Search results for: dengue cases

Authors: Ya-Mei Chang

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This research is intended to apply spatio-temporal point process methods to the dengue fever data in Tainan. The spatio-temporal intensity function of the dataset is assumed to be separable. The kernel estimation is a widely used approach to estimate intensity functions. The intensity function is very helpful to study the relation of the spatio-temporal point process and some covariates. The covariate effects might be nonlinear. An nonparametric smoothing estimator is used to detect the nonlinearity of the covariate effects. A fitted parametric model could describe the influence of the covariates to the dengue fever. The correlation between the data points is detected by the K-function. The result of this research could provide useful information to help the government or the stakeholders making decisions.

Keywords: dengue fever, spatial point process, kernel estimation, covariate effect

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Authors: Sadia Imran, Zenab Naseem

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Dengue fever is one of the most alarming mosquito-borne viral diseases. Dengue virus has been distributed over the years exponentially throughout the world be it tropical or sub-tropical regions of the world, particularly in the last ten years. Changing topography, climate change in terms of erratic seasonal trends, rainfall, untimely monsoon early or late and longer or shorter incidences of either summer or winter. Globalization, frequent travel throughout the world and viral evolution has lead to more severe forms of Dengue. Global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. In recent years, Pakistan experienced a deadly outbreak of the disease. The reason could be that they have the maximum exposure outdoors. Public organizations have observed that changing climate, especially lower average summer temperature, and increased vegetation have created tropical-like conditions in the city, which are suitable for Dengue virus growth. We will conduct a time-series analysis to study the interrelationship between dengue incidence and diurnal ranges of temperature and humidity in Pakistan, Lahore being the main focus of our study. We have used annual data from 2005 to 2015. We have investigated the relationship between climatic variables and dengue incidence. We used time series analysis to describe temporal trends. The result shows rising trends of Dengue over the past 10 years along with the rise in temperature & rainfall in Lahore. Hence this seconds the popular statement that the world is suffering due to Climate change and Global warming at different levels. Disease outbreak is one of the most alarming indications of mankind heading towards destruction and we need to think of mitigating measures to control epidemic from spreading and enveloping the cities, countries and regions.

Keywords: Dengue, epidemic, globalization, climate change

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Authors: Chanya Jetsukontorn

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Dengue hemorrhagic fever is the most important Mosquito-borne disease and the major public health problem in Thailand. The most important vector is Aedes aegypti. Environmental factors such as temperature, relative humidity, and biting rate affect dengue virus infection. The most effective measure for prevention is controlling of vector mosquitoes. In addition, surveillance of field-caught mosquitoes is imperative for determining the natural vector and can provide an early warning sign at risk of transmission in an area. In this study, Aedes aegypti mosquitoes were collected in Amphur Muang, Phetchabun Province, Thailand. The mosquitoes were collected in the rainy season and the dry season both indoor and outdoor. During mosquito’s collection, the data of environmental factors such as temperature, humidity and breeding sites were observed and recorded. After identified to species, mosquitoes were pooled according to genus/species, and sampling location. Pools consisted of a maximum of 10 Aedes mosquitoes. 70 pools of 675 Aedes aegypti were screened with RT-PCR for flaviviruses. To confirm individual infection for determining True infection rate, individual mosquitoes which gave positive results of flavivirus detection were tested for dengue virus by RT-PCR. The infection rate was 5.93% (4 positive individuals from 675 mosquitoes). The probability to detect dengue virus in mosquitoes at the neighbour’s houses was 1.25 times, especially where distances between neighboring houses and patient’s houses were less than 50 meters. The relative humidity in dengue-infected villages with dengue-infected mosquitoes was significantly higher than villages that free from dengue-infected mosquitoes. Indoor biting rate of Aedes aegypti was 14.87 times higher than outdoor, and biting times of 09.00-10.00, 10.00-11.00, 11.00-12.00 yielded 1.77, 1.46, 0.68mosquitoes/man-hour, respectively. These findings confirm environmental factors were related to Dengue infection in Thailand. Data obtained from this study will be useful for the prevention and control of the diseases.

Keywords: Aedes aegypti, Dengue virus, environmental factors, one health, PCR

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Authors: Mohd Shazad, K. K. Gupta

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Vector borne diseases are a serious global concern. Aedes aegypti, the primary vector for viruses that cause dengue fever, dengue haemorrhagic fever, chikungunya and yellow fever is widespread over large areas of the tropics and subtropics. In last decade, diseases transmitted by Aedes aegypti are of serious concern. In past decade, number of cases of dengue fever, dengue hemorrhagic fever, and chikungunya has increased multifold. Present research work focused on impact of ethanol extract of Ocimum sanctum on dengue vector Aedes aegypti. 0-24 hr. old fourth instar larvae of lab-bred population of Aedes aegypti were exposed to ethanol leaf extract of Ocimum with concentrations ranging from 50 ppm to 400 ppm. Survival and development and the treated larvae and reproductive behaviour of the adults emerged from the treated larvae was evaluated. Our results indicated larvicidal potential of the leaf ethanol extract. The influence of the extract was dose dependent. 77.2% mortality was observed in the larvae exposed to 400 ppm for 24 hr. Treatment at lower concentrations revealed delayed toxicity. The larvae survived after treatment showed severe developmental anomalies. Consequently, there was the significant increase in duration of fourth instar larva. The L4 treated with 400-ppm extract moulted after 4.6 days; this was in sharp contrast to control where the larval period of the fourth instar lasts three days. The treated fourth instar larvae in many cases transformed into larva-pupa intermediates with the combination of larva, pupa characters. The larva-pupa intermediates had reduced life span and failed to moult successfully. The adults emerged from the larvae treated with lower doses had reduced reproductive potential. The females exhibited longer preoviposition period, reduced oviposition rate, abnormal oviposition behaviour and decreased fertility. Our studies indicated the possibility of the presence of JH mimic or JH analogue in the leaf ethanol extract of Ocimum. The present research work explored the potentials of Ocimum sanctum, also known as the queen of herbs, in integrated vector management programme of Aedes aegypti, which is a serious threat to human health.

Keywords: Aedes aegypti, development, mortality, Ocimum sanctum reproduction

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Authors: Sumiko Anno, Keiji Imaoka, Takeo Tadono, Tamotsu Igarashi, Subramaniam Sivaganesh, Selvam Kannathasan, Vaithehi Kumaran, Sinnathamby Noble Surendran

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Dengue outbreaks are affected by biological, ecological, socio-economic and demographic factors that vary over time and space. These factors have been examined separately and still require systematic clarification. The present study aimed to investigate the spatial-temporal clustering relationships between these factors and dengue outbreaks in the northern region of Sri Lanka. Remote sensing (RS) data gathered from a plurality of satellites were used to develop an index comprising rainfall, humidity and temperature data. RS data gathered by ALOS/AVNIR-2 were used to detect urbanization, and a digital land cover map was used to extract land cover information. Other data on relevant factors and dengue outbreaks were collected through institutions and extant databases. The analyzed RS data and databases were integrated into geographic information systems, enabling temporal analysis, spatial statistical analysis and space-time clustering analysis. Our present results showed that increases in the number of the combination of ecological factor and socio-economic and demographic factors with above the average or the presence contribute to significantly high rates of space-time dengue clusters.

Keywords: ALOS/AVNIR-2, dengue, space-time clustering analysis, Sri Lanka

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Authors: Koon Weng Lau, Chee Dhang Chen, Abdul Aziz Azidah, Mohd Sofian-Azirun

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Recently, Sarawak state of Malaysia encounter an outbreak of dengue fever. Aedes albopictus has incriminated as one of the important vectors of dengue transmission. Without an effective vaccine, approaches to control or prevent dengue will be a focus on the vectors. The control of Aedes mosquitoes is still dependent on the use of chemical insecticides and insecticide resistance represents a threat to the effectiveness of vector control. This study was conducted to determine the resistance status of 11 active ingredients representing four major insecticide classes: DDT, dieldrin, malathion, fenitrothion, bendiocarb, propoxur, etofenprox, deltamethrin, lambda-cyhalothrin, cyfluthrin, and permethrin. Standard WHO test procedures were conducted to determine the insecticide susceptibility. Aedes albopictus collected from Kapit (resistance ratio, RR = 1.04–3.02), Kuching (RR = 1.17–4.61), and Sibu (RR = 1.06–3.59) exhibited low resistance toward all insecticides except dieldrin. This study reveled that dieldrin is still effective against Ae. albopictus, followed by fenitrothion, cyfluthrin, and deltamethrin. In conclusion, Ae. albopictus in Sarawak exhibited different resistance levels toward various insecticides and alternative solutions should be implemented to prevent further deterioration of the condition.

Keywords: Aedes albopictus, dengue, insecticide resistance, Malaysia

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Authors: Luna Degife, Desalegn Belay, Yoseph Worku, Tigist Tesfaye, Assefa Tufa, Abyot Bekele, Zegeye Hailemariam, Abay Hagos

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Half of the world’s population is at risk of Dengue Fever (DF), a highly under-recognized and underreported mosquito-borne viral disease with high prevalence in the tropical and subtropical regions. Globally, an estimated 50 to 200 million cases and 20, 000 DF deaths occur annually as per the world health organization report. In Ethiopia, the first outbreak occurred in 2013 in Diredawa administration city. Afterward, three outbreaks have been reported from the eastern part of the country. We received a report of the fifth DF outbreak for Ethiopia and the second for Diredawa city on October 4, 2015. We conducted the investigation to confirm the outbreak, identify the risk factors for the repeatedly occurrence of the disease and implement control measures. We conducted un- matched case-control study and defined a suspected DF case as any person with fever of 2-7 days and 2 or more of the following: a headache, arthralgia, myalgia, rash, or bleeding from any part of the body. Controls were residents of Diredawa city without DF symptoms. We interviewed 70 Cases and 140 controls from all health facilities in Diredawa city from October 7 to 15; 2015. Epi Info version 7.1.5.0 was used to analyze the data and multivariable logistic regression was conducted to assess risk factors for DF. Sixty-nine blood samples were collected for Laboratory confirmation.The mean age for cases was 23.7±9.5 standard deviation (SD) and for controls 31.2±13 SD. Close contact with DF patient (Adjusted odds ratio (AOR)=5.36, 95% confidence interval(CI): 2.75-10.44), nonuse of long-lasting insecticidal nets (AOR=2.74, 95% CI: 1.06-7.08) and availability of stagnant water in the village (AOR=3.61, 95% CI:1.31-9.93) were independent risk factors associated with higher rates of the disease. Forty-two samples were tested positive. Endemicity of DF is becoming a concern for Diredawa city after the first outbreak. Therefore, effective vector control activities need to be part of long-term preventive measures.

Keywords: dengue fever, Diredawa, outbreak, risk factors, second

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Authors: Sudha T., Naveen C.

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Dengue is a serious public health issue that causes significant annual economic and welfare burdens on nations. However, enhanced optimization techniques and quantitative modeling approaches can predict the incidence of dengue. By advocating for a data-driven approach, public health officials can make informed decisions, thereby improving the overall effectiveness of sudden disease outbreak control efforts. The National Oceanic and Atmospheric Administration and the Centers for Disease Control and Prevention are two of the U.S. Federal Government agencies from which this study uses environmental data. Based on environmental data that describe changes in temperature, precipitation, vegetation, and other factors known to affect dengue incidence, many predictive models are constructed that use different machine learning methods to estimate weekly dengue cases. The first step involves preparing the data, which includes handling outliers and missing values to make sure the data is prepared for subsequent processing and the creation of an accurate forecasting model. In the second phase, multiple feature selection procedures are applied using various machine learning models and optimization techniques. During the third phase of the research, machine learning models like the Huber Regressor, Support Vector Machine, Gradient Boosting Regressor (GBR), and Support Vector Regressor (SVR) are compared with several optimization techniques for feature selection, such as Harmony Search and Genetic Algorithm. In the fourth stage, the model's performance is evaluated using Mean Square Error (MSE), Mean Absolute Error (MAE), and Root Mean Square Error (RMSE) as assistance. Selecting an optimization strategy with the least number of errors, lowest price, biggest productivity, or maximum potential results is the goal. In a variety of industries, including engineering, science, management, mathematics, finance, and medicine, optimization is widely employed. An effective optimization method based on harmony search and an integrated genetic algorithm is introduced for input feature selection, and it shows an important improvement in the model's predictive accuracy. The predictive models with Huber Regressor as the foundation perform the best for optimization and also prediction.

Keywords: deep learning model, dengue fever, prediction, optimization

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Authors: Siddharth Jain, Abhenil Mittal, Surendra Kumar Sharma

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Background: With its recent emergence and re-emergence, dengue has become a major international public health concern, imposing significant financial burden especially in developing countries. Despite aggressive control measures in place, India experienced one of its largest outbreaks in 2015 with Delhi being most severely affected. There is a lack of reliable predictors of disease severity and mortality in dengue. The present study was carried out to identify these predictors during the 2015 outbreak. Methods: This prospective observational study conducted at an apex tertiary care center in Delhi, India included confirmed adult dengue patients admitted between August-November 2015. Patient demographics, clinical details, and laboratory findings were recorded in a predesigned proforma. Appropriate statistical tests were used to summarize and compare the clinical and laboratory characteristics and derive predictors of mortality and severe disease, while developing a clinical risk score for mortality. Serotype analysis was also done for 75 representative samples to identify the dominant serotypes. Results: Data of 369 patients were analyzed (mean age 30.9 years; 67% males). Of these, 198 (54%) patients had dengue fever, 125 (34%) had dengue hemorrhagic fever (DHF Grade 1,2)and 46 (12%) developed dengue shock syndrome (DSS). Twenty two (6%) patients died. Late presentation to the hospital (≥5 days after onset) and dyspnoea at rest were identified as independent predictors of severe disease. Age ≥ 24 years, dyspnoea at rest and altered sensorium were identified as independent predictors of mortality. A clinical risk score was developed (12*age + 14*sensorium + 10*dyspnoea) which, if ≥ 22, predicted mortality with a high sensitivity (81.8%) and specificity (79.2%). The predominant serotypes in Delhi (2015) were DENV-2 and DENV-4. Conclusion: Age ≥ 24 years, dyspnoea at rest and altered sensorium were identified as independent predictors of mortality. Platelet counts did not determine the outcome in dengue patients. Timely referral/access to health care is important. Development and use of validated predictors of disease severity and simple clinical risk scores, which can be applied in all healthcare settings, can help minimize mortality and morbidity, especially in resource limited settings.

Keywords: dengue, mortality, predictors, severity

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Authors: Hadura Abu Hasan, Zairi Jaal, P. J. McCall

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Dengue is a serious problem in Malaysia, particularly in high-density urban communities with lower socio-economic levels. This study evaluated the susceptibility of local populations of Aedesaegypti (Linnaeus), Aedesalbopictus (Skuse) and Culexquinquefasciatus (Say) from the traditional community of BaganDalam, Penang, Malaysia to lambdacyhalothrin and pirimiphos-methyl using standard World Health Organization (WHO) adult bioassay test. Unfed female mosquitoes aged 3-5 days were exposed to WHO recommended dosages of insecticides over fixed time periods with results presented as knock-down time (KT50) for each strain.The insecticide susceptible VCRU laboratory strain was usedas control. All three specieswere highly resistant to lambda-cyhalothrin with less than 10% mortality at 24 hours after treatment. In contrast, Ae.aegypti and Ae. albopictus were susceptible to pirimiphos-methyl, showing 100% mortality recorded 24 hoursafter treatment. Cx. quinquefasciatuswasclassed as ‘suspected resistant’ to pirimiphos-methyl as mortality recorded 24 hours after treatment was 94-96%. The results indicate that organophosphates such as pirimiphos-methyl might be used as alternative to pyrethroid for dengue vector control in this dengue-prone area.

Keywords: vector control, aedes aegypti, aedes albopictus, dengue, culex quinquefasciatus, residuals insecticides, pyrethroid, organophosphate, resistant, mosquito

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Authors: Ida Bagus Mandhara Brasika, I Dewa Gde Sathya Deva

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Wolbachia is recently developed as the natural enemy of Dengue virus (DENV). It inhibits the replication of DENV in Aedes aegypti. Both DENV and its vector, Aedes aegypty, are sensitive to climate factor especially temperature. The changing of climate has a direct impact on temperature which means changing the vector transmission. Temperature has been known to effect Wolbachia density as it has an ideal temperature to grow. Some scenarios, which are known as Representative Concentration Pathways (RCPs), have been developed by Intergovernmental Panel on Climate Change (IPCC) to predict the future climate based on greenhouse gases concentration. These scenarios are applied to mitigate the future change of Aedes aegypti migration and how Wolbachia could control the virus. The prediction will determine the schemes to release Wolbachia-injected Aedes aegypti to reduce DENV transmission.

Keywords: Aedes aegypti, climate change, dengue virus, Intergovernmental Panel on Climate Change, representative concentration pathways, Wolbachia

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Authors: Monika Soni, Chandra Bhattacharya, Siraj Ahmed Ahmed, Prafulla Dutta

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Dengue is now a globally important arboviral disease. Extensive vector surveillance has already established A.aegypti as a primary vector, but A.albopictus is now accelerating the situation through gradual adaptation to human surroundings. Global destabilization and gradual climatic shift with rising in temperature have significantly expanded the geographic range of these species These versatile vectors also host Chikungunya, Zika, and yellow fever virus. Biggest challenge faced by endemic countries now is upsurge in co-infection reported with multiple serotypes and virus co-circulation. To foster vector control interventions and mitigate disease burden, there is surge for knowledge on vector susceptibility and viral tolerance in response to multiple infections. To address our understanding on transmission dynamics and reproductive fitness, both the vectors were exposed to single and dual combinations of all four dengue serotypes by artificial feeding and followed up to third generation. Artificial feeding observed significant difference in feeding rate for both the species where A.albopictus was poor artificial feeder (35-50%) compared to A.aegypti (95-97%) Robust sequential screening of viral antigen in mosquitoes was followed by Dengue NS1 ELISA, RT-PCR and Quantitative PCR. To observe viral dissemination in different mosquito tissues Indirect immunofluorescence assay was performed. Result showed that both the vectors were infected initially with all dengue(1-4)serotypes and its co-infection (D1 and D2, D1 and D3, D1 and D4, D2 and D4) combinations. In case of DENV-2 there was significant difference in the peak titer observed at 16th day post infection. But when exposed to dual infections A.aegypti supported all combinations of virus where A.albopictus only continued single infections in successive days. There was a significant negative effect on the fecundity and fertility of both the vectors compared to control (PANOVA < 0.001). In case of dengue 2 infected mosquito, fecundity in parent generation was significantly higher (PBonferroni < 0.001) for A.albopicus compare to A.aegypti but there was a complete loss of fecundity from second to third generation for A.albopictus. It was observed that A.aegypti becomes infected with multiple serotypes frequently even at low viral titres compared to A.albopictus. Possible reason for this could be the presence of wolbachia infection in A.albopictus or mosquito innate immune response, small RNA interference etc. Based on the observations it could be anticipated that transovarial transmission may not be an important phenomenon for clinical disease outcome, due to the absence of viral positivity by third generation. Also, Dengue NS1 ELISA can be used for preliminary viral detection in mosquitoes as more than 90% of the samples were found positive compared to RT-PCR and viral load estimation.

Keywords: co-infection, dengue, reproductive fitness, viral quantification

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Authors: Chiu-Wen Chang, I-Yun Chang, Wei-Ting Chen, Hui-Ping Ho, Chao-Ying Pan, Joh-Jong Huang

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Dengue is a ‘community disease’ or ‘environmental disease’, as long as the environment exist suitable container (including natural and artificial) for mosquito breeding, once the virus invade will lead to the dengue epidemic. Surveillance of vector density is critical to effective infectious disease control and play an important role in monitoring the dynamics of mosquitoes in community, such as mosquito species, density, distribution area. The objective of this study was to examine the relationship in vector density survey (Breteau index, Adult index, House index, Container index, and Larvae index) form 2014 to 2016 in Kaohsiung City and evaluate the effects of introducing the Breeding Elimination and Appraisal Team (hereinafter referred to as BEAT) as an intervention measure on eliminating dengue vector breeding site started from May 2016. BEAT were performed on people who were suspected of contracting dengue fever, a surrounding area measuring 50 meters by 50 meters was demarcated as the emergency prevention and treatment zone. BEAT would perform weekly vector mosquito inspections and vector mosquito inspections in regions with a high Gravitrap index and assign a risk assessment index to each region. These indices as well as the prevention and treatment results were immediately reported to epidemic prevention-related units every week. The results indicated that, vector indices from 2014 to 2016 showed no statistically significant differences in the Breteau index, adult index, and house index (p > 0.05) but statistically significant differences in the container index and larvae index (p <0.05). After executing the integrated elimination work, container index and larvae index are statistically significant different from 2014 to 2016 in the (p < 0.05). A post hoc test indicated that the container index of 2014 (M = 12.793) was significantly higher than that of 2016 (M = 7.631), and that the larvae index of 2015 (M = 34.065) was significantly lower than that of 2014 (M = 66.867). The results revealed that effective vector density surveillance could highlight the focus breeding site and then implement the immediate control action (BEAT), which successfully decreased the vector density and the risk of dengue epidemic.

Keywords: Breteau index, dengue control, monitoring method, vector density

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Authors: Monika Soni, Shovonlal Bhowmick, Chandra Bhattacharya, Jitendra Sharma, Prafulla Dutta, Jagadish Mahanta

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Aedes aegypti and Aedes albopictus are considered as two major vectors to transmit dengue virus. In North-east India, two states viz. Assam and Arunachal Pradesh are known to be high endemic zone for dengue and Chikungunya viral infection. The taxonomical classification of medically important vectors are important for mapping of actual evolutionary trends and epidemiological studies. However, misidentification of mosquito species in field-collected mosquito specimens could have a negative impact which may affect vector-borne disease control policy. DNA barcoding is a prominent method to record available species, differentiate from new addition and change of population structure. In this study, a combined approach of a morphological and molecular technique of DNA barcoding was adopted to explore sequence variation in mitochondrial cytochrome c oxidase subunit I (COI) gene within dengue vectors. The study has revealed the map distribution of the dengue vector from two states i.e. Assam and Arunachal Pradesh, India. Approximate five hundred mosquito specimens were collected from different parts of two states, and their morphological features were compared with the taxonomic keys. The analysis of detailed taxonomic study revealed identification of two species Aedes aegypti and Aedes albopictus. The species aegypti comprised of 66.6% of the specimen and represented as dominant dengue vector species. The sequences obtained through standard DNA barcoding protocol were compared with public databases, viz. GenBank and BOLD. The sequences of all Aedes albopictus have shown 100% similarity whereas sequence of Aedes aegypti has shown 99.77 - 100% similarity of COI gene with that of different geographically located same species based on BOLD database search. From dengue prevalent different geographical regions fifty-nine sequences were retrieved from NCBI and BOLD databases of the same and related taxa to determine the evolutionary distance model based on the phylogenetic analysis. Neighbor-Joining (NJ) and Maximum Likelihood (ML) phylogenetic tree was constructed in MEGA6.06 software with 1000 bootstrap replicates using Kimura-2-Parameter model. Data were analyzed for sequence divergence and found that intraspecific divergence ranged from 0.0 to 2.0% and interspecific divergence ranged from 11.0 to 12.0%. The transitional and transversional substitutions were tested individually. The sequences were deposited in NCBI: GenBank database. This observation claimed the first DNA barcoding analysis of Aedes mosquitoes from North-eastern states in India and also confirmed the range expansion of two important mosquito species. Overall, this study insight into the molecular ecology of the dengue vectors from North-eastern India which will enhance the understanding to improve the existing entomological surveillance and vector incrimination program.

Keywords: COI, dengue vectors, DNA barcoding, molecular identification, North-east India, phylogenetics

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Authors: Sandeep Mohindra

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Since 2013, the authors have operated on 568 cases of pituitary tumors through the trans-sphenoidal route, using the binostril approach. The distribution included 486 cases of non-functioning pituitary tumors, 24 cases of Growth hormone(GH) secreting tumors(acromegaly), and 28 cases of adrenocorticotrophic(ACTH) secreting tumors(Cushing's Disease). The authors utilized neuro-navigation for 18 cases, and all belonged to the functional tumor category. Complications included ICA injury in 2 cases, fatal meningitis in 5 cases, while CSF leak required repair in 28 cases. Satisfactory excision was noted in 512 cases, while recurrence/residual required repeat surgery in 32 cases. Authors conclude that trans sphenoidal route remains the best and optimal way of managing sellar tumors, especially pituitary adenomas.

Keywords: pituitary, adenoma, trans-sphenoidal, endonasal, neuronavigation

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Authors: Jiun-Nan Hou, Tien-Huang Chen, Wei-June Chen

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Dengue viruses (DENVs) are naturally transmitted between humans by mosquito vectors. Mosquito cells usually survive DENV infection, allowing infected mosquitoes to retain an active status for virus transmission. In this study, we found that DENV2 virus infection in mosquito cells causes the unfolded protein response (UPR) that activates the protein kinase RNA-like endoplasmic reticulum kinase (PERK) signal pathway, leading to shutdown of global protein translation in infected cells which was apparently regulated by the PERK signal pathway. According to observation in this study, the PERK signal pathway in DENV2-infected C6/36 cells alleviates ER stress, and reduces initiator and effector caspases, as well as the apoptosis rate via shutdown of cellular proteins. In fact, phosphorylation of eukaryotic initiation factor 2ɑ (eIF2ɑ) by the PERK signal pathway may impair recruitment of ribosomes that bind to the mRNA 5’-cap structure, resulting in an inhibitory effect on canonical cap-dependent cellular protein translation. The resultant pro-survival “byproduct” of infected mosquito cells is undoubtedly advantageous for viral replication. This finding provides insights into elucidating the PERK-mediated modulating web that is actively involved in dynamic protein synthesis, cell survival, and viral replication in mosquito cells.

Keywords: cap-dependent protein translation, dengue virus, endoplasmic reticulum stress, mosquito cells, PERK signal pathway

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Authors: Gabriela C. Caldas, Fernanda C. Jacome, Arthur da C. Rasinhas, Ortrud M. Barth, Flavia B. dos Santos, Priscila C. G. Nunes, Yuli R. M. de Souza, Pedro Paulo de A. Manso, Marcelo P. Machado, Debora F. Barreto-Vieira

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The establishment of animal models for studies of DENV infections has been challenging, since circulating epidemic viruses do not naturally infect nonhuman species. Such studies are of great relevance to the various areas of dengue research, including immunopathogenesis, drug development and vaccines. In this scenario, the main objective of this study is to verify possible morphological changes, as well as the presence of antigens and viral RNA in lung samples from BALB/c mice experimentally infected with an epidemic and non-neuroadapted DENV-3 strain. Male BALB/c mice, 2 months old, were inoculated with DENV-3 by intravenous route. After 72 hours of infection, the animals were euthanized and the lungs were collected. Part of the samples was processed by standard technique for analysis by light and transmission electronic microscopies and another part was processed for real-time PCR analysis. Morphological analyzes of lungs from uninfected mice showed preserved tissue areas. In mice infected with DENV-3, the analyzes revealed interalveolar septum thickening with presence of inflammatory infiltrate, foci of alveolar atelectasis and hyperventilation, bleeding foci in the interalveolar septum and bronchioles, peripheral capillary congestion, accumulation of fluid in the blood capillary, signs of interstitial cell necrosis presence of platelets and mononuclear inflammatory cells circulating in the capillaries and/or adhered to the endothelium. In addition, activation of endothelial cells, platelets, mononuclear inflammatory cell and neutrophil-type polymorphonuclear inflammatory cell evidenced by the emission of cytoplasmic membrane prolongation was observed. DEN-like particles were seen in the cytoplasm of endothelial cells. The viral genome was recovered from 3 in 12 lung samples. These results demonstrate that the BALB / c mouse represents a suitable model for the study of the histopathological changes induced by DENV infection in the lung, with tissue alterations similar to those observed in human cases of DEN.

Keywords: BALB/c mice, dengue, histopathology, lung, ultrastructure

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Authors: I. Nyoman Mahayasa Adiputra

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Data in the field of health can be useful for the purposes of data analysis, one example of health data is disease data. Disease data is usually in a geographical plot in accordance with the area. Where the data was collected, in the city of Denpasar, Bali. Disease data report is still published in tabular form, disease information has not been mapped in GIS form. In this research, disease information in Denpasar city will be digitized in the form of a geographic information system with the smallest administrative area in the form of district. Denpasar City consists of 4 districts of North Denpasar, East Denpasar, West Denpasar and South Denpasar. In this research, we use Google fusion table technology for map digitization process, where this technology can facilitate from the administrator and from the recipient information. From the administrator side of the input disease, data can be done easily and quickly. From the receiving end of the information, the resulting GIS application can be published in a website-based application so that it can be accessed anywhere and anytime. In general, the results obtained in this study, divided into two, namely: (1) Geolocation of Denpasar and all of Denpasar districts, the process of digitizing the map of Denpasar city produces a polygon geolocation of each - district of Denpasar city. These results can be utilized in subsequent GIS studies if you want to use the same administrative area. (2) Dengue fever mapping in 2014 and 2015. Disease data used in this study is dengue fever case data taken in 2014 and 2015. Data taken from the profile report Denpasar Health Department 2015 and 2016. This mapping can be useful for the analysis of the spread of dengue hemorrhagic fever in the city of Denpasar.

Keywords: geographic information system, Google fusion table technology, delivery of disease data information, Denpasar city

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Hueiwang Anna Jeng, Norou Diawara, Nancy Welch, Cynthia Jackson, Rekha Singh, Kyle Curtis, Raul Gonzalez, David Jurgens, Sasanka Adikari

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Modeling effort is needed to predict the COVID-19 trends for developing management strategies and adaptation measures. The objective of this study was to assess whether SARS-CoV-2 viral load in wastewater could serve as a predictor for forecasting COVID-19 cases, hospitalization cases, and death cases using copula-based time series modeling. SARS-CoV-2 RNA load in raw wastewater in Chesapeake VA was measured using the RT-qPCR method. Gaussian copula time series marginal regression model, incorporating an autoregressive moving average model and the copula function, served as a forecasting model. COVID-19 cases were correlated with wastewater viral load, hospitalization cases, and death cases. The forecasted trend of COVID-19 cases closely paralleled one of the reported cases, with over 90% of the forecasted COVID-19 cases falling within the 99% confidence interval of the reported cases. Wastewater SARS-CoV-2 viral load could serve as a predictor for COVID-19 cases and hospitalization cases.

Keywords: COVID-19, modeling, time series, copula function

Procedia PDF Downloads 38

Authors: Yichao Liu, Peter Fransson, Julian Heidecke, Jonas Wallin, Joacim Rockloev

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Dengue, a mosquito-borne viral disease, poses a significant public health challenge in endemic tropical or subtropical countries, including Sri Lanka. To reveal insights into the complexity of the dynamics of this disease and study the drivers, a comprehensive model capable of both robust forecasting and insightful inference of drivers while capturing the co-circulating of several virus strains is essential. However, existing studies mostly focus on only one aspect at a time and do not integrate and carry insights across the siloed approach. While mechanistic models are developed to capture immunity dynamics, they are often oversimplified and lack integration of all the diverse drivers of disease transmission. On the other hand, purely data-driven methods lack constraints imposed by immuno-epidemiological processes, making them prone to overfitting and inference bias. This research presents a hybrid model that combines machine learning techniques with mechanistic modelling to overcome the limitations of existing approaches. Leveraging eight years of newly reported dengue case data, along with socioeconomic factors, such as human mobility, weekly climate data from 2011 to 2018, genetic data detecting the introduction and presence of new strains, and estimates of seropositivity for different districts in Sri Lanka, we derive a data-driven vector (SEI) to human (SEIR) model across 16 regions in Sri Lanka at the weekly time scale. By conducting ablation studies, the lag effects allowing delays up to 12 weeks of time-varying climate factors were determined. The model demonstrates superior predictive performance over a pure machine learning approach when considering lead times of 5 and 10 weeks on data withheld from model fitting. It further reveals several interesting interpretable findings of drivers while adjusting for the dynamics and influences of immunity and introduction of a new strain. The study uncovers strong influences of socioeconomic variables: population density, mobility, household income and rural vs. urban population. The study reveals substantial sensitivity to the diurnal temperature range and precipitation, while mean temperature and humidity appear less important in the study location. Additionally, the model indicated sensitivity to vegetation index, both max and average. Predictions on testing data reveal high model accuracy. Overall, this study advances the knowledge of dengue transmission in Sri Lanka and demonstrates the importance of incorporating hybrid modelling techniques to use biologically informed model structures with flexible data-driven estimates of model parameters. The findings show the potential to both inference of drivers in situations of complex disease dynamics and robust forecasting models.

Keywords: compartmental model, climate, dengue, machine learning, social-economic

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Authors: Jihene Bettaieb, Ghassen kharroubi, Rym mallekh, Ines Cherif, Taoufik Atawa, Kaouther Harrabech

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Brucellosis is a major worldwide zoonosis. It is a reportable condition in Tunisia where the disease remains endemic, especially in rural areas. The aim of this study was to describe the epidemiological, clinical, and bacteriological profile of human brucellosis cases notified in the district of Tunis. It was a retrospective descriptive study of cases reported in the district of Tunis through the national surveillance system between the 1st January and 31th December 2017. During the study period, 133 brucellosis confirmed cases were notified. The mean age was 37.5 ± 18.0 years, and 54.9% of cases were males. More than four-fifths (82.7%) of cases were reported in spring and summer with a peak in the month of May (36 cases). Fever and sweats were the most common symptoms; they occurred in 95% and 72% of cases, respectively. Osteoarticular complications occurred in 10 cases, meningitis in one case and endocarditis in one other case. Wright agglutination test and Rose Bengale test were positive in 100% and 91% of cases, respectively. While blood culture was positive in 9 cases and PCR in 2 cases. Brucella melitensis was the only identified specie (9 cases). Almost all cases (99.2%) reported the habit of consuming raw dairy products. Only 5 cases had a suspect contact with animals; among them, 3 persons were livestock breeders. The transmission was essentially due to raw dairy product consumption. It is important to enhance preventive measures to control animal Brucellosis and to educate the population regarding the risk factors of the disease.

Keywords: brucellosis, risk factors, surveillance system, Tunisia

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Authors: V. Baweja, K. K. Gupta, V. Dubey, C. Keshavam

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Antimicrobial activity of six indigenous plants such as Tulsi Ocimum sanctum, Neem Azadirachta indica, Aloe vera, Turmeric Curcuma longa, Lantana Lantana camara, and Clove Syzygium aromaticum was assessed against the gut microbiota of the dengue fever mosquito Aedes aegypti, keeping in view that the presence of midgut bacteria may affect the ability of the vector to transmit pathogens. Eleven different types of bacterial clones were isolated from the midgut of lab-reared fourth instar larvae of Aedes aegypti and were grown on LB agar medium at an optimum temperature of 25 ºC. Identification of these bacteria was done on the basis of their colony characteristic such as colony size, shape, opacity, elevation, consistency, and growth. Light microscopic studies of the gut microbiota revealed dominance of Gram-negative cocci over gram positive cocci and bacilli and Gram-negative bacilli. Identification of species was done by chemical characterization of the colonies. Crude extracts of all test plants were screened for their antimicrobial activities against gut microbiota by disc diffusion assay. The zone of exclusion seen after 24 hr of incubation in different assays revealed the most potent antibacterial activities in neem followed by clove and turmeric. Lantana and Aloe vera were least effective.

Keywords: plant extract, aedes, dengue, antimicrobial activity

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Authors: M. D. Nirmani, K. L. N. Perera, G. H. Galhena

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Dengue has become one of the most important arbo-viral disease in all tropical and subtropical regions of the world. Aedes aegypti, is the principal vector of the virus, vary in both epidemiological and behavioral characteristics, which could be finely measured through DNA sequence comparison at their population level. Such knowledge in the population differences can assist in implementation of effective vector control strategies allowing to make estimates of the gene flow and adaptive genomic changes, which are important predictors of the spread of Wolbachia infection or insecticide resistance. As such, this study was undertaken to investigate the phylogenetic relationships of Ae. aegypti from Galle and Colombo, Sri Lanka, based on the ribosomal protein region which spans between two exons, in order to understand the geographical distribution of genetically distinct mosquito clades and its impact on mosquito control measures. A 320bp DNA region spanning from 681-930 bp, corresponding to the ribosomal protein, was sequenced in 62 Ae. aegypti larvae collected from Galle (N=30) and Colombo (N=32), Sri Lanka. The sequences were aligned using ClustalW and the haplotypes were determined with DnaSP 5.10. Phylogenetic relationships among haplotypes were constructed using the maximum likelihood method under Tamura 3 parameter model in MEGA 7.0.14 including three previously reported sequences of Australian (N=2) and Brazilian (N=1) Ae. aegypti. The bootstrap support was calculated using 1000 replicates and the tree was rooted using Aedes notoscriptus (GenBank accession No. KJ194101). Among all sequences, nineteen different haplotypes were found among which five haplotypes were shared between 80% of mosquitoes in the two populations. Seven haplotypes were unique to each of the population. Phylogenetic tree revealed two basal clades and a single derived clade. All observed haplotypes of the two Ae. aegypti populations were distributed in all the three clades, indicating a lack of genetic differentiation between populations. The Brazilian Ae. aegypti haplotype and one of the Australian haplotypes were grouped together with the Sri Lankan basal haplotype in the same basal clade, whereas the other Australian haplotype was found in the derived clade. Phylogram showed that Galle and Colombo Ae. aegypti populations are highly related to each other despite the large geographic distance (129 Km) indicating a substantial genetic similarity between them. This may have probably arisen from passive migration assisted by human travelling and trade through both land and water as the two areas are bordered by the sea. In addition, studied Sri Lankan mosquito populations were closely related to Australian and Brazilian samples. Probably this might have caused by shipping industry between the three countries as all of them are fully or partially enclosed by sea. For example, illegal fishing boats migrating to Australia by sea is perhaps a good mean of transportation of all life stages of mosquitoes from Sri Lanka. These findings indicate that extensive mosquito migrations occur between populations not only within the country, but also among other countries in the world which might be a main barrier to the successful vector control measures.

Keywords: Aedes aegypti, dengue control, extensive mosquito migration, haplotypes, phylogeny, ribosomal protein

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Authors: Reza Hedayati, Meysam Jahanbakhshi

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Fracture Mechanics is used to predict debonding propagation in adhesive joint between aluminum and composite plates. Three types of loadings and two types of glass-epoxy composite sequences: [0/90]2s and [0/45/-45/90]s are considered for the composite plate and their results are compared. It was seen that generally the cases with stacking sequence of [0/45/-45/90]s have much shorter lives than cases with [0/90]2s. It was also seen that in cases with λ=0 the ends of the debonding front propagates forward more than its middle, while in cases with λ=0.5 or λ=1 it is vice versa. Moreover, regardless of value of λ, the difference between the debonding propagations of the ends and the middle of the debonding front is very close in cases λ=0.5 and λ=1. Another main conclusion was the non-dimensionalized debonding front profile is almost independent of sequence type or the applied load value.

Keywords: adhesive joint, debonding, fracture, LEFM, APDL

Procedia PDF Downloads 331

Authors: Reza Hedayati, Meysam Jahanbakhshi

Abstract:

Fracture Mechanics is used to predict debonding propagation in adhesive joint between aluminum and composite plates. Three types of loadings and two types of glass-epoxy composite sequences: [0/90]2s and [0/45/-45/90]s are considered for the composite plate and their results are compared. It was seen that generally the cases with stacking sequence of [0/45/-45/90]s have much shorter lives than cases with [0/90]2s. It was also seen that in cases with λ=0 the ends of the debonding front propagates forward more than its middle, while in cases with λ=0.5 or λ=1 it is vice versa. Moreover, regardless of value of λ, the difference between the debonding propagations of the ends and the middle of the debonding front is very close in cases λ=0.5 and λ=1. Another main conclusion was the non-dimensionalized debonding front profile is almost independent of sequence type or the applied load value.

Keywords: fatigue, debonding, Paris law, APDL, adhesive

Procedia PDF Downloads 335

Authors: Reetika Sharma, Lalit Tejwani, Himanshu Shekhar, Arun Singhvi

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Purpose: Advanced Glaucoma with Failed trab is not an uncommon sight in glaucoma clinic, and such cases usually tend to present with high intraocular pressure (IOP) and advanced cupping, or even glaucomatous atrophy stage. Re-surgery is needed for such cases, and wound modulation poses a major challenge in these cases. We share our experience in this case series with the use of Ologen (collagen matrix implant) along with MMC 0.04% used in surgery. The purpose of the study was to evaluate the efficacy and outcome of collagen matrix implant in re-trabeculectomy in advanced glaucoma cases. Methodology: Eleven eyes of 11 patients (one eye of one patient) underwent re-trabeculectomy surgery with MMC and Ologen. Ologen implant was used in sub scleral and subconjunctival space, as a spacer and wound modulator. In five cases, triple modulation with implant soaked in anti-VEGF was used. Results: All patients had cupping more than 0.9, and one case was GOA. All cases were on maximal medication at presentation and majority were on systemic anti-glaucoma therapy also. Post-surgery, follow-up ranged from 13 – 34 months, and all cases had a follow longer than the gap between previous surgery (which was failed) and re-trab. One case needed AC reformation and one needling was done. Phaco was done at same sitting in four cases. All cases had their IOP lowered post surgery, and vision was maintained in all, however one case was considered as failed re-surgery case. Topical medication was needed in seven cases post-surgery also. Conclusion: Ologen as adjuvant should be considered in all re-trab cases and all high risk and advanced cases, and triple modulation can be next step in these cases. Aggressive IOP control and non- reluctance to continue topical medications post second surgery should be considered in such cases, to give them best possible vision.

Keywords: failed trabeculectomy, ologen, trabeculectomy, advanced glaucoma

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Authors: Muhammad Farhan Ul Moazzam, Tamkeen Urooj Paracha, Ghani Rahman, Byung Gul Lee, Nasir Farid, Adnan Arshad

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The novel coronavirus pandemic disease (COVID-19) affected the whole globe, though there is a lack of clinical studies and its epidemiological features. But as per the observation, it has been seen that most of the COVID-19 infected patients show mild to moderate symptoms, and they get better without any medical assistance due to a better immune system to generate antibodies against the novel coronavirus. In this study, the active cases, serious cases, recovered cases, deaths and total confirmed cases had been analyzed using the geospatial inverse distance weightage technique (IDW) within the time span of 2nd March to 3rd June 2020. As of 3rd June, the total number of COVID-19 cases in Italy were 231,238, total deaths 33,310, serious cases 350, recovered cases 158,951, and active cases were 39,177, which has been reported by the Ministry of Health, Italy. March 2nd-June 3rd, 2020 a sum of 231,238 cases has been reported in Italy out of which 38.68% cases reported in the Lombardia region with a death rate of 18%, which is high from its national mortality rate followed by Emilia-Romagna (14.89% deaths), Piemonte (12.68% deaths), and Vento (10% deaths). As per the total cases in the region, the highest number of recoveries has been observed in Umbria (92.52%), followed by Basilicata (87%), Valle d'Aosta (86.85%), and Trento (84.54%). The COVID-19 evolution in Italy has been particularly found in the major urban area, i.e., Rome, Milan, Naples, Bologna, and Florence. Geospatial technology played a vital role in this pandemic by tracking infected patient, active cases, and recovered cases. Geospatial techniques are very important in terms of monitoring and planning to control the pandemic spread in the country.

Keywords: COVID-19, public health, geospatial analysis, IDW, Italy

Procedia PDF Downloads 114

Authors: Supachai Supmak, Yachai Limpiyakorn

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Mutation testing can be applied for the quality assessment of test cases. Prioritization of mutation test generation has been a critical element of the industry practice that would contribute to the evaluation of test cases. The industry generally delivers the product under the condition of time to the market and thus, inevitably sacrifices software testing tasks, even though many test cases are required for software verification. This paper presents an approach of applying a social network centrality measure, PageRank, to prioritize mutation test generation. The source code with the highest values of PageRank will be focused first when developing their test cases as these modules are vulnerable to defects or anomalies which may cause the consequent defects in many other associated modules. Moreover, the approach would help identify the reducible test cases in the test suite, still maintaining the same criteria as the original number of test cases.

Keywords: software testing, mutation test, network centrality measure, test case prioritization

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Authors: Mohd Jaish Siddiqui

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Laryngeal TB is extremely rare in the pediatric population, accounting for 1% of all cases. Here, we present a case of laryngeal TB with miliary tuberculosis and tuberculous encephalitis, presented with sore throat, hoarseness, severe cough and, acute obstruction the larynx, sputum for AFB was negative, T-SPOT was positive and X-pert was positive, bronchoscopy revealed multiple nodules and edema around the larynx, epiglottis, bilateral arytenopharyngeal folds and vocal cord. Enhanced MRI revealed multiple small nodules in bilateral cerebral hemispheres and right thalamus, however CSF was negative. We reviewed the LTB cases that were published up to 2021. A total of twenty fine cases were identified in English literature. The most common manifestation was hoarseness of voice with 80% followed by stridor 40% of cases. Pulmonary involvement was found in 36% of cases, whereas, 45% of cases had no underlying TB. We did not find any case who developed tuberculous encephalitis in the literature.

Keywords: laryngeal tb, treatment, tuberculous encephalitis, children

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