Heritability of antibody isotype and subclass responses to Plasmodium falciparum antigens.

Background: It is important to understand the extent to which genetic factors regulate acquired immunity to common infections. A classical twin study design is useful to estimate the heritable component of variation in measurable immune parameters.

Methodology/principal Findings: This study assessed the relative heritability of different plasma antibody isotypes and subclasses (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE) naturally acquired to P.

Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals.

Background: Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens.

Methods: We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies.

Results: Subjects with one minor allele smoked on average 0.

Effects of genetic variation at the CYP2C19/CYP2C9 locus on pharmacokinetics of chlorcycloguanil in adult Gambians.

Aims: Antimalarial biguanides are metabolized by CYP2C19, thus genetic variation at the CYP2C locus might affect pharmacokinetics and so treatment outcome for malaria.

Materials & Methods: Polymorphisms in CYP2C19 and CYP2C9 in 43 adult Gambians treated with chlorproguanil/dapsone for uncomplicated malaria were assessed. Chlorcycloguanil pharmacokinetics were measured and associations with CYP2C19 and CYP2C9 alleles and CYP2C19 metabolizer groups investigated.

Effect of two different house screening interventions on exposure to malaria vectors and on anaemia in children in The Gambia: a randomised controlled trial.

Background: House screening should protect people against malaria. We assessed whether two types of house screening--full screening of windows, doors, and closing eaves, or installation of screened ceilings--could reduce house entry of malaria vectors and frequency of anaemia in children in an area of seasonal malaria transmission.

Methods: During 2006 and 2007, 500 occupied houses in and near Farafenni town in The Gambia, an area with low use of insecticide-treated bednets, were randomly assigned to receive full screening, screened ceilings, or no screening (control).

Gene copy number variation throughout the Plasmodium falciparum genome.

Background: Gene copy number variation (CNV) is responsible for several important phenotypes of the malaria parasite Plasmodium falciparum, including drug resistance, loss of infected erythrocyte cytoadherence and alteration of receptor usage for erythrocyte invasion. Despite the known effects of CNV, little is known about its extent throughout the genome.

Results: We performed a whole-genome survey of CNV genes in P.

Tackling socially determined dental inequalities: ethical aspects of Childsmile, the national child oral health demonstration programme in Scotland.

Many ethical issues are posed by public health interventions. Although abstract theorizing about these issues can be useful, it is the application of ethical theory to real cases which will ultimately be of benefit in decision-making. To this end, this paper will analyse the ethical issues involved in Childsmile, a national oral health demonstration programme in Scotland that aims to improve the oral health of the nation's children and reduce dental inequalities through a combination of targeted and universal interventions.

Components of socioeconomic risk associated with head and neck cancer: a population-based case-control study in Scotland.

The complex associations between socioeconomic circumstances and risk for head and neck cancer are under-explored. We investigated components of social class and their relative influence on the risk of head and neck cancers by studying 103 patients (age range 24-80 years) who had been diagnosed with cancer of the head and neck between April 2002 and December 2004, and 91 controls who were randomly selected from general practitioners' lists. Information about occupation, education, smoking, and alcohol consumption was collected at personal interview.

Genome-wide and fine-resolution association analysis of malaria in West Africa.

We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa.

Prospective identification of malaria parasite genes under balancing selection.

Background: Endemic human pathogens are subject to strong immune selection, and interrogation of pathogen genome variation for signatures of balancing selection can identify important target antigens. Several major antigen genes in the malaria parasite Plasmodium falciparum have shown such signatures in polymorphism-versus-divergence indices (comparing with the chimpanzee parasite P. reichenowi), and in allele frequency based indices.

Quantitative detection of Plasmodium falciparum DNA in saliva, blood, and urine.

Background: Current methods for detecting malaria parasites are invasive and associated with poor compliance when repeated sampling is required. New methods to detect and quantify parasites in a less-invasive manner would greatly enhance the potential for longitudinal surveillance in clinical trials.

Methods: Saliva, urine, and blood samples from 386 Gambian outpatients with suspected malaria infections were analyzed by nested polymerase chain reaction (nPCR) to detect infection and to evaluate diagnostic accuracy in comparison to expert microscopy.

Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria.

Background: Studies to identify phenotypically-associated polymorphisms in the Plasmodium falciparum 23 Mb genome will require a dense array of marker loci. It was considered promising to undertake initial allelic association studies to prospect for virulence polymorphisms in Thailand, as the low endemicity would allow higher levels of linkage disequilibrium (LD) than would exist in more highly endemic areas.

Methodology/principal Findings: Assessment of LD was first made with 11 microsatellite loci widely dispersed in the parasite genome, and 16 microsatellite loci covering a approximately 140 kb region of chromosome 2 (an arbitrarily representative non-telomeric part of the genome), in a sample of 100 P.

Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture.

We have cultured Plasmodium falciparum directly from the blood of infected individuals to examine patterns of mature-stage gene expression in patient isolates. Analysis of the transcriptome of P. falciparum is complicated by the highly periodic nature of gene expression because small variations in the stage of parasite development between samples can lead to an apparent difference in gene expression values.

Distinct roles for FOXP3 and FOXP3 CD4 T cells in regulating cellular immunity to uncomplicated and severe Plasmodium falciparum malaria.

Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to pathogenesis of severe malaria. To determine whether this balance is maintained by classical regulatory T cells (CD4(+) FOXP3(+) CD127(-/low); Tregs) we compared cellular responses between Gambian children (n = 124) with severe Plasmodium falciparum malaria or uncomplicated malaria infections. Although no significant differences in Treg numbers or function were observed between the groups, Treg activity during acute disease was inversely correlated with malaria-specific memory responses detectable 28 days later.

Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.

Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer.

Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission.

An important aspect of clinical immunity to malaria is the ability to down-regulate inflammatory responses, once parasitaemia is under control, in order to avoid immune-mediated pathology. The role of classical (CD4(+)CD25(+)CD127(lo/-)FOXP3(+)) Treg in this process, however, remains controversial. Thus, we have characterized the frequency, phenotype and function of Treg populations, over time, in healthy individuals in The Gambia.

Oral health, mouthwashes and cancer--what is the story?

Design: Two hospital-based case-control studies were conducted in central and eastern Europe and Latin America. CASE / CONTROL SELECTION: Cases and controls were recruited in Moscow (Russia), Bucharest (Romania) and Lodz and Warsaw (Poland) from 1998 to 2002, and from 1998 to 2003 in Buenos Aires (Argentina), La Habana (Cuba) and the Brazilian towns Rio de Janeiro, São Paulo, Pelotas, Porto Alegre and Goiânia. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and oesophagus, as well as age- (in quinquennia) and sex frequency-matched controls, were enrolled from 1998 to 2003.

Diet and upper-aerodigestive tract cancer in Europe: the ARCAGE study.

There is suggestive, but inconclusive, evidence that dietary factors may affect risk of cancers of the upper aerodigestive tract (UADT). In the context of the alcohol-related cancers and genetic susceptibility in Europe study, we have examined the association of dietary factors with UADT cancer risk. We have analyzed data from 2,304 patients with UADT cancer and 2,227 control subjects recruited in 14 centers in 10 European countries.

Polymorphisms in erythrocyte binding antigens 140 and 181 affect function and binding but not receptor specificity in Plasmodium falciparum.

Invasion of human erythrocytes by the malaria parasite Plasmodium falciparum utilizes multiple ligand-receptor interactions involving erythrocyte receptors and parasite erythrocyte binding proteins of the Duffy binding-like family. Erythrocyte binding antigen 175 (EBA-175) binds to glycophorin A, the most abundant protein on the human erythrocyte surface and EBA-140 (also known as BAEBL) binds to glycophorin C, while the receptor for EBA-181 (also known as JESEBL) remains unknown. EBA binding is mediated via region II, a highly structured extracellular domain that shows a degree of sequence variability between different laboratory strains/isolates.

Oral cancer risk and smokeless tobacco products--clouded by smoke?

Data Sources: Medline, Embase, Cancerlit, Toxline were searched, followed by the reference lists of identified reviews and articles.

Study Selection: Human cohort or case-control studies in peer-reviewed journals or that were publicly available were selected if they specified study location; examined any form of oral cancer as the outcome; and described use of chewing tobacco, orally used moist snuff or unspecified smokeless tobacco as the exposure. Studies in Asian populations and those with insufficient power where risk estimates and confidence intervals were not reported or could not be calculated were excluded.

Alcohol-related cancers and genetic susceptibility in Europe: the ARCAGE project: study samples and data collection.

Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity, pharynx (other than nasopharynx), larynx, and esophagus. Tobacco smoking and consumption of alcoholic beverages are established causes of UADT cancers, whereas reduced intake of vegetables and fruits are likely causes. The role of genetic predisposition and possible interactions of genetic with exogenous factors, however, have not been adequately studied.

Anopheles gambiae complex along The Gambia river, with particular reference to the molecular forms of An. gambiae s.s.

Background: The geographic and temporal distribution of M and S molecular forms of the major Afrotropical malaria vector species Anopheles gambiae s.s. at the western extreme of their range of distribution has never been investigated in detail.

Dry season ecology of Anopheles gambiae complex mosquitoes in The Gambia.

Background: Malaria in The Gambia is highly seasonal, with transmission occurring as Anopheles gambiae s.l. populations expand during and immediately after a single annual rainy season that lasts from June to October.

Socioeconomic factors influence selection and participation in a population-based case-control study of head and neck cancer in Scotland.

Objective: We aimed to investigate the association between socioeconomic factors and selection and participation biases in a population-based case-control study of head and neck cancer conducted in the city of Glasgow, UK.

Methods: General Practices (GP) of the case subjects were the sampling frame from which age and sex-matched controls were randomly selected. Participant and nonparticipant postcodes of cases and controls were linked to the area-based Scottish Index of Multiple Deprivation.