23 results on '"Albert Dompreh"'
Search Results
2. Screening for
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Franziska, Weinreich, Felix, Weinreich, Andreas, Hahn, Ralf Matthias, Hagen, Holger, Rohde, Fred Stephen, Sarfo, Torsten, Feldt, Albert, Dompreh, Shadrack Osei, Asibey, Richard, Boateng, Hagen, Frickmann, and Kirsten Alexandra, Eberhardt
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Both
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- 2022
3. The Clinical Features and Immunological Signature of
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Fred Stephen, Sarfo, Albert, Dompreh, Shadrack Osei, Asibey, Richard, Boateng, Felix, Weinreich, Edmund Osei, Kuffour, Betty, Norman, Veronica, Di Cristanziano, Hagen, Frickmann, Torsten, Feldt, and Kirsten Alexandra, Eberhardt
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There is a paucity of information on the contemporary burden, disease patterns, and immunological profile of people living with HIV who are co-infected withFor this cross-sectional study, stool samples of 640 HIV-positive and 83 HIV-negative individuals in Ghana were tested forThe prevalence ofIn the modern post-combined antiretroviral therapy (cART) era, the acquisition of
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- 2022
4. Policy adherence and clinical effect of early infant diagnosis of HIV exposed children: impact on Elimination of mother to child transmission (EMTCT
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Anthony Enimil, Albert Dompreh, Augustina Appiah, Adwoa Konadu Owusu, and Charles Martyn-Dickens
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General Medicine - Abstract
BackgroundWorld Health Organizations aims to eliminate mother to child transmission of HIV by 2030. Timely HIV infant diagnostics are required to save the lives of HIV-infected babies which fits into Sustainable development goal 3 (Good health and wellbeing). This study reviews early infant diagnosis (EID) practices at Komfo Anokye Teaching Hospital from January 2020 to August 2021 to assess how this aligns with national policy and its impact on infected infants.MethodsEarly Infant diagnosis tests done on KATH samples were extracted focusing on age, gender, dates sample was drawn/ PCR test was done, and results of tests. Dates were converted to days since birth. Descriptive and inferential statistics were used with statistical significance at p< 0.05 ResultsA total of 400 infants had samples within study period. Test results were available for 98% (392). Data on gender was available for 37% (148) only. Positive results were 8.9% (35/392). By the time infants were sampled for storage, 24.5% (96/392) were within 6 weeks and 8.7% (34/392) were 9 months. The rest, 66.8% (262/392) deviated from protocol. By the time PCR test was done on stored samples, 5.6% (22/392) were within 6 weeks and 3.1% (12/392) were 9 months. The rest, 91.3% (358/392) deviated from protocol. Positive PCR results for deviated protocol was 8.9% (32/358)The median duration from birth to getting samples taken for positive EID case was 97 days compared to 52 days for negative results, p< 0.002. The median duration from birth to getting test results for positive EID case was 186 days compared to 88 days for negative results, p< 0.0002. ConclusionProtocol deviations from EMTCT policy due to delay in reporting contributes to positive EID results. Delay in testing affects start in treatment and negatively impacts neurodevelopment. Positive EID should be fully audited to identify risks.
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- 2022
5. A Comparative Study Between Nasopharyngeal/Oropharyngeal, Faecal and Saliva Viral Shedding In Ghanaian COVID-19 Patients attending Komfo Anokye Teaching Hospital (KATH), Kumasi from October – December, 2020
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Kwabena Adjei Asante, Lydia Sarponmaa Asante, Faustina Acheampong, Ernest Badu-Boateng, Albert Dompreh, Laud Anthony Basing Wihibeturo, Albert Adubofour, Chris Oppong, and Sylvia Karikari
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medicine.medical_specialty ,Saliva ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Internal medicine ,Sample (material) ,Medicine ,Sampling (medicine) ,Saliva sample ,Viral shedding ,business ,Feces - Abstract
BackgroundDiagnostic testing for the current SARS-CoV-2 infections involves the collection and testing of invasive pharyngeal specimens by qualified Health workers. Though fully clad in personal protective equipment, the concern is that sampling in close proximity to the patient poses as a major health hazard. The present study sought to verify if saliva or faeces could become a possible surrogate for pharyngeal samples for SARS-CoV 2 testing in suspected Ghanaian COVID-19 patients.ObjectivesTo ascertain if there is SARS-CoV 2 viral shedding in the saliva and faecal samples of Ghanaian COVID-19 patients, their sensitivity and specificity as compared to pharyngeal samples.MethodFifty (50) recruited COVID-19 patients who have been confirmed via RT-PCR using their nasopharyngeal/oropharyngeal samples and twenty (20) SARS-CoV 2 negative suspected patients each provided some faecal and saliva sample for RT-PCR analysis for SARS-CoV 2.ResultsForty-three (43) out of the fifty (50) COVID-19 patients recruited representing 86% tested positive for SARS-CoV 2 via their saliva sample whiles all their faecal samples tested positive for SARS-CoV 2 representing 100%. The sensitivity of saliva samples was 86% whiles the specificity was 100% but the sensitivity and specificity of the faecal samples were all 100%.ConclusionThere is indeed viral shedding of SARS-CoV 2 in the saliva and faeces of Ghanaian COVID-19 patients just like their counterparts in other parts of the world. Saliva and faeces could possibly become an alternative sample to the current in place of the invasive pharyngeal samples for SARS-CoV 2 testing in resource limited settings. Further research to explore this possibility at different testing sites with larger sample size is recommended.
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- 2021
6. Intestinal Colonization with
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Kirsten Alexandra, Eberhardt, Fred Stephen, Sarfo, Eva-Maria, Klupp, Albert, Dompreh, Veronica, Di Cristanziano, Edmund, Osei Kuffour, Richard, Boateng, Betty, Norman, Richard Odame, Phillips, Martin, Aepfelbacher, and Torsten, Feldt
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enteric infections ,Africa ,virus diseases ,epidemiology ,Whipple’s disease ,Sub-Sahara ,Article - Abstract
Background: Recent studies demonstrated higher prevalence rates of Tropheryma whipplei (T. whipplei) in HIV positive than in HIV negative subjects. However, associations with the immune status in HIV positive participants were conflicting. Methods: For this cross-sectional study, stool samples of 906 HIV positive and 98 HIV negative individuals in Ghana were tested for T. whipplei. Additionally, sociodemographic parameters, clinical symptoms, medical drug intake, and laboratory parameters were assessed. Results: The prevalence of T. whipplei was 5.85% in HIV positive and 2.04% in HIV negative participants. Within the group of HIV positive participants, the prevalence reached 7.18% in patients without co-trimoxazole prophylaxis, 10.26% in subjects with ART intake, and 12.31% in obese participants. Frequencies of clinical symptoms were not found to be higher in HIV positive T. whipplei carriers compared to T. whipplei negative participants. Markers of immune activation were lower in patients colonized with T. whipplei. Multivariate regression models demonstrated an independent relationship of a high CD4+ T cell count, a low HIV-1 viral load, and an obese body weight with the presence of T. whipplei. Conclusions: Among HIV positive individuals, T. whipplei colonization was associated with a better immune status but not with clinical consequences. Our data suggest that the withdrawal of co-trimoxazole chemoprophylaxis among people living with HIV on stable cART regimen may inadvertently increase the propensity towards colonization with T. whipplei.
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- 2021
7. Screening for Schistosoma spp. and Leishmania spp. DNA in Serum of Ghanaian Patients with Acquired Immunodeficiency
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Franziska Weinreich, Felix Weinreich, Andreas Hahn, Ralf Matthias Hagen, Holger Rohde, Fred Stephen Sarfo, Torsten Feldt, Albert Dompreh, Shadrack Osei Asibey, Richard Boateng, Hagen Frickmann, and Kirsten Alexandra Eberhardt
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Microbiology (medical) ,Infectious Diseases ,General Immunology and Microbiology ,schistosomiasis ,leishmaniasis ,HIV ,Ghana ,epidemiology ,molecular diagnosis ,Immunology and Allergy ,Molecular Biology - Abstract
Both Schistosoma spp. (species) and Leishmania spp. are prevalent in Ghana in West Africa. However, little is known about their local occurrence in immunocompromised individuals. In the study presented here, the real-time PCR-(polymerase chain reaction-)based screening for repetitive DNA (deoxyribonucleotide acid) sequences from the genomes of Leishmania (L.) spp. and Schistosoma (S.) spp. was performed in the serum of HIV-(human immunodeficiency virus-)infected Ghanaian patients. In 1083 assessed serum samples from HIV-positive and HIV-negative Ghanian patients, Leishmania spp.-specific DNA was not detected, while the diagnostic accuracy-adjusted prevalence estimation suggested a 3.6% prevalence of the S. mansoni complex and a 0.5% prevalence of the S. haematobium complex. Associations of schistosomiasis with younger age, as well as with the male sex, could be shown but not with an HIV status. Weakly significant signals for the associations of schistosomiasis with an increased viral load, reduced CD4+ (CD = cluster of differentiation) T cell count, and a reduced CD4+/CD8+ ratio could be observed but was inconsistently lost in the case of the stratification on the species complex level. So, it is concluded that factors other than HIV status are more likely to have influenced the occurrence of Schistosoma spp. infections in the assessed Ghanaian patients. Potential associations between HIV infection-associated factors, such as the viral load and the immune status of the patients, for which weak signals were observed in this hypothesis-forming retrospective assessment, should be confirmed by prospective, sufficiently powered investigations.
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- 2022
8. Population pharmacokinetics of efavirenz in HIV and TB/HIV coinfected children: the significance of genotype-guided dosing
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Sampson Antwi, Charles A. Peloquin, Albert Dompreh, Awewura Kwara, Hongmei Yang, Wael A. Alghamdi, Anthony Enimil, Taimour Y. Langaee, and Lubbe Wiesner
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Cyclopropanes ,Male ,0301 basic medicine ,Pharmacogenomic Variants ,Antitubercular Agents ,HIV Infections ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,Drug Interactions ,Pharmacology (medical) ,030212 general & internal medicine ,Child ,Prospective cohort study ,Original Research ,education.field_of_study ,Biological Variation, Individual ,Coinfection ,virus diseases ,Infectious Diseases ,Alkynes ,Child, Preschool ,Reverse Transcriptase Inhibitors ,Female ,Drug Monitoring ,medicine.drug ,Microbiology (medical) ,medicine.medical_specialty ,Tuberculosis ,Efavirenz ,Adolescent ,Genotype ,Anti-HIV Agents ,030106 microbiology ,Population ,03 medical and health sciences ,Pharmacokinetics ,Internal medicine ,Humans ,Dosing ,education ,Pharmacology ,business.industry ,Models, Theoretical ,medicine.disease ,Benzoxazines ,Pharmacogenomic Testing ,chemistry ,business ,Rifampicin - Abstract
Objectives The current WHO weight-based dosing recommendations for efavirenz result in a wide variability of drug exposure in children. Our objectives are to characterize the effects of rifampicin- and isoniazid-containing anti-TB therapy and CYP2B6 activity on efavirenz concentrations in children, using non-linear mixed-effects modelling. Methods This is a pharmacokinetic (PK) substudy of a prospective study that examined the interactions between anti-TB therapy and efavirenz in HIV-infected children with and without TB. PK samples were obtained 4 weeks after starting efavirenz (PK1) and repeated 4 weeks after completing TB therapy (PK2) in TB/HIV coinfected patients. Drug concentrations were measured using LC-MS/MS. Composite CYP2B6 516/983/15582 genotype was determined. Population PK modelling was performed in Monolix. Simulations were performed to obtain the predicted mid-dose concentrations (C12). Results One hundred and five HIV-infected Ghanaian children (46 with TB/HIV) were included. The median age and weight were 7 years and 19 kg. The efavirenz concentrations over time were adequately described using a one-compartment model. Weight, composite CYP2B6 genotype and PK visit had a significant influence on the PK parameters, while TB therapy had no significant effect. Simulations showed adequate C12 for intermediate composite CYP2B6 metabolizers only. Conclusions Our model showed that rifampicin- and isoniazid-containing anti-TB therapy does not influence efavirenz PK parameters. On the other hand, it describes the effect of efavirenz autoinduction after completing TB treatment. In addition, dosing efavirenz in children based only on weight results in a large variability in drug exposure. We propose dose adjustments for slow and extensive composite CYP2B6 metabolizers.
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- 2019
9. Pharmacogenetic predictors of nevirapine pharmacokinetics in Ghanaian children living with HIV with or without TB coinfection
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Hongmei Yang, Elizabeth Lima, Mohammad H. Al-Shaer, Charles A. Peloquin, Albert Dompreh, Awewura Kwara, Lubbe Wiesner, Taimour Y. Langaee, Wael A. Alghamdi, Yan Gong, Sampson Antwi, and Anthony Enimil
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0301 basic medicine ,Microbiology (medical) ,Oncology ,Male ,medicine.medical_specialty ,Nevirapine ,Anti-HIV Agents ,030106 microbiology ,HIV Infections ,Biology ,Microbiology ,Ghana ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Zidovudine ,Cmin ,Abacavir ,immune system diseases ,Internal medicine ,Genetics ,medicine ,Humans ,Tuberculosis ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Reverse-transcriptase inhibitor ,Coinfection ,Lamivudine ,virus diseases ,Infant ,medicine.disease ,Cytochrome P-450 CYP2B6 ,030104 developmental biology ,Infectious Diseases ,Pharmacogenetics ,Child, Preschool ,Reverse Transcriptase Inhibitors ,Female ,medicine.drug - Abstract
Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of human immunodeficiency virus (HIV) infection in children younger than 3 years old. Identifying genetic predictors of NVP pharmacokinetics (PK) in young children is important because inter-individual variability in NVP concentrations contributes to variable treatment response and the information may be used to individualize dosing decisions. We examined the relationship between genetic variations in relevant drug disposition genes and NVP PK parameters in Ghanaian children living with HIV eligible to initiate NVP-based antiretroviral therapy. Participants received NVP plus zidovudine and lamivudine or abacavir and lamivudine twice daily, and those with tuberculosis (TB) coinfection received concurrent anti-TB therapy with NVP. Pharmacokinetic sampling was performed after at least 4 weeks of antiretroviral therapy. Nevirapine minimum concentration (Cmin), area under the concentration-time curve from time 0 to 12 h (AUC0–12h), and apparent clearance (CL/F) were calculated using non-compartmental analysis using Phoenix v8.0 software. Genotyping for CYP2B6, CYP2A6, CYP3A5, ABCB1, NR1I2, and NR1I3 single nucleotide polymorphism (SNPs) was performed by TaqMan® allelic discrimination method. The median (range) NVP dose received was 10 (7–14) mg/kg. Of the 53 participants, the median (range) Cmin was 3.3 (0.0–14.0) mg/L and AUC0–12h was 56.0 (16.7–202.6) mg.hr/L. Using step-wise regression, CYP2B6 rs3745274 and NR1I2 rs6785049 SNPs were independent as well as joint predictors of NVP AUC0–12h, Cmin, and CL/F. We concluded that genotyping for CYP2B6 rs3745274, and the NR1I2 rs6785049 G > A SNP (which encodes the transcriptional factor, pregnane X receptor), could improve prediction of NVP PK for individualized therapy.
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- 2020
10. Evaluation of the Adequacy of the 2010 Revised World Health Organization Recommended Dosages of the First-line Antituberculosis Drugs for Children
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Charles A. Peloquin, Hongmei Yang, Eugene Adu Awhireng, Albert Dompreh, Maxwell Owusu, Awewura Kwara, Anthony Enimil, Lubbe Wiesner, Sampson Antwi, Fizza S. Gillani, and Antoinette Ortsin
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Male ,0301 basic medicine ,Microbiology (medical) ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Dose ,Arylamine N-Acetyltransferase ,030106 microbiology ,Antitubercular Agents ,Cmax ,HIV Infections ,Reference range ,World Health Organization ,Ghana ,Article ,03 medical and health sciences ,Pharmacokinetics ,Interquartile range ,polycyclic compounds ,medicine ,Humans ,Tuberculosis ,Prospective Studies ,Child ,Ethambutol ,Coinfection ,business.industry ,Isoniazid ,Infant ,Pyrazinamide ,Infectious Diseases ,Child, Preschool ,Practice Guidelines as Topic ,Pediatrics, Perinatology and Child Health ,Female ,Rifampin ,business ,medicine.drug - Abstract
BACKGROUND The World Health Organization recommended increased dosages of the first-line antituberculosis (anti-TB) drugs for children in 2010. We examined the frequency of and factors associated with low plasma maximum concentration (Cmax) of each drug in children treated with the revised dosages. METHODS Children on anti-TB therapy for at least 4 weeks underwent pharmacokinetic testing. Plasma Cmax below the lower limit of proposed reference range was considered low. Bivariate and multivariate analyses were used to examine the factors associated with low Cmax of each drug. RESULTS Of the 100 children, 58% were male, 50% HIV-infected and 49% younger than 5 years old. The median (interquartile range) Cmax was 5.9 (4.5-7.7) µg/mL for isoniazid, 6.5 (4.9-8.8) µg/mL for rifampin, 26.0 (21.2-33.4) µg/mL for pyrazinamide and 1.7 (0.9-2.7) µg/mL for ethambutol. There was a strong correlation between Cmax and AUC0-8h for all drugs. Low Cmax occurred in 9/100 (9.0%), 61/100 (61.0%), 17/97 (17.5%) and 60/97 (61.9%) for isoniazid, rifampin, pyrazinamide and ethambutol, respectively. In addition, 75/97 (77.3%) children had pyrazinamide Cmax < 35 µg/mL. Factors associated with low Cmax were NAT2 metabolizer phenotype status for isoniazid; height, dosage and HIV coinfection status for rifampin; height for pyrazinamide; and age, dosage and HIV coinfection status for ethambutol. CONCLUSIONS The high frequency of low rifampin and ethambutol Cmax in our study is consistent with emerging pharmacokinetic data in children treated according to the new WHO recommendations. Higher dosages than currently recommended especially for rifampin may be necessary in children.
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- 2018
11. Effect of First-Line Antituberculosis Therapy on Nevirapine Pharmacokinetics in Children Younger than Three Years Old
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Albert Dompreh, Awewura Kwara, Lubbe Wiesner, Charles A. Peloquin, Theresa Opoku, Fizza S. Gillani, David J. Greenblatt, Anthony Enimil, Jennifer Norman, Hongmei Yang, Sampson Antwi, Dennis Bosomtwe, Wael A. Alghamdi, Taimour Y. Langaee, Michael H. Court, and Antoinette Orstin
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Male ,medicine.medical_specialty ,Tuberculosis ,Nevirapine ,Multivariate analysis ,Genotype ,Anti-HIV Agents ,Antitubercular Agents ,HIV Infections ,Clinical Therapeutics ,03 medical and health sciences ,Cmin ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,Medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Pharmacology ,0303 health sciences ,030306 microbiology ,business.industry ,Coinfection ,Infant ,Liter ,medicine.disease ,Regimen ,Cytochrome P-450 CYP2B6 ,Infectious Diseases ,Child, Preschool ,Female ,business ,medicine.drug - Abstract
Nevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection. In the coinfected group, nevirapine PK was evaluated while on anti-TB therapy and after completing an anti-TB therapy regimen. Of 53 participants, 23 (43%) had TB-HIV coinfection. While the mean difference in nevirapine PK parameters between the two groups was not significant (P > 0.05), 14/23 (61%) of the children with TB-HIV coinfection and 9/30 (30%) with HIV infection had a nevirapine minimum concentration (C(min)) below the proposed target of 3.0 mg/liter (P = 0.03). In multivariate analysis, anti-TB therapy and the CYP2B6 516G>T genotype were joint predictors of nevirapine PK parameters. Differences in nevirapine PK parameters between the two groups were significant in children with CYP2B6 516GG but not the GT or TT genotype. Among 14 TB-HIV-coinfected participants with paired data, the geometric mean C(min) and area under the drug concentration-time curve from time zero to 12 h (AUC(0–12)) were about 34% lower when patients were taking anti-TB therapy, while the nevirapine apparent oral clearance (CL/F) was about 45% higher. While the induction effect of anti-TB therapy on nevirapine PK in our study was modest, the CYP2B6 genotype-dependent variability in the TB drug regimen effect would complicate any dose adjustment strategy in young children with TB-HIV coinfection. Alternate ART regimens that are more compatible with TB treatment in this age group are needed. (This study has been registered at ClinicalTrials.gov under identifier NCT01699633.)
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- 2019
12. Effect of Rifampin-Isoniazid-Containing Antituberculosis Therapy on Efavirenz Pharmacokinetics in HIV-Infected Children 3 to 14 Years Old
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Hongmei Yang, Anthony Enimil, Sampson Antwi, Charles A. Peloquin, Lubbe Wiesner, Antoinette Ortsin, Michael H. Court, Theresa Opoku, Jennifer Norman, Anima Sarfo, Fizza S. Gillani, Dennis Bosomtwe, David J. Greenblatt, Wael A. Alghamdi, Taimour Y. Langaee, Albert Dompreh, and Awewura Kwara
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Cyclopropanes ,Male ,drug-drug interactions ,Antitubercular Agents ,HIV Infections ,chemistry.chemical_compound ,immune system diseases ,Tandem Mass Spectrometry ,antituberculosis therapy ,heterocyclic compounds ,Drug Interactions ,Pharmacology (medical) ,Child ,0303 health sciences ,Coinfection ,Area under the curve ,virus diseases ,efavirenz ,3. Good health ,Infectious Diseases ,tuberculosis ,Anti-Retroviral Agents ,Alkynes ,Child, Preschool ,Reverse Transcriptase Inhibitors ,Female ,Rifampin ,medicine.medical_specialty ,Efavirenz ,Tuberculosis ,Adolescent ,tuberculosis coinfection ,Cmax ,Clinical Therapeutics ,03 medical and health sciences ,Cmin ,children ,Pharmacokinetics ,Internal medicine ,parasitic diseases ,Isoniazid ,medicine ,Humans ,Dosing ,Tuberculosis, Pulmonary ,Pharmacology ,030306 microbiology ,business.industry ,HIV ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Benzoxazines ,chemistry ,business ,Chromatography, Liquid - Abstract
We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments., We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments. The new World Health Organization-recommended antituberculosis drug dosages were used in the coinfected participants. Steady-state efavirenz concentrations after 4 weeks of antiretroviral therapy were measured using validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays. Pharmacokinetic parameters were calculated using noncompartmental analysis. Between groups, PK parameters were compared by Wilcoxon rank-sum test and within group by signed-rank test. Of the 105 participants, 43 (41.0%) had TB coinfection. Children with TB/HIV coinfection compared to those with HIV infection were younger, had lower median weight-for-age Z score, and received a higher median efavirenz weight-adjusted dose. Geometric mean (GM) efavirenz peak concentration (Cmax), concentration at 12 h (C12h), Cmin, and total area under the curve from time 0 to 24 h (AUC0–24h) values were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz C12h, Cmin, and AUC0–24h values were lower in TB/HIV-coinfected patients off anti-TB therapy than in the children with HIV infection or TB/HIV coinfection on anti-TB therapy. Efavirenz clearance was lower and AUC0–24h was higher on than in patients off anti-TB therapy. Reduced efavirenz clearance by first-line anti-TB therapy at the population level led to similar PK parameters in HIV-infected children with and without TB coinfection. Our findings do not support modification of efavirenz weight-band dosing guidelines based on TB coinfection status in children. (The study was registered with ClinicalTrials.gov under registration number NCT01704144.)
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- 2019
13. Sero-prevalence of Hepatitis B and C viral co-infections among HIV-1 infected ART-naïve individuals in Kumasi, Ghana
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Albert Dompreh, Patrick Williams Narkwa, Michael Owusu, Richard Boateng, Enoch Odame Anto, Mohamed Mutocheluh, and Dorcas Obiri-Yeboah
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0301 basic medicine ,Adult ,Male ,HBsAg ,Adolescent ,Science ,Hepatitis C virus ,030106 microbiology ,HIV Infections ,medicine.disease_cause ,Ghana ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Seroepidemiologic Studies ,Antiretroviral Therapy, Highly Active ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Hepatitis B virus ,Multidisciplinary ,business.industry ,Coinfection ,virus diseases ,Hepatitis B ,Middle Aged ,Viral Load ,medicine.disease ,Virology ,Hepatitis C ,digestive system diseases ,CD4 Lymphocyte Count ,HBeAg ,HIV-1 ,Medicine ,Female ,Viral hepatitis ,business ,Viral load - Abstract
BackgroundThe study assessed the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection paradigm among the human immunodeficiency virus (HIV) infected patients attending a tertiary hospital in Ghana. Also, the immunological and virological characterisation of these viruses, prior to antiretroviral therapy (ART) initiation was investigated.MethodA total of 400 HIV infected (HIV type-1) treatment naïve subjects ≥18 years were enrolled and tested for HBsAg and anti-HCV. Hepatitis B virus serological profile was performed on samples that were HBV positive. CD4+ T-cell count and HIV-1 RNA viral loads were determined using BD FacsCalibur analyzer (USA) and COBAS AmpliPrep/COBAS TaqMan Analyzer (USA) respectively.ResultsThe overall prevalence of HBV/HCV co-infection among the HIV-1 patients was 18.0%. The prevalence of HIV-HBV and HIV-HCV co-infections were 12.5% and 5.5% respectively. The prevalence of active viral hepatitis (HBeAg-positive) among HIV-HBV co-infected patients was 40%. None of the patients had anti-HBc IgM. HIV-HBV co-infection was associated with lower CD4+ T-cell count as well as higher HIV-1 viral load compared to both HIV mono- infection and HIV-HCV co- infection (pConclusionThe present study highlights the predominance of HBV exposure among the HIV infected patients in Ghana. HBV coinfection was associated with severe immunosuppression and higher HIV-1 viral load.
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- 2018
14. Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis
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Sampson Antwi, Xiaoli Tang, Ariel Topletz, A Enimil, Albert Dompreh, Awewura Kwara, Taimour Y. Langaee, Michael H. Court, Hongmei Yang, Eugene Adu Ahwireng, Charles A. Peloquin, and Jianlin Zhou
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0301 basic medicine ,Pharmacology ,biology ,business.industry ,030106 microbiology ,Isoniazid ,Single-nucleotide polymorphism ,biology.organism_classification ,Mycobacterium tuberculosis ,03 medical and health sciences ,Infectious Diseases ,Pharmacokinetics ,Genetic variation ,Genotype ,medicine ,biology.protein ,Pharmacology (medical) ,business ,SLCO1B1 ,Genotyping ,medicine.drug - Abstract
Isoniazid and rifampin are essential components of first-line antituberculosis (anti-TB) therapy. Understanding the relationship between genetic factors and the pharmacokinetics of these drugs could be useful in optimizing treatment outcomes, but this is understudied in children. We investigated the relationship between N-acetyltransferase type 2 ( NAT2 ) genotypes and isoniazid pharmacokinetics, as well as that between the solute carrier organic anion transporter family member 1B1 (encoded by SLCO1B1 ) and carboxylesterase 2 ( CES2 ) single nucleotide polymorphisms (SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental analysis. Genotyping of NAT2 , SLCO1B1 , and CES2 SNPs were performed using validated TaqMan genotyping assays. The Kruskal-Wallis test was used to compare pharmacokinetic parameters among the three genotypic groups and was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children with a slow acetylator phenotype but not the rapid genotype. For rifampin, only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics. Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have minimal clinical utility in dosing decisions at the population level in Ghanaian children, but it could be useful at the individual level or in populations that have a high frequency of implicated genotypes. Further studies in other populations are warranted.
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- 2018
15. Evaluation of the Adequacy of WHO Revised Dosages of the First-Line Antituberculosis Drugs in Children with Tuberculosis Using Population Pharmacokinetic Modeling and Simulations
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Lubbe Wiesner, Abdullah Alsultan, Albert Dompreh, Awewura Kwara, Hongmei Yang, Yasuhiro Horita, Charles A. Peloquin, A Enimil, Sampson Antwi, and Antoinette Ortsin
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0301 basic medicine ,Drug ,Male ,medicine.medical_specialty ,Tuberculosis ,media_common.quotation_subject ,030106 microbiology ,Population ,Cmax ,Antitubercular Agents ,India ,World Health Organization ,Ghana ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,education ,Child ,Ethambutol ,media_common ,Pharmacology ,education.field_of_study ,business.industry ,Isoniazid ,Bayes Theorem ,Pyrazinamide ,medicine.disease ,Infectious Diseases ,Area Under Curve ,Child, Preschool ,Female ,France ,business ,medicine.drug - Abstract
Optimal doses for antituberculosis (anti-TB) drugs in children have yet to be established. In 2010, the World Health Organization (WHO) recommended revised dosages of the first-line anti-TB drugs for children. Pharmacokinetic (PK) studies that investigated the adequacy of the WHO revised dosages to date have yielded conflicting results. We performed population PK modeling using data from one of these studies to identify optimal dosage ranges. Ghanaian children with tuberculosis on recommended therapy with rifampin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods. Nonlinear mixed-effects models were applied to describe the population PK of those drugs using MonolixSuite2016R1 (Lixoft, France). Bayesian estimation was performed, the correlation coefficient, bias, and precision between the observed and predicted areas under the concentration-time curve (AUCs) were calculated, and Bland-Altman plots were analyzed. The population PK of RIF and PZA was described by a one-compartment model and that for INH and EMB by a two-compartment model. Plasma maximum concentration (C(max)) and AUC targets were based on published results for children from India. The lowest target values for pediatric TB patients were attainable at the WHO-recommended dosage schedule for RIF and INH, except for N-acetyltransferase 2 non-slow acetylators (rapid and intermediate acetylators) in the lower-weight bands. However, higher published adult targets were not attainable for RIF and INH. The targets were not achieved for PZA and EMB. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.)
- Published
- 2018
16. Effect of Genetic Variation of
- Author
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Albert, Dompreh, Xiaoli, Tang, Jianlin, Zhou, Hongmei, Yang, Ariel, Topletz, Eugene, Adu Ahwireng, Sampson, Antwi, Antony, Enimil, Taimour, Langaee, Charles A, Peloquin, Michael H, Court, and Awewura, Kwara
- Subjects
Male ,Genotype ,Arylamine N-Acetyltransferase ,Liver-Specific Organic Anion Transporter 1 ,Antitubercular Agents ,Gene Expression ,Mycobacterium tuberculosis ,Clinical Therapeutics ,Polymorphism, Single Nucleotide ,Drug Administration Schedule ,Statistics, Nonparametric ,Carboxylesterase ,Area Under Curve ,Child, Preschool ,Isoniazid ,Humans ,Female ,Rifampin ,Child ,Tuberculosis, Pulmonary ,Biotransformation - Abstract
Isoniazid and rifampin are essential components of first-line antituberculosis (anti-TB) therapy. Understanding the relationship between genetic factors and the pharmacokinetics of these drugs could be useful in optimizing treatment outcomes, but this is understudied in children. We investigated the relationship between N-acetyltransferase type 2 (NAT2) genotypes and isoniazid pharmacokinetics, as well as that between the solute carrier organic anion transporter family member 1B1 (encoded by SLCO1B1) and carboxylesterase 2 (CES2) single nucleotide polymorphisms (SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental analysis. Genotyping of NAT2, SLCO1B1, and CES2 SNPs were performed using validated TaqMan genotyping assays. The Kruskal-Wallis test was used to compare pharmacokinetic parameters among the three genotypic groups and was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children with a slow acetylator phenotype but not the rapid genotype. For rifampin, only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics. Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have minimal clinical utility in dosing decisions at the population level in Ghanaian children, but it could be useful at the individual level or in populations that have a high frequency of implicated genotypes. Further studies in other populations are warranted.
- Published
- 2017
17. Helicobacter pyloriCoinfection Is Associated With Decreased Markers of Immune Activation in ART-Naive HIV-Positive and in HIV-Negative Individuals in Ghana
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Richard Phillips, Gerd D. Burchard, Anna Maria Eis-Hübinger, Marei Schachscheider, George Bedu-Addo, Christof Geldmacher, Jan Felix Drexler, Fred Stephen Sarfo, Betty Norman, Torsten Feldt, Mareike Soltau, Kirsten Alexandra Eberhardt, Albert Dompreh, Edmund Osei Kuffour, and Dieter Häussinger
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Microbiology (medical) ,HIV Infections ,CD38 ,Ghana ,Helicobacter Infections ,Flow cytometry ,Young Adult ,Immune system ,Acquired immunodeficiency syndrome (AIDS) ,T-Lymphocyte Subsets ,medicine ,Humans ,medicine.diagnostic_test ,biology ,Coinfection ,business.industry ,Middle Aged ,Helicobacter pylori ,medicine.disease ,biology.organism_classification ,Cross-Sectional Studies ,Infectious Diseases ,Immunology ,Female ,business ,Viral load ,Biomarkers ,CD8 - Abstract
Background Helicobacter pylori coinfection in human immunodeficiency virus (HIV) patients has been associated with higher CD4+ cell counts and lower HIV-1 viral loads, with the underlying mechanisms being unknown. The objective of this study was to investigate the impact of H. pylori infection on markers of T-cell activation in HIV-positive and HIV-negative individuals. Methods In a cross-sectional, observational study, HIV patients (n = 457) and HIV-negative blood donors (n = 79) presenting to an HIV clinic in Ghana were enrolled. Data on clinical and sociodemographic parameters, CD4+/CD8+ T-cell counts, and HIV-1 viral load were recorded. Helicobacter pylori status was tested using a stool antigen test. Cell surface and intracellular markers related to T-cell immune activation and turnover were quantified by flow cytometry and compared according to HIV and H. pylori status. Results Helicobacter pylori infection was associated with decreased markers of CD4+ T-cell activation (HLA-DR+CD38+CD4+; 22.55% vs 32.70%; P = .002), cell proliferation (Ki67; 15.10% vs 26.80%; P = .016), and immune exhaustion (PD-1; 32.45% vs 40.00%; P = .005) in 243 antiretroviral therapy (ART)-naive patients, but not in 214 patients on ART. In HIV-negative individuals, H. pylori infection was associated with decreased frequencies of activated CD4+ and CD8+ T cells (6.31% vs 10.40%; P = .014 and 18.70% vs 34.85%, P = .006, respectively). Conclusions Our findings suggest that H. pylori coinfection effectuates a systemic immune modulatory effect with decreased T-cell activation in HIV-positive, ART-naive patients but also in HIV-negative individuals. This finding might, in part, explain the observed association of H. pylori infection with favorable parameters of HIV disease progression. Clinical trials registration Clinicaltrials.gov NCT01897909.
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- 2015
18. Pharmacokinetics of the First-Line Antituberculosis Drugs in Ghanaian Children with Tuberculosis with or without HIV Coinfection
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Sampson Antwi, Antoinette Orstin, Theresa Opoku, Anthony Enimil, Lubbe Wiesner, Daniel Ansong, Fizza S. Gillani, Dennis Bosomtwe, Charles A. Peloquin, Hongmei Yang, Jennifer Norman, Albert Dompreh, Awewura Kwara, and Anima Sarfo
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Male ,0301 basic medicine ,Drug ,medicine.medical_specialty ,Tuberculosis ,media_common.quotation_subject ,030106 microbiology ,Antitubercular Agents ,HIV Infections ,Pharmacology ,03 medical and health sciences ,Pharmacokinetics ,Internal medicine ,Isoniazid ,medicine ,Humans ,Pharmacology (medical) ,Risk factor ,Child ,Ethambutol ,media_common ,AIDS-Related Opportunistic Infections ,Coinfection ,business.industry ,Pyrazinamide ,medicine.disease ,Infectious Diseases ,Child, Preschool ,Female ,Rifampin ,business ,medicine.drug - Abstract
Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with TB with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide, and ethambutol for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods and pharmacokinetic parameters calculated using noncompartmental analysis. The area under the concentration-time curve from 0 to 8 h (AUC 0–8 ), maximum concentration ( C max ), and apparent oral clearance divided by bioavailability (CL/F) for each drug were compared between children with and without HIV coinfection. Of 113 participants, 59 (52.2%) had HIV coinfection. The baseline characteristics were similar except that the coinfected patients were more likely to have lower weight-for-age and height-for-age Z scores ( P < 0.05). Rifampin, pyrazinamide, and ethambutol median body weight-normalized CL/F values were significantly higher, whereas the plasma AUC 0–8 values were lower, in the coinfected children than in those with TB alone. In the multivariate analysis, drug dose and HIV coinfection jointly influenced the apparent oral clearance and AUC 0–8 for rifampin, pyrazinamide, and ethambutol. Isoniazid pharmacokinetics were not different by HIV coinfection status. HIV coinfection was associated with lower plasma exposure of three of the four first-line anti-TB drugs in children. Whether TB/HIV-coinfected children need higher dosages of rifampin, pyrazinamide, and ethambutol requires further investigation. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.)
- Published
- 2017
19. Helicobacter pylori Infection Is Associated with Higher CD4 T Cell Counts and Lower HIV-1 Viral Loads in ART-Naïve HIV-Positive Patients in Ghana
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Gerd D. Burchard, Kirsten Alexandra Eberhardt, Edmund Osei Kuffour, Richard Phillips, Dieter Häussinger, Emelia Efua Oteng-Seifah, Marei Schachscheider, Fred Stephen Sarfo, Betty Norman, Mareike Soltau, George Bedu-Addo, Albert Dompreh, Anna Maria Eis-Hübinger, Jan Felix Drexler, and Torsten Feldt
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Adult ,Male ,medicine.drug_class ,medicine.medical_treatment ,T cell ,Antibiotics ,CD4-CD8 Ratio ,lcsh:Medicine ,HIV Infections ,Ghana ,Helicobacter Infections ,Young Adult ,Risk Factors ,Antiretroviral Therapy, Highly Active ,medicine ,Prevalence ,Humans ,Young adult ,lcsh:Science ,Multidisciplinary ,biology ,Helicobacter pylori ,business.industry ,Coinfection ,lcsh:R ,Immunosuppression ,Middle Aged ,Viral Load ,medicine.disease ,biology.organism_classification ,CD4 Lymphocyte Count ,medicine.anatomical_structure ,Socioeconomic Factors ,Immunology ,HIV-1 ,lcsh:Q ,Female ,business ,Viral load ,Research Article - Abstract
Background Worldwide, there is a high co-endemicity of HIV and H. pylori infection and there is growing evidence that H. pylori co-infection is associated with parameters of HIV disease progression. The objective of this study was to investigate the prevalence of H. pylori infection, and the association with clinical, immunological and virological parameters in a large cohort of HIV-infected individuals and uninfected controls in a West African country. Methods HIV-patients (n = 1,095) and HIV-negative individuals (n = 107) were recruited at a university hospital in Ghana. H. pylori status was determined using stool antigen testing. HIV-related, clinical and socio-demographic parameters were recorded and analyzed according to H. pylori status. Results The prevalence of H. pylori infection was significantly lower in HIV-positive compared to HIV-negative individuals (51.5 vs. 88%, p
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- 2015
20. GB virus C genotype 1 is rarely transmitted vertically but acquired during infancy in West Africa
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Chengyao Li, Emmanuel Addo-Yobo, Francis Sarkodie, Albert Dompreh, Shirley Owusu-Ofori, Jean-Pierre Allain, and K. A. Danso
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Adult ,Veterinary medicine ,Genotype ,Hepatitis, Viral, Human ,Immunology ,Population ,GB virus C ,Ghana ,Virus ,West africa ,law.invention ,Pregnancy ,law ,Humans ,Immunology and Allergy ,Medicine ,Pregnancy Complications, Infectious ,education ,education.field_of_study ,biology ,business.industry ,Infant, Newborn ,Infant ,Flaviviridae Infections ,Viral Load ,Fetal Blood ,biology.organism_classification ,Virology ,Infectious Disease Transmission, Vertical ,Infectious Diseases ,Transmission (mechanics) ,Child, Preschool ,Female ,business ,Viral load ,Horizontal transmission - Abstract
Paired Ghanaian plasma and cord blood from pregnant women, alongside plasma samples from children aged 1 day to 70 months, were tested for GBV-C, HIV-1 RNA loads and anti-E2. Frequency of GBV-C vertical transmission in West Africa is significantly lower than in Europe, the USA or East Asia where genotype 2 or 3 is prevalent. While horizontal transmission appears predominant in West Africa, the lower viral load of African genotype 1 might explain limited vertical transmission.
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- 2006
21. GB virus C and HIV-1 RNA load in single virus and co-infected West African individuals
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K. A. Danso, Paul Collini, Shirley Owusu-Ofori, Ohene Opare-Sem, Chengyao Li, Jean-Pierre Allain, Daniel Candotti, and Albert Dompreh
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Adult ,Adolescent ,Hepatitis, Viral, Human ,Immunology ,Population ,Viremia ,GB virus C ,HIV Infections ,Ghana ,Virus ,Pregnancy ,medicine ,Prevalence ,Immunology and Allergy ,Humans ,Pregnancy Complications, Infectious ,education ,Child ,Aged ,education.field_of_study ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Infant, Newborn ,virus diseases ,RNA ,Infant ,RNA virus ,Flaviviridae Infections ,Middle Aged ,Viral Load ,biology.organism_classification ,medicine.disease ,Virology ,Infectious Diseases ,Child, Preschool ,Lentivirus ,HIV-1 ,RNA, Viral ,Female ,Viral load - Abstract
Background: Investigations on the impact of GB virus C (GBV-C) co-infection on HIV disease progression relied essentially on clinical follow-up but not on virologic parameters. Objectives: To detect and quantify GBV-C RNA in West African populations co-infected or not with HIV-1 and to correlate the RNA load of HIV-1 and GBV-C in co-replicating patients with different clinical conditions. Methods: Three Ghanaian populations (blood donors, pregnant women and HIV-infected patients) were subdivided into six groups according to HIV-1 and clinical status and GBV-C and HIV-1 RNA load was tested by quantitative real time reverse transcriptase-polymerase chain reaction. In one population with HIV-1 disease, CD4+ cell count was also measured. Results: Prevalence of GBV-C markers in HIV-1-infected groups and HIV-1 non-infected pregnant women were significantly higher than in healthy blood donors. Similar levels and distribution of GBV-C RNA load were found in each population irrespective of HIV-1 status except for a lower GBV-C RNA load in AIDS patients. There was a significant shift of HIV-1 load towards lower value when GBV-C RNA was present and a trend towards an inverse correlation between HIV-1 and GBV-C RNA load. A positive correlation between CD4+ cell count and GBV-C RNA load in symptomatic HIV-1-infected patients was observed. Conclusions: The moderate impact of GBV-C on HIV-1 viremia is unlikely to entirely account for a favourable clinical outcome of replicating co-infections.
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- 2006
22. Maternal-fetal transmission of human parvovirus B19 genotype 3
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Jean-Pierre Allain, Armen Parsyan, Albert Dompreh, K. A. Danso, and Daniel Candotti
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Genotype ,viruses ,Umbilical cord ,Virus ,Immunoglobulin G ,Parvoviridae Infections ,Pregnancy ,Seroepidemiologic Studies ,hemic and lymphatic diseases ,medicine ,Parvovirus B19, Human ,Immunology and Allergy ,Seroprevalence ,Humans ,Pregnancy Complications, Infectious ,Fetus ,biology ,Infant, Newborn ,virus diseases ,Viral Load ,Virology ,Infectious Disease Transmission, Vertical ,Infectious Diseases ,medicine.anatomical_structure ,DNA, Viral ,biology.protein ,Female ,Antibody ,Viral load - Abstract
Plasma samples obtained at delivery from 885 pregnant Ghanaian women were tested for human parvovirus B19 DNA and B19-specific antibodies. Maternal-fetal transmission was evaluated by testing paired maternal plasma and umbilical cord blood samples, as well as newborn whole-blood samples when they were available. The B19 DNA seroprevalence rate in women was 1.8% (94% had genotype 3 strains), and the immunoglobulin G (IgG) seroprevalence rate in women was 81%. Two of 3 cases of primary maternal B19 infection resulted in fetal transmission. Coexistence of B19 DNA and B19-specific IgG (persistence) was detected in 13 women (1.5%), but no transmission of the virus was observed. Contrary to the situation in pregnant women with primary B19 infection and high viral loads, pregnant women with low viral loads and B19-specific IgG do not appear to be vertically infectious.
- Published
- 2006
23. Vertical transmission of HIV in Ghanaian women diagnosed in cord blood and post-natal samples
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Albert Dompreh, Victor Addo, Jean-Pierre Allain, K. A. Danso, Lars R. Haaheim, and Lucia Fischetti
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Molecular Sequence Data ,HIV Infections ,Viral quasispecies ,Ghana ,Virus ,Pregnancy ,Virology ,Prevalence ,Medicine ,Humans ,Pregnancy Complications, Infectious ,Phylogeny ,biology ,business.industry ,Transmission (medicine) ,Infant, Newborn ,virus diseases ,Sequence Analysis, DNA ,Viral Load ,medicine.disease ,biology.organism_classification ,Fetal Blood ,Infectious Disease Transmission, Vertical ,Infectious Diseases ,Cord blood ,Lentivirus ,HIV-1 ,Gestation ,RNA, Viral ,Female ,business ,Viral load - Abstract
HIV RNA detection in the newborn is the main diagnostic tool for vertical transmission. Most infections are thought to occur peri- or post-natally, hence preventive antiviral therapy administered days before and during delivery. This study used cord blood for molecular diagnosis, examined viral load and HIV-1 subtypes as determinants of transmission, and compared molecular variability of maternal, cord blood, and post-natal quasispecies. Ninety-seven seropositive mother-cord blood paired plasmas from Ghana were tested for HIV RNA. Viral load was quantified and a subgroup of 45 random women samples was typed and subtyped. HIV-1 from infected pairs was cloned, sequenced, and analyzed phylogenetically. The prevalence of HIV infection in pregnant women was 3.3%. 13/97 cord blood samples (13.5%) contained HIV RNA. No correlation between either viral load at labor (range 10(3)-10(7)) or HIV-1 subtype and in utero transmission was found. In both transmitting and non-transmitting mothers, 56% of HIV-1 strains were CRF02_AG. In three pairs, maternal and cord blood quasispecies were closely related, suggesting late pregnancy or perinatal transmission, while in four pairs, genetic distances suggested transmission earlier during gestation. Maternal viral load and genotype did not correlate with HIV-1 pre-natal transmission. HIV infection during gestation appears relatively frequent.
- Published
- 2005
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