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1. Paediatric Bronchiectasis in a Resource-Constrained Centre: A Case Series

Author

Kuti BP, Jallow M, and Jobarteh ML

Subjects
Medicine (General), R5-920, Public aspects of medicine, RA1-1270
Abstract

Bronchiectasis denotes fixed and often irreversible dilatation of the bronchial wall caused by persistent inflammation and infection. Children with bronchiectasis in developing countries suffer recurrent hospitalisation and poor quality of life and usually succumb to the condition. These children are poorly recognised, misdiagnosed, and under-reported. We report five cases of computerised tomography-diagnosed paediatric bronchiectasis managed at the Edward Francis Small Teaching Hospital (EFSTH), Banjul, The Gambia. The ages of the children at presentation ranged from 3 to 14 years, and they all had recurrent chest infections. Four out of the five cases had Pulmonary Tuberculosis, among whom two cases had HIV/TB co-infections, and the only non-TB, non-HIV case had features of Down syndrome with congenital heart lesions. All the cases had growth impairment; digital clubbing was observed in four, and low peripheral oxygen saturation in room air in three of the five children. These cases are reported to increase the index of suspicion among clinicians working in resource-limited settings to consider the diagnosis of bronchiectasis in children with recurrent chest infections. Early diagnosis and prompt management, including appropriate follow-up care, will improve the quality of life of these children and ensure better management outcomes.

Published
2024
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2. The impact of single nucleotide polymorphisms in human genes that regulate hepcidin and iron on oral iron absorption and the risk of anaemia in Africans

Author

Jallow, M. W. and Campino, S.

Abstract

Background: Up to 60% of women and children living in low- and middle-income countries (LMICs) are anaemic. Food fortification and iron supplementation are the most common measures employed to combat anaemia. However, these are not effective treatments for anaemias caused by non-nutritional factors. Genome-wide association studies (GWAS) mainly in Europeans and Asians have identified single nucleotide polymorphisms (SNPs) within the hepcidin and iron regulatory genes that are associated with the risk of anaemia. Several of these SNPs are in the TMPRSS6 gene, which encodes matriptase-2, a protein that regulates the expression of hepcidin. This thesis examined the impact of SNPs in the iron regulatory genes previously reported in non-African populations, on the risk of anaemia and on impaired oral iron absorption in Africans. Methods: First, the literature was searched for genetic variants identified in the hepcidin and iron regulatory genes, that are associated with low iron status. Second, we investigated the effects of common TMPRSS6 and transferrin (TF) SNPs on iron status in a cohort of healthy individuals from rural Gambia (n=1315). Third, a recallby- genotype (RbG) study was conducted to investigate the impact of carrying single or multiple alleles at the common TMPRSS6 SNPs on oral iron absorption in healthy individuals from rural Gambia. Results: TMPRSS6 rs855791, rs4820268 and rs2235321, and TF rs3811647 are the most common SNPs that associated with low iron status. We did not find effects of any of the TMPRSS6 SNPs on the risk of anaemia. However, we found that TMPRSS6 rs2235321 was associated with serum hepcidin concentration, with a more substantial effect on individuals with low haemoglobin or ferritin. Also, TF rs3811647 had a significant influence on transferrin and its binding capacity, with a single allele effect of 8-12%. In the RbG study, we did not find any effect of the three TMPRSS6 SNPs on oral iron absorption. However, we found that each of the TMPRSS6 SNPs affects hepcidin, with carriers of major alleles having higher hepcidin compared to minor allele carriers. Also, we found that heterozygotes at both rs2235321 and rs855791 did not alter their hepcidin concentration after an oral iron dose, whereas, individuals in all the other genotype groups did. Conclusions: This thesis confirms the previously observed association between the TF rs3811647 and transferrin in other Africans and Europeans replicates in West Africans. However, we could not demonstrate that the previous associations between TMPRSS6 gene variants and iron status, exist in West Africans. This lack of replication might be due to the high genetic diversity that exists in African populations. We identified an effect of TMPRSS6 rs2235321 on serum hepcidin concentration. In the RbG study, the three TMPRSS6 SNPs studied influenced serum hepcidin levels but not oral iron absorption in healthy individuals. This finding suggests that there might be an alternate pathway of iron regulation independent of hepcidin at the enterocytes. These findings highlight the need to conduct more research on genetic determinants of iron status in African populations. Investigating more genetic markers and in different populations may provide a clearer insight into the role of genetic risk factors on iron deficiency and anaemia in African populations. Identifying the role of genetic risk factors of iron status may pave the way for the formulation of population specific anaemia control measures.

Published
2021
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3. Malaria protection due to sickle haemoglobin depends on parasite genotype

Author

Band, G, Leffler, EM, Jallow, M, Sisay-Joof, F, Ndila, CM, Macharia, AW, Hubbart, C, Jeffreys, AE, Rowlands, K, Nguyen, T, Gonçalves, S, Ariani, CV, Stalker, J, Pearson, RD, Amato, R, Drury, E, Sirugo, G, d'Alessandro, U, Bojang, KA, Marsh, K, Peshu, N, Saelens, JW, Diakité, M, Taylor, SM, Conway, DJ, Rockett, KA, Kwiatkowski, DP, Williams, TN, and Wellcome Trust

Subjects
EXPRESSION, Male, RESISTANCE LOCI, Genotype, PROTEINS, General Science & Technology, Genes, Protozoan, Hemoglobin, Sickle, Plasmodium falciparum, DIVERSITY, Host Adaptation, Linkage Disequilibrium, MOLECULAR-BASIS, parasitic diseases, Animals, Humans, Parasites, GENOME-WIDE ASSOCIATION, Malaria, Falciparum, Child, Alleles, Science & Technology, Polymorphism, Genetic, Multidisciplinary, PLASMODIUM-FALCIPARUM, Kenya, EXPORT, Multidisciplinary Sciences, Science & Technology - Other Topics, VIRULENCE, Female, Gambia, PLASMEPSIN V
Abstract

Host genetic factors can confer resistance against malaria1, raising the question of whether this has led to evolutionary adaptation of parasite populations. Here we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria caused by Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, which is not explained by population structure or other covariates, and which is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the gene for the acyl-CoA synthetase family member2–4PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations.

Published
2021
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5. Results-based financing to increase uptake of skilled delivery services in The Gambia: using the 'three delays' model to interpret midline evaluation findings

Author

Ferguson, L., Hasan, R., Boudreaux, C., Thomas, H., Jallow, M., Fink, G., and Project Implementation Committee

Subjects
Adult, medicine.medical_specialty, Referral, Adolescent, Psychological intervention, Reproductive medicine, Qualitative property, Health Services Accessibility, Interviews as Topic, Young Adult, Health facility, Pregnancy, Intervention (counseling), Surveys and Questionnaires, Medicine, Humans, Maternal Health Services, Baseline (configuration management), Qualitative Research, business.industry, Obstetrics and Gynecology, Prenatal Care, Focus Groups, Middle Aged, Patient Acceptance of Health Care, Delivery, Obstetric, Focus group, The Gambia, Maternity care, Maternal Mortality, Family medicine, Multivariate Analysis, Linear Models, Female, Gambia, Health Facilities, Maternal health, business, Results-based financing, Research Article
Abstract

Background Delays in accessing skilled delivery services are a major contributor to high maternal mortality in resource-limited settings. In 2015, the government of The Gambia initiated a results-based financing intervention that sought to increase uptake of skilled delivery. We performed a midline evaluation to determine the impact of the intervention and explore causes of delays. Methods A mixed methods design was used to measure changes in uptake of skilled delivery and explore underlying reasons, with communities randomly assigned to four arms: (1) community-based intervention, (2) facility-based intervention, (3) community- and facility-based intervention, and (4) control. We obtained quantitative data from household surveys conducted at baseline (n = 1423) and midline (n = 1573). Qualitative data came from semi-structured interviews (baseline n = 20; midline n = 20) and focus group discussions (baseline n = 27; midline n = 39) with a range of stakeholders. Multivariable linear regression models were estimated using pooled data from baseline and midline. Qualitative data were recorded, transcribed, translated and thematically analyzed. Results No increase was found in uptake of skilled delivery services between baseline and midline. However, relative to the control group, significant increases in referral to health facilities for delivery were found in areas receiving the community-based intervention (beta = 0.078, p p Conclusions Focusing efforts on informing the decision to seek care and overcoming transportation barriers can reduce delays in care-seeking among pregnant women and facilitate efforts to increase uptake of skilled delivery services through results-based financing mechanisms.

Published
2020
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14. Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania

Author

Band, G, Le, QS, Clarke, GM, Kivinen, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Leffler, EM, Jallow, M, Conway, DJ, Sisay-Joof, F, Sirugo, G, d'Alessandro, U, Toure, OB, Thera, MA, Konate, S, Sissoko, S, Mangano, VD, Bougouma, EC, Sirima, SB, Amenga-Etego, LN, Ghansah, AK, Hodgson, AVO, Wilson, MD, Enimil, A, Ansong, D, Evans, J, Ademola, SA, Apinjoh, TO, Ndila, CM, Manjurano, A, Drakeley, C, Reyburn, H, Nguyen, HP, Nguyen, TNQ, Cao, QT, Tran, TH, Teo, YY, Manning, L, Laman, M, Michon, P, Karunajeewa, H, Siba, P, Allen, S, Allen, A, Bahlo, M, Davis, TME, Simpson, V, Shelton, J, Spencer, CCA, Busby, GBJ, Kerasidou, A, Drury, E, Stalker, J, Dilthey, A, Mentzer, AJ, McVean, G, Bojang, KA, Doumbo, O, Modiano, D, Koram, KA, Agbenyega, T, Amodu, OK, Achidi, E, Williams, TN, Marsh, K, Riley, EM, Molyneux, M, Taylor, T, Dunstan, SJ, Farrar, J, Mueller, I, Rockett, KA, Kwiatkowski, DP, Band, G, Le, QS, Clarke, GM, Kivinen, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Leffler, EM, Jallow, M, Conway, DJ, Sisay-Joof, F, Sirugo, G, d'Alessandro, U, Toure, OB, Thera, MA, Konate, S, Sissoko, S, Mangano, VD, Bougouma, EC, Sirima, SB, Amenga-Etego, LN, Ghansah, AK, Hodgson, AVO, Wilson, MD, Enimil, A, Ansong, D, Evans, J, Ademola, SA, Apinjoh, TO, Ndila, CM, Manjurano, A, Drakeley, C, Reyburn, H, Nguyen, HP, Nguyen, TNQ, Cao, QT, Tran, TH, Teo, YY, Manning, L, Laman, M, Michon, P, Karunajeewa, H, Siba, P, Allen, S, Allen, A, Bahlo, M, Davis, TME, Simpson, V, Shelton, J, Spencer, CCA, Busby, GBJ, Kerasidou, A, Drury, E, Stalker, J, Dilthey, A, Mentzer, AJ, McVean, G, Bojang, KA, Doumbo, O, Modiano, D, Koram, KA, Agbenyega, T, Amodu, OK, Achidi, E, Williams, TN, Marsh, K, Riley, EM, Molyneux, M, Taylor, T, Dunstan, SJ, Farrar, J, Mueller, I, Rockett, KA, and Kwiatkowski, DP

Abstract

The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as ~23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations.

Published
2019

15. Proteomic profiling of the plasma of Gambian children with cerebral malaria

Author

Moussa, E, Huang, H, Thézénas, M, Fischer, R, Ramaprasad, A, Sisay‑Joof, F, Jallow, M, Pain, A, Kwiatkowski, D, Kessler, B, Casals-Pascual, C, and Universitat de Barcelona

Subjects
Male, Proteomics, lcsh:Arctic medicine. Tropical medicine, Adolescent, Proteome, lcsh:RC955-962, Plasmodium falciparum, Malalties infeccioses en els infants, Malaria, Cerebral, Malària, lcsh:Infectious and parasitic diseases, Humans, lcsh:RC109-216, Malaria, Falciparum, Child, Cerebral malaria, Coagulation, Proteasome, Acute phase reaction, Infant, Gàmbia, Blood Proteins, Communicable diseases in children, Malaria, Child, Preschool, Female, Gambia, Biomarkers
Abstract

BackgroundCerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection. A number of pathological findings have been correlated with pediatric CM including sequestration, platelet accumulation, petechial haemorrhage and retinopathy. However, the molecular mechanisms leading to death in CM are not yet fully understood. MethodsA shotgun plasma proteomic study was conducted using samples form 52 Gambian children with CM admitted to hospital. Based on clinical outcome, children were assigned to two groups: reversible and fatal CM. Label-free liquid chromatography–tandem mass spectrometry was used to identify and compare plasma proteins that were differentially regulated in children who recovered from CM and those who died. Candidate biomarkers were validated using enzyme immunoassays. ResultsThe plasma proteomic signature of children with CM identified 266 proteins differentially regulated in children with fatal CM. Proteins from the coagulation cascade were consistently decreased in fatal CM, whereas the plasma proteomic signature associated with fatal CM underscored the importance of endothelial activation, tissue damage, inflammation, haemolysis and glucose metabolism. The concentration of circulating proteasomes or PSMB9 in plasma was not significantly different in fatal CM when compared with survivors. Plasma PSMB9 concentration was higher in patients who presented with seizures and was significantly correlated with the number of seizures observed in patients with CM during admission. ConclusionsThe results indicate that increased tissue damage and hypercoagulability may play an important role in fatal CM. The diagnostic value of this molecular signature to identify children at high risk of dying to optimize patient referral practices should be validated prospectively.

Published
2018

17. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia

Author

Clarke, GM, Rockett, K, Kivinen, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Jallow, M, Conway, DJ, Bojang, KA, Pinder, M, Usen, S, Sisay-Joof, F, Sirugo, G, Toure, O, Thera, MA, Konate, S, Sissoko, S, Niangaly, A, Poudiougou, B, Mangano, VD, Bougouma, EC, Sirima, SB, Modioano, D, Amenga-Etego, LN, Ghansah, A, Koram, KA, Wilson, MD, Enimil, A, Evans, J, Amodu, OK, Olaniyan, S, Apinjoh, T, Mugri, R, Ndi, A, Ndila, CM, Uyoga, S, Macharia, A, Peshu, N, Williams, TN, Manjurano, A, Sepulveda, N, Clark, TG, Riley, E, Drakeley, C, Reyburn, H, Nyirongo, V, Kachala, D, Molyneux, M, Dunstan, SJ, Nguyen, HP, Nguyen, NQ, Cao, QT, Tran, TH, Manning, L, Laman, M, Siba, P, Karunajeewa, H, Allen, S, Allen, A, Davis, TME, Michon, P, Mueller, I, Molloy, SF, Campino, S, Kerasidou, A, Cornelius, VJ, Hart, L, Shah, SS, Band, G, Spencer, CCA, Agbenyega, T, Achidi, E, Doumbo, OK, Farrar, J, Marsh, K, Taylor, T, Kwaitkowski, DP, Clarke, GM, Rockett, K, Kivinen, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Jallow, M, Conway, DJ, Bojang, KA, Pinder, M, Usen, S, Sisay-Joof, F, Sirugo, G, Toure, O, Thera, MA, Konate, S, Sissoko, S, Niangaly, A, Poudiougou, B, Mangano, VD, Bougouma, EC, Sirima, SB, Modioano, D, Amenga-Etego, LN, Ghansah, A, Koram, KA, Wilson, MD, Enimil, A, Evans, J, Amodu, OK, Olaniyan, S, Apinjoh, T, Mugri, R, Ndi, A, Ndila, CM, Uyoga, S, Macharia, A, Peshu, N, Williams, TN, Manjurano, A, Sepulveda, N, Clark, TG, Riley, E, Drakeley, C, Reyburn, H, Nyirongo, V, Kachala, D, Molyneux, M, Dunstan, SJ, Nguyen, HP, Nguyen, NQ, Cao, QT, Tran, TH, Manning, L, Laman, M, Siba, P, Karunajeewa, H, Allen, S, Allen, A, Davis, TME, Michon, P, Mueller, I, Molloy, SF, Campino, S, Kerasidou, A, Cornelius, VJ, Hart, L, Shah, SS, Band, G, Spencer, CCA, Agbenyega, T, Achidi, E, Doumbo, OK, Farrar, J, Marsh, K, Taylor, T, and Kwaitkowski, DP

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Published
2017

18. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

Author

Burton, PR, Clayton, DG, Cardon, LR, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Samani, NJ, Todd, JA, Donnelly, P, Barrett, JC, Davison, D, Easton, D, Evans, DM, Leung, HT, Marchini, JL, Morris, AP, Spencer, CC, Tobin, MD, Attwood, AP, Boorman, JP, Cant, B, Everson, U, Hussey, JM, Jolley, JD, Knight, AS, Koch, K, Meech, E, Nutland, S, Prowse, CV, Stevens, HE, Taylor, NC, Walters, GR, Walker, NM, Watkins, NA, Winzer, T, Jones, RW, McArdle, WL, Ring, SM, Strachan, DP, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon-Smith, K, Jones, L, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskivina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGuffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, TD, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Thompson, JR, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Forbes, A, Lewis, CM, Onnie, CM, Prescott, NJ, Sanderson, J, Matthew, CG, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Webster, J, Brown, MJ, Lathrop, MG, Connell, J, Dominiczak, A, Marcano, CA, Burke, B, Dobson, R, Gungadoo, J, Lee, KL, Munroe, PB, Newhouse, SJ, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hilder, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DP, Thomson, W, Worthington, J, Dunger, DB, Widmer, B, Frayling, TM, Freathy, RM, Lango, H, Perry, JR, Shields, BM, Weedon, MN, Hattersley, AT, Hitman, GA, Walker, M, Elliott, KS, Groves, CJ, Lindgren, CM, Rayner, NW, Timpson, NJ, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, AV, Bradbury, LA, Farrar, C, Pointon, JJ, Wordsworth, P, Brown, MA, Franklyn, JA, Heward, JM, Simmonds, MJ, Gough, SC, Seal, S, Stratton, MR, Rahman, N, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Conway, D, Jallow, M, Rockett, KA, Bumpstead, SJ, Chaney, A, Downes, K, Ghori, MJ, Gwilliam, R, Hunt, SE, Inouye, M, Keniry, A, King, E, McGinnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdo'ttir, IB, Howie, BN, Su, Z, Teo, YY, Vukcevic, D, Bentley, D, Mitchell, SL, Newby, PR, Brand, OJ, Carr-Smith, J, Pearce, SH, Reveille, JD, Zhou, X, Sims, AM, Dowling, A, Taylor, J, Doan, T, Davis, JC, Savage, L, Ward, MM, Learch, TL, Weisman, MH, and Brown, M

Subjects
Linkage disequilibrium, Multiple Sclerosis, Genotype, Population, Single-nucleotide polymorphism, Genome-wide association study, Autoimmunity, Breast Neoplasms, Biology, medicine.disease_cause, Aminopeptidases, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Article, Minor Histocompatibility Antigens, Genetics, medicine, Humans, Spondylitis, Ankylosing, Receptors, Immunologic, education, Genetic association, education.field_of_study, Ankylosing spondylitis, Thyroiditis, Autoimmune, Chromosome Mapping, Receptors, Interleukin, medicine.disease, Endoplasmic reticulum aminopeptidase 2, Genetics, Population, Haplotypes, Case-Control Studies, Immunology, North America
Abstract

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Published
2016
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19. Investigating the potential for ethnic group harm in collaborative genomics research in Africa: Is ethnic stigmatisation likely?

Author

de Vries, J, Jallow, M, Williams, T, Kwiatkowski, D, Parker, M, and Fitzpatrick, R

Subjects
Typology, Genetic Research, Health (social science), Ethnic group, Criminology, 0603 philosophy, ethics and religion, Risk Assessment, Article, Health(social science), 03 medical and health sciences, 0302 clinical medicine, Empirical research, History and Philosophy of Science, Ethnicity, Humans, Medicine, 030212 general & internal medicine, Cooperative Behavior, 10. No inequality, Qualitative Research, Stereotyping, MalariaGEN, business.industry, Social environment, Gender studies, 06 humanities and the arts, Genomics, Kenya, The Gambia, Malaria, 3. Good health, Stigma, Harm, Africa, Normative, 060301 applied ethics, Risk assessment, business, Genome-Wide Association Study, Qualitative research
Abstract

A common assumption in genomics research is that the use of ethnic categories has the potential to lead to ethnic stigmatisation - particularly when the research is done on minority populations. Yet few empirical studies have sought to investigate the relation between genomics and stigma, and fewer still with a focus on Africa. In this paper, we investigate the potential for genomics research to lead to harms to ethnic groups. We carried out 49 semi-structured, open-ended interviews with stakeholders in a current medical genomics research project in Africa, MalariaGEN. Interviews were conducted with MalariaGEN researchers, fieldworkers, members of three ethics committees who reviewed MalariaGEN project proposals, and with members of the two funding bodies providing support to the MalariaGEN project. Interviews were conducted in Kenya, The Gambia and the UK between June 2008 and October 2009. They covered a range of aspects relating to the use of ethnicity in the genomics project, including views on adverse effects of the inclusion of ethnicity in such research. Drawing on the empirical data, we argue that the risk of harm to ethnic groups is likely to be more acute in specific types of genomics research. We develop a typology of research questions and projects that carry a greater risk of harm to the populations included in genomics research. We conclude that the potential of generating harm to ethnic groups in genomics research is present if research includes populations that are already stigmatised or discriminated against, or where the research investigates questions with particular normative implications. We identify a clear need for genomics researchers to take account of the social context of the work they are proposing to do, including understanding the local realities and relations between ethnic groups, and whether diseases are already stigmatised. © 2012 Elsevier Ltd.

Published
2016

20. Discovery and validation of biomarkers to guide clinical management of pneumonia in African children

Author

Huang, H., Ideh, R. C., Gitau, Evelyn, Thezenas, M. L., Jallow, M., Ebruke, B., Chimah, O., Oluwalana, C., Karanja, H., Mackenzie, G., Adegbola, R. A., Kwiatkowski, D., Kessler, B. M., Berkley, J. A., Howie, S. R. C., and Casals-Pascual, C.

Subjects
wb_102, qy_4, parasitic diseases, ws_280, qu_460
Abstract

Background\ud \ud Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management.\ud \ud Methods\ud \ud We conducted a mass spectrometry–based proteomic study to identify and validate markers of severity in 390 Gambian children with pneumonia (n = 204) and age-, sex-, and neighborhood-matched controls (n = 186). Independent validation was conducted in 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with Plasmodium falciparum malaria, and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUC).\ud \ud Results\ud \ud Lipocalin 2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUC, 0.71 [95% confidence interval, .64–.79]) and highly predictive of bacteremia (78% [64%–92%]), pneumococcal bacteremia (84% [71%–98%]), and “probable bacterial etiology” (91% [84%–98%]). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the World Health Organization definition of pneumonia. The combination of Lpc-2 and haptoglobin distinguished bacterial versus malaria origin of respiratory distress with high sensitivity and specificity in Gambian children (AUC, 99% [95% confidence interval, 99%–100%]) and Kenyan children (82% [74%–91%]).\ud \ud Conclusions\ud \ud Lpc-2 and haptoglobin can help discriminate the etiology of clinically defined pneumonia and could be used to improve clinical management. These biomarkers should be further evaluated in prospective clinical studies.

Published
2016

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

Author

Muminatou, Jallow, Yik Ying Teo, Small, Kerrin S., Rockett, Kirk A., Panos, Deloukas, Clark, Taane G., Katja, Kivinen, Bojang, Kalifa A., Conway, David J., Margaret, Pinder, Giorgio, Sirugo, Fatou Sisay Joof, Stanley, Usen, Sarah, Auburn, Bumpstead, Suzannah J., Susana, Campino, Alison, Coffey, Andrew, Dunham, Fry, Andrew E., Angela, Green, Rhian, Gwilliam, Hunt, Sarah E., Michael, Inouye, Jeffreys, Anna E., Alieu, Mendy, Aarno, Palotie, Simon, Potter, Jiannis, Ragoussis, Jane, Rogers, Kate, Rowlands, Elilan, Somaskantharajah, Pamela, Whittaker, Claire, Widden, Peter, Donnelly, Bryan, Howie, Jonathan, Marchini, Andrew, Morris, Miguel, Sanjoaquin, Eric Akum Achidi, Tsiri, Agbenyega, Angela, Allen, Olukemi, Amodu, Patrick, Corran, Abdoulaye, Djimde, Amagana, Dolo, Doumbo, Ogobara K., Chris, Drakeley, Sarah, Dunstan, Jennifer, Evans, Jeremy, Farrar, Hien Tt, Fernando D., Horstmann, R. D., Ibrahim, M., Karunaweera, N., Kokwaro, G., Koram, K. A., Lemnge, M., Makani, J., Marsh, K., Michon, P., David, Modiano, Molyneux, M. E., Mueller, I., Parker, M., Peshu, N., Plowe, C. V., Puijalon, O., Reeder, J., Reyburn, H., Riley, E. M., Sakuntabhai, A., Singhasivanon, P., Sirima, S., Tall, A., Taylor, T. E., Thera, M., Troye Blomberg, M., Williams, T. N., Wilson, M., Wellcome Trust Case Control Consortium Kwiatkowski, D. P., Epidemiology Network: Achidi, Malaria Genomic E. A., Agbenyega, T., Ahmad, T., Alcock, D., Allen, S., Amenga Etego, L., Amodu, O., Apinjoh, T. O., Attwood, A. P., Auburn, S., Ball, S. G., Balmforth, A. J., Ban, M., Barbour, J., Barnwell, D., Barrett, J. C., Barrett, J. H., Barton, A., Bentley, D., Bishop, D. T., Bojang, K., Boorman, J. P., Bougouma, E., Bradbury, L. A., Braga Marcano, C. A., Braund, P. S., Bredin, F., Breen, G., Brown, M. A., Brown, M. J., Bruce, I. N., Bryan, C., Bull, S., Bumpstead, S. J., Burke, B., Burton, P. R., Caesar, S., Campino, S., Cant, B., Cardin, N. J., Cardon, L. R., Carucci, D., Caulfield, M., Chaney, A., Clark, T., Clayton, D. G., Collier, D. A., Compston, A., Compston, D. A., Connell, J., Conway, D., Cook, K., Corran, P., Craddock, N., Cummings, F. R., Davison, D., Deloukas, P., Devries, J., Dewasurendra, R., Diakite, M., Dixon, R. J., Djimde, A., Dobson, R., Dolo, A., Dominiczak, A., Donnelly, P., Donovan, H., Doumbo, O., Downes, K., Doyle, A., Drakeley, C., Drummond, H., Duffy, P., Duncanson, A., Dunger, D. B., Dunstan, S., Duombo, O., Easton, D., Elkin, A., Elliott, K. S., Elzein, A., Enimil, A., Evans, D., Evans, J., Everson, U., Eyre, S., Farmer, A., Farrall, M., Farrar, C., Farrar, J., Fernando, D., Ferreira, T., Ferrier, I. N., Fisher, S. A., Fitzpatrick, K., Forbes, A., Franklyn, J. A., Fraser, C., Frayling, T. M., Freathy, R. M., Ghansah, A., Ghori, J., Gilbert, P. D., Gordon Smith, K., Goris, A., Gottlieb, M., Gough, S. C., Green, A., Green, E. K., Groves, C. J., Grozeva, D., Gungadoo, J., Gwilliam, R., Hall, A. S., Hallgrimsdóttir, I. B., Hamshere, M. L., Hart, L., Hattersley, A. T., Heward, J. M., Hider, S. L., Tran Tinh Hien, Hill, A. V., Hilton, E., Hinks, A. M., Hitman, G. A., Holmans, P. A., Horstmann, Rolf D., Howie, B. N., Hubbart, C., Hughes, C., Hunt, S. E., Hussein, A., Hussey, J. M., Muntaser, Ibrahim, Iles, M. M., Inouye, M., Ishengoma, D., Jallow, M., Jeffreys, A. E., Jewell, D. P., John, Sl, Jolley, J. D., Jones, I. R., Jones, L., Jones, R. W., Nadira, Karunaweera, Keniry, A., King, E., Kirov, G., Kivinen, K., Knight, A. S., Koch, K., Gilbert, Kokwaro, Koram, Kwadwo A., Lango, H., Lathrop, G. M., Lee, K. L., Lees, C. W., Martha, Lemnge, Leung, H. T., Lewis, C. M., Lin, E., Lindgren, C. M., Ly, A., Macinnis, B., Julie, Makani, Mangano, Valentina, Mangino, M., Manjurano, A., Manning, L., Mansfield, J. C., Manske, M., Maqbool, A., Marchini, J. L., Kevin, Marsh, Maslen, G., Mathew, C. G., Mcardle, W. L., Mccarthy, M. I., Mccreight, M., Mcginnis, R., Mcguffin, P., Meech, E., Mendy, A., Pascal, Michon, Mohiuddin, M. K., Molyneux, Malcolm E., Morris, A. P., Moskvina, V., Moyes, C., Ivo, Mueller, Munroe, P. B., Mutabingwa, T., Ndila, C. M., Newhouse, S. J., Newport, M., Nikolov, I., Nimmo, E. R., Nutland, S., Nyirongo, V., O'Donovan, M. C., Oluoch, T., Onipinla, A., Onnie, C. M., Ouwehand, W. H., Owen, M. J., Michael, Parker, Parkes, M., Pembrey, M., Pereira Gale, J., Perry, J. R., Norbert, Peshu, Plowe, Christopher V., Pointon, J. J., Potter, C., Potter, S., Prescott, N. J., Prowse, C. V., Odile, Puijalon, Quyen, N. T., Ragoussis, J., Rahman, N., Ravindrarajah, R., Rayner, N. W., John, Reeder, Hugh, Reyburn, Riley, Eleanor M., Ring, S. M., Risley, P., Rockett, K. A., Rogers, J., Rowlands, K., Anavaj, Sakuntabhai, Samani, N. J., Sanderson, J., Sanjoaquin, M., Satsangi, J., Sawcer, S. J., Seal, S., Shields, B. M., Silman, A. J., Simmonds, M. J., Pratap, Singhasivanon, Sodiomon, Sirima, Sirugo, G., Small, K. S., Somaskantharajah, E., Spencer, C. C., St Clair, D., Stevens, H. E., Stevens, M., Stevens, S., Strachan, D. P., Stratton, M. R., Su, Z., Suriyaphol, P., Symmons, D. P., Adama, Tall, Taylor, N. C., Taylor, Terrie E., Teo, Y., Teo, Y. Y., Mahamadou, Thera, Thompson, J. R., Thomson, W., Timpson, N. J., Tobin, M. D., Todd, J. A., Todhunter, C. E., Toure, O., Tremelling, M., Marita Troye Blomberg, Vanderwal, A., Vukcevic, D., Walker, M., Walker, N. M., Wallace, C., Walters, G. R., Walton, R., Watkins, N. A., Watson, R., Webster, J., Weedon, M. N., Whittaker, P., Widmer, B., Williams, Thomas N., Williamson, R., Michael, Wilson, Winzer, T., Withers, D., Wordsworth, P., Worthington, J., Wrigley, R., Xue, M., Young, A. H., Yuldasheva, N., and Zeggini, E.

Subjects
Linkage disequilibrium, Hemoglobin, Sickle, Population, Genome-wide association study, Locus (genetics), Biology, Population stratification, Polymorphism, Single Nucleotide, Severity of Illness Index, Linkage Disequilibrium, Article, Gene mapping, Reference Values, Ethnicity, Genetics, Humans, education, Genetic association, education.field_of_study, Polymorphism, Genetic, Chromosome Mapping, Genetic Variation, Malaria, Gambia, Imputation (genetics), Genome-Wide Association Study
Abstract

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. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.

Published
2009
Full Text
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22. Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia

Author

Howie, SRC, Schellenberg, J, Chimah, O, Ideh, RC, Ebruke, BE, Oluwalana, C, Mackenzie, G, Jallow, M, Njie, M, Donkor, S, Dionisio, KL, Goldberg, G, Fornace, K, Bottomley, C, Hill, PC, Grant, CC, Corrah, T, Prentice, AM, Ezzati, M, Greenwood, BM, Smith, PG, Adegbola, RA, Mulholland, K, Howie, SRC, Schellenberg, J, Chimah, O, Ideh, RC, Ebruke, BE, Oluwalana, C, Mackenzie, G, Jallow, M, Njie, M, Donkor, S, Dionisio, KL, Goldberg, G, Fornace, K, Bottomley, C, Hill, PC, Grant, CC, Corrah, T, Prentice, AM, Ezzati, M, Greenwood, BM, Smith, PG, Adegbola, RA, and Mulholland, K

Abstract

SETTING: Greater Banjul and Upper River Regions, The Gambia. OBJECTIVE: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia. DESIGN: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2-59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season. RESULTS: Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2-8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1-13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2-17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP. CONCLUSION: Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.

Published
2016

23. Admixture into and within sub-Saharan Africa

Author

Busby, GBJ, Band, G, Le, QS, Jallow, M, Bougama, E, Mangano, VD, Amenga-Etego, LN, Enimil, A, Apinjoh, T, Ndila, CM, Manjurano, A, Nyirongo, V, Doumbo, O, Rockett, KA, Kwiatkowski, DP, Spencer, CCA, Busby, GBJ, Band, G, Le, QS, Jallow, M, Bougama, E, Mangano, VD, Amenga-Etego, LN, Enimil, A, Apinjoh, T, Ndila, CM, Manjurano, A, Nyirongo, V, Doumbo, O, Rockett, KA, Kwiatkowski, DP, and Spencer, CCA

Abstract

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology.

Published
2016

24. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies

Author

Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ, Qasim AN, DerOhannessian SL, Qu L, Cappola TP, Chen Z, Matthai W, Hakonarson HH, Wilensky R, Kent KM, Lindsay JM, Pichard AD, Satler L, Waksman R, Knoupf CW, Walker MC, Waterworth DM, Mosser V, Braund PS, Wright B, Balmforth AJ, Ball SG, Chen L, Wells GA, McPherson R, Lackner K, Munzel TF, Schillert A, Schnabel R, Zeller T, Ziegler A, Absher D, Hlatky MA, Iribaren C, Knowles JW, Linsel Nitschke P, König IR, Hengstenberg C, Nahrstaedt J, Peters A, Schreiber S, Wichmann E, Willenborg C, Su S, Bouzyk M, Vaccarino V, Zafari AM, Carlquist JF, Muhlestein JB, Olivieri O, Barnard J, Hartiala J, Tang WH, Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Dixon RJ, Mangino M, Stevens S, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop M, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Ferreira T, Pereira Gale J, Hallgrimsdóttir IB, Bowie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Meigs JB, Williams G, Nathan DM, MacRae CA, O'Donnell CJ, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, CASARI , GIORGIO NEVIO, Reilly, Mp, Li, M, He, J, Ferguson, Jf, Stylianou, Im, Mehta, Nn, Burnett, M, Devaney, Jm, Knouff, Cw, Thompson, Jr, Horne, Bd, Stewart, Af, Assimes, Tl, Wild, P, Allayee, H, Nitschke, Pl, Patel, R, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Martinelli, N, Girelli, D, Quyyumi, Aa, Anderson, Jl, Erdmann, J, Hall, A, Schunkert, H, Quertermous, T, Blankenberg, S, Hazen, Sl, Roberts, R, Kathiresan, S, Samani, Nj, Epstein, Se, Rader, Dj, Qasim, An, Derohannessian, Sl, Qu, L, Cappola, Tp, Chen, Z, Matthai, W, Hakonarson, Hh, Wilensky, R, Kent, Km, Lindsay, Jm, Pichard, Ad, Satler, L, Waksman, R, Knoupf, Cw, Walker, Mc, Waterworth, Dm, Mosser, V, Braund, P, Wright, B, Balmforth, Aj, Ball, Sg, Chen, L, Wells, Ga, Mcpherson, R, Lackner, K, Munzel, Tf, Schillert, A, Schnabel, R, Zeller, T, Ziegler, A, Absher, D, Hlatky, Ma, Iribaren, C, Knowles, Jw, Linsel Nitschke, P, König, Ir, Hengstenberg, C, Nahrstaedt, J, Peters, A, Schreiber, S, Wichmann, E, Willenborg, C, Su, S, Bouzyk, M, Vaccarino, V, Zafari, Am, Carlquist, Jf, Muhlestein, Jb, Olivieri, O, Barnard, J, Hartiala, J, Tang, Wh, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, Dp, Mccarthy, Mi, Ouwehand, Wh, Todd, Ja, Donnelly, P, Barrett, Jc, Davison, D, Easton, D, Evans, Dm, Leung, Ht, Marchini, Jl, Morris, Ap, Spencer, Cc, Tobin, Md, Attwood, Ap, Boorman, Jp, Cant, B, Everson, U, Hussey, Jm, Jolley, Jd, Knight, A, Koch, K, Meech, E, Nutland, S, Prowse, Cv, Stevens, He, Taylor, Nc, Walters, Gr, Walker, Nm, Watkins, Na, Winzer, T, Jones, Rw, Mcardle, Wl, Ring, Sm, Strachan, Dp, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon Smith, K, Jones, L, Fraser, C, Green, Ek, Grozeva, D, Hamshere, Ml, Holmans, Pa, Jones, Ir, Kirov, G, Moskvina, V, Nikolov, I, O'Donovan, Mc, Owen, Mj, Collier, Da, Elkin, A, Farmer, A, Williamson, R, Mcguffin, P, Young, Ah, Ferrier, In, Barrett, Jh, Bishop, Dt, Iles, Mm, Maqbool, A, Yuldasheva, N, Dixon, Rj, Mangino, M, Stevens, S, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, Cw, Nimmo, Er, Satsangi, J, Fisher, Sa, Forbes, A, Lewis, Cm, Onnie, Cm, Prescott, Nj, Sanderson, J, Mathew, Cg, Barbour, J, Mohiuddin, Mk, Todhunter, Ce, Mansfield, Jc, Ahmad, T, Cummings, Fr, Jewell, Dp, Webster, J, Brown, Mj, Lathrop, M, Connell, J, Dominiczak, A, Marcano, Ca, Burke, B, Dobson, R, Gungadoo, J, Lee, Kl, Munroe, Pb, Newhouse, Sj, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, In, Donovan, H, Eyre, S, Gilbert, Pd, Hider, Sl, Hinks, Am, John, Sl, Potter, C, Silman, Aj, Symmons, Dp, Thomson, W, Worthington, J, Dunger, Db, Widmer, B, Frayling, Tm, Freathy, Rm, Lango, H, Perry, Jr, Shields, Bm, Weedon, Mn, Hattersley, At, Hitman, Ga, Walker, M, Elliott, K, Groves, Cj, Lindgren, Cm, Rayner, Nw, Timpson, Nj, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, Av, Bradbury, La, Farrar, C, Pointon, Jj, Wordsworth, P, Brown, Ma, Franklyn, Ja, Heward, Jm, Simmonds, Mj, Gough, Sc, Seal, S, Stratton, Mr, Rahman, N, Ban, M, Goris, A, Sawcer, Sj, Compston, A, Conway, D, Jallow, M, Rockett, Ka, Bumpstead, Sj, Chaney, A, Downes, K, Ghori, Mj, Gwilliam, R, Hunt, Se, Inouye, M, Keniry, A, King, E, Mcginnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, Nj, Ferreira, T, Pereira Gale, J, Hallgrimsdóttir, Ib, Bowie, Bn, Su, Z, Teo, Yy, Vukcevic, D, Bentley, D, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, O'Donnell, Cj, Ardissino, D, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, GIORGIO NEVIO, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Mannucci, Pm, Schwartz, Sm, Siscovick, D, Yee, J, Friedlander, Y, Elosua, R, Marrugat, J, Lucas, G, Subirana, I, Sala, J, Ramos, R, Salomaa, V, Havulinna, A, Peltonen, L, Melander, O, Berglund, G, Voight, Bf, Hirschhorn, Jn, Asselta, R, Duga, S, Spreafico, M, Musunuru, K, Daly, Mj, Purcell, S, Surti, A, Guiducci, C, Gianniny, L, Mirel, D, Parkin, M, Burtt, N, and Gabriel, Sb

Subjects
Adult, Male, medicine.medical_specialty, Linkage disequilibrium, ABO, ADAMTS7 Protein, ADAMTS7, Genome-wide association study, Coronary Angiography, Polymorphism, Single Nucleotide, Linkage Disequilibrium, ABO Blood-Group System, Coronary artery disease, Gene Frequency, ABO blood group system, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Myocardial infarction, Genetic risk factor, genetic locus, Coronary atherosclerosis, Aged, business.industry, coronary atherosclerosis, General Medicine, Middle Aged, medicine.disease, ADAM Proteins, myocardial infarction, Genetic Loci, Cardiology, Myocardial infarction complications, Female, business, coronary artery disease, Genome-Wide Association Study
Abstract

BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. METHODS: We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). FINDINGS: In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. INTERPRETATION: Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. FUNDING: The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.

Published
2011

25. Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia

Author

Howie, S. R. C., primary, Schellenberg, J., additional, Chimah, O., additional, Ideh, R. C., additional, Ebruke, B. E., additional, Oluwalana, C., additional, Mackenzie, G., additional, Jallow, M., additional, Njie, M., additional, Donkor, S., additional, Dionisio, K. L., additional, Goldberg, G., additional, Fornace, K., additional, Bottomley, C., additional, Hill, P. C., additional, Grant, C. C., additional, Corrah, T., additional, Prentice, A. M., additional, Ezzati, M., additional, Greenwood, B. M., additional, Smith, P. G., additional, Adegbola, R. A., additional, and Mulholland, K., additional

Published
2016
Full Text
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26. Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Author

Howie, SRC, Morris, GAJ, Tokarz, R, Ebruke, BE, Machuka, EM, Ideh, RC, Chimah, O, Secka, O, Townend, J, Dione, M, Oluwalana, C, Njie, M, Jallow, M, Hill, PC, Antonio, M, Greenwood, B, Briese, T, Mulholland, K, Corrah, T, Lipkin, WI, Adegbola, RA, Howie, SRC, Morris, GAJ, Tokarz, R, Ebruke, BE, Machuka, EM, Ideh, RC, Chimah, O, Secka, O, Townend, J, Dione, M, Oluwalana, C, Njie, M, Jallow, M, Hill, PC, Antonio, M, Greenwood, B, Briese, T, Mulholland, K, Corrah, T, Lipkin, WI, and Adegbola, RA

Abstract

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae.

Published
2014

27. Reappraisal of known malaria resistance loci in a large multicenter study

Author

Rockett, KA, Clarke, GM, Fitzpatrick, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Craik, R, Jallow, M, Conway, DJ, Bojang, KA, Pinder, M, Usen, S, Sisay-Joof, F, Sirugo, G, Toure, O, Thera, MA, Konate, S, Sissoko, S, Niangaly, A, Poudiougou, B, Mangano, VD, Bougouma, EC, Sirima, SB, Modiano, D, Amenga-Etego, LN, Ghansah, A, Koram, KA, Wilson, MD, Enimil, A, Evans, J, Amodu, O, Olaniyan, S, Apinjoh, T, Mugri, R, Ndi, A, Ndila, CM, Uyoga, S, Macharia, A, Peshu, N, Williams, TN, Manjurano, A, Riley, E, Drakeley, C, Reyburn, H, Nyirongo, V, Kachala, D, Molyneux, M, Dunstan, SJ, Nguyen, HP, Nguyen, TNQ, Cao, QT, Tran, TH, Manning, L, Laman, M, Siba, P, Karunajeewa, H, Allen, S, Allen, A, Davis, TME, Michon, P, Mueller, I, Green, A, Molloy, S, Johnson, KJ, Kerasidou, A, Cornelius, V, Hart, L, Vanderwal, A, SanJoaquin, M, Band, G, Le, SQ, Pirinen, M, Sepulveda, N, Spencer, CCA, Clark, TG, Agbenyega, T, Achidi, E, Doumbo, O, Farrar, J, Marsh, K, Taylor, T, Kwiatkowski, DP, Rockett, KA, Clarke, GM, Fitzpatrick, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Craik, R, Jallow, M, Conway, DJ, Bojang, KA, Pinder, M, Usen, S, Sisay-Joof, F, Sirugo, G, Toure, O, Thera, MA, Konate, S, Sissoko, S, Niangaly, A, Poudiougou, B, Mangano, VD, Bougouma, EC, Sirima, SB, Modiano, D, Amenga-Etego, LN, Ghansah, A, Koram, KA, Wilson, MD, Enimil, A, Evans, J, Amodu, O, Olaniyan, S, Apinjoh, T, Mugri, R, Ndi, A, Ndila, CM, Uyoga, S, Macharia, A, Peshu, N, Williams, TN, Manjurano, A, Riley, E, Drakeley, C, Reyburn, H, Nyirongo, V, Kachala, D, Molyneux, M, Dunstan, SJ, Nguyen, HP, Nguyen, TNQ, Cao, QT, Tran, TH, Manning, L, Laman, M, Siba, P, Karunajeewa, H, Allen, S, Allen, A, Davis, TME, Michon, P, Mueller, I, Green, A, Molloy, S, Johnson, KJ, Kerasidou, A, Cornelius, V, Hart, L, Vanderwal, A, SanJoaquin, M, Band, G, Le, SQ, Pirinen, M, Sepulveda, N, Spencer, CCA, Clark, TG, Agbenyega, T, Achidi, E, Doumbo, O, Farrar, J, Marsh, K, Taylor, T, and Kwiatkowski, DP

Abstract

Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10(-4) with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

Published
2014

30. A global network for genomic epidemiology of malaria

Author

Malaria Genomic Epidemiology Network, Achidi, Ea, Agbenyega, T, Allen, S, Amodu, O, Bojang, K, Conway, D, Corran, P, Deloukas, P, Djimde, A, Dolo, A, Doumbo, O, Drakeley, C, Duffy, P, Dunstan, S, Evans, J, Farrar, J, Fernando, D, Tran, Th, Horstmann, R, Ibrahim, M, Karunaweera, N, Kokwaro, G, Koram, K, Kwiatkowski, D, Lemnge, M, Makani, J, Marsh, K, Michon, P, Modiano, D, Molyneux, Me, Mueller, I, Mutabingwa, T, Parker, M, Peshu, N, Plowe, C, Puijalon, O, Ragoussis, J, Reeder, J, Reyburn, H, Riley, E, Rogers, J, Sakuntabhai, A, Singhasivanon, P, Sirima, S, Sirugo, G, Tall, A, Taylor, T, Thera, M, Troye Blomberg, M, Williams, T, Wilson, M, Amenga Etego, L, Apinjoh, To, Bougouma, E, Dewasurendra, R, Diakite, M, Enimil, A, Hussein, A, Ishengoma, D, Jallow, M, Lin, E, Ly, A, Mangano, Valentina, Manjurano, A, Manning, L, Ndila, Cm, Nyirongo, V, Oluoch, T, Nguyen, Tn, Suriyaphol, P, Toure, O, Rockett, Ka, Vanderwal, A, Clark, T, Wrigley, R, Alcock, D, Auburn, S, Barnwell, D, Bull, S, Campino, S, Devries, J, Elzein, A, Fitzpatrick, K, Ghansah, A, Green, A, Hart, L, Hilton, E, Hubbart, C, Hughes, C, Jeffreys, Ae, Kivinen, K, Macinnis, B, Manske, M, Maslen, G, Mccreight, M, Mendy, A, Moyes, C, Nyika, A, Potter, C, Risley, P, Rowlands, K, Sanjoaquin, M, Small, K, Somaskantharajah, E, Stevens, M, Teo, Y, Watson, R, Carucci, D, Cook, K, Doyle, A, Duombo, O, Gottlieb, M, and Kwiatkowski, D.

Published
2008

35. An epidemiological study of RSV infection in the Gambia

Author

Mw, Weber, Paul Milligan, Sanneh M, Awemoyi A, Dakour R, Schneider G, Palmer A, Jallow M, Oparaogu A, Whittle H, Ek, Mulholland, and Bm, Greenwood

Subjects
viruses
Abstract

OBJECTIVE: To describe the epidemiology of respiratory syncytial virus (RSV) infection in a developing country. METHODS: The work was carried out in three hospitals for primary cases and in the community for secondary cases in the western region of the Gambia, West Africa. RSV infection was diagnosed by immunofluorescence of nasopharyngeal aspirate samples in children younger than two years admitted to hospital with acute lower respiratory infection (ALRI). Routine records of all children with ALRI were analysed, and the incidence rates of ALRI, severe RSV-associated respiratory illness and hypoxaemic RSV infections were compared. A community-based study was undertaken to identify secondary cases and to obtain information about spread of the virus. FINDINGS: 4799 children with ALRI who were younger than two years and lived in the study area were admitted to the study hospitals: 421 had severe RSV-associated respiratory illness; 55 of these were hypoxaemic. Between 1994 and 1996, the observed incidence rate for ALRI in 100 children younger than one year living close to hospital was 9.6 cases per year; for severe RSV-associated respiratory illness 0.83; and for hypoxaemic RSV-associated respiratory illness 0.089. The proportion of all ALRI admissions due to RSV was 19%. Overall, 41% of children younger than five years in compounds in which cases lived and 42% in control compounds had evidence of RSV infection during the surveillance period. CONCLUSION: RSV is an important cause of ALRI leading to hospital admission in the Gambia. Morbidity is considerable and efforts at prevention are worthwhile.

Published
2002

36. Further evidence supporting a role for gs signal transduction in severe malaria pathogenesis

Author

Auburn, Sarah, Fry, A, Clark, T, Campino, S, Diakite, M, Green, A, Richardson, A, Jallow, M, Sisay-Joof, F, Pinder, M, Molyneux, M, Taylor, T, Haldar, K, Rockett, K, DP Kwiatkowski, D, Auburn, Sarah, Fry, A, Clark, T, Campino, S, Diakite, M, Green, A, Richardson, A, Jallow, M, Sisay-Joof, F, Pinder, M, Molyneux, M, Taylor, T, Haldar, K, Rockett, K, and DP Kwiatkowski, D

Published
2010

37. Tumor necrosis factor and lymphotoxin-α polymorphisms and severe malaria in African populations

Author

Clark, T, Diakite, M, Auburn, Sarah, Campino, S, Fry, A, Green, A, Richardson, A, Small, K, Teo, Y, Wilson, J, Jallow, M, Sisay-Joof, F, Pinder, M, Griffiths, M, N Peshu, N, Williams, T, Marsh, K, Molyneux, M, Taylor, T, Rockett, K, Kwiatkowski, D, Clark, T, Diakite, M, Auburn, Sarah, Campino, S, Fry, A, Green, A, Richardson, A, Small, K, Teo, Y, Wilson, J, Jallow, M, Sisay-Joof, F, Pinder, M, Griffiths, M, N Peshu, N, Williams, T, Marsh, K, Molyneux, M, Taylor, T, Rockett, K, and Kwiatkowski, D

Published
2009

38. Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes

Author

Fry, A, Ghansa, A, Small, K, Palma, A, Auburn, Sarah, Diakite, M, Green, A, Campino, S, Teo, Y, Clark, T, Jeffreys, A, Wilson, J, Jallow, M, Sisay-Joof, F, M Pinder, M, Griffiths, M, Peshu, N, Williams, T, Newton, C, Marsh, K, Molyneux, M, Taylor, T, Koram, K, Oduro, A, Rogers, W, Rockett, K, Sabeti, P, Kwiatkowski, D, Fry, A, Ghansa, A, Small, K, Palma, A, Auburn, Sarah, Diakite, M, Green, A, Campino, S, Teo, Y, Clark, T, Jeffreys, A, Wilson, J, Jallow, M, Sisay-Joof, F, M Pinder, M, Griffiths, M, Peshu, N, Williams, T, Newton, C, Marsh, K, Molyneux, M, Taylor, T, Koram, K, Oduro, A, Rogers, W, Rockett, K, Sabeti, P, and Kwiatkowski, D

Published
2009

39. A genetic association study in the Gambia using tagging polymorphisms in the major histocompatibility complex class III region implicates a HLA-B associated transcript 2 polymorphism in severe malaria susceptibility

Author

Diakite, M, Clark, T, Auburn, Sarah, Campino, S, Fry, A, Green, A, Morris, A, Richardson, A, Jallow, M, Sisay-Joof, F, Pinder, M, Kwiatkowski, D, Rockett, K, Diakite, M, Clark, T, Auburn, Sarah, Campino, S, Fry, A, Green, A, Morris, A, Richardson, A, Jallow, M, Sisay-Joof, F, Pinder, M, Kwiatkowski, D, and Rockett, K

Published
2009

40. Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility

Author

Clark, T, Fry, A, Auburn, Sarah, Campino, S, Diakite, M, Green, A, Richardson, A, Teo, Y, Small, K, Wilson, J, Jallow, M, Sisay-Joof, F, Pinder, M, Sabeti, P, DP Kwiatkowski, D, Rockett, K, Clark, T, Fry, A, Auburn, Sarah, Campino, S, Diakite, M, Green, A, Richardson, A, Teo, Y, Small, K, Wilson, J, Jallow, M, Sisay-Joof, F, Pinder, M, Sabeti, P, DP Kwiatkowski, D, and Rockett, K

Published
2009

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

Author

Jallow, M, Teo, Y, Small, K, Rockett, K, Deloukas, P, Clark, T, Kivinen, K, Bojang, K, Conway, D, Pinder, M, Sirugo, G, Sisay-Joof, F, Usen, S, Auburn, Sarah, SJ Bumpstead, S, Campino, S, Coffey, A, Dunham, A, Fry, A, Green, A, Gwilliam, R, Hunt, S, Inouye, M, Jeffreys, A, Mendy, A, Palotie, A, Potter, S, Ragoussis, J, Rogers, J, Rowlands, K, Somaskantharajah, E, Whittaker, P, Widden, C, Donnelly, P, Howie, B, Marchini, J, Morris, A, Sanjoaquin, M, Achidi, E, Agbenyega, T, Allen, A, Amodu, O, Corran, P, Djimde, A, Dolo, A, Doumbo, O, Drakeley, C, Dunstan, S, Evans, J, Farrar, J, Fernando, D, Hien, T, Horstmann, R, Ibrahim, M, Karunaweera, N, Kokwaro, G, Koram, K, Lemnge, M, Makani, J, Marsh, K, Michon, P, Modiano, D, Molyneux, M, Mueller, I, Parker, M, Peshu, N, Plowe, C, Puijalon, O, Reeder, J, Reyburn, H, Riley, E, Sakuntabhai, A, Singhasivanon, P, Sirima, S, Tall, A, Taylor, T, Thera, M, Troye-Blomberg, M, Williams, T, Wilson, M, Kwiatkowski, D, Jallow, M, Teo, Y, Small, K, Rockett, K, Deloukas, P, Clark, T, Kivinen, K, Bojang, K, Conway, D, Pinder, M, Sirugo, G, Sisay-Joof, F, Usen, S, Auburn, Sarah, SJ Bumpstead, S, Campino, S, Coffey, A, Dunham, A, Fry, A, Green, A, Gwilliam, R, Hunt, S, Inouye, M, Jeffreys, A, Mendy, A, Palotie, A, Potter, S, Ragoussis, J, Rogers, J, Rowlands, K, Somaskantharajah, E, Whittaker, P, Widden, C, Donnelly, P, Howie, B, Marchini, J, Morris, A, Sanjoaquin, M, Achidi, E, Agbenyega, T, Allen, A, Amodu, O, Corran, P, Djimde, A, Dolo, A, Doumbo, O, Drakeley, C, Dunstan, S, Evans, J, Farrar, J, Fernando, D, Hien, T, Horstmann, R, Ibrahim, M, Karunaweera, N, Kokwaro, G, Koram, K, Lemnge, M, Makani, J, Marsh, K, Michon, P, Modiano, D, Molyneux, M, Mueller, I, Parker, M, Peshu, N, Plowe, C, Puijalon, O, Reeder, J, Reyburn, H, Riley, E, Sakuntabhai, A, Singhasivanon, P, Sirima, S, Tall, A, Taylor, T, Thera, M, Troye-Blomberg, M, Williams, T, Wilson, M, and Kwiatkowski, D

Published
2009

42. Lack of association of interferon regulatory factor 1 with severe malaria in affected child-parental trio studies across three african populations

Author

Mangano, V, Clark, T, Auburn, Sarah, Campino, S, Diakite, M, Fry, A, Green, A, Richardson, A, Jallow, M, Sisay-Joof, F, Pinder, M, Griffiths, M, Newton, C, Peshu, N, TN Williams, T, Marsh, K, Molyneux, M, Taylor, T, Modiano, D, Kwiatkowski, D, Rockett, K, Mangano, V, Clark, T, Auburn, Sarah, Campino, S, Diakite, M, Fry, A, Green, A, Richardson, A, Jallow, M, Sisay-Joof, F, Pinder, M, Griffiths, M, Newton, C, Peshu, N, TN Williams, T, Marsh, K, Molyneux, M, Taylor, T, Modiano, D, Kwiatkowski, D, and Rockett, K

Published
2009

43. Association of the GNAS locus with severe malaria

Author

Auburn, Sarah, Diakite, M, Fry, A, Ghansah, A, Campino, S, Richardson, A, Jallow, M, Sisay-Joof, F, Pinder, M, Griffiths, M, Peshu, N, Williams, T, Marsh, K, Molyneux, M, TE Taylor, T, Koram, K, Oduro, A, Rogers, W, Rockett, K, Haldar, K, Kwiatkowski, D, Auburn, Sarah, Diakite, M, Fry, A, Ghansah, A, Campino, S, Richardson, A, Jallow, M, Sisay-Joof, F, Pinder, M, Griffiths, M, Peshu, N, Williams, T, Marsh, K, Molyneux, M, TE Taylor, T, Koram, K, Oduro, A, Rogers, W, Rockett, K, Haldar, K, and Kwiatkowski, D

Published
2008

44. Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria

Author

Fry, A, Griffiths, M, Auburn, Sarah, Diakite, M, Forton, J, Green, A, Richardson, A, Wilson, J, Jallow, M, Sisay-Joof, F, Pinder, M, Peshu, N, Williams, T, Marsh, K, ME Molyneux, M, Taylor, T, Rockett, K, Fry, A, Griffiths, M, Auburn, Sarah, Diakite, M, Forton, J, Green, A, Richardson, A, Wilson, J, Jallow, M, Sisay-Joof, F, Pinder, M, Peshu, N, Williams, T, Marsh, K, ME Molyneux, M, Taylor, T, and Rockett, K

Published
2008

45. An epidemiological study of RSV infection in the Gambia

Author

Weber, MW, Milligan, P, Sanneh, M, Awemoyi, A, Dakour, ER, Schneider, G, Palmer, A, Jallow, M, Oparaogu, A, Whittle, H, Mulholland, EK, Greenwood, BM, Weber, MW, Milligan, P, Sanneh, M, Awemoyi, A, Dakour, ER, Schneider, G, Palmer, A, Jallow, M, Oparaogu, A, Whittle, H, Mulholland, EK, and Greenwood, BM

Abstract

OBJECTIVE: To describe the epidemiology of respiratory syncytial virus (RSV) infection in a developing country. METHODS: The work was carried out in three hospitals for primary cases and in the community for secondary cases in the western region of the Gambia, West Africa. RSV infection was diagnosed by immunofluorescence of nasopharyngeal aspirate samples in children younger than two years admitted to hospital with acute lower respiratory infection (ALRI). Routine records of all children with ALRI were analysed, and the incidence rates of ALRI, severe RSV-associated respiratory illness and hypoxaemic RSV infections were compared. A community-based study was undertaken to identify secondary cases and to obtain information about spread of the virus. FINDINGS: 4799 children with ALRI who were younger than two years and lived in the study area were admitted to the study hospitals: 421 had severe RSV-associated respiratory illness; 55 of these were hypoxaemic. Between 1994 and 1996, the observed incidence rate for ALRI in 100 children younger than one year living close to hospital was 9.6 cases per year; for severe RSV-associated respiratory illness 0.83; and for hypoxaemic RSV-associated respiratory illness 0.089. The proportion of all ALRI admissions due to RSV was 19%. Overall, 41% of children younger than five years in compounds in which cases lived and 42% in control compounds had evidence of RSV infection during the surveillance period. CONCLUSION: RSV is an important cause of ALRI leading to hospital admission in the Gambia. Morbidity is considerable and efforts at prevention are worthwhile.

Published
2002

50. Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations.

Author

Clark TG, Diakite M, Auburn S, Campino S, Fry AE, Green A, Richardson A, Small K, Teo YY, Wilson J, Jallow M, Sisay-Joof F, Pinder M, Griffiths MJ, Peshu N, Williams TN, Marsh K, Molyneux ME, Taylor TE, and Rockett KA

Abstract

The tumor necrosis factor gene (TNF) and lymphotoxin-alpha gene (LTA) have long attracted attention as candidate genes for susceptibility traits for malaria, and several of their polymorphisms have been found to be associated with severe malaria (SM) phenotypes. In a large study involving >10,000 individuals and encompassing 3 African populations, we found evidence to support the reported associations between the TNF -238 polymorphism and SM in The Gambia. However, no TNF/LTA polymorphisms were found to be associated with SM in cohorts in Kenya and Malawi. It has been suggested that the causal polymorphisms regulating the TNF and LTA responses may be located some distance from the genes. Therefore, more-detailed mapping of variants across TNF/LTA genes and their flanking regions in the Gambian and allied populations may need to be undertaken to find any causal polymorphisms. [ABSTRACT FROM AUTHOR]

Published
2009
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