In Africa, more sequencing is needed to better monitor variants

The rapid spread of the Omicron variant, identified for the first time in South Africa and Botswana, once again raises the question of variant surveillance.

Alpha Kabinet Keita, University of MontpellierDramane Kania and Richard Njouom, Center Pasteur du Cameroun

A man receives the Covid-19 vaccine in Yaoundé, Cameroon, on November 29, 2021. In this African country, as in others around the world, preconceived ideas and misinformation on social networks are holding back the vaccination campaign.

Alpha Keita, virologist at IRD and Deputy Director of Cerfig (Centre de recherche et formation en infectiologie de Guinée), Dramane Kania, pharmacist virologist at the Muraz Center of Burkina Faso's Institut national de Santé publique, and Richard Njouom, Head of the Virology Department at the Centre Pasteur du Cameroun in Yaoundé, report on the situation of the Covid-19 epidemic in Africa, and look back at the challenges linked to sequencing.


The Conversation: What's the latest on the epidemic in Africa? What do we know about the circulation of the virus today?

Dramane Kania: If we compare the situation on the African continent with that on other continents, the impact of the pandemic seems less significant: the number of cases recorded is lower, as is the number of deaths.

However, we must not jump to conclusions: these appearances are probably misleading, and in reality the virus is certainly circulating more widely than these figures indicate. This discrepancy can be explained by problems specific to the African continent: in many countries, diagnostic capacities are limited and data is lacking, even though projects such as APHRO-COV and other initiatives have strengthened diagnostic capacities in several countries. What's more, a large proportion of the population is not necessarily accustomed to referring to healthcare structures in the event of a health problem. For these reasons, the actual number of Covid-19 cases is almost certainly underestimated.

This hypothesis is corroborated by the fact that, in countries with greater resources and where diagnosis is therefore more routine (such as South Africa and the Maghreb countries), the number of reported cases is higher. In West Africa, on the other hand, the existence of an underestimation has been confirmed by seroprevalence studies, which detect the antibodies produced after infection with the virus. These studies have shown that in some places, more than half the population has been exposed to SARS-CoV-2 in recent months.

Alpha Keita: As of January 2, there were over 9.5 million cases of the disease in Africa, and almost 230,000 deaths. This is less than on other continents, but there are major disparities from one country to another: most of the deaths recorded are in countries with the best-performing health systems, and which are able to correctly collect data relating to the epidemic. This lends credence to the hypothesis that cases are under-reported.

As part of the Ariacov project, which supported the African response in the fight against the coronavirus, we carried out a serological study in Guinea on samples taken from the population of the capital, Conakry. This work, which consisted of three surveys carried out a few months apart, revealed that by December 2020, 17% of Conakry's population had been in contact with the virus. By late February - early March, this figure had risen to over 30% of the population. By June-July, it had risen to almost 50%.

These results clearly indicate that the number of cases is underestimated. The number of deaths is also underestimated, as only those occurring in hospitals and centers affiliated to the CHU are included. In short, while the pandemic was not the slaughter we had hoped for, it is important to understand that the numbers of cases and deaths were underestimated.

Richard Njouom: The situation of the Covid-19 epidemic in Cameroon is identical to that in other sub-Saharan African countries: the number of confirmed cases of SARS-CoV-2 infection is low, as is the number of deaths attributed to the virus, probably due to underestimation.

To better understand the impact of the Covid-19 pandemic and monitor the evolution of SARS-CoV-2 on the African continent, we launched a collaborative research program called REPAIR in the spring of 2020, with all the African institutes that are members of the Pasteur Network. This work covers a range of areas: development and performance evaluation of diagnostic tests (at the Centre Pasteur in Cameroon, we have developed an easy-to-use colorimetric test, currently being evaluated in the field and in other Pasteur Network institutes), molecular epidemiology studies on the virus, mathematical modeling of its spread, etc. Seroprevalence surveys for SARS-CoV-2 have also been carried out among several "sentinel" populations, such as healthcare workers and blood donors.

TC: Could this circulation of SARS-CoV-2 encourage the emergence of variants?

DK: What theory tells us is that the more a virus circulates, the greater the risk of variants emerging. When a virus multiplies in an infected cell, it copies its genetic material countless times. In doing so, it can commit errors known as mutations. Some of these mutations are deleterious, and the viruses carrying them become extinct; others are repaired; still others persist.

The question is whether these changes in the genome (which is the "construction plan of the viral particles", editor's note) will translate into changes in the structure of the virus, and if so, what will be the consequences: will they modify its transmissibility? Its virulence? Other characteristics?

To be able to detect this, you need a good monitoring or surveillance system, based in particular on extensive sequencing capabilities. Unfortunately, the majority of laboratories in Africa do not have the requisite technical capabilities. In most cases, we can't go beyond diagnostic tests, which only detect the presence of the virus or confirm its absence.

While it is sometimes possible to sequence the genome of viruses from samples that have tested positive, this can only be done on an ad hoc basis, and sometimes only 3 or 4 months after the samples have been collected. Our ability to monitor variants in real time is highly inadequate; for this reason, our view of the evolution of the epidemic and the number of variants actually circulating on the continent is certainly distorted.

Countries that are able to set up this type of surveillance detect more variants, which probably partly explains why South Africa has identified at least two variants of concern on its territory since the start of the pandemic. This enabled the authorities to alert the international community very early on. Proof of the importance of sequencing, at the Muraz center in Bobo Dioulasso, an ANRS | Emerging Infectious Diseases partner, we were able to detect two cases of infection with the Omicron variant in mid-December, which means that it is also circulating in Burkina Faso.

TC: In practical terms, how are variants monitored?

AK: It depends essentially on the capacity of countries to sequence circulating viruses. At present, when we look at contributions to the databases in which researchers deposit the sequences obtained (such as the GISAID platform, for example), we see that Africa participates very little. Guinea, for example, has deposited just 311 genomes on GISAID since January 10, 2020.

(Over the same period, South Africa filed nearly 25,000, France 16,000, the UK nearly 1.5 million and the USA 1.9 million. China filed 1,299, editor's note).

To improve the situation, the Afroscreen project was launched. Funded by the Agence Française de Développement (AFD) and coordinated by ANRS | Emerging Infectious Diseases, in collaboration with Institut Pasteur and IRD, it has enabled us to perform routine sample screening in Guinea over the last two months.

This approach involves screening positive samples for mutation profiles corresponding to the known variants listed by the World Health Organization (WHO). This screening is carried out on samples taken from patients hospitalized in one of the capital's three major healthcare centers, from people who come for spontaneous testing, or from travellers. Results can be obtained within a few hours, enabling real-time monitoring.

However effective it may be, screening nevertheless has its limitations, since it focuses on variants that are already known (variants of interest or variants of concern), and whose mutations have already been identified. The mutation profiles of unclassified variants are all listed as "wild", which provides no additional information and makes it impossible to exhaustively monitor emerging variants.

Only full genome sequencing can provide a detailed analysis of the mutations that may occur in the new variants, and determine whether or not they are cause for concern, or whether there is reason to fear that they will make the virus more transmissible, or enable it to evade immunity - whether natural or conferred by vaccines, etc. - in the future.

We therefore need to strengthen these capacities in as many countries as possible (in particular, to be able to compare data from one country to another), which is also the aim of the Afroscreen network.

RN: Sequencing is indeed essential for studying the spread of SARS-CoV-2 over time and space, and tracking the emergence of dangerous variants. In Cameroon, we have been able to strengthen our capacities, both in terms of equipment and staff training. In January 2021, we were able to set up genomic surveillance, which resulted in the sequencing of 116 complete genomes. The results confirmed the circulation of Alpha, Beta, Delta and Gamma variants in the country. We hope that the Afroscreen network will increase this effort tenfold.

Another advantage of being part of a network of this size, which brings together 13 African countries, is the sharing of knowledge and data. Thanks to the publication of the results obtained in the open GISAID database, it will be possible to monitor and better understand traffic in the region.

TC: What's the situation with vaccinations on the continent?

DK: Many countries initially encountered difficulties in obtaining the vaccine. To overcome this problem, various initiatives were launched. Beyond the question of accessibility, which is certainly essential, there is a second problem: that of public support, which generally lacks scientific information to answer their questions. Fake news, on the other hand, is abundantly relayed on social networks, fuelling people's mistrust of vaccination. At present, we have the impression that only citizens who are obliged to travel resolve to be vaccinated... Reversing this trend is another challenge.

RN : In Cameroon, the vaccination situation is lagging far behind: only 1.1% of the target population has a complete vaccination schedule. People are distrustful of the vaccines available in the country. One of the challenges is to convince people that vaccines are worthwhile. The delay in vaccination observed in Africa makes it all the more important to strengthen the monitoring of variants through sequencing. If we can determine which variants are circulating in which territories, it will be easier for health authorities to decide on targeted vaccination campaigns, which will be more effective in containing the epidemic.The Conversation

Alpha Kabinet Keita, Microbiologist, researcher at the TransVIHMI Unit (Univ Montpellier, IRD, INSERM), Deputy Director of CERFIG, University of MontpellierDramane Kania, Pharmacist-Virologist, Centre MURAZ (Bobo-Dioulasso, Burkina Faso) - Institut National de Santé Publique and Richard Njouom, Head of Virology, Centre Pasteur du Cameroun, Center Pasteur du Cameroun

This article is republished from The Conversation under a Creative Commons license. Read theoriginal article.