In Africa, more sequencing is needed to better monitor variants
The rapid spread of the Omicron variant, first identified in South Africa and Botswana, once again raises the question of variant surveillance.
Alpha Kabinet Keita, University of Montpellier; Dramane Kania and Richard Njouom, Pasteur Center of Cameroon
Alpha Keita, virologist at IRD and deputy director of Cerfig (Guinea Center for Research and Training in Infectious Diseases), Dramane Kania, pharmacist and virologist at the Muraz Center of the National Institute of Public Health in Burkina Faso, and Richard Njouom, Head of the Virology Department at the Pasteur Center of Cameroon in Yaoundé, provide an update on the Covid-19 epidemic in Africa and discuss the challenges associated with sequencing.
The Conversation: What is the current situation regarding the epidemic in Africa? What do we know about the spread of the virus today?
Dramane Kania: If we compare the situation on the African continent with that observed on other continents, the impact of the pandemic seems to be 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 circulation of the virus is certainly greater than these figures indicate. This discrepancy can be explained by issues specific to the African continent: in many countries, diagnostic capabilities are limited and data is lacking, even though projects such as APHRO-COV and other initiatives have helped to strengthen diagnostic capabilities in several countries. In addition, a large part of the population is not necessarily accustomed to seeking medical care when they have health problems. For these reasons, the actual number of COVID-19 cases is therefore most certainly underestimated.
This hypothesis is corroborated by the fact that in countries with greater resources, where diagnosis can therefore be carried out more routinely (such as South Africa or the Maghreb countries), the number of reported cases is higher. In West Africa, on the other hand, the existence of underestimation has been confirmed by seroprevalence studies, which detect antibodies produced after infection with the virus. These studies have shown that in some places, more than half of the population has been exposed to SARS-CoV-2 in recent months.
Alpha Keita: As of January 2, there were more than 9.5 million cases and nearly 230,000 deaths in Africa. This is less than on other continents, but there are significant disparities between countries: most of the deaths recorded are in countries with the most efficient health systems, which are able to collect data on the epidemic accurately. This supports the hypothesis that cases are being underreported.
As part of the Ariacov project, which supported Africa's response to the coronavirus pandemic, we conducted a serological study in Guinea on samples taken from the population of the capital, Conakry. This work, which consisted of three surveys conducted a few months apart, revealed that in December 2020, 17% of the population of Conakry had been in contact with the virus. By late February/early March, this figure had risen to over 30% of the population. In June/July, it reached 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 with the CHU are counted. Ultimately, while the pandemic has not been the catastrophe that was expected, it is important to understand that the numbers of cases and deaths have been underestimated.
Richard Njouom: In Cameroon, the Covid-19 epidemic situation 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 underreporting.
In order to better understand the impact of the Covid-19 pandemic and monitor the evolution of SARS-CoV-2 on the African continent, in spring 2020 we launched a collaborative research program called REPAIR, involving all African institutes that are members of the Pasteur Network. This work covers various areas: development and evaluation of diagnostic test performance (at the Pasteur Center in Cameroon, we have developed an easy-to-use colorimetric test, currently being evaluated in the field and in other institutes of the Pasteur Network), molecular epidemiology studies of the virus, mathematical modeling of its spread, etc. SARS-CoV-2 seroprevalence surveys have also been conducted among several "sentinel" populations, such as healthcare workers and blood donors.
TC: Could this circulation of SARS-CoV-2 promote the emergence of variants?
DK: What the theory tells us is that, indeed, 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 make mistakes, or mutations. Some of these mutations are harmful, and the viruses that carry them die out; others are repaired; and still others persist.
The question is whether these changes in the genome (which is, in a way, the "blueprint for viral particles," editor's note) will result in changes to the structure of the virus, and if so, what the consequences will be: will they alter its transmissibility? Its virulence? Other characteristics?
To detect this, a good tracking or surveillance system is needed, based in particular on significant sequencing capabilities. Unfortunately, in Africa, most laboratories do not have the necessary technical capabilities. In most cases, it is not possible to 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 test positive, this can only be done on an ad hoc basis, and sometimes only 3 or 4 months after the samples have been taken. The ability to track variants in real time is very limited; 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 implement this type of surveillance detect more variants, which probably explains in part 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 at a very early stage. As proof of the importance of sequencing, at the Muraz center in Bobo Dioulasso, a partner of ANRS | Emerging Infectious Diseases, 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 mainly on countries' ability to sequence circulating viruses. Currently, when we look at contributions to databases where researchers deposit the sequences they obtain (such as the GISAID platform, for example), we see that Africa's participation is very limited. Guinea, for example, has only deposited 311 genomes on GISAID since January 10, 2020.
(During the same period, South Africa filed nearly 25,000, France 16,000, the United Kingdom nearly 1.5 million, and the United States 1.9 million. China filed 1,299, editor's note.)
To improve the situation, the Afroscreen project was launched. Funded by the French Development Agency (AFD) and coordinated by ANRS | Emerging Infectious Diseases, in collaboration with the Pasteur Institute and IRD, it has enabled us, in Guinea, to routinely screen samples over the last two months.
This approach involves searching positive samples for mutation profiles corresponding to 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, people who come in for testing on their own initiative, or travelers. Results can be obtained within a few hours, enabling real-time monitoring.
However effective it may be, screening nevertheless has its limitations, as it focuses on already known variants (variants of interest or variants of concern), whose mutations have already been identified. The mutation profiles of unclassified variants are all listed as "wild-type," which provides no additional information and does not allow for comprehensive monitoring of emerging variants.
Only whole genome sequencing can provide a detailed analysis of the mutations that may occur in new variants and determine whether or not they are cause for concern, 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.
These capabilities must therefore be strengthened in as many countries as possible (in particular to enable data to be compared between countries), which is also the purpose 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 capabilities, both in terms of equipment and staff training. This has enabled us to set up genomic surveillance in January 2021, which has resulted in the sequencing of 116 complete genomes. The results obtained have confirmed the circulation of the Alpha, Beta, Delta, and Gamma variants in the country. We hope that the Afroscreen network will enable us to increase this effort tenfold.
Another benefit of being part of such a large network, which brings together 13 African countries, is the sharing of knowledge and data. By publishing the results obtained in the open database GISAID, it will be possible to monitor and better understand the circulation of the virus in the region.
TC: Regarding vaccination, what is the current situation on the continent?
DK: Many countries initially encountered difficulties in obtaining the vaccine. Various initiatives have been launched to address this problem. Beyond this issue of accessibility, which is certainly essential, a second problem arises: that of public acceptance, as people generally lack the scientific information they need to answer their questions. Fake news, on the other hand, is widely shared on social media, fueling people's mistrust of vaccination. At present, it seems that only citizens who are required to travel are willing to get vaccinated... Reversing this trend is another challenge.
RN: In Cameroon, vaccination coverage is severely lagging: only 1.1% of the target population has been fully vaccinated. People are distrustful of the vaccines available in the country. One of the challenges is therefore to convince people of the benefits of vaccines. This vaccination gap in Africa makes it all the more important to strengthen surveillance of variants through sequencing. If we can determine which variants are circulating in which areas, it will be easier for health authorities to decide on targeted vaccination campaigns, which are more effective in containing the epidemic.
Alpha Kabinet Keita, Microbiologist, researcher at the TransVIHMI Unit (University of Montpellier, IRD, INSERM), Deputy Director of CERFIG, University of Montpellier; Dramane Kania, Pharmacist-Virologist, MURAZ Center (Bobo-Dioulasso, Burkina Faso) – National Institute of Public Health; and Richard Njouom, Head of the Virology Department at the Pasteur Center in Cameroon, Pasteur Center of Cameroon
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