In our Paper of the Week, published in Clinical Infectious Diseases, Shiraz Moosa, Gary Maartens, Hannah Gunter, Shaazia Allie, Mohamed Chughlay, Mashiko Setshedi, Sean Wasserman, Nicole Hickman, Mark Sonderup, Wendy Spearman and Karen Cohen report on a randomised controlled trial of intravenous N-acetylcysteine (NAC) in the management of anti-tuberculous drug-induced liver injury. Drug-induced liver injury (DILI) is common in patients taking anti-tuberculous medication. NAC is widely used in patients with paracetamol toxicity with limited evidence of benefit in liver injury due to other causes. In this study, they conducted a randomised, double-blind, placebo-controlled trial to assess whether intravenous NAC reduces time to liver recovery in hospitalised patients with anti-tuberculosis DILI; the primary endpoint was time for serum alanine aminotransferase (ALT) to fall below 100 U/L. Secondary endpoints included length of hospital stay, in-hospital mortality and adverse events. In this small RCT (53 randomised to NAC and 49 to placebo), median time to ALT<100 and mortality did not differ between the study and control arms; however, hospital stay was shorter in the NAC arm. From this study, while the primary endpoint was not med, NAC should still be considered in the management of anti-tuberculous DILI as it shortens hospital stay substantially.
It is a pleasure to share with you a recent publication in Clinical and Translational Medicine by Ambroise Wonkam, Emile Chimusa, Khuthala Mnika, Gift Pule and Valentina Bitoungui from the Division of Human Genetics in collaboration with others from our Faculty and colleagues from the NIH. Sickle cell anemia (SCA) is a clinically heterogeneous, monogenic disorder. Medical care has less-than-optimal impact on clinical outcomes in SCA in Africa due to several factors, including patient access, limited resources, and non-availability of specific effective interventions for SCA. Against this background, Wonkam and colleagues investigated 192 African participants who underwent whole exome sequencing and found new insights into the pathophysiology of SCA by identifying gene sets with deleterious/loss-of-function variants that contribute to variability in SCA clinical expression; in the “long survivor” group (age over 40 years), enriched genes included CLCN6 (a voltage-dependent chloride channel for which rare deleterious variants have been associated with lower blood pressure) and OGHDL (important in arginine metabolism, which is a therapeutic target in SCA); in the “stroke” group, enriched genes implicated increased activity of the blood coagulation cascade and increased complement activation, notable among these genes is SERPINC1 that encodes antithrombin; and they also identified genes and pathways that suggest new avenues for novel interventions.
To our knowledge, this is the first study that used this approach in SCA, as represent an important contribution to science and innovation from Africa. The scientific approach can be extended to exploring genetic modifiers of other genetics and complex diseases. Finally, and importantly, until this publication, major discoveries on SCA, for which Africa is the epicentre, were from research based in USA and Europe. Therefore, this study will hopefully signal a new paradigm shift in science policy and diplomacy.
The SARS-CoV-2 pandemic has presented clinicians with an enormous challenge in managing a respiratory virus that is not only capable of causing severe pneumonia and acute respiratory distress syndrome, but also multisystem disease. The extraordinary pace of clinical research, and particularly the surge in adaptive trials of new and repurposed treatments, have provided rapid answers to questions of whether such treatments work, and has resulted in corticosteroids taking centre stage in the management of hospitalised patients requiring oxygen support. Some treatment modalities, such as the role of anticoagulation to prevent and treat potential thromboembolic complications, remain controversial, as does the use of high-level oxygen support, outside of an intensive care unit setting. In this paper, we describe the clinical management of COVID-19 patients admitted to Groote Schuur Hospital, a major tertiary level hospital at the epicentre of South Africa’s SARS-CoV-2 epidemic during its first 4 months.
The SARS-CoV-2 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town’s tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves.
In our Paper of the Week, we focus on an old disease. Our COVID-centricity in the last 6 months has resulted in neglect of the management of patients with many other conditions – TB, HIV, cardiovascular disease, cancer and many others. Keertan Dheda, together with other members of our Department: Grant Theron, Jason Limberis, Liezel Smith, Elize Pietersen, Ali Esmail, Greg Calligaro, Julian te Riele, Tawanda Gumbo, Taane Clark and collaborators, have recently had an important article published in Nature Medicine.
Their article addressed the question of attenuated infectiousness of individuals with drug-resistant TB, and demonstrated that patients with drug-resistant TB generated infectious culture positive aerosols as frequently as those with newly diagnosed drug-sensitive TB. Interestingly, they could not identify mycobacterial genetic variants that explained heterogeneity in cough aerosol positivity. There were numerous interesting clinical findings, suggesting that relatively well patients with minimal symptoms produce highly infectious aerosol. Their work supports targeting community-based active case finding of minimally symptomatic but infectious individuals, and focussing on studying host pathogen interactions. Super-spreading events and generation of infectious aerosol are features shared in common between TB and COVID‑19.
I hope that you find this read as interesting as I did. I also hope you will as inspired as I am by the publication of work from the tip of our continent in a leading medical journal.