Africa

A genomic survey of typhoid fever in Zimbabwe has shown how the bacteria behind recent outbreaks evolved extra levels of antimicrobial resistance. Researchers from the National Microbiology Reference Laboratory, Quadram Institute and University of East Anglia were part of the locally-led effort to trace the spread of resistance genes, which is now supporting management of the disease. The COVID-19 pandemic highlighted how genome sequencing can be used to track the evolution of disease-causing microbes. By reading the genetic sequence of thousands of virus samples, scientists could track the smallest changes in the genetic code and link these to different variants’ abilities to cause infection or evade vaccines. Now, in a study published in The Lancet Microbe journal, genome sequencing has been used to study another deadly disease, typhoid fever, and how it’s starting to overcome our defences against it. Typhoid fever claims over 135,000 lives annually, and with up to 18 million infections it presents a significant burden on healthcare, especially in low-resource countries in South Asia and Africa. It’s caused by Salmonella enterica serotype Typhi (S. Typhi) bacteria that live in humans, infecting the gut and spreading to the liver, spleen and gall bladder. Typhoid is highly infectious, most often transmitted through contaminated food and water. Treating typhoid relies on antimicrobials but in the last couple of decades, antimicrobial resistance (AMR) has made controlling it much harder. This has been seen in Zimbabwe, where since 2009 there have been multiple typhoid outbreaks, caused by resistant S. Typhi strains. In response, an emergency reactive vaccination campaign using Typhoid Conjugate Vaccine (TCV) was initiated in suburbs of Harare in 2019, providing moderate protection. To get a picture of the strains of S. Typhi responsible, and how they evolved antimicrobial resistance, researchers from the NMRL in Harare and University of Pretoria, along with an international consortium, including the Quadram Institute and the World Health Organization, turned to genomic sequencing. The researchers were funded by the Bill & Melinda Gates Foundation and the Biotechnology and Biological Sciences Research Council, part of UKRI. Working with local health authorities in Harare, they sequenced the genomes of 85 S. Typhi samples obtained from people with confirmed typhoid fever from 2012 to 2019, plus an extra 10 from clinical infections in the UK that were associated with travel to Zimbabwe. From this they could construct a “family tree” showing how the strains were related and evolved over time. Most of the strains sequenced came from a subbranch of a globally-distributed multi-drug resistant S. Typhi, known as 4.3.1.1. Their genomic detective work linked these to a common ancestor first seen in Zimbabwe in 2009, coinciding with renewed typhoid outbreaks. This transmission looks to have derived from S. Typhi previously tracked from Southern Asia into Kenya and Tanzania and subsequent spread south into Malawi. Of concern is that since 2009, S. Typhi in Zimbabwe has become even more resistant to antimicrobials. Within three years nearly two thirds of isolates studied had gained extra genes including those conferring additional resistance to antibiotics. The insidious increase in resistance is a major concern, but this study does start to give a handle on the current state of the problem. Diagnostic tests to identify which resistance genes are present can help decide on the most effective treatment and help in the clinical management of typhoid fever in Zimbabwe. The genomic analysis contributed to the decision to initiate a mass typhoid vaccination campaign in Harare, Zimbabwe. This study will be valuable in assessing the effectiveness of the campaign by providing a baseline view of the S. Typhi population beforehand. Ongoing genomic surveillance could also identify any “escape mutants” allowing healthcare authorities in Zimbabwe to react swiftly and help control typhoid fever and its devastating effects on morbidity and mortality. Reference: Population structure of Salmonella enterica Typhi in Harare, Zimbabwe (2012-2019) before typhoid conjugate vaccine rollout: a genomic epidemiology study, Gaetan Thilliez, Tapfumanei Mashe et al The Lancet Microbe DOI: 10.1016/S2666-5247(23)00214-8

Quadram Institute researchers working with scientists in Zimbabwe have built up a detailed picture of how SARS-CoV-2 variants were introduced and transmitted in the southern African country during 2020. Their findings, published in The Lancet Global Health, are based on the genomic sequencing of 156 positive samples taken across eight provinces (including metropolitan Bulawayo and Harare) in Zimbabwe between March and October 2020. The epidemiological analysis identified two distinct phases of the SARS-CoV-2 pandemic in Zimbabwe. The first phase between March and June 2020 saw cases linked to international travel from Asia, Europe or the USA, and travel from neighbouring African countries. Public health measures in this first phase, such as quarantine arrangements and suspension of tourism-related travel, appear to have been effective in delaying domestic spread. After July 2020, a rapid increase in probable community transmission took place with cases centered around densely populated cities with proximity to land borders or international airports. The genomic analysis of Zimbabwe’s samples showed there were at least 26 separate independent introductions of SARS-CoV-2 into the country that were associated with 12 global lineages. The same lineages that were observed during the initial period of introduction of SARS-CoV-2 into the country later spread through the community in the first epidemic wave. Part of the public health measures taken by Zimbabwe included identifying the need to understand the detailed genetic epidemiology of SARS-CoV-2 and especially its behaviour in terms of transmission, capacity to mutate, and virulence. Genomic surveillance of SARS-CoV-2 was key in order to help Zimbabwe understand and track the virus as it evolved, identify where the virus was coming from, how it was spreading, and inform public health control measures needed to limit its spread. To complete the initiative, with this kind of detailed genetic detective work involved, the Ministry of Health and Child Care tasked its National Microbiology Reference Laboratory (NMRL) in Harare. Key objectives for NMRL sought to help understand initial transmission of the disease, gain insight into domestic transmission of the virus, add context to the regional and global scientific data and to evaluate the role genomic sequencing could play in analysing infection outbreak. The Quadram Institute on the Norwich Research Park, UK, as part of the COVID-19 Genomics UK (COG-UK) consortium was also undertaking genomic sequencing for the UK government. Given the longstanding relationship and partnership between Zimbabwe and the UK in terms of academic and scientific research, the Quadram Institute was ideally placed to help provide support and expertise to NMRL in Zimbabwe where necessary. Professor Rob Kingsley, Group Leader at the Quadram Institute and Professor of Microbiology at the University of East Anglia, said: “The UK has been able to sequence COVID-19 at considerable scale but far less is known about the epidemiology of this disease in Africa. This research, undertaken with our colleagues in Zimbabwe, helped track the spread and evolution of the virus in order to help inform public health measures.” NMRL Research Scientist Tapfumanei Mashe, reiterated the importance of research towards the development of vaccines. “Our experience of genomic sequencing of SARS-CoV-2 highlights the value of being able to build a very detailed picture of the virus and track its mutations for the potential to increase transmissibility, change virulence or influence the development of effective vaccines,” said Mashe. Reference:  Genomic epidemiology and the role of international and regional travel in the SARS-CoV-2 epidemic in Zimbabwe: a retrospective study of routinely collected surveillance data. Tapfumanei Mashe, Faustinos Tatenda Takawira, Leonardo de Oliveira Martins, Muchaneta Gudza-Mugabe, Joconiah Chirenda, Manes Munyanyi, Blessmore V Chaibva, Andrew Tarupiwa, Hlanai Gumbo, Agnes Juru, Charles Nyagupe, Vurayai Ruhanya, Isaac Phiri, Portia Manangazira, Alexander Goredema, Sydney Danda, Israel Chabata, Janet Jonga, Rutendo Munharira, Kudzai Masunda, Innocent Mukeredzi, Douglas Mangwanya, Alex Trotter, Thanh Le Viet, Steven Rudder, Gemma Kay, David Baker, Gaetan Thilliez, Ana Victoria Gutierrez, Justin O’Grady, Maxwell Hove, Sekesai Mutapuri-Zinyowera, Andrew J Page, Robert A Kingsley, Gibson Mhlanga. The Lancet Global Health https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00434-4/fulltext    

The spread of the COVID-19 pandemic in Africa has been outlined using genomic surveillance, providing insights into how the virus entered and spread across the continent, and how new variants of concern emerged. The findings drawn from 33 countries over the past year have today been published in the journal Science, and show that unless we ensure that Africa is not left behind in the global pandemic response, it could become a breeding ground for new variants of the virus. And that threatens further waves of the pandemic across the globe. Genomic surveillance involves sequencing the genetic code of the virus, and using naturally occurring minor changes in the genome to trace how different lines, or variants, spread. As soon as the gravity of the pandemic was realised, scientist across the globe started genomic sequencing samples, sharing this data internationally to try to keep tabs on its spread from its origins in Wuhan, China. The first COVID-19 cases were detected in Africa in late February 2020, and within a month almost every country was affected. From the outset, African laboratories started rapid genomic sequencing to help in tracing outbreaks and points of transmission, and identifying the emergence of new variants. Other scientists across the world supported these efforts, especially where there were potential gaps in the surveillance net. Researchers from the Quadram Institute in the UK contributed material, equipment and their experience as part of the COVID-19 Genomics UK Consortium. For example, they helped to train scientists from Zimbabwe’s National Microbiology Reference Laboratory to do their first genome sequencing ever and analyse their own data. Professor Rob Kingsley said: “We were already working with scientists at NMRL to study typhoid fever in Zimbabwe and we used this close working relationship to rapidly pivot in response to the Covid-19 emergency. Our Zimbabwe colleagues continue to strive to apply the most recent technologies to address the ongoing epidemic.” Over the next 12 months thousands more COVID-19 genomic sequences were read and uploaded to international databases. Now, in a paper published today in the journal Science, the researchers are able to present a dynamic view of how COVID-19 spread across Africa, and the lessons we must learn from this genomic data to prevent the future waves of the pandemic. The dataset shows that there were many different introductions of the virus into Africa, and that 64% of these came from Europe. The introductions came to a halt in April 2020, coinciding with the complete halt in air travel. The pandemic then entered a new phase characterised by low levels of within-country movements and occasional between neighbouring countries, reflecting how trade continued to some extent during country lockdowns. The second wave of the pandemic that broke across the world in late 2020 was clearly shown in the genomic data, with half of the sequences coming in the first 10 weeks of 2021. This second wave was more severe in Africa, in part because of the emergence of Variants of Concern (VOCs) that are more transmissible and/or cause more severe symptoms. Genomic surveillance is crucial in identifying these variants. The current study clearly maps the emergence and spread of the “Beta” variant (B.1.351), originally detected in South Africa. Following its emergence in the Eastern Cape, it spread extensively within South Africa and then into neighbouring Botswana and Mozambique and then further to Zambia. By March 2021, Beta had become dominant across Southern African countries as well as the overseas territories of Mayotte and Réunion. The apparently unimpeded spread of the Beta variant shows that current land border controls are ineffective at controlling the virus. The genomic surveillance analysis not only shows how rapidly new variants spread across Africa, but also how they are exported, mainly to Europe and Asia, making the second wave of the pandemic more severe globally, not just in Africa. It’s vital that we learn the lessons highlighted in this study to prevent more pandemic waves driven by other variants. Other variants have also been identified and are rising in frequency in the areas they were detected. Genomic surveillance has shown its value in identifying and tracking these, and the collaborations and networks now established in Africa will be needed to catch future variants as they emerge. Whilst this surveillance network is wide, it is thinly stretched and there are gaps. Supply problems and a lack of support leads to a lag between sampling and obtaining data, preventing a rapid public health response. This is being addressed; one of the  main outcomes of this work has been to strengthen collaboration across African countries through training and data sharing in a timely manner. But of biggest concern is the slow rollout of vaccines across much of Africa. This creates an environment that allows the virus to mutate and evolve, which left unchecked will inevitably lead to the emergence of new Variants of Concern, potentially even more transmissible than Beta, perhaps even able to escape the effects of current vaccines. The evidence from this year of genomic surveillance in Africa is clear: No-one is safe until everyone is safe.   Reference: A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa, Eduan Wilkinson, Marta Giovanetti, Houriiyah Tegall, James E. San et al was published by Science on Thursday 9th September at 19:00 UK BST, 2pm US ET https://www.science.org/doi/10.1126/science.abj4336  

Professor Rob Kingsley and Dr Gaetan Thilliez from the Quadram Institute are teaming up with Prof. Neil Hall of the Earlham Institute and Dr Sekesai Zinyowera and Tapfumanei Mashe of the National Microbiology Reference Laboratory in Harare to investigate the association of Salmonella Typhi with protists in the aquatic environment of Zimbabwe. Typhoid fever remains a major public health problem in Zimbabwe, with Harare the most affected city. Poor sanitation in some areas of Harare results in reduced drinking water quality, a key risk factor for Salmonella Typhi transmission. Protists, minute unicellular organisms, have been proposed to be a safe harbour for Salmonella Typhi, in intracellular vacuoles, and may be an evolved strategy for survival in water. The project will bring to bear cutting-edge whole genome and metagenome sequencing technologies and will pave the way for a deeper understanding of the survival and transmission strategies employed by Salmonella in the environment. This project is being funded by the Bill and Melinda Gates Foundation, through a new Global Grand Challenge Exploration (GCE) to examine the environmental niches of S. Typhi. It will bring together scientists from the Zimbabwe National Microbiological Reference Laboratory with scientists from the Quadram Institute and the Earlham Institute in the United Kingdom to investigate the co-existence of protozoa and Salmonella Typhi, and the epidemiological link to typhoid fever in residents of Harare, Zimbabwe. The project builds on a collaboration between Zimbabwe and UK organizations that has begun to reveal for the first time, the molecular epidemiology of typhoid fever in Zimbabwe. Quadram Institute researchers are also involved in two further grants from this Global Grand Challenge Exploration: Exploring the micro-ecology of sediment associated biofilms in high typhoid incidence settings in Fiji led by Dr Aaron Jenkins, University of Sydney. QI: Dr Gemma Langridge, Dr Alison Mather. Investigating persistence of S. Typhi in the aquatic environment in Madagascar, led by Prof. France Daigle, Université de Montréal. QI: Dr Gemma Langridge and Prof. John Wain.

The Quadram Institute, in partnership with other leading organisations, has organised a workshop to help researchers from across Africa exploit food composition data, improving local nutrition policies and public health advice. The workshop, which is being hosted by the new confirmed African Research University Alliance (ARUA) Centre of Excellence in Food Security at the University of Pretoria, is bringing together scientists, nutritionists and policy-makers from 11 African countries to share best practice in generating reliable, standardised data on the composition of foods, and set up networks to share data online. [caption id="attachment_13461" align="alignright" width="350"] Mark Roe (QI), Paul Finglas (QI, EuroFIR), Prof Hettie Schönfeldt (UP, AFROFOODS) Paul Hulshof (WUR) Beulah Pretorius (UP), Henriette Ene-Obong (AFROFOODS)[/caption] These data, and the tools to access and exploit it, underpin the development and implementation of local food and nutrition policies, regulatory measures, labelling and health advice. The Quadram Institute (UK), Wageningen University (NL), the University of Pretoria (ZA) and EuroFIR AISBL (BE) are contributing to this event, which was funded through the RCUK Global Challenges Research Fund; this aims to ensure that UK research takes a leading role in addressing the problems faced by developing countries. Over the course of the five-day workshop, participants will receive expert training in designing sampling protocols, calculating nutrient values, assessing data quality, and using appropriate tools for data compilation, management and data sharing. Through working closely with regional networks, including the FAO International Network of Food Data Systems’ AFROFOODS network, outcomes from the workshop will benefit not just the participants, but also the wider community of public health researchers who rely on these data. These networks will also provide a conduit for further future training and capacity building, by hosting online information resources and e-learning, and facilitating scientist exchanges. “We hope that this workshop will help to build local capacity in food composition data management, that will benefit countries across Africa” said Paul Finglas, head of the Quadram Institute Food Databanks National Capability and Managing Director of EuroFIR. “By giving researchers the knowledge and tools to generate data that matches shared standards, we can get more up-to-date data online and searchable so that it can provide a sound basis for nutrition and public health advice.” According to the 2017 Global Nutrition Report, nutrition programme have a $16 return of investment. “Towards attaining the 169 Targets of the 17 Global Goals Sustainable Development Goals (SDGs) approved by each of our governments” stated Hettie Schönfeldt, director of the new ARUA CoE for Food Security led by the University of Pretoria, South Africa in collaboration with the University of Ghana, Legon and the University of Nairobi ”targeted approaches to facilitate agricultural and food system transformation are as essential as partnerships in research and innovation in order to attain sustainable food security and nutrition in Future Africa and elsewhere”.

Pioneering a low cost method for Covid-19 DNA sequencing “When the covid pandemic started in early 2020, the COVID-19 Genomics UK Consortium (known as COG-UK) approached us to be one of the academic partners of the consortium. The government invested about £20 million into sequencing or looking for the variants and sequencing Sars-Cov-2. At the time, the protocols used were based on a similar method from when Ebola emerged, developed by Josh Quick and Nick Loman (ARTIC Network). At the beginning of 2020, this method for DNA sequencing Covid had low throughput (up to 24 at a time) which required a lot of labour and was slow. I had the idea to pivot the methods I’d been developing for sequencing bacteria quickly and cheaply at the Quadram Institute, over to Covid sequencing. The DNA sequencing method for Covid-19 that I developed with Alp Aydin and Alex Trotter, called CoronaHiT (High Throughput Corona Virus Sequencing), was ten times cheaper than the alternative methods out there at the time. In 2021 we published the CoronaHiT method in Genome Medicine. We were able to sequence 3,000 samples on a single run. In the end over 2020 to 2022 we sequenced over 87,000 samples. In the early stages of the pandemic , it was said, if the Quadram Institute were a country we’d be the fifth largest country in the world in terms of the number of uploads to the covid database. It was an impressive amount of sequencing we were doing from the middle of Norfolk. There was an incident where a patient had arrived from overseas and the Norfolk and Norwich University Hospital needed to know if it was the Delta variant. The sample came into the Quadram Institute building and within a couple of hours the sample was sequenced using the faster Oxford Nanopore method. During the pandemic we were able to use both Illumina short-read sequencing technology together with Oxford nanopore long-read sequencing, so we had a two-pronged attack in terms of sequencing samples dependent upon throughput verses speed of result considerations. Types of DNA sequencing There are two types of DNA sequencing. Short read technologies are limited in the amount of base pairs they can sequence but give a high-quality sequence, where we be confident of the order of base pairs. In long-read sequencing you can go much further. It’s also known as single molecule sequencing and you can get a better picture overall of the whole genome. However, due to each base pair being detected by differences in the voltage as the DNA passes through a pore, means it is less accurate than short read technologies, it has less accuracy than short read technologies. Using both short-read and long-read sequencing together can give us an overall better picture of the DNA sequence. DNA sequencing informing public health policy During the covid pandemic we were part of the REACT-study too, which was real-time surveillance of the variants in the UK conducted by Imperial College London. The Quadram Institute was the only sequencing hub in the UK to be sequencing REACT samples. Our DNA sequencing had a massive impact on policymaking within the government. We were looking at the movement of variants across the country and the effectiveness of the vaccines. This helped to form recommendations of which vaccines to use. There was an incident where we sequenced samples from Zimbabwe. They were ready to rollout vaccines, and they had several vaccines to choose from. Because of the sequencing we were doing at the Quadram Institute we were able to recommend switching to the vaccine which was more effective at the time. Towards the end of the pandemic, sequencing was tailing off and COG-UK was dissolved. But we remained as one of three sequencing surge sites, with Northumbria and UCL. The other two Covid Sequencing surge sites implemented our method, CoronaHiT, due to the cost-effectiveness, the robustness of the method and the speed. It was quite a proud moment. Ready for the next pandemic The Quadram Institute is a national capability for the country. In the future, if there is another pandemic with a different pathogen or virus, we can use our DNA sequencing method to track it. Our method is agnostic to the source. As long as we can generate double stranded DNA, it’s future proof for another event similar to the covid-19 pandemic. We use the same method we developed for Covid-19 sequencing, for lots of different applications at Quadram, mainly looking at bacteria, microbiomes and bacteriophages. A career across Norwich Research Park It’s amazing there’s a hub of different research institutes and labs in a small area in Norwich. It’s been a privilege to work on the Norwich Research Park over the years. The Norwich Research Park attracts people from all over the world to work at the institutes. The John Innes Centre and the Sainsbury Laboratory lead in plant and microbial science, Earlham Institute has built up expertise in bioinformatics and here at the Quadram Institute we apply fundamental science to improve human health. I’ve been on the Norwich Research Park nearly 30 years. I graduated in Mechanical Engineering and came to Norfolk to do teacher training. I found I didn’t like teacher training very much and got a job at the Sainsbury Lab on Norwich Research Park running early DNA sequences. My engineering background helped me learn DNA sequencing technology which was new at the time. After seven years at the Sainsbury Laboratory, I joined the John Innes Centre to work in their Genome Lab at the time. I helped run the DNA sequencing and other platforms for about seven years up until 2009. Around that time, the Biotechnology and Biological Sciences Research Council (BBSRC) had the inception of what is now the Earlham Institute and then was called The Genome Analysis Centre (TGAC). TGAC was established in Norwich by the BBSRC in partnership with regional economic development partners – The East of England Development Agency (EEDA), Norfolk County Council, South Norfolk Council, Norwich City Council and the Greater Norwich Development Partnership. I was the first person to generate a library and run an Illumina short read sequencer at the Earlham Institute. I ended up being there for nine years. Over those nine years, I got my hands on a lot of cutting-edge sequencing instruments and ventured into long read sequencing too. After nine years at the Earlham Institute, I left to work in a company for a short time before returning to the Norwich Research Park to join the Quadram Institute as the new Head of Sequencing. I love working in academia and having the freedom of playing around and do your own thing. After I started at the Quadram Institute I implemented some of the high-throughput low-cost technologies I had developed while at the Earlham Institute. Over the past five or six years, we’ve sequenced 200,000 different samples, which is quite impressive for such a small team of myself and one technician. At the Quadram we do both short-read and long-read sequencing. We take a bacterium and “shotgun sequence” it in short fragments for high-quality short-read sequences where there is very little or no errors. Then we can do longer reads which give a more zoomed out perspective, which although they have a higher error rate, can act as a scaffold to take on the high-quality short read sequences. In the future we may not need to use short read sequencing so much, because the base reading quality of the long-read sequencing is improving due to chemistry improvements and more advanced algorithms for identifying bases.” [embed]https://www.youtube.com/watch?v=wxNKT5Xbjoc[/embed]

The worldwide spread of SARS-CoV-2 variants of concern has highlighted the urgent need for truly global vigilance in a world where less than 5% of the SARS-CoV-2 genomes sequenced to date are from countries with 80% of the world’s population. In our recent correspondence in The Lancet Microbe, genomic surveillance work undertaken by Zimbabwe’s National Microbiology Reference Laboratory, supported by the Quadram Institute in Norwich, UK, has underlined the dangers of mutating variants. [caption id="attachment_22798" align="alignleft" width="300"] 3D rendered illustration of the coronavirus with RNA molecule inside.[/caption] The Zimbabwe research shows that between December 2020 and January 2021, the period of Zimbabwe’s second wave of Covid-19 infections, that new variants were predominant with 89% of 107 sequenced cases featuring mutations of concern. The identified variants included the previously reported B.1.351 (501Y.V2) and A.23.1 variants, along with a novel variant under investigation (C.2). The B.1.1.7, B.1.525, P.1, and P.2 and variants were not identified in Zimbabwe. Variants with concerning mutations have all replaced previously identified lineages in Zimbabwe. Firstly, the B.1.351 variant of concern, originally identified in South Africa, accounted for 74 (69%) of 107 sequenced cases in December 2020, and 99 (95%) of 104 sequenced cases in January 2021. The population structure was consistent with multiple separate introductions. Zimbabwe is the second country other than South Africa to report B.1.351 as the dominant variant to date. As in other countries, this variant has been associated with increased transmissibility, resulting in overwhelmed healthcare systems and in higher mortality than the first wave. Secondly, the A.23.1 variant of concern, first reported in Uganda, was observed in 3 (3%) of 107 sequenced cases in December, but was not observed in 104 sequenced cases in January. Thirdly, a variant designated C.2 and containing a spike protein mutation (N501T) that was previously reported in another lineage of SARS-CoV-2 found in mink was present in Zimbabwe in both December 2020, and January 2021. N501T is thought to improve ACE2 receptor binding in mink. A mutation in the same location, N501Y, is associated with increased transmissibility in humans. In December 2020, 18 (15%) of 117 of cases were found to be of the C.2 variant, whereas in January, 2021, this number fell to 3 (3%) of 104. Phylogenetic analysis of international genomes of the C.2 variant indicated that they were interspersed with C.2 genomes from Zimbabwean cases, indicating that Zimbabwe was a possible source. In conclusion, variants with concerning mutations identified in December 2020, and January 2021, have replaced previously identified lineages in Zimbabwe. This observation highlights the importance of global surveillance by whole-genome sequencing of SARS-CoV-2 to identify sources and transmission routes, and to provide supporting evidence for policy decisions. This research was partly funded by the Biotechnology and Biological Sciences Research Council Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10352. We declare no competing interests.   Our correspondence is dedicated to the memory of Sekesai Mtapuri-Zinyowera, who died on March 4, 2021.

Isolating a new bacteriophage (or phage), a virus that infects bacteria, is for many students their first venture into microbiology. Once you can see that first lysis zone or plaque on a lawn of bacteria, you know you’re in for an exciting scientific journey. In this age of genomics, the discovery of a new phage opens up the opportunity to sequence its genome and marvel at its diversity. But how do we go about making sense out of the sequence data, the phage genome and how does it fit in the known virosphere? As a Group Leader working with novel bacteriophages and as the Chair of the Bacterial Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV), I try to answer these questions on a near-daily basis. So when I was asked to present a webinar on phage genome annotation and classification for the Africa Phage Forum (apf.phage.directory), I was honoured and very happy to help early career scientists and scientists new to the phage field get started. In the webinar, I focused on specific features of phage genomes, the decision-making process that is important to get to a well-annotated genome, and how to name and classify your phage. With more time, I would have told much more, but I hope the webinar and the slides will get everyone started. You can watch Dr Adriaenssens' webinar below and download the slides here [pdf]

Today’s announcement by Health Secretary Matt Hancock of UK support with genomics expertise to help other countries identify new COVID-19 variants comes as researchers at the Quadram Institute outline their work supporting scientists in Zimbabwe. Today’s UK government announcement of the New Variant Assessment Platform will see other countries offered UK laboratory capacity and advice to analyse new strains of coronavirus. In common with many other countries facing the start of the coronavirus pandemic, Zimbabwe recorded its first recorded case of the SARS-CoV-2 in March 2020. Extensive public health interventions were swiftly put in place to help control transmission and protect people. Part of the public health measures taken by Zimbabwe included identifying the need to understand the detailed genetic epidemiology of SARS-CoV-2 and especially its behaviour in terms of transmission, capacity to mutate, and virulence. Genomic surveillance of SARS-CoV-2 was key in order to help Zimbabwe understand and track the virus as it evolved, identify where the virus was coming from, how it was spreading, and inform public health control measures needed to limit its spread. To complete the initiative, with this kind of detailed genetic detective work involved, the Ministry of Health and Child Care tasked its National Microbiology Reference Laboratory (NMRL) in Harare, with sequencing of the genetic material of positive samples from 100 coronavirus patients, between March and June 2020. Key objectives for NMRL sought to help understand initial transmission of the disease, gain insight into domestic transmission of the virus, add context to the regional and global scientific data and to evaluate the role genomic sequencing could play in analysing infection outbreak. The Quadram Institute on the Norwich Research Park, UK, as part of the COVID-19 Genomics UK (COG-UK) consortium was also undertaking genomic sequencing for the UK government. Given the longstanding relationship and partnership between Zimbabwe and the UK in terms of academic and scientific research, the Quadram Institute was ideally placed to help provide the much-needed support and expertise to NMRL in Zimbabwe where necessary. The Quadram Institute’s Professor Rob Kingsley said: “We were already working with scientists at NMRL to study typhoid fever in Zimbabwe and we used this close working relationship to rapidly pivot in response to the Covid-19 emergency. Our Zimbabwe colleagues continue to strive to apply the most recent technologies to address the ongoing epidemic.” As a result, Zimbabwe’s NMRL has successfully sequenced genomes to help develop what could be called a “family tree,” or phylogenetic analysis, for the virus in Zimbabwe, based on the whole genome sequencing of positive samples taken from 100 people over 120 days. The findings of the NMRL indicate that regional migration in southern Africa played a significant role in the transmission of the virus, certainly more so that intercontinental travel. Whilst early cases of COVID-19 in Zimbabwe were introductions from travel from the USA, UK and Dubai, later cases centred around continental migration, largely from South Africa. The genomic analysis of Zimbabwe’s 100 samples showed there were at least 25 separate independent introductions of SARS-CoV-2 into the country that were associated with eight global lineages. Ninety-five per cent featured the D614G genotype, a variant linked to increased transmissibility. From May 2020 onwards, surveillance highlighted a rise in cases originating with Zimbabwean residents returning from neighbouring countries, especially South Africa. With a two-week residential quarantine system in place, and most of the returnees were asymptomatic, testing was undertaken and on multiple occasions generated positive results for SARS-CoV-2. The genomic sequencing showed the cases were all from the same lineage implicating local transmission within the quarantine accommodation. NMRL Research Scientist Tapfumanei Mashe, reiterated the importance of research towards the development of vaccines. “Our experience of genomic sequencing of SARS-CoV-2 highlights the value of being able to build a very detailed picture of the virus and track its mutations for the potential to increase transmissibility, change virulence or influence the development of effective vaccines”, said Mashe. A pre-print on the genomic epidemiology of the SARS-CoV-2 epidemic in Zimbabwe is available on MedRxiv https://www.medrxiv.org/content/10.1101/2021.01.04.20232520v1?rss=1