Lack of Consistent Malaria Incidence Hotspots in a Highland Kenyan Area During a 10-Year Period of Very Low and Unstable Transmission.
Ontology highlight
ABSTRACT:
SUBMITTER: Hamre KES
PROVIDER: S-EPMC7695093 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundMalaria in highland areas of Kenya affects children and adults. Local clinicians include symptoms other than fever when screening for malaria because they believe that fever alone does not capture all cases of malaria.MethodsIndividuals who presented to dispensaries in a highland Kenya site of low, unstable malaria transmission from 2007-2011 with 1 or more of 11 symptoms were tested by microscopy for malaria. Clinical malaria was defined as asexual Plasmodium falciparum infection on peripheral blood smear in an individual with any screening symptom. Asymptomatic P. falciparum infection was assessed in a cohort at ten time points to determine the extent to which symptomatic episodes with parasitaemia might be attributable to baseline (asymptomatic) parasitaemia in the community.Results3,420 individuals were screened for malaria, 634?<?5 years of age and 2,786???5 years of age. For the diagnosis of clinical malaria, the symptom of fever had a sensitivity and specificity of 88.9% and15.4% in children <5 years, and 55.8% and 54.4% in children ?5 years, respectively. Adding the symptom of headache increased sensitivity to 94. 4% in children <5 years and 96.8% in individuals ?5 years, but decreased specificity to 9.9% and 11.6%, respectively, and increased the number of individuals who would be tested by 6% and 92%, respectively. No combination of symptoms improved upon the presence fever or headache for detection of clinical malaria. In the cohort of asymptomatic individuals, P. falciparum parasitaemia was infrequent (0.1%).ConclusionIn areas of low, unstable malaria transmission, fever is a sensitive indicator of clinical malaria in children <5 years, but not in older children and adults. Adding headache to fever as screening symptom increases sensitivity of detection in individuals ?5 years old at the cost of decreased specificity. Screening for symptoms in addition to fever may be required to accurately capture all cases of clinical malaria in individuals ?5 years old in areas of low malaria transmission.
| S-EPMC4021053 | biostudies-literature
Project description:BackgroundInfectious diseases often demonstrate heterogeneity of transmission among host populations. This heterogeneity reduces the efficacy of control strategies, but also implies that focusing control strategies on "hotspots" of transmission could be highly effective.Methods and findingsIn order to identify hotspots of malaria transmission, we analysed longitudinal data on febrile malaria episodes, asymptomatic parasitaemia, and antibody titres over 12 y from 256 homesteads in three study areas in Kilifi District on the Kenyan coast. We examined heterogeneity by homestead, and identified groups of homesteads that formed hotspots using a spatial scan statistic. Two types of statistically significant hotspots were detected; stable hotspots of asymptomatic parasitaemia and unstable hotspots of febrile malaria. The stable hotspots were associated with higher average AMA-1 antibody titres than the unstable clusters (optical density [OD] = 1.24, 95% confidence interval [CI] 1.02-1.47 versus OD = 1.1, 95% CI 0.88-1.33) and lower mean ages of febrile malaria episodes (5.8 y, 95% CI 5.6-6.0 versus 5.91 y, 95% CI 5.7-6.1). A falling gradient of febrile malaria incidence was identified in the penumbrae of both hotspots. Hotspots were associated with AMA-1 titres, but not seroconversion rates. In order to target control measures, homesteads at risk of febrile malaria could be predicted by identifying the 20% of homesteads that experienced an episode of febrile malaria during one month in the dry season. That 20% subsequently experienced 65% of all febrile malaria episodes during the following year. A definition based on remote sensing data was 81% sensitive and 63% specific for the stable hotspots of asymptomatic malaria.ConclusionsHotspots of asymptomatic parasitaemia are stable over time, but hotspots of febrile malaria are unstable. This finding may be because immunity offsets the high rate of febrile malaria that might otherwise result in stable hotspots, whereas unstable hotspots necessarily affect a population with less prior exposure to malaria.
| S-EPMC2897769 | biostudies-literature
Project description:Malaria represents a major public health problem in Africa. In the East African highlands, the high-altitude areas were previously considered too cold to support vector population and parasite transmission, rendering the region particularly prone to epidemic malaria due to the lack of protective immunity of the population. Since the 1980's, frequent malaria epidemics have been reported and these successive outbreaks may have generated some immunity against Plasmodium falciparum amongst the highland residents. Serological studies reveal indirect evidence of human exposure to the parasite, and can reliably assess prevalence of exposure and transmission intensity in an endemic area. However, the vast majority of serological studies of malaria have been, hereto, limited to a small number of the parasite's antigens. We surveyed and compared the antibody response profiles of age-stratified sera from residents of two endemic areas in the western Kenyan highlands with differing malaria transmission intensities, during two distinct seasons, against 854 polypeptides of P. falciparum using high-throughput proteomic microarray technology. We identified 107 proteins as serum antibody targets, which were then characterized for their gene ontology biological process and cellular component of the parasite, and showed significant enrichment for categories related to immune evasion, pathogenesis and expression on the host's cell and parasite's surface. Additionally, we calculated age-fitted annual seroconversion rates for the immunogenic proteins, and contrasted the age-dependent antibody acquisition for those antigens between the two sampling sites. We observed highly immunogenic antigens that produce stable antibody responses from early age in both sites, as well as less immunogenic proteins that require repeated exposure for stable responses to develop and produce different seroconversion rates between sites. We propose that a combination of highly and less immunogenic proteins could be used in serological surveys to detect differences in malaria transmission levels, distinguishing sites of unstable and stable transmission.
| S-EPMC3846730 | biostudies-literature
Project description:Volcano seismicity is one of the key parameters to understand magma dynamics of erupting volcanoes. However, the physical process at the origin of the resulting complex and broadband seismic signals remains unclear. Syn-eruptive very long period (VLP) seismic signals have been explained in terms of the sudden expansion of gas pockets rising in the liquid melt. Their origin is linked to a magma dynamics which triggers the explosive process occurring before the explosive onset. We provide evidence based on acoustic, thermal, and ground deformation data to demonstrate that VLP signals at Stromboli are generated at the top of the magma column mainly after the explosion onset. We show that VLP amplitude and duration scale with the eruptive flux which induces a decompression of 103-104 Pa involving the uppermost ~ 250 m of the feeding conduit. The seismic VLP source represents the final stage of a ~ 200 s long charge and discharge mechanism the magma column has to release excess gas accumulated at the base of a denser and degassed magma mush. The position of the VLP seismic source coincides with the centroid of the shallow mush plug and tracks elevation changes of the magma free surface.
| S-EPMC8501111 | biostudies-literature
Project description:BackgroundSedative agents such as dexmedetomidine have been found to transiently exacerbate or unmask limb motor dysfunction in patients with eloquent area brain gliomas. The present study aims to investigate whether dexmedetomidine can inhibit motor plasticity in patients with glioma via fMRI.Methods21 patients with brain glioma were prospectively recruited between September 2017 and December 2018. Patients were classified into pre-M1 (primary motor cortex) group (n=9), post-M1 group (n=6), and non-eloquent group (control group) (n=6) according to the tumor position related to M1. The hand movement task-fMRI and resting state fMRI (rs-fMRI) were performed before and after sedation using dexmedetomidine. The lateralization index (LI) of activation voxels and magnitude and the functional connectivity (FC) of motor network were compared before and after sedation and among different groups.ResultsPermanent postoperative motor deficit of the upper limb was found in 5 of 6 patients in the pre-M1 group, and none in other groups (P < .01). Task-fMRI showed the LI of activation volume and activation magnitude at M1 significantly increased only in the pre-M1 group after sedation (P < .05). Rs-fMRI showed 60.0% (27 of 45) FCs of motor network decreased in pre-M1 group after sedation (p[FDR] < .05); whereas there was no FC reduction in post-M1 and control groups (p[FDR] > .05).ConclusionsIn patients with eloquent area gliomas, dexmedetomidine can inhibit the unstable compensative motor plasticity on both task- and rs-fMRI. fMRI may be a promising method for elucidating the effect of sedative agents on motor plasticity.
| S-EPMC8221338 | biostudies-literature
Project description:BackgroundStudies in Southeast Asia reported a strong relationship between polymorphisms at the propeller domain of the Kelch 13 (K13) protein encoded by the Plasmodium falciparum k13 (pfk13) gene and delayed parasite clearance after artemisinin treatment. In Africa, P. falciparum remains susceptible and combination therapy regimens which include an artemisinin component display good efficacy. Using quantitative real-time PCR (qPCR), sub-microscopic persistence of P. falciparum has previously been reported in one-third of children treated with artemisinin combination therapy (ACT) in western Kenya. In this study, further investigation was made to evaluate whether these sub-microscopic residual parasites also harbour mutations at the propeller region of pfk13 and whether the mutations, if any, affect treatment outcome.MethodsThe pfk13 propeller domain was genotyped in DNA samples obtained in 2009 from Kenyan children treated with artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Paired samples at pre-treatment (day 0) and day of treatment failure (day 28 or 42) for 32 patients with documented recurrent parasitaemia were available for genotyping. Additional day 3 DNA samples were available for 10 patients.ResultsNo mutation associated with artemisinin resistance in Southeast Asia was observed. Only one DP-treated patient harboured a non-synonymous mutation at codon 578 (A578S) of pfk13-propeller gene in the day 0 sample, but this allele was replaced by the wild-type (A578) form on day 3 and on the day of recurrent parasitaemia. The mutation at amino acid codon 578 showed no association with any phenotype. Polymorphisms in pfk13 were not responsible for parasite persistence and gametocyte carriage in the children treated with ACT.ConclusionThis study contributes to the ongoing surveillance of suspected artemisinin resistance parasites in Africa by providing baseline prevalence of k13-propeller mutations in western Kenya with samples collected from a longitudinal study. Clinical Trials Registration NCT00868465.
| S-EPMC4722670 | biostudies-literature
Project description:Very small embryonic-like (VSEL) cells have been described as putatively pluripotent stem cells present in murine bone marrow and human umbilical cord blood (hUCB) and as such are of high potential interest for regenerative medicine. However, there remain some questions concerning the precise identity and properties of VSEL cells, particularly those derived from hUCB. For this reason, we have carried out an extensive characterisation of purified populations of VSEL cells from a large number of UCB samples. Consistent with a previous report, we find that VSEL cells are CXCR4+, have a high density, are indeed significantly smaller than HSC and have an extremely high nuclear/cytoplasmic ratio. Their nucleoplasm is unstructured and stains strongly with Hoechst 33342. A comprehensive FACS screen for surface markers characteristic of embryonic, mesenchymal, neuronal or hematopoietic stem cells revealed negligible expression on VSEL cells. These cells failed to expand in vitro under a wide range of culture conditions known to support embryonic or adult stem cell types and a microarray analysis revealed the transcriptional profile of VSELs to be clearly distinct both from well-defined populations of pluripotent and adult stem cells and from the mature hematopoietic lineages. Finally, we detected an aneuploid karyotype in the majority of purified VSEL cells by fluorescence in situ hybridisation. These data support neither an embryonic nor an adult stem cell like phenotype, suggesting rather that hUCB VSEL are an aberrant and inactive population that is not comparable to murine VSEL.
2011-09-03 | GSE31869 | GEO
Project description:Insomnia disorder is a prevalent sleep disorder, which affects about 10% of general population. However, its neural mechanisms are poorly understood. Recently, several structural and functional neuroimaging studies have been conducted in patients with insomnia disorder, but these studies have yielded diverse findings. Here, we aimed to identify consistent patterns of abnormal brain alterations in insomnia disorder by performing a quantitative coordinate-based meta-analysis. Following the preferred reporting for systematic reviews and meta-analyses statement, we searched PubMed database and used reference tracking and finally retrieved 19 eligible studies (six task-based functional magnetic resonance imaging, eight resting-state functional magnetic resonance imaging, three voxel-based morphometry, and two positron emission tomography). We extracted peak coordinates from these studies and tested for convergence using the activation likelihood estimation method. Using this method, we found no significant convergent evidence for combination of structural atrophy and functional disturbances across previous studies (p = 0.914). Inconsistencies across these studies might be related to heterogonous clinical populations, the explorative nature of these studies in combination with small sample sizes, different experimental designs, and various preprocessing and statistical approaches. Future neuroimaging studies on insomnia disorder should include larger well-characterized samples, as well as standard imaging and analysis protocols.
| S-EPMC7965842 | biostudies-literature
Project description:BackgroundAntimicrobial responses have been shown to be profoundly attenuated in very preterm neonates when examined on cord blood. However, we lack data on these responses at the time these neonates are most vulnerable to infections.MethodsMultiple cytokine responses to two prototypic Toll-like receptor (TLR) agonists: lipopolysaccharide (LPS) (TLR4) and R848 (TLR7/8) were prospectively measured in preterm neonates born ≤30 wk of gestation (n = 50) during the first 28 d of age using whole blood and single-cell multiparameter flow cytometry assays. Results were compared to term neonates (n = 30) and adult controls (n = 25).ResultsIn preterm neonates, LPS and R848 responses remained attenuated in both cord blood and in the first 28 d of age. These responses showed significant maturation over time after adjusting for gestational age and were confirmed in monocytes and dendritic cells on a per-cell basis. We detected no major contribution of chorioamnionitis, maternal antenatal corticosteroids or magnesium sulfate treatment, labor, or mode of delivery to the maturation of cytokine responses.ConclusionInnate immune antimicrobial defenses are profoundly attenuated developmentally in very preterm neonates during the neonatal period, suggesting that exogenous factors drive the sustained systemic inflammation that has been linked to increased morbidities in these infants.
| S-EPMC5059157 | biostudies-literature
Project description:AIM:To define biome-scale hotspots of phylogenetic and functional mammalian biodiversity (PD and FD, respectively) and compare them to 'classical' hotspots based on species richness (SR) only. LOCATION:Global. METHODS:SR, PD & FD were computed for 782 terrestrial ecoregions using distribution ranges of 4616 mammalian species. We used a set of comprehensive diversity indices unified by a recent framework that incorporates the species relative coverage in each ecoregion. We build large-scale multifaceted diversity-area relationships to rank ecoregions according to their levels of biodiversity while accounting for the effect of area on each diversity facet. Finally we defined hotspots as the top-ranked ecoregions. RESULTS:While ignoring species relative coverage led to a relative good congruence between biome top ranked SR, PD and FD hotspots, ecoregions harboring a rich and abundantly represented evolutionary history and functional diversity did not match with top ranked ecoregions defined by species richness. More importantly PD and FD hotspots showed important spatial mismatches. We also found that FD and PD generally reached their maximum values faster than species richness as a function of area. MAIN CONCLUSIONS:The fact that PD/FD reach faster their maximal value than SR may suggest that the two former facets might be less vulnerable to habitat loss than the latter. While this point is expected, it is the first time that it is quantified at global scale and should have important consequences in conservation. Incorporating species relative coverage into the delineation of multifaceted hotspots of diversity lead to weak congruence between SR, PD and FD hotspots. This means that maximizing species number may fail at preserving those nodes (in the phylogenetic or functional tree) that are relatively abundant in the ecoregion. As a consequence it may be of prime importance to adopt a multifaceted biodiversity perspective to inform conservation strategies at global scale.
| S-EPMC4110700 | biostudies-literature