Samj South African Medical Journal最新文献

Background: HIV-infected kidney transplant recipients with COVID-19 are at increased risk of acute illness and death owing to their underlying comorbidities and chronic immunosuppression.

Objectives: To describe the incidence, clinical presentation and course of COVID-19, vaccination status, and SARS-CoV-2 antibody positivity rate among HIV-infected-to-HIV-infected kidney transplant recipients in South Africa (SA).

Methods: This retrospective study reports on rates of SARS-CoV-2 infection, COVID-19 and mortality among SA HIV-infected kidney transplant recipients who received organs from HIV-infected donors (HIV positive to HIV positive), before and after vaccination. Patient demographics, clinical presentation, course, management and disease outcomes were analysed. Antibody serology tests were performed between May and September 2022.

Results: Among 39 HIV-positive-to-HIV-positive transplant recipients, 11 cases of COVID-19 were diagnosed from March 2020 to September 2022. Six patients (55%) required hospitalisation, of whom 3 were admitted to a high-care unit or intensive care unit. Two patients required mechanical ventilation, and 2 received acute dialysis. One patient was declined access to intensive care. Four patients (10%) died of COVID-19 pneumonia. All the COVID-19-positive patients had at least one comorbidity. Vaccination data were available for 24 patients, of whom 5 had refused SARS-CoV-2 vaccination. SARS-CoV-2 antibody data were available for 20 patients; 4 vaccinated patients had a negative nucleocapsid protein antibody test and a positive spike protein antibody test, suggesting vaccination-acquired immunity. The remaining 16 patients demonstrated immunity that was probably due to COVID infection, and of these, 14 were also vaccinated. Of the 11 COVID-19 cases, only 1 was observed after vaccination.

Conclusion: In our case series, ~10% of the HIV-positive-to-HIV-positive transplant recipients died of COVID-19 pneumonia. This mortality rate appears higher than figures reported in other transplant cohorts. However, it is likely that the actual number of cases of SARS-CoV-2 infection was much higher, as the study only included polymerase chain reaction-confirmed cases. It remains unclear whether HIV infection, transplant or the combination of the two drives poorer outcomes, and larger studies adjusting for important demographic and biological factors may isolate these effects.

Background: 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.

Background: At Groote Schuur Hospital in Cape Town, South Africa, the number of deceased organ donors has declined over the past 2 decades, necessitating a more liberal approach to donor selection. In 2007, measures to expand the deceased kidney donor pool were implemented, including an HIV positive-to-positive transplant programme and the utilisation of extended-criteria donors as well as donors after circulatory death (DCDs).

Objectives: To report on our institutional experience with DCD kidney transplants and to encourage this approach among other African centres to improve access to transplantation.

Methods: An observational cohort study of consecutive DCD kidney transplants at Groote Schuur Hospital over a 17-year period was performed. Primary endpoints were 1-, 2- and 5-year graft and patient survival. Secondary endpoints included the incidence of delayed graft function (DGF), 30-day morbidity, length of stay, and donor and recipient clinical characteristics.

Results: Fifteen DCD procurements were performed, with no kidneys discarded. Thirty kidney transplants were performed, with a median (interquartile range) cold ischaemic time of 11.5 (8 - 14) hours. The incidence of DGF was 60.0%, and 30-day morbidity (other than DGF) was 20.0%. Graft survival at 1, 2 and 5 years was 100%, 96.0% and 73.7%, respectively. Patient survival at 1, 2 and 5 years was 93.3%, 93.3% and 88.4%, respectively.

Conclusion: Long-term graft and patient survival was comparable with the international literature. DCD may present a unique opportunity to expand deceased donation throughout Africa, particularly in areas affected by a lack of brain death legislation and religious or cultural objections to donation after brain death.

Pregnancy in kidney and liver transplant recipients presents unique challenges and risks for both maternal and fetal health. This article examines the management of pregnancy in kidney and liver transplant recipients, focusing on pre-pregnancy counselling, trimester-specific care, the teratogenic effects of immunosuppressive drugs, and the role of the multidisciplinary team. While South African (SA) data on this topic are limited, the Transplant Pregnancy Registry International has provided valuable insights. Despite the increased risk of maternal and fetal complications, the overall risk of graft loss during pregnancy is low. Graft survival rates are comparable between pregnant and non- pregnant transplant recipients, except for pregnancies occurring within 1 year of transplantation. By addressing the complexities of managing pregnant women with kidney or liver transplants, this article underscores the importance of tailored care and the involvement of various medical specialists. It also explores the safety of and potential complications associated with specific immunosuppressive therapies during pregnancy. Further research is needed to enhance our understanding and optimise the management of these high-risk pregnancies in SA.

Diabetes mellitus (DM) is a growing public health concern in South Africa (SA) and poses a substantial economic burden on healthcare globally. A century has passed since the discovery of insulin, and despite advances in diabetes management, exogenous insulin remains a primary treatment for type 1 DM, posing challenges of hyperglycaemia and hypoglycaemia. Pancreas transplantation should be considered a treatment for insulin-deficient DM, offering sustained euglycaemia and preventing complications associated with the disease. However, there has been a global decrease in the number of transplants performed. In SA, only a few pancreas transplants have been performed, primarily because of surgical risks and the need for immunosuppression. Islet transplantation is an alternative but faces limitations due to donor scarcity and immunosuppression requirements. This review explores recent progress in pancreas and islet transplants for DM, with the aim of providing insights into expanding treatment options for people with insulin-deficient DM.

Background: Heart transplantation in South Africa faces numerous challenges related to organ scarcity and unequal access to advanced heart therapy. There is an urgent need to analyse the current transplant referral pathway to optimise equitable access to transplantation.

Objectives: To provide an audit of heart transplant referrals to Groote Schuur Hospital, Cape Town, over a 23-year period, focusing on patient demographics, indications for referral, waiting-list dynamics, and transplant referral outcomes.

Methods: The study utilised a retrospective patient folder review for the period 1 January 1997 - 31 December 2019 and audited the trends in heart transplant referrals and associated outcomes of the referral at a tertiary academic hospital.

Results: A total of 625 recipients were referred for heart transplantation, with the majority being male (n=412; 65.9%), while gender was undocumented for 69 cases (11.0%). The mean age was 38.1 (14.6) years, and 153 (24.5%) were listed for transplant, while 215 (34.4%) were deemed ineligible for listing. Contraindications for listing included social (n=106; 49.3%), medical (n=83; 38.6%) and psychological (n=26; 12.0%) factors, while 134 patients (21.4%) were considered too well. Poor social circumstances (n=38; 39.6%), poor insight (n=28; 29.2%) and poor compliance (n=21; 21.9%) were the most common non-medical reasons for not listing recipients, while obesity (n=30; 31.3%) and smoking (n=23; 24.0%) were notable medical contraindications. Forty-nine patients (7.8%) died during work-up, while 130 (85.0%) of the listed patients received a heart transplant. Of the 429 donor referrals, 139 (32.4%) were accepted for organ procurement. Reasons for declining donors included unsuitability for transplantation (30.3%), lack of capacity (1.8%), and recipient-donor mismatch (66.9%).

Conclusion: Three-quarters of the referred patients were deemed unsuitable for heart transplantation for medical and/or social reasons. The ratio of referral to listing has decreased over time. However, once listed, the likelihood of receiving a transplant was high.

Introduction Autoimmune hepatitis (AIH) has scarcely been reported on in patients of black African descent. Similarly, few studies have focused on the relationship between AIH and Human-Immunodeficiency Virus (HIV) infection. Aim We aim to describe the presenting features of AIH from a single referral centre in a Sub-Sahara African setting. We also compare the presenting features of HIV-infected and HIV-uninfected patients. Methods This study was a retrospective chart review. Patients were included if they fulfilled criteria for the International AIH Group simplified score for probable or definite AIH, were 18 years or older at inclusion, and attended the adult Gastroenterology clinic at Inkosi Albert Luthuli Central Hospital (IALCH) for the period 1/1/2015 to 31/12/2020 on at least 2 occasions. Results Forty cases were included, of which 33 (82.5%) were female and 33 (82.5%) were black African. Median age at diagnosis was 26 years. A diagnosis of a coexistent autoimmune disease was made in 22.5% of patients, with Systemic Lupus Erythematosus (SLE) being the most common (12.5%). Sixteen patients were HIV-infected, all of whom were female (p =0.03), with a significantly older age of disease onset as compared to their HIV-uninfected counterparts (median age 38 vs 17.5 years, p <0.001). Conclusion AIH is a disease most commonly affecting young females. Female sex and older age of onset is associated with AIH in HIV-infected individuals.

Background: The ability to access effective hospital care for children is a significant determinant of good health outcomes. The Western Cape is a large land area with a wide array of human settlements- both in urban and rural spaces. For many children in the Western Cape, after-hours access to healthcare becomes constrained when primary care clinics close and hospitals are either far away or difficult to get to. The cumulative travel burden of communities across this area is not known. The recently established data gathering capacity of the Provincial Health Data Centre of the Western Cape represents a new capacity to study this.

Objectives: This study intends to describe the cumulative travel burdens of children in communities throughout the Western Cape, and how they compare relative to one another, with a particular focus on the after-hours period in a week.

Methods: Over a period of 5 years from 2017-2021, all the admission details to every hospital in the Western Cape of children under 18 years of age were collected, with basic demographic and disease data including place of residence. The distance each child travelled to their first admission facility was calculated and represented within defined communities across the metro of Cape Town and the rural Western Cape.

Results: There were 574 220 admissions over the 5-year period, of which 360 783 were able to be used for travel analysis. The majority of admissions were for children under 5 years of age, were in the City of Cape Town and occurred after hours. Median travel distance was less for children outside of Cape Town, but the range of travelled distances was greater. Communities across the Western Cape, particularly rural communities, reflected significant variation in their cumulative travel burdens.

Conclusion: Using a large health dataset, this study demonstrates in a novel way for South Africa, the distances children travel to access admission facilities. A wide variation exists across all parts of the province, but particularly in rural areas. These findings could be further interrogated for people's choices of facility and method of travel. Detailed service area modelling and extending primary care working hours are potential considerations for improving access at scale and at the local community level.

Background Predicting severe Crohn's disease (SCD) can assist in planning risk reduction therapy for SCD, thereby improving disease outcomes. Objective To determine the prevalence and predictors of SCD in a sample of South African patients. Methods This was a retrospective chart review of patients with Crohn's disease (CD) attending the Gastroenterology Unit at a tertiary hospital in Durban, South Africa. Demographic and clinical variables at diagnosis of CD were collected and analysed for statistical association with development of SCD (defined as the presence of >/= 1 of the following over the course of CD: complex perianal disease, colonic resection >/= 2 small bowel resections, a single small bowel resection > 50cm, or construction of a definitive stoma). The prognostic utility of statistically significant variables was investigated by establishing their sensitivity, specificity, and predictive values for SCD.  Results The study consisted of 93 patients. The rate of SCD was 64.5%, with 63.3 % of patients developing SCD within 1 year of CD diagnosis. Ileocolonic location (p = 0.046) and penetrating disease at initial diagnosis of CD (p = 0.021) were statistically associated with SCD. The sensitivity, specificity, positive predictive value, and negative predictive value of ileocolonic location for SCD was 72.7%, 47.4%, 66.7% and 54.6%. The sensitivity, specificity, positive predictive value, and negative predictive value of penetrating disease for SCD was 85.7%, 41.7%, 30.0% and 91.0%. Conclusion Most patients with CD developed SCD within 1 year of their CD diagnosis. CD with a penetrating phenotype at diagnosis is a good predictor for the devleopment of SCD and should be further investigated.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men, with a rising global incidence. Currently, the PCa landscape is vastly different between developed countries and Africa. Of note, owing to various biological, socioeconomic and institutional factors, black African men often present with more advanced disease and suffer greater mortality. This review will focus on the burden of PCa globally and in Africa, compare the state of the disease in Africa with that in more developed regions of the world, and answer the question why it can sometimes look like a 'different' disease compared with developed regions. In addition, we address the racial disparities of PCa.