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

Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

Three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern predominantly drove South Africa's fourth COVID-19 wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild type amino acid at Q493.The two lineages only differ outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature . BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.08 - 0.09) and 0.10 (95% CI: 0.09 - 0.11) per day respectively over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus

Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants, respectively1-3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity

From lamins to lamina: a structural perspective

Lamin proteins are the major constituents of the nuclear lamina, a proteinaceous network that lines the inner nuclear membrane. Primarily, the nuclear lamina provides structural support for the nucleus and the nuclear envelope; however, lamins and their associated proteins are also involved in most of the nuclear processes, including DNA replication and repair, regulation of gene expression, and signaling. Mutations in human lamin A and associated proteins were found to cause a large number of diseases, termed 'laminopathies.' These diseases include muscular dystrophies, lipodystrophies, neuropathies, and premature aging syndromes. Despite the growing number of studies on lamins and their associated proteins, the molecular organization of lamins in health and disease is still elusive. Likewise, there is no comprehensive view how mutations in lamins result in a plethora of diseases, selectively affecting different tissues. Here, we discuss some of the structural aspects of lamins and the nuclear lamina organization, in light of recent results

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

Evaluating the effects of biogeography and fragmentation on the taxonomic, functional, and genetic diversity of forest-utilising bats in a South African biodiversity hotspot

Thesis (PhD)--Stellenbosch University, 2020.ENGLISH ABSTRACT: Bats are a highly diverse mammalian order and are some of the most economically important non-domesticated vertebrates, providing many ecosystem services that contribute to the global economy. Yet, they remain a largely understudied taxon, particularly in the Eastern Cape province of South Africa, in which basic surveys of bat assemblages utilising indigenous forests are lacking. Indigenous forests constitute South Africa’s smallest and most fragmented biome yet support disproportionally high biodiversity. They have been fragmented throughout most of their evolutionary history due to global palaeoclimatic shifts; the responses of bats to forest fragmentation and historical climatic shifts in this habitat have been poorly studied. This study addresses these gaps with the broad aims of compiling a species inventory from 17 forests across the Eastern Cape and KwaZulu-Natal provinces; assessing the effects of fragmentation and biogeography on taxonomic and functional diversity of bat assemblages; and determining how genetic diversity and population genetic structure are informed by forest habitat associations and fragmentation. A multi-faceted approach of sampling methods, including capture and acoustic recording, and species identification techniques (morphology, acoustics, and DNA barcoding) were used to assemble an inventory of 25 species, with range extensions noted for six species. The first reference call library of hand released bats for forests in this region is presented, which may be used for species identification in further acoustic surveys. A minimum acoustic monitoring period of 6 to 7 nights per forest is recommended for future surveys. Forest biogeography was an important determinant of the functional diversity of insectivorous bat assemblages. Forest edge effects were found to demonstrate a positive relationship with functional evenness, thus motivating for maintenance and conservation of forest edges, particularly in temperate regions. Larger forearm length and low wing loading were identified as morphological traits exhibiting greater sensitivity to fragmentation, flagging species exhibiting these traits as potentially vulnerable to habitat fragmentation. The effect of historical climate-induced fluctuations of forest extent on population genetic structuring and demographic histories for six species was investigated using two mitochondrial markers, cytochrome b and D-loop. Population genetic trends were not informed by forest habitat associations, but rather by species-specific traits of dispersal ability, philopatry, and roost utilisation. Low genetic diversity and high population structure identify two species, Rhinolophus swinnyi and Laephotis botswanae, for conservation priority. Demographic responses to the Last Glacial Maximum (LGM) were not detected, with all six species displaying population expansions over this time. It appears that volant insectivores in eastern South Africa were less affected by the harsh conditions of the LGM than elsewhere. The dusky pipistrelle (Pipistrellus hesperidus) was used as a model organism to investigate the gene flow, genetic diversity, and migration of a forest-utilising species across the region with the use of eight microsatellite markers. The effects of urbanisation and agricultural development on gene flow were also examined. Findings of low population structure, low migration rates, and two genetic discontinuities were presented. This species does not depict dependence on forested habitats to maintain genetic connectivity on the landscape. The data also suggest that agricultural development and urbanisation have not yet had an impact on gene flow, thus providing a baseline with which to monitor the effects of future anthropic development on this species. Overall, this study has provided novel insights into the taxonomic, functional, and genetic diversity of forest-utilising bats in relation to biogeographical history and fragmentation within eastern South AfricaAFRIKAANSE OPSOMMING: Vlermuise is 'n baie diverse soogdierorde en is van die mees ekonomies belangrike nie-domestiese gewerwelde diere, wat baie ekosisteemdienste lewer en sodoende bydra tot die wêreldekonomie. Tog bly hulle 'n grootliks onderbestudeerde takson, veral in die Oos-Kaap en KwaZulu-Natal provinsies van Suid-Afrika, waar basiese opnames oor vlermuis samestellings ontbreek. Inheemse woude vorm die kleinste en mees gefragmenteerde bioom van Suid-Afrika, maar nogtans ondersteun dit ‘n buitensporige hoë biodiversiteit. Hulle is deur die grootste deel van hul evolusionêre geskiedenis gefragmenteer as gevolg van wêreldwye paleoklimatiese verskuiwings; die reaksie van vlermuise op woudfragmentering en historiese klimaatverskuiwings in hierdie habitat is swak bestudeer. Hierdie studie spreek hierdie leemtes aan met die breë doelstellings om 'n spesies-inventaris vanaf 17 woude regoor die Oos-Kaap en KwaZulu-Natal provinsies saam te stel; die gevolge van fragmentasie en biogeografie op taksonomiese en funksionele diversiteit van vlermuis samestellings te evalueer; en vas te stel hoe genetiese diversiteit en genetiese struktuur van die populasie bepaal kan word deur woud habitat assosiasies en fragmentasie. 'n Veelsydige benadering van monsternemingsmetodes, insluitend vang- en akoestiese opname, asook spesie-identifikasietegnieke (morfologie, akoestiek en DNS-strepieskodering) is gebruik om 'n inventaris van 25 spesies saam te stel met uitbreidings in geografiese omvang aangeteken vir ses spesies. Die eerste biblioteek met roep verwysings vir hand vrygestelde vlermuise van woude in hierdie streek word aangebied wat in verdere akoestiese opnames gebruik kan word vir die identifisering van spesies. 'n Minimum akoestiese moniteringstydperk van 6 tot 7 nagte per woud word aanbeveel vir toekomstige opnames. Die biogeografie van ‘n woud was 'n belangrike bepalende faktor van die funksionele diversiteit van insekvretende vlermuise. Daar is gevind dat woud rand-effekte 'n positiewe verwantskap met funksionele egaligheid toon en bied dus motivering vir die instandhouding en bewaring van woud rande veral in gematigde streke. Groter voorarmlengte en lae vlerklading is geïdentifiseer as morfologiese eienskappe wat meer sensitiwiteit getoon het vir fragmentasie wat sodoende spesies wat hierdie eienskappe toon as potensieel kwesbaar vir fragmentasie van die habitat uitlig. Met behulp van twee mitokondriale merkers, sitokroom b en D-lus, is die effek van historiese klimaat-geïnduseerde wissellinge van die omvang van die woud op die genetiese strukturering en demografiese geskiedenis van die populasie vir ses spesies ondersoek. Populasie genetiese neigings is nie deur woud habitat assosiasies gevorm nie, maar eerder deur spesiespesifieke eienskappe van verspreidingsvermoë, filopatrie en nes gebruik. Lae genetiese diversiteit en hoë populasie struktuur identifiseer twee spesies, Rhinolophus swinnyi en Laephotis botswanae, vir prioriteitsbewaring. Demografiese reaksies op die Laaste Glasiale Maximum (LGM) is nie opgespoor nie met al ses spesies wat gedurende hierdie tyd uitbreiding in populasie getoon het. Dit lyk asof vlieënde insekvreters in oos Suid-Afrika minder geraak is deur die haglike toestande van die LGM as elders. Die Kuhl-vlermuis (Pipistrellus hesperidus) is as 'n modelorganisme gebruik om die geenvloei, genetiese diversiteit en migrasie van 'n woud-bruikende spesie oor die hele streek te ondersoek met behulp van agt mikrosatellietmerkers. Die gevolge van verstedeliking en landbou ontwikkeling op geenvloei is ook ondersoek. Bevindinge van lae populasie struktuur, lae migrasietempo, en twee genetiese diskontinuïteite word aangebied. Hierdie spesie toon nie ‘n afhanklikheid van bewoude habitatte om genetiese konnektiwiteit in die landskap te handhaaf nie. Die data dui ook daarop dat landbou ontwikkeling en verstedeliking nog nie 'n invloed op geenvloei gehad het nie wat dus 'n basis bied om die gevolge van toekomstige antropiese ontwikkeling te montior op hierdie spesie. Hierdie studie lewer as geheel nuwe insigte tot die taksonomiese, funksionele en genetiese diversiteit van woud-bruikende vlermuise in verband met biogeografiese geskiedenis en fragmentasie in oos Suid-Afrika.Doctora

The habitat use, temporal distribution and preferred weather conditions of Tadarida aegyptiaca and Neoromicia capensis, and its application to wind farm development in South Africa

M.Sc. (Biodiversity and Conservation)The relative activity levels of the Egyptian free-tailed bat (Tadarida aegyptiaca) and Cape serotine bat (Neoromicia capensis) were monitored in eight study areas spanning across the Eastern Cape, Western Cape and Northern Cape of South Africa. The detected activity levels were then used to study the habitat use and temporal distribution (across the night and months of monitoring period) of both species. The effect of weather conditions (namely temperature, relative humidity, wind speed, precipitation and barometric pressure), moon phase and moonlight on activity was also examined. The understanding of these aspects of the ecology of N. capensis and T. aegyptiaca were then used as guidelines to conserve these species with regards to wind farm development in South Africa. Bat activity was monitored by means of a total of seventeen passive monitoring systems consisting of SM2BAT+ bat detectors. The monitoring systems were deployed on the study areas to detect and record bat echolocation calls on a continuous basis throughout the night. Activity was recorded for a variable length of time, between 3 and 12 months, for each study area. The bat detectors were powered by solar energy systems. Habitat use by these species was analysed by comparing the activity amongst the different study areas. Both species showed considerable activity in most study areas depicting them to mostly be generalists inhabiting many habitats across the country. Bat activity amongst the different land use types, vegetation types and climate regions was studied. N. capensis showed significantly higher activity in a fruit farming area and T. aegyptiaca was significantly less abundant in dry and arid conditions than cooler humid environments. The preference for habitat based on altitude and height above the ground was assessed. The highest activity occurred in coastal regions of 0 – 500 m altitude. N. capensis was found to prefer activity at canopy height, and T. aegyptiaca is more of an opportunistic species making use of the most profitable vertical airspace at any one time Analysis of the hourly and monthly distribution of bat activity showed that it can be highly variable across a range of temporal scales from all study areas. On a broad scale, N. capensis was found to limit nightly activity within the first four hours of sunset, mostly peaking within the second hour. T. aegyptiaca tends towards peak activity within the first three hours of the evening, thereafter sustaining more or less constant activity until the ninth hour after sunset. For both N. capensis and T. aegyptiaca, activity in the Eastern Cape is greater over the months of September to March. Western Cape activity shows a general increase into the warm months of September – December followed by a decrease over the hot months of January and February. From the limited data set, activity in the Northern Cape seems to be highest over the months of November, December and April..

Ancestral Origin and Dissemination Dynamics of Reemerging Toxigenic Vibrio cholerae, Haiti

The 2010 cholera epidemic in Haiti was thought to have ended in 2019, and the Prime Minister of Haiti declared the country cholera-free in February 2022. On September 25, 2022, cholera cases were again identified in Port-au-Prince. We compared genomic data from 42 clinical Vibrio cholerae strains from 2022 with data from 327 other strains from Haiti and 1,824 strains collected worldwide. The 2022 isolates were homogeneous and closely related to clinical and environmental strains circulating in Haiti during 2012–2019. Bayesian hypothesis testing indicated that the 2022 clinical isolates shared their most recent common ancestor with an environmental lineage circulating in Haiti in July 2018. Our findings strongly suggest that toxigenic V. cholerae O1 can persist for years in aquatic environmental reservoirs and ignite new outbreaks. These results highlight the urgent need for improved public health infrastructure and possible periodic vaccination campaigns to maintain population immunity against V. cholerae