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

Etude de la sensibilité différentielle de l'hypothalamus à l'oestradiol pour induire le pic préovulatoire de LH et le comportement sexuel : comparaison entre brebis Ile-de-France et Romanov

Diplôme : Dr. d'Universit

Differential estradiol requirement for the induction of estrous behaviour and the LH surge in two breeds of sheep : comparison between Ile de France and Romanov ewes

En utilisant un modèle de phase folliculaire artificielle, la quantité minimale d’œstradiol (E) nécessaire pour induire le pic préovulatoire de LH et le comportement sexuel a été comparée chez des brebis de prolificité différentes : Ile de France (IF) vs Romanov (ROM). Un signal œstrogénique très faible induit le comportement sexuel chez la brebis ROM mais pas chez l’IF. L’induction du pic préovulatoire de LH nécessite des quantités d’E très supérieures chez la ROM par comparaison à l’IF. Le pic de LH apparaît plus tard chez la ROM. L’étude de la sensibilité hypophysaire et hypothalamique à l’E a montré que le moment du pic préovulatoire de LH est essentiellement contrôlé par l’hypothalamus. Chez la ROM, des doses modérées d’E stimulent une faible libération de GnRH dans le liquide céphalorachidien, sans qu’elle ne soit traduite au niveau hypophysaire par une augmentation de libération parallèle de LH. Ce peptide, participerait au contrôle du comportement sexuel induit par l’E. La grande différence de sensibilité à l’E entre les deux races semble être liée à un seuil de « lecture » différent du signal œstrogénique pour induire le pic de LH et le comportement sexuel.Using an artificial follicular phase model, the minimum estradiol (E) requirement to induce the preovulatory LH surge and estrous behaviour, was compared between two breeds of ewes having either single (Ile de France= IF) or multiple (Romanov= ROM) ovulations. While a small E signal is sufficient to induce estrous behaviour, in ROM ewe, the same treatment has no effect on IF ewe. A much larger amount of E is required to induce the LH surge in the ROM compared to the IF. The onset of the LH surge occurred earlier in IF. Pituitary and hypothalamic sensitivity to E were studied in vivo and in vitro. The timing of the LH surge is essentially under the control of the hypothalamus. The latency to the onset of the LH surge is timed by a negative feedback effect of E at the hypothalamic level which is longer in ROM ewes. A moderate E signal stimulates a light GnRH secretion into the cerebrospinal fluid, which was not accompanied by a parallel pituitary LH discharge. GnRH appears involved in the control of estrous behaviour. The difference in sensitivity to E between IF and ROM ewes to induce LH surge and estrous behaviour is more than likely due to a different threshold in the lecture of the E signal

Etude de la sensibilité différentielle de l'hypothalamus à l'œstradiol pour induire le pic préovulatoire de LH et le comportement sexuel (comparaison entre Brebis Ile-de-France et Romanov.)

En utilisant un modèle de phase folliculaire artificielle, la quantité minimale d œstradiol (E) nécessaire pour induire le pic préovulatoire de LH et le comportement sexuel a été comparée chez des brebis de prolificité différentes : Ile de France (IF) vs Romanov (ROM). Un signal œstrogénique très faible induit le comportement sexuel chez la brebis ROM mais pas chez l IF. L induction du pic préovulatoire de LH nécessite des quantités d E très supérieures chez la ROM par comparaison à l IF. Le pic de LH apparaît plus tard chez la ROM. L étude de la sensibilité hypophysaire et hypothalamique à l E a montré que le moment du pic préovulatoire de LH est essentiellement contrôlé par l hypothalamus. Chez la ROM, des doses modérées d E stimulent une faible libération de GnRH dans le liquide céphalorachidien, sans qu elle ne soit traduite au niveau hypophysaire par une augmentation de libération parallèle de LH. Ce peptide, participerait au contrôle du comportement sexuel induit par l E. La grande différence de sensibilité à l E entre les deux races semble être liée à un seuil de lecture différent du signal œstrogénique pour induire le pic de LH et le comportement sexuel.Using an artificial follicular phase model, the minimum estradiol (E) requirement to induce the preovulatory LH surge and estrous behaviour, was compared between two breeds of ewes having either single (Ile de France= IF) or multiple (Romanov= ROM) ovulations. While a small E signal is sufficient to induce estrous behaviour, in ROM ewe, the same treatment has no effect on IF ewe. A much larger amount of E is required to induce the LH surge in the ROM compared to the IF. The onset of the LH surge occurred earlier in IF. Pituitary and hypothalamic sensitivity to E were studied in vivo and in vitro. The timing of the LH surge is essentially under the control of the hypothalamus. The latency to the onset of the LH surge is timed by a negative feedback effect of E at the hypothalamic level which is longer in ROM ewes. A moderate E signal stimulates a light GnRH secretion into the cerebrospinal fluid, which was not accompanied by a parallel pituitary LH discharge. GnRH appears involved in the control of estrous behaviour. The difference in sensitivity to E between IF and ROM ewes to induce LH surge and estrous behaviour is more than likely due to a different threshold in the lecture of the E signal.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF

The preovulatory LH surge in the ewe appears to be essentially timed by the hypothalamus

International audienc

Long-term exposure to GnRH agonist does not modify the sheep ovarian response to a superovulation FSH treatment

International audienc

Induction de l'ovulation chez la brebis en anoestrus par administration de kisspeptide : mécanismes impliqués?

National audienc

GnRH and the control of estrous behavior in a prolific breed of sheep: the case of the Romanov ewe

National audienc

Post-partum Period in Tunisian Arab Mares%253A Which Factors Influence the Foaling Heat%253F

This work aims to study the influence of some factors on the expression of the foaling heat in Arab mares. This study was held in Tunisia, from January to May 2018. For this, 59 Tunisian Arab mares were separated into 2 groups (young mares, age lt%253B15 years, n%253D41%253B and old mares, age ge%253B15 years, n%253D18), and monitored amid the post partum period. The parturition mode (eutocic, dystocic) was noted, and the onset of the foaling heat and its duration recorded. Follicular activity was monitored using ultrasonography to track the side at which the ovulation occurred. ANOVA was carried out using the software SAS (SAS Institute Inc.reg%253B) to study the effect of age and parturition mode on the onset of foaling heat and its duration. The Duncan test was used to compare the variations according to the age and the parturition mode. The onset of the foaling heat and its duration did not vary with the age class (7.5plusmn%253B0.2 vs 7.3plusmn%253B0.2 days%253B 5plusmn%253B0.5 vs 7.8plusmn%253B0.3 days), but had more important values in mares with dystocia (8plusmn%253B1.2 vs 7.4plusmn%253B0.2 days, plt%253B0.05%253B 6plusmn%253B1.8 vs 5plusmn%253B0.5 days, plt%253B0.05). Significantly more ovulations occurred in the left ovary than in the right one (55%25 vs 45%25). Furthermore, silent heat occurred at the rate of 20%25, while all females resumed an ovulatory function. Our results suggest that dystocia increase the onset delay of the foaling heat and its duration, and that the left ovary tends to retrieve its function faster than the right one