In early 2018 Nigeria experienced an unprecedented increase in Lassa fever cases with widespread geographic distribution. We report 77 Lassa virus genomes generated from patient samples, 14 from 2018, to investigate whether recent changes in the virus genome contributed to this surge. Our data argue that the surge is not attributable to a single Lassa virus variant, nor has it been sustained by human-to-human transmission. We observe extensive viral diversity structured by geography, with major rivers appearing to act as barriers to migration of the rodent reservoir. Together our results support that the 2018 Lassa fever surge was driven by crossspecies transmission from local rodent populations of multiple viral variants from different lineages.

Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time 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 shed light on 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 re-emerging 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.

As the threat of arboviral diseases continues to escalate worldwide, the question of, “What types of human communities are at the greatest risk of infection?” persists as a key gap in the existing knowledge of arboviral diseases transmission dynamics. Here, we comprehensively review the existing literature on the socioeconomic drivers of the most common Aedes mosquito-borne diseases and Aedes mosquito presence/abundance. We reviewed a total of 182 studies on dengue viruses (DENV), chikungunya virus (CHIKV), yellow fever virus (YFVV), Zika virus (ZIKV), and presence of Aedes mosquito vectors. In general, associations between socioeconomic conditions and both Aedes -borne diseases and Aedes mosquitoes are highly variable and often location-specific. Although 50% to 60% of studies found greater presence or prevalence of disease or vectors in areas with lower socioeconomic status, approximately half of the remaining studies found either positive or null associations. We discuss the possible causes of this lack of conclusiveness as well as the implications it holds for future research and prevention efforts.

Effective disease outbreak response has historically been a challenging accomplishment for the Nigerian health system due to an array of hurdles not unique to Nigeria but also found in other African nations which share its large size and complexity. However, the efficiency of the response mounted against the Ebola Virus Disease (EVD) outbreak of 2014 proved that indeed, though challenging, proactive and effective outbreak response is not impossible. With over 20 public health emergencies and infectious disease outbreaks between 2016 and 2018 alone, Nigeria is one of only five members of the World Health Organization (WHO) African Region to report five or more public health events per annum. There are many lessons that can be drawn from Nigeria's experience in handling outbreaks of infectious diseases. In this review, we discuss the history of emerging and re-emerging infectious disease outbreaks in Nigeria and explore the response strategies mounted towards each. We also highlight the significant successes and note-worthy limitations, which we have then utilized to proffer policy recommendations to strengthen the Nigerian public health emergency response systems.

Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks.One-Sentence SummaryExpanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.

oyewale tomori 1 , chikwe ihekweazu 9 , pardis c. Sabeti 3,5,7,10 & christian t. Happi 1,2,6,7* fifty patients with unexplained fever and poor outcomes presented at irrua Specialist teaching Hospital (ISTH) in Edo State, Nigeria, an area endemic for Lassa fever, between September 2018-January 2019. After ruling out Lassa fever, plasma samples from these epidemiologically-linked cases were sent to the African centre of excellence for Genomics of infectious Diseases (AceGiD), Redeemer's University, ede, osun State, nigeria, where we carried out metagenomic sequencing which implicated yellow fever virus (YFV) as the etiology of this outbreak. Twenty-nine of the 50 samples were confirmed positive for YFV by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), 14 of which resulted in genome assembly. Maximum likelihood phylogenetic analysis revealed that these YfV sequences formed a tightly clustered clade more closely related to sequences from Senegal than sequences from earlier nigerian isolates, suggesting that the YfV clade responsible for this outbreak in edo State does not descend directly from the Nigerian YFV outbreaks of the last century, but instead reflects a broader diversity and dynamics of YfV in West Africa. Here we demonstrate the power of metagenomic sequencing for identifying ongoing outbreaks and their etiologies and informing real-time public health responses, resulting in accurate and prompt disease management and control. Yellow fever (YF) is an acute mosquito-borne viral haemorrhagic fever that is endemic in forty-seven countries across Africa, Central and South America. A 2013 mathematical model study using African data from the previous 25 years estimated that the burden of severe YF ranged from 84 000-170 000 cases with 29 000-60 000 deaths 1. Once common in Nigeria 2 YF was largely absent for twenty years, until 2017 when a new and still ongoing outbreak was reported 3. A total of 112 confirmed cases with 11 deaths have been recorded between September 2017 and March 2019, prompting the vaccination of more than 10 million people in the affected states 4. However, the relative absence of yellow fever (YF) in Nigeria over prior years led to unintended consequences of reducing vigilance for a disease whose clinical presentation overlaps other endemic infections such as malaria and Lassa

While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE—detected in the Yoruba population of Nigeria—conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the “emerging” nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz’s critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts.

We report here the use of metagenomic sequencing to identify and characterize yellow fever virus (YFV) in a cluster of undiagnosed febrile patients from Edo State, Nigeria. Yellow fever, an acute mosquito-borne viral haemorrhagic fever, re-emerged in Nigeria in 2017 after decades of relative control. 1 Once a major public health concern in the region, 2 the prolonged absence of yellow fever has left a gap in knowledge about circulating virus and lowered clinical suspicion for a disease whose spectrum overlaps with endemic infections ( e.g. , malaria and Lassa fever) . In this context, metagenomic sequencing can be a powerful tool for identifying and tracking pathogens causing infectious disease. 3 Plasma samples from thirteen epidemiologically-linked patients with unexplained, often fatal, fever were sent from Irrua Specialist Teaching Hospital to the African Center of Excellence for Genomics of Infectious Disease at Redeemer's University for investigation. Unbiased metagenomic sequencing revealed YFV in seven samples, from which four genomes were assembled (two full and two partial). We confirmed this by RT-qPCR, which also detected YFV in two additional samples ( Supplementary Table 1). No other viral pathogens were detected in any of the samples, including those negative for YFV ( Supplementary Figure 2). YFV has a short period of viraemia, 4 which may explain the absence of detectable virus in the four other patients.To determine the source of the outbreak in Edo State, we compared these genomes to all previous African YFV sequences available in GenBank, using the portion of the genome (prM/E gene) most widely sequenced in historical samples . In a maximum likelihood phylogeny, the 2018 YFV sequences formed a tightly clustered clade (Figure 1), more closely related to samples from other West African countries (mean pairwise identity = 99·4%) than to earlier Nigerian sequences (mean pairwise identity = 89·8%). This provides the first evidence that YFV responsible for the 2018 outbreak in Edo State does not descend directly from the Nigerian YFV outbreaks of the last century but is instead part of the broader diversity of current YFV in West Africa.We established the presence of YFV in Edo State within four days of receiving samples and shared this information immediately with the referring hospital and national health authorities.Based in part on these findings, the Nigeria Centre for Disease Control declared an outbreak in Edo the following day. 5 Notably, these are the only sequence data reported from recent Nigerian YFV cases, and the first complete Nigerian YFV genomes from patient samples collected after 1950. This ability to rapidly identify and characterize a re-emerging virus -in an unusual cluster identified by local health officials -highlights the value of in-country genomics capacity. The integration of this capacity into the established, but siloed, pathogen-specific diagnostic platforms developed over the past 20 years provides exciting opportunities for public health surveillance.