#19,239
In January of 2023 Ecuador reported its first (and as far as we know, only) human infection with H5N1; in a 9-year-old girl with reported contact with backyard poultry.
The initial report included no details on when she was infected, her symptoms, or her current condition.
But the following day PAHO published a report stating : The patient is currently hospitalized in a pediatric intensive care unit, in isolation and with antiviral and supportive treatment.
A week later the WHO published a far more detailed report which stated:
The case is a nine-year-old girl, with no known comorbidities, from Bolívar Province, Ecuador. She developed symptoms of conjunctival pruritus and coryza on 25 December 2022. On 27 December, she was brought to a local health center for medical evaluation and treatment. On 30 December, due to the persistent symptoms including nausea, vomiting and constipation, she was admitted to a general hospital where empirical treatment for meningitis was started with antibiotics and antipyretics. On 3 January 2023, she was transferred to a pediatric hospital in critical condition where she was admitted to the intensive care unit (ICU) with septic shock and was treated with antivirals and mechanical ventilation due to pneumonia.
Eight months later a report appeared in Travel Medicine which stated:
The patient was a 9-year-old girl without co-morbidities from Bolivar Province, who was admitted to a hospital due to severe flu symptoms in 30 December 2022. She was transferred to the ICU of a paediatric hospital on 3 January 2023 due to complications with septic shock and pneumonia. She received complex support antiviral treatment, including oseltamivir, managing to improve her critical condition; She continued in interdisciplinary management with favorable progress and was finally discharged from the hospital.
I mention these prior reports because today we have a new case report - published in the journal Viruses - which paints a far different picture of this patient's course of illness; one which had much more neurological involvement than previously acknowledged.
Other than a vague mention that `empirical treatment for meningitis was started' during hospitalization in the WHO report, there was little to suggest this case presented as anything other than severe flu symptoms & pneumonia leading to septic shock.
Whereas, today's report states:
They also indicate that respiratory symptoms were minimal upon admission, instead citing `progressive neurological symptoms', which prompted urgent medical evaluationThe clinical course was characterized by an atypical initial presentation of bilateral periorbital edema and headache, progressing to acute encephalitis, cerebral ischemia, flaccid tetraplegia, central diabetes insipidus, and refractory septic shock.
Those early reports become problematic because clinicians require timely information on the full range of symptoms and/or presentation of novel flu infection, if they are to consider them in their differential.
First, I've posted some brief excerpts from the case report, but the paper is very much worth reading in its entirety. After the break we'll look back at some other recent reports of severe neurological involvement from H5N1 infection.
First Ecuadorian Pediatric Case of Multisystem and Neurological Involvement Associated with Influenza A—H5N1 Virus—Case Report
Frances Fuenmayor 1,*, Santiago Chávez 2, María de los Ángeles Costta 1, Mateo Carvajal 3, Denisse Benítez 3,Rommel Guevara 3, Erika Muñoz 3, Paúl Cárdenas 3,Marisol Carrillo 4 … Melanie Orellana 2
Viruses 2026, 18(7), 749;
https://doi.org/10.3390/v18070749
Abstract
Influenza A (H5N1) is a highly pathogenic zoonotic virus with a human fatality rate of approximately 60%. Pediatric cases and associated neurological manifestations remain poorly documented in Latin America. This report describes the first confirmed Ecuadorian pediatric case of H5N1-associated encephalitis and multisystem organ failure in a previously healthy 9-year-old female following direct contact with infected poultry.
The clinical course was characterized by an atypical initial presentation of bilateral periorbital edema and headache, progressing to acute encephalitis, cerebral ischemia, flaccid tetraplegia, central diabetes insipidus, and refractory septic shock.
Diagnostic confirmation was achieved via nasopharyngeal RT-PCR, with additional RT-PCR and sequencing performed on cerebrospinal fluid, which identified conserved influenza A M1/M2 gene fragments, while laboratory markers—including marked elevations in IL-6, ferritin, and CRP—indicated a severe hyperinflammatory state.
Management involved an intensive multidisciplinary approach utilizing oseltamivir, intravenous immunoglobulin, modulated-dose corticosteroids, desmopressin, and mechanical ventilation. Despite a severe clinical course, the patient achieved a favorable recovery, with a Glasgow Coma Scale score of 15/15 at discharge and only partial residual paresis and left hypoacusia as sequelae. This landmark case provides rare evidence of H5N1 neuroinvasion in a pediatric patient and demonstrates that timely detection combined with aggressive immunotherapy and antiviral treatment can improve survival.
Furthermore, it underscores the critical necessity for strengthened regional molecular surveillance and clinical training to recognize atypical presentations of emerging zoonoses in Latin America, especially in cases involving contact with sick poultry.
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This case underscores the severity of multisystemic involvement in influenza A H5N1 in pediatric patients, as well as the importance of a structured follow-up protocol for managing neurological and metabolic sequelae. Our findings highlight the need for active surveillance in children exposed to avian-influenza risk factors and for protocols covering early identification, continuous monitoring, and rehabilitation after resolution of the acute illness. Given the magnitude of these clinical implications, primary prevention through zoonotic control remains a fundamental pillar for reducing the incidence of new cases.
(Continue . . . )
Many recent cases - particularly from genotype B3.13 - have been mild, often with conjunctivitis and minor respiratory symptoms. Some are even asymptomatic.
But avian H5N1 also has a history of causing severe neurological manifestations both in humans, and in other avian and mammalian hosts.
- A 2009 PNAS study (Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration) found that the H5N1 virus was highly neurotropic in lab mice, and in the words of the authors `could initiate CNS disorders of protein aggregation including Parkinson's and Alzheimer's diseases’.
- Six years later - following the 2014 death of the first imported H5N1 case in Canada - we saw a study (see CJ ID & MM: Case Study Of A Neurotropic H5N1 Infection - Canada), where the authors wrote: `These reports suggest the H5N1 virus is becoming more neurologically virulent and adapting to mammals'.
- In a 2015 Scientific Reports study on the genetics of the H5N1 clade 2.3.2.1c virus - Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015 – the authors described its neurotropic effects, and warned that it could pose a ` . . . significant threat to humans if these viruses develop the ability to bind human-type receptors more effectively.'
Since 2022 we've seen a steady stream of reports of spillover of avian H5N1 into mammalian hosts, with many exhibiting severe (often fatal) neurological manifestations. A few of many recent blogs include:
While severe neurological involvement from human H5Nx infection remains relatively rare:
In 2022 (see Clinical Features of the First Critical Case of Acute Encephalitis Caused by Avian Influenza A (H5N6) Virus), we reviewed the first known case of neuroinfluenza in an H5N6 patient; a 6-year-old girl who was admitted to a hospital with mild pneumonia - but severe encephalitis - in January of that year.
That was followed 15 months ago (April 2025) by a preliminary report on a neuroinvasive infection in an 8-y.o. girl (see Vietnam: Ho Chi Minh DOH Reports A Rare H5N1 Encephalitis Case In a Child), which reported:
As noted by infectious experts, this is a rare case in which the A/H5N1 avian influenza virus damages the central nervous system and does not attack the respiratory tract.
We followed up on that case last May in OFID: Central Nervous System Involvement by Novel Clade 2.3.2.1e H5N1 Avian Influenza Virus in a Paediatric Patient, where the authors warned:
Testing for IAV and A(H5N1) virus should be considered in patients presenting with CNS infection with a history of exposure (e.g. dead poultry). Clinicians should be aware of meningoencephalitis associated with A(H5N1) infection in the absence of respiratory symptoms.
A reminder that while it can sometimes be mild, H5N1 isn't your father's influenza.
