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Ethiopia is the second most populous country in Africa and the sixth most affected by COVID-19 on the continent. Despite having experienced five infection waves, >499,000 cases, and ~7500 COVID-19-related deaths as of January 2023, there is still no detailed genomic epidemiological report on the introduction and spread of SARS-CoV-2 in Ethiopia. In this study, we reconstructed and elucidated the COVID-19 epidemic dynamics. Specifically, we investigated the introduction, local transmission, ongoing evolution, and spread of SARS-CoV-2 during the first four infection waves using 353 high-quality near-whole genomes sampled in Ethiopia. Our results show that whereas viral introductions seeded the first wave, subsequent waves were seeded by local transmission. The B.1.480 lineage emerged in the first wave and notably remained in circulation even after the emergence of the Alpha variant. The B.1.480 was outcompeted by the Delta variant. Notably, Ethiopia’s lack of local sequencing capacity was further limited by sporadic, uneven, and insufficient sampling that limited the incorporation of genomic epidemiology in the epidemic public health response in Ethiopia. These results highlight Ethiopia’s role in SARS-CoV-2 dissemination and the urgent need for balanced, near-real-time genomic sequencing.

Introduction: Limited data is available with regard to the epidemiology of primary malignant orthopaedic tumours in the South African clinical setting. As a result, orthopaedic surgeons have to rely on data from other countries when formulating differential diagnoses for malignant bone lesions. Existing data, however, demonstrates variance in the incidence between different geographic regions. By analysing the tumour epidemiology at our centre and comparing it to published data from other parts of the world, we aim to better define the local prevalence of primary malignant bone tumours. Materials and methods: A retrospective review of all patients with biopsy confirmed malignant primary bone tumours that presented between January 2008 and June 2015 were conducted. Patients with multiple myeloma and lymphoma were excluded. Epidemiological data pertaining to patient demographics, tumour location and histological diagnosis were recorded and analysed. Results: Included for review were 117 patients with biopsy-confirmed primary malignant bone tumours. Tumours involving the proximal humerus, distal femur, proximal tibia and pelvis accounted for 80% of all tumours. Osteosarcoma was the most common histological diagnosis (72.6%) and higher than reported figures from any other country. It was followed by chondrosarcoma (11.4%), Ewing's sarcoma (9.4%), spindle cell sarcoma (4.2%) and malignant giant cell tumour (GCT) (1.7%). A single patient was diagnosed with adamantinoma. HIV infection had no significant association with primary bone tumour incidence. Conclusion: Epidemiological data from this review reflect small but significant differences compared to international literature. The incidence of osteosarcoma appeared to be higher than in previous reports from other regions. Future study in this area may identify a reason for this difference, socioeconomic reasons may be responsible.

HIV has been implicated in adverse birth outcomes, due to increased oxidative stress and inflammation. In addition, HIV has been reported to increase nitric oxide levels. Therefore the combined exposures to HIV and traffic-related air pollution, within South Durban, South Africa (SA), may lead to adverse birth outcomes. However, the exact mechanism is still unknown; this study aimed to identify a potential mechanism. First, the influence of HIV on oxidative and nitrosative stress markers in pregnant women was assessed. Secondly, the effect of these stress makers and exposure to oxides of nitrogen (NOx) on neonatal birthweight (BW) was evaluated. Finally, the effect HIV and traffic-related pollution exposure has on the oxidative and endoplasmic profile and epigenetic regulation of Nrf2-Keap1 pathway by miR-144 and miR-28 in pregnant women was determined. Women, in their third trimester with singleton pregnancies, who were HIV+ and HIV-, were recruited from Durban, SA. Biomarker levels of serum nitrites/nitrates (NO) and malondialdehyde (MDA) were analysed and mRNA expression levels of oxidative and endoplasmic stress response genes were assessed. Land regression modelling was performed to determine NOx exposure levels. HIV exposure during pregnancy was associated with increased NO levels. NO was shown to reduce neonatal BW. NO and MDA was found to reciprocally increase each other, with HIV differentially influencing MDA's effect on BW. HIV down-regulated miR-144 which was negatively associated with Nrf2, suggesting a potential mechanism for HIV associated chronic oxidative stress. This study proposes that NO plays a key role in neonatal BW reduction in response to HIV and traffic-related air pollution.

Patulin (PAT) is a common mycotoxin contaminant of apple products linked to impaired metabolic and kidney function. Adenosine monophosphate activated protein kinase (AMPK), abundantly expressed in the kidney, intercedes metabolic changes and renal injury. The alpha-1-adrenergic receptors (α1-AR) facilitate Epinephrine (Epi)-mediated AMPK activation, linking metabolism and kidney function. Preliminary molecular docking experiments examined potential interactions and AMPK-gamma subunit 3 (PRKAG3). The effect of PAT exposure (0.2–2.5 µM; 24 h) on the AMPK pathway and α1-AR was then investigated in HEK293 human kidney cells. AMPK agonist Epi determined direct effects on the α1-AR, metformin was used as an activator for AMPK, while buthionine sulphoximine (BSO) and N-acetyl cysteine (NAC) assessed GSH inhibition and supplementation respectively. ADRA1A and ADRA1D expression was determined by qPCR. α1-AR, ERK1/2/MAPK and PI3K/Akt protein expression was assessed using western blotting. PAT (1 µM) decreased α1-AR protein and mRNA and altered downstream signalling. This was consistent in cells stimulated with Epi and metformin. BSO potentiated the observed effect on α1-AR while NAC ameliorated these effects. Molecular docking studies performed on Human ADRA1A and PRKAG3 indicated direct interactions with PAT. This study is the first to show PAT modulates the AMPK pathway and α1-AR, supporting a mechanism of kidney injury.