Early warning systems for malaria outbreaks in Thailand: an anomaly detection approach

Background: Malaria continues to pose a significant health threat. Rapid identification of malaria infections and the deployment of active surveillance tools are crucial for achieving malaria elimination in regions where malaria is endemic, such as certain areas of Thailand. In this study, an anomaly detection system is introduced as an early warning mechanism for potential malaria outbreaks in countries like Thailand. Methods: Unsupervised clustering-based, and time series-based anomaly detection algorithms are developed and compared to identify abnormal malaria activity in Thailand. Additionally, a user interface tailored for anomaly detection is designed, enabling the Thai malaria surveillance team to utilize these algorithms and visualize regions exhibiting unusual malaria patterns. Results: Nine distinct anomaly detection algorithms we developed. Their efficacy in pinpointing verified outbreaks was assessed using malaria case data from Thailand spanning 2012 to 2022. The historical average threshold-based anomaly detection method triggered three times fewer alerts, while correctly identifying the same number of verified outbreaks when compared to the current method used in Thailand. A limitation of this analysis is the small number of verified outbreaks; further consultation with the Division of Vector Borne Disease could help identify more verified outbreaks. The developed dashboard, designed specifically for anomaly detection, allows disease surveillance professionals to easily identify and visualize unusual malaria activity at a provincial level across Thailand. Conclusion: An enhanced early warning system is proposed to bolster malaria elimination efforts for countries with a similar malaria profile to Thailand. The developed anomaly detection algorithms, after thorough comparison, have been optimized for integration with the current malaria surveillance infrastructure. An anomaly detection dashboard for Thailand is built and supports early detection of abnormal malaria activity. In summary, the proposed early warning system enhances the identification process for provinces at risk of outbreaks and offers easy integration with Thailand’s established malaria surveillance framework

A Scaled Linear Mixed Model for Multiple Outcomes

We propose a scaled linear mixed model to assess the effects of exposure and other covariates on multiple continuous outcomes. The most general form of the model allows a different exposure effect for each outcome. An important special case is a model that represents the exposure effects using a common global measure that can be characterized in terms of effect sizes. Correlations among different outcomes within the same subject are accommodated using random effects. We develop two approaches to model fitting, including the maximum likelihood method and the working parameter method. A key feature of both methods is that they can be easily implemented by repeatedly calling software for fitting standard linear mixed models, e.g., SAS PROC MIXED. Compared to the maximum likelihood method, the working parameter method is easier to implement and yields fully efficient estimators of the parameters of interest. We illustrate the proposed methods by analyzing data from a study of the effects of occupational pesticide exposure on semen quality in a cohort of Chinese men.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66256/1/j.0006-341X.2000.00593.x.pd

Beneficial effects of 2 years of administration of parenteral testosterone undecanoate on the metabolic syndrome and on non-alcoholic liver steatosis and C-reactive protein

Abstract Background: Elderly men often show a concurrence of a decline of testosterone with attributes of the metabolic syndrome. This study tested the effects of normalization of testosterone. Materials and methods: A total of 122 hypogonadal men (18-83 years, mean 59.6"8.0 years; ns11-45 years, ns25-55 years, ns53-65 years) were included in the study. Their baseline testosterone levels were between 0.14 and 4.51 ng/mL (n)4.90 ng/mL) and were treated with parenteral testosterone undecanoate for 2 years as the sole intervention (administration at 0 and 6 weeks, and thereafter every 12 weeks). Results: Plasma testosterone increased from 3.3"1.9 ng/mL to 4.1"1.5 ng/mL (p-0.01) at 3 months, and then stabilized at 6.8"1.3 ng/mL after the first 6 months. There was a remarkable progressive linear decline in body weight, body mass index, and waist circumference over the entire study period. Plasma cholesterol decreased significantly over the first 12 months, and then stabilized. Plasma glucose, triglycerides, low-density lipoprotein cholesterol, and C-reactive protein decreased significantly and high-density lipoprotein cholesterol increased significantly over the 24-month study period in a non-linear manner. There was a significant decrease in aspartate aminotransferase and alanine aminotransferase levels over the first 9 and 12 months, and then values leveled off. Changes in variables were largely corre

Exploring the Socioeconomic Importance of Antimicrobial Use in the Small-Scale Pig Sector in Vietnam

Antimicrobial resistance (AMR) is influenced by antimicrobial use in human and animal health. This use exerts selection pressure on pathogen populations with the development of resistance and the exchange of resistance genes. While the exact scale of AMR in Vietnam remains uncertain, recent studies suggest that it is a major issue in both human and animal health. This study explored antimicrobial use behaviors in 36 pig farms in the Nam Dinh Province (North) and the Dong Nai Province (South) of Vietnam (with a median of 5.5 breeding sows and 41 fattening pigs). It also estimated the economic costs and benefits of use for the producer. Data were collected through a structured face-to-face interview with additional productivity data collected by farmers during a six-week period following the initial interview. Overall, antimicrobial use was high across the farms; however, in-feed antimicrobial use is likely to be under-reported due to misleading and imprecise labelling on premixed commercial feeds. An economic analysis found that the cost of antimicrobials was low relative to other farm inputs (~2% of total costs), and that farm profitability was precariously balanced, with high disease and poor prices leading to negative and low profits. Future policies for smallholder farms need to consider farm-level economics and livestock food supply issues when developing further antimicrobial use interventions in the region

Semen quality in Peruvian pesticide applicators: association between urinary organophosphate metabolites and semen parameters

<p>Abstract</p> <p>Background</p> <p>Organophosphates are broad class of chemicals widely used as pesticides throughout the world. We performed a cross-sectional study of associations between dialkylphosphate metabolites of organophosphates and semen quality among pesticide applicators in Majes (Arequipa), Peru.</p> <p>Methods</p> <p>Thirty-one men exposed to organophosphate (OP) pesticides and 31 non-exposed were recruited (age, 20–60 years). In exposed subjects, semen and a blood sample were obtained one day after the last pesticide application. Subjects were grouped according to levels of OP metabolites in urine. Semen samples were analyzed for sperm concentration, percentage of sperm motility, percentage of normal morphology, semen leucocytes and concentrations of fructose and zinc. Exposure to OP was assessed by measuring six urinary OP metabolites (dimethyl and diethyl phosphates and thiophosphates) by gas chromatography using a single flame photometric detector.</p> <p>Results</p> <p>Diethyldithiophosphate (p = 0.04) and diethylthiophosphate (p = 0.02) better reflected occupational pesticide exposure than other OP metabolites. Semen analysis revealed a significant reduction of semen volume and an increase in semen pH in men with OP metabolites. Multiple regression analysis showed that both occupational exposure to pesticides and the time of exposure to pesticides were more closely related to alterations in semen quality parameters than the single measurement of OP metabolites in urine.</p> <p>Conclusion</p> <p>The study demonstrated that occupational exposure to OP pesticides was more closely related to alterations in semen quality than a single measurement of urine OP metabolites. Current measurement of OP metabolites in urine may not reflect the full risk.</p

Transmission of highly pathogenic avian influenza in the nomadic free-grazing duck production system in Viet Nam.

The presence of free-grazing ducks (FGD) has consistently been shown to be associated with highly pathogenic avian influenza virus (HPAIV) H5N1 outbreaks in South-East Asia. However, the lack of knowledge about the transmission pathways limits the effectiveness of control efforts. To address this gap, we developed a probabilistic transmission model of HPAIV H5N1 in the nomadic FGD production system in Viet Nam, assuming different scenarios to address parameter uncertainty. Results suggested that HPAIV H5N1 could spread within the nomadic FGD production system, with an estimated flock-level effective reproduction number (re) ranging from 2.16 (95% confidence interval (CI): 1.39-3.49) to 6.10 (95%CI: 3.93-9.85) depending on the scenario. Indirect transmission via boats and trucks was shown to be the main transmission route in all scenarios. Results suggest that re could be reduced below one with 95% confidence if 86% of FGD flocks were vaccinated in the best-case scenario or 95% in the worst-case scenario. If vaccination was combined with cleaning and disinfection of transport vehicles twice a week, vaccination coverage could be lowered to 60% in the best-case scenario. These findings are of particular relevance for prioritising interventions for effective control of HPAIV in nomadic free-grazing duck production systems

Characterizing Antimicrobial Use in the Livestock Sector in Three South East Asian Countries (Indonesia, Thailand, and Vietnam)

A framework was developed to characterize the antimicrobial use/antimicrobial resistance complex in livestock systems in Indonesia, Vietnam, and Thailand. Farm profitability, disease prevention, and mortality rate reduction were identified as drivers toward antimicrobial use in livestock systems. It revealed that antimicrobial use was high in all sectors studied, and that routine preventative use was of particular importance to broiler production systems. Misleading feed labeling was identified as a hurdle to the collection of accurate antimicrobial use data, with farmers being unaware of the antimicrobials contained in some commercial feed. Economic analysis found that the cost of antimicrobials was low relative to other farm inputs, and that farm profitability was precariously balanced. High disease and poor prices were identified as potential drivers toward economic loss. The research indicates that antimicrobial use in small-scale poultry production systems improves feed conversion ratios and overall productivity. However, data were limited to quantify adequately these potential gains and their impacts on the food supply. During the study, all countries embraced and implemented policies on better management of antimicrobial use in livestock and surveillance of antimicrobial resistance. Future policies need to consider farm-level economics and livestock food supply issues when developing further antimicrobial use interventions in the region

Reducing Antimicrobial Usage in Small-Scale Chicken Farms in Vietnam: A 3-Year Intervention Study

Indiscriminate antimicrobial use (AMU) in animal production is a driver of antimicrobial resistance globally. There is a need to define sustainable interventions to reduce AMU in small-scale production systems, which currently represent the most widespread farming systems in South East Asia and many low- and middle-income countries. We conducted a before-and-after intervention study on a random sample of small-scale chicken farms in the Mekong Delta of Vietnam from 2016 to 2019. The study included a baseline followed by an intervention phase where farmers were provided with regular veterinary advice on flock health and husbandry, as well as antimicrobial replacement products. Of 102 recruited farms (raising &amp;gt;100 chickens per flock cycle), thirty-five (34.2%) entered the intervention phase, whilst the rest stopped raising chickens, mainly due to suboptimal flock performance. Through the implementation of our intervention, chicken flocks reduced levels of AMU by 66% [adjusted hazard ratio (HR) = 0.34; p = 0.002) from a baseline of 343.4 Animal Daily Doses per 1,000 chicken-days and decreased weekly mortality by 40% (adjusted HR = 0.60; p = 0.005) from a baseline mortality of 1.60 per 100 birds. Chicken bodyweight increased by 100 g (p = 0.002) in intervention flocks. Our findings demonstrate that the provision of veterinary advice can achieve substantial reductions in AMU in small-scale production systems without compromising flock health and productivity.</jats:p

DNMT3L Is a Regulator of X Chromosome Compaction and Post-Meiotic Gene Transcription

Previous studies on the epigenetic regulator DNA methyltransferase 3-Like (DNMT3L), have demonstrated it is an essential regulator of paternal imprinting and early male meiosis. Dnmt3L is also a paternal effect gene, i.e., wild type offspring of heterozygous mutant sires display abnormal phenotypes suggesting the inheritance of aberrant epigenetic marks on the paternal chromosomes. In order to reveal the mechanisms underlying these paternal effects, we have assessed X chromosome meiotic compaction, XY chromosome aneuploidy rates and global transcription in meiotic and haploid germ cells from male mice heterozygous for Dnmt3L. XY bodies from Dnmt3L heterozygous males were significantly longer than those from wild types, and were associated with a three-fold increase in XY bearing sperm. Loss of a Dnmt3L allele resulted in deregulated expression of a large number of both X-linked and autosomal genes within meiotic cells, but more prominently in haploid germ cells. Data demonstrate that similar to embryonic stem cells, DNMT3L is involved in an auto-regulatory loop in germ cells wherein the loss of a Dnmt3L allele resulted in increased transcription from the remaining wild type allele. In contrast, however, within round spermatids, this auto-regulatory loop incorporated the alternative non-coding alternative transcripts. Consistent with the mRNA data, we have localized DNMT3L within spermatids and sperm and shown that the loss of a Dnmt3L allele results in a decreased DNMT3L content within sperm. These data demonstrate previously unrecognised roles for DNMT3L in late meiosis and in the transcriptional regulation of meiotic and post-meiotic germ cells. These data provide a potential mechanism for some cases of human Klinefelter's and Turner's syndromes