The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Palliative Radiotherapy and Hormonal Deprivation for Prostate Cancer Induced Urinary Obstruction at a Sub-Saharan Tertiary Hospital

The occurrence of bladder outlet obstruction (BOO) in men with prostate cancer is common. Although relieving the obstruction may not change prognosis, it is highly valued by patients and is generally associated with improvement in general functioning and wellbeing in the short-term. The aim of this study was to assess the efficacy of high-dose external beam radiation therapy (EBRT) combined with bilateral subcapsular orchidectomy (BSO) to relieve BOO due to prostate cancer. A retrospective study design was employed and conducted at the Mulago National Referral Hospital. Records of all patients with high-risk prostate cancer who presented with urinary obstructive symptoms and treated with the BSO and EBRT were retrieved. The study variables were age, clinical stage, and pathological Gleason score. The endpoint of the study was for patients to be able to pass urine after removing the urethral catheter, analysed as follows: complete failure to pass urine; partial emptying with a post-void volume &gt;100 mL, and passing urine with complete emptying and a post-void volume &lt;100 mL. In total, 46 patients were analysed in the period of January 2011–December 2012. Mean age was 71 years (range: 63–93). Eight patients failed to pass urine, while six passed urine incompletely (partial emptying). Thirty-two passed urine with a good stream and emptied the bladder completely. The success rate was 32/46 (70%). All patients had T3 and T4 stage disease with Gleason scores &gt;8. In conclusion, orchidectomy combined with EBRT was found to be an effective and feasible option for relieving BOO due to prostate cancer.</jats:p

Genomic characterization of SARS-CoV-2 from Uganda using MinION nanopore sequencing

Abstract SARS-CoV-2 undergoes frequent mutations, affecting COVID-19 diagnostics, transmission and vaccine efficacy. Here, we describe the genetic diversity of 49 SARS-CoV-2 samples from Uganda, collected during the COVID-19 waves of 2020/2021. Overall, the samples were similar to previously reported SARS-CoV-2 from Uganda and the Democratic Republic of Congo (DRC). The main lineages were AY.46 and A.23, which are considered to be Delta SARS-CoV-2 variants. Further, a total of 268 unique single nucleotide variants and 1456 mutations were found, with more than seventy percent mutations in the ORF1ab and S genes. The most common mutations were 2042C>G (83.4%), 14143C>T (79.5%), 245T>C (65%), and 1129G>T (51%), which occurred in the S, ORF1ab, ORF7a and N genes, respectively. As well, 28 structural variants—21 insertions and 7 deletions, occurred in 16 samples. Our findings point to the possibility that most SARS-CoV-2 infections in Uganda at the time arose from local spread and were not newly imported. Moreover, the relatedness of variants from Uganda and the DRC reflects high human mobility and interaction between the two countries, which is peculiar to this region of the world

Whole-genome sequencing of SARS-CoV-2 in Uganda: implementation of the low-cost ARTIC protocol in resource-limited settings

Background: In January 2020, a previously unknown coronavirus strain was identified as the cause of a severe acute respiratory syndrome (SARS-CoV-2). The first viral whole-genome was sequenced using high-throughput sequencing from a sample collected in Wuhan, China. Whole-genome sequencing (WGS) is imperative in investigating disease outbreak transmission dynamics and guiding decision-making in public health. Methods: We retrieved archived SARS-CoV-2 samples at the Integrated Biorepository of H3Africa Uganda, Makerere University (IBRH3AU). These samples were collected previously from individuals diagnosed with coronavirus disease 2019 (COVID-19) using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). 30 samples with cycle thresholds (Cts) values &lt;25 were selected for WGS using SARS-CoV-2 ARTIC protocol at Makerere University Molecular Diagnostics Laboratory. Results: 28 out of 30 (93.3%) samples generated analyzable genomic sequence reads. We detected SARS-CoV-2 and lineages A (22/28) and B (6/28) from the samples. We further show phylogenetic relatedness of these isolates alongside other 328 Uganda (lineage A = 222, lineage B = 106) SARS-CoV-2 genomes available in GISAID by April 22, 2021 and submitted by the Uganda Virus Research Institute. Conclusions: Our study demonstrated adoption and optimization of the low-cost ARTIC SARS-CoV-2 WGS protocol in a resource limited laboratory setting. This work has set a foundation to enable rapid expansion of SARS-CoV-2 WGS in Uganda as part of the Presidential Scientific Initiative on Epidemics (PRESIDE) CoV-bank project and IBRH3AU.</ns3:p

Beyond the fever:shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness

BackgroundNon-malarial febrile illnesses (NMFI) pose significant challenges in HIV-infected children, often leading to severe complications and increased morbidity. While traditional diagnostic approaches focus on specific pathogens, shotgun metagenomic sequencing offers a comprehensive tool to explore the microbial landscape underlying NMFI in this vulnerable population ensuring effective management.MethodsIn this study, we employed shotgun metagenomics to analyse stool samples from HIV-infected children at the Baylor Children’s Clinic Uganda presenting with non-malarial febrile illness. Samples were collected and subjected to DNA extraction at the Molecular and Genomics Laboratory, Makerere University followed by shotgun metagenomics sequencing at the Chan Zuckerberg Biohub San Francisco. Bioinformatics analysis was conducted to identify and characterise the microbial composition and potential pathogenic taxa associated with NMFI using the CZID pipeline.ResultsOur findings reveal a diverse array of microbial taxa in the stool samples of HIV-infected children with NMFI. Importantly, shotgun metagenomics revealed potentially pathogenic players including Trichomonas vaginalis, Candida albicans, Giardia, and Bacteroides in stool from this patient population. This sheds light on the complexities of microbial interactions that potentially underpin non-malarial febrile illness in this group. Taxonomic profiling identified recognised pathogens and comorbidities and revealed possible new correlations with NMFI, shedding light on the pathophysiology of fever in HIV-infected children.ConclusionShotgun metagenomics is a valuable method for understanding the gut microbial landscape of NMFI in HIV-infected children, providing a comprehensive approach to pathogen identification and characterisation. By revealing potential pathogenic actors beyond the fever, this work demonstrates how metagenomic sequencing may improve our knowledge of infectious illnesses in vulnerable groups and inspire targeted therapies for better clinical care and outcomes