Researchers are anxiously awaiting data from the midwestern state about a mysterious bird flu infection in a person who had no known contact with potential animal carriers of the disease. The data could reveal whether the ongoing US bird flu outbreak in dairy cattle has reached a dreaded turning point: the emergence of a virus capable of spreading from human to human.
Thus far, data from the mysterious infection are few and far between: small snippets of the H5N1 virus’s genome sequence and an incomplete infection timeline. Ratcheting up concerns is the fact that no Missouri dairy farms have reported a bird flu outbreak; this might be because there really are no infections, or because the state does not require farmers to test their cows for the virus.
“The fear is that the virus is spreading within the community at low levels, and this is the first time that we’re detecting it,” says Scott Hensley, a viral immunologist at the University of Pennsylvania Perelman School of Medicine in Philadelphia. “There’s no data to suggest that to be the case, but that’s the fear.”
A mystery case
On 6 September, Missouri public-health officials and the US Centers for Disease Control and Prevention (CDC) announced that an adult in the state had developed symptoms including chest pain, nausea, vomiting and diarrhea, and was hospitalized owing to other medical conditions. That person did not become severely ill and has recovered from the infection. Tests revealed it to be H5N1 influenza, often referred to as bird flu.
Since March, when the H5N1 virus was first detected in US dairy cattle, there have been more than a dozen cases of human infection that were traced back to contact with infected animals, including cows and birds. The Missouri case stands out because investigators found no such link and no tie to unprocessed food products, such as raw milk, from potentially infected livestock.
This raised the possibility that the virus might have evolved to not only infect humans, but also to spread between people. If so, this increases the risk of it sweeping through human populations, potentially triggering a dangerous outbreak.
But that’s not the only possibility, cautions Jürgen Richt, a veterinary virologist at Kansas State University in Manhattan. “It’s a mystery case,” he says. “So you have to throw your net a little wider. Maybe they cleaned out a bird feeder in the household. Did they go to a state fair? What kind of food did they consume?”
More concerns were raised about the Missouri case on 13 September, when the CDC announced that two people who had close contact with the hospitalized person had also become ill around the same time. One of them was not tested for flu; the other tested negative.
That test result is encouraging but not definitive, says Hensley, because the sample could have been collected when the individual’s viral levels were too low for detection — after they started to recover, for instance. A key next step will be to test all three people for antibodies against the strain of H5N1 bird flu that has been infecting cattle. Such antibodies, particularly in the two contacts, would be definitive evidence of past infection.
Genomic sleuthing
While researchers await the antibody results, they are combing through patchy genome-sequence data from virus samples from the hospitalized person. This could yield any signs that the virus might have adapted to human hosts. The search is a challenge, however: the samples contained very low levels of viral RNA — so little that some researchers have shied away from analysing the sequences altogether.
“What I would want to see is higher quality,” says Ryan Langlois, a viral immunologist at the University of Minnesota Medical School in Minneapolis. “I am very leery about interpreting anything from partial sequences.”
But for Hensley, one feature of the sequence fragments immediately leapt out: a single change in the string of amino acids that form a flu protein called hemagglutinin (the ‘H’ in H5N1). That protein sits on the surface of influenza viruses, where it helps the viruses bind to and infect host cells. It is also a target of flu vaccines.
The change that Hensley found creates a site to which a large sugar molecule can bind. That sugar, he says, could then act as an umbrella, shielding the swath of hemagglutinin beneath it. It is a change that his laboratory has studied in other flu strains, and it could affect how the virus binds to host cells — as well as whether vaccines being developed against the H5N1 virus found in cattle can recognize and perform well against the virus detected in Missouri.
Surveillance gaps
Even if the sequences were available, researchers know little about which genetic changes might allow bird flu viruses to better infect humans or to become airborne, says virologist Yoshihiro Kawaoka at the University of Wisconsin–Madison. Previous studies1,2 had suggested that changes to a gene encoding a protein responsible for copying the viral genome could be crucial for allowing the virus to replicate in mammalian cells. But researchers were unable to sequence that gene from the isolate from Missouri.
Meanwhile, the CDC has issued contracts to five companies in the United States to provide testing services for H5N1 and other emerging pathogens. Testing of cattle also needs to be improved so that public-health officials will know which regions of the country to surveil for infections in humans, says Seema Lakdawala, a virologist at Emory University in Atlanta, Georgia. In the United States, most testing of cattle is regulated at the state level, but only a handful of states have required routine testing on some dairy farms.
Public-health workers still don’t have a good handle on how many US herds have cows infected with H5N1, or whether cattle have immunity after contracting bird flu or can become reinfected, she says.
While researchers wait for more information, Hensley cautions against panic. “This could still be a one-off case and not the sign of something bigger,” he says.
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All eyes are on Missouri.
Researchers are anxiously awaiting data from the midwestern state about a mysterious bird flu infection in a person who had no known contact with potential animal carriers of the disease. The data could reveal whether the ongoing US bird flu outbreak in dairy cattle has reached a dreaded turning point: the emergence of a virus capable of spreading from human to human.
Thus far, data from the mysterious infection are few and far between: small snippets of the H5N1 virus’s genome sequence and an incomplete infection timeline. Ratcheting up concerns is the fact that no Missouri dairy farms have reported a bird flu outbreak; this might be because there really are no infections, or because the state does not require farmers to test their cows for the virus.
“The fear is that the virus is spreading within the community at low levels, and this is the first time that we’re detecting it,” says Scott Hensley, a viral immunologist at the University of Pennsylvania Perelman School of Medicine in Philadelphia. “There’s no data to suggest that to be the case, but that’s the fear.”
A mystery case
On 6 September, Missouri public-health officials and the US Centers for Disease Control and Prevention (CDC) announced that an adult in the state had developed symptoms including chest pain, nausea, vomiting and diarrhea, and was hospitalized owing to other medical conditions. That person did not become severely ill and has recovered from the infection. Tests revealed it to be H5N1 influenza, often referred to as bird flu.
Since March, when the H5N1 virus was first detected in US dairy cattle, there have been more than a dozen cases of human infection that were traced back to contact with infected animals, including cows and birds. The Missouri case stands out because investigators found no such link and no tie to unprocessed food products, such as raw milk, from potentially infected livestock.
This raised the possibility that the virus might have evolved to not only infect humans, but also to spread between people. If so, this increases the risk of it sweeping through human populations, potentially triggering a dangerous outbreak.
But that’s not the only possibility, cautions Jürgen Richt, a veterinary virologist at Kansas State University in Manhattan. “It’s a mystery case,” he says. “So you have to throw your net a little wider. Maybe they cleaned out a bird feeder in the household. Did they go to a state fair? What kind of food did they consume?”
More concerns were raised about the Missouri case on 13 September, when the CDC announced that two people who had close contact with the hospitalized person had also become ill around the same time. One of them was not tested for flu; the other tested negative.
That test result is encouraging but not definitive, says Hensley, because the sample could have been collected when the individual’s viral levels were too low for detection — after they started to recover, for instance. A key next step will be to test all three people for antibodies against the strain of H5N1 bird flu that has been infecting cattle. Such antibodies, particularly in the two contacts, would be definitive evidence of past infection.
Genomic sleuthing
While researchers await the antibody results, they are combing through patchy genome-sequence data from virus samples from the hospitalized person. This could yield any signs that the virus might have adapted to human hosts. The search is a challenge, however: the samples contained very low levels of viral RNA — so little that some researchers have shied away from analysing the sequences altogether.
“What I would want to see is higher quality,” says Ryan Langlois, a viral immunologist at the University of Minnesota Medical School in Minneapolis. “I am very leery about interpreting anything from partial sequences.”
But for Hensley, one feature of the sequence fragments immediately leapt out: a single change in the string of amino acids that form a flu protein called hemagglutinin (the ‘H’ in H5N1). That protein sits on the surface of influenza viruses, where it helps the viruses bind to and infect host cells. It is also a target of flu vaccines.
The change that Hensley found creates a site to which a large sugar molecule can bind. That sugar, he says, could then act as an umbrella, shielding the swath of hemagglutinin beneath it. It is a change that his laboratory has studied in other flu strains, and it could affect how the virus binds to host cells — as well as whether vaccines being developed against the H5N1 virus found in cattle can recognize and perform well against the virus detected in Missouri.
Surveillance gaps
Even if the sequences were available, researchers know little about which genetic changes might allow bird flu viruses to better infect humans or to become airborne, says virologist Yoshihiro Kawaoka at the University of Wisconsin–Madison. Previous studies1,2 had suggested that changes to a gene encoding a protein responsible for copying the viral genome could be crucial for allowing the virus to replicate in mammalian cells. But researchers were unable to sequence that gene from the isolate from Missouri.
Meanwhile, the CDC has issued contracts to five companies in the United States to provide testing services for H5N1 and other emerging pathogens. Testing of cattle also needs to be improved so that public-health officials will know which regions of the country to surveil for infections in humans, says Seema Lakdawala, a virologist at Emory University in Atlanta, Georgia. In the United States, most testing of cattle is regulated at the state level, but only a handful of states have required routine testing on some dairy farms.
Public-health workers still don’t have a good handle on how many US herds have cows infected with H5N1, or whether cattle have immunity after contracting bird flu or can become reinfected, she says.
While researchers wait for more information, Hensley cautions against panic. “This could still be a one-off case and not the sign of something bigger,” he says.
". Don't add the title at the beginning of the created content. Write it as if you want to inform the readers about who, what, when, where, why and how. Dont exceed 120 characters. Style: Maintain a professional level of formality suitable for a newspaper, but avoid overly complex language to ensure the content is accessible to a wide audience. Include keywords related to the news event and phrases likely to be used by readers searching for information on the topic. Tone: While keeping the tone professional, use engaging language to capture the reader's interest without sensationalizing. Reply in plain Text without putting the meta-description into any quotes. Excerpt:">
Vogelgrippe: Ausbreitung unter Menschen und wachsende Datenlücken stellen Forscher vor Herausforderungen
Forscher warten gespannt auf Daten aus dem Bundesstaat über eine rätselhafte Vogelgrippeinfektion bei einer Person, die keinen bekannten Kontakt zu möglichen Tierträgern der Krankheit hatte. Die Daten könnten zeigen, ob der anhaltende Ausbruch der Vogelgrippe in den USA bei Milchkühen einen gefürchteten Wendepunkt erreicht hat: das Auftreten eines Virus, das sich von Mensch zu Mensch verbreiten kann.
Bisher sind die Informationen über die mysteriöse Infektion spärlich: kleine Teile der Genomsequenz des H5N1-Virus und eine unvollständige Infektionschronologie. Besorgniserregend ist, dass keine Milchbetriebe in Missouri einen Vogelgrippe -Ausbruch gemeldet haben; dies könnte daran liegen, dass es tatsächlich keine Infektionen gibt oder dass der Staat keine Testpflicht für seine Kühe angeordnet hat.
„Die Angst besteht, dass sich das Virus in der Gemeinschaft auf niedrigem Niveau ausbreitet und wir es nun zum ersten Mal nachweisen“, sagt Scott Hensley, ein viraler Immunologe an der Perelman School of Medicine der University of Pennsylvania in Philadelphia. „Es gibt keine Daten, die darauf hindeuten, dass es so ist, aber das ist die Angst.“
Ein mysteriöser Fall
Am 6. September gaben die Gesundheitsbehörden von Missouri und die US-Zentren für Krankheitskontrolle und -prävention (CDC) bekannt, dass ein Erwachsener im Bundesstaat Symptome wie Brustschmerzen, Übelkeit, Erbrechen und Durchfall entwickelt hatte und aufgrund anderer medizinischer Bedingungen ins Krankenhaus eingeliefert wurde. Diese Person wurde nicht schwer krank und hat sich von der Infektion erholt. Tests ergaben, dass es sich um H5N1-Influenza handelt, oft als Vogelgrippe bezeichnet.
Seit März als das H5N1-Virus erstmals in US-Milchkühen nachgewiesen wurde, gab es mehr als ein Dutzend Fälle von Mensch-zu-Tier-Infektionen, die auf den Kontakt mit infizierten Tieren, darunter Kühe und Vögel, zurückzuführen sind. Der Fall aus Missouri sticht hervor, weil die Ermittler keine solche Verbindung fanden und keinen Bezug zu unverarbeiteten Lebensmitteln wie Rohmilch von potenziell infizierten Nutztieren herstellen konnten.
Das wirft die Möglichkeit auf, dass sich das Virus dahingehend entwickelt haben könnte, nicht nur Menschen zu infizieren, sondern auch zwischen Menschen zu übertragen. Wenn dies der Fall ist, erhöht es das Risiko, dass es sich in menschlichen Populationen ausbreitet und möglicherweise einen gefährlichen Ausbruch auslöst.
„Es handelt sich um einen mysteriösen Fall“, warnt Jürgen Richt, ein veterinärmedizinischer Virologe an der Kansas State University in Manhattan. „Man muss das Netz ein wenig weiter werfen. Vielleicht haben sie einen Vogelfeeder im Haushalt gereinigt. Sind sie auf einer Landesmesse gewesen? Welche Art von Lebensmitteln haben sie konsumiert?“
Am 13. September wurden weitere Bedenken bezüglich des Falls aus Missouri laut, als die CDC ankündigte, dass zwei Personen, die engen Kontakt mit der hospitalisierten Person hatten, ebenfalls zu diesem Zeitpunkt erkrankt waren. Eine von ihnen wurde nicht auf Influenza getestet; die andere testete negativ.
Dieses Testergebnis ist ermutigend, aber nicht eindeutig, sagt Hensley, da die Probe möglicherweise zu einem Zeitpunkt entnommen wurde, als die viralen Belastungen der Person zu niedrig für eine Erkennung waren – zum Beispiel nach Beginn der Genesung. Ein wesentlicher nächster Schritt wird sein, alle drei Personen auf Antikörper gegen den Stamm von H5N1-Vogelgrippe zu testen, der Kühe infiziert hat. Solche Antikörper, insbesondere bei den zwei Kontakten, wären ein definitiver Nachweis einer früheren Infektion.
Genomische Spurensuche
Während die Forscher auf die Antikörpersergebnisse warten, durchforsten sie die spärlichen genomischen Sequenzdaten von Virusproben der hospitalisierten Person. Dies könnte Hinweise darauf liefern, dass das Virus sich an menschliche Wirte angepasst hat. Die Suche ist jedoch eine Herausforderung: Die Proben enthielten nur sehr geringe Mengen an viraler RNA – so wenig, dass einige Forscher von einer Analyse der Sequenzen ganz abgesehen haben.
„Was ich sehen möchte, ist eine höhere Qualität“, sagt Ryan Langlois, ein viraler Immunologe an der University of Minnesota Medical School in Minneapolis. „Ich bin sehr skeptisch, was die Interpretation von etwas aus unvollständigen Sequenzen betrifft.“
Aber für Hensley sticht ein Merkmal der Sequenzfragmente sofort ins Auge: eine einzelne Veränderung in der Aminosäurekette, die ein Influenza-Protein namens Hämagglutin (das ‚H‘ in H5N1) bildet. Dieses Protein befindet sich an der Oberfläche von Influenza-Viren, wo es den Viren hilft, sich an Wirtszellen zu binden und diese zu infizieren. Es ist auch ein Ziel für Influenza-Impfstoffe.
Die von Hensley gefundene Veränderung schafft eine Bindungsstelle für ein großes Zuckermolekül. Dieses Zuckermolekül könnte dann als Schirm wirken und den Bereich des Hämagglutin darunter abschirmen. Es ist eine Veränderung, die sein Labor bei anderen Influenza-Stämmen untersucht hat, und sie könnte Einfluss darauf haben, wie das Virus an Wirtszellen bindet – sowie darauf, ob die gegen das in Rindern vorkommende H5N1-Virus entwickelten Impfstoffe das in Missouri nachgewiesene Virus erkennen und gut darauf reagieren können.
Überwachungsdefizite
Selbst wenn die Sequenzen verfügbar wären, wissen die Forscher wenig darüber, welche genetischen Veränderungen es dem Vogelgrippevirus ermöglichen könnten, Menschen besser zu infizieren oder sich luftgetragen zu verbreiten, sagt der Virologe Yoshihiro Kawaoka von der University of Wisconsin–Madison. Frühere Studien1,2 hatten nahegelegt, dass Veränderungen eines Gens, das ein Protein zur Kopie des viralen Genoms kodiert, entscheidend dafür sein könnten, dass sich das Virus in Säugetierzellen replizieren kann. Aber die Forscher konnten dieses Gen aus dem Isolat aus Missouri nicht sequenzieren.
Unterdessen hat die CDC Verträge mit fünf Unternehmen in den Vereinigten Staaten abgeschlossen, um Testdienste für H5N1 und andere aufkommende Pathogene bereitzustellen. Auch die Tests von Rindern müssen verbessert werden, damit die Gesundheitsbehörden wissen, welche Regionen des Landes sie auf Infektionen bei Menschen überwachen sollten, sagt Seema Lakdawala, eine Virologin an der Emory University in Atlanta, Georgia. In den USA wird die Testung von Rindern größtenteils auf staatlicher Ebene geregelt, aber nur eine Handvoll Staaten hat eine routinemäßige Testung in einigen Milchbetrieben verlangt.
Öffentliche Gesundheitsmitarbeiter haben noch kein genaues Bild davon, wie viele Herden in den USA mit H5N1 infizierten Kühen betroffen sind oder ob Rinder nach einer Infektion mit Vogelgrippe immun sind oder erneut infiziert werden können, sagt sie.
Während die Forscher auf weitere Informationen warten, warnt Hensley vor Panik. „Es könnte sich immer noch um einen Einzelfall handeln und nicht um ein Zeichen für etwas Größeres“, sagt er.
