We have modified an existing semi-nested multiplex polymerase chain reaction (PCR) by adding one Plasmodium knowlesi-specific nested PCR, and validated the latter against laboratory and clinical ...samples. This new method has the advantage of being relatively affordable in low resource settings while identifying the five human Plasmodium species with a three-step PCR.
Air pollution is a major global public health issue causing considerable morbidity and mortality. Measuring levels of air pollutants and facilitating access to the data has been identified as a ...pathway to raise awareness and initiate dialogue between relevant stakeholders. Low-and middle-income countries (LMICs) urgently need simple, low-cost approaches to generate such data, especially in settings with no or unreliable data. We established a network of easy-to-use low-cost air quality sensors (PurpleAir-II-SD) to monitor fine particulate matter (PMsub.2.5 ) concentrations at 15 sites, in 11 cities across eight sub-Saharan Africa (sSA) countries between February 2020 and January 2021. Annual PMsub.2.5 concentrations, seasonal and temporal variability were determined. Time trends were modelled using harmonic regression. Annual PMsub.2.5 concentrations ranged between 10 and 116 µg/msup.3 across study sites, exceeding the current WHO annual mean guideline level of 5 µg/msup.3 . The largest degree of seasonal variation was seen in Nigeria, where seven sites showed higher PMsub.2.5 levels during the dry than during the wet season. Other countries with less pronounced dry/wet season variations were Benin (20 µg/msup.3 versus 5 µg/msup.3 ), Uganda (50 µg/msup.3 versus 45 µg/msup.3 ), Sukuta (Gambia) (20 µg/msup.3 versus 15 µg/msup.3 ) and Kenya (30 µg/msup.3 versus 25 µg/msup.3 ). Diurnal variation was observed across all sites, with two daily PMsub.2.5 peaks at about 06:00 and 18:00 local time. We identified high levels of air pollution in the 11 African cities included in this study. This calls for effective control measures to protect the health of African urban populations. The PMsub.2.5 peaks around ‘rush hour’ suggest traffic-related emissions should be a particular area for attention.
Apolipoprotein A-IV (apoA-IV) has been observed to be associated with lipids, kidney function, adiposity- and diabetes-related parameters. To assess the causal relationship of apoA-IV with these ...phenotypes, we conducted bidirectional Mendelian randomization (MR) analyses using publicly available summary-level datasets from GWAS consortia on apoA-IV concentrations (n = 13,813), kidney function (estimated glomerular filtration rate (eGFR), n = 133,413), lipid traits (HDL cholesterol, LDL cholesterol, triglycerides, n = 188,577), adiposity-related traits (body-mass-index (n = 322,206), waist-hip-ratio (n = 210,088)) and fasting glucose (n = 133,010). Main analyses consisted in inverse-variance weighted and multivariable MR, whereas MR-Egger regression and weighted median estimation were used as sensitivity analyses. We found that eGFR is likely to be causal on apoA-IV concentrations (53 SNPs; causal effect estimate per 1-SD increase in eGFR = -0.39; 95% CI = -0.54, -0.24; p-value = 2.4e-07). Triglyceride concentrations were also causally associated with apoA-IV concentrations (40 SNPs; causal effect estimate per 1-SD increase in triglycerides = -0.06; 95% CI = -0.08, -0.04; p-value = 4.8e-07), independently of HDL-C and LDL-C concentrations (causal effect estimate from multivariable MR = -0.06; 95% CI = -0.10, -0.02; p-value = 0.0014). Evaluating the inverse direction of causality revealed a possible causal association of apoA-IV on HDL-cholesterol (2 SNPs; causal effect estimate per one percent increase in apoA-IV = -0.40; 95% CI = -0.60, -0.21; p-value = 5.5e-05).
A recently published comment on a report of Plasmodium knowlesi infections in Vietnam states that this may not accurately represent the situation in the study area because the PCR primers used may ...cross-hybridize with Plasmodium vivax. Nevertheless, P. knowlesi infections have been confirmed by sequencing. In addition, a neighbour-joining tree based on the 18S S-Type SSUrRNA gene shows that the Vietnamese samples clearly cluster with the P. knowlesi isolates identified in Malaysia and are distinct from the corresponding P. vivax sequences. All samples came from asymptomatic individuals who did not consult for fever during the months preceding or following the survey, indicating that asymptomatic P. knowlesi infections occur in this population, although this does not exclude the occurrence of symptomatic cases. Large-scale studies to determine the extent and the epidemiology of P. knowlesi malaria in Vietnam are further needed.
Despite the large burden of Plasmodium vivax, little is known about its transmission dynamics. This study explored the population structure and spatio-temporal dynamics of P. vivax recurrent ...infections after radical cure in a two-year cohort study carried out in a rural community of the Peruvian Amazon.
A total of 37 P. vivax participants recruited in San Carlos community (Peru) between April and December 2008 were treated radically with chloroquine and primaquine and followed up monthly for two years with systematic blood sampling. All samples were screened for malaria parasites and subsequently all P. vivax infections genotyped using 15 microsatellites. Parasite population structure and dynamics were determined by computing different genetic indices and using spatio-temporal statistics.
After radical cure, 76% of the study participants experienced one or more recurrent P. vivax infections, most of them sub-patent and asymptomatic. The parasite population displayed limited genetic diversity (He = 0.49) and clonal structure, with most infections (84%) being monoclonal. Spatio-temporal clusters of specific haplotypes were found throughout the study and persistence of highly frequent haplotypes were observed over several months within the same participants/households.
In San Carlos community, P. vivax recurrences were commonly observed after radical treatment, and characterized by asymptomatic, sub-patent and clustered infections (within and between individuals from a few neighbouring households). Moreover low genetic diversity as well as parasite inbreeding are likely to define a clonal parasite population which has important implications on the malaria epidemiology of the study area.
We have shown that the thrombin G-protein coupled receptors (GPCR) designated as protease-activated receptors (PAR-1) are expressed in primary cancer cells isolated from peritoneal and pleural ...malignant effusions. Here, our main goal was to evaluate several coagulation and thrombin activation effectors and markers in a series of 136 malignant effusions from cancer patients with gastrointestinal, lung and mammary carcinomas. All these patients present a highly activated coagulation system in blood and their malignant effusions, as indicated by high levels of prothrombin F1.2 fragments and D-dimers. Notably, we detected in the effusions all the coagulation factors of the tissue factor pathway inducing thrombin activation, namely factors VII, V, X and II, as well as high VEGF levels and IGF-II in mature and precursor forms. Fibrin clot formation also correlated with higher levels of free ionized calcium (iCa), suggesting that iCa and its binding protein albumin are regulatory factors for fibrinogenesis in effusions. Consequently, thrombin, VEGF and IGFII appear to converge in the promotion of survival and invasivity of the metastatic cancer cells from blood to the malignant effusions. Thus, we add new insights on the interconnections between blood coagulation disorders in cancer patients and thrombin activation in malignant effusions, including their functional interaction with PAR in metastatic cancer cells. Based on these data we propose to counteract the metastatic cascades by targeted invalidation of key effectors of the coagulation system. Therefore, potential therapeutic approaches include the application of thrombin protease inhibitors, VEGF-blocking antibodies, and drugs targeting the VEGF and thrombin signaling pathways, such as tyrosine kinase or GPCR inhibitors.
Background The burden of malaria in Vietnam has drastically reduced, prompting the National Malaria Control Program to officially engage in elimination efforts. Plasmodium vivax is becoming ...increasingly prevalent, remaining a major problem in the country's central and southern provinces. A better understanding of P. vivax genetic diversity and structure of local parasite populations will provide baseline data for the evaluation and improvement of current efforts for control and elimination. The aim of this study was to examine the population genetics and structure of P. vivax isolates from four communities in Tra Leng commune, Nam Tra My district in Quang Nam, Central Vietnam. Methodology/Principal Findings P. vivax mono infections collected from 234 individuals between April 2009 and December 2010 were successfully analyzed using a panel of 14 microsatellite markers. Isolates displayed moderate genetic diversity (He = 0.68), with no significant differences between study communities. Polyclonal infections were frequent (71.4%) with a mean multiplicity of infection of 1.91 isolates/person. Low but significant genetic differentiation (FST value from -0.05 to 0.18) was observed between the community across the river and the other communities. Strong linkage disequilibrium ( = 0.113, p < 0.001) was detected across all communities, suggesting gene flow within and among them. Using multiple approaches, 101 haplotypes were grouped into two genetic clusters, while 60.4% of haplotypes were admixed. Conclusions/Significance In this area of Central Vietnam, where malaria transmission has decreased significantly over the past decade, there was moderate genetic diversity and high occurrence of polyclonal infections. Local human populations have frequent social and economic interactions that facilitate gene flow and inbreeding among parasite populations, while decreasing population structure. Findings provide important information on parasites populations circulating in the study area and are relevant to current malaria elimination efforts.
Background Characterizing the parasite dynamics and population structure provides useful information to understand the dynamic of transmission and to better target control interventions. Despite ...considerable efforts for its control, vivax malaria remains a major health problem in Peru. In this study, we have explored the population genetics of Plasmodium vivax isolates from Iquitos, the main city in the Peruvian Amazon, and 25 neighbouring peri-urban as well as rural villages along the Iquitos-Nauta Road. Methodology/ Results From April to December 2008, 292 P. vivax isolates were collected and successfully genotyped using 14 neutral microsatellites. Analysis of the molecular data revealed a similar proportion of monoclonal and polyclonal infections in urban areas, while in rural areas monoclonal infections were predominant (p = 0.002). Multiplicity of infection was higher in urban (MOI = 1.5-2) compared to rural areas (MOI = 1) (p = 0.003). The level of genetic diversity was similar in all areas (He = 0.66-0.76, p = 0.32) though genetic differentiation between areas was substantial (PHIPT = 0.17, p<0.0001). Principal coordinate analysis showed a marked differentiation between parasites from urban and rural areas. Linkage disequilibrium was detected in all the areas ( = 0.08-0.49, for all p<0.0001). Gene flow among the areas was stablished through Bayesian analysis of migration models. Recent bottleneck events were detected in 4 areas and a recent parasite expansion in one of the isolated areas. In total, 87 unique haplotypes grouped in 2 or 3 genetic clusters described a sub-structured parasite population. Conclusion/Significance Our study shows a sub-structured parasite population with clonal propagation, with most of its components recently affected by bottleneck events. Iquitos city is the main source of parasite spreading for all the peripheral study areas. The routes of transmission and gene flow and the reduction of the parasite population described are important from the public health perspective as well for the formulation of future control policies.
We have modified an existing semi-nested multiplex polymerase chain reaction (PCR) by adding one Plasmodium knowlesi-specific nested PCR, and validated the latter against laboratory and clinical ...samples. This new method has the advantage of being relatively affordable in low resource settings while identifying the five human Plasmodium species with a three-step PCR.
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