Non-linear effect of different humidity types on scrub typhus occurrence in endemic provinces, Thailand.

BACKGROUND: Reported monthly scrub typhus (ST) cases in Thailand has an increase in the number of cases during 2009-2014. Humidity is a crucial climatic factor for the survival of chiggers, which is the disease vectors. The present study was to determine the role of humidity in ST occurrence in Thailand and its delayed effect. METHODS: We obtained the climate data from the Department of Meteorology, the disease data from Ministry of Public Health. Negative binomial regression combined with a distributed lag non-linear model (NB-DLNM) was employed to determine the non-linear effects of different types of humidity on the disease. This model controlled overdispersion and confounder, including seasonality, minimum temperature, and cumulative total rainwater. RESULTS: The occurrence of the disease in the 6-year period showed the number of cases gradually increased summer season (Mid-February - Mid-May) and then reached a plateau during the rainy season (Mid-May - Mid-October) and then steep fall after the cold season (Mid-October - Mid-February). The high level (at 70%) of minimum relative humidity (RHmin) was associated with a 33% (RR 1.33, 95% CI 1.13-1.57) significant increase in the number of the disease; a high level (at 14 g/m3) of minimum absolute humidity (AHmin) was associated with a 30% (RR 1.30, 95% CI 1.14-1.48); a high level (at 1.4 g/kg) of minimum specific humidity (SHmin) was associated with a 28% (RR 1.28, 95% CI 1.04-1.57). The significant effects of these types of humidity occurred within the past month. CONCLUSION: Humidity played a significant role in enhancing ST cases in Thailand, particularly at a high level and usually occurred within the past month. NB-DLNM had good controlled for the overdispersion and provided the precise estimated relative risk of non-linear associations. Results from this study contributed the evidence to support the Ministry of Public Health on warning system which might be useful for public health intervention and preparation in Thailand

Factors associated with dengue prevention behaviour in Lowokwaru, Malang, Indonesia: a cross-sectional study

Abstract Background Dengue prevention is important for controlling the spread of dengue infection. Transmission of dengue can be prevented by controlling mosquito breeding sites. Indonesia has dengue a prevention program to minimize mosquito breeding sites known as 3 M Plus. This study aimed to investigate factors associated with dengue prevention behaviour among respondents in the Lowokwaru subdistrict, an urban area in Malang, Indonesia. Methods This cross-sectional study used a semi-structured questionnaire that was conducted by face-to-face interview. Results Older respondents (> 60 years and 41–60 years) showed better dengue prevention behaviour than younger respondents (21–40 years and < 21 years) (p value = 0.01). Proportionally more male respondents showed poor dengue prevention behaviour compared with female respondents (p value = 0.007). Respondents who lived in Malang for long durations showed better dengue prevention behaviour compared with those who lived there for a shorter period (p value = 0.016). Those with more family members in their households practiced better dengue prevention behaviour compared with those with fewer family members (p value = 0.004). Perception was associated with dengue prevention behaviour. Respondents who had higher perceived susceptibility showed better dengue prevention behaviour compared with those who had moderate perceptions (p value = 0.000). Conclusions Age, gender, duration of stay in Malang, number of family members, and perception of dengue susceptibility were associated with dengue prevention behaviour

Effect of Praziquantel on Schistosoma mekongi Proteome and Phosphoproteome

Schistosoma mekongi causes schistosomiasis in southeast Asia, against which praziquantel (PZQ) is the only treatment option. PZQ resistance has been reported, thus increasing the requirement to understand mechanism of PZQ. Herein, this study aimed to assess differences in proteome and phosphoproteome of S. mekongi after PZQ treatment for elucidating its action. Furthermore, key kinases related to PZQ effects were predicted to identify alternative targets for novel drug development. Proteomes of S. mekongi were profiled after PZQ treatment at half maximal inhibitory concentration and compared with untreated worms. A total of 144 proteins were differentially expressed after treatment. In parallel, immunohistochemistry indicated a reduction of phosphorylation, with 43 phosphoproteins showing reduced phosphorylation, as identified by phosphoproteomic approach. Pathway analysis of mass spectrometric data showed that calcium homeostasis, worm antigen, and oxidative stress pathways were influenced by PZQ treatment. Interestingly, two novel mechanisms related to protein folding and proteolysis through endoplasmic reticulum-associated degradation pathways were indicated as a parasiticidal mechanism of PZQ. According to kinase&ndash;substrate predictions with bioinformatic tools, Src kinase was highlighted as the major kinase related to the alteration of phosphorylation by PZQ. Interfering with these pathways or applying Src kinase inhibitors could be alternative approaches for further antischistosomal drug development

Comprehensive analysis of miRNA profiling in Schistosoma mekongi across life cycle stages

Abstract Schistosoma mekongi, a significant schistosome parasite, has various life stages, including egg, cercaria, female, and male, that play crucial roles in the complex life cycle. This study aimed to explore the microRNA (miRNA) profiles across these developmental stages to understand their potential functions and evolutionary significance, which have not been studied. Pre-processed sequencing reads of small RNA (sRNA) were obtained, and annotations were performed against the S. japonicum reference miRNA database. Results indicated marked variations in miRNA profiles across different life stages, with notable similarities observed between female and male S. mekongi. Principal Coordinate Analysis (PCoA) and unsupervised clustering revealed distinct miRNA signatures for each stage. Gene ontology (GO) analysis unveiled the potential roles of these miRNAs in various biological processes. The differential expression of specific miRNAs was prominent across stages, suggesting their involvement in crucial developmental processes. Furthermore, orthologous miRNA analysis against various worm species revealed distinct presence–absence patterns, providing insights into the evolutionary relationships of these miRNAs. In conclusion, this comprehensive investigation into the miRNA profiles of S. mekongi offers valuable insights into the functional and evolutionary aspects of miRNAs in schistosome biology

Snail-borne parasitic diseases: an update on global epidemiological distribution, transmission interruption and control methods

Abstract Background Snail-borne parasitic diseases, such as angiostrongyliasis, clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, paragonimiasis and schistosomiasis, pose risks to human health and cause major socioeconomic problems in many tropical and sub-tropical countries. In this review we summarize the core roles of snails in the life cycles of the parasites they host, their clinical manifestations and disease distributions, as well as snail control methods. Main body Snails have four roles in the life cycles of the parasites they host: as an intermediate host infected by the first-stage larvae, as the only intermediate host infected by miracidia, as the first intermediate host that ingests the parasite eggs are ingested, and as the first intermediate host penetrated by miracidia with or without the second intermediate host being an aquatic animal. Snail-borne parasitic diseases target many organs, such as the lungs, liver, biliary tract, intestines, brain and kidneys, leading to overactive immune responses, cancers, organ failure, infertility and even death. Developing countries in Africa, Asia and Latin America have the highest incidences of these diseases, while some endemic parasites have developed into worldwide epidemics through the global spread of snails. Physical, chemical and biological methods have been introduced to control the host snail populations to prevent disease. Conclusions In this review, we summarize the roles of snails in the life cycles of the parasites they host, the worldwide distribution of parasite-transmitting snails, the epidemiology and pathogenesis of snail-transmitted parasitic diseases, and the existing snail control measures, which will contribute to further understanding the snail-parasite relationship and new strategies for controlling snail-borne parasitic diseases

Untargeted serum metabolomic profiling for early detection of Schistosoma mekongi infection in mouse model

Mekong schistosomiasis is a parasitic disease caused by blood flukes in the Lao People’s Democratic Republic and in Cambodia. The standard method for diagnosis of schistosomiasis is detection of parasite eggs from patient samples. However, this method is not sufficient to detect asymptomatic patients, low egg numbers, or early infection. Therefore, diagnostic methods with higher sensitivity at the early stage of the disease are needed to fill this gap. The aim of this study was to identify potential biomarkers of early schistosomiasis using an untargeted metabolomics approach. Serum of uninfected and S. mekongi-infected mice was collected at 2, 4, and 8 weeks post-infection. Samples were extracted for metabolites and analyzed with a liquid chromatography-tandem mass spectrometer. Metabolites were annotated with the MS-DIAL platform and analyzed with Metaboanalyst bioinformatic tools. Multivariate analysis distinguished between metabolites from the different experimental conditions. Biomarker screening was performed using three methods: correlation coefficient analysis; feature important detection with a random forest algorithm; and receiver operating characteristic (ROC) curve analysis. Three compounds were identified as potential biomarkers at the early stage of the disease: heptadecanoyl ethanolamide; picrotin; and theophylline. The levels of these three compounds changed significantly during early-stage infection, and therefore these molecules may be promising schistosomiasis markers. These findings may help to improve early diagnosis of schistosomiasis, thus reducing the burden on patients and limiting spread of the disease in endemic areas

Transcriptomic analysis of male and female Schistosoma mekongi adult worms

Abstract Background Schistosoma mekongi is one of five major causative agents of human schistosomiasis and is endemic to communities along the Mekong River in southern Lao People’s Democratic Republic (Laos) and northern Cambodia. Sporadic cases of schistosomiasis have been reported in travelers and immigrants who have visited endemic areas. Schistosoma mekongi biology and molecular biology is poorly understood, and few S. mekongi gene and transcript sequences are available in public databases. Results Transcriptome sequencing (RNA-Seq) of male and female S. mekongi adult worms (a total of three biological replicates for each sex) were analyzed and the results demonstrated that approximately 304.9 and 363.3 million high-quality clean reads with quality Q30 (> 90%) were obtained from male and female adult worms, respectively. A total of 119,604 contigs were assembled with an average length of 1273 nt and an N50 of 2017 nt. From the contigs, 20,798 annotated protein sequences and 48,256 annotated transcript sequences were obtained using BLASTP and BLASTX searches against the UniProt Trematoda database. A total of 4658 and 3509 transcripts were predominantly expressed in male and female worms, respectively. Male-biased transcripts were mostly involved in structural organization while female-biased transcripts were typically involved in cell differentiation and egg production. Interestingly, pathway enrichment analysis suggested that genes involved in the phosphatidylinositol signaling pathway may play important roles in the cellular processes and reproductive systems of S. mekongi worms. Conclusions We present comparative transcriptomic analyses of male and female S. mekongi adult worms, which provide a global view of the S. mekongi transcriptome as well as insights into differentially-expressed genes associated with each sex. This work provides valuable information and sequence resources for future studies of gene function and for ongoing whole genome sequencing efforts in S. mekongi

Chromosome-scale genome of the human blood fluke Schistosoma mekongi and its implications for public health

Abstract Background Schistosoma mekongi is a human blood fluke causing schistosomiasis that threatens approximately 1.5 million humans in the world. Nonetheless, the limited available S. mekongi genomic resources have hindered understanding of its biology and parasite-host interactions for disease management and pathogen control. The aim of our study was to integrate multiple technologies to construct a high-quality chromosome-level assembly of the S. mekongi genome. Methods The reference genome for S. mekongi was generated through integrating Illumina, PacBio sequencing, 10 × Genomics linked-read sequencing, and high-throughput chromosome conformation capture (Hi-C) methods. In this study, we conducted de novo assembly, alignment, and gene prediction to assemble and annotate the genome. Comparative genomics allowed us to compare genomes across different species, shedding light on conserved regions and evolutionary relationships. Additionally, our transcriptomic analysis focused on genes associated with parasite-snail interactions in S. mekongi infection. We employed gene ontology (GO) enrichment analysis for functional annotation of these genes. Results In the present study, the S. mekongi genome was both assembled into 8 pseudochromosomes with a length of 404 Mb, with contig N50 and scaffold N50 lengths of 1168 kb and 46,759 kb, respectively. We detected that 43% of the genome consists of repeat sequences and predicted 9103 protein-coding genes. We also focused on proteases, particularly leishmanolysin-like metalloproteases (M8), which are crucial in the invasion of hosts by 12 flatworm species. Through phylogenetic analysis, it was discovered that the M8 gene exhibits lineage-specific amplification among the genus Schistosoma. Lineage-specific expansion of M8 was observed in blood flukes. Additionally, the results of the RNA-seq revealed that a mass of genes related to metabolic and biosynthetic processes were up-regulated, which might be beneficial for cercaria production. Conclusions This study delivers a high-quality, chromosome-scale reference genome of S. mekongi, enhancing our understanding of the divergence and evolution of Schistosoma. The molecular research conducted here also plays a pivotal role in drug discovery and vaccine development. Furthermore, our work greatly advances the understanding of host-parasite interactions, providing crucial insights for schistosomiasis intervention strategies. Graphical Abstrac