Assessing impacts of climate change on water resources and agriculture: A case study of Tonle Sap basin, Cambodia : A thesis submitted in partial fulfilment of the requirements for the Degree of Master of Water Resource Management at Lincoln University

Cambodia’s Tonle Sap Lake is the largest permanent freshwater body not just in Cambodia, but in Southeast Asia, and is also one of the world’s richest lacustrine-wetland ecosystems. Agriculture and fisheries provide the primary livelihoods of people living in the area. Despite a high abundance of natural resources, the area around Tonle Sap Lake is known to be one of the poorest areas in Cambodia, where most people derive their livelihoods directly from the resources provided by the lake. This study aims to assess the impacts caused by climate change on water resources and agricultural production in the basin by looking into future changes of streamflow of the tributary rivers, flood pulse and the paddy rice areas supported by the Mekong River’s flood pulse. For this study, six climate change scenarios were employed to assess future change in rainfall and river flow. They are the result of the combinations between three global circulation models (GFDL-CM3, GISS-E2-R-CC and IPSL-CM5A-MR) and two representative concentration pathways (RCP4.5 and RCP8.5). HEC-HMS was used for simulating rainfall and runoff for 11 sub-basins that feed the Tonle Sap Lake. HEC-RAS was used for computing inundation areas around the lake. Both models were calibrated and validated using data for the year 2000–2005 and 2006–2007, respectively. The results from HEC-RAS were exported in a format that enabled further analysis in GIS to examine changes to paddy rice areas at both the basin- and sub-basin scales. Both HEC-HMS and HEC-RAS model performances were evaluated using statistical indices NSE and R2. The indices indicated satisfactory performance for both simulation models with NSE > 0.40 and R2 > 0.60 for HEC-HMS and NSE > 0.60 and R2 ≥ 0.90 for HEC-RAS. The main findings in the study were the reduction of annual streamflow that is projected to occur in almost every sub-basin under all climate change scenarios up to the year 2030. The Dauntri sub-basin is projected to experience the highest streamflow decrease, up to 62.53%, while streamflow in the Sen and Boribor sub-basins showed a slight increase. The results from HEC-RAS suggest a decrease of flood pulse extent under all climate change scenarios. The magnitudes of decrease are almost the same for each scenario with an average decrease of around 10%. The Sen sub-basin showed the greatest reduction of flooded areas (13.82%) while Sangker was projected to decrease the least (2.00%). Though the Sen and Boribor catchments show an increase in streamflow, the increase is offset by the reduced flows in the remaining catchments, thus contributing less flow to the lake overall, leading to its reduced area. The results also suggest a decrease in paddy rice areas supported by the flood pulse. Stuang is the sub-basin with the highest reduction of paddy rice areas of up to 28.36%, while Sangker remains the sub-basin with the least reduction (2.67%). Some noteworthy implications arise from the main findings. The decrease of flows in the tributary rivers suggests an increase in drought risk and consequences for household water supply and surface irrigation that divert or extract water from those rivers. The change of the extent of flood pulse suggests that there will be lower nutrients and sediment loads and this would substantially impact the ecosystems in the lake and other connected parts. The reduction of paddy rice areas underscores the potential implications for social and economic development such as food insecurity, unemployment and economic impacts

Evaluation of cutaneous immune response in a controlled human in vivo model of mosquito bites

International audienceMosquito-borne viruses are a growing global threat. Initial viral inoculation occurs in the skin via the mosquito ‘bite’, eliciting immune responses that shape the establishment of infection and pathogenesis. Here we assess the cutaneous innate and adaptive immune responses to controlled Aedes aegypti feedings in humans living in Aedes -endemic areas. In this single-arm, cross-sectional interventional study (trial registration #NCT04350905), we enroll 30 healthy adult participants aged 18 to 45 years of age from Cambodia between October 2020 and January 2021. We perform 3-mm skin biopsies at baseline as well as 30 min, 4 h, and 48 h after a controlled feeding by uninfected Aedes aegypti mosquitos. The primary endpoints are measurement of changes in early and late innate responses in bitten vs unbitten skin by gene expression profiling, immunophenotyping, and cytokine profiling. The results reveal induction of neutrophil degranulation and recruitment of skin-resident dendritic cells and M2 macrophages. As the immune reaction progresses T cell priming and regulatory pathways are upregulated along with a shift to T h 2-driven responses and CD8 + T cell activation. Stimulation of participants’ bitten skin cells with Aedes aegypti salivary gland extract results in reduced pro-inflammatory cytokine production. These results identify key immune genes, cell types, and pathways in the human response to mosquito bites and can be leveraged to inform and develop novel therapeutics and vector-targeted vaccine candidates to interfere with vector-mediated disease

Evaluation of the CareStart™ glucose-6-phosphate dehydrogenase (G6PD) rapid diagnostic test in the field settings and assessment of perceived risk from primaquine at the community level in Cambodia.

BACKGROUND:Primaquine is an approved radical cure treatment for Plasmodium vivax malaria but treatment can result in life-threatening hemolysis if given to a glucose-6-phosphate dehydrogenase deficient (G6PDd) patient. There is a need for reliable point-of-care G6PD diagnostic tests. OBJECTIVES:To evaluate the performance of the CareStart™ rapid diagnostic test (RDT) in the hands of healthcare workers (HCWs) and village malaria workers (VMWs) in field settings, and to better understand user perceptions about the risks and benefits of PQ treatment guided by RDT results. METHODS:This study enrolled 105 HCWs and VMWs, herein referred to as trainees, who tested 1,543 healthy adult male volunteers from 84 villages in Cambodia. The trainees were instructed on G6PD screening, primaquine case management, and completed pre and post-training questionnaires. Each trainee tested up to 16 volunteers in the field under observation by the study staff. RESULTS:Out of 1,542 evaluable G6PD volunteers, 251 (16.28%) had quantitative enzymatic activity less than 30% of an adjusted male median (8.30 U/g Hb). There was no significant difference in test sensitivity in detecting G6PDd between trainees (97.21%), expert study staff in the field (98.01%), and in a laboratory setting (95.62%) (p = 0.229); however, test specificity was different for trainees (96.62%), expert study staff in the field (98.14%), and experts in the laboratory (98.99%) (p < 0.001). Negative predictive values were not statistically different for trainees, expert staff, and laboratory testing: 99.44%, 99.61%, and 99.15%, respectively. Knowledge scores increased significantly post-training, with 98.7% willing to prescribe primaquine for P.vivax malaria, an improvement from 40.6% pre-training (p < 0.001). CONCLUSION:This study demonstrated ability of medical staff with different background to accurately use CareStart™ RDT to identify G6PDd in male patients, which may enable safer prescribing of primaquine; however, pharmacovigilance is required to address possible G6PDd misclassifications

Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system.

SignificanceMetagenomic pathogen sequencing offers an unbiased approach to characterizing febrile illness. In resource-scarce settings with high biodiversity, it is critical to identify disease-causing pathogens in order to understand burden and to prioritize efforts for control. Here, metagenomic next-generation sequencing (mNGS) characterization of the pathogen landscape in Cambodia revealed diverse vector-borne and zoonotic pathogens irrespective of age and gender as risk factors. Identification of key pathogens led to changes in national program surveillance. This study is a "real world" example of the use of mNGS surveillance of febrile individuals, executed in-country, to identify outbreaks of vector-borne, zoonotic, and other emerging pathogens in a resource-scarce setting