US - Human H5N1 bird flu case confirmed in Missouri - September 06, 2024+

[Commonground]

[I guess everyone is speaking behind closed doors...]
URL=https://twitter.com/HelenBranswell
URL="https://twitter.com/HelenBranswell"]Helen Branswell @HelenBranswell

Updated this with more info: The contact and the confirmed case became ill the same day, suggesting a possible mutual exposure. Missouri's Dept of Health & Senior Services says serological testing "is being considered."

#H5N1 #birdflu A health worker experienced mild symptoms, but tested negative for flu.

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I really can't think of a better time to do serological testing, they should do this for everyone who had a respiratory panel done at that hospital in August IMO.

[sharon sanders]

[I guess everyone is speaking behind closed doors...]
URL=https://twitter.com/HelenBranswell
URL="https://twitter.com/HelenBranswell"]Helen Branswell @HelenBranswell

Updated this with more info: The contact and the confirmed case became ill the same day, suggesting a possible mutual exposure. Missouri's Dept of Health & Senior Services says serological testing "is being considered."

#H5N1 #birdflu A health worker experienced mild symptoms, but tested negative for flu.

Helen's info was posted using this new report:


CDC A(H5N1) Bird Flu Response Update September 13, 2024


snip


Missouri Case Update


Missouri continues to lead the investigation into the H5 case reported last week with technical assistance from CDC in Atlanta. The case was in a person who was hospitalized as a result of significant underlying medical conditions. They presented with chest pain, nausea, vomiting, diarrhea, and weakness. The person was not severely ill, nor were they in the intensive care unit. They were treated with influenza antiviral medications, subsequently discharged, and have since recovered. One household contact of the patient became ill with similar symptoms on the same day as the case, was not tested, and has since recovered. The simultaneous development of symptoms does not support person-to-person spread but suggests a common exposure. Also shared by Missouri, subsequently, a second close contact of the case – a health care worker – developed mild symptoms and tested negative for flu. A 10-day follow-up period has since passed, and no additional cases have been found. There is no epidemiologic evidence to support person-to-person transmission of H5 at this time. CDC's original report about the case in Missouri is available: CDC Confirms Human H5 Bird Flu Case in Missouri | CDC Newsroom.

CDC has attempted to sequence the full genome of the virus from the most recent case of H5 reported by Missouri. Because of low amounts of genetic material (viral RNA) in the clinical specimen, sequencing produced limited data for analyses. Full-length gene sequences were obtained for the matrix gene (M) and non-structural (NS) genes and partial gene sequences were obtained for the hemagglutinin (HA) and neuraminidase (NA) genes. The available gene sequences are all closely related to U.S. dairy cow viruses, and similar sequences have been found in birds and other animals around dairy farms, raw milk, and poultry.

The HA gene sequence confirms that the virus is clade 2.3.4.4b, and the NA sequence was confirmed as N1. There are two amino acid differences in the HA that have not been seen in sequences from previous human cases. These amino acid differences are not known to be associated with changes to the virus's ability to infect and spread among people. However, both differences are in locations that may impact the cross-reactivity of clade 2.3.4.4b candidate vaccine viruses (CVVs). Additional antigenic testing is planned. One of the two amino acid differences (HA A156T) has been identified in fewer than 1 percent of viruses detected in dairy cows. The other amino acid difference (HA P136S) has been seen in only a single dairy cow sequence.

In addition to the HA analysis, no markers of reduced susceptibility to neuraminidase inhibitors and no markers of mammalian adaptation were found. These findings suggest that currently available neuraminidase inhibitors for influenza are expected to maintain their effectiveness and that the virus from this person does not show signs of increased potential to spread from person to person. Sequence data for A/Missouri/121/2024 was submitted to GISAID (EPI_ISL_19413343) and GenBank (not yet available). Additionally, multiple attempts to propagate virus from the clinical specimen were not successful.

more....

https://www.cdc.gov/bird-flu/spotlights/h5n1-response-09132024.html

[Commonground]

[/URL]
@HelenBranswell
·
17m
In the end,
@CDCgov
was able to subtype the neuraminidase — the N of this #birdflu virus' name. It is the same #H5N1 that has been spreading in cows. CDC submitted the genetic sequences of the hemagglutinin & the neuraminidase proteins to GISAID.

[Pathfinder]

CDC says close contact of Missouri bird flu patient showed symptoms
...
Sept. 12, 2024, 3:21 PM CST / Updated Sept. 14, 2024, 6:37 AM CST
By Berkeley Lovelace Jr.

A day after the Centers for Disease Control and Prevention said it had yet to identify “a clear source” of infection in a Missouri patient who tested positive for the bird flu virus, the agency quietly disclosed in its weekly influenza report that a close contact was sick around the same time as the Missouri patient but was not tested for influenza.
...
“One close contact of the patient was also ill at the same time, was not tested, and has since recovered,” the agency wrote in its FluView report Friday.

A CDC spokesperson said in an email Friday the close contact was within the household of the Missouri patient and developed symptoms that weren’t typical of flu. The simultaneous development of symptoms, the spokesperson said, doesn’t provide evidence of person-to-person spread.

Additionally, a second close contact — a health care worker — subsequently developed mild symptoms and tested negative for influenza.

The household contact’s symptoms “should have been mentioned” in a briefing Thursday, the spokesperson said, along with the additional context “to fully highlight all available information about the case and to further demonstrate why CDC hasn’t changed its risk assessment.”
...

https://www.nbcnews.com/health/health-news/cdc-says-no-clear-source-bird-flu-infection-missouri-patient-rcna170871

[Pathfinder]

SEPTEMBER 20, 2024

CDC A(H5N1) Bird Flu Response Update September 20, 2024
...

Missouri Case Update


Missouri continues to lead the investigation into the H5 case with technical assistance from CDC in Atlanta. CDC's original report about the case in Missouri is available: CDC Confirms Human H5 Bird Flu Case in Missouri | CDC Newsroom. Earlier this week, the Missouri Department of Health and Senior Services collected blood samples from the person who tested positive for H5N1 in Missouri and a household contact who became ill on the same day and was not tested. Both persons have since recovered. The samples are being sent to CDC for serologic testing to look for antibodies to avian influenza A(H5) virus, which would indicate a previous infection. The simultaneous development of symptoms in two people does not support person-to-person spread but suggests a common exposure. As part of the ongoing contact investigation, Missouri identified one additional health care worker contact who had developed mild respiratory symptoms and was not tested for influenza as the illness had resolved before the investigation began. Serologic testing will be offered to this second health care worker. As CDC previously reported, one health care worker with exposure to the infected individual was tested for influenza and was negative. CDC continues to closely monitor available data from influenza surveillance systems, particularly in affected states, and there has been no sign of unusual influenza activity in people, including in Missouri.

Last week, CDC reported on sequencing of the clinical specimen from the Missouri case.
...

https://flutrackers.com/forum/forum/...tember-20-2024

[sharon sanders]

from CDC update -

snip

Missouri Case Update


Missouri continues to lead the investigation into that state's only reported H5 case with technical assistance from CDC in Atlanta. As CDC learns new information from Missouri about its investigation, we are sharing it as quickly as possible in this space to help keep the public up to date. The Missouri Department of Health and Senior Services has not, to date, identified ongoing transmission among close contacts of the case, first reported on September 6, 2024. Missouri identified two health care workers who were exposed to the hospitalized case before droplet precautions were instituted (i.e., higher risk exposure) and subsequently developed mild respiratory symptoms (among 18 workers with this higher risk exposure); one tested negative for influenza by PCR, as previously reported, and the second provided a blood specimen for testing by CDC for potential influenza A(H5N1) antibodies. Missouri has since identified four additional health care workers who later developed mild respiratory symptoms. One of these workers was in the higher risk category and provided a blood specimen for H5 antibody testing. Three of these workers are among 94 workers who were exposed to the hospitalized case of avian influenza A(H5) after droplet precautions were instituted (i.e., lower risk exposure); blood specimens for those who became symptomatic have been collected for H5 antibody testing at CDC. Aside from the one health care worker reported to have tested negative for influenza by PCR, the five remaining exposed health care workers had only mild symptoms and were not tested by PCR for respiratory infections. PCR testing would have been unreliable at the time of discovery of these individuals' prior symptoms. The health care worker monitoring effort has been part of the ongoing investigation as previously reported. Results of serology testing at CDC on the positive case and their previously identified household contact are still pending. To date, only one case of influenza A(H5N1) has been detected in Missouri. No contacts of that case have tested positive for influenza A(H5N1). CDC continues to closely monitor available data from influenza surveillance systems, particularly in affected states, and there has been no sign of unusual influenza activity in people, including in Missouri.

more.....

https://flutrackers.com/forum/forum/national-international-government-ngo-preparation-response/cdc/h5n1-information/997606-us-cdc-a-h5n1-bird-flu-response-update-september-27-2024

[Pathfinder]

‘This is not a cluster’: The latest on the Missouri bird flu case

Analysis by Fenit Nirappil and McKenzie Beard
October 3, 2024 at 7:52 a.m. EDT
...
George Turabelidze, Missouri’s state epidemiologist who is leading the investigation, said in his first extensive interview that further testing could confirm whether the patient, who has since recovered, actually had bird flu despite testing positive.

Turabelidze said the patient didn’t develop typical symptoms and had no exposures to known vectors. The patient doesn’t work, travel or use public transportation and primarily stays at home because of their chronic medical condition and age, he noted.

According to Turabelidze, the illnesses experienced by the patient’s contacts could have been caused by common pathogens such as coronavirus. He also said the hospital where the patient was admitted is in an agricultural area, opening up the possibility that the health-care workers could have had other exposures.

Blood samples that hold the key to the mystery arrived at the Centers for Disease Control and Prevention’s Atlanta headquarters this week. Investigators will search for antibodies to learn whether, in fact, the patient and the people who were exposed had H5N1 infections.

Yes, but: Results aren’t expected until mid-October because scientists need time to reverse-engineer the virus. And even if the testing does reveal signs of a bird flu case, the results won’t explain when and how the patient — and the people exposed — was infected, officials said.

Some public health experts say there should be more transparency and urgency in investigating the cases. Experts also want to see a more detailed timeline of when people were exposed, developed symptoms and were tested.

Health officials at the vanguard of the investigation are calling for patience. “Sometimes people jump to judgment without having enough information … And we should know everything soon enough,” Turabelidze said.
...

https://www.washingtonpost.com/politics/2024/10/03/this-is-not-cluster-latest-missouri-bird-flu-case/

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https://www.cdc.gov/bird-flu/spotlights/missouri-h5n1-serology-testing.html

CDC Report on Missouri H5N1 Serology Testing

What to know


This spotlight was posted on October 24, 2024.

Topline Summary of Findings


In August 2024, healthcare providers in Missouri had a patient who had gastrointestinal symptoms with a history of chronic respiratory illness. The person was hospitalized and tested for multiple respiratory pathogens, and was positive for influenza A. They recovered from their illness and were discharged. Follow-up surveillance testing was conducted at the Missouri Department of Health and Senior Services Public Health Laboratory using polymerase chain reaction (PCR) that is part of routine national influenza surveillance. Testing found that the patient tested presumptive positive for avian influenza A(H5) ("H5 bird flu"). There was no history of exposure to infected animals or humans. The specimen was forwarded to CDC as part of routine protocol. CDC confirmed the specimen as H5N1 bird flu and this was reported as a case on September 6, 2024.

Missouri state and local officials performed a lengthy retrospective investigation of everyone who came into close contact with the patient and identified seven people (6 health care workers and one family member) who had symptoms that warranted additional investigation given their potential exposure to this patient. CDC, in support of this investigation, conducted a series of tests on blood specimens from 6 of these people – and the original patient – to help identify signs of previous infection or exposure to H5N1 well after full resolution of their symptoms. This was not possible for the others, whose suggestive symptoms had completely resolved at the time of interview. None of the results of this extensive testing and investigation support that human-to-human spread occurred. The health care workers who were tested showed no signs of previous H5N1 infection. They were all "sero-negative." This finding rules out person-to-person spread between the MO case patient and any of health care workers tested. The Missouri case and a household contact both had some evidence – though inconsistent – which suggested exposure to – or a previous infection with – H5N1 using these serologic tests.

To date, human-to-human spread of H5 bird flu has not been identified in the United States. CDC believes the immediate risk to the general public from H5N1 bird flu remains low, but people with exposure to infected animals are at higher risk of infection.

Following these tests, CDC continues to assess that the risk that someone who has not had contact with an infected animal will become infected with H5N1 remains low.

Background on serological testing methodology:


Serological testing for H5N1 was performed on single time point serum specimens taken from retrospectively identified, previously symptomatic, exposed people after enough time had passed to allow their immune system to create antibodies. These tests assess whether the antibodies produced by patients or close contacts of the patient are able to neutralize or bind to the H5N1 virus. If they are able to neutralize or bind to the virus, that suggests a previous infection or exposure to the virus.

The samples were collected by state and local officials from:

• One confirmed H5 case (reported on Sept 6, 2024) who tested positive for H5 by PCR through routine influenza surveillance;
• One household contact of that case who was not tested at the time because their symptoms had resolved;
• Five health care workers with possible work-related exposures to the case who had not been tested since their symptoms had resolved.

Note that there was also one additional previously identified health care worker with exposure to the confirmed H5 case. This person was tested for influenza at the time and was found to be negative, so no serological testing was performed on this person. Since such a low amount of virus was detected in the clinical specimen from the confirmed case in Missouri, a complete genomic sequence from the virus could not be recovered. CDC was able to obtain some sequence data from what little virus was present in the clinical specimen. This sequence data – publicly available as "A/Missouri/121/2024" – showed some changes in the hemagglutinin (HA) that might impact how the patient's immune system responded to the infection (antigenicity). These antigenic changes meant that the antibodies that developed by a person's immune response after exposure to this virus might not bind to the H5N1 viruses isolated from other H5N1 cases used in CDC's H5 serology test.

To ensure accurate serology results, CDC experts developed two reverse genetics (RG) viruses with the same antigenic changes that were documented in the A/Missouri/121/2024 HA sequence. The creation of those viruses took 3 weeks. CDC then used those RG viruses to test the blood specimens from the seven people from MO to look for an immune response to that specific virus, which would suggest exposure/infection.

The human population has complex pre-existing immunity to influenza viruses. In public health investigation of possible influenza infections, blood specimens taken at two different times are recommended for serological testing to assess for infection, one specimen collected within seven days of illness onset, and a second specimen collected after the patient has recovered at ≥ 21 days (ideally 21 to 28 days) after symptom onset. The rise in antibodies measured between the two specimens provides definitive evidence of an immune response to infection. In the Missouri investigation, only one specimen was available, which was collected weeks after the initial case was identified. This added another layer of complexity for serologic analysis in this situation given the retrospective nature of this investigation.

Laboratory Methods:


There is no commercially available H5N1 serology test since such testing does not currently have a clinical role in patient care. CDC does flu serology testing mainly to inform public health investigations and policy. Unlike clinically available serologies for other infections, non-clinical serologic testing for seasonal influenza viruses takes about a week. Serologic testing for H5 takes even longer because of the need for biosafety level 3 enhanced (BSL-3E) handling. Testing in this particular situation required additional steps to ensure valid results. Testing was conducted against four different target viruses: the two RG viruses developed for this investigation (described above), the H5N1 virus isolated from the first human case during this outbreak (posted as "A/Texas/37/2024"), and a seasonal A(H1N1)pdm09 virus. Both RG viruses developed by CDC were used in testing in order to provide additional assurance regarding the validity of the findings.

The following testing was conducted in multiple replicates:

• Microneutralization (MN) assay: The main serology test is called a microneutralization (MN) test. This is a highly sensitive and specific test for identifying influenza virus-specific antibodies in blood sera. The MN assay was performed to measure for neutralizing antibodies against the RG H5 viruses.
• Hemagglutinin inhibition (HI) assay: The HI assay tests for antibodies to the hemagglutinin of the specific influenza virus using red blood cells (RBC). Multiple types of RBCs were assessed in the HI assays to detect antibodies in the sera.
• The Multiplex Antibody Detection Assay (MIADA): a test which looks for antibody binding to 28 different influenza antigen targets (28-plex), it also measures the total immunoglobulin (Ig), IgG, IgM and IgA antibody responses.
• Seasonal Influenza Serum Absorption: an additional step that removes antibodies against seasonal influenza viruses that might be cross-reactive prior to testing against A(H5N1) viruses was also performed. This step helps to rule out the possibility of cross-reactivity from prior exposure to seasonal influenza viruses (through infection or vaccination) which might generate a false positive H5N1 serology result.

Serologic Findings and Interpretation:


CDC and historic WHO criteria for H5N1 seropositivity suggestive of infection requires two positive tests: a MN assay and either an HI or another immunologic assay, like MIADA (See End Note).

• The 5 health care workers who had exposure to the MO case patient were all seronegative using the MN, HI, and MIADA assays. This means they did not have any serologic evidence of past infection with H5N1 bird flu.
• The Missouri case and their household contact had some evidence of a humoral immune response to H5N1 bird flu virus suggestive of possible infection, but it was not detected across assays.
  • The MN assay detected neutralizing antibodies against the RG viruses in the index patient and their household contact. (Neutralizing antibodies are antibodies that defend a cell from a pathogen by disrupting its ability to infect a cell.)
  • The HI assay was negative in both the case and their household .
  • In the MIADA assay, neither the MO case or their household contact were positive.

Conclusion of Missouri Investigation:


The 5 health care workers were definitively seronegative against H5 in all assays, which means they were not infected with H5. This finding rules out person-to-person spread between the index MO case patient and any of five health care workers. Symptoms reported by these contacts were not caused by their exposure to this patient.

Testing results of the sera from the MO case patient and their household contact were similar: both showed evidence of an antibody immune response to H5 in only one assay (that detects H5 neutralizing antibodies), but not on the other serologic assays used to detect infection. The weak immune signal suggests that it is possible that both of these people may have been exposed to H5 bird flu despite the fact that they did not meet accepted thresholds for seropositivity. These similar immunologic results coupled with the epidemiologic data that these two individuals had identical symptom onset dates support a single common exposure to bird flu rather than person-to-person spread within the household. Intensive epidemiologic investigation has not identified an exposure to an animal or animal product exposure to explain these possible infections, and these serologic data cannot further elucidate the exposure leading to these possible infections. End Note:


Historical World Health Organization serological case definition using single serum

Single convalescent serum, collected at ≥ 21 days after symptom onset (or last exposure to infected animals/persons), with a microneutralization antibody titer ≥ 1:40 to an A(H5) virus,

AND either

• 1) a positive result using a different serological assay (e.g., hemagglutination inhibition (HI) antibody titer≥40) or
• 2) an H5-specific positive result from another immunological assay such as ELISA or multiplex binding antibody assay.