also evaluated antibodies in blood samples from 308 close contacts of recovered COVID-19 patients. We found that viral RNA remained detectable in 6.6% of recovered COVID-19 cases and up to 105 days. IgM, IgG, and IgA antibodies against SARS-CoV-2 were detected in 13.8%, 88.5%, and 83.4% of the recovered cases 4-12 weeks after disease onset, respectively. Higher levels of antibodies detected were associated with severe illness patients experienced while hospitalized. Fifteen of the 308 contacts (4.9%) of COVID-19 cases tested positive for IgG antibodies, suggesting probable exposure. Viral clearance and the pattern of antibody responses in infected individuals are both crucial for effectively combating SARS-CoV-2. Our study provides additional information on the natural history of this newly emerging disease related to both natural host defenses and antibody duration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236905PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595404PMC
November 2020

IL-18: a suggested target for immunomodulation in chikungunya virus infection.

Arch Virol 2021 Jan 19;166(1):219-223. Epub 2020 Oct 19.

Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.

Chronic joint pain is the most common pathology found in chikungunya virus (CHIKV)-infected patients. Eight cytokines were compared in CHIKV patients with and without joint pain. IL-4 and IL-13 levels were significantly lower in patients with joint pain (p = 0.006 and p < 0.0001, respectively). IL-18 levels were higher in the group of patients with joint pain (p < 0.0001) and were significantly higher on days 3 and 4 after onset (p = 0.0012 and p = 0.003, respectively). Moreover, TNF-α levels were significantly higher in patients with joint pain on day 3 (p = 0.028). This study demonstrated that cytokines, particularly IL-18, may be candidates for immunomodulation.
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http://dx.doi.org/10.1007/s00705-020-04849-3DOI Listing
January 2021

Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020.

Sci Rep 2020 10 6;10(1):16602. Epub 2020 Oct 6.

Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major global concern. Several SARS-CoV-2 gene mutations have been reported. In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. Forty samples were collected at different time points during the outbreak, and parts of the SARS-CoV-2 genome sequence were used to assess genomic variation patterns. The phylogenetics of the 40 samples were clustered into L, GH, GR, O and T types. T types were predominant in Bangkok during the first local outbreak centered at a boxing stadium and entertainment venues in March 2020. Imported cases were infected with various types, including L, GH, GR and O. In southern Thailand introductions of different genotypes were identified at different times. No clinical parameters were significantly associated with differences in genotype. The results indicated local transmission (type T, Spike protein (A829T)) and imported cases (types L, GH, GR and O) during the first wave in Thailand. Genetic and epidemiological data may contribute to national policy formulation, transmission tracking and the implementation of measures to control viral spread.
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http://dx.doi.org/10.1038/s41598-020-73554-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538975PMC
October 2020

High prevalence of DS-1-like rotavirus infection in Thai adults between 2016 and 2019.

PLoS One 2020 25;15(6):e0235280. Epub 2020 Jun 25.

Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Rotavirus infection is the most common cause of viral diarrhea in infants and young children but uncommon and usually asymptomatic in adults. In the winter of 2017-2018, a large-scale outbreak of rotavirus in both children and adults was reported in Thailand. The current study focused on the prevalence, genotyping, and molecular characterization of rotavirus infections in Thai adults from July 2016 to December 2019. In 2,598 stool samples collected from adult residents of Bangkok (aged #x2265; 15 years) with acute gastroenteritis, rotavirus was detected via real-time RT-PCR analysis of the VP6 gene. G, P and I genotypes were determined by direct sequencing of VP7, VP4, and VP6 genes, respectively. Our results showed 8.7% (226/2,598) of stool samples were positive for rotavirus. The incidence of rotavirus was high during the winter season of 2017-2018 (17.7%) compared to another studied periods (4.5% between July 2016- October 2017 and 2.8% between March 2018- December 2019). Nucleotide sequencing of VP7 and VP4 revealed G3P[8] as the predominant strain (33.2%,75/226), followed by G9P[8] (17.3%,39/226), and G2P[4] (15.0%,34/226). Uncommon G and P combinations were additionally detected at low frequencies. VP6 sequencing was conducted to discriminate I genotype between the Wa and DS-1 genogroup. The unusual DS-1-like G3P[8] strain was most prevalent amomg rotavirus strains detected in this study (29.6%, 67/226), and the corresponding VP7 sequences showed high nucleotide identity with unusual DS-1-like globally circulating strains. Our study demonstrates that rotavirus outbreaks in adults are attributable not only to high prevalence of RV infection but also the unusual DS-like genogroup. The collective findings reinforce the importance of investigating rotavirus diagnosis in adults suffering from acute gastroenteritis and taking appropriate preventive measures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235280PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316273PMC
September 2020

Cytokines and Chemokines in Chikungunya Virus Infection: Protection or Induction of Pathology.

Pathogens 2020 May 27;9(6). Epub 2020 May 27.

Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Chikungunya virus (CHIKV) infection has been commonly detected in tropical countries. The clinical manifestations of CHIKV infection are similar to those of rheumatoid arthritis. Outbreaks of CHIKV infection in Thailand have been reported, and the inductions of various cytokines and chemokines in CHIKV patients during those outbreaks have been shown. Although immune responses in CHIKV infection have been increasingly reported, the mechanisms associated with pathology induction are still not clearly understood. This review focuses on cytokine and chemokine production in CHIKV infection, in association with the severity of joint inflammation. Several cytokines and chemokines involved in the induction or regulation of inflammatory responses were shown to associate with the severe and persistent symptoms in CHIKV infection. Further studies on the difference in immune responses observed in an autoimmune disease, rheumatoid arthritis, infectious disease, and CHIKV infection, would provide additional insights useful for proper CHIKV therapy, especially in patients with severe joint pains.
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http://dx.doi.org/10.3390/pathogens9060415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350363PMC
May 2020

Hepatitis E virus infection in Thai blood donors.

Transfusion 2019 03 15;59(3):1035-1043. Epub 2018 Nov 15.

Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Hepatitis E virus (HEV) infection in several industrialized and developing countries is associated with the consumption of pork and other meat products, an exposure risk among the majority of blood donors. We aimed to evaluate the prevalence of HEV in plasma from healthy blood donors in Thailand.

Study Design And Methods: We screened blood samples collected between October and December 2015, from 30,115 individual blood donors in 5020 pools of six, for HEV RNA using in-house real-time reverse-transcription polymerase chain reaction (RT-PCR). Thrice-reactive samples were subjected to a commercial real-time RT-PCR (cobas HEV test) and evaluated for anti-HEV immunoglobulin M and immunoglobulin G antibodies. Genotyping using nested RT-PCR, nucleotide sequencing, and phylogenetic analysis was performed.

Results: Twenty-six donors were positive for HEV RNA by the in-house assay, nine of whom were also positive by cobas test. None of the latter were reactive for anti-HEV immunoglobulin M or immunoglobulin G antibodies. Six samples were successfully genotyped and found to be HEV genotype 3. Thus, the frequency of HEV infection among healthy Thai blood donors is 1 in 1158.

Conclusion: The presence of HEV RNA in the Thai blood supply was comparable to the rates reported in western European countries, but higher than in North America and Australia.
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http://dx.doi.org/10.1111/trf.15041DOI Listing
March 2019

Vitamin D supplementation improves serum markers associated with hepatic fibrogenesis in chronic hepatitis C patients: A randomized, double-blind, placebo-controlled study.

Sci Rep 2017 08 21;7(1):8905. Epub 2017 Aug 21.

Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Hepatic fibrosis is the net accumulation of matrix tissue components which controlled by pro-fibrolytic enzymes, matrix metalloproteinases (MMPs), and pro-fibrotic cytokine, TGF-β, and enzymes, tissue inhibitors of MMPs (TIMPs). Vitamin D (VD) supplementation has been shown to reverse these processes in vitro and in vivo. This study sought to determine the effect of VD supplementation on serum fibrotic markers in chronic hepatitis C (CHC) patients. Fifty-four CHC patients with VD deficiency were randomized into two groups, a VD group (n = 29) and a placebo group (n = 29). The serum levels of 25-hydroxy VD, TGF-β, TIMP-1, MMP2 and MMP9 were measured at baseline and at the end of the 6-week study period. Upon correction of VD levels, TGF-β and TIMP-1 levels were decreased, and the MMP2 and MMP9 levels were significantly increased in the VD group. A comparison of the mean changes (delta) in the markers between groups showed that TGF-β and TIMP-1 levels were significantly decreased and the MMP2 and MMP9 were significantly higher in the VD group than in the placebo group. By using CHC patients as a model, this study provides additional evidence that VD plays an important role in the reversal of hepatic fibrogenesis.
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http://dx.doi.org/10.1038/s41598-017-09512-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566364PMC
August 2017

Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial.

PLoS One 2017 4;12(4):e0174608. Epub 2017 Apr 4.

Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Vitamin D deficiency was common among patients with chronic hepatitis C (CHC) and had negative influence on treatment outcome. Correction of vitamin D deficiency improved treatment response. Interferon gamma-induced protein 10 (IP-10) and enzyme dipeptidyl peptidase-4 (DPP IV) involved in inflammatory responses in CHC. Their higher levels at pretreatment of CHC could predict poorer responses. Vitamin D suppressed expression of IP-10 from monocytes in vitro. In CHC patients, DPP IV involved in IP-10 regulation. We hypothesized that correction of vitamin D insufficiency or deficiency in CHC patients might restore immune dysregulation through a pathway linked to the TH1/Th2 cytokines, IP-10 or DPP IV. We conducted a double-blind, placebo-controlled trial. 80 CHC patients with vitamin D levels less than 30 ng/mL were assigned to receive vitamin D (40) or placebo (40) supplements for 6 weeks. The levels of 25-hydroxyvitamin D [25(OH)D], Th1/Th2 cytokines, IP-10 and DPP IV were measured at baseline and at the 6th week. At the end of study, the mean 25(OH)D level in vitamin D group was significantly increased and normalised. There were no changes in the level of Th1/Th2 cytokines. Our important finding revealed that upon correction of vitamin D insufficiency or deficiency, the serum IP-10 and DPP IV levels were decreased significantly as compare to the placebo group (delta changes; 83.27 vs -133.80; 95% CI [-326.910, -40.758], p = 0.0125, and 271.04 vs -518.69; 95% CI [-1179,15, -59.781], p = 0.0305, respectively. As previous evidences suggested that each factor individually influenced and predicted outcome of CHC treatment. Our results offer a new insight and help to piece the puzzle of vitamin D deficiency, IP-10 and DPP IV together in CHC.

Trial Registration: Thai Clinical Trials Registry TCTR20160429001.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174608PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380326PMC
August 2017

Hepatitis E Virus in Pork and Variety Meats Sold in Fresh Markets.

Food Environ Virol 2017 03 31;9(1):45-53. Epub 2016 Aug 31.

Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Swine is an economically important livestock, yet pork consumption and close contact with pigs are associated with the risk of hepatitis E virus (HEV) infection. Limited data on the prevalence of HEV in Southeast Asia have mainly examined farm animals. To investigate the potential zoonotic transmission of HEV from dietary consumption of pork and variety meats (i.e., offal or organ meats), we obtained 1090 liver, 559 pork meat, and 556 intestine samples from fresh markets in the Bangkok metropolitan area between November 2014 and February 2015. The presence of HEV was assessed using reverse-transcription polymerase chain reaction. Concurrently, 720 bile and 553 fecal samples from a slaughterhouse were also examined. Overall, HEV RNA was found in 0.23 % of the market samples and 3.93 % of the slaughterhouse samples. Fecal and bile samples were more likely to test positive compared to liver, pork, and intestine samples (p < 0.001). Phylogenetic analysis showed that all HEV sequences obtained in this study formed a cluster closely related to genotype 3f. Pork and variety meats derived from pigs are commonly sold in fresh markets throughout Southeast Asia. Here, a relatively low HEV prevalence from pork and variety meats sold in Bangkok was found. Additional studies will be required to further assess potential dietary transmission of HEV elsewhere in the region.
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http://dx.doi.org/10.1007/s12560-016-9258-0DOI Listing
March 2017

Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand.

PLoS One 2015 2;10(12):e0143367. Epub 2015 Dec 2.

Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143367PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667882PMC
June 2016

Hepatitis E virus infection: Epidemiology and treatment implications.

World J Virol 2015 Nov;4(4):343-55

Ga Young Lee, Kittiyod Poovorawan, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

Hepatitis E virus (HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylated interferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable.
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http://dx.doi.org/10.5501/wjv.v4.i4.343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641226PMC
November 2015

Interpretation of microscopic agglutination test for leptospirosis diagnosis and seroprevalence.

Asian Pac J Trop Biomed 2014 May;4(Suppl 1):S162-4

National Institute of Animal Health, Department of Livestock Development, Bangkok, Thailand.

Determination of antibody titer by microscopic agglutination test (MAT) has been used as a tool for leptospirosis diagnosis. Four fold or greater rise in antibody titers between acute and convalescent sera suggests recent Leptospira infection. In addition, results obtained by MAT have been used to predict infecting serovars. However, cross reactivity among various Leptospira serovars have been reported when patient sera were tested with a battery of Leptospira serovars. This study demonstrates cross- reactivity among several Leptospira serovars when MAT was performed on leptospirosis sera. The data support a role of MAT as a tool for diagnosis. However, for information on infecting serovars, Leptospira isolation and molecular identification should be performed.
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http://dx.doi.org/10.12980/APJTB.4.2014C580DOI Listing
May 2014

Development of an immunochromatographic test with anti-LipL32-coupled gold nanoparticles for Leptospira detection.

New Microbiol 2014 Apr 1;37(2):201-7. Epub 2014 Apr 1.

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Detection of antibody specific to Leptospira by various immunological techniques has been used for leptospirosis diagnosis. However, the sensitivity of antibody detection during the first few days after infection is low. Molecular techniques are suggested to provide earlier diagnosis than antibody detection, but a rapid and easy to perform assay for Leptospira antigen detection would provide an additional useful tool for disease diagnosis. In this study, we coupled gold nanoparticles with antibody to LipL32, a protein commonly found in pathogenic Leptospira. This coupled gold reagent was used in the immunochromatographic strip for Leptospira detection. We demonstrated that the sensitivity of Leptospira detection by this strip was 10(3) ml(-1). There was no positive result detected when strips were tested with non-pathogenic Leptospira, Staphylococcus aureus, Streptococcus group B, Acinetobacter baumannii, Escherichia coli, Salmonella typhi, Klebsiella pneumoniae, Enterococcus faecalis or Enterococcus faecium. These data suggest that gold nanoparticles coupled with antibody to LipL32 could be used for Leptospira detection by a rapid test based on an immunochromatographic technique.
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April 2014

Circulating cytokines and histological liver damage in chronic hepatitis B infection.

Hepat Res Treat 2013 31;2013:757246. Epub 2013 Oct 31.

Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Each phase of hepatitis B infection stimulates distinct viral kinetics and host immune responses resulting in liver damage and hepatic fibrosis. Our objective has been to correlate host inflammatory immune response including circulating Th1 and Th2 cytokines in patients with chronic hepatitis B infection with liver histopathology. Sixty-four patients with chronic hepatitis B without previous treatment were recruited. The liver histology and histological activity index were assessed for various degrees of necroinflammation and hepatic fibrosis. We determined circulating levels of the Th1 and Th2 cytokines. Forty-six males and 18 females at a median age of 34.5 years were studied. HBeAg was present in 28/64 (43.75%) of the patients. In patients negative for HBeAg, IL-10 and IFN-gamma were significantly correlated with degrees of necroinflammation (r = 0.34, r = 0.38, resp.; P < 0.05). Moreover, TNF-alpha was significantly correlated with degrees of fibrosis (r = 0.35; P < 0.05), and IL-10 and TNF-alpha were significantly correlated with significant fibrosis (r = 0.39, r = 0.35, resp.; P < 0.05). These correlations were found in the HBeAg negative group as opposed to the HBeAg positive group. In HBeAg negative patients, circulating cytokines IL-10 and IFN-gamma were correlated with degrees of necroinflammation, whereas IL-10 and TNF-alpha were correlated with significant fibrosis.
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http://dx.doi.org/10.1155/2013/757246DOI Listing
November 2013

Immune responses to Leptospira infection: roles as biomarkers for disease severity.

Braz J Infect Dis 2014 Jan-Feb;18(1):77-81. Epub 2013 Nov 22.

Master of Science Program in Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Various leptospiral components have been identified and shown to be involved in tissue destruction. In addition, immune responses to leptospires have been implicated in target organ damages in severe leptospirosis cases. Several inflammatory mediators were shown to be higher in susceptible animals than in resistant hosts. Moreover, cytokines/chemokines and serum proteins induced following Leptospira infection were suggested to be biomarkers for disease severity in human leptospirosis. This review focuses on the role of immune responses in the severity of leptospirosis. Studies in both animal models and humans are discussed.
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http://dx.doi.org/10.1016/j.bjid.2013.08.002DOI Listing
June 2014

Cytokine levels in patients with chikungunya virus infection.

Asian Pac J Trop Med 2013 Aug;6(8):631-4

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Objective: To investigate cytokine profile in patients with chikungunya virus (CHIKV) infection.

Methods: Twenty eight pairs of serum samples collected from CHIKV infected patients during the outbreak of chikungunya fever in South Thailand in 2008 were obtained. A multiple cytokine assay for detection of 17 cytokines was performed.

Results: In the acute stage of CHIKV infection, the patients had significantly higher levels of interleukin-6, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1 and tumor necrosis factor alpha than the control (P<0.001, P=0.023, P=0.015, P<0.001 and P=0.024, respectively). When the disease developed to the recovery stage, the patients had significantly lower levels of interleukin-6, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1 and macrophage inflammatory protein beta than in the acute stage (P<0.001).

Conclusions: This study provides additional information that these cytokines could play roles in pathogenesis of CHIKV infection and could be used as disease biomarkers or drug targets.
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http://dx.doi.org/10.1016/S1995-7645(13)60108-XDOI Listing
August 2013

In vivo gene expression and immunoreactivity of Leptospira collagenase.

Microbiol Res 2013 Jun 8;168(5):268-72. Epub 2013 Jan 8.

Master of Science Program in Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Pulmonary hemorrhage is an increasing cause of death of leptospirosis patients. Bacterial collagenase has been shown to be involved in lung hemorrhage induced by various infectious agents. According to Leptospira whole genome study, colA, a gene suggested to code for bacterial collagenase has been identified. We investigated colA gene expression in lung tissues of Leptospira infected hamsters. Golden Syrian Hamsters were injected intraperitoneally with Leptospira interrogans serovar Pyrogenes. The hamsters were sacrificed on days 3, 5 and 7 post-infection and lung tissues were collected for histological examination and RNA extraction. Lung pathologies including atelectasis and hemorrhage were observed. Expression of colA gene in lung tissues was demonstrated by both RT-PCR and real time PCR. In addition, ColA protein was cloned and the purified protein could react with sera from leptospirosis patients. Leptospira ColA protein may play a role in Leptospira survival or pathogenesis in vivo. Its reaction with leptospirosis sera suggests that this protein is immunogenic and could be another candidate for vaccine development.
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http://dx.doi.org/10.1016/j.micres.2012.12.005DOI Listing
June 2013

Correlation of connective tissue growth factor with liver stiffness measured by transient elastography in biliary atresia.

Hepatol Res 2013 Jul 27;43(7):795-800. Epub 2012 Nov 27.

Department of Biochemistry, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Aim: Biliary atresia (BA) is a neonatal liver disease defined as chronic progressive fibrotic obliteration of extrahepatic bile ducts. The objective of this study was to determine the association of serum connective tissue growth factor (CTGF) with clinical outcome and liver stiffness measurement.

Methods: Eighty-two BA patients post-Kasai operation and 28 healthy controls were recruited. BA patients were categorized into two groups based on their portal hypertension (PH) status. Serum CTGF levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by transient elastography.

Results: BA patients had greater CTGF levels (905.9 ± 57.7 vs 238.3 ± 23.5 pg/mL, P < 0.001) and higher liver stiffness values than controls (28.2 ± 2.6 vs 5.0 ± 0.5 kPa, P < 0.001). Serum CTGF levels were remarkably elevated in BA patients with PH compared to those without PH (1092.4 ± 73.9 vs 582.6 ± 45.7 pg/mL, P < 0.001). Furthermore, BA patients with PH had significantly higher liver stiffness values compared to those without PH (37.3 ± 3.0 vs 10.6 ± 1.1 kPa, P < 0.001). Additionally, serum CTGF was positively correlated with liver stiffness (r = 0.875, P < 0.001) and total bilirubin (r = 0.462, P < 0.001). There was an inverse correlation between serum CTGF and serum albumin (r = -0.579, P < 0.001).

Conclusion: High serum CTGF was associated with a poor outcome in BA patients. Accordingly, serum CTGF and transient elastography may serve as non-invasive biomarkers reflecting the disease severity in postoperative BA patients.
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http://dx.doi.org/10.1111/hepr.12015DOI Listing
July 2013

HIV-1 replication in HIV-infected individuals is significantly reduced when peripheral blood mononuclear cells are superinfected with HSV-1.

ScientificWorldJournal 2012 2;2012:102843. Epub 2012 Sep 2.

Interdisciplinary Program of Medical Microbiology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.

Herpes simplex virus (HSV) can cause generalized infection in human immunodeficiency virus- (HIV-) infected patients leading to death. This study investigated HSV-1 replication in PBMCs from 25 HIV-infected individuals and 15 healthy donors and the effects of HSV-1 superinfection on HIV-1 production. Herpes viral entry mediator (HVEM) receptor on T lymphocytes was also evaluated. Our results confirmed that the number of activated (CD3+ and CD38+) T lymphocytes in HIV-infected individuals (46.51 ± 17.54%) was significantly higher than in healthy donors (27.54 ± 14.12%, P value = 0.001) without any significant differences in HVEM expression. Even though the percentages of HSV-1 infected T lymphocytes between HIV-infected individuals (79.25 ± 14.63%) and healthy donors (80.76 ± 7.13%) were not different (P value = 0.922), yet HSV-1 production in HIV-infected individuals (47.34 ± 11.14 × 10³ PFU/ml) was significantly greater than that of healthy donors (34.17 ± 8.48 × 10³ PFU/ml, P value = 0.001). Moreover, HSV-1 virions were released extracellularly rather than being associated with the cells, and superinfection of HSV-1 at a multiplicity of infection (MOI) of 5 significantly decreased HIV production (P value < 0.001).
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http://dx.doi.org/10.1100/2012/102843DOI Listing
March 2013

Plasma and synovial fluid connective tissue growth factor levels are correlated with disease severity in patients with knee osteoarthritis.

Biomarkers 2012 Jun 15;17(4):303-8. Epub 2012 Mar 15.

Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Background: Connective tissue growth factor (CTGF) has been implicated in development of osteoarthritis (OA).

Objective: To determine the correlation between plasma and synovial fluid CTGF levels and the severity in knee osteoarthritis patients.

Methods: A total of 100 subjects were recruited into this study (75 OA patients and 25 controls). CTGF concentrations in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay.

Results: Plasma and synovial fluid CTGF concentrations were correlated with radiographic severity. There was a positive correlation between plasma and synovial fluid CTGF levels.

Conclusion: CTGF could be useful for monitoring the severity and progression of OA.
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http://dx.doi.org/10.3109/1354750X.2012.666676DOI Listing
June 2012

Serum IL-18 and IL-18BP levels in patients with Chikungunya virus infection.

Viral Immunol 2010 Feb;23(1):113-7

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Chikungunya virus infection has recently emerged in several countries. The inflammatory response is suggested to be involved in the pathology observed in this infectious disease. Interleukin-18 (IL-18) is an inducer of interferon-gamma (IFN-gamma) production and has been shown to play a role in several inflammatory diseases. IL-18 binding protein (IL-18BP) is a natural regulator of IL-18. In this study, we determined the levels of IL-18 and IL-18BP in patients with Chikungunya virus infection. Acute and convalescent sera were collected from each patient. The levels of both IL-18 and IL-18BP were measured by ELISA assays. IL-18 and IL-18BP levels were higher in patients than in controls. In addition, the level of IL-18 was higher in convalescent than in acute sera. However, the level of IL-18BP was lower in convalescent than in acute sera. These data suggest that production of both IL-18 and IL-18BP was induced following Chikungunya virus infection. IL-18BP was increased to regulate the activity of IL-18. The ratio of IL-18 to IL-18BP was higher in convalescent than in acute sera. The lower level of IL-18BP in convalescent sera was probably due to loss following IL-18 neutralization. Our data suggest that Chikungunya virus infection promotes the T helper-1 (Th-1) response by inducing IL-18 production. Manipulation of IL-18 and IL-18BP levels could be a promising therapeutic approach to alleviate symptoms in patients with Chikungunya virus infection.
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http://dx.doi.org/10.1089/vim.2009.0077DOI Listing
February 2010

Detection of Leptospira in urine using anti-Leptospira-coated gold nanoparticles.

Comp Immunol Microbiol Infect Dis 2011 Jan 16;34(1):31-4. Epub 2009 Dec 16.

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Serological assays for antibody detection have been widely used for Leptospirosis diagnosis. However, antibody is usually undetectable during the first week after infection. Detection of Leptospira DNA can be done by PCR but this technique requires special equipments and the cost is still relatively high. Here we demonstrate that gold nanoparticles can be used to facilitate Leptospira detection. Gold nanoparticles were coated with rabbit antibody specific to Leptospira interrogans serovar Bratislava and these coated particles were used to detect Leptospira in urine. Agglutination of gold particles indicated the presence of Leptospira in samples tested. The sensitivity of detection was 10 leptospires/ml. No agglutination was observed when anti-Leptospira-coated particles were tested with urine containing the organisms commonly found in urine such as Klebsiella pneumoniae, Escherichia coli and Enterococcus faecalis. This assay is very easy to perform and results could be observed with the naked eyes. Fresh or frozen urine samples could be used. The stability of antibody-coated particles was at least 2 months when kept at 4°C. In conclusion, we have demonstrated that the technique using antibody-coated gold nanoparticles is a promising tool for further validation as a rapid assay for Leptospirosis diagnosis.
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http://dx.doi.org/10.1016/j.cimid.2009.10.006DOI Listing
January 2011

Expression of TNF-alpha, TGF-beta, IP-10 and IL-10 mRNA in kidneys of hamsters infected with pathogenic Leptospira.

Comp Immunol Microbiol Infect Dis 2010 Sep 25;33(5):423-34. Epub 2009 Jun 25.

Medical Science Master Program, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira. Although several components of this organism have been identified, the molecular mechanisms underlying pathogenesis of this infectious disease are still poorly understood. Besides, direct injury by microbial factors, cytokines produced in response to infection have been proposed to be involved in pathogenesis of leptospirosis. In this study, cytokine gene expression in kidneys was investigated. Hamsters were injected with pathogenic Leptospira interrogans serovar Pyrogenes and were sacrificed on days 3, 5 and 7 after infection. RNA was extracted from kidney tissues. Real-time PCR was performed to demonstrate expression of TNF-alpha, TGF-beta, IP-10 and IL-10 mRNA in kidneys. TNF-alpha, TGF-beta and IP-10 expression could be demonstrated since day 3 post-infection whereas IL-10 expression was detected later on day 5. Leptospira infection resulted in not only expression of a proinflammatory cytokine, TNF-alpha, but also a T cell chemokine, IP-10. Detection of IP-10 suggested the involvement of T cell recruitment in the immune response or pathology in infected kidneys. Expressions of anti-inflammatory cytokines, TGF-beta and IL-10 were also observed. However, the level of TGF-beta expression was prominent since day 3 post-infection whereas IL-10 expression was clearly observed on day 5. Further experiments will provide additional information whether there is a correlation between the expression of these cytokines and pathologies found in an affected organ.
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http://dx.doi.org/10.1016/j.cimid.2009.05.001DOI Listing
September 2010
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