South African Medical Journal (SAMJ)
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Impact of donor CYP3A5 genotype on pharmacokinetics of tacrolimus in South African paediatric liver transplant patients
Get PDFBackground. In the paediatric liver transplant programme in Johannesburg, South Africa (SA), tacrolimus is the calcineurin inhibitor of choice, comprising an essential component of the immunosuppression regimen. It is characterised by a narrow therapeutic index and wide interpatient variability, necessitating therapeutic drug monitoring of whole-blood concentrations. Pharmacogenetic research, although not representative of SA population groups, suggests that single-nucleotide polymorphisms within the cytochrome P450 3A5 (CYP3A5) gene contribute to the variability in tacrolimus dosing requirements. The rs776746 polymorphism, CYP3A5*3, results in a splice defect and a non-functional enzyme. Clinically, to reach the same tacrolimus concentration-to-dose ratio (CDR), expressors (CYP3A5*1/*1 and *1/*3) require a higher tacrolimus dose than non-expressors (*3/*3).
Objectives. To compare the pharmacokinetics of tacrolimus in paediatric liver transplant recipients with their donors’ CYP3A5 genotypes, considering both donor and recipient characteristics.
Methods. Blood samples from 46 living liver donors were collected, their genomic DNA was extracted, and their CYP3A5 genotype was established (polymerase chain reaction and restriction fragment length polymorphism analysis, validated by Sanger sequencing). The relationship of donor and recipient characteristics with the mean tacrolimus CDR was analysed using a general linear model. Non- confounding significant variables were included in a multiple regression model.
Results. The study showed that all expressor donors genotyped as CYP3A5*1/*1 were of black African self-reported race and ethnicity. During the first 15 days post-transplant, we found that children who received grafts from donor CYP3A5 expressors (CYP3A5*1/*1 and *1/*3) had significantly lower mean tacrolimus CDRs compared with those who received grafts from donor CYP3A5 non-expressors (*3/*3); the recipients of CYP3A5 expressor grafts therefore require higher doses of oral tacrolimus to achieve the same therapeutic target range. In addition, graft-to-recipient weight ratio and the CYP3A5 donor genotypes were independent factors that significantly (p<0.05) affected mean tacrolimus CDRs in recipients.
Conclusion. In this study, we showed that all CYP3A5*1 homozygote donors were of black African self-reported race and ethnicity, and tacrolimus CDRs in paediatric living-donor liver transplant recipients were significantly affected by donor graft size and donor CYP3A5 genotypes. Information from this study may inform the development of an Afrocentric tacrolimus precision-medicine algorithm to optimise recipient safety and graft outcomes
Introduction to the South African Rheumatism and Arthritis Association 2024 guidelines
Get PDFThe guidelines in this series provide evidence-based practical guidance for the diagnosis, treatment and follow-up of persons with inflammatory joint diseases. The purpose of these guidelines is to aid in shared decision-making between patient and physician, aiming to support high-quality clinical care. These guidelines have been prepared using the AGREE II instrument and based on adoption and, where appropriate, adaptation of international guidelines
Missed rifampicin and isoniazid resistance by commercial molecular assays
Get PDFDrug-resistant tuberculosis (TB) has poor outcomes unless resistance is detected early, ideally by commercially available molecular tests. We present a case of occult multidrug-resistant TB where both rifampicin and isoniazid resistance were missed by molecular testing and were only identified by phenotypic testing
The impact of COVID-19 on patients affected by rare diseases and congenital disorders in South Africa: A scoping review
Get PDFRare diseases (RDs) are individually rare but collectively common, affecting an estimated 1 in 15 individuals in South Africa (SA). Patients with an RD often face a long diagnostic odyssey (>5 years on average) and many obstacles in accessing healthcare. A scoping review was conducted to assess the impact of the COVID-19 pandemic on the SA RD community. Fourteen studies met the inclusion criteria and were explored using thematic analysis, which showed that RD patients were further marginalised during the pandemic, particularly in access to healthcare. Increased inclusivity in policy creation and integrated community-based healthcare are recommended to ensure that RD patients are not an afterthought in future crises
Frequent outbreaks of cholera in Zimbabwe: Urgent need for strengthened public health interventions
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Comparison of ultraviolet C light and isopropyl alcohol for the disinfection of cellular phones in a paediatric intensive care unit setting
Get PDFBackground. A considerable proportion of cellular phones (cell phones) used by healthcare workers (HCWs) have been shown to be contaminated with pathogenic micro-organisms, making these devices reservoirs to infect susceptible patients. Although many units have well-defined infection control protocols, methods for the decontamination of cell phones are scarce.
Objectives. To compare the efficacy of ultraviolet C (UVC) light with that of 70% isopropyl alcohol in disinfecting cell phones used by HCWs in a paediatric intensive care unit (ICU).
Methods. A randomised controlled study in a paediatric ICU setting was conducted. Cell phones of HCWs or other personnel entering the ICU were swabbed prior to and after decontamination with either the 70% isopropyl alcohol or UVC light method. The reduction ratio of colony-forming units (CFUs) before and after intervention was analysed using the Mann-Whitney U-test. In addition, the effectiveness of the disinfection methods was compared using the Wilcoxon signed-rank paired test.
Results. A total of 74 cell phones were acquired from HCWs working in the paediatric ICU. After excluding 5, 69 samples were therefore available for statistical analysis, with 34 samples subjected to disinfection using 70% isopropyl alcohol-based swabs and 35 samples treated with UVC light disinfection. Disinfection with 70% isopropyl alcohol (z=5.16; p<0.000001) and with UVC light (z=3.28; p<0.005) were individually statistically significantly effective in reducing CFUs. The CFU reduction ratio indicated that disinfection using a 70% isopropyl alcohol solution was 67% more effective than UVC light disinfection (Mann-Whitney U-test score 968; p<0.001).
Conclusion. Although both 70% isopropyl alcohol and UVC light disinfection effectively reduced CFUs following decontamination, 70% isopropyl alcohol was determined to be much more effective
Case report: First reported case of spondylodiscitis caused by Gemella morbillorum in South Africa
Get PDFPyogenic spondylodiscitis is an uncommon but important clinical condition that often requires medical and/or surgical management. We report a case of spondylodiscitis caused by a rare pathogen, Gemella morbillorum. To date, worldwide, only six such cases of confirmed spondylodiscitis infection with this rare pathogen have been documented, and this is the first reported case in South Africa. The patient was a 55-year-old female who presented to us with a 1-month history of severe back pain radiating to her left leg. She reported to us that she visited the dentist around the time of onset of the symptoms. A workup showed raised inflammatory markers, and a positron emission tomography scan indicated features of discitis at level L2/L3. Tissue cultures from a biopsy identified G. morbillorum species infection, and she was treated successfully with antibiotics for 6 weeks. It is important to have a high index of suspicion when a patient has a history of dental work, and to rule out associated infection such as endocarditis. Treatment with culture-driven antibiotics yields good results
Prescribed Minimum Benefits complaints: a five-year retrospective review
No full textBackground: No matter which benefit option members have chosen, medical schemes are required by the Medical Schemes Act no. 131 of 1998 to pay costs associated with the diagnosis, treatment, or care of a specified set of benefits known as Prescribed Minimum Benefits (PMBs). Medical scheme beneficiaries have the right to lodge complaints with the Council for Medical Schemes (CMS) when their claims are denied.
Objective: To determine and describe the pattern of PMBs complaints received by CMS from January 2014 to December 2018.
Methods: This was a cross-sectional study that utilised the CMS’ clinical complaints. Data for PMBs, complainants, medical scheme types, and reasons for payment denial were extracted. The CMS’ lists of chronic conditions, PMBs, and registered schemes were used to confirm PMBs and to categorise schemes as either restricted (i.e., to only members of specific organisations) or open (i.e., to all South Africans). Extracted and coded data were analysed using SAS v.9.4 software.
Results: A total of 2141 complaints were retrieved and 1124 PMBs complaints were included in the study. The median of PMBs complaints per year was 225. Most of the complaints (43.6%, n=490/1124) were lodged by members themselves. Non-Communicable Diseases (NCDs) constituted most of the PMBs conditions that members complained about. Medicine and surgery were the services that were mostly denied full payment by medical schemes. Open medical schemes accounted for more (73.8%, n=830/1124) of the complaints.
Conclusion: Chronic conditions are the main diseases that medical scheme members complained about. Member education and clear definition of PMBs should be prioritised by medical schemes and the Council for Medical Schemes
Mortality trends during the first three waves of the COVID-19 pandemic at an urban district hospital in South Africa: A retrospective comparative analysis
Get PDFBackground. Severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) is the virus responsible for the COVID‐19 (C19) pandemic. South Africa (SA) experienced multiple periods of increased transmission. Tertiary, regional and central hospitals were overwhelmed, resulting in low acceptance rates.
Objectives. To compare mortality trends of patients who died in hospital from SARS‐CoV‐2 infection during the first three waves of infection as defined by the National Institute of Communicable Diseases of South Africa.
Methods. This was a retrospective cohort study at a district level hospital of 311 adults who died within the first three waves of COVID‐19. The study analysed case and crude fatality rates, baseline characteristics, symptomatology, clinical presentation and management of patients.
Results. Waves 1, 2 and 3 yielded case fatality rates of 14.5%, 27.6% and 6.3%, respectively, and crude fatality rates of 16.7%, 33.0% and 12.2%, respectively. Black Africans were less likely to die during the third wave (odds ratio (OR) 0.54; 95% confidence interval (CI) 0.31 ‐ 0.94). Patients in the second wave had clinical frailty scores of <5 (OR 2.51; 95% CI 1.56 ‐ 4.03). Obesity was most prevalent in the second wave (OR 1.87; 95% CI 1.01 ‐ 3.46), and dyslipidaemia (OR 3.03; 95% CI 1.59 ‐ 5.77) and ischaemic heart disease (OR 3.77; 95% CI .71 ‐ 8.33) were most prevalent during the third wave. Severe ground glass appearance was most common during the second wave (OR 2.37; 95% CI 1.49 ‐ 3.77). Renal impairment was most prevalent during the first wave (OR 3.28; 95% CI 1.59 ‐ 6.77), and thrombo‐ embolic phenomena were less common during wave three (OR 0.12; 95% CI 0.02 ‐ 0.91).
Conclusion. The Beta variant was the most virulent, with the highest case and crude fatality rates in wave 2