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Despite being an LPAI (low path avian influenza) virus, and generally producing relatively mild symptoms in humans, H9N2 is viewed by many as an important and influential player in the avian flu world.
Although most cases undoubtedly go undetected, 2024 saw a near-record 22 confirmed cases (see FluTrackers H9N2 list), with cases reported by 4 nations (China - 19, India - 1, Ghana -1, and Vietnam - 1).
As an LPAI virus, H9N2 is not considered a `reportable' disease by WOAH (formerly the OIE), even though it is clearly zoonotic. We've seen seroprevalence studies which suggest people with exposure to infected poultry often develop H9 antibodies, suggesting a significant number of unreported mild or asymptomatic infections.
Over the past 15 years we've watched as H9N2 has expanded its geographic range - spreading out of Asia into Europe, the Middle East and Africa. While it occasionally spills over into humans, H9N2's biggest threat may come from its unique ability to reassort with other, potentially more dangerous, avian viruses.
H9N2 is such a versatile virus, it has even been detected in Egyptian Fruit bats (see Preprint: The Bat-borne Influenza A Virus H9N2 Exhibits a Set of Unexpected Pre-pandemic Features).
While admittedly not at the very top of our list of pandemic concerns, the CDC has 2 different lineages (A(H9N2) G1 and A(H9N2) Y280) on their short list of influenza viruses with zoonotic potential (see CDC IRAT SCORE), and several candidate vaccines have been developed.
Last April Vietnam reported their first confirmed H9N2 cases (see Vietnam MOH Statements On A/H9 Case In Tien Giang Province). Aside from being Vietnam's first case, this report was unusual in that it involved an adult, and the patient (who had significant comorbidities) was described as being severely ill.
As this report explains, surveillance and testing for novel flu viruses in Southern Vietnam is patchy at best. The delay between the patient's admission date (March 16th) and a positive H9N2 subtype test (April 8th), was 23 days.
These types of delays are not unusual, even here in the United States, which is why yesterday the CDC issued a HAN advisory, urging hospitals to speed up the subtyping of all influenza a patients (see CDC HAN: Accelerated Subtyping of Influenza A in Hospitalized Patients).
The exact source of exposure for this Vietnamese patient is unknown, although genetic analysis suggest a poultry source. I've posted some excerpts from their report below, but follow the link to read it in its entirety.
I'll return with a postscript after the break.
Human Infection with Avian Influenza A(H9N2) Virus, Vietnam, April 2024
Minh Hang Duong, Thi Ngoc Uyen Phan, Trung Hieu Nguyen, Ngoc Hien Nhon Ho, Thu Ngoc Nguyen, Viet Thinh Nguyen, Minh Thang Cao, Chan Quang Luong, Vu Thuong Nguyen, and Vu Trung Nguyen
Author affiliation: Pasteur Institute in Ho Chi Minh City, Ho Chi Minh City, Vietnam
Abstract
In April 2024, Vietnam confirmed its first human case of influenza A(H9N2) in a 37-year-old man, marking a critical point in regional infectious disease monitoring and response. This case underscores the importance of robust surveillance systems and One Health collaboration in managing emerging zoonotic threats.
Influenza A(H9N2) virus is a low-pathogenicity avian influenza virus endemic in poultry across the world. The virus presents ongoing zoonotic risk; according to the GISAID database (https://www.gisaid.orgExternal Link), ≈100 human cases were detected since 2010, and the virus’s unique evolutionary trajectory shows it could cause pandemics (1).
The risk for transmission and genetic mixing of avian influenza viruses, including H9N2, among wild birds, swine, and humans highlights the necessity for robust surveillance systems to manage the potential threat of these influenza viruses (2–4). In Vietnam, H9N2 accounts for 36% of detected avian influenza viruses (5) and shares genetic similarities with strains from neighboring countries, particularly China (3,6). Although human H9N2 cases have been reported in Asia (7,8), Vietnam had not previously reported a human case until 2024. The first human case of H9N2 influenza in Vietnam was officially confirmed in April 2024, marking a significant event in regional surveillance and response efforts.
A 37-year-old man with a known history of alcohol abuse from Tien Giang Province, Vietnam, experienced fever and cough on March 9, 2024. He sought medical care on March 16 at a provincial hospital, where he received a diagnosis of cirrhosis and was transferred to the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, the same day. Initially, his chest radiograph results were unremarkable. However, on March 19, he had pneumonia with dyspnea, fatigue, and extensive alveolar and interstitial damage evident on chest radiograph. He was intubated on March 21; osletamivir treatment was initiated, which improved his condition and enabled him to be weaned from the ventilator. He continued treatment in a negative-pressure intensive care unit; diagnoses were sepsis, influenza A, invasive fungal infection, respiratory failure, pulmonary hemorrhage, gastrointestinal bleeding, acute kidney injury, alcohol-related cirrhosis, and a suspected liver tumor. On May 5, 2024, he was discharged from the hospital to receive palliative care; he died on May 6, 2024.
The patient had not received influenza or COVID-19 vaccinations and had no known exposure to sick or dead poultry. All 15 close contacts, including family, neighbors, a driver, and healthcare workers, remained asymptomatic during 24 days of monitoring; we did not collect samples from them. His neighborhood had informal markets for poultry and other animals, but no avian influenza outbreaks were reported in the preceding 3 months. Testing geese from his home 27 days after symptom onset found no influenza H5 or H9 viruses, whereas 1 sample from nearby poultry markets tested positive for H5N1 virus but none for H9 viruses.
At the time of this case, southern Vietnam lacked surveillance for severe acute respiratory infection, and influenza-like illness surveillance was limited to 6 sentinel sites, excluding the hospitals involved in this study. The patient was enrolled in Pasteur Institute in Ho Chi Minh City (PIHCM) severe viral pneumonia (SVP) surveillance system, active since 2020, after developing pneumonia with significant respiratory symptoms and chest radiograph findings. On April 1, 2024, PIHCM received the patient’s sample, which had been collected by Hospital for Tropical Diseases on March 21, 2024.On April 8, we performed real-time reverse transcription PCR in accordance with the H9N2 protocol of the Regional Animal Health Office No. 6 Vietnam (RAHO6). The Ct value for H9 was 28.81 and for N2, 29.6, indicating significant viral presence.
(SNIP)
The genetic distances between our sequence and other human and poultry viruses in Asia and America (Figure 2) suggest household poultry as the likely source of exposure. In addition, our findings highlight the geographic spread of H9N2 virus.
Moving forward, several key research questions arise from this case. First, it is crucial to understand the progression of the disease, particularly the mechanism by which H9N2 influenza contributed to the worsening of the patient’s condition, ultimately leading to multiorgan failure. Second, analyzing samples from close contacts to determine H9N2 positivity is important to identify potential human-to-human transmission, understand transmission dynamics, and guide public health interventions.
Although Vietnam lacks a formal One Health rapid response team, this case highlighted the value of cross-sector collaboration. Contributions from public health and animal health sectors, including sequencing expertise and environmental testing, underscore the need to strengthen One Health partnerships for effective surveillance and outbreak response.
Dr. Duong is a medical doctor at the National Influenza Center Respiratory Viruses Laboratory of the microbiology and immunology department of Pasteur Institute in Ho Chi Minh City, Vietnam. Her research focuses on influenza viruses, SARS-CoV-2, and other viruses such as RSV and measles.
While we count and obsess over every reported novel flu detection, at best we are probably only hearing about a small fraction of actual infections. Many countries do little or no testing, while others hold data close to their vest (see From Here To Impunity).
Seven years ago, in EID Journal: Two H9N2 Studies Of Note, we looked at two reports which suggested that H9N2 continues to evolve away from current (pre-pandemic and poultry) vaccines and is potentially on a path towards better adaptation to human hosts.Some more recent (2024) H9N2 studies, include:But even where there is relatively robust surveillance and reporting, official case counts can be deceivingly low (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).
Recent Papers On The Zoonotic Potential of Bat-borne H9N2
Infectious Medicine: Rapid Adaptive Substitution of L226Q in HA protein Increases the Pathogenicity of H9N2 Viruses in Mice
Transboundary & Emerg. Dis.: Novel Human-Avian Reassortment H9N2 Virus in Guangdong Province, China
Frontiers in Public Health: Human Infections of H9N2 Avian Influenza Virus in China (in 2021)
