Candice Laverne Hendricks

Current pediatric allogeneic hematopoietic stem cell transplantation (HSCT) services in South Africa do not meet the substantial demand in the country. The factors leading to this paucity are multifactorial, including a limited number of appropriate donors on our local registries, inadequate identification and referral of appropriate patients, long distances to travel to health facilities, socioeconomic inequality, and inadequate infrastructure and clinical expertise for the number of transplants required. We describe a model for a large HSCT unit that caters to insured and uninsured patients in order to ensure equitable access, and which is in line with the WHO health system building blocks. The scale at which transplantation will be achieved will allow for the development of local skills and expertise, which can be decentralized in the future to further improve HSCT access.

Improvements in administration and efficacy of antiretroviral therapy (ART) have reduced rates of mother‐to‐child transmission (MTCT) of human immunodeficiency virus (HIV) to < 2%. However, in utero exposure to antiretrovirals (ARVs) leads to abnormalities in HIV‐exposed uninfected (HEU) infants. We determined the effect of five ARVs on human umbilical cord blood (UCB)‐derived haematopoietic stem/progenitor cells (HSPC) with the aim of exploring a potential causal relationship with haematological abnormalities. Efavirenz (EFV) was cytotoxic to HSPCs alone and in combination with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Dolutegravir (DTG) had a biphasic effect on HSPC expansion. Immunophenotypic analysis showed increased erythroid and granulocyte precursors after 7‐day culture with these drugs. Finally, using colony forming unit (CFU) assays, we observed impairment in the formation of CFU‐GEMM and CFU/Burst forming unit (BFU) erythroid (E) in the presence of DTG, lamivudine (3TC) and TDF, both visually and immunophenotypically. We conclude that multiple potential HSPC toxicities exist with ARVs commonly used in pregnancy, prompting the need for further research to confirm the safety of these drugs in this vulnerable group.

PURPOSE: Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers. METHODS: Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers. RESULTS: Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%. CONCLUSION: Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

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.

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.

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.

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.