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2. Effect of Eugenol, Vanillin, and β-Resorcylic Acid on Foodborne Pathogen Survival in Marinated Camel Meat

Author

Osaili, Tareq M., primary, Al-Nabulsi, Anas A., additional, Hasan, Fayeza, additional, Dhanasekaran, Dinesh K., additional, Hussain, Ayman Z.S., additional, Cheikh Ismail, Leila, additional, Naja, Farah, additional, Radwan, Hadia, additional, Faris, MoezAlIslam Ezzat, additional, Olaimat, Amin N., additional, Ayyash, Mutamed, additional, Obaid, Reyad S., additional, and Holley, Richard, additional

Published
2023
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3. Inhibition of spoilage bacteria on marinated chicken by essential oils under aerobic and vacuum packaging

Author

Osaili, Tareq M., primary, Al‐Nabulsi, Anas A., additional, Hasan, Fayeza, additional, Dhanasekaran, Dinesh K., additional, Ismail, Leila Cheikh, additional, Hashim, Mona, additional, Hasan, Hayder, additional, Ayyash, Mutamed, additional, Olaimat, Amin, additional, Hussain, Ayman Z. S., additional, Darra, Nada El, additional, Savvaidis, Ioannis N., additional, Obaid, Reyad S., additional, and Holley, Richard, additional

Published
2022
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4. Inhibition of spoilage bacteria on marinated chicken by essential oils under aerobic and vacuum packaging.

Author

Osaili, Tareq M., Al‐Nabulsi, Anas A., Hasan, Fayeza, Dhanasekaran, Dinesh K., Ismail, Leila Cheikh, Hashim, Mona, Hasan, Hayder, Ayyash, Mutamed, Olaimat, Amin, Hussain, Ayman Z. S., Darra, Nada El, Savvaidis, Ioannis N., Obaid, Reyad S., and Holley, Richard

Subjects
VACUUM packaging, ESSENTIAL oils, LACTIC acid bacteria, ANAEROBIC microorganisms, AEROBIC bacteria, MICROORGANISM populations
Abstract

"Chicken tawook" is a marinated boneless chicken entrée consumed in the Middle East. The aim of this study was to determine whether bioactive essential oil (EO) components carvacrol (CA), cinnamaldehyde (CI), and thymol (TH) would delay the growth of microorganisms causing tawook spoilage during aerobic (AP) or vacuum (VP) packed storage. The EOs at 1% and 2% were mixed individually with the marinade. The samples (10 g of chicken cubes with 1.2 g of marinade – with or without EOs) were stored in bags under AP and VP (Geryon®) for 7 days at 4 ± 1°C and abusive conditions (10 ± 1°C). Two control samples consisting of meat chunks and tawook without EO were used. The microflora numbers were greater at 10°C than at 4°C, and the marinade worked additively with AP against anaerobes, yeast and mold (Y & M) and lactic acid bacteria. It also worked additively with VP against aerobic bacteria recovered as Pseudomonas and the total plate count. EO components were observed to decrease microbial populations by a maximum of 4 to 6 log colony‐forming unit (CFU)/g depending on the type of microorganism. The combined mixture of marinade and 2% EO (CA, CI, and TH) resulted in the greatest reductions of all spoilage microorganisms at 10°C under AP on the last day of storage. Overall, VP was more effective (p < 0.05) than AP in controlling microorganisms at both 4 and 10°C. This study provides an affordable and natural alternative for extending product life. Practical Application: The use of EOs in marinated chicken (tawook) is expected to help producers reduce spoilage and extend shelf‐life of the product when stored at refrigeration temperatures. EOs provide a cheaper alternative and are naturally sourced. Vacuum packaging will increase the shelf‐life of marinated chicken tawook and facilitate its storage and transportation. [ABSTRACT FROM AUTHOR]

Published
2023
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6. Malaria infection by sporozoite challenge induces high functional antibody titres against blood stage antigens after a DNA prime, poxvirus boost vaccination strategy in Rhesus macaques

Author

Thomas Alan W, Narum David L, Hussain Ayman A, El Hassan Ibrahim M, Remarque Edmond J, Mahdi Abdel Hamid Muzamil, Kocken Clemens HM, Weiss Walter R, and Faber Bart W

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background A DNA prime, poxvirus (COPAK) boost vaccination regime with four antigens, i.e. a combination of two Plasmodium knowlesi sporozoite (csp/ssp2) and two blood stage (ama1/msp142) genes, leads to self-limited parasitaemia in 60% of rhesus monkeys and survival from an otherwise lethal infection with P. knowlesi. In the present study, the role of the blood stage antigens in protection was studied in depth, focusing on antibody formation against the blood stage antigens and the functionality thereof. Methods Rhesus macaques were immunized with the four-component vaccine and subsequently challenged i.v. with 100 P. knowlesi sporozoites. During immunization and challenge, antibody titres against the two blood stage antigens were determined, as well as the in vitro growth inhibition capacity of those antibodies. Antigen reversal experiments were performed to determine the relative contribution of antibodies against each of the two blood stage antigens to the inhibition. Results After vaccination, PkAMA1 and PkMSP119 antibody titres in vaccinated animals were low, which was reflected in low levels of inhibition by these antibodies as determined by in vitro inhibition assays. Interestingly, after sporozoite challenge antibody titres against blood stage antigens were boosted over 30-fold in both protected and not protected animals. The in vitro inhibition levels increased to high levels (median inhibitions of 59% and 56% at 6 mg/mL total IgG, respectively). As growth inhibition levels were not significantly different between protected and not protected animals, the ability to control infection appeared cannot be explained by GIA levels. Judged by in vitro antigen reversal growth inhibition assays, over 85% of the inhibitory activity of these antibodies was directed against PkAMA1. Conclusions This is the first report that demonstrates that a DNA prime/poxvirus boost vaccination regimen induces low levels of malaria parasite growth inhibitory antibodies, which are boosted to high levels upon challenge. No association could, however, be established between the levels of inhibitory capacity in vitro and protection, either after vaccination or after challenge.

Published
2011
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7. Loss of balancing selection in the βS globin locus

Author

Ishag Hani B, Khalil Eltahir AG, Elhassan Ibrahim M, Elzein Abeir M, Almugtaba Ibrahim A, Hussain Ayman A, Salih Niven A, Mohammed Hiba S, Kwiatkowski Dominic, and Ibrahim Muntaser E

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations. Methods We investigated the association of haemoglobin HbS in protection from clinical episodes of malaria in two populations/villages where malaria is endemic, but mostly presenting in mild clinical forms. Five-hundred and forty-six individuals comprising 65 and 82 families from the Hausa and Massalit villages respectively were genotyped for HbS. Allele and genotype frequencies as well as departure from Hardy-Weinberg Equilibrium were estimated from four-hundred and seventy independent genotypes across different age groups. Age-group frequencies were used to calculate the coefficient-of-fitness and to simulate the expected frequencies in future generations. Results Genotype frequencies were within Hardy-Weinberg expectations in Hausa and Massalit in the total sample set but not within the different age groups. There was a trend for a decrease of the HbS allele frequency in Hausa and an increase of frequency in Massalit. Although the HbS allele was able to confer significant protection from the clinical episodes of malaria in the two populations, as suggested by the odds ratios, the overall relative fitness of the HbS allele seems to have declined in Hausa. Conclusions Such loss of balancing selection could be due to a combined effect of preponderance of non-clinical malaria in Hausa, and the deleterious effect of the homozygous HbS under circumstances of endogamy.

Published
2010
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8. Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

Author

Suleiman, Suleiman H, Koko, Mahmoud E, Nasir, Wafaa H, Elfateh, Ommnyiah, Elgizouli, Ubai K, Abdallah, Mohammed O. E, Alfarouk, Khalid O, Hussain, Ayman, Faisal, Shima, Ibrahim, Fathelrahamn M. A, Sultan, Ali, Banks, Lawrence, Newport, Melanie, Baralle, Francesco, Elhassan, Ahmed M, Mohamed, Hiba S, Ibrahim, Muntaser E., ROMANO, MAURIZIO, Suleiman, Suleiman H, Koko, Mahmoud E, Nasir, Wafaa H, Elfateh, Ommnyiah, Elgizouli, Ubai K, Abdallah, Mohammed O. E, Alfarouk, Khalid O, Hussain, Ayman, Faisal, Shima, Ibrahim, Fathelrahamn M. A, Romano, Maurizio, Sultan, Ali, Banks, Lawrence, Newport, Melanie, Baralle, Francesco, Elhassan, Ahmed M, Mohamed, Hiba S, and Ibrahim, Muntaser E.

Subjects
lcsh:QH426-470, colorectal cancer, NFkB, pathway analysis, lcsh:Genetics, ELAVL1/HuR, exome sequencing, network analysis, Genetics, network analysi, Molecular Medicine, Genetics (clinical), Original Research
Abstract

The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions-deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions-deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6). NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins.

Published
2015

9. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer MG, Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G, Band, Gavin, Clarke, Geraldine M, Spencer, Christopher CA, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimdé, Abdoulaye, Maiga, Boubacar, Touré, Ousmane, Doumbo, Ogobara K, Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D, Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B, Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J, Riley, Eleanor M, Kwiatkowski, Dominic P, Rockett, Kirk A, MalariaGEN Consortium, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], London School of Hygiene and Tropical Medicine (LSHTM), National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare Products Regulatory Agency (MHRA), Nuffield Department of Population Health [Oxford], The Wellcome Trust Sanger Institute [Cambridge], Unité d'Epidémiologie des Maladies Infectieuses, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Immunologie Moléculaire des Parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Stockholm University, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), University of Khartoum, KEMRI-Wellcome Trust Research Programme (KWTRP), Tumaini University Makumira, National Institute for Medical Research [Tanzania] (NIMR), University of Edinburgh, University of Colombo [Sri Lanka], MalariaGEN is supported by the Wellcome Trust (077383/Z/05/Z) and by the Foundation for the National Institutes of Health (566) as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative. The Resource Centre for Genomic Epidemiology of Malaria is supported by the Wellcome Trust (090770/Z/09/Z). Support was also provided by the Medical Research Council (G0600718). DPK receives support from the Medical Research Council (G19/9). CCAS was supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). The Wellcome Trust also provides core awards to The Wellcome Trust Centre for Human Genetics (075491/Z/04, 090532/Z/09/Z) and the Wellcome Trust Sanger Institute (077012/Z/05/Z). MTB and BM received funding through the EU Network of Excellence EviMalar. VDM was funded by a Biomalpar (European Community’s Sixth Framework Programme) PhD fellowship. FV was funded by the Italian Malaria Network, sponsored by Compagnia di San Paolo, Turin, Italy. TNW is supported by a Senior Research Fellowship from the Wellcome Trust (091758/Z/10/Z). This study was conducted as part of the Joint Malaria Programme, a collaboration between the National Institute for Medical Research (NIMR), Kilimanjaro Christian Medical College (KCMC), the London School of Hygiene and Tropical Medicine (LSHTM) and the Centre for Medical Parasitology, University of Copenhagen (CMP) with funding from the UK Medical Research Council (GG9901439) and the Danish International Development Agency. CJD is supported by the Wellcome Trust (091924). RD is supported by the University of Colombo Research Grants 2011 (AP/3/2011/PG/15)., European Project: 26843,BIOMALPAR, University of Oxford, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)

Subjects
Male, Hemoglobin, Sickle, Antibodies, Protozoan, Sickle, MESH: Linear Models, MESH: Child, Child, HbAS, MESH: Infant, Newborn, Antibody, CD36, Genotype, Malaria, Sickle cell trait, Adolescent, Adult, Africa South of the Sahara, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Linear Models, Sri Lanka, Young Adult, Infectious Diseases, Parasitology, MESH: Infant, MESH: Young Adult, Protozoan, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Malaria, Antibodies, parasitic diseases, MESH: Antibodies, Protozoan, Hemoglobin, MESH: Africa South of the Sahara, Preschool, MESH: Sri Lanka, MESH: Adolescent, MESH: Humans, Research, MESH: Child, Preschool, MESH: Adult, Newborn, MESH: Hemoglobin, Sickle, MESH: Male, antibody, cd36, genotype, hbas, malaria, sickle cell trait, infectious diseases, parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract

Background Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0833-x) contains supplementary material, which is available to authorized users.

Published
2015
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10. Additional file 3: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Abstract

Additional File LFST1A: Details of gene regions selected for genotyping and the SNP assay design details. This file contains a list of the genes from which SNPs were selected and typed for this study. Information is provided on the gene and its genomic location with respect to the Human Reference genome build GRCh37. Also provided is a table containing the assay design details for each SNP used in this study for the Agena Biosciences iPLEX genotyping platform. SNPs are grouped into multiplexes as assigned by the assay design software.

Published
2015
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11. Additional file 17: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Abstract

Additional Figure SF5: Plot for 178 SNPs with logged anti-malarial antibody levels. Plot for the P-values of the analyses of 178 SNPs with logged anti-malarial antibody levels Adjusted for age, gender, parasite density, village (>20), ethnicity (>20), sample month (>20) and study. This is an extension to that shown in the main text and is a reduced dataset as not all sites provided parasitaemia data.

Published
2015
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12. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer M. G., Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G., Band, Gavin, Clarke, Geraldine M., Spencer, Christopher C. A., Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimde, Abdoulaye, Maiga, Boubacar, Toure, Ousmane, Doumbo, Ogobara K., Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D., Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B., Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N., Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J., Riley, Eleanor M., Kwiatkowski, Dominic P., Rockett, Kirk A., Shelton, Jennifer M. G., Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G., Band, Gavin, Clarke, Geraldine M., Spencer, Christopher C. A., Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimde, Abdoulaye, Maiga, Boubacar, Toure, Ousmane, Doumbo, Ogobara K., Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D., Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B., Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N., Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J., Riley, Eleanor M., Kwiatkowski, Dominic P., and Rockett, Kirk A.

Abstract

Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP) 4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)(4) epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demons

Published
2015
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14. Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

Author

Suleiman, Suleiman H., primary, Koko, Mahmoud E., additional, Nasir, Wafaa H., additional, Elfateh, Ommnyiah, additional, Elgizouli, Ubai K., additional, Abdallah, Mohammed O. E., additional, Alfarouk, Khalid O., additional, Hussain, Ayman, additional, Faisal, Shima, additional, Ibrahim, Fathelrahamn M. A., additional, Romano, Maurizio, additional, Sultan, Ali, additional, Banks, Lawrence, additional, Newport, Melanie, additional, Baralle, Francesco, additional, Elhassan, Ahmed M., additional, Mohamed, Hiba S., additional, and Ibrahim, Muntaser E., additional

Published
2015
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15. Malaria infection by sporozoite challenge induces high functional antibody titres against blood stage antigens after a DNA prime, poxvirus boost vaccination strategy in Rhesus macaques

Author

Mahdi Abdel Hamid, Muzamil, primary, Remarque, Edmond J, additional, El Hassan, Ibrahim M, additional, Hussain, Ayman A, additional, Narum, David L, additional, Thomas, Alan W, additional, Kocken, Clemens HM, additional, Weiss, Walter R, additional, and Faber, Bart W, additional

Published
2011
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16. Loss of balancing selection in the βS globin locus

Author

Salih, Niven A, primary, Hussain, Ayman A, additional, Almugtaba, Ibrahim A, additional, Elzein, Abeir M, additional, Elhassan, Ibrahim M, additional, Khalil, Eltahir AG, additional, Ishag, Hani B, additional, Mohammed, Hiba S, additional, Kwiatkowski, Dominic, additional, and Ibrahim, Muntaser E, additional

Published
2010
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19. Candidate gene analysis supports a role for polymorphisms at TCF7L2 as risk factors for type 2 diabetes in Sudan.

Author

Ibrahim, Amir T., Salih, Mohamed A. M., Hussain, Ayman, Ibrahim, Muntaser E., Mohamed, Hiba S., Ibrahim, Omima Abdeen, Jamieson, Sarra E., and Blackwell, Jenefer M.

Subjects
TYPE 2 diabetes risk factors, GENETIC polymorphism research, SUDANESE, DISEASES
Abstract

Background: Genetic susceptibility to type 2 diabetes (T2D) is multifactorial. A growing number of genes have been identified as risk factors for T2D across multiple ethnicities in trans-ancestry meta-analysis of large-scale genome-wide association studies. Few studies have looked at these genes in Sub-Saharan African populations. This study was undertaken to look for associations between T2D and single nucleotide polymorphisms (SNPs) in a number of the top candidate genes in a selected Sudanese population. Methods: A total 240 T2D cases and 128 unrelated healthy control subjects were included in this study. Age, sex, weight and height were recorded, blood pressure and biochemical profiles of glucose and lipids were analysed. Single nucleotide polymorphism (SNP) genotyping was performed using the Sequenom MassARRAY® system. Fourteen SNPs were selected across 7 genes: CAPN10 (rs2975760 and rs5030952), PPARG (rs17036314 and rs1801282), IGF2BP2 (rs4402960 and rs1470579), CDKAL1 (rs9465871), HHEX (rs1111875), TCF7L2 (rs7903146, rs11196205 and rs12255372), and KCNJ11 (rs5215, rs1800467 and rs5219). Allelic and haplotype association analyses were performed under additive models in PLINK. P ≤ 0.007 (=0.05/7 genes) was the P-value required to achieve correction for multiple testing. Results: A significant genetic association between the SNPs rs7903146 (odds ratio 1.69, 95 % confidence interval 1.21-2.38, P = 0.002) and rs12255372 (odds ratio 1.70, 95 % confidence interval 1.20-2.41, P = 0.003) at TCF7L2 and T2D was found in Sudanese population. These associations were retained after adjusting for age, sex and BMI (e.g. rs7903146: odds ratio 1.70, Padj:age/sex/BMI = 0.005). The strongest haplotype association (odds ratio 2.24; Padj:age/sex/BMI = 0.0003) comprised the two point haplotype T_C across rs7903146 and rs11196205. Stepwise logistic regression demonstrated that SNP rs7903146 added significant main effects to rs11196205 or rs12255372, whereas the reverse was not true, indicating that the main effect for association with T2D in this population is most strongly tagged by SNP rs7903146. Adjusted analyses also provided support for protection from T2D associated with minor alleles at SNPs rs2975760 at CAPN10 (odds ratio 0.44, 95 % confidence interval 0.20-0.97, Padj:age/sex/BMI = 0.042) and rs1111876 at HHEX (odds ratio 0.60, 95 % confidence interval 0.39-0.93, Padj:age/sex/BMI = 0.022). Conclusions: Multiethnic associations between T2D and SNPs at TCF7L2, CAPN10 and HHEX extend to Sub-Saharan Africa, specifically Sudan. [ABSTRACT FROM AUTHOR]

Published
2016
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20. Malaria infection by sporozoite challenge induces high functional antibody titres against blood stage antigens after a DNA prime, poxvirus boost vaccination strategy in Rhesus macaques.

Author

Hamid, Muzamil Mahdi Abdel, Remarque, Edmond J., Hassan, Ibrahim M. El, Hussain, Ayman A., Narum, David L., Thomas, Alan W., Kocken, Clemens H. M., Weiss, Walter R., and Faber, Bart W.

Subjects
POXVIRUSES, VACCINATION, ANTIGENS, PLASMODIUM, RHESUS monkeys
Abstract

Background: A DNA prime, poxvirus (COPAK) boost vaccination regime with four antigens, i.e. a combination of two Plasmodium knowlesi sporozoite (csp/ssp2) and two blood stage (ama1/msp142) genes, leads to self-limited parasitaemia in 60% of rhesus monkeys and survival from an otherwise lethal infection with P. knowlesi. In the present study, the role of the blood stage antigens in protection was studied in depth, focusing on antibody formation against the blood stage antigens and the functionality thereof. Methods: Rhesus macaques were immunized with the four-component vaccine and subsequently challenged i.v. with 100 P. knowlesi sporozoites. During immunization and challenge, antibody titres against the two blood stage antigens were determined, as well as the in vitro growth inhibition capacity of those antibodies. Antigen reversal experiments were performed to determine the relative contribution of antibodies against each of the two blood stage antigens to the inhibition. Results: After vaccination, PkAMA1 and PkMSP119 antibody titres in vaccinated animals were low, which was reflected in low levels of inhibition by these antibodies as determined by in vitro inhibition assays. Interestingly, after sporozoite challenge antibody titres against blood stage antigens were boosted over 30-fold in both protected and not protected animals. The in vitro inhibition levels increased to high levels (median inhibitions of 59% and 56% at 6 mg/mL total IgG, respectively). As growth inhibition levels were not significantly different between protected and not protected animals, the ability to control infection appeared cannot be explained by GIA levels. Judged by in vitro antigen reversal growth inhibition assays, over 85% of the inhibitory activity of these antibodies was directed against PkAMA1. Conclusions: This is the first report that demonstrates that a DNA prime/poxvirus boost vaccination regimen induces low levels of malaria parasite growth inhibitory antibodies, which are boosted to high levels upon challenge. No association could, however, be established between the levels of inhibitory capacity in vitro and protection, either after vaccination or after challenge. [ABSTRACT FROM AUTHOR]

Published
2011
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21. Additional file 13: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST7Aâ E: Results of site-specific linear regression analysis investigating the effect of age, gender and malaria status as determined by microscopy on antibody levels to the different antibodies measured in the study. This data shows the site-specific analyses of the various epidemiological parameters and antibody measurements.

22. Additional file 16: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST10: Meta-analysis p-values obtained for 178 SNPs passing QC criteria detailed in materials and methods. Details of the analyses for each SNP and antibody across all sites for different genetic inheritance models.

23. Additional file 10: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF4: Scatter plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site and age-group. This plot shows the pairwise correlations (as r2) for each malariaâ malaria antibody pair as a function of each study site. The sites are ordered according to malaria microscopically-positive-prevalence recorded at sample collection (low to high). Several panels are shown according to age-group.

24. Additional file 4: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

MalariaGEN Supplementary Sample Handling Procedures. This file includes more detail on sample handling procedures including extracting DNA, genotyping methodology, ELISA protocols with ELISA data processing.

25. Additional file 9: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF3: Heatmap matrix plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site. Matrix plot of the pairwise correlations as r2 between antibody titres using data from all sites.

26. Additional file 14: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Table ST8: Results of linear regression analysis investigating the effect of age, gender, malaria status as determined by microscopy and bednet use* on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. This table shows the results of the analysis of antibody levels with bednet use. Results shown as betas indicating the direction of effect of the clinical covariates on antibody levels.

27. Additional file 10: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF4: Scatter plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site and age-group. This plot shows the pairwise correlations (as r2) for each malariaâ malaria antibody pair as a function of each study site. The sites are ordered according to malaria microscopically-positive-prevalence recorded at sample collection (low to high). Several panels are shown according to age-group.

28. Additional file 7: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
Statistics::Machine Learning, Statistics::Theory, Statistics::Methodology, Statistics::Computation, 3. Good health
Abstract

Additional Table ST3A-D: Details of the linear regression models used in this study. Model formulae for the various linear regression analyses showing how the different co-variates were used.

29. Additional file 6: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF2: Histograms of residuals from antibody linear regression models with non-genetic factors. Histograms of the residuals from the antibody linear regression model analysis with non-genetic factors.

30. Additional file 13: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST7Aâ E: Results of site-specific linear regression analysis investigating the effect of age, gender and malaria status as determined by microscopy on antibody levels to the different antibodies measured in the study. This data shows the site-specific analyses of the various epidemiological parameters and antibody measurements.

31. Additional file 2: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST2: Details of covariates adjusted for in linear regression analysis of non-genetic factors with logged antibody levels, their relevance to the study and their previous association(s) with malaria or anti-malarial antibodies. Information on the covariates used in this study as con-variates in the various analyses.

32. Additional file 5: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, endocrine system, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF1: Histograms of logged antibody levels before further manipulations were made. Histograms of the logged antibody titres across all samples for each antibody measured in this study.

33. Additional file 15: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST9: Details of 196 genotyped SNPs and their derived allele frequencies at each site. This table shows allele frequencies for each SNP analysed in this study according to each study site.

34. Additional file 16: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST10: Meta-analysis p-values obtained for 178 SNPs passing QC criteria detailed in materials and methods. Details of the analyses for each SNP and antibody across all sites for different genetic inheritance models.

35. Additional file 11: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional table ST5: Linear regression analysis of the correlations between residuals from the malaria antibody pairs. This data shows the results of the analysis of the correlations between antibodies.

36. Additional file 8: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Table ST4: Results of linear regression analysis investigating the effect of age, gender and HbS genotype on parasite density in malaria-positive individuals using combined site data. Results of linear regression analysis investigating the effect of age, gender and HbS genotype on parasite density in malaria-positive individuals using combined data. This is an extension to that shown in the main text and is a reduced dataset as not all sites provided parasitaemia data.

37. Additional file 15: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST9: Details of 196 genotyped SNPs and their derived allele frequencies at each site. This table shows allele frequencies for each SNP analysed in this study according to each study site.

38. Additional file 6: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF2: Histograms of residuals from antibody linear regression models with non-genetic factors. Histograms of the residuals from the antibody linear regression model analysis with non-genetic factors.

39. Additional file 4: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

MalariaGEN Supplementary Sample Handling Procedures. This file includes more detail on sample handling procedures including extracting DNA, genotyping methodology, ELISA protocols with ELISA data processing.

40. Additional file 18: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Figure SF6: Forest plot of the association of A: CD36 (rs3211938), B: LOC441108 (rs2522051), C: RTN3 (rs542998) and D: P4HA2 (rs156029) with antibody levels to AMA1, MSP1, MSP2 and NANP. Forest plots of the betas obtained from meta-analysis of results obtained from linear regression models of SNP with logged antibody levels, adjusted for relevant clinical covariates.

41. Additional file 11: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional table ST5: Linear regression analysis of the correlations between residuals from the malaria antibody pairs. This data shows the results of the analysis of the correlations between antibodies.

42. Additional file 7: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
Statistics::Machine Learning, Statistics::Theory, Statistics::Methodology, Statistics::Computation, 3. Good health
Abstract

Additional Table ST3A-D: Details of the linear regression models used in this study. Model formulae for the various linear regression analyses showing how the different co-variates were used.

43. Additional file 1: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
education, 3. Good health
Abstract

Additional Table ST1 Details of Principal Investigators and Ethics Review Committees for each site. Details of Principal Investigators and Ethics Review Committees for each site.

44. Additional file 9: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF3: Heatmap matrix plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site. Matrix plot of the pairwise correlations as r2 between antibody titres using data from all sites.

45. Additional file 14: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Table ST8: Results of linear regression analysis investigating the effect of age, gender, malaria status as determined by microscopy and bednet use* on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. This table shows the results of the analysis of antibody levels with bednet use. Results shown as betas indicating the direction of effect of the clinical covariates on antibody levels.

46. Additional file 5: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, endocrine system, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF1: Histograms of logged antibody levels before further manipulations were made. Histograms of the logged antibody titres across all samples for each antibody measured in this study.

47. Additional file 2: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST2: Details of covariates adjusted for in linear regression analysis of non-genetic factors with logged antibody levels, their relevance to the study and their previous association(s) with malaria or anti-malarial antibodies. Information on the covariates used in this study as con-variates in the various analyses.

48. Additional file 1: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
education, 3. Good health
Abstract

Additional Table ST1 Details of Principal Investigators and Ethics Review Committees for each site. Details of Principal Investigators and Ethics Review Committees for each site.

49. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study.

Author

Shelton JM, Corran P, Risley P, Silva N, Hubbart C, Jeffreys A, Rowlands K, Craik R, Cornelius V, Hensmann M, Molloy S, Sepulveda N, Clark TG, Band G, Clarke GM, Spencer CC, Kerasidou A, Campino S, Auburn S, Tall A, Ly AB, Mercereau-Puijalon O, Sakuntabhai A, Djimdé A, Maiga B, Touré O, Doumbo OK, Dolo A, Troye-Blomberg M, Mangano VD, Verra F, Modiano D, Bougouma E, Sirima SB, Ibrahim M, Hussain A, Eid N, Elzein A, Mohammed H, Elhassan A, Elhassan I, Williams TN, Ndila C, Macharia A, Marsh K, Manjurano A, Reyburn H, Lemnge M, Ishengoma D, Carter R, Karunaweera N, Fernando D, Dewasurendra R, Drakeley CJ, Riley EM, Kwiatkowski DP, and Rockett KA

Subjects
Adolescent, Adult, Africa South of the Sahara epidemiology, Antibodies, Protozoan blood, Child, Child, Preschool, Female, Hemoglobin, Sickle genetics, Humans, Infant, Infant, Newborn, Linear Models, Male, Sri Lanka epidemiology, Young Adult, Antibodies, Protozoan immunology, Malaria epidemiology, Malaria genetics, Malaria immunology
Abstract

Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels., Methods: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels., Results: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2., Conclusion: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

Published
2015
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