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Common TLR1 Genetic Variation Is Not Associated with Death from Melioidosis, a Common Cause of Sepsis in Rural Thailand  [PDF]
Narisara Chantratita, Sarunporn Tandhavanant, Nicolle D. Myers, Wirongrong Chierakul, Vanaporn Wuthiekanun, Weera Mahavanakul, Direk Limmathurotsakul, Sharon J. Peacock, T. Eoin West
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0083285
Abstract: Melioidosis, infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is a common cause of sepsis in northeast Thailand. In white North Americans, common functional genetic variation in TLR1 is associated with organ failure and death from sepsis. We hypothesized that TLR1 variants would be associated with outcomes in Thais with melioidosis. We collated the global frequencies of three TLR1 variants that are common in white North American populations: rs5743551 (-7202A/G), rs4833095 (742A/G), and rs5743618 (1804G/T). We noted a reversal of the minor allele from white North American subjects to Asian populations that was particularly pronounced for rs5743618. In the Utah residents of European ancestry, the frequency of the rs5743618 T allele was 17% whereas in Vietnamese subjects the frequency was >99%. We conducted a genetic association study in 427 patients with melioidosis to determine the association of TLR1 variation with organ failure or death. We genotyped rs5743551 and rs4833095. The variants were in high linkage disequilibrium but neither variant was associated with organ failure or in-hospital death. In 300 healthy Thai individuals we further tested the association of TLR1 variation with ex vivo blood responses to Pam3CSK4, a TLR1 agonist. Neither variant was robustly associated with blood cytokine responses induced by Pam3CSK4. We identified additional common variation in TLR1 by searching public databases and the published literature and screened three additional TLR1 variants for associations with Pam3CSK4-induced responses but found none. We conclude that the genetic architecture of TLR1 variation differs substantially in southeast Asians compared to other populations and common variation in TLR1 in Thais is not associated with outcome from melioidosis or with altered blood responses to Pam3CSK4. Our findings highlight the need for additional studies of TLR1 and other innate immune genetic modulators of the inflammatory host response and determinants of sepsis in southeast Asian populations.
Burkholderia pseudomallei Is Spatially Distributed in Soil in Northeast Thailand  [PDF]
Direk Limmathurotsakul ,Vanaporn Wuthiekanun,Narisara Chantratita,Gumphol Wongsuvan,Premjit Amornchai,Nicholas P. J. Day,Sharon J. Peacock
PLOS Neglected Tropical Diseases , 2010, DOI: 10.1371/journal.pntd.0000694
Abstract: Background Melioidosis is a frequently fatal infectious disease caused by the soil dwelling Gram-negative bacterium Burkholderia pseudomallei. Environmental sampling is important to identify geographical distribution of the organism and related risk of infection to humans and livestock. The aim of this study was to evaluate spatial distribution of B. pseudomallei in soil and consider the implications of this for soil sampling strategies. Methods and Findings A fixed-interval sampling strategy was used as the basis for detection and quantitation by culture of B. pseudomallei in soil in two environmental sites (disused land covered with low-lying scrub and rice field) in northeast Thailand. Semivariogram and indicator semivariogram were used to evaluate the distribution of B. pseudomallei and its relationship with range between sampling points. B. pseudomallei was present on culture of 80/100 sampling points taken from the disused land and 28/100 sampling points from the rice field. The median B. pseudomallei cfu/gram from positive sampling points was 378 and 700 for the disused land and the rice field, respectively (p = 0.17). Spatial autocorrelation of B. pseudomallei was present, in that samples taken from areas adjacent to sampling points that were culture positive (negative) for B. pseudomallei were also likely to be culture positive (negative), and samples taken from areas adjacent to sampling points with a high (low) B. pseudomallei count were also likely to yield a high (low) count. Ranges of spatial autocorrelation in quantitative B. pseudomallei count were 11.4 meters in the disused land and 7.6 meters in the rice field. Conclusions We discuss the implications of the uneven distribution of B. pseudomallei in soil for future environmental studies, and describe a range of established geostatistical sampling approaches that would be suitable for the study of B. pseudomallei that take account of our findings.
Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis
Rungnapa Pankla, Surachat Buddhisa, Matthew Berry, Derek M Blankenship, Gregory J Bancroft, Jacques Banchereau, Ganjana Lertmemongkolchai, Damien Chaussabel
Genome Biology , 2009, DOI: 10.1186/gb-2009-10-11-r127
Abstract: We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) from the whole blood of patients with septicemic melioidosis (n = 32), patients with sepsis caused by other pathogens (n = 31), and uninfected controls (n = 29). Unsupervised analyses demonstrated the existence of a whole blood transcriptional signature distinguishing patients with sepsis from control subjects. The majority of changes observed were common to both septicemic melioidosis and sepsis caused by other infections, including genes related to inflammation, interferon-related genes, neutrophils, cytotoxic cells, and T-cells. Finally, class prediction analysis identified a 37 transcript candidate diagnostic signature that distinguished melioidosis from sepsis caused by other organisms with 100% accuracy in a training set. This finding was confirmed in 2 independent validation sets, which gave high prediction accuracies of 78% and 80%, respectively. This signature was significantly enriched in genes coding for products involved in the MHC class II antigen processing and presentation pathway.Blood transcriptional patterns distinguish patients with septicemic melioidosis from patients with sepsis caused by other pathogens. Once confirmed in a large scale trial this diagnostic signature might constitute the basis of a differential diagnostic assay.Melioidosis is an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei. The disease is endemic in northern Australia, Southeast Asia, and northeast Thailand, where it is a common cause of community-acquired sepsis [1,2]. Cases of melioidosis have also been reported from other regions around the world [3]. In Thailand, the incidence rate of melioidosis was estimated as 4.4 cases per 100,000 individuals, but melioidosis cases are under-reported due to a lack of adequate laboratory testing [1,4]. The disease is the leading cause of community-acquired septicemia in northeast Thailand [5]. The
Burkholderia pseudomallei Is Genetically Diverse in Agricultural Land in Northeast Thailand  [PDF]
Vanaporn Wuthiekanun,Direk Limmathurotsakul,Narisara Chantratita,Edward J. Feil,Nicholas P. J. Day,Sharon J. Peacock
PLOS Neglected Tropical Diseases , 2009, DOI: 10.1371/journal.pntd.0000496
Abstract: Background The soil-dwelling Gram-negative bacterium Burkholderia pseudomallei is the cause of melioidosis. Extreme structuring of genotype and genotypic frequency has been demonstrated for B. pseudomallei in uncultivated land, but its distribution and genetic diversity in agricultural land where most human infections are probably acquired is not well defined. Methods Fixed-interval soil sampling was performed in a rice paddy in northeast Thailand in which 100 grams of soil was sampled at a depth of 30 cm from 10×10 sampling points each measuring 2.5 m by 2.5 m. Soil was cultured for the presence of B. pseudomallei and genotyping of colonies present on primary culture plates was performed using a combination of pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Principal Findings B. pseudomallei was cultured from 28/100 samples. Genotyping of 630 primary colonies drawn from 11 sampling points demonstrated 10 PFGE banding pattern types, which on MLST were resolved into 7 sequence types (ST). Overlap of genotypes was observed more often between sampling points that were closely positioned. Two sampling points contained mixed B. pseudomallei genotypes, each with a numerically dominant genotype and one or more additional genotypes present as minority populations. Conclusions Genetic diversity and structuring of B. pseudomallei exists despite the effects of flooding and the physical and chemical processes associated with farming. These findings form an important baseline for future studies of environmental B. pseudomallei.
Factors Associated with Multidrug-Resistant Tuberculosis Patients in the Upper Northeast Thailand
K. Trinnawoottipong,P. Suggaravetsiri,N. Tesana,S. Chaiklieng
Research Journal of Medical Sciences , 2012, DOI: 10.3923/rjmsci.2012.208.213
Abstract: A matched case-control study was conducted to identify the factors associated with MDR in the Upper Northeast Thailand. The ratio of MDR per non-MDR was 1:2 and medical records were retrospectively reviewed. To identify the factors associated with MDR by conditional logistic regression analysis and were presented by adjusted matched Odds Ratio (mORadj) and 95% confidence interval (95% CI). In total 273 cases were included, divided into 91 MDR and 182 non-MDR. The factors associated with MDR; irregular TB follow up in the past was 264.6 times higher risk (95% CI: 23.1-3036.4) to have MDR. DOT by self administrative was 36.0 times higher risk (95% CI: 2.3-576.2) as compared with DOT by health care providers. Co-morbidity diseases were 5.8 times higher risk to have MDR (95% CI: 1.5-21.9). Strengthening DOTs strategy for shorting the delay of diagnosis and treatment, decreasing irregular TB follow up that aimed to increase success rate and prevent MDR. Should be developed TB/DM collaborative strategies and guidelines for preventing the transmission of M. tuberculosis in DM patients.
Rubber Tree Distribution Mapping in Northeast Thailand  [PDF]
Zhe Li, Jefferson M. Fox
International Journal of Geosciences (IJG) , 2011, DOI: 10.4236/ijg.2011.24060
Abstract: In many parts of mainland Southeast Asia rubber plantations are expanding rapidly in areas where the crop was not historically found. Monitoring and mapping the distribution of rubber trees in the region is necessary for developing a better understanding of the consequences of land-cover and land-use change on carbon and water cycles. In this study, we conducted rubber tree growth mapping in Northeast Thailand using Landsat 5 TM data. A Mahalanobis typicality method was used to identify different age rubber trees. Landsat 5 TM 30 m non-thermal reflective bands, NDVI and tasseled cap transformation components were selected as the model input metrics. The validation was carried out using provincial level agricultural statistical data on the rubber tree growth area. At regional (Northeast Thailand) and provincial scales, the estimates of mature and middle-age rubber stands produced from 30 m Landsat 5 TM data compared well (high statistical significance) with the provincial rubber tree growth statistical data.
Host Responses to Melioidosis and Tuberculosis Are Both Dominated by Interferon-Mediated Signaling  [PDF]
Gavin C. K. W. Koh, M. Fernanda Schreiber, Ruben Bautista, Rapeephan R. Maude, Susanna Dunachie, Direk Limmathurotsakul, Nicholas P. J. Day, Gordon Dougan, Sharon J. Peacock
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054961
Abstract: Melioidosis (Burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in Northeast Thailand and northern Australia. B. pseudomallei is a soil saprophyte endemic to Southeast Asia and northern Australia. The clinical presentation of melioidosis may mimic tuberculosis (both cause chronic suppurative lesions unresponsive to conventional antibiotics and both commonly affect the lungs). The two diseases have overlapping risk profiles (e.g., diabetes, corticosteroid use), and both B. pseudomallei and Mycobacterium tuberculosis are intracellular pathogens. There are however important differences: the majority of melioidosis cases are acute, not chronic, and present with severe sepsis and a mortality rate that approaches 50% despite appropriate antimicrobial therapy. By contrast, tuberculosis is characteristically a chronic illness with mortality <2% with appropriate antimicrobial chemotherapy. We examined the gene expression profiles of total peripheral leukocytes in two cohorts of patients, one with acute melioidosis (30 patients and 30 controls) and another with tuberculosis (20 patients and 24 controls). Interferon-mediated responses dominate the host response to both infections, and both type 1 and type 2 interferon responses are important. An 86-gene signature previously thought to be specific for tuberculosis is also found in melioidosis. We conclude that the host responses to melioidosis and to tuberculosis are similar: both are dominated by interferon-signalling pathways and this similarity means gene expression signatures from whole blood do not distinguish between these two diseases.
Municipal Human Excreta Management in Northeast Thailand
Weerasak Suebsoh,Lertchai Charerntanyarak
Pakistan Journal of Social Sciences , 2012,
Abstract: The study aimed at exploring the situation of municipal Human Excreta Management (HEM) in Northeast Thailand. Both qualitative and quantitative methods were used for data collection. The findings indicated that nearly all municipalities (98%) had their own legislation regarding HEM. However, the HEM policies were not clear (89%). Regarding collection and transportation services, 78% were serviced by private licensed companies, 13.04% by unlicensed private companies and 9% by the municipalities. Municipalities had only 26% appropriate disposal sites. Only 4% of these disposal sites could be used in practice because of long transfer distances, lack of maintenance, or inappropriate treatment system or model. Municipalities that had no disposal system took them into public land, grassland, or orchard and rice fields, with or without permission from the landowner. Thus, having no disposal system and untreated human excreta is the principal cause in the transmission of pathogens leading to human illnesses. Therefore, for effective management of sanitation, it is necessary for related organizations to balance the sometimes-competing requirements for planning, design and construction of facilities, as well as to monitor the safe operation of their HEM.
Two New Records of Coleochaetalean Algae (Coleochaetales, Chlorophyta) from Northeast Thailand
W. Mahakham,P. Theerakulpisut
International Journal of Botany , 2010,
Abstract: This study is an attempt to contribute and add information on the freshwater algal floral in Thailand. In this study, two members of coleochaetalean green algae, viz., Chaetosphaeridium globosum (Norstedt) Klebahn and Coleochaete nitellarum Jost are reported for the first time for Thailand. Both of them were found as epiphytes on charophyte algae in a mesotrophic reservoir, namely Hui Nam Sab from Amnat Charoen province, Northeast Thailand. Illustrated descriptions of the newly recorded species along with a short note on the species and its distribution are provided. In addition, some ecological aspects of the studied reservoir and coleochaetalean algae are discussed.
Glyburide Reduces Bacterial Dissemination in a Mouse Model of Melioidosis  [PDF]
Gavin C. K. W. Koh ,Tassili A. Weehuizen,Katrin Breitbach,Kathrin Krause,Hanna K. de Jong,Liesbeth M. Kager,Arjan J. Hoogendijk,Antje Bast,Sharon J. Peacock,Tom van der Poll,Ivo Steinmetz,W. Joost Wiersinga
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002500
Abstract: Background Burkholderia pseudomallei infection (melioidosis) is an important cause of community-acquired Gram-negative sepsis in Northeast Thailand, where it is associated with a ~40% mortality rate despite antimicrobial chemotherapy. We showed in a previous cohort study that patients taking glyburide ( = glibenclamide) prior to admission have lower mortality and attenuated inflammatory responses compared to patients not taking glyburide. We sought to define the mechanism underlying this observation in a murine model of melioidosis. Methods Mice (C57BL/6) with streptozocin-induced diabetes were inoculated with ~6×102 cfu B. pseudomallei intranasally, then treated with therapeutic ceftazidime (600 mg/kg intraperitoneally twice daily starting 24 h after inoculation) in order to mimic the clinical scenario. Glyburide (50 mg/kg) or vehicle was started 7 d before inoculation and continued until sacrifice. The minimum inhibitory concentration of glyburide for B. pseudomallei was determined by broth microdilution. We also examined the effect of glyburide on interleukin (IL) 1β by bone-marrow-derived macrophages (BMDM). Results Diabetic mice had increased susceptibility to melioidosis, with increased bacterial dissemination but no effect was seen of diabetes on inflammation compared to non-diabetic controls. Glyburide treatment did not affect glucose levels but was associated with reduced pulmonary cellular influx, reduced bacterial dissemination to both liver and spleen and reduced IL1β production when compared to untreated controls. Other cytokines were not different in glyburide-treated animals. There was no direct effect of glyburide on B. pseudomallei growth in vitro or in vivo. Glyburide directly reduced the secretion of IL1β by BMDMs in a dose-dependent fashion. Conclusions Diabetes increases the susceptibility to melioidosis. We further show, for the first time in any model of sepsis, that glyburide acts as an anti-inflammatory agent by reducing IL1β secretion accompanied by diminished cellular influx and reduced bacterial dissemination to distant organs. We found no evidence for a direct effect of glyburide on the bacterium.
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