A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

No abstract

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.

BackgroundTo date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.Methods and FindingsFrom 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0–5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0–6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir.ConclusionsThis is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.

Background Orofacial clefts are the most common malformations of the head and neck with a World-wide prevalence of 1/700 births. They are commonly divided into CL(P) and CP based on anatomical, genetic and embryological findings. A Nigerian craniofacial anomalies study “NigeriaCRAN” was set up in 2006 to investigate the role of gene-environment interaction in the etiology of orofacial clefts in Nigeria. Subjects and Methods DNA isolated from saliva from the Nigerian probands was used for genotype association studies and direct sequencing on the cleft candidate genes: MSX1, IRF6, FOXE1, FGFR1, FGFR2, BMP4, MAFB, ABCA4, PAX7 and VAX1, and the chromosome 8q region. Results A missense mutation A34G in MSX1 was observed in nine cases and four hap map controls. No other apparent etiologic variations were identified. A deviation from HWE was observed in the cases (p= 0.00002). There was a significant difference between the affected side for unilateral CL (p=0.03) and, between bilateral clefts and clefts on either side (p=0.02). A significant gender difference was also observed for CP (p=0.008). Conclusions The replication of a mutation previously implicated in other populations suggests a role for the MSX1 A34G variant in the etiology of CL(P).