Avian Influenza: Where we are where we’re going
by Prof. Hervé Fleury, MD-PhD | Ventum Biotech Scientific Board Member
The avian reservoir
Influenza A viruses are present in humans and animals. Wild birds and bats are the reservoir of influenza A viruses, especially since they are chronic carriers. The variety of hemagglutinins (HA) and neuraminidases (NA), which are the targets of neutralizing antibodies, is very large in these animals; thus 18 HA and 11 different NAs were recorded from H1 to H18 and from N1 to N11; the H17N11 and H18N11 viruses were observed only in bats, all the others being described in wild birds.
These wild bird viruses (which are emitted by the contents of the cloaca and by respiratory secretions) can be transmitted to domestic birds (direct contacts, contacts through food sources and water reserves); a distinction is made between low pathogenic strains (LPAI) and highly pathogenic strains (HPAI); in farmed birds LPAI causes little pathogenic effect (especially in ducks); there can be a drop in appetite and egg-laying as well as feather bristling; HPAI can cause massive clinical damage (especially respiratory, digestive and nervous) of farms with a high percentage of mortality.
Current situation
Since the end of summer 2021, outbreaks of H5N1 HPAI avian influenza have been observed first on the Baltic and then in the Netherlands, Germany, Italy in wild birds and domestic birds (turkeys, ducks, chickens, laying hens); in France, as of February 16, 2022, there are about 400 outbreaks of infection, particularly in the Landes and the Basque Country.
On a global level, the map below shows the geographical distribution of identified cases of influenza A infection in birds
The fight against avian influenza in birds
In birds, it is impossible to control the circulation of wild birds that are the basis of epidemics during their migrations. Consequently, the action to be taken is, from the signal given of an infection in a wild bird in a given area, the claustration of domestic birds avoiding contact with wild birds. If the infection begins on a farm, slaughter is the rule; but other factors of contamination must be taken into account, these factors being related to human activities: movement of infected animals from one area to another by vehicles, transport of viruses via contaminated clothing and boots not or insufficiently disinfected, contamination of the vehicles themselves (wheels, tires, tailgates) ; it is very difficult to control such an epidemic.
Vaccines against H5N1 in particular exist (inactivated or recombinant vaccines) that can be used on farms; like the SARS CoV 2 vaccine, they do not prevent infection of a herd but decrease mortality and viral circulation. They should be used in addition to enhanced general hygiene methods. Note that a recombinant H5N1 vaccine can be given as an aerosol to chicks. Such vaccines are used in China, Vietnam, Mongolia and Egypt. In France, vaccination is allowed only in wild birds in zoos when they cannot be confined.
From a virological point of view, it is obvious that the monitoring of strains and their molecular characterization must be carried out at the global level in wild and domestic birds.
Avian influenza in humans
Human influenza A viruses that cause influenza pandemics have been defined as H1N1 (Spanish flu of 1918), H2N2 (Singapore), H3N2 (Hong Kong) and H1N1pdm of 2009. The origin of human influenza A pandemics is mainly related to the recombination in an intermediate animal (pigs) of human and avian influenza viruses, recombination being facilitated by the fact that influenza viruses have a segmented genome; thus H3N2 would have been obtained by recombination between H2N2 and an avian virus with a different HA that became H3 in the new emerging virus in humans. It can be imagined that the potential for the emergence of new subtypes of HA and NA in humans from the avian reservoir is very high.
An important issue concerns human infection with avian viruses; this has been described for H5N1 (first cases in 1997 in Hong Kong) and H7N9 in particular; it is rare but very dangerous since mortality is around 50%; human-to-human transmission is difficult but the fear is the adaptation of an avian virus to exacerbated human-to-human transmission leading to a pandemic; It should be noted that treatments exist against these influenza viruses: these are neuraminidase inhibitors (oseltamivir, zanamivir); it should also be remembered that the resistance of the influenza virus to this class of antiviral drugs has been objectified in some treated patients.
Of course, we will ask ourselves the question of vaccination in humans. The U.S. federal government has stockpiled an inactivated H5N1 vaccine developed in Pennsylvania by the French company Sanofi; this vaccine would be used in the event of a declared human H5N1 pandemic.
Surveillance of influenza infections in humans in contact with birds is fundamental. Indeed, the contamination of a human already infected by a human H3N2 strain and superinfected by an H5N1 or H5N8 avian virus could generate a recombinant corresponding to a human H5N2 virus with a possibility of epidemic or even pandemic departure. Beware also of the contamination of intermediate animals such as pigs by humans infected with human influenza. Also to be avoided visits to market areas where potentially infected poultry are locked up; during more than 4O stays in Bombay (Mumbai), India, I avoided the poultry storage area at Crawford market; for the rest I recommend visiting this fascinating market.
Crawford market, Mumbai
