University of Cape Town

Vally A., Maswoswere G., Bowden N., Paine S., Amayo P., Markham A., Patel A.

Mkhatshwa S., Nitschke G.

In biological societies, complex interactions between the behavior and morphology of evolving organisms and their environment have given rise to a wide range of complex and diverse social structures. Similarly, in artificial counterparts such as swarm-robotics systems, collective behaviors emerge via the interconnected dynamics of robot morphology (sensory-motor configuration), behavior (controller), and environment (task). Various studies have demonstrated morphological and behavioral diversity enables biological groups to exhibit adaptive, robust, and resilient collective behavior across changing environments. However, in artificial (swarm robotic) systems there is little research on the impact of changing environments on morphological and behavioral (body-brain) diversity in emergent collective behavior, and the benefits of such diversity. This study uses evolutionary collective robotics as an experimental platform to investigate the impact of increasing task environment complexity (collective behavior task difficulty) on the evolution and benefits of morphological and behavioral diversity in robotic swarms. Results indicate that body-brain evolution using coupled behavior and morphology diversity maintenance yields higher behavioral and morphological diversity, which is beneficial for collective behavior task performance across task environments. Results also indicate that such behavioral and morphological diversity maintenance coupled with body-brain evolution produces neuro-morpho complexity that does not increase concomitantly with task complexity.

Ganaie F.A., Beall B.W., Yu J., van der Linden M., McGee L., Satzke C., Manna S., Lo S.W., Bentley S.D., Ravenscroft N., Nahm M.H.

SUMMARY Streptococcus pneumoniae (the “pneumococcus”) is a significant human pathogen. The key determinant of pneumococcal fitness and virulence is its ability to produce a protective polysaccharide (PS) capsule, and anti-capsule antibodies mediate serotype-specific opsonophagocytic killing of bacteria. Notably, immunization with pneumococcal conjugate vaccines (PCVs) has effectively reduced the burden of disease caused by serotypes included in vaccines but has also spurred a relative upsurge in the prevalence of non-vaccine serotypes. Recent advancements in serotyping and bioinformatics surveillance tools coupled with high-resolution analytical techniques have enabled the discovery of numerous new capsule types, thereby providing a fresh perspective on the dynamic pneumococcal landscape. This review offers insights into the current pneumococcal seroepidemiology highlighting important serotype shifts in different global regions in the PCV era. It also comprehensively summarizes newly discovered serotypes from 2007 to 2024, alongside updates on revised chemical structures and the de-novo determinations of structures for previously known serotypes. Furthermore, we spotlight emerging evidence on non-pneumococcal Mitis-group strains that express capsular PS that are serologically and biochemically related to the pneumococcal capsule types. We further discuss the implications of these recent findings on capsule nomenclature, pneumococcal carriage detection, and future PCV design. The review maps out the current status and also outlines the course for future research and vaccine strategies, ensuring a continued effective response to the evolving pneumococcal challenge.

Schwab T.C., Joseph L., Moono A., Göller P.C., Motsei M., Muula G., Evans D., Neuenschwander S., Günther G., Bolton C., Keller P.M., Ramette A., Egger M., Omar S.V., Fenner L.

ABSTRACT Rapid and comprehensive drug susceptibility testing (DST) is essential for diagnosing and treating drug-resistant tuberculosis effectively, and next-generation sequencing can be an effective genotypic DST method. We implemented and evaluated the performance of a nanopore targeted sequencing assay, called the Tuberculosis Drug Resistance Test (TBDR, Oxford Nanopore Diagnostics, Ltd., United Kingdom), which predicts drug resistance to 16 TB drugs, at a South African reference laboratory and a district diagnostic laboratory in Zambia. We compared the sequencing success rates between unprocessed and decontaminated sputum samples and determined the diagnostic accuracy against local DST (Xpert MTB/RIF Ultra, Xpert MTB/XDR, and BD BACTEC MGIT phenotypic DST). We prospectively sequenced 236 samples and have 148 samples with sequencing results from unprocessed and decontaminated sputum. We obtained successful sequencing results from 66.4% (94/148) unprocessed sputum samples and 75% (111/148) decontaminated samples. Sequencing success rates at the two sites differed, with 50.7% (36/71) successful sequencing results from unprocessed sputum in Zambia and 75.3% (58/77) in South Africa. Samples with “low” bacterial load, measured by Xpert MTB/RIF Ultra, tended to produce fewer successful sequencing results. TBDR sequencing predicted resistances in 48 samples, detecting resistance for rifampicin ( n = 41) and isoniazid ( n = 20), as well as 10 second-line drugs ( n = 15). Sensitivity was variable compared to phenotypic DST, ranging from 33 (ethionamide) to 94% (rifampicin), while specificity remained above 90% for all drugs, except clofazimine. The TBDR assay can provide rapid, comprehensive genotypic DST. Technical and operational challenges need to be addressed for its broader implementation in high tuberculosis-burden settings. IMPORTANCE This study illustrates the use of the Tuberculosis Drug Resistance Test (TBDR, Oxford Nanopore Diagnostics, Ltd., United Kingdom) as a rapid drug susceptibility testing (DST) approach for diagnosing drug-resistant TB in the high TB-burden countries of South Africa and Zambia. The TBDR assay predicts resistance to 16 TB drugs, including first- and second-line treatments. By implementing the TBDR assay in a national reference laboratory in South Africa and a district diagnostic laboratory in Zambia, we demonstrate how this technology can provide faster diagnostic results (days) compared to traditional phenotypic DST methods (~2 months), with adequate sensitivity. Missed resistances compared to phenotypic DST indicate that technical improvements are needed. Successful sequencing from unprocessed and decontaminated sputum samples at different sites suggests feasibility in diverse settings, though operational challenges remain. Implementing this rapid, comprehensive DST approach could enhance drug-resistant tuberculosis diagnosis and treatment, ultimately improving patient outcomes and helping to combat tuberculosis in high-burden regions.

Ghasoub M., Scholten C., Geeraert B., Long X., Joshi S., Wedderburn C.J., Roos A., Subramoney S., Hoffman N., Narr K., Woods R., Zar H.J., Stein D.J., Donald K., Lebel C.

Abstract Introduction: Prenatal alcohol exposure (PAE) is associated with various neurological, behavioral and cognitive deficits, including reading and language. Previous studies have demonstrated altered white matter in children and adolescents with PAE and associations with reading and language performance in children aged 3 years and older. However, little research has focused on the toddler years, despite this being a critical period for behavioral and neural development. We aimed to determine associations between structural brain connectivity and early language skills in toddlers, in the context of PAE. Methods: 88 toddlers (2–3 years, 56 males), 23 of whom had PAE, underwent a diffusion MRI scan in Cape Town, South Africa, with language skills assessed using the Expressive and Receptive Communication subtests from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Diffusion scans were preprocessed to create a structural network of regions associated with language skills using graph theory analysis. Linear regression models were used to examine moderation effects of PAE on structural network properties and language skills. Results: Toddlers with PAE had higher structural connectivity in language networks than unexposed children. PAE moderated the relationship between structural network properties and Expressive Communication scores. None of the effects survived correction for multiple comparisons. Conclusion: Our findings show weak moderation effects of PAE on structural language network properties and language skills. Our study sheds light on the structural connectivity correlates of early language skills in an understudied population during a critical neurodevelopmental period, laying the foundation for future research.

Akande M., Orchowski L., Harrison A., Berkowitz A., Mathews C., Kuo C.

Collins N., Sawczuk T., Whitehead S., Jones B.

Manjra S., Kagee A.

Mall A.S.

Baldwin-Ragaven L., Wadee S.A., Reynolds L., Pointer R., Sibanda S., Mohamed N., van Heusden P., Lewins K.

Willmer T., Mabasa L., Sharma J., Muller C.J., Johnson R.

Non-communicable diseases (NCDs) are the leading cause of death worldwide, with cardiovascular disease (CVD) accounting for half of all NCD-related deaths. The biological onset of CVD may occur long before the development of clinical symptoms, hence the urgent need to understand the molecular alterations underpinning CVD, which would facilitate intervention strategies to prevent or delay the onset of the disease. There is evidence to suggest that CVD develops through a complex interplay between genetic, lifestyle, and environmental factors. Epigenetic modifications, including DNA methylation, serve as proxies linking genetics and the environment to phenotypes and diseases. In the past decade, a growing list of studies has implicated DNA methylation in the early events of CVD pathogenesis. In this regard, screening for these epigenetic marks in asymptomatic individuals may assist in the early detection of CVD and serve to predict the response to therapeutic interventions. This review discusses the current literature on the relationship between blood-based DNA methylation alterations and CVD in humans. We highlight a set of differentially methylated genes that show promise as candidates for diagnostic and prognostic CVD biomarkers, which should be prioritized and replicated in future studies across additional populations. Finally, we discuss key limitations in DNA methylation studies, including genetic diversity, interpatient variability, cellular heterogeneity, study confounders, different methodological approaches used to isolate and measure DNA methylation, sample sizes, and cross-sectional study design.

de Jong H.K., Grobusch M.P.

Purpose of review Although cases of Zika virus disease (ZVD) have declined globally since 2017, new outbreaks have been reported, such as in Asia in 2024. As there is no vaccine or treatment available to date, both vaccines and mAbs neutralizing Zika virus would be of great interest, especially for pregnant women and immunocompromised patients such as those living with HIV. This review focuses on new insights regarding ZVD in the last two years and summarizes the key literature on global epidemiology, transmission, diagnostics, clinical features, preventive measures, and treatment options. Recent findings At the time of writing, ZVD is endemic across tropical and subtropical regions of the world, with the highest risk of infection in Latin America and the Caribbean, but no significant peaks in outbreak activity across endemic regions. There are ongoing efforts to further investigate the clinical and epidemiological long-term sequelae of the large outbreak in the Americas 2015–2018; further refinement of diagnostic tools to improve specificity in view of significant cross-reactivity potential, particularly with dengue virus. Multiple vaccines are in different clinical development stages; however, phase 3 trials are awaiting the next epidemic. Summary While there is no current major zika virus outbreak, progress has been made in the epidemiological work-up of clinical-epidemiological data, refinement of diagnostic tools, and mainly preventive (vaccines) rather than curative (drugs) tools.

Ghebrekristos Y., Ahmed A., Beylis N., Singh S., Opperman C., Naufal F., Folkerts M., Engelthaler D., Auma E., Venter R., Booley G., Metcalfe J., Warren R., Theron G.

ABSTRACT Xpert MTB/RIF Ultra (Ultra)-detected rifampicin-resistant tuberculosis (TB) is often programmatically confirmed using MTBDR plus . There are limited data on discordant results, including when re-tested using newer methods, like FluoroType MTBDR (FT-MTBDR) and targeted deep sequencing. MTBDR plus rifampicin-susceptible isolates from people with Ultra rifampicin-resistant sputum were identified from a South African programmatic laboratory. FT-MTBDR and single molecule-overlapping reads (SMOR; rpoB , inhA , katG ) on isolate DNA were done (SMOR was used as a reference standard). Between 1 April 2021 and 30 September 2022, 8% (109/1347) of Ultra rifampicin-resistant specimens were MTBDR plus -susceptible. Of 89% (97/109) isolates with a sequenceable rpoB , SMOR resolved most in favor of Ultra (79% [77/97]). Sputum with lower mycobacterial load was associated with Ultra false-positive resistance (46% [11/24] of “very low” Ultra had false resistance vs 12% [9/73; P = 0.0004] of ≥“low”), as were Ultra heteroresistance calls (all wild-type probes, ≥1 mutant probe) (62% [23/37 vs 25% 15/60] for Ultra without heteroresistance calls; P = 0.0003). Of the 91% (88/97) of isolates successfully tested by FT-MTBDR, 55% (48/88) were FT-MTBDR rifampicin-resistant and 45% (40/88) susceptible, translating to 69% (47/68) sensitivity and 95% (19/20) specificity. In the 91% (99/109) of isolates with inhA and katG sequenced, 62% (61/99) were SMOR isoniazid-susceptible. When Ultra and MTBDR plus rifampicin results are discordant, Ultra is more likely to be correct, and FT-MTBDR agrees more with Ultra than MTBDR plus ; however, lower load and the Ultra heteroresistance probe pattern were risk factors for Ultra false rifampicin-resistant results. Most people with Ultra–MTBDR plus discordant resistance results were isoniazid-susceptible. These data have implications for drug-resistant TB diagnosis.

Kander V., Valente K.D., Carrizosa J., Vidaurre J., Patel A.A., Triki C.C., Aljandeel G., Singh G., Kato M., Seck L., Kone Z., Beniczky S., Asukile M.T., Birbeck G.L., Jones K., et. al.

AbstractIdeally, pediatric electroencephalograms (EEGs) should be performed by accredited neurophysiology technologists and interpreted by specialists trained in epileptology However, low‐ and middle‐income countries (LMICs) lack such specialists.AimTo collate expert consensus on essential curriculum content for non‐epilepsy specialists in EEG interpretation and safe post‐training practice.MethodA qualitative study on pediatric EEG training curricula needs was designed in collaboration with an adult education specialist. Data were collected via interviews from 15 epilepsy experts with training experience across high‐ to low‐income settings. Thematic analysis was used to identify sub‐themes. The experts voted on the key statements in a two‐round Delphi to ascertain consensus.ResultsTwelve aspects of pediatric EEG training were identified and categorized thematically: relevance; exposure to pediatrics; focus on pediatrics; barriers; resource‐limited setting; entry skills; best pedagogy; assessment; critical skills; reinforcement of skills; training model; and recommendations.ConclusionThis study was driven by the inadequate access to training in pediatric EEG for non‐epilepsy specialists, which is further exacerbated by the lack of epileptologists and neurophysiologists. The outcomes from the expert consensus opinions promoted consolidation, adaptation, and evolution of existing models that are viable for practice and to be used worldwide. The Delphi consensus demonstrated alignment among regionally located specialists towards the promotion of effective and maintained training for non‐epilepsy specialists, as well as highlighting barriers that should be considered and addressed.

Zhao Y., Holtman M., Mudaly V., van Zyl G., Maartens G., Meintjes G.

Background: Dolutegravir resistance has been reported more frequently in patients with prior treatment experience compared to those on dolutegravir in first-line antiretroviral therapy (ART). The widespread use of dolutegravir in resource-limited programmatic settings might facilitate the emergence of resistance. Data on the prevalence of dolutegravir resistance from programmatic settings in Africa are scarce. Methods: This retrospective observational cohort study assessed dolutegravir resistance in routine care settings of the Western Cape provincial public healthcare sector program between February 2021 and June 2024. Treatment-experienced adults who developed virologic failure (two HIV-1 RNA ≥1000 copies/mL), who had received dolutegravir-based ART for >24 months, were eligible for genotypic antiretroviral resistance testing (GART). Drug resistance mutations (DRMs) and resistance levels were classified using the Stanford database. Results: Among 99 eligible patients, 76 had GART performed, and 68 had successful sequences. Among these 68, 43 (63%) had dolutegravir DRMs with: 1 potential low, 1 low, 15 intermediate, and 26 high resistance levels. The median time on dolutegravir-based ART was 24 months (IQR, 23–31). Of the 43 patients with dolutegravir DRMs, 21 (49%) were receiving zidovudine-lamivudine-dolutegravir and 19 (44%) were receiving tenofovir-lamivudine-dolutegravir; 42/43 had prior ART experience. Conclusions: Over 60% of patients with prior treatment experience who had been on dolutegravir-based ART for over two years and experienced virologic failure had intermediate or high level dolutegravir resistance. This suggests that criteria for GART used are too stringent, which has resource implications in programmatic settings where access to resistance testing for individual management is limited.