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

A household serosurvey to estimate the magnitude of a dengue outbreak in Mombasa, Kenya, 2013.

Dengue appears to be endemic in Africa with a number of reported outbreaks. In February 2013, several individuals with dengue-like illnesses and negative malaria blood smears were identified in Mombasa, Kenya. Dengue was laboratory confirmed and an investigation was conducted to estimate the magnitude of local transmission including a serologic survey to determine incident dengue virus (DENV) infections. Consenting household members provided serum and were questioned regarding exposures and medical history. RT-PCR was used to identify current DENV infections and IgM anti-DENV ELISA to identify recent infections. Of 1,500 participants from 701 households, 210 (13%) had evidence of current or recent DENV infection. Among those infected, 93 (44%) reported fever in the past month. Most (68, 73%) febrile infected participants were seen by a clinician and all but one of 32 participants who reportedly received a diagnosis were clinically diagnosed as having malaria. Having open windows at night (OR = 2.3; CI: 1.1-4.8), not using daily mosquito repellent (OR = 1.6; CI: 1.0-2.8), and recent travel outside of Kenya (OR = 2.5; CI: 1.1-5.4) were associated with increased risk of DENV infection. This survey provided a robust measure of incident DENV infections in a setting where cases were often unrecognized and misdiagnosed

Risk factors associated with dengue virus infections (DENV) among residents of Tudor, Mombasa, Kenya, May 2013.

<p>* Weighted percentages are reported, reflecting the stratified sampling design. Responses were weighted to account for the different probabilities of household inclusion across strata, within-household participation rates, and inter-household clustering of infections.</p><p>** Significance level, p = 0.05. Weighted logistic regression models were used to assess risk factors for recent or current infections, and CIs were based on the modeling accounted for the sampling design. Breeding containers queried included potted plants, vegetation, wells, septic tanks, trash, buckets, water cisterns, fountains, old tires, water storage tank without lids.</p><p>Risk factors associated with dengue virus infections (DENV) among residents of Tudor, Mombasa, Kenya, May 2013.</p

Epidemiological curve of 267 suspected dengue cases detected at hospitals from January–May, 2013, of which 155 (58%) were confirmed to have a current DENV infection and included a single fatal case.

<p>Epidemiological curve of 267 suspected dengue cases detected at hospitals from January–May, 2013, of which 155 (58%) were confirmed to have a current DENV infection and included a single fatal case.</p

Map of 210 dengue virus (DENV) infected participants in Tudor, Mombasa, Kenya.

<p>Participants with evidence of current or recent DENV infection were distributed throughout the Tudor district, and there was no statistically significant clustering by area. Solid black circles represent IgM anti-DENV positive participants, white circles represent RT-PCR positive participants.</p

Demographic characteristics, symptoms and medical outcomes reported by 1,500 residents of Tudor, Mombasa, participating in serologic survey for dengue virus infection (DENV), April through May 2013.

<p>* Bleeding manifestations included nose bleeding, bleeding from gums, blood in vomitus, blood in urine, blood in stool, or heavy vaginal bleeding.</p><p>Demographic characteristics, symptoms and medical outcomes reported by 1,500 residents of Tudor, Mombasa, participating in serologic survey for dengue virus infection (DENV), April through May 2013.</p

Comparison of enzyme-linked immunosorbent assay systems using rift valley fever virus nucleocapsid protein and inactivated virus as antigens

BACKGROUND: Rift Valley Fever(RVF)is a mosquito-borne viral zoonosis.To detect RVF virus(RVFV)infection,indirect immunoglobulin G(IgG)and immunoglobulin M(IgM)enzyme linked immunosorbent assays(ELISAs)which utilize recombinant RVFV nucleocapsid(RVFV-N)protein as assay antigen, have reportedly been used, however, there is still a need to develop more sensitive and specific methods of detection. METHODS: RVFV-N protein was expressed in Escherichia coli (E. coli) and purified by histidine-tag based affinity chromatography. This recombinant RVFV-N (rRVFV-N) protein was then used as antigen to develop an IgG sandwich ELISA and IgM capture ELISAs for human sera. Ninety six serum samples collected from healthy volunteers during the RVF surveillance programme in Kenya in 2013, and 93 serum samples collected from RVF-suspected patients during the 2006-2007 RVF outbreak in Kenya were used respectively, to evaluate the newly established rRVFV-N protein-based IgG sandwich ELISA and IgM capture ELISA systems in comparison with the inactivated virus-based ELISA systems. RESULTS: rRVFV-N protein-based-IgG sandwich ELISA and IgM capture ELISA for human sera were established.Both the new ELISA systems were in 100% concordance with the inactivated virus-based ELISA systems, with a sensitivity and specificity of 100%. CONCLUSIONS: Recombinant RVFV-N is a safe and affordable antigen for RVF diagnosis.Our rRVFV-N-based ELISA systems are safe and reliable tools for diagnosis of RVFV infection in humans and especially useful in large-scale epidemiological investigation and for application in developing countries