Avian flu H7N9

from Wikipedia, the free encyclopedia

Avian influenza H7N9 is the colloquial term for a viral disease in birds , caused by the influenza A virus H7N9 (also A / H7N9 ), i.e. a subtype of the influenza virus that occurs particularly in chickens . A low pathogenic, reassorted variant of the virus led - probably for the first time in February 2013 - to human infections in the People's Republic of China ; highly pathogenic variants have also been known from China since 2017.

The term avian influenza is vague: On the one hand , it refers to the term " avian influenza " used in veterinary literature and in animal disease legislation - in the English-language specialist literature HPAI (high pathogen avian influenza) - from which birds die. But this can also mean LPAI (low pathogenic avian influenza = low pathogenic avian influenza), a flu-like infection of birds. More recently, the term “avian flu” has been used in popular science for those sub-forms of the disease which - as in the case of the H5N1 avian flu - have passed from animals to humans .

Like all other by influenza poultry diseases caused viruses is the bird flu in captive birds is a notifiable animal disease and in wild birds a notifiable animal disease. In individual cases, the viruses have also been transmitted to mammals and humans in recent years, so the disease is a zoonosis .

Description of the virus

Influenza A virus H7N9
Electron micrograph of Influenza A H7N9.png

Transmission electron microscope image of
A / H7N9 virus particles, partly spherical,
partly filamentous (thread-like)

Systematics
Classification : Viruses
Area : Riboviria
Empire : Orthornavirae
Phylum : Negarnaviricota
Subphylum : Polyploviricotina
Class : Insthoviricetes
Order : Articulavirales
Family : Orthomyxoviridae
Genre : Alpha influenza virus
Type : Influenza A Virus
Subspecies : H7N9
Taxonomic characteristics
Genome : (-) ssRNA segmented
Baltimore : Group 5
Symmetry : helical
Cover : available
Scientific name
Influenza A virus A / H7N9
Short name
FLUAV / (H7N9)
Left
NCBI  Taxonomy: 333278
ICTV Taxon History: 201853956

The influenza A virus H7N9 was initially considered to be harmless ( LPAI ) in chickens because it did not cause any symptoms of disease in them. This non-pathogenic property in chickens allowed it to spread unnoticed in these populations. In January 2017, however, genetic changes were detected for the first time (in three sick adults in China) that were classified as highly pathogenic (HPAI) by the World Health Organization, without, however, resulting in an increased risk of human-to-human transmission.

The Friedrich Loeffler Institute explained on April 8, 2013 its website: "Genetic studies suggest that it is a previously unknown variant of a avian comes reservoir and gene segments of three different avian contributes parent viruses'. Come from the eight gene segments 6 apparently the subtype H9N2, which for H7 coding gene segments and N9 of different other avian viruses. "The features known as PB2, PB1 and PA have the greatest proximity to the 2012 in bramblings isolated virus variant A / brambling / Beijing / 16/2012 (H9N2). Up until the start of the infection on the Chinese east coast, only 25 data sets for A / H7N9 were stored in GenBank . The pathogenicity of A / H7N9 for humans is caused in particular by a point mutation that arose in the year 2000 in the subtype A / H9N2 and was adopted by this.

A genetic study of viruses from four seriously ill patients from Zhejiang and poultry from local fresh meat markets in June 2013 found almost identical H7 and N9-coding gene segments in viruses isolated from a chicken and a patient. The gene segment coding for H7 was almost identical to the A / H7N3 viruses from domestic ducks, which had been examined in Zhejiang in 2011; the gene segment coding for N9 was related to A / H7N9 viruses that had been isolated from birds in South Korea. A mutation in the gene segment coding for H7, known as PB2 Asp701Asn , was interpreted as an adaptation to the patient during the disease. In August 2013, another study confirmed that genes from H7 viruses, which had passed from ducks to chickens in at least two cases, and genes from an H9N2 virus contributed to the formation of the H7N9 virus by means of reassortment .

From a comparison of H7N9 virus samples with virus material from an H7N7 outbreak in the Netherlands in 2003 and an H7N1 epidemic in Italy (1999–2000) in 2013 it was concluded that the H7N9 viruses had already spread widely before they were first discovered because they have a large number of genetic changes compared to the older H7 variants. In 2015 it was shown that several virus lines with reassortment variants had already formed within China.

Course of disease / symptoms in humans

Most people infected with A / H7N9 develop a high fever , cough , shortness of breath, and , if left untreated, rapidly progressive, severe pneumonia , which is why intensive care is often required. Complications that occur include Acute Respiratory Distress Syndrome (ARDS), septic shock, and multiple organ failure . Particularly severe disease courses have been observed in pregnant women, in the elderly and in sick people with additional chronic diseases.

Course of the outbreak in the People's Republic of China since 2013

First infections in humans

People were infected with the A / H7N9 virus for the first time in February 2013 after contact with poultry, initially two men in Shanghai . Further cases became known in early March from the neighboring east Chinese provinces of Anhui and Zhejiang and from Jiangsu Province . From mid-April 2013, infections were also known elsewhere in China, initially in the north in Beijing and in the Henan Province in central China, and at the end of April also from the eastern Chinese provinces of Fujian , Shandong and Jiangxi and from Hunan in the eastern interior of the country. After the first illnesses were reported from the southern Chinese autonomous region of Guangxi in January 2014 , concerns grew in neighboring Vietnam that the epidemic could spread to the neighboring country due to cross-border animal trade.

On April 3, 2013, three deaths were confirmed, including a man who died on March 4. Pigeons carrying the virus were found in Shanghai at the beginning of April , and chickens shortly afterwards. As a preventive measure, 98,000 chickens, ducks, geese and pigeons were killed there immediately; Furthermore, tissue samples were taken from around 20,000 dead pigs that have been floating in the Huangpu Jiang River since March 10, 2013 , but no A / H7N9 viruses could be detected in them.

According to official information, 18 people in eastern China were infected on April 6, 2013, six of whom had died as a result of the infection; a month later, on May 7, 2013, the number of registered infected people was 130, of which 31 had died; By the end of May 2013, the number of people infected increased to 132 people, 37 of whom had died. After that, only three more new cases were known by mid-August 2013, which, according to WHO spokesman Keiji Fukuda, was interpreted as a result of the warmer weather and the associated poorer transmission of viruses.

From October 2013, further infected people became known from several provinces of the PRC; in mid-December 2013 the number was 143 people, 45 of whom had died. By mid-July 2015, the number of registered infected people rose to 677, of which at least 275 had died. In the summer months that followed, only a few other diseases became known. However, by May 9, 2016, the number of registered infected people rose to 770, of which 306 had died.

Infection from 2017

In the winter half of 2016/17, the number of infected people increased particularly sharply: By mid-February 2017, a total of 1223 sick people were registered, of which 380 had died; Between January 17 and February 14 alone, there were 305 new diseases in China, and at least 79 people died in January 2017 as a result of the infection.

A / H7N9 was first detected in the USA in March 2017; During routine controls at a poultry farm in Tennessee , a variant of LPAI was discovered, resulting in the killing of 16,500 broilers.

On June 15, 2017, the WHO was aware of a total of 1533 confirmed infected people, of which at least 592 people had died; on September 27, 2017, the WHO reported 1564 confirmed infected people, of which 612 people had died according to the China National Health and Family Planning Commission . By May 28, 2018, the number of cases known to the WHO increased slightly to 1567, including 615 deaths, and by November 25, 2019 to 1568 diseases.

Transmission routes

The exact circumstances that lead to infection with the virus are considered unclear; not all sick people had direct contact with poultry beforehand. Laboratory experiments have shown that chickens and quails are particularly easily infected . It is still unclear how many people carry the A / H7N9 virus without showing symptoms of the disease.

According to its official statements, the World Health Organization does not have any indications of "sustained" virus transmissions from person to person (status: February 20, 2017). However, a family with several sick people had already become known on April 17, 2013; On the same day, a WHO spokesman had therefore admitted that such a chain of infection may have occurred in “rare exceptions”. At the beginning of August 2013, the case of a 32-year-old woman from Wuxi became known who had already “most likely” (“probable”) infected her father in March; both died of multiple organ failure . No evidence of infection with A / H7N9 was found in 43 people who had contact with the two patients. Two more human-to-human transmissions presumably occurred in a Chinese hospital in 2015, where two doctors were infected by a patient.

In several animal experiments with ferrets , whose immune system reacts to influenza viruses in a similar way to that of humans, the H7N9 isolate A / Shanghai / 2/2013 (SH2) was shown to be airborne from one animal to another; The researchers deduced from this that "under suitable conditions", human-to-human transmission is also possible. While one of these studies found that viruses that were transmitted in exhaled liquid droplets have not been able to penetrate new host cells particularly effectively, another study found that the viruses that were spread in this way were "highly transmissible".

On the other hand, influenza viruses such as H4, H5, H6 or H7, which are much more common in birds, have not yet caused influenza epidemics in humans; these were always caused by H1, H2 and H3, which in turn occur much less frequently in birds. In addition, the transmission rate is currently very low because the H7N9 virus has so far still exhibited a strong adaptation to avian receptors and the circulating virus variants - contrary to the in vitro findings - have so far mostly only bound to human receptors in the upper respiratory tract but in the lungs. In addition, the previously understandable flu epidemics did not arise from direct virus transmission from poultry animals, but rather from genetic variations of the known virus types that existed in humans.

At the regional level, it was calculated for China in 2020 that the spread of avian influenza viruses will also take place along the trade routes for poultry.

Risk situation

The pathogenicity in humans is still unknown due to a lack of data on the contagion index , i.e. how many of the infected people become ill.

The World Health Organization (WHO) recommends to date (as of February 20, 2017) does not offer direct entry checks nor travel restrictions, warns travelers but before visiting poultry farms and poultry markets in China.

“In order to prevent the epidemic from spreading abroad”, the Chinese health authorities ordered at the end of January 2014 that all departures at Chinese airports “have flu-like symptoms such as fever, cough and difficulty breathing,” should be examined more closely and isolated in good time if H7N9 is suspected become."

The first sick person outside the People's Republic of China became known from Taiwan on April 24, 2013 ; the man was previously in Suzhou , PRC. As a result, several Asian countries announced that they would check people entering airports for febrile illnesses, for example with the help of thermal imaging cameras. One of the illnesses diagnosed in Malaysia in February 2014 was a traveler from China who had been treated for fever and cough before starting her trip.

According to Thomas Mettenleiter , President of the Friedrich Loeffler Institute, the risk of the H7N9 virus spreading beyond China is comparable to that of the H5N1 avian flu in 2004. However, the H7N9 influenza A virus appears to be easier from poultry People pass over as the influenza A virus H5N1 ; A / H7N9 was therefore described by WHO spokesman Keiji Fukuda on April 24, 2013 as one of the “most lethal influenza viruses we have seen so far”, as “one of the deadliest influenza viruses we have seen so far”. Since the virus has not yet circulated among people, it is expected that people of all ages and around the world would be susceptible to A / H7N9. Experiments with ex vivo material from human trachea and lung tissue showed that the viruses particularly attack the epithelial cells of the lower respiratory tract and type II pneumocytes and that the usual seasonal influenza vaccines do not offer any protection against the viruses.

Drug development

An effective and proven influenza vaccine against A / H7N9 is not yet commercially available (as of March 2017), however, several “candidate vaccines” have been tested in clinical studies since 2014. Virus samples had already been given to specialist laboratories outside of China for the purpose of vaccine development in April 2013 in order to characterize the RNA code, and on May 2, 2013 the WHO had also announced that virus samples would be made available to vaccine manufacturers. According to initial findings, A / H7N9 seems to induce a significantly weaker immune response than most other influenza viruses. On the one hand, this increases the risk that the viruses will spread even without recognizable symptoms of the disease; on the other hand, compared to other influenza viruses, a lot more “seed viruses” are required for the production of vaccines against A / H7N9.

In mid-April 2013, the US Food and Drug Administration (FDA) announced that the A / H7N9 viruses have “significant potential for a health hazard”; The authority had therefore given an “emergency permit” to allow virus detection methods (test kits) to be used even if the usual approval process by the FDA has not yet been completed.

In early August 2013, a group of virologists around the Dutch researcher Ron Fouchier asked for the A / H7N9 virus to be modified in the laboratory so that it could be transmitted from person to person; in this way it could be better estimated which mutations would lead to a pandemic . Comparable experiments, which were controversial among researchers and the public, had previously also been carried out with the influenza A virus H5N1 . The virologists' request met with some approval and some rejection from other experts. The US Department of Health and Human Services announced that it would conduct a risk assessment.

The antiviral substance amantadine has only limited effectiveness against A / H7N9 - if at all - as it was used extensively in poultry farming in China and resistant influenza strains have therefore formed; In one human infection, Tamiflu also proved to be ineffective against A / H7N9.

According to a study published in 2017, all tested H7N9 strains were found to be susceptible to the inhibitor of a viral RNA polymerase called “Favipiravir” (also: “T-705”), which could therefore be considered as a possible antiviral option in the event of an infection .

literature

  • Jian Zhong Shi et al .: Isolation and characterization of H7N9 viruses from live poultry markets - Implication of the source of current H7N9 infection in humans. In: Chinese Science Bulletin. April 2013, doi: 10.1007 / s11434-013-5873-4
  • Rongbao Gao et al .: Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus. In: New England Journal of Medicine . Volume 368, 2013, pp. 1888-1897, doi: 10.1056 / NEJMoa1304459
  • Yu Chen et al .: Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterization of viral genome. In: The Lancet . Volume 381, No. 9881, 2013, pp. 1916-1925, doi: 10.1016 / S0140-6736 (13) 60903-4
  • Di Liu et al .: Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyzes. In: The Lancet. Volume 381, No. 9881, 2013, pp. 1926-1932, doi: 10.1016 / S0140-6736 (13) 60938-1
  • Benyun Shi et al .: Inferring the potential risks of H7N9 infection by spatiotemporally characterizing bird migration and poultry distribution in eastern China. In: Infectious Diseases of Poverty. Volume 2, No. 8, 2013, doi: 10.1186 / 2049-9957-2-8
  • Hai-Nv Gao et al .: Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection. In: New England Journal of Medicine. Volume 368, 2013, pp. 2277-2285, doi: 10.1056 / NEJMoa1305584

See also

Web links

Specialist authorities

Background information

Individual evidence

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