Publications

@article{Boua2022,

title = {Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans.},

author = {Palwende Romuald Boua and Jean-Tristan Brandenburg and Ananyo Choudhury and Hermann Sorgho and Engelbert A. Nonterah and Godfred Agongo and Gershim Asiki and Lisa Micklesfield and Solomon Choma and Francesc Xavier G\'{o}mez-Oliv\'{e} and Scott Hazelhurst and Halidou Tinto and Nigel J. Crowther and Christopher G. Mathew and Mich\`{e}le Ramsay},

doi = {10.1038/s41467-022-28276-x},

year  = {2022},

date = {2022-02-01},

urldate = {2022-02-01},

journal = {Nature communications},

volume = {13},

issue = {1},

pages = {855},

abstract = {Atherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT, SIRPA (p = 4.7E-08), and FBXL17 (p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus, SNX29 (p = 6.3E-09), and two female-specific loci, LARP6 (p = 2.4E-09) and PROK1 (p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies.},

keywords = {Adult, Africa South of the Sahara, Atherosclerosis/*genetics/*pathology, Autoantigens/genetics, Cardiovascular Diseases/genetics, Carotid Intima-Media Thickness/*statistics \& numerical data, Endocrine-Gland-Derived/genetics, Female, Gastrointestinal Hormones/genetics, Genetic Predisposition to Disease/*genetics, Genome/genetics, Histones/genetics, Humans, Male, Middle Aged, Polymorphism, Ribonucleoproteins/genetics, Sex Factors, Single Nucleotide/genetics, Sorting Nexins/genetics, Vascular Endothelial Growth Factor},

pubstate = {published},

tppubtype = {article}

}

@article{Adoke2021-el,

title = {A randomized, double-blind, phase 2b study to investigate the  efficacy, safety, tolerability and pharmacokinetics of a  single-dose regimen of ferroquine with artefenomel in adults and  children with uncomplicated Plasmodium falciparum malaria},

author = {Yeka Adoke and Rella Zoleko-Manego and Serge Ouoba and Alfred B Tiono and Grace Kaguthi and Juv^encio Eduardo Bonzela and Tran Thanh Duong and Alain Nahum and Marielle Bouyou-Akotet and Bernhards Ogutu and Alphonse Ouedraogo and Fiona Macintyre and Andreas Jessel and Bart Laurijssens and Mohammed H Cherkaoui-Rbati and Cathy Cantalloube and Anne Claire Marrast and Rapha"el Bejuit and David White and Timothy N C Wells and Florian Wartha and Didier Leroy and Afizi Kibuuka and Ghyslain Mombo-Ngoma and Daouda Ouattara and Ir`ene Mugenya and Bui Quang Phuc and Francis Bohissou and Denise P Mawili-Mboumba and Fredrick Olewe and Issiaka Soulama and Halidou Tinto and FALCI Study Group},

doi = {10.1186/s12936-021-03749-4},

issn = {1475-2875},

year  = {2021},

date = {2021-05-19},

urldate = {2021-05-19},

journal = {Malar. J.},

volume = {20},

number = {1},

pages = {222},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: For uncomplicated Plasmodium falciparum malaria, 

 highly efficacious single-dose treatments are expected to 

 increase compliance and improve treatment outcomes, and thereby 

 may slow the development of resistance. The efficacy and safety 

 of a single-dose combination of artefenomel (800 mg) plus 

 ferroquine (400/600/900/1200 mg doses) for the treatment of 

 uncomplicated P. falciparum malaria were evaluated in Africa 

 (focusing on children $\leq$ 5 years) and Asia. METHODS: The 

 study was a randomized, double-blind, single-dose, multi-arm 

 clinical trial in patients aged > 6 months to 5 years and 20 

 Asian patients. None of the treatment arms met the target 

 efficacy criterion for PCR-adjusted ACPR at Day 28 (lower limit 

 of 95% confidence interval [CI] > 90%). PCR-adjusted ACPR at 

 Day 28 [95% CI] in the PP Set ranged from 78.4% [64.7; 88.7%] 

 to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg ferroquine 

 dose. Efficacy rates were low in Vietnamese patients, ranging 

 from 20 to 40%. A clear relationship was found between drug 

 exposure (artefenomel and ferroquine concentrations at Day 7) 

 and efficacy (primary endpoint), with higher concentrations of 

 both drugs resulting in higher efficacy. Six distinct kelch-13 

 mutations were detected in parasite isolates from 10/272 African 

 patients (with 2 mutations known to be associated with 

 artemisinin resistance) and 18/20 Asian patients (all C580Y 

 mutation). Vomiting within 6 h of initial artefenomel 

 administration was common (24.6%) and associated with lower 

 drug exposures. CONCLUSION: The efficacy of 

 artefenomel/ferroquine combination was suboptimal in African 

 children aged $\leq$ 5 years, the population of interest, and 

 vomiting most likely had a negative impact on efficacy. Trial 

 registration ClinicalTrials.gov, NCT02497612. Registered 14 Jul 

 2015, https://clinicaltrials.gov/ct2/show/NCT02497612?term=NCT02497612\&draw=2\&rank=1.},

note = {PMID: 34011358 

PMCID: PMC8135182},

keywords = {Adamantane/administration \& dosage/analogs \& derivatives, Adolescent, Adult, Aged, Aminoquinolines/administration \& dosage, Benin, Burkina Faso, C580Y, Child, Combination treatment, Double-Blind Method, Drug Combinations, Exposure\textendashresponse, Falciparum/prevention \& control, Female, Ferroquine, Ferrous Compounds/administration \& dosage, Gabon, Humans, Infant, Kelch-13 mutation, Kenya, Malaria, Male, Metallocenes/administration \& dosage, Middle Aged, Mozambique, Parasite clearance, Peroxides/administration \& dosage, Pharmacokinetics/pharmacodynamics, Plasmodium falciparum/drug effects, Preschool, resistance, Uganda, Vietnam, Vomiting, Young Adult},

pubstate = {published},

tppubtype = {article}

}

@article{Nonterah2021-pc,

title = {Adiposity phenotypes and subclinical atherosclerosis in adults  from sub-Saharan Africa: An H3Africa AWI-gen study},

author = {Engelbert A Nonterah and Michiel L Bots and Abraham Oduro and Godfred Agongo and Cassandra C Soo and Lisa K Micklesfield and Felistas Mashinya and Palwend\'{e} R Boua and Shukri F Mohamed and Alisha N Wade and Catherine Kyobutungi and Halidou Tinto and Shane A Norris and Stephen M Tollman and Mich`ele Ramsay and Diederick E Grobbee and Kerstin Klipstein-Grobusch and Nigel J Crowther and AWI-Gen and H3Africa Consortium},

doi = {10.5334/gh.863},

issn = {2211-8179 2211-8160},

year  = {2021},

date = {2021-03-19},

urldate = {2021-03-19},

journal = {Glob. Heart},

volume = {16},

number = {1},

pages = {19},

publisher = {Ubiquity Press, Ltd.},

abstract = {Background: Obesity and adipose tissue distribution contribute 

 to an increased risk of cardiovascular disease (CVD) by 

 promoting atherosclerosis. This association has been poorly 

 studied in sub-Saharan Africa (SSA) despite the rising 

 prevalence of cardiovascular disease. Objectives: We determined 

 the association between various adiposity phenotypes and carotid 

 intima-media thickness (CIMT), a proxy of subclinical 

 atherosclerosis, in a large SSA population. Methods: A 

 population-based cross-sectional study was performed from 

 2013-2016 in Burkina Faso, Ghana, Kenya and South Africa. Body 

 mass index (BMI), waist (WC), hip circumferences (HC), visceral 

 (VAT) and subcutaneous adipose tissue (SCAT) using B-mode 

 ultrasound were measured. Ultrasonography of left and right far 

 wall CIMT of the common carotid artery was used as an indicator 

 of subclinical atherosclerosis. Individual participant data 

 meta-analyses were used to determine the associations between 

 adiposity phenotypes and CIMT in the pooled sample while 

 adjusted multivariable linear regression analyses were used for 

 site specific analyses. Results: Data were obtained from 9,010 

 adults (50.3% women and a mean age of 50$pm$ 6years). Men had 

 higher levels of visceral fat than women while women had higher 

 BMI, waist and hip circumference and subcutaneous fat than men 

 at all sites except Burkina Faso. In the pooled analyses, BMI 

 ($beta$-value [95% CIs]: 19.5 [16.8, 22.3] $mu$m) showed the 

 strongest relationship with CIMT followed by VAT (5.86 [4.65, 

 7.07] $mu$m), SCAT (5.00 [2.85, 7.15] $mu$m), WC (1.27 [1.09, 

 1.44] $mu$m) and HC (1.23 [1.04, 1.42] $mu$m). Stronger 

 associations were observed in men than in women. Conclusion: 

 Obesity within SSA will likely result in higher levels of 

 atherosclerosis and promote the occurrence of cardio- and 

 cerebrovascular events, especially in males, unless addressed 

 through primary prevention of obesity in both rural and urban 

 communities across Africa. The inverse association of VAT with 

 CIMT in Burkina Faso and Ghana requires further investigation. 

 Highlights: All adiposity phenotypes were positively associated 

 with common carotid intima-media thickness (CIMT) in the entire 

 cohort (pooled analyses).BMI had the strongest association with 

 CIMT compared to other phenotypes.The magnitude of association 

 between adiposity phenotypes and CIMT was higher in men than in 

 women.Subcutaneous adipose tissue was inversely associated with 

 CIMT only in women.An unexpected finding was the inverse 

 association of visceral adipose tissue with CIMT in Burkina Faso 

 and Ghana.},

note = {Copyright: © 2021 The Author(s).

PMID: 33833943 

PMCID: PMC7977036},

keywords = {adiposity, Adult, Body Mass Index, cardiovascular   disease, Carotid intima-media thickness, Cross-Sectional Studies, Female, Ghana, Humans, Male, Middle Aged, obesity, Obesity/complications/epidemiology, Phenotype, Risk Factors, sub-Saharan Africa, subclinical   atherosclerosis},

pubstate = {published},

tppubtype = {article}

}