A descriptive study of the single-nucleotide polymorphisms known to affect the Tacrolimus trough concentration per dose, among a population of kidney failure patients in a tertiary hospital in Ghana.

BACKGROUND: The burden of chronic kidney disease (CKD) and kidney failure in Ghana is on the ascendency, with the prevalence of CKD estimated at 13.3%. Patients with CKD who progress to kidney failure require life sustaining kidney replacement therapy (KRT) which is almost exclusively available in Ghana as haemodialysis. Kidney transplantation is considered the best KRT option for patients with irreversible kidney failure due to its relative cost efficiency as well as its superiority in terms of survival and quality of life. However, because transplants may trigger an immune response with potential organ rejection, immunosuppressants such as tacrolimus dosing are required. OBJECTIVE: This study sought to determine single nucleotide polymorphisms in CYP3A5, CYP3A4 and MDR1 genes that affect the pharmacokinetics of Tacrolimus in a population of Ghanaian patients with kidney failure. METHOD: This cross-sectional study comprised of 82 kidney failure patients undergoing maintenance haemodialysis at the Renal and Dialysis unit of Korle-Bu Teaching Hospital (KBTH). Clinical and demographic data were collected and genomic DNA isolated. Samples were genotyped for specific SNPs using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Participants, 58/82 (70.73%) harbored the wildtype CYP3A5*1/*1 AA genotype, 20/82 (24.39%) carried the heterozygous CYP3A5*1/*3 AG genotype, and 4/82 (4.88%) had the homozygous mutant CYP3A5*3/*3 GG genotype. Also, 6/82 (7.32%) carried the wildtype AA genotype, 11/82 (13.41%) had the heterozygous AG genotype, and 65/82 (79.27%) harbored the homozygous mutant GG genotype of CYP3A4*1B (-290 A>G). For MDR1_Ex21 (2677 G>T), 81/82 (98.78%) carried the wildtype GG genotype, while 1/82 (1.22%) had the heterozygous GT genotype. For MDR1_Ex26 (3435 C>T), 63/82 (76.83%) had the wildtype CC genotype, while 18/82 (21.95%) carried the heterozygous CT genotype, and 1/82 (1.22%) harbored the mutant TT genotype. CONCLUSION: SNPs in CYP3A4, CYP3A5, and MDR1 genes in a population of Ghanaian kidney failure patients were described. The varying SNPs of the featured genes suggest the need to consider the genetic status of Ghanaians kidney failure patients prior to transplantation and tacrolimus therapy.

Quality of Life after Mastectomy with or without Breast Reconstruction and Breast-Conserving Surgery in Breast Cancer Survivors: A Cross-Sectional Study at a Tertiary Hospital in Ghana.

(1) Background: Breast cancer is the leading malignancy worldwide, and in Ghana, it has a poor overall survival rate. However, approximately 50% of cases are cases of early-stage disease, and with advances in breast cancer treatment and improvements in survival, quality of life (QOL) is becoming as important as the treatment of the disease. (2) Methodology: This was a cross-sectional study of survivors who had breast-conserving surgery (BCS), mastectomy only (M) and mastectomy with breast reconstruction (BRS) from 2016 to 2020 at a tertiary hospital in Ghana, comparatively assessing their QOL using EORTC QLQ C-30 and EORTC QLQ BR-23. (3) Results: The study participants had an overall global health status (GHS) median score of 83.3 [IQR: 66.7-91.7] with no significant differences between the surgery types. The BRS group had statistically significant lower median scores for the functional scale (82.8 and 51.0) and the highest scores for the symptomatic scale (15.7 and 16.5). Body image was significantly lowest for the BRS group (83.3) [68.8-91.7] and highest (100) [91.7-100] for the BCS group (p < 0.001). (4) Conclusion: There is a need to develop support systems tailored at improving the QOL of breast cancer survivors taking into consideration the type of surgery performed.

Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria in Ghana. Artemisinin (ART) tolerance in Plasmodium falciparum has arisen in Southeast Asia and recently, in parts of East Africa. This is ascribed to the survival of ring-stage parasites post treatment. The present study sought to assess and characterize correlates of potential ART tolerance based on post-treatment parasite clearance, ex vivo and in vitro drug sensitivity, and molecular markers of drug resistance in P. falciparum isolates from children with uncomplicated malaria in Ghana. METHODS: Six months to fourteen years old children presenting with acute uncomplicated malaria (n = 115) were enrolled in two hospitals and a Health Centre in Ghana's Greater Accra region and treated with artemether-lumefantrine (AL) according to body weight. Pre- and post-treatment parasitaemia (day 0 and day 3) was confirmed by microscopy. The ex vivo ring-stage survival assay (RSA) was used to detect percent ring survival while the 72 h SYBR Green I assay was used to measure the 50% inhibition concentration (IC50s) of ART and its derivatives and partner drugs. Genetic markers of drug tolerance /resistance were evaluated using selective whole genome sequencing. RESULTS: Of the total of 115 participants, 85 were successfully followed up on day 3 post-treatment and 2/85 (2.4%) had parasitaemia. The IC50 values of ART, artesunate (AS), artemether (AM), dihydroartemisinin (DHA), amodiaquine (AQ), and lumefantrine (LUM) were not indicative of drug tolerance. However, 7/90 (7.8%) pre-treatment isolates had > 10% ring survival rates against DHA. Of the four isolates (2 RSA positive and 2 RSA negative) with high genomic coverage, P. falciparum (Pf) kelch 13 K188* and Pfcoronin V424I mutations were only present in the two RSA positive isolates with > 10% ring survival rates. CONCLUSIONS: The observed low proportion of participants with day-3 post-treatment parasitaemia is consistent with rapid ART clearance. However, the increased rates of survival observed in the ex vivo RSA against DHA, maybe a pointer of an early start of ART tolerance. Furthermore, the role of two novel mutations in PfK13 and Pfcoronin genes, harboured by the two RSA positive isolates that had high ring survival in the present study, remains to be elucidated.

Antibiotic use in a tertiary healthcare facility in Ghana: a point prevalence survey.

Background: The global rise and spread of antibiotic resistance is limiting the usefulness of antibiotics in the prevention and treatment of infectious diseases. The use of antibiotic stewardship programs guided by local data on prescribing practices is a useful strategy to control and reduce antibiotic resistance. Our objective in this study was to determine the prevalence and indications for use of antibiotics at the Korle-Bu Teaching Hospital Accra, Ghana. Methods: An antibiotic point prevalence survey was conducted among inpatients of the Korle-Bu Teaching Hospital between February and March 2016. Folders and treatment charts of patients on admission at participating departments were reviewed for antibiotics administered or scheduled to be administered on the day of the survey. Data on indication for use were also collected. Prevalence of antibiotic use was determined by dividing the number of inpatients on antibiotics at the time of survey by the total number of patients on admission. Results: Of the 677 inpatients surveyed, 348 (51.4%, 95% CI, 47.6-55.2) were on treatment with antibiotics. Prevalence was highest among Paediatric surgery where 20/22 patients (90.9%, 95% CI, 70.8-98.9) were administered antibiotics and lowest among Obstetrics patients with 77/214 (36%, 95% CI, 29.5-42.8). The indications for antibiotic use were 245/611 (40.1%) for community-acquired infections, 205/611 (33.6%) for surgical prophylaxis, 129/611 (21.1%) for healthcare associated infections and 33/611 (5.4%) for medical prophylaxis. The top five antibiotics prescribed in the hospital were metronidazole 107 (17.5%), amoxicillin-clavulinic acid 82 (13.4%), ceftriaxone 17(12.1%), cefuroxime 61 (10.0%), and cloxacillin 52 (8.5%) respectively. Prevalence of meropenem and vancomycin use was 12(2%) and 1 (.2%) respectively. The majority of patients 181 (52%) were being treated with two antibiotics. Conclusion: This study indicated a high prevalence of antibiotic use among inpatients at the Korle-Bu Teaching Hospital. Metronidazole was the most commonly used antibiotic; mainly for surgical prophylaxis. There is the need to further explore factors contributing to the high prevalence of antibiotic use and develop strategies for appropriate antibiotic use in the hospital.

Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population.

BACKGROUND: Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR. Influence of patient specific factors and gene variations within VKORC1, CYP2C9 and CYP4F2 were determined in patients on either high or low warfarin maintenance dose. RESULTS: One hundred and forty-one patients took part in the study with 79 (56%) participants being Female. The median age of the study participants was 48 years [IQR: 34-58]. The median duration for patients to be on warfarin therapy was 24 months [IQR: 10-72]. Majority of the study participants (80.9%, n = 114) did not have any side effects to warfarin. CYP2C9*2 and CYP2C9*3 variant alleles were not detected. VKORC1 variant allele was observed at 6% and CYP4F2 variant allele was observed at 41%. Duration of patients on warfarin therapy was marginally associated with high warfarin dose (adjusted OR = 1.01 [95% CI 1.00-1.02], p = 0.033) while the odds of heterozygous individuals (G/A) for VKORC1 gene to have high warfarin dose compared to persons with homozygous (G/G) (adjusted OR = 0.06 [95% CI 0.01-0.63], p = 0.019). Age, gender, diagnosis, presence of side effects and other medications were not associated with warfarin dose (p = 0.05). CONCLUSION: This study provides data on VKORC1 and CYP4F2 variants among an indigenous African population. Duration of patients on warfarin therapy was marginally associated with high warfarin dose. CYP2C9*2 and *3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians.