In France, mosquitoes also transmit the Usutu virus

The events took place two years ago, but scientists have only just discovered that this was the first case of human infection with the Usutu virus in France. On November 10, 2016, a 39-year-old man was hospitalized for three days in neurology at Montpellier University Hospital for sudden paralysis of half his face.

Yannick Simonin, University of Montpellier

The patient recovered all his faculties within a few weeks, with no after-effects. Subsequent tests showed that he had been infected by the virus.

It was the work carried out by our team of biologists from the University of Montpellier, Inserm and Montpellier University Hospital, which enabled us to understand the origin of the disorders presented by this man. We analyzed 666 cerebrospinal fluid samples taken from patients hospitalized in 2016 in Montpellier and Nîmes, as explained in thearticle we have just published in the journal Infectious Emerging Diseases. Only one revealed the presence of the Usutu virus: his own.

The most likely scenario is that the man was infected by a mosquito, after it bit a bird that is a reservoir for the virus. Transmitted to humans mainly by the Culex mosquito, common in France, this virus has been circulating in our country since at least 2015, according to a study by the French National Food Safety Agency (Anses). Along with chikungunya, dengue and West Nile, Usutu is now among the mosquito-borne viruses that have caused at least one indigenous case in France - i.e. in a person who has not traveled to a foreign country. Although Usutu is not the most fearsome of the viruses that the French must learn to deal with, it does merit the attention of scientists and health authorities.

Named after a river in Swaziland, Africa

The Usutu virus was an illustrious unknown until recently. It is now attracting the attention of the scientific community due to its widespread distribution in Europe. Usutu is an arbovirus of the Flaviviridae family and the flavivirus genus, comprising over 70 members.

These include some of the most dangerous arboviruses for humans, such as the Zika virus, dengue fever, yellow fever and West Nile fever. Usutu was named after the river of the same name located in Swaziland, a small African country sharing a border with South Africa. It was first identified there in 1959.

Little is known about Usutu's target cells. Nevertheless, our team recently described its ability, like other flaviviruses, to infect nervous system cells in vitro (in the laboratory).

Birds as hosts, mosquitoes as vectors

Usutu's natural transmission cycle is enzootic, i.e. localized in a given area. It mainly involves passeriform (e.g. blackbirds or magpies) and strigiform (e.g. Great Gray Owls) birds as "amplifying" hosts, i.e. enabling active multiplication of the virus. Ornithophilic (bird-biting) mosquitoes act as vectors for transmission to humans.

Various studies have demonstrated the involvement of several mosquito species in the maintenance of the Usutu cycle in avifauna, i.e. birds occupying the same area. The virus was isolated from Aedes albopictus (better known as the tiger mosquito), Aedes caspiuis, Anopheles maculipennis, Culex quinquefasciatus, Culex perexiguus, Culex perfuscus, Coquillettidia aurites, Mansonia Africana and Culex pipiens. All these species are ornithophiles, but also bite humans.

Mosquitoes transmit the virus to humans, as well as horses. These species are susceptible to Usutu, but are considered accidental hosts and epidemiological "dead-ends" - i.e. they cannot transmit the virus to a conspecific.

High bird mortality

Usutu has also been found in numerous bird species. Several migratory species are thought to be responsible for the introduction of Usutu into Europe, while others are thought to be responsible for its spread. Among those susceptible to Usutu infection, blackbirds ( Turdus merula ) show the highest mortality rate.

Central nervous disorders have been reported in birds infected with Usutu. These include prostration, disorientation, motor incoordination and weight loss. Autopsies frequently reveal inflammation of the liver (hepatomegaly) and spleen (splenomegaly).

Lesions were also reported in the hearts, livers, kidneys, spleens and brains of infected birds. These observations show that Usutu can be highly pathogenic in avifauna due to its replication and virulence in a wide range of tissues and organs. Usutu is thus causing major bird mortality in various parts of Europe.

A virus first discovered in Europe in 2001

The virus was first spotted in Europe in 2001, in Austria, on bird corpses. Since then, it has been reported in numerous European countries, both on mosquitoes and on birds.

In 2015, France in turn detected this virus in common blackbirds, following an increase in their mortality in the Haut-Rhin and Rhône departments, analyzed by Anses and the Office national de la chasse et de la faune sauvage (ONCFS).

Furthermore, it has since been established that Usutu has been circulating in Culex pipiens mosquitoes in the Camargue since at least 2015. In the summer of 2016, a major Usutu epizootic affecting birds was once again recorded in Europe, with widespread virus activity in Belgium, Germany, France and, for the first time, the Netherlands. This phenomenon underlines the continuing geographical spread of Usutu, but also the emergence of new ecological niches.

The recurrence of Usutu infection in various European countries suggests a persistent transmission cycle in the affected areas, either via overwintering mosquitoes (the cold slows down their bodies and they don't move again until spring) or via multiple reintroduction of the virus by migratory birds from Africa.

Symptoms to be better characterized

The risk of animal-to-human transmission associated with Usutu was first described in Africa. The first human case was reported in the Central African Republic in the 1980s, the second in Burkina Faso in 2004. In both cases, symptoms were moderate, with a rash and mild liver involvement.

To date, there have been 28 cases of acute human infection with Usutu in Europe, mainly in Italy. In addition, more than 70 individuals have been reported to have antibodies against the virus, demonstrating that they have been exposed to the pathogen. Human infection is probably mostly symptomless, or has a mild clinical expression. However, neurological complications such as encephalitis (inflammation of the encephalon, the part of the brain housed in the skull) or meningoencephalitis (inflammation of the encephalon and meninges, the membranes that surround it) have been described, with some fifteen cases in Europe.

Our team's description of the atypical presence of facial paralysis in the first French case suggests that the extent of symptoms in Usutu virus infections is not fully known.

A virus with an expanding range

Recent outbreaks of other arboviruses have prompted the scientific community to exercise the utmost vigilance with regard to the Usutu virus. Its range now extends to a large number of European countries. Epizootics involving avian mortality are frequent. Genetically very different strains are circulating at the same time. These are all warning signs.

Although all too rare, a few seroprevalence studies (the presence of antibodies to the virus in the blood) support the hypothesis that humans are more exposed to the risk of Usutu infection than previously thought.

Knowledge of the pathophysiology of this emerging virus is currently very sketchy. Ongoing research is aimed in particular at gaining a better understanding of its biology and the mechanisms associated with neurological damage. Research work, accompanied by surveillance and prevention should be set up in France, in the areas most at risk.

Yannick Simonin, Inserm researcher and lecturer in infectious disease control, University of Montpellier

The original version of this article was published on The Conversation.