Haematopoietic stem-cell transplantation in an HIV endemic area: time to consider donors exposed to or living with HIV.

South Africa has more than 8 million people living with HIV. However, the number of patients undergoing haematopoietic stem-cell transplantation (HSCT) in South Africa is far below the target number. Donor numbers are insufficient to meet demand. Both HSCT and solid organ transplantation have proved successful in people living with HIV. Solid organ transplantation also has good outcomes when both donors and recipients have HIV. This Personal View explores the possible inclusion of people living with HIV and umbilical cord blood from HIV-negative infants exposed to HIV as donor sources for HSCT. Beyond the risk of HIV transmission, additional complications must be considered, such as delayed or inadequate immune reconstitution and an increased risk of haematological abnormalities and malignancies. Interactions between antiretroviral drugs and drugs used in the conditioning regimen, as well as the need to maintain virological suppression when gastrointestinal absorption deteriorates, are additional complicating factors. The process also requires more stringent ethical processes to be in place to minimise physical and emotional harm. However, in an HIV endemic country, people living with HIV or donors exposed to HIV must be considered as part of a multidisciplinary collaborative effort to provide more patients with the opportunity to have a life-saving HSCT.

Cellular therapy in lymphoma.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has had a dramatic impact on the natural history and survival of patients with high-risk B-cell non-Hodgkin lymphoma. Accompanying this success has been the development of new fields of medicine and investigation into toxicity risks and mitigation therapies, mechanisms of resistance and the development of novel and next generation products and strategies in order to address relapse, and issues related to global access and health care economics. This article is a survey of each of these areas as it pertains to the rapidly evolving field of CAR T-cell therapy, written by an International community of lymphoma experts, who also happen to be women.

Childhood aplastic anaemia with paroxysmal nocturnal haemoglobinuria clones: A retrospective single-centre study in South Africa.

Background: Paroxysmal nocturnal haemoglobinuria (PNH) clones in children are rare but commonly associated with aplastic anaemia (AA) and myelodysplasia. Objective: This study aimed to determine the prevalence of PNH clones in paediatric patients with idiopathic AA, identify differences in clinical and laboratory features and outcomes, and determine the impact of clone size on clinical presentation. Methods: Patients with confirmed idiopathic AA who were tested for PNH between September 2013 and January 2018 at the Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, were included. PNH clones were detected in neutrophils and monocytes by flow cytometry using fluorescent aerolysin, CD24, CD66b and CD14. Results: Twenty-nine children with AA were identified and 11 were excluded. Ten patients (10/18, 55.6%) had PNH clones ranging from 0.11% to 24%. Compared to the PNH-negative group, these children were older (median: 10 years vs 4 years, p = 0.02) and had significantly lower total white cell counts (median 1.7 × 109/L vs 3.2 × 109/L; p = 0.04). There was no difference in median absolute neutrophil count or haemoglobin concentration. Four patients in each group received immunosuppressive therapy (IST). At six months, all four patients with PNH clones had responded, compared to one in the PNH-negative group. Conclusion: More than half of children with AA had a PNH clone. The size of the clone did not impact clinical severity; however, IST use may positively impact prognosis. We recommend early initiation of IST in patients with AA to avoid delays associated with human leukocyte antigen typing.

Social Media and COVID-19-Perceptions and Public Deceptions of Ivermectin, Colchicine and Hydroxychloroquine: Lessons for Future Pandemics.

The capacity for social media to influence the utilization of re-purposed medicines to manage COVID-19, despite limited availability of safety and efficacy data, is a cause for concern within health care systems. This study sought to ascertain links between social media reports and utilization for three re-purposed medicines: hydroxychloroquine (HCQ), ivermectin and colchicine. A combined retrospective analysis of social media posts for these three re-purposed medicines was undertaken, along with utilization and clinical trials data, in South Africa, between January 2020 and June 2021. In total, 77,257 posts were collected across key social media platforms, of which 6884 were relevant. Ivermectin had the highest number of posts (55%) followed by HCQ (44%). The spike in ivermectin use was closely correlated to social media posts. Similarly, regarding chloroquine (as HCQ is not available in South Africa), social media interest was enhanced by local politicians. Sentiment analysis revealed that posts regarding the effectiveness of these repurposed medicines were positive. This was different for colchicine, which contributed only a small number of mentions (1%). Of concern is that the majority of reporters in social media (85%) were unidentifiable. This study provides evidence of social media as a driver of re-purposed medicines. Healthcare professionals have a key role in providing evidence-based advice especially with unidentifiable posts.

Coronavirus Host Genetics South Africa (COHG-SA) database-a variant database for gene regions associated with SARS-CoV-2 outcomes.

The SARS-CoV-2 virus is responsible for the COVID-19 global public health emergency, and the disease it causes is highly variable in its clinical presentation. Clinical phenotypes are heterogeneous both in terms of presentation of symptoms in the host and response to therapy. Several studies and initiatives have been established to analyse and review host genetic epidemiology associated with COVID-19. Our research group curated these articles into a web-based database using the python application-server framework Django. The database provides a searchable research tool describing current literature surrounding COVID-19 host genetic factors associated with disease outcome. This paper describes the COHG-SA database and provides an overview of the analyses that can be derived from these data.

Bacteraemia and antibiotic sensitivity in a tertiary neonatal intensive care unit.

BACKGROUND: Neonatal sepsis is an important cause of mortality and morbidity in neonatal intensive care populations worldwide. Data on rates of bacteraemia and antibiotic resistance patterns are limited, particularly in the developing world. METHODS: We retrospectively reviewed positive blood cultures obtained in the neonatal intensive care unit between 01 January 2015 and 31 December 2015. All neonates, either born at the tertiary hospital or transferred from referral units, regardless of diagnosis, who had a positive blood culture were included. RESULTS: There were 702 admissions during the study period and 437 positive cultures. Male patients made up 55.1% (65/118), and the gender was unknown for 11.0% (13/118). Late onset sepsis accounted for 85.7% (102/119) and early onset sepsis, 14.3% (17/119). Of the 119 organisms cultured, 76 (63.8%) were Gram-negative, 35 (29.4%) were Gram-positive and 8 (6.7%) were Candida species. Klebsiella was the most common genus at 42% (50/119). Of the clinically relevant organisms recovered, 37.0% (44/119) were susceptible to the empiric first-line regimen of penicillin and gentamycin. Furthermore, 69.7% (53/76) of the Gram-negative organisms produced extended-spectrum beta-lactamases. CONCLUSION: The majority of organisms cultured were considered contaminants and were not clinically relevant. Improvements in culture collection processes are needed. The majority of organisms considered clinically relevant were resistant to the first-line antibiotic regimen. To improve the likelihood of clinical success, empiric antibiotic regimens should be based on local data, if possible.

Perspectives on establishing a public cord blood inventory in South Africa.

The South African population is highly diverse, both ethnically and genetically. This diversity is particularly true for the African ancestry and various mixed ancestry population groups. These groups are under-represented in national and international bone marrow and peripheral blood donor registries, making it challenging to identify HLA-matched and mismatched unrelated donors when patients from these groups require allogeneic hematopoietic stem and progenitor cell transplantation. In most high-income countries, banked cord blood (CB) units provide an attractive source of hematopoietic progenitor cells for genetically diverse populations. SA does not have a public CB inventory, leaving many patients without access to this important treatment modality. Haploidentical transplantation provides an alternative. In recent years, the use of post-transplant cyclophosphamide has significantly reduced the incidence of graft-versus-host disease after haploidentical transplantation and has improved transplantation outcomes. However, it is difficult to identify suitable haploidentical donors in SA because of family disruption and a high prevalence of HIV. Here the authors provide a brief historical overview of the ethnic and genetic diversity of the country and region. The authors provide a southern African perspective on HLA diversity, consider the allogeneic hematopoietic stem and progenitor cell transplantation landscape and explore the need to establish a public CB bank (CBB) in SA. The health policy and regulatory frameworks that will impact on a CBB in the country SA are also explored. Finally, the authors discuss several matters we believe require attention when considering the establishment of a sustainable public CBB in the South African context.

The COVID-19 Treatment Landscape: A South African Perspective on a Race Against Time.

The pandemic caused by SARS-CoV-2 has infected more than 94 million people worldwide (as of 17 January 2020). Severe disease is believed to be secondary to the cytokine release syndrome (CRS or "cytokine storm") which causes local tissue damage as well as multi-organ dysfunction and thrombotic complications. Due to the high mortality rates in patients receiving invasive ventilation, practice has changed from "early-intubation" for acute respiratory distress syndrome (ARDS) to a trial of non-invasive ventilation (NIV) or high flow nasal cannula (HFNC) oxygen. Reports indicating the benefit of NIV and HFNC have been encouraging and have led to more than 20,000 such devices being manufactured and ready for roll-out in South Africa (SA) as of July 2020. The need to identify drugs with clear clinical benefits has led to an array of clinical trials, most of which are repurposing drugs for COVID-19. The treatment landscape reflects the need to target both the virus and its effects such as the CRS and thrombotic complications. Conflicting results have the potential to confuse the implementation of coordinated treatment strategies and guidelines. The purpose of this review is to address pertinent areas in the current literature on the available medical treatment options for COVID-19. Remdesivir, tocilizumab, and dexamethasone are some of the treatment options that have shown the most promise, but further randomized trials are required to particularly address timing and dosages to confidently create standardized protocols. For the SA population, two healthcare sectors exist. In the private sector, patients with medical insurance may have greater access to a wider range of treatment options than those in the public sector. The latter serves >80% of the population, and resource constraints require the identification of drugs with the most cost-effective use for the greatest number of affected patients.

Factors Present on Admission Associated with Increased Mortality in Children Admitted to a Paediatric Intensive Care Unit (PICU)

Background. The admission of children to an intensive care unit (ICU) necessitates the selection of children who will benefit most from scarce ICU resources. Decisions should be based on objective data available on outcomes related to particular conditions and resource availability. Objective. To determine which sociodemographic factors and paediatric scoring systems can be used on admission to identify patients who would derive the most benefit.Methods. A retrospective review was undertaken of the charts of children admitted to a paediatric ICU (PICU) over a 6-month period. Charts were analysed according to health status; biographical and demographic data; as well as Pediatric Risk of Mortality (PRISM); Pediatric Logistic Organ Dysfunction (PELOD) and Paediatric Index of Mortality 3 (PIM3) scores to determine which factors were associated with an increased mortality risk.Results. Two hundred and two children were admitted during the study period. Ninety-six children were included in the study; 79 files were not found and 27 children were ineligible. The median age was 14 months and the mortality rate was 15.6%. The significant factor associated with mortality was severe malnutrition. In total 88% of required data were available for the calculation of both the PRISM and PELOD scores and 95% for PIM3 score. The PRISM; PELOD and PIM3 standardised mortality ratios were 2.5; 4.8 and 2.9; respectively. P-values for PRISM; PELOD and PIM3 were 0.05.Conclusion. Severe malnutrition is a statistically significant factor in predicting mortality. This possibly reflects the social context in which the children live. PRISM; PELOD and PIM3 underpredict mortality in our setting. A larger sample is required to verify these outcomes and to determine whether other factors play a role