Research in high-impact factor journals:

Nature (IF - 64,8)

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK. Here an investigation of 38 cases is reported, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods.

This paper detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases.

Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers Instead, a AAV2 DNA complexes reflecting both HAdV-mediated and HHV6B-mediated replication was identified

It is hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

Metagenomic analysis and HAdV sequencing were carried out by the routine diagnostic service at Great Ormond Street Hospital (GOSH) Additional PCRs, immunohistochemistry and proteomics on samples received for metagenomics are part of the GOSH protocol for confirmation of new and unexpected pathogens

Initial diagnostic testing by metagenomics and PCR was performed at GOSH Microbiology and Virology clinical laboratories Further WGS and characterization were performed at UCL

In conclusion the livers of these children have a distinctive pattern of damage which does not indicate a specific aetiology, it does not exclude but does not offer positive support for either autoimmune hepatitis or a direct cytopathic effect of virus on hepatocytes. Each image shows a representative result from histology carried out on a minimum of five cases

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Together, Michèle and June will illustrate the potential for precision medicine approaches to managing diseases in African populations Ideally, precision medicine helps to inform an individual’s susceptibility to disease and its progression and response to treatment. As it relies on patient-specific genetic data, precision medicine has the potential to significantly improve prognosis and outcomes As Michèle explains, “It is about individualising diagnosis and treatment for the best possible health outcome and not using a ‘one size fits all’ approach”

Of the 8 billion people on earth, African populations harbour the greatest level of genetic diversity, creating a complex genetic environment that also impacts disease susceptibility However, African populations remain largely underrepresented in genomic studies and delays in conducting research means there won’t be development of appropriate diagnostic tests, treatments, and interventions that can save lives. Their lecture will address how local data and research are essential when seeking solutions for the continent and how the academic community at Wits needs to be at the forefront of this research

Susceptibility to developing common diseases like hypertension, diabetes and cancer is only partly genetic Additional factors such as behaviour, lifestyle, and the environment call for more comprehensive data, novel analysis approaches, and nuanced interpretations in our populations

The rich historical links between genetic variants and environmental selection can also strengthen a population’s ability to resist some diseases

Drug use is relatively recent and all drug development occurs in non-African populations. So despite widespread use, there is much for us to learn about the

science and collaboration stating that

“There are many unwanted consequences, some include adverse drug reactions and increased sideeffects in those who don’t metabolise drugs quickly, or the opposite, where the drug may be ineffective and patients do not respond to treatment,” emphasises June current global data do not perform well in African populations. More research and larger well-characterised cohorts are critical to ensure that Africa is not left behind in the era of precision medicine,”

“precision medicine approaches are the future, but we need to ensure that African populations are adequately represented – not an easy task given the genetic diversity within Africa The solution is for us to work closely with other African countries to establish new (and expand current) research collaborations that prioritise our needs and impact the care we offer We also need to develop strong partnerships with industry to ensure equitable and affordable access to treatments - as seen with lessons learned from COVID.”

June further presents important views on translational says Michèle.

Dr June Fabian

Nephrologist and Research Director of the Wits

Gordon Medical Centre

Wits Faculty of Health Sciences much of the research effort is directed towards serious health issues that are affecting our communities. There are currently 28 research entities based in the Faculty and two Research Thrusts (Diseases of Lifestyle and Molecular Biosciences). The quality of the Faculty’s research output ranks amongst the best in South Africa and is respected internationally

The Developing Excellence in Leadership, Training, and Science in Africa (DELTAS Africa) was launched as a bold endeavour that continues to redefine and shift the centre of science gravity to the African region. The launch included 14 programmes, and among them was the Sub-Saharan Africa Consortium for Advanced Biostatistics (SSACAB-II) led by Professor Tobias Chirwa, Wits School of Public Health.

Signed through Wits Health Consortium, SSACAB-II is a biostatistics collaborative initiative consisting of seven partner institutions based in Africa and the north, and several collaborating institutions. The initiative is funded by the Wellcome and the UK Foreign Commonwealth & Development Office (FCDO) to the tune of US$4 4 million over 4 years and is being implemented through the Science for Africa (SFA) Foundation.

SSACAB-II aims to develop by providing answers by addressing seven biostatistical research questions that have direct policy implications for the population health and health needs of Sub-Saharan Africa. This programme will contribute towards building highstandard biostatistical capacity in Africa Specialists with such competencies are limited and often inundated with the demand for their expertise

To bridge the gap, this programme assembles likeminded academic and research institutions to increase and strengthen researchers' biostatistical expertise thereby contributing to the growth of the biostatistical network – particularly in Africa.

The first round of SSACAB, which ran from 2015 to 2021, was notably successful in supporting numerous African universities to develop Masters’s programmes in biostatistics To date, 150 fellows have been awarded scholarships, of which 123 were Masters fellowships This programme produced graduates who are employed in both African academia and research institutions, enhancing the programme’s objective to feed highstandard biostatisticians into the continent

In 2019, the University of the Witwatersrand became the first African institution to gain Royal Statistical Society accreditation for a Biostatistics Masters programme. It is thus encouraging that Wits is leading the strides to guide other African institutions to the same capacity SSACAB is invested to upskill the biostatisticians who were already in the field through facilitated conferences as well as face-to-face and online short courses. This has been an effective strategy for developing and teaching advanced biostatistics methods, supervision and mentoring of PhD candidates

In looking to a successful, period ahead for this programme, Professor Chirwa says that

Funding initiatives have hugely increased the volume of highquality data generated, but there are clear discrepancies between the amount of data and the capacity to analyse it, says the SSACAB Programme Director, Professor Tobias Chirwa

SSACAB II aims to develop regional nodes of biostatistics excellence in Africa which will be able to work with research and training institutions by applying advanced biostatistical and data science methodology to address cutting edge public health challenges.