Leishmaniasis: An Evolving Public Health Concern in Thailand

Leishmaniasis is a parasitic disease caused by flagellated protozoa of the genus Leishmania. It is transmitted by the bite of an infected sandfly. The 3 main clinical forms of the disease are cutaneous leishmaniasis (CL), visceral leishmaniasis (VL) and mucocutaneous leishmaniasis (MCL). Prior to 1996, all leishmaniasis cases were infected during the visit to the endemic areas. Thereafter, autochthonous leishmaniasis cases have been reported in Thailand. From 1996 to the present, at least 21 cases of autochthonous leishmaniasis have been confirmed in Thailand. Leishmania siamensis, a novel species of Leishmania, was suspected of being the causative pathogens in some of those cases, However, the data supporting the existence of this new species is limited. Until recently, in-depth investigation using molecular characterization and isoenzyme analysis revealed that this suspected novel species consists of 2 different, but closely related strains: L. siamensis and L. martiniquensis. L. martiniquensis, a rare species firstly discovered on Martinique Island, is the cause of leishmaniasis in the majority of cases. Meanwhile, L. siamensis, a true novel species firstly and only reported from Thailand, was confirmed as the cause of leishmaniasis in two autochthonous cases. Two clinical forms (CL and VL) have been observed in both L. martiniquensis and L. siamensis infection. The DNA of L. martiniquensis was found in black rats, suggesting their role as a natural reservoir. The presence of L. martiniquensis DNA in two sandfly species (Sergentomyia gemmea and Sergentomyia barraudi) that are commonly found in affected areas may also suggest their role as potential vectors. Here, we update the status of leishmaniasis in Thailand and its emergence as a potential public health concern

Transcriptomic-wide discovery of direct and indirect HuR RNA targets in activated CD4+ T cells

Due to poor correlation between steady state mRNA levels and protein product, purely transcriptomic profiling methods may miss genes posttranscriptionally regulated by RNA binding proteins (RBPs) and microRNAs (miRNAs). RNA immunoprecipitation (RIP) methods developed to identify in vivo targets of RBPs have greatly elucidated those mRNAs which may be regulated via transcript stability and translation. The RBP HuR (ELAVL1) and family members are major stabilizers of mRNA. Many labs have identified HuR mRNA targets; however, many of these analyses have been performed in cell lines and oftentimes are not independent biological replicates. Little is known about how HuR target mRNAs behave in conditional knock-out models. In the present work, we performed HuR RIP-Seq and RNA-Seq to investigate HuR direct and indirect targets using a novel conditional knock-out model of HuR genetic ablation during CD4+ T activation and Th2 differentiation. Using independent biological replicates, we generated a high coverage RIP-Seq data set (>160 million reads) that was analyzed using bioinformatics methods specifically designed to find direct mRNA targets in RIP-Seq data. Simultaneously, another set of independent biological replicates were sequenced by RNA-Seq (>425 million reads) to identify indirect HuR targets. These direct and indirect targets were combined to determine canonical pathways in CD4+ T cell activation and differentiation for which HuR plays an important role. We show that HuR may regulate genes in multiple canonical pathways involved in T cell activation especially the CD28 family signaling pathway. These data provide insights into potential HuR-regulated genes during T cell activation and immune mechanisms

Posttranscriptional gene regulation of CD4+ T cell cytokine expression by the RNA binding protein HuR

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Posttranscriptional gene regulation by RNA-binding proteins such as HuR fine tunes gene expression in T cells leading to powerful effects on immune responses. HuR can stabilize target mRNAs and/or promote translation by interacting with their 3-UTR AUrich elements. We discovered that the interaction of HuR with the Il2ra (CD25) mRNA transcript is required for its optimal translation. Conditional HuR knockout (KO) in CD4+ T cells resulted in loss of IL-2 homeostasis and defects in Th2 cytokine production. In an allergic airway inflammatory model, OVA-challenged HuR KO mice had decreased lung cellular infiltration, eosinophilia and IL-13. These results demonstrate that HuR plays a pivotal role in maintaining normal IL-2 homeostasis, augmenting Th2 differentiation and promoting allergic airway inflammation

Leishmaniasis: An Evolving Public Health Concern in Thailand

Leishmaniasis is a parasitic disease caused by flagellated protozoa of the genus Leishmania. It is transmitted by infection from the bite of an infected sandfly. The 3 main clinical forms of the disease are cutaneous leishmaniasis (CL), visceral leishmaniasis (VL) and mucocutaneous leishmaniasis (MCL). Prior to 1996, all leishmaniasis cases were infected during the visit to the endemic areas. Thereafter, autochthonous leishmaniasis cases have been reported in Thailand. During 1996 to the present, at least 21 cases of autochthonous leishmaniasis have been confirmed in Thailand. Leishmania siamensis, a novel species of Leishmania, was suspected of being the causative pathogens in some of those cases, although the data supporting the existence of this new species is limited. Until recently, in-depth investigation using molecular characterization and isoenzyme analysis revealed that a suspected novel species consists of 2 different, but closely related strains: L. siamensis and L. martiniquensis. L. martiniquensis, a rare species firstly discovered on Martinique Island, is the cause of leishmaniasis in the majority of cases. Meanwhile, L. siamensis, a true novel species first and only reported from Thailand, was confirmed as the cause of leishmaniasis in two autochthonous cases. Two clinical forms (CL and VL) have been observed in both L. martiniquensis and L. siamensis infection. DNA of L. martiniquensis was found in black rats, suggesting their role as a natural reservoir. The presence of L. martiniquensis DNA in two sandfly species (Sergentomyia gemmea and Sergentomyia barraudi) that are commonly found in affected areas may also suggest their role as potential vectors. Here, we update the status of leishmaniasis in Thailand and its emergence as a potential public health concern

Prevalence and Health Effects of Intestinal Parasitic Infection in School Children in Satun Province, Thailand: A Cross-Sectional Study

Objective: Intestinal parasitic infection is a major health problem in the southern region of Thailand. Despite an established annual deworming program, many school age children still suffer from parasitic infection. The aim of this study was to investigate the prevalence and health effects of intestinal parasitic infection in school children in Satun Province, Thailand. Methods: This cross-sectional study was conducted in children aged of 3 to 15 years during the period December 2014 to January 2015. Body mass index and hematocrit measurements were performed. Stool samples were collected for parasite detection by direct examination and concentration technique. Results: The prevalence of intestinal parasitic infection was 18.42%. B.hominis (29%), Giardia lamblia (13.3%), Trichuris trichiura (13.3%), and hookworm (13.3%) were the most commonly isolated parasites. School KY had the highest rate of intestinal parasitic infection, followed by schools RC, YT, and SD. Rate of soil-transmitted helminthic (STH) infection was highest at school RC, while the highest rate of protozoa infection was found at school KY. Only STH infection was significantly associated with anemia. No significant association was observed between weight status and parasitic infection. Conclusion: Intestinal parasitic infection continues to be a problem in school children in Satun Province, Thailand. STH infection was found to be significantly associated with anemia. The majority of parasite types detected at each school varied substantially, which may indicate distinctly different sanitation-related problems at each school. Therefore, improvement in personal sanitation and health education should be emphasized at every school in the area to prevent parasitic infection

Top 50 RNA-Seq significantly different genes sorted by magnitude of fold change (KO/CTL).

<p>The official symbol of the top 50 (significant) genes found via RNA-Seq are given, along with fold change (KO/CTL), raw p-value for differential expression, and q (false discovery rate value based on method of Benjamini-Hochberg).</p

Top canonical pathway (iCOS-iCOSL Signaling in T Helper Cells) overlaid with hits from union of RIP-Seq and RNA-Seq analyses.

<p>Significant pathway nodes are shaded according to size of fold change (red >1; green <1), with white nodes indicating genes that were not detected in the samples and gray indicating genes that were detected, but not significant. Nodes with multicolor gradients denote nodes with significant genes with fold changes in different directions (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129321#pone.0129321.t002" target="_blank">Table 2</a> for more details). Fold change is defined as KO/CTL (RNA-Seq) or IP/CTL (RIP-Seq). Colored double borders indicate that the molecule is a complex.</p

Canonical pathway for CD28 Signaling in T Helper Cells overlaid with hits from union of RIP-Seq and RNA-Seq analyses.

<p>Significant pathway nodes are shaded according to size of fold change (red >1; green <1), with white nodes indicating genes that were not detected in the samples and gray indicating genes that were detected, but not significant. Nodes with multicolor gradients denote nodes with significant genes with fold changes in different directions (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129321#pone.0129321.t003" target="_blank">Table 3</a> for more details). Fold change is defined as KO/CTL (RNA-Seq) or IP/CTL (RIP-Seq). Colored double borders indicate that the molecule is a complex.</p

Top 50 canonical pathways for union of RIP-Seq and RNA-Seq analyses sorted by p-value.

<p>Size indicates the number of molecules that comprise a pathway and DE indicates the number of significant genes identified by either RIP-Seq or RNA-Seq, where % represents DE/size. <i>p</i> is based on Fisher’s Exact Test and indicates pathways that are enriched for genes from RIP-Seq or RNA-Seq.</p