16 research outputs found
Effects of cytochrome P450 2B6 and constitutive androstane receptor genetic variation on Efavirenz plasma concentrations among HIV patients in Kenya.
No full textThe effects of genetic variation of cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) on efavirenz (EFV) plasma concentration was evaluated among 312 HIV patients in Nairobi Kenya. The EFV plasma concentration at steady-state were determined using ultra-high-performance liquid chromatography with a tandem quadruple mass spectrometer (LC-MS/MS). Thirteen CYP2B6 (329G>T, 341T>C, 444 G>T/C, 15582C>T, 516G>T, 548T>G, 637T>C, 785A>G, 18492C>T, 835G>C, 1459C>T and 21563C>T) and one CAR (540C>T) single nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction. HIV drug resistance mutations were detected using an in-house genotypic assay. The EFV concentration of patients ranged from 4 ng/mL to 332697 ng/mL (median 2739.5 ng/mL, IQR 1878-4891.5 ng/mL). Overall, 22% patients had EFV concentrations beyond therapeutic range of 1000-4000 ng/mL (4.5%% 4000 ng/mL). Five SNPs (15582C>T, 516G>T, 785A>G, 983T>C and 21563C>T) were associated with higher EFV plasma concentration while 18492C>T with lower EFV plasma concentration (pT, 516G>T, 785A>G, 18492C>T, 983T>C, 21563C>T, 1459C>T and CAR 540C>T. Sixteen haplotypes were observed and CTGCTTCC, CTGCTTCT, TTGCTTCT and CGACCCCT were associated with high EFV plasma concentration. In multivariate analysis, factors significantly associated with EFV plasma concentration included; the presence of skin rash (β = 1379, 95% confidence interval (CI) = 3216.9-3416.3; p T (β = 1868.9, 95% CI 3216.9-3416.3; p C (β = 2638.3, 95% CI = 1348-3929; p T (β = 1737, 95% CI = 972.2-2681.9; p T, CYP2B6 983T>C, 21563C>T, presence of higher numbers of SNPs per patient and haplotypes CTGCTTCC, CTGCTTCT, TTGCTTCT and CGACCCCT could efficiently serves as genetic markers for EFV plasma concentration and could guide personalization of EFV based ART treatment in Kenya
Genetic diversity and evolutionary analysis of human respirovirus type 3 strains isolated in Kenya using complete hemagglutinin-neuraminidase (HN) gene.
No full textHuman respirovirus type 3 (HRV3) is a leading etiology of lower respiratory tract infections in young children and ranks only second to the human respiratory syncytial virus (HRSV). Despite the public health importance of HRV3, there is limited information about the genetic characteristics and diversity of these viruses in Kenya. To begin to address this gap, we analyzed 35 complete hemagglutinin-neuraminidase (HN) sequences of HRV3 strains isolated in Kenya between 2010 and 2013. Viral RNA was extracted from the isolates, and the entire HN gene amplified by RT-PCR followed by nucleotide sequencing. Phylogenetic analyses of the sequences revealed that all the Kenyan isolates grouped into genetic Cluster C; sub-clusters C1a, C2, and C3a. The majority (54%) of isolates belonged to sub-cluster C3a, followed by C2 (43%) and C1a (2.9%). Sequence analysis revealed high identities between the Kenyan isolates and the HRV3 prototype strain both at the amino acid (96.5-97.9%) and nucleotide (94.3-95.6%) levels. No amino acid variations affecting the catalytic/active sites of the HN glycoprotein were observed among the Kenyan isolates. Selection pressure analyses showed that the HN glycoprotein was evolving under positive selection. Evolutionary analyses revealed that the mean TMRCA for the HN sequence dataset was 1942 (95% HPD: 1928-1957), while the mean evolutionary rate was 4.65x10-4 nucleotide substitutions/site/year (95% HPD: 2.99x10-4 to 6.35x10-4). Overall, our results demonstrate the co-circulation of strains of cluster C HRV3 variants in Kenya during the study period. This is the first study to describe the genetic and molecular evolutionary aspects of HRV3 in Kenya using the complete HN gene
Diagnostic performance of a colorimetric RT -LAMP for the identification of SARS-CoV-2: A multicenter prospective clinical evaluation in sub-Saharan Africa
No full textManagement and control of the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus SARS-CoV-2 is critically dependent on quick and reliable identification of the virus in clinical specimens. Detection of viral RNA by a colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a simple, reliable and cost-effective assay, deployable in resource-limited settings (RLS). Our objective was to evaluate the intrinsic and extrinsic performances of RT-LAMP in RLS
Linkage disequilibrium analysis of 7 SNPs of CYP2B6 and 1 CAR.
No full textDark red squares: strong evidence of LD, dark yellow/orange squares: uninformative, light yellow squares: strong evidence of recombination. SNP1-15582C>T; SNP2 - 516G>T; SNP3 - 785A>G; SNP4-18492C>T; SNP5- 983T>C; SNP6-21563C>T; SNP7- 1459C>T and SNP8—CAR 540C>T. (PDF)</p
Summary of % distribution of presenting symptoms of patients with human respirovirus 3 infections in Kenya from June 2010 to June 2013.
No full textSummary of % distribution of presenting symptoms of patients with human respirovirus 3 infections in Kenya from June 2010 to June 2013.</p
The differences in log<sub>10</sub>-transformed EFV plasma concentrations by genotypes of 7 CYP2B6 and 1 CAR SNPs.
No full text15582C>T, 516G>T, 785A>G, 983T>C, 21563C>T and 18492C>T significantly influence EFV plasma concentration (pT and CAR 540C>T. (PDF)</p
Positively selected sites by at least two algorithms (in bold) on the HN gene of Kenyan HRV3 strains.
No full textPositively selected sites by at least two algorithms (in bold) on the HN gene of Kenyan HRV3 strains.</p
Allele and genotype frequencies of CYP2B6 gene and CAR SNPs and their relationship with EFV plasma concentrations.
No full textAllele and genotype frequencies of CYP2B6 gene and CAR SNPs and their relationship with EFV plasma concentrations.</p
Maximum Clade Credibility (MCC) tree of HRV3 strains based on complete HN coding sequences, constructed using the BEAST program.
No full textThe Kenyan strains are shown in blue. The numbers at the nodes represent posterior probability values.</p
Summary of patient demographics and clinical characteristics of patients.
No full textSummary of patient demographics and clinical characteristics of patients.</p
