#18,429
It's been a busy week, with HPAI reported for the first time in Hawaii, the first human infection in Oregon, another huge jump in infected dairy herds in California, and the addition of 7 human cases to the CDC's list.
Late yesterday the CDC published a lengthy update on HPAI H5, including a summary of the latest laboratory findings (see below).
Of particular interest, they report finding the NA-S247N mutation in 3 poultry workers from Washington state, which has been previously linked to modestly reduced susceptibility to the antiviral oseltamivir (aka Tamiflu).
Regular readers will recognize this as one of two mutations (I223V/S247N) which have increasingly turned up in A(H1N1)pdm09 viruses in recent yeas, which have sparked a number of studies, including:
The Lancet Correspondence: Global Emergence of Neuraminidase Inhibitor-Resistant Influenza A(H1N1)pdm09 Viruses with I223V and S247N Mutations
Compared to the more common H275Y mutation- which can produce a 900-fold reduction in oseltamivir effectiveness - the impact of the NA-S247N mutation alone is relatively small, but in combination with other known resistance mutations, it can have a much more serious impact.
Due to its length, I've only posted some excerpts, so follow the link to read it in its entirety.
November 18, 2024 – CDC continues to respond to the public health challenge posed by a multistate outbreak of avian influenza A(H5N1) virus, or "H5N1 bird flu," in dairy cows, poultry and other animals in the United States. CDC is working in collaboration with the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), Administration for Strategic Preparedness and Response (ASPR), state public health and animal health officials, and other partners using a One Health approach.
Since April 2024, CDC, working with state public health departments, has confirmed avian influenza A(H5) virus infections in 52 people in the United States. Twenty-one of these cases were associated with exposure to avian influenza A(H5N1) virus -infected poultry and 30 were associated with exposure to infected dairy cows [A][B]. The source of the exposure in one case, which was reported by Missouri on September 6, could not be determined.
The 52 cases include 26 cases among dairy farm workers in California, five of which were confirmed by CDC on November 13 and 14, and one additional case in a poultry farm worker in Oregon. This is the first human case of H5N1 bird flu reported in Oregon. All recent cases have occurred in workers on affected farms. All available data so far suggest sporadic instances of animal-to-human spread. These farm workers all described mild symptoms, many with eye redness or discharge (conjunctivitis). Some workers who tested positive in Washington reported some mild upper respiratory symptoms. None of the workers were hospitalized.
CDC is aware of the human case of H5N1 bird flu reported in Canada and is in communication with the Public Health Agency of Canada (PHAC), which has confirmed that the case was caused by an H5N1 virus that is different than those causing outbreaks in dairy cows and other animals in the United States. More information about the case in Canada and ongoing epidemiological investigation is available in a statement from PHAC. Updated case counts for the United States, including by state and source of exposure, are recorded in a table on CDC's website. To date, person-to-person spread of H5 bird flu has not been identified in the United States. CDC believes the immediate risk to the general public from H5 bird flu remains low, but people with exposure to infected animals are at higher risk of infection.
On the animal health side, since March 2024, USDA has confirmed infected cattle in 505 dairy herds in 15 U.S. states. The number of affected herds continues to grow nationally, with almost all new infections identified in herds in California. USDA reports that, since April 2024, there have been H5 detections in 50 commercial poultry flocks and 38 backyard flocks, for a total of 25.61 million birds affected.
Among other activities reported in previous spotlights and ongoing, recent highlights of CDC's response to this include:
Laboratory Update
To date, CDC has confirmed 11 human cases of H5 bird flu in poultry farm workers in Washington. Genetic sequencing of influenza virus from clinical specimens from these cases showed no changes in the hemagglutinin (HA) associated with increased infectivity or transmissibility among people. However, in influenza specimens from three of these H5 cases, CDC identified a change, NA-S247N, that may slightly reduce susceptibility to the neuraminidase inhibitor oseltamivir in laboratory tests.
NA-S247N has been detected sporadically in seasonal influenza viruses and has rarely been found in A(H5N1) viruses. Historically, two H5N1 viruses with the NA-S247N change have been tested for susceptibility to oseltamivir: an A(H5N1) virus collected from a chicken in Laos in 2008 (A/chicken/Laos/13/2008; PMID: 20016036) and a clade 2.3.4.4b H5N1 virus collected from a dolphin in Florida in 2022 (A/dolphin/Florida/2022; PMID: 37494978 and PMID: 38637646). These laboratory studies found either mildly reduced or reduced inhibition by oseltamivir, with results well below what has been reported for oseltamivir resistance of other influenza viruses.
It is important to note that this change is not spreading in H5 viruses. Additionally, this change is not expected to have an impact on the ability of influenza viruses to replicate or spread more easily. While NA-S247N may slightly reduce antiviral susceptibility in laboratory testing, that is NOT the same as resistance. Results of laboratory studies demonstrating mildly reduced or reduced inhibition by oseltamivir may not indicate reduced effectiveness of antiviral treatment of a patient with H5N1 virus infection. NA-S247N is unlikely to have a meaningful impact on the clinical benefit of oseltamivir, which is the currently recommended antiviral for treatment for H5 bird flu. CDC continues to recommend oseltamivir for treatment of patients with H5N1 and for post-exposure prophylaxis of close contacts of confirmed H5N1 patients and those with higher risk exposures to animals infected with H5N1 viruses.
Due to low viral RNA concentrations in clinical specimens from these three cases and unsuccessful attempts to isolate virus in culture, multiple sequencing attempts were required to generate data sufficient to meet CDC quality thresholds for posting of partial NA sequences.
CDC also identified a different change in the polymerase acidic (PA) protein of a virus collected from a recently confirmed human case of H5N1 bird flu in California (A/California/150/2024). This change, PA-I38M, is associated with decreased susceptibility to the influenza antiviral medication baloxavir marboxil and has been sporadically detected in a small number of avian influenza viruses.
Baloxavir is not currently recommended for treatment or post-exposure prophylaxis of H5N1 virus infection. As indicated above, oseltamivir is the recommended antiviral treatment for H5N1 bird flu. No H5N1 patients in the U.S. have received baloxavir treatment for H5N1. There are no available data on baloxavir treatment of H5N1 patients worldwide. And the optimal dosing and duration of baloxavir for treatment or post-exposure prophylaxis of H5N1 virus infection in humans are unknown.
Influenza genetic sequence data from these and other recently confirmed cases of H5 bird flu in humans have been posted in GISAID and GenBank. Additional laboratory investigations are ongoing and planned at CDC to better understand the implications of these changes in the context of the currently spreading H5 viruses. In summary, although these particular changes have not been detected widely and are not spreading among dairy cattle or birds, these findings underscore the importance of ongoing surveillance and testing to analyze H5 viruses for any changes that could potentially impact their susceptibility to flu antiviral medications.
Continued monitoring for this, and other resistance mutations, remains critically important.
For more on antiviral resistance in HPAI H5 viruses, you may wish to revisit:
