Monitoring resistance of Plasmdium vivax: Point mutations in dihydrofolate reductase gene in isolates from Central China

<p>Abstract</p> <p>Background</p> <p>Malaria still represents a significant public health problem in China, and the cases dramatically increased in Central China after 2001. Antifolate resistance in <it>Plasmodium vivax </it>is caused by point mutations in genes encoding dihydrofolate reductase (<it>pvdhfr</it>) and dihydropteroate synthase (<it>pvdhps</it>). In this study, we used direct sequencing to investigate genetic variation in <it>pvdhfr </it>of malaria patients' samples from Central China.</p> <p>Results</p> <p>Among all the samples, 21.4% were wild-type, whereas mutations were detected at three codons (58, 61 and 117) including single mutant (34.6%) and double mutants (43.8%). The most prevalent mutant allele was the one with double mutation at codons 58 and 117 (24.6%). Three types of single mutation (S58R, T61M and S117N) were found in 2.1%, 11.8% and 20.9% of parasite isolates, respectively. The four <it>P. vivax </it>parasite populations in Central China also differed in <it>pvdhfr </it>allele frequencies.</p> <p>Conclusions</p> <p>This study suggested that <it>P. vivax </it>in Central China may be relatively susceptible to pyrimethamine. And it also highlights genotyping in the <it>pvdhfr </it>genes remains a useful tool to monitor the emergence and spread of <it>P. vivax </it>pyrimethamine resistance.</p

Temporal correlation analysis between malaria and meteorological factors in Motuo County, Tibet

<p>Abstract</p> <p>Background</p> <p>Malaria has been endemic in Linzhi Prefecture in the Tibet Autonomous Region (TAR) over the past 20 years, especially in Motou County with a highest incidence in the country in recent years. Meteorological factors, such as rainfall, temperature and relative humidity in Motou County were unique compared to other areas in Tibet as well as other parts of China, thus the objective of this work was to analyse the temporal correlation between malaria incidence and meteorological factors in Motou County, in order to seek the particular interventions for malaria control.</p> <p>Methods</p> <p>The meteorological and malaria data during 1986-2009 in Motuo County were studied to analyse the statistical relationship between meteorological data time series and malaria incidence data series. Temporal correlation between malaria incidence and meteorological factors were analyzed using several statistical methods. Spearman correlation analysis was conducted to examine the association between monthly malaria incidence and meteorological variables. Cross-correlation analysis of monthly malaria incidence series and monthly meteorological data time series revealed the time lag(s) of meteorological factors preceding malaria at which the series showed strongest correlation. Multiplicative seasonal auto-regressive integrated moving average (SARIMA) models were used in the cross-correlation analysis with pre-whitening which remove seasonality and auto-correlation of meteorological data series. Differenced data analysis which called inter-annual analysis was carried out to find underlying relationship between malaria data series and meteorological data series.</p> <p>Results</p> <p>It has been revealed that meteorological variables, such as temperature, relative humidity and rainfall were the important environmental factors in the transmission of malaria. Spearman correlation analysis demonstrated relative humidity was greatest relative to malaria incidence and the correlation coefficient was 0.543(<it>P </it>< 0.01). Strong positive correlations were found for malaria incidence time series lagging one to three months behind rainfall (<it>r </it>> 0.4) and lagging zero to two months behind temperature and relative humidity (<it>r </it>> 0.5) by the cross-correlation. Correlations were weaker with pre-whitening than without. The cross-correlograms between malaria incidence and various meteorological variables were entirely different. It was fluctuated randomly for temperature but with trend for the other two factors, which showed positive correlated to malaria when lag was from 0 to 5 months and negative from 6 to 12 months. Besides, the inter-annual analysis showed strong correlation between differenced annual malaria incidence and differenced meteorological variables (annual average maximum temperature, annual average relative humidity and annual average rainfall). The correlations coefficients were -0.668 (<it>P </it>< 0.01), 0.451(<it>P </it>< 0.05) and 0.432(<it>P </it>< 0.05), respectively.</p> <p>Conclusion</p> <p>Meteorological variables play important environmental roles in malaria transmission in Motou County. Relative humidity was the greatest influence factors, which affected the mosquito survival directly. The relationship between malaria incidence and rainfall was complex and it was not directly and linearly. The lags of temperature and relative humidity were similar and smaller than that of rainfall. Since the lags of meteorological variables affecting malaria transmission were short, it was difficult to do accurate long-term malaria incidence prediction using meteorological variables.</p

Malaria Elimination in the People’s Republic of China: Current Progress, Challenges, and Prospects

In China, the malaria elimination program was launched in 2010 with the objective to eliminate this disease by 2020. Large-scale malaria control and elimination actions have been conducted with significant success since inception of the nationwide program. The incidence of locally acquired malaria has declined sharply along with the concomitant decrease of malaria-endemic areas from 762 counties reporting malaria in 2010 to just two counties adjacent to border areas (Yunnan, China-Myanmar and Tibet, China-India) in 2016. In total, 1723 counties (79%) and 134 prefectures (52%) had completed the malaria elimination internal assessment by the end of 2016. The year 2017 was the first year without report of indigenous malaria cases throughout the country. Hence, this chapter is meant to share the lessons learned from malaria elimination in China benefiting countries on the way to malaria elimination

Development and validation of a model for predicting the risk of brain arteriovenous malformation rupture based on three-dimensional morphological features

ObjectiveBrain arteriovenous malformation (bAVM) is an important reason for intracranial hemorrhage. This study aimed at developing and validating a model for predicting bAVMs rupture by using three-dimensional (3D) morphological features extracted from Computed Tomography (CT) angiography.Materials and methodsThe prediction model was developed in a cohort consisting of 412 patients with bAVM between January 2010 and December 2020. All cases were partitioned into training and testing sets in the ratio of 7:3. Features were extracted from the 3D model built on CT angiography. Logistic regression was used to develop the model, with features selected using L1 Regularization, presented with a nomogram, and assessed with calibration curve, receiver operating characteristic (ROC) curve and decision curve analyze (DCA).ResultsSignificant variations in associated aneurysm, deep located, number of draining veins, type of venous drainage, deep drainage, drainage vein entrance diameter (Dv), type of feeding arteries, middle cerebral artery feeding, volume, Feret diameter, surface area, roundness, elongation, mean density (HU), and median density (HU) were found by univariate analysis (p &lt; 0.05). The prediction model consisted of associated aneurysm, deep located, number of draining veins, deep drainage, Dv, volume, Feret diameter, surface area, mean density, and median density. The model showed good discrimination, with a C-index of 0.873 (95% CI, 0.791–0.931) in the training set and 0.754 (95% CI, 0.710–0.795) in the testing set.ConclusionsThis study presented 3D morphological features could be conveniently used to predict hemorrhage from unruptured bAVMs

Elimination du paludisme en chine, évolution et défis de la transmission transfrontalière

Malaria has occurred in 80% of the counties in China in the past. After several decades of effort, malaria prevalence decreased drastically and China is currently approaching elimination throughout the country. Information on malaria vectors is still found not well documented, which could hinder the development of appropriate surveillance strategies and WHO certification. The major risk to malaria elimination is the re-introduction of the disease from imported malaria cases. There are an increasing number of imported malaria cases caused by Chinese citizens returning from malaria-affected countries recently. The information about their characters, drivers and route of introduction in different areas will provide evidence-based data to policy makers where and when to carry out the interventions. This will in turn allow them to develop efficient guidelines for risk-assessment of malaria re-introduction and for allocating appropriate resources. As a country with over 1.3 billion population and a territory covering different climatic zones, lessons learnt from malaria elimination in China that could serve as references to other countries. According to the Belt and Road initiatives, China will participate more globally to governance related activities. Partners and stakeholders within Global malaria elimination campaign are interested to the future opportunity and potential fields that would involve Chinese expertise. 1.A summary analysis was conducted on the nationwide distribution of malaria vectors, their bionomic characteristics, control measures and related studies. The distribution in China of the principal malaria vectors was found reduced, in particular for Anopheles lesteri and Anopheles dirus s.l., including the two main malaria vector species, An. dirus and An. baimaii, which nearly disappeared after several years of malaria control effort. Anopheles sinensis, which was previously reported to be less efficient in malaria transmission, is becoming the predominant species in Southwestern China. The field sampling results indicated the existence of high efficient malaria vectors, e.g. An. minimus and An. harrisoni at the China-Myanmar border. In addition, elevated human-biting rates, high adult and larval densities, and parous rates were found in both An. sinensis and An. harrisoni, which reveal a very high receptivity and risk of malaria re-introduction along the China–Myanmar border. 2.The comparative analysis of imported malaria cases reported from former non-endemic areas and former endemic areas in China showed that all former non-endemic areas are now reporting imported malaria cases. 3. A summary analysis on malaria elimination progress since 2010, was carried out with specific focus on mapping the residual malaria foci and the distribution of malaria cases in China. The incidence of locally acquired malaria has declined sharply along with the concomitant decrease of malaria-endemic areas from 762 counties reporting malaria in 2010 to just two counties adjacent to border areas (Yunnan Province: China-Myanmar and Tibet, China-India) in 2016. In 2017, China achieved zero indigenous malaria case report for the first time. In conclusion, China is on the track to achieve malaria elimination by 2020. The risk of re-introduction caused by the emergence of imported malaria cases and the occurrence of highly efficient malaria vectors present in the country is still the target of malaria surveillance. To maintain malaria elimination, intensified international collaboration with specific focus on cross-border areas and mobile/migrant population is called to take actions. The pilot studies on how to introduce the lessons learned from malaria elimination in China and the Chinese expertise are on the list to take action in future, which would harmonize the China aid to malaria elimination in the target countries.Le paludisme a déjà sévi dans 80% des pays chinois. Après plusieurs décennies d’efforts, la prévalence du paludisme a considérablement diminué et la Chine est sur le point de l’éliminer dans tout le pays. Les informations sur les vecteurs du paludisme ne sont toujours pas bien documentées, ce qui pourrait entraver l'élaboration de stratégies de surveillance appropriées et la certification par l'OMS. Le principal risque pour l'élimination du paludisme est la réintroduction de la maladie à partir de cas de paludisme importés. De plus en plus de cas de paludisme importés sont causés par des citoyens chinois revenant récemment de pays touchés par le paludisme. Les informations sur leurs personnages, leurs conducteurs et leur voie d’introduction dans différentes zones fourniront aux décideurs politiques des données factuelles où et quand effectuer les interventions. Avec plus de 1,3 milliard d’habitants et un territoire couvrant différentes zones climatiques, les enseignements tirés de l’élimination du paludisme en Chine pourraient servir de référence à d’autres pays. Selon les initiatives Belt and Road, la Chine participera plus globalement aux activités liées à la gouvernance. Les partenaires et les parties prenantes de la campagne mondiale pour l’élimination du paludisme s'intéressent aux opportunités futures et aux domaines potentiels qui impliqueraient une expertise chinoise. 1.Une analyse récapitulative a été réalisée sur la distribution à l'échelle nationale des vecteurs du paludisme, leurs caractéristiques bionomiques, leurs mesures de contrôle et les études connexes. La distribution en Chine des principaux vecteurs du paludisme a été réduite. Anopheles sinensis, qui avait déjà été signalé comme étant moins efficace dans la transmission du paludisme, est en train de devenir l’espèce prédominante dans le sud-ouest de la Chine. Les résultats de l'échantillonnage sur le terrain ont indiqué l'existence de vecteurs du paludisme hautement efficaces, par ex. An. minimus et An. harrisoni à la frontière Sino-Birmane. De plus, des taux élevés de piqûres humaines, des densités élevées d'adultes et de larves et des taux de parous ont été observés chez An. sinensis et An. harrisoni, qui révèlent une très grande réceptivité et un risque élevé de réintroduction du paludisme le long de la frontière Sino-Birmane. 2. L'analyse comparative des cas importés de paludisme signalés dans d'anciennes zones non endémiques et d'anciennes zones endémiques en Chine a montré que toutes les anciennes zones non endémiques signalaient désormais des cas importés de paludisme. 3. Une analyse résumée des progrès accomplis en matière d'élimination du paludisme depuis 2010 a été réalisée, avec un accent particulier sur la cartographie des foyers de paludisme résiduels et la répartition des cas de paludisme en Chine. L'incidence du paludisme contracté localement a fortement diminué, parallèlement à la diminution concomitante des zones d'endémie palustre de 762 comtés signalant le paludisme en 2010 à seulement deux comtés adjacents aux zones frontalières (Province du Yunnan: Chine-Myanmar et Tibet, Chine-Inde). En 2017, la Chine a atteint pour la première fois zéro cas de paludisme autochtone. En conclusion, la Chine est sur la voie de l’élimination du paludisme d’ici 2020. Le risque de réintroduction lié à l’émergence de cas importés de paludisme et à la présence de vecteurs du paludisme hautement efficaces présents dans le pays reste la cible de la surveillance du paludisme. Afin de maintenir l'élimination du paludisme, une collaboration internationale intensifiée, axée sur les zones transfrontalières et la population mobile / migrante, est appelée à prendre des mesures. Les études pilotes sur la manière de présenter les leçons tirées de l'élimination du paludisme en Chine et l'expertise Chinoise sont sur la liste des mesures à prendre, qui harmoniseraient l'aide de la Chine à l'élimination du paludisme dans les pays cibles

Malaria elimination in China, evolution and challenges with respect to cross border transmission

Le paludisme a déjà sévi dans 80% des pays chinois. Après plusieurs décennies d’efforts, la prévalence du paludisme a considérablement diminué et la Chine est sur le point de l’éliminer dans tout le pays. Les informations sur les vecteurs du paludisme ne sont toujours pas bien documentées, ce qui pourrait entraver l'élaboration de stratégies de surveillance appropriées et la certification par l'OMS. Le principal risque pour l'élimination du paludisme est la réintroduction de la maladie à partir de cas de paludisme importés. De plus en plus de cas de paludisme importés sont causés par des citoyens chinois revenant récemment de pays touchés par le paludisme. Les informations sur leurs personnages, leurs conducteurs et leur voie d’introduction dans différentes zones fourniront aux décideurs politiques des données factuelles où et quand effectuer les interventions. Avec plus de 1,3 milliard d’habitants et un territoire couvrant différentes zones climatiques, les enseignements tirés de l’élimination du paludisme en Chine pourraient servir de référence à d’autres pays. Selon les initiatives Belt and Road, la Chine participera plus globalement aux activités liées à la gouvernance. Les partenaires et les parties prenantes de la campagne mondiale pour l’élimination du paludisme s'intéressent aux opportunités futures et aux domaines potentiels qui impliqueraient une expertise chinoise. 1.Une analyse récapitulative a été réalisée sur la distribution à l'échelle nationale des vecteurs du paludisme, leurs caractéristiques bionomiques, leurs mesures de contrôle et les études connexes. La distribution en Chine des principaux vecteurs du paludisme a été réduite. Anopheles sinensis, qui avait déjà été signalé comme étant moins efficace dans la transmission du paludisme, est en train de devenir l’espèce prédominante dans le sud-ouest de la Chine. Les résultats de l'échantillonnage sur le terrain ont indiqué l'existence de vecteurs du paludisme hautement efficaces, par ex. An. minimus et An. harrisoni à la frontière Sino-Birmane. De plus, des taux élevés de piqûres humaines, des densités élevées d'adultes et de larves et des taux de parous ont été observés chez An. sinensis et An. harrisoni, qui révèlent une très grande réceptivité et un risque élevé de réintroduction du paludisme le long de la frontière Sino-Birmane. 2. L'analyse comparative des cas importés de paludisme signalés dans d'anciennes zones non endémiques et d'anciennes zones endémiques en Chine a montré que toutes les anciennes zones non endémiques signalaient désormais des cas importés de paludisme. 3. Une analyse résumée des progrès accomplis en matière d'élimination du paludisme depuis 2010 a été réalisée, avec un accent particulier sur la cartographie des foyers de paludisme résiduels et la répartition des cas de paludisme en Chine. L'incidence du paludisme contracté localement a fortement diminué, parallèlement à la diminution concomitante des zones d'endémie palustre de 762 comtés signalant le paludisme en 2010 à seulement deux comtés adjacents aux zones frontalières (Province du Yunnan: Chine-Myanmar et Tibet, Chine-Inde). En 2017, la Chine a atteint pour la première fois zéro cas de paludisme autochtone. En conclusion, la Chine est sur la voie de l’élimination du paludisme d’ici 2020. Le risque de réintroduction lié à l’émergence de cas importés de paludisme et à la présence de vecteurs du paludisme hautement efficaces présents dans le pays reste la cible de la surveillance du paludisme. Afin de maintenir l'élimination du paludisme, une collaboration internationale intensifiée, axée sur les zones transfrontalières et la population mobile / migrante, est appelée à prendre des mesures. Les études pilotes sur la manière de présenter les leçons tirées de l'élimination du paludisme en Chine et l'expertise Chinoise sont sur la liste des mesures à prendre, qui harmoniseraient l'aide de la Chine à l'élimination du paludisme dans les pays cibles.Malaria has occurred in 80% of the counties in China in the past. After several decades of effort, malaria prevalence decreased drastically and China is currently approaching elimination throughout the country. Information on malaria vectors is still found not well documented, which could hinder the development of appropriate surveillance strategies and WHO certification. The major risk to malaria elimination is the re-introduction of the disease from imported malaria cases. There are an increasing number of imported malaria cases caused by Chinese citizens returning from malaria-affected countries recently. The information about their characters, drivers and route of introduction in different areas will provide evidence-based data to policy makers where and when to carry out the interventions. This will in turn allow them to develop efficient guidelines for risk-assessment of malaria re-introduction and for allocating appropriate resources. As a country with over 1.3 billion population and a territory covering different climatic zones, lessons learnt from malaria elimination in China that could serve as references to other countries. According to the Belt and Road initiatives, China will participate more globally to governance related activities. Partners and stakeholders within Global malaria elimination campaign are interested to the future opportunity and potential fields that would involve Chinese expertise. 1.A summary analysis was conducted on the nationwide distribution of malaria vectors, their bionomic characteristics, control measures and related studies. The distribution in China of the principal malaria vectors was found reduced, in particular for Anopheles lesteri and Anopheles dirus s.l., including the two main malaria vector species, An. dirus and An. baimaii, which nearly disappeared after several years of malaria control effort. Anopheles sinensis, which was previously reported to be less efficient in malaria transmission, is becoming the predominant species in Southwestern China. The field sampling results indicated the existence of high efficient malaria vectors, e.g. An. minimus and An. harrisoni at the China-Myanmar border. In addition, elevated human-biting rates, high adult and larval densities, and parous rates were found in both An. sinensis and An. harrisoni, which reveal a very high receptivity and risk of malaria re-introduction along the China–Myanmar border. 2.The comparative analysis of imported malaria cases reported from former non-endemic areas and former endemic areas in China showed that all former non-endemic areas are now reporting imported malaria cases. 3. A summary analysis on malaria elimination progress since 2010, was carried out with specific focus on mapping the residual malaria foci and the distribution of malaria cases in China. The incidence of locally acquired malaria has declined sharply along with the concomitant decrease of malaria-endemic areas from 762 counties reporting malaria in 2010 to just two counties adjacent to border areas (Yunnan Province: China-Myanmar and Tibet, China-India) in 2016. In 2017, China achieved zero indigenous malaria case report for the first time. In conclusion, China is on the track to achieve malaria elimination by 2020. The risk of re-introduction caused by the emergence of imported malaria cases and the occurrence of highly efficient malaria vectors present in the country is still the target of malaria surveillance. To maintain malaria elimination, intensified international collaboration with specific focus on cross-border areas and mobile/migrant population is called to take actions. The pilot studies on how to introduce the lessons learned from malaria elimination in China and the Chinese expertise are on the list to take action in future, which would harmonize the China aid to malaria elimination in the target countries

Biology, Bionomics and Molecular Biology of Anopheles sinensis Wiedemann 1828 (Diptera: Culicidae), Main Malaria Vector in China

China has set a goal to eliminate all malaria in the country by 2020, but it is unclear if current understanding of malaria vectors and transmission is sufficient to achieve this objective. Anopheles sinensis is the most widespread malaria vector specie in China, which is also responsible for vivax malaria outbreak in central China. We reviewed literature from 1954 to 2016 on An. sinensis with emphasis on biology, bionomics, and molecular biology. A total of 538 references were relevant and included. An. sienesis occurs in 29 Chinese provinces. Temperature can affect most life-history parameters. Most An. sinensis are zoophilic, but sometimes they are facultatively anthropophilic. Sporozoite analysis demonstrated An. sinensis efficacy on Plasmodium vivax transmission. An. sinensis was not stringently refractory to P. falciparum under experimental conditions, however, sporozoite was not found in salivary glands of field collected An. sinensis. The literature on An. sienesis biology and bionomics was abundant, but molecular studies, such as gene functions and mechanisms, were limited. Only 12 molecules (genes, proteins or enzymes) have been studied. In addition, there were considerable untapped omics resources for potential vector control tools. Existing information on An. sienesis could serve as a baseline for advanced research on biology, bionomics and genetics relevant to vector control strategies

Digital Form Generation of Heritages in Historical District Based on Plan Typology and Shape Grammar: Case Study on Kulangsu Islet

Architectural heritage in historic districts, as a complex type of heritage, encompasses both the uniqueness of the building itself and also shows cultural and regional characteristics as a group, especially for the heritage site that contains multi-culture features. The digitalization research of this type of heritage often focuses on the digital archiving and modeling of heritages but rarely considers the combination of culture analysis and digitalization. This paper develops a digital form generation method for the heritages in historical districts by means of typological plan analysis, the Shape Grammar method, and Grasshopper software. Based on the case study of the modern Western-style house on Kulangsu, a world heritage site and historical district, this paper include three results: (1) dividing the layout plans of Kulangsu modern Western-style houses into three types, that is, native prototypes, foreign prototypes, and mixed prototypes, with 39 sub-types in total; (2) establishing shape grammar for the layout plans of Kulangsu modern Western-style houses with shape grammar sets and “S, L, R, I” expression rules; (3) creating a digital form generation method based on shape grammar result by Grasshopper software, including function cluster creation, function cluster connection and final model generation. This paper presents an example of quantitative analysis of heritage culture and a rapid modeling method of heritage, providing a reference for the construction of a heritage culture database and digital heritage management in historic districts

Effects of configuration parameters on lateral dynamics of tractor–two trailer combinations

The optimum configuration parameters of tractor–trailer combinations for lateral stability performance are proposed by adjusting the length of dolly and the second trailer’s center of gravity. A linear yaw plane model of vehicle combinations is adopted for dynamic analysis, and the model is calibrated by TruckSim. According to the yaw rate rearward amplification ratio of lateral response index, and combining the simulation results of MATLAB/Simulink, dolly and the second trailer are the dominate factors for lateral stability of vehicle combinations. Simulation results show that the distance between articulation joints of dolly is 1.6 m; simultaneously, the rate of distance between front hitch and center of gravity of the second trailer to its front and rear wheelbase is 0.41 and may gain the best lateral performance. Compared with configuration parameters of the original vehicle combinations, the results also illustrate that the one derived from adjustment approach reduces high-speed rearward amplification ratio by 11.4%. The proposed approach might be used for identifying desired design variables of the tractor–two trailer combinations and provided theoretical basis for stability tests