Translation of genomic epidemiology of infectious pathogens: Enhancing African genomics hubs for outbreaks.

BACKGROUND: Deadly emerging infectious pathogens pose an unprecedented challenge to health systems and economies, especially across Africa, where health care infrastructure is weak, and poverty rates remain high. Genomic technologies are vital for enhancing the understanding and development of intervention approaches against these pathogens, including Ebola and the novel coronavirus disease 2019 (COVID-19). DISCUSSION: Africa has contributed few genomes of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) to the global pool in growing open access repositories. To bridge this gap, the Africa Centre for Disease Control and Prevention (ACDC) is coordinating continent-wide initiatives to establish genomic hubs in selected well-resourced African centres of excellence. This will allow for standardisation and efficient and rapid data generation and curation. However, the strategy to ensure capacity for high-throughput genomics at selected hubs should not overshadow the deployment of portable, field-friendly and technically less demanding genomics technologies in all affected countries. This will enhance small-scale local genomic surveillance in outbreaks, leaving validation and large-scale approaches to be taken at central genomic hubs. CONCLUSION: The ACDC needs to scale-up its campaign for government support across African Union countries to ensure the sustainable financing of its strategy for increased pathogen genomic intelligence and other interventions in current and inevitable future epidemics in Africa

Effect of intra-partum azithromycin on the development of the infant nasopharyngeal microbiota: A post hoc analysis of a double-blind randomized trial.

BACKGROUND: Sepsis is a leading cause of neonatal death. Intrapartum azithromycin reduces neonatal nasopharyngeal carriage of potentially pathogenic bacteria, a prerequisite for sepsis. Early antibiotic exposure has been associated with microbiota perturbations with varying effects. This study aims to understand the effect of intrapartum azithromycin intervention on the developing nasopharyngeal microbiota of the child. METHODS: Using 16S rRNA gene sequencing, we analysed the microbiota of 343 nasopharyngeal samples collected from birth to 12 months from 109 healthy infants selected from a double-blind randomized placebo-controlled clinical trial conducted in the Gambia (PregnAnZI-1). In the trial, 829 women were given 2g oral azithromycin or placebo (1:1) during labour with the objective of reducing bacterial carriage in mother and child during the neonatal period. The post-hoc analysis presented here assessed the effect of the intervention on the child nasopharyngeal microbiota development. FINDINGS: 55 children were from mothers given azithromycin and 54 from mothers given placebo. Comparing arms, we found an increase in alpha-diversity at day-6 (p = 0·018), and a significant effect on overall microbiota composition at days 6 and 28 (R2 = 4.4%, q = 0·007 and R2 = 2.3%, q = 0·018 respectively). At genus level, we found lower representation of Staphylococcus at day-6 (q = 0·0303) and higher representation of Moraxella at 12 months (q = 0·0443). Unsupervised clustering of samples by microbial community similarity showed different community dynamics between the intervention and placebo arms during the neonatal period. INTERPRETATION: These results indicate that intrapartum azithromycin caused short-term alterations in the nasopharyngeal microbiota with modest overall effect at 12 months of age. Further exploration of the effects of these variations on microbiome function will give more insight on the potential risks and benefits, for the child, associated with this intervention. FUNDING: This work was jointly funded by the Medical Research Council (UK) (MC_EX_MR/J010391/1/MRC), Bill & Melinda Gates Foundation (OPP1196513), and MRCG@LSHTM Doctoral Training Program

A METAGENOMIC ASSESSMENT OF BACTERIAL CONTAMINATION OF DUST EVENTS IN SENEGAL

Previous work in the Caribbean and West Africa have shown that air samples taken during dust events contain microorganisms (bacteria, fungi, viruses), including human pathogens that can cause many respiratory diseases. To better understand the potential downstream effect of bacteria dust on human health and public ecosystems, it is important to characterize the source population. In this study, we aimed to explore the bacterial populations of African dust samples collected between 2013-2017. The dust samples were collected using the spatula method, then the hypervariable regions (V3 and V4) of the 16S rRNA gene were amplified using PCR followed byMiSeq Illumina sequencing. Analysis of the sequencing data were performed using MG-RAST. At the phylum level, the proportions of Actinobacteria (22%), Firmicutes (20%), Proteobacteria (19%), and Bacteroidetes (13%) were respectively predominant in all dust samples. At the genus level, Bacillus(16%), Pseudomonas(10%), Nocardiodes and Exiguobacterium (5%) are the most dominated genera in African dust samples collected in this study.The study showed that molecular characterization of dust microbial population remains a very efficient method, also applicable to the search for viruses and fungi in this type of sample. It is important to note that the majority of microorganisms identified in this study can cause respiratory diseases.</jats:p

Invasive atypical non-typhoidal Salmonella serovars in The Gambia.

Invasive non-typhoidal Salmonella (iNTS) disease continues to be a significant public health problem in sub-Saharan Africa. Common clinical misdiagnosis, antimicrobial resistance, high case fatality and lack of a vaccine make iNTS a priority for global health research. Using whole genome sequence analysis of 164 invasive Salmonella isolates obtained through population-based surveillance between 2008 and 2016, we conducted genomic analysis of the serovars causing invasive Salmonella diseases in rural Gambia. The incidence of iNTS varied over time. The proportion of atypical serovars causing disease increased over time from 40 to 65 % compared to the typical serovars Enteritidis and Typhimurium that decreased from 30 to 12 %. Overall iNTS case fatality was 10%, but case fatality associated with atypical iNTS alone was 10 %. Genetic virulence factors were identified in 14/70 (20 %) typical serovars and 45/68 (66 %) of the atypical serovars and were associated with: invasion, proliferation and/or translocation (Clade A); and host colonization and immune modulation (Clade G). Among Enteritidis isolates, 33/40 were resistant to four or more of the antimicrobials tested, except ciprofloxacin, to which all isolates were susceptible. Resistance was low in Typhimurium isolates, but all 16 isolates were resistant to gentamicin. The increase in incidence and proportion of iNTS disease caused by atypical serovars is concerning. The increased proportion of atypical serovars and the high associated case fatality may be related to acquisition of specific genetic virulence factors. These factors may provide a selective advantage to the atypical serovars. Investigations should be conducted elsewhere in Africa to identify potential changes in the distribution of iNTS serovars and the extent of these virulence elements

Origin of imported SARS-CoV-2 strains in The Gambia identified from whole genome sequences.

The SARS-CoV-2 disease, first detected in Wuhan, China, in December 2019 has become a global pandemic and is causing an unprecedented burden on health care systems and the economy globally. While the travel history of index cases may suggest the origin of infection, phylogenetic analysis of isolated strains from these cases and contacts will increase the understanding and link between local transmission and other global populations. The objective of this analysis was to provide genomic data on the first six cases of SARS-CoV-2 in The Gambia and to determine the source of infection. This ultimately provide baseline data for subsequent local transmission and contribute genomic diversity information towards local and global data. Our analysis has shown that the SARS-CoV-2 virus identified in The Gambia are of European and Asian origin and sequenced data matched patients' travel history. In addition, we were able to show that two COVID-19 positive cases travelling in the same flight had different strains of SARS-CoV-2. Although whole genome sequencing (WGS) data is still limited in sub-Saharan Africa, this approach has proven to be a highly sensitive, specific and confirmatory tool for SARS-CoV-2 detection

Genomic Epidemiology of SARS-CoV-2 in Western Burkina Faso, West Africa.

BACKGROUND: After its initial detection in Wuhan, China, in December 2019, SARS-CoV-2 has spread rapidly, causing successive epidemic waves worldwide. This study aims to provide a genomic epidemiology of SARS-CoV-2 in Burkina Faso. METHODS: Three hundred and seventy-seven SARS-CoV-2 genomes obtained from PCR-positive nasopharyngeal samples (PCR cycle threshold score &lt; 35) collected between 5 May 2020, and 31 January 2022 were analyzed. Genomic sequences were assigned to phylogenetic clades using NextClade and to Pango lineages using pangolin. Phylogenetic and phylogeographic analyses were performed to determine the geographical sources and time of virus introduction in Burkina Faso. RESULTS: The analyzed SARS-CoV-2 genomes can be assigned to 10 phylogenetic clades and 27 Pango lineages already described worldwide. Our analyses revealed the important role of cross-border human mobility in the successive SARS-CoV-2 introductions in Burkina Faso from neighboring countries. CONCLUSIONS: This study provides additional insights into the genomic epidemiology of SARS-CoV-2 in West Africa. It highlights the importance of land travel in the spread of the virus and the need to rapidly implement preventive policies. Regional cross-border collaborations and the adherence of the general population to government policies are key to prevent new epidemic waves

SARS-CoV-2 sequencing collaboration in west Africa shows best practices.

Correspondence - No abstract available

COVID-19 reinfections in The Gambia by phylogenetically distinct SARS-CoV-2 variants-first two confirmed events in west Africa.

At the beginning of the COVID-19 pandemic, in early 2020, the scientific community hypothesised that SARS-CoV-2 transmission would eventually be hindered by herd immunity, conferred by natural infection, vaccination, or both.1 However, essential questions about whether infection with SARS-CoV-2 confers protection against reinfection and the length of time the protection lasts after either infection or vaccination remain open. These answers are crucial for the development of appropriate health control measures worldwide and become more important as new viral variants spread

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