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

Hutchinson-Gilford Progeria Syndrome: Clinical and Molecular Analysis in an African Patient

peer reviewedHutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disease characterized by an early onset of several clinical features including premature ageing in children. Approximately 80% of HGPS cases are caused by a de novo single-base pair substitution c.1824 C>T (GGC > GGT, p.Gly608Gly) within the exon 11 of the LMNA gene which codes for lamins A and C proteins. This mutation creates an abnormal splice donor site, leading to the formation of a truncated lamin A protein. Only a very few cases of African patients with HGPS have been reported, but none of them has been characterized at the molecular level. We report here a 12 year-old-girl African patient with HGPS, in whom the p.Gly608Gly heterozygous disease-causing mutation was found

IN-HOUSE ASSAY SET UP FOR GENOTYPING AND RESISTANCE PROFILE OF HEPATITIS C (HCV) BY SEQUENCING THE NS5B (CENTRAL REGION) AND NS3 USING A SINGLE METHOD

Hepatitis C virus (HCV) infection remains a major public health concern affecting approximately 185 million people worldwide (Childs-Kean, L.M et al.). There is a high variability between circulating strains of hepatitis C virus. This variability determines and influences the response and duration of treatment (Petruzziello, A. et al.). Currently, there is limited data available on the HCV viral strains in Rwanda and there is no systematic laboratory genotyping and sequencing tools for optimal management of patients in the country. The purpose of this work is to develop and set up an in-house method within the Clinical Microbiology Laboratory in the CHU-Liege that allow simultaneous genotyping and Direct acting antivirals (DAAs) resistance profiling by direct sequencing the HCV NS3 and NS5B genes which is applicable to a wide range of genotypes. The developed tool will be subsequently transferred to Rwanda. This will aid in determining the HCV genotype among infected patients; ascertaining the epidemiological surveillance of circulating strains in Rwanda; and help in monitoring of patients under antiviral treatment in various health care facilities. The first objective was to validate the detection and identification of the common circulating HCV genotypes 1-6 using in-lab developed or literature cited primes. The second objective was to evaluate the sensitivity of the method and its capacity to monitor resistance of HCV to antiviral treatment especially to DAAs currently used in various clinical settings; and finally, to analyze clinical samples from patients routinely followed up in CHU of Liege

Precocious puberty associated with partial trisomy 18q and monosomy 11q

We report a 10-years-old female patient with a partial trisomy 18q and monosomy 11q due to a maternal translocation. The phenotype of our proband is partially common with Jacobsen syndrome and duplication 18q but she has also some atypical anomalies such as precocious puberty, a retinal albinism and hypermetropia. Based on cytogenetics and FISH analysis, the karyotype of the proband was 46,XX,der(11)t(11;18)(q24;q13). To the best of our knowledge, this is the first report of precocious puberty associated with either dup(18q) or del(11q) syndromes

Molecular Analysis in Two Siblings African Patients with Severe Form of Hunter Syndrome: Identification of a Novel (P.Y54x) Nonsense Mutation

Hunter syndrome (or Mucopolysaccharidosis type II, MPS II) is an X-linked recessive disorder due to the deficiency of the iduronate-2-sulfatase (IDS) enzyme, resulting in the accumulation of heparan and dermatan sulfates in the lysosomes. The heterogeneity of clinical phenotypes, ranging from mild-to-severe forms, is a result of different mutations in the IDS gene. We report here, a novel nonsense mutation (p.Y54X) in two siblings MPS II African patients affected with a severe form of the disease. We postulated that the p.Y54X mutation which causes a loss of the IDS region highly conserved among sulfatase enzymes, could be predicted as a severe disease-causing mutation for Hunter syndrome

L'épidémie de SARS-CoV-2 en Afrique Sub-Saharienne, questions, craintes et espoir

Les fréquences de cas détectés d’infection et de décès consécutifs à l’épidémie d’infection par SARS-CoV-2 semblent moins élevées en Afrique sub-saharienne. Cette situation correspond probablement à un démarrage plus tardif de l’épidémie sur le continent. Cependant, certains éléments propres à cette région du monde pourraient influencer son cours. Les conditions socio-économiques moins favorables et la promiscuité qui y est associée, la situation difficile des services de santé pour répondre à l’épidémie, ainsi que la fréquence dans certains pays d’affections aggravantes pourraient entraîner une situation sanitaire particulièrement difficile. Inversement, la pyramide des âges, de potentielles caractéristiques génétiques et les effets immuno-régulateurs d’infections courantes concomitantes pourraient avoir pour conséquence une sévérité moins importante de cette infection. Afin de limiter l’impact direct et indirect de l’épidémie dans ces pays, il est très important de renforcer leur capacité de diagnostic, de prise en charge des patients et d’analyse scientifique des facteurs de risque locaux

The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis

Transmission of parental post-traumatic stress disorder (PTSD) to offspring might be explained by transmission of epigenetic processes such as methylation status of the glucocorticoid receptor (GR) gene (NR3C1)

Fragile X checklists: A meta-analysis and development of a simplified universal clinical checklist.

Clinical checklists available have been developed to assess the risk of a positive Fragile X syndrome but they include relatively small sample sizes. Therefore, we carried out a meta-analysis that included statistical pooling of study results to obtain accurate figures on the prevalence of clinical predictors of Fragile X syndrome among patients with intellectual disability, thereby helping health professionals to improve their referrals for Fragile X testing. All published studies consisting of cytogenetic and/or molecular screening for fragile X syndrome among patients with intellectual disability, were eligible for the meta-analysis. All patients enrolled in clinical checklists trials of Fragile X syndrome were eligible for this review, with no exclusion based on ethnicity or age. Odds ratio values, with 95% confidence intervals as well as Cronbach coefficient alpha, was reported to assess the frequency of clinical characteristics in subjects with intellectual disability with and without the fragile X mutation to determine the most discriminating. The following features were strongly associated with Fragile X syndrome: skin soft and velvety on the palms with redundancy of skin on the dorsum of hand [OR: 16.85 (95% CI 10.4-27.3; α:0.97)], large testes [OR: 7.14 (95% CI 5.53-9.22; α: 0.80)], large and prominent ears [OR: 18.62 (95% CI 14.38-24.1; α: 0.98)], pale blue eyes [OR: 8.97 (95% CI 4.75-16.97; α: 0.83)], family history of intellectual disability [OR: 3.43 (95% CI 2.76-4.27; α: 0.81)] as well as autistic-like behavior [OR: 3.08 (95% CI 2.48-3.83; α: 0.77)], Flat feet [OR: 11.53 (95% CI 6.79-19.56; α:0.91)], plantar crease [OR: 3.74 (95% CI 2.67-5.24; α: 0.70)]. We noted a weaker positive association between transverse palmar crease [OR: 2.68 (95% CI 1.70-4.18; α: 0.51)], elongated face [OR: 3.69 (95% CI 2.84-4.81; α: 0.63)]; hyperextensible metacarpo-phalangeal joints [OR: 2.68 (95% CI 2.15-3.34; α: 0.57)] and the Fragile X syndrome. This study has identified the highest risk features for patients with Fragile X syndrome that have been used to design a universal clinical checklist

Neonatal screening for sickle cell disease in Central Africa: a study of 1825 newborns with a new enzyme-linked immunosorbent assay test

peer reviewedObjectives To evaluate the feasibility of systematic neonatal screening for sickle cell disease in the region of Great Lakes in Central Africa using a new approach with limited costs. Methods Between July 2004 and July 2006, 1825 newborn dried blood samples were collected onto filter papers in four maternity units from Burundi, Rwanda and the East of the Democratic Republic of Congo. We tested for the presence of haemoglobin C and S in the eluted blood by an enzyme-linked immunosorbent assay (ELISA) test using a monoclonal antibody. All ELISA-positive samples (multiple of the median (MoM) >= 1.5) were confirmed by a simple molecular test. The statistica software version 7.1 was used to create graphics and to fix the MoM cut-off, and the chi(2) of Pearson was used to compare the genotype incidences between countries. Results Of the 1825 samples screened, 97 (5.32%) were positive. Of these, 60 (3.28%) samples were heterozygous for Hb S, and four (0.22%) for Hb C; two (0.11%) newborns were Hb SS homozygotes. Conclusions The lower cost and the high specificity of ELISA test are appropriate for developing countries, and such systematic screening for sickle cell anaemia is therefore feasible