#19,121
On Thursday the Journal Eurosurveillance published the most detailed report to date, which outlined not only their clinical findings and virus characterization; it describes the timeline, and the challenges in identifying the virus.
As we've discussed often, it can require a bit of luck to accurately diagnose a novel flu infection, and it is assumed that some - perhaps many - go unidentified.
In 2024 the ECDC issued guidance for member nations on Enhanced Influenza Surveillance to Detect Avian Influenza Virus Infections in the EU/EEA During the Inter-Seasonal Period., which cautioned:Novel viruses can often present with only mild-to-moderate symptoms in otherwise healthy individuals, and testing by GPs and clinics are unlikely to differentiate between seasonal and novel flu strains.
Sentinel surveillance systems are important for the monitoring of respiratory viruses in the EU/EEA, but these systems are not designed and are not sufficiently sensitive to identify a newly emerging virus such as avian influenza in the general population early enough for the purpose of implementing control measures in a timely way.
Generally speaking, hospitalized patients with severe symptoms are most likely to receive the type of testing needed to diagnose novel flu.
On day two of their hospitalization the patient was subjected to a more invasive BAL (Bronchoalveolar lavage), which confirmed the presence of Mycobacterium tuberculosis and revealed an untypable influenza A virus.In this case, the patient - who presented to the ER severely ill with suspected miliary tuberculosis - initially tested negative for influenza A/B, RSV & COVID from a standard nasal-pharyngeal swab (NPS).
Although a novel influenza virus was now suspected - and the patient was started on oseltamivir - it would take another 4 days (Day 6) for H9N2 to be confirmed by their National Influenza Centre (NIC).
Elena Pariani1 , Simona Puzelli2 , Gabriele Del Castillo3,4 , Greta Romano4,5 , Luca Mezzadri6,7 , Cristina Galli1 , Irene Maria Sciabica8 , Luigi Vezzosi3 , Francesca Sabbatini6 , Cristina Paduraru1 , Irene Mileto4,5 , Marcello Tirani9 , Anna Teresa Palamara2 , Paola Stefanelli2 , Fausto Baldanti4,5,10 , Danilo Cereda3,4 , Paolo Bonfanti6,7 , Collaborating Centres’ Study Group on Influenza11
In March 2026, avian influenza A(H9N2) virus was identified in Italy in a patient with weakened immune system. They had recently travelled to West Africa, which raised concerns about the potential importation of zoonotic influenza viruses into Europe, as H9N2 has been endemic in poultry across the region since 2017, with widespread outbreaks and two human cases reported in Senegal (one in 2020) and Ghana (one in 2024) [1,2]. Here we present the results of the virological and epidemiological investigation of this case, including molecular characterisation of the virus and an assessment of the likelihood of onward transmission.
Case description and virological findings
In mid-March 2026, an adult patient presented to the emergency department of our hospital, major tertiary referral centre in the Lombardy Region, Italy. They had experienced fever and cough since mid-January, accompanied by notable weight loss. They had returned from Senegal on the day of admission, having stayed there for more than 6 months [2]. The patient did not seek medical care or take any medication during their stay in West Africa. They recognised and self-monitored fever. Upon arrival, they were clinically stable, with an oxygen saturation of 97% on room air and a body temperature of 38.1°C.
Laboratory findings showed anaemia, hyponatraemia and elevated lactate dehydrogenase (Table 1). A nasal-pharyngeal swab (NPS) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), influenza B virus and respiratory syncytial virus (RSV) (Table 2).
A chest X-ray showed consolidation in the right middle and lower lung fields, and a small pleural effusion. A chest computer tomography (CT) scan revealed extensive consolidation of the left upper lobe, diffuse bilateral micronodules and a large right pleural effusion. An abdominal CT scan showed multiple hypodense lesions on the spleen and moderate ascites.
As miliary tuberculosis was suspected, the patient was admitted to a single negative-pressure isolation room under airborne isolation precautions. Two days after admission, analysis of a sample from bronchoalveolar lavage (BAL) confirmed the presence of Mycobacterium tuberculosis. Anti-tuberculosis therapy comprising rifampicin, isoniazid, ethambutol and pyrazinamide was initiated. Further immunological evaluation revealed considerable cellular immunosuppression (Table 1).
The sample from BAL was tested using two commercial multiplex assays for respiratory virus detection, revealing a positive result for IAV. However, the H1pdm09 and H3 subtyping assays were negative (Table 2). According to the regional pandemic preparedness plan for influenza, all respiratory samples testing positive for IAV but negative for the seasonal subtypes should be sent immediately to a regional reference laboratory (RRL).
There are three RRLs in the Lombardy region: the University of Milan, the Fondazione IRCCS Policlinico San Matteo and the ASST Fatebenefratelli-Sacco [3]. Further real-time RT-PCR testing at the University of Milan RRL confirmed the presence of IAV, with no detection of the H1pdm09 or H3 seasonal subtypes or avian A(H5N1) or A(H7N9). Given the suspicion of a zoonotic IAV infection, the regional authorities and the National Influenza Centre (NIC) were alerted at once, and oseltamivir therapy (75 mg twice daily) was initiated.
On day 6 after admission, real-time RT-PCR was performed to detect avian IAV subtypes H5, H7 and H9, and a positive result was obtained for H9. On that day, nasal and throat swabs were collected from the patient, with only the throat swab testing positive for IAV. According to the national procedure [4,5], an aliquot of BAL sample was sent to the NIC where it was confirmed as an IAV subtype H9 (Table 2). The virus was isolated in Madin–Darby canine kidney (MDCK) cells (American Type Culture Collection (ATCC), CRL-2935) at both Fondazione IRCCS Policlinico San Matteo RRL and NIC.
(SNIP)
Discussion
To our knowledge, this is the first reported human case of avian influenza A(H9N2) in Europe [2,17]. The detection of an unsubtypable IAV in the patient with severely weakened immune system prompted a thorough molecular investigation, including characterisation of the virus, which highlights the effectiveness of the diagnostic and surveillance system.
The regional public health authorities identified, tested and interviewed 13 contact persons. Nevertheless, contact tracing is challenging when airline companies and tour operators are involved. Several individuals could not be traced; however, all those who were successfully traced and tested, returned negative results.
The genetic similarity of the virus to previously detected strains in West Africa suggests that the patient may have been exposed to the virus during their time in the region, despite reporting no direct contact with animals. The presence of molecular markers associated with human receptor binding further highlights the zoonotic potential of A(H9N2) viruses. However, there is currently no evidence of human-to-human transmission.
Notably, the initial NPS was negative for IAV, potentially due to inadequate specimen collection or a low viral load in the upper respiratory tract at the time of sampling. In this patient with weakened immune system, the infection was initially detected in the lower respiratory tract, as evidenced by BAL positivity. Later NPS positivity, however, was associated with high quantification cycle (Cq) values and suggested the detection of residual viral RNA rather than active replication in the nasopharynx [18].
Conclusion
The potential for prolonged replication in patients with weakened immune systems raises concerns about the emergence of escape variants, emphasising the need for continued vigilance. This case underlines the importance of considering non-seasonal influenza viruses in patients with compatible symptoms and relevant travel history and highlights the added value of genomic characterisation in the public health response.
The patient had reportedly been ill in Senegal for at least a month, and while his route of exposure to H9N2 is unknown, his lack of contact with poultry or farm environments suggests at least the possibility of a community acquired infection.
Recent surveillance reports, however, have indicated that H9N2, along with H7 and H5 viruses, have been detected in both pigs and poultry in Senegal (see Influenza A Virus in Pigs in Senegal & Risk Assessment of AIV Emergence and Transmission to Humans).While we comfort ourselves with our current low number of human novel flu detections, we are probably missing some number of cases.
For more on this, you may wish to revisit UK Novel Flu Surveillance: Quantifying TTD, which suggests it might take weeks, and hundreds of cases, before our surveillance systems would detect low-level community spread of a novel flu virus.
And of course by that time, our options for containment would be limited.
