29/01/2021 - Article
An article published in French on The Conversation deciphers the mechanisms behind the emergence of new diseases. It is this type of knowledge that will be used to draft plans for preventing future pandemics.
A team of international experts commissioned by the WHO arrived in China on 14 January 2021. Their aim, starting with a visit to Wuhan, the city where the first cases of Covid-19 were officially declared in January 2020, is to meet Chinese scientists and help to pinpoint the origin of the SARS-CoV-2 responsible for the pandemic.
The Covid-19 crisis has shown that past plans aimed at preparing for pandemics were not sufficient to contain their global spread. To prevent emergence in future, strategies must be drafted before viruses even begin to develop in humans, in other words within the animal kingdom and at the animal-human interface.
It is therefore essential to identify the origin, the evolutionary processes and the initial chains of transmission that led to the current pandemic. This must also be seen in the light of the ecological and economic determinants of that emergence.
It is thought that the coronaviruses transmissible to humans that have emerged in recent years (SARS, MERS-CoV) circulate in bats and were transmitted to humans by intermediate host animals (or relay hosts). These diseases are known as zoonoses. The intervention of a domestic or wild animal is classically observed in the case of zoonotic coronaviruses – the dromedary for MERS-CoV and the masked palm civet for SARS, although doubts persist about whether it is indeed this small mammal that is involved, rather than other wild animals raised in China.
The World Health Organization (WHO) defines a zoonosis as a disease or infection naturally transmissible from vertebrates to humans – and vice versa. The current pandemic caused by SARS-CoV-2 has been class as a zoonosis, but no animal reservoir or intermediate host has yet been formally identified. This classification therefore seems premature to some authors who identify this disease as an "emerging infectious disease (EID) probably of animal origin".
The first patients officially declared to have Covid-19 in China were probably exposed to the virus at a seafood market in Wuhan. However, while some of the swab samples taken from surfaces and cages in the market tested positive for SARS- CoV-2, no virus has been isolated directly from animals and no animal reservoir has yet been identified. Nevertheless, the hypothesis (animal lead) is that the coronavirus evolved from an ancestral virus found in bats, via an as yet unidentified mammal.
The virus has been detected in animals exposed to infected humans – domestic cats, dogs and ferrets, captive lions and tigers, farmed mink – as well as recently in gorillas, indicating possible transmission from humans to animals (reverse zoonosis) and the receptivity and susceptibility of carnivores, in particular mustelids.
One of the recent hypotheses as to the intermediate host that may have allowed the evolution of an ancestral virus into SARS-CoV-2 (the Covid-19 virus) concerns mink, which are raised in China for their fur. In China, the rearing of wild animals in captivity for food, and for therapeutic purposes and fur production, has assumed considerable importance over time, and it now supports several million people.
Fur production has grown rapidly in China since the 1990s and most farms were built recently, with little technical or veterinary supervision. Its economic importance is now considerable, with fur farming employing around 7 million people. The main fur species farmed in China are mink, fox, and raccoon dog, with annual production estimated at 21 million, 17 million and 12 million animals slaughtered respectively in 2018. The mink farming industry is very heterogeneous and largely unstructured. According to 2016 estimates, almost half of farms are small-scale family businesses with fewer than 1000 mink, while the remainder are medium-sized farms as well as a minority of integrated factory farms with between 10 000 and 52 000 animals.
American mink distribution areas. The species was introduced into Eurasia for the production of fur, but many individuals escape from farms or are released into the wild). The cases of Covid-19 (OIE) declared on farms correspond to transmission from humans to animals © CIRAD
The receptivity and susceptibility to SARS-CoV-2 of mustelids, including the American mink (Neovison vison ), documented in the context of transmission from humans carrying the virus, and taking into account other genetic, economic, ecological and epidemiological elements, direct suspicions towards these species. Moreover, work on cell receptors (ACE2) has shown that many species could be receptive to SARS-CoV-2, particularly primates or carnivores. However, the authors of this study stress the importance of avoiding over-interpreting the predictions put forward and point out that experimental and observational data in the field are required.
In general, emergence of infectious diseases, the frequency of which has increased since the mid-twentieth century, is more probable in geographical zones marked by an increase in the pressure exerted by man on natural areas, by great animal biodiversity, by the transformation of natural spaces into agricultural land, and by the hunting and capture of wild animals. In developing countries, more than cultural factors, it is often the combination of economic insecurity and low agricultural productivity that lead poor rural communities to harvest wild animals or their products, to use as food (bushmeat), commercial products, or agricultural inputs. This is the case with bat guano, which is used as a fertilizer in Southeast Asia.
Domestic and wild animal production promotes the spread and increased virulence of emerging pathogens, due among other things to the transport of animals over long distances, and to the storage of high densities of animals with shirt life cycles and often with limited attention to biosecurity. In addition, breeders, who run high economic risks, follow cost-cutting strategies that can hinder the early detection and control of emerging diseases: animals showing clinical symptoms are quickly sold. The lack of transparency in animal supply chains often allows sick animals to be marketed along with others that are healthy.
These elements provide a better understanding of how mink farms could have acted as an intermediary between bats and humans in the case of SARS-CoV-2. This phenomenon was observed for avian influenza, with the virus being introduced through contact with asymptomatic wild reservoirs (palmipeds), followed by the amplification of the disease in intensive, high-density farms and the eventual production of mutant viral strains that are virulent for the initial wild reservoir species.
The acceptability of health surveillance systems also comes up against economic logic, with farmers fearing the impact of announcements of disease outbreaks on market prices and their export possibilities. On the other hand, the massive slaughter of farm animals, because they lead to an increase in selling prices, as observed in China since the slaughter of farmed mink in Denmark, paradoxically increases the profits of farmers not targeted by these control measures.
The acceptability of health surveillance systems also comes up against economic strategies, with farmers fearing the impact of announcements of disease outbreaks on market prices and their export possibilities. Conversely, the mass slaughter of farm animals often pushes up prices, as seen in China since the slaughter of farmed mink in Denmark, and paradoxically increases the profits of farmers not affected by the control measures.
In addition to ecological factors, economic factors are frequently encountered in low- and middle-income countries: economic insecurity of poor rural livestock farmers, rapid growth in exploitation of wild and farmed species to meet growing demand for animal products, and a lack of transparency in agricultural sectors.
Studies are necessary in a One Health perspective. This would involve looking for viruses and antibodies in samples collected and stored before the Covid-19 pandemic through various studies in animals and humans; analysing samples from mink farms, but also raccoon dogs (Nyctereutes procyonoides ) and foxes (Vulpes spp.) for coronavirus and typing any viruses found; conducting epidemiological studies based on serologies specific to a response to SARS-CoV-2 on those farms, on animals and exposed human populations; and analysing and modelling the links between bats and wildlife farms and between these farms and human populations.
Fur breeders should be surveyed on how they manage infectious disease cases, since their response (attempted treatment, selective sale of sick animals, etc.) can influence the risk of emergence in humans. Studies are required relating to the organization of the fur industry and its links with wild animal or wild animal product supply chains.
Field projects are focusing on studying the risks of the emergence of coronaviruses from wildlife and the wildlife trade. The ZooCoV project, which began in Cambodia and associates CIRAD, the Institut Pasteur in Cambodia and IRD, should help prevent the transmission of coronavirus from wild animals to humans. It is also important to mention the Bat-CoV project in Africa.
On a more global scale, it is necessary to prevent the risks of zoonotic emergencies and pandemics. To this end, the PREZODE initiative, announced during the January 2021 One Planet Summit, will build on and strengthen existing cooperation with the world regions most exposed to the risk of zoonotic disease emergence. PREZODE will support the integration and strengthening of human, animal and environmental health networks, in line with the One Health approach, in order to better assess and detect threats of zoonotic disease emergence and develop prevention operations with the entire range of stakeholders so as to protect people, the planet and socio-ecosystems and thus reduce pandemic risks.
The experts appointed by the WHO will be working in close collaboration with their Chinese scientific colleagues to explore the various hypotheses as to the origin of the virus behind the Covid-19 pandemic: an ancestral virus originating from a natural host other than bats; via an intermediate host or direct from the natural host to humans; a virus found in the field which then escaped from a laboratory, etc., and thus those pointing to the possible role of mink or other wild animals reared for their fur.
The original version of this article was published in French on The Conversation , on 21 January 2021.